Researchers Database

OCHI, Hirofumi

    Graduate School of Medicine Program for Medical Sciences Senior Assistant Professor
Last Updated :2020/09/16

Researcher Information

Degree

  • Doctor(Medical)(Kyushu University)

J-Global ID

Research Interests

  • 神経免疫学   Neuroimmurology   

Research Areas

  • Life sciences / Neurology

Academic & Professional Experience

  • 2019/04 - Today  Ehime UniversityGraduate School of Medicine准教授
  • 2012/11 - 2019/03  Ehime UniversityGraduate School of Medicine講師
  • 2011/04 - 2012/10  Ehime UniversityGraduate School of Medicine特任講師
  • 2009/04 - 2011/03  医療法人 大乗会 福岡リハビリテーション病院神経内科部長
  • 2008/06 - 2009/03  Kyushu University神経内科講師
  • 2008/06  Kyushu University HospitalAssistant Professor
  • 2006/04 - 2008/05  Kyushu University神経内科助教
  • 2005/10 - 2006/03  (株)麻生飯塚病院神経内科医長
  • 2003/10 - 2005/09  Harvard Medical School, Brigham and Women’s Hospital,Center for Neurologic DiseasesResearch Fellow
  • 2002/06 - 2005/09  Kyushu UniversitySchool of Medicine
  • 2000/10 - 2002/03  財団法人 長寿科学振興財団脳科学研究推進事業リサーチレジデント
  • 2002  - Lecture Facully of Medicine, Kyushu University
  • 2000/04 - 2000/09  Kyushu UniversitySchool of Medicine助手

Education

  •        -   Kyushu University  Faculty of Medicine
  •        -   Kyushu University  Graduate School, Division of Medical Sciences  Internal Medicine

Association Memberships

  • JAPAN SOCIETY FOR DEMENTIA RESEARCH   THE JAPAN GERIATRICS SOCIETY   THE JAPAN SOCIETY FOR MEDICAL EDUCATION   JAPANESE SOCIETY FOR APHERESIS   日本脳卒中学会   神経治療学会   日本神経免疫学会   日本内科学会   日本神経学会   Jaanese Society of Neurology   

Published Papers

  • Ochi H
    Brain and nerve = Shinkei kenkyu no shinpo 71 (2) 143 - 152 1881-6096 2019/02 [Peer-reviewed]
  • Ochi H
    Journal of neurology, neurosurgery, and psychiatry 0022-3050 2018/10 [Peer-reviewed]
  • Yoichiro Okada, Hirofumi Ochi, Chihiro Fujii, Yuichiro Hashi, Mio Hamatani, Shinji Ashida, Kazuyuki Kawamura, Hirofumi Kusaka, Sadayuki Matsumoto, Masanori Nakagawa, Toshiki Mizuno, Ryosuke Takahashi, Takayuki Kondo
    Journal of Autoimmunity 88 103 - 113 1095-9157 2018/03 [Peer-reviewed]
     Scientific journal 
    Background: B cells play an important role in the development of multiple sclerosis (MS), but can also exhibit regulatory functions through IL-10 production. Toll-like receptors (TLR) and CD40 signaling are likely to be involved in this process. Objective: To investigate the ability of MS B cells to produce IL-10 in response to TLR stimulation in the presence or absence of CD40 co-stimulation. Methods: Peripheral blood mononuclear cells obtained from 34 MS patients and 24 matched healthy participants (HS) were stimulated through either TLR4 or TLR9 alone, or together with CD40. Intracellular cytokine production was analyzed by flow cytometry. Results: The frequency of IL-10-producing cells in total B cells after either TLR9 or CD40 stimulation was significantly lower in MS than HS, regardless of disease phase. The frequency of IL-10 producing B cells after TLR4 stimulation did not differ significantly between HS and MS, regardless of disease phase. TLR4 and CD40 co-stimulation synergistically increased the frequency of IL-10-producing but not pro-inflammatory cytokine-producing B cells at MS relapse. This effect was observed in both CD27− naïve and CD27+ memory B cells. The frequency of IL-10-producing B cells following CD40 stimulation was significantly higher in interferon-β responders than non-treated MS patients. Finally, we confirmed that the frequency of IL-10-producing B cells positively correlated with IL-10 production quantity by B cells using magnetic-isolated B cells. Conclusions: Cross-talk between TLR4 and CD40 signaling plays a crucial role in regulating IL-10 production by B cells during MS relapses, which may promote recovery from relapse. CD40 signaling in B cells is involved in the response to interferon-β in MS. Collectively, TLR4 and CD40 signaling in B cells may provide a promising target for MS therapy.
  • Guangrui Li, Ryo Yamasaki, Mei Fang, Katsuhisa Masaki, Hirofumi Ochi, Takuya Matsushita, Jun-Ichi Kira
    Scientific reports 8 (1) 1933 - 1933 2045-2322 2018/01 [Peer-reviewed]
     
    We aimed to elucidate the effects of iguratimod, a widely used anti-rheumatic drug with no severe side effects, on chronic experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Iguratimod was orally administered to mice immunised with myelin oligodendrocyte glycoprotein peptide 35-55. Preventive administration of iguratimod from the time of immunisation was found to markedly reduce the clinical severity of acute and chronic EAE. Pathologically, iguratimod treatment significantly reduced demyelination and infiltration of CD3+ T, F4/80+, and CD169+ cells into the spinal cord, and suppressed macrophage/microglia activation in the parenchyma at the acute and chronic stages compared with vehicle treatment. Therapeutic administration of iguratimod after the onset of clinical symptoms significantly ameliorated the clinical severity of chronic EAE and reduced demyelination, T helper (Th)1/Th17 cell infiltration, macrophage/microglia activation, and nuclear factor (NF)-κB p65 and cyclooxygenase-2 expression in the spinal cord. In vitro, iguratimod treatment inhibited nuclear translocation of NF-κB p65 and down-regulated pro-inflammatory responses in macrophages and microglia. Our results suggest that iguratimod ameliorates acute and chronic EAE by suppressing inflammatory cell infiltration and immune cell activation, partly through inhibition of NF-κB p65, supporting the therapeutic potential of this drug for not only acute, but also chronic MS.
  • Chihiro Fujii, Takayuki Kondo, Hirofumi Ochi, Yoichiro Okada, Yuichiro Hashi, Tetsuya Adachi, Masaharu Shin-Ya, Sadayuki Matsumoto, Ryosuke Takahashi, Masanori Nakagawa, Toshiki Mizuno
    SCIENTIFIC REPORTS 6 35314  2045-2322 2016/10 [Peer-reviewed]
     Scientific journal 
    Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7(+) central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects. The frequency of CD56(+) T cells and granzyme B-, perforin-, and Fas ligand-positive T cells significantly increased during fingolimod treatment. Each T cell subpopulation further increased during relapse. Interestingly, T cells from fingolimod-treated patients exhibited interferon-gamma biased production, and more myelin basic protein-reactive cells was noted in CD56(+) than in CD56(-)T cells. It is likely that the altered T cell phenotypes play a role in MS relapse in fingolimod-treated patients. Further clinical studies are necessary to investigate whether altered T cell phenotypes are a biomarker for relapse under fingolimod therapy.
  • Ryo Yamasaki, Takuya Matsushita, Toshiyuki Fukazawa, Kazumasa Yokoyama, Kazuo Fujihara, Mieko Ogino, Takanori Yokota, Katsuichi Miyamoto, Masaaki Niino, Kyoichi Nomura, Ryo Tomioka, Masami Tanaka, Izumi Kawachi, Takashi Ohashi, Ken-ichi Kaida, Makoto Matsui, Yuji Nakatsuji, Hirofumi Ochi, Hikoaki Fukaura, Takashi Kanda, Akiko Nagaishi, Kanae Togo, Hidehiro Mizusawa, Hiroyuki Murai, Jun-ichi Kira
    MULTIPLE SCLEROSIS JOURNAL 22 (10) 1337 - 1348 1352-4585 2016/09 [Peer-reviewed]
     Scientific journal 
    Background: No large-scale studies have compared the efficacy of intravenous methylprednisolone pulse therapy (IVMP) for multiple sclerosis (MS) and neuromyelitis optica (NMO). Objective: To explain differences in treatment responses of MS and NMO patients to IVMP. Methods: Changes in neurological symptoms/signs and Expanded Disability Status Scale (EDSS) scores before and within 1week of IVMP completion were obtained in 2010 at 28 institutions, and retrospectively collated from 271 MS (478 courses) and 73 NMO (118 courses) cases. Results: In MS patients, decreased EDSS score was significant after the first (-0.80.9), second (-0.7 +/- 0.9), and third (-0.7 +/- 0.8) courses (p<0.05), but not after the fourth (-0.3 +/- 0.7) and fifth (-0.5 +/- 0.6). However, decreased EDSS score was only significant after the first course (-0.5 +/- 1.5, p<0.05) in NMO patients. EDSS score was significantly decreased in MS compared with NMO patients at the first course (p<0.05), but not thereafter. Model analysis for EDSS score improvement at the first course, adjusting for covariates, showed significantly greater decreases in MS compared with NMO patients (p<0.05). Conclusion: IVMP is effective in MS from the first to third courses, and in NMO at the first course. Additionally, IVMP is more efficacious in MS than NMO patients, even at the first course.
  • Hirofumi Ochi, Kazuo Fujihara
    CURRENT OPINION IN NEUROLOGY 29 (3) 222 - 228 1350-7540 2016/06 [Peer-reviewed]
     
    Purpose of review The present review aims to discuss the recent advances in inflammatory demyelinating diseases of the central nervous system in Asia. Recent findings Prevalence of multiple sclerosis (MS) in Asia is lower than that in Western countries, although it has been increasing recently. Meanwhile, there seems to be no major difference in neuromyelitis optica (NMO) prevalence in various regions or ethnicities. Thus, the ratios of NMO/NMO spectrum disorder (NMOSD) to MS are higher in Asia as compared with Western countries, indicating that the differential diagnosis between NMO/NMOSD and MS is a major challenge in Asia. Although the detection of aquaporin-4 (AQP4)-antibody is critical in distinguishing NMO/NMOSD from MS, some patients with NMO/NMOSD phenotype are seronegative for AQP4-antibody, and a fraction of those patients possess autoantibody against myelin oligodendrocyte glycoprotein. The clinical profile of Asian MS seems to be essentially similar to that in Western MS after careful exclusion of NMO/NMOSD, although some unique genetic and/or environmental factors may modify the disease in Asians. Summary MS prevalence has been low but is increasing in Asia. In contrast, NMO/NMOSD prevalence seems relatively constant in the world. Asian MS is not fundamentally different from Western MS, but some genetic and/or environmental differences may cause some features unique to Asian patients.
  • [Emerging new disease--modifying therapies for multiple sclerosis].
    Ochi H
    Nihon rinsho. Japanese journal of clinical medicine 73 Suppl 7 221 - 227 0047-1852 2015/09 [Peer-reviewed]
  • [Use of interferon-β in the treatment of multiple sclerosis].
    Ochi H
    Nihon rinsho. Japanese journal of clinical medicine 72 (11) 2003 - 2009 0047-1852 2014/11 [Peer-reviewed]
  • Chihiro Fujii, Yoichiro Okada, Kimitoshi Kimura, Masanori Nakagawa, Sadayuki Matsumoto, Ryosuke Takahashi, Hirofumi Ochi, Takayuki Kondo, Toshiki Mizuno
    JOURNAL OF NEUROIMMUNOLOGY 275 (1-2) 199 - 199 0165-5728 2014/10 [Peer-reviewed]
  • Hirofumi Ochi
    Brain and Nerve 66 (10) 1201 - 1209 1881-6096 2014/10 [Peer-reviewed]
     
    Cognitive impairment may occur in up to 70% of all patients with multiple sclerosis (MS). Although MS can affect various sites within the central nervous system, a specific pattern of cognitive deficits tends to be seen, especially in the early stages of the disease. These deficits include problems with attention, information processing speed, and working memory. This constellation of deficits can occur with any disease course, and a minimal correlation has been found between physical disability assessed by EDSS and cognitive impairment. Many studies have shown that cognitive impairment is correlated with brain lesion volume, as well as brain atrophy. There are promising neuroimaging indicators that may be useful for identifying patients at risk for cognitive impairment, such as diffusion tensor imaging, the magnetization transfer ratio, and N-acetyl aspartate levels. Cognitive dysfunction is associated with adverse effects on quality of life, employment status, and social activities. Today, there are three avenues for treatment: disease modifying therapies, symptomatic treatments, and cognitive rehabilitation. Unfortunately, data linking therapeutic interventions are limited. A better understanding of cognitive function and its correlation with disease mechanisms will assist in providing a new comprehensive treatment strategy that begins immediately with the diagnosis of MS.
  • Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Katsuhisa Masaki, Shinya Sato, Yuji Kawano, Hirofumi Ochi, Jun-ichi Kira
    PLOS ONE 9 (4) e95367  1932-6203 2014/04 [Peer-reviewed]
     Scientific journal 
    Background: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. Methodology: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658). Principal Findings: CSF IgG abnormality was found in 59 of 94 (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1*1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1*0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. Conclusions: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1*1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1*0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative MS, respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status.
  • Hiromi Kikuchi, Nobuhiro Mifune, Masaaki Niino, Jun-ichi Kira, Tatsuo Kohriyama, Kohei Ota, Masami Tanaka, Hirofumi Ochi, Shunya Nakane, Seiji Kikuchi
    BMC NEUROLOGY 13 10  1471-2377 2013/01 [Peer-reviewed]
     Scientific journal 
    Background: To improve quality of life (QOL) in patients with multiple sclerosis (MS), it is important to decrease disability and prevent relapse. The aim of this study was to examine the causal and mutual relationships contributing to QOL in Japanese patients with MS, develop path diagrams, and explore interventions with the potential to improve patient QOL. Methods: Data of 163 Japanese MS patients were obtained using the Functional Assessment of MS (FAMS) and Nottingham Adjustment Scale-Japanese version (NAS-J) tests, as well as four additional factors that affect QOL (employment status, change of income, availability of disease information, and communication with medical staff). Data were then used in structural equation modeling to develop path diagrams for factors contributing to QOL. Results: The Expanded Disability Status Scale (EDSS) score had a significant effect on the total FAMS score. Although EDSS negatively affected the FAMS symptom score, NAS-J subscale scores of anxiety/depression and acceptance were positively related to the FAMS symptom score. Changes in employment status after MS onset negatively affected all NAS-J scores. Knowledge of disease information improved the total NAS-J score, which in turn improved many FAMS subscale scores. Communication with doctors and nurses directly and positively affected some FAMS subscale scores. Conclusions: Disability and change in employment status decrease patient QOL. However, the present findings suggest that other factors, such as acquiring information on MS and communicating with medical staff, can compensate for the worsening of QOL.
  • Mitsuru Watanabe, Hirofumi Ochi, Hajime Arahata, Tomohito Matsuo, Seiho Nagafuchi, Yasumasa Ohyagi, Jun-Ichi Kira
    MUSCLE & NERVE 45 (6) 904 - 908 0148-639X 2012/06 [Peer-reviewed]
     Scientific journal 
    Introduction: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by monogenic mutations in the autoimmune regulator (AIRE) gene. No attention has been paid to muscle manifestations in this disorder. We aimed to uncover whether progressive myopathy is a component of this disorder. Methods: A case description and literature search for APECED cases presenting with myopathy and analysis of AIRE gene expression in biopsied muscles from 4 healthy volunteers and the patient by reverse transcriptase polymerase chain reaction. Results: A 52-year-old woman with APECED caused by AIRE gene mutations developed progressive myopathy involving proximal limb and paraspinal muscles. Muscle biopsy specimens showed myopathic changes without inflammatory cell infiltrate. We detected AIRE gene expression in all muscle tissues examined. An extensive literature search uncovered 5 cases of APECED with myopathy, all of whom had similar features. Conclusions: Progressive myopathy involvement could be a hitherto unknown manifestation of APECED. Muscle Nerve 45: 904-908, 2012
  • Thigh Muscle Mass Decline Was Associated Brain Small Vessel Diseases in Men; Possible Link between Sarcopenia and Dementia
    Masayuki Ochi, Katsuhiko Kohara, Yasuharu Tabara, Rie Takita, Tokihisa Nagai, Nako Shinohara, Yoko Okada, Hirofumi Ochi, Michiya Igase, Tetsuro Miki
    NEUROLOGY 78 0028-3878 2012/04 [Peer-reviewed]
  • Hiromi Kikuchi, Nobuhiro Mifune, Masaaki Niino, Sadayoshi Ohbu, Jun-ichi Kira, Tatsuo Kohriyama, Kohei Ota, Masami Tanaka, Hirofumi Ochi, Shunya Nakane, Masaji Maezawa, Seiji Kikuchi
    QUALITY OF LIFE RESEARCH 20 (1) 119 - 131 0962-9343 2011/02 [Peer-reviewed]
     Scientific journal 
    To evaluate health-related quality of life (HRQOL) in Japanese patients with multiple sclerosis (MS) and investigate associations between the results of these QOL assessments and disease severity. One-hundred sixty-three Japanese MS patients completed a questionnaire battery comprising the Functional Assessment of MS (FAMS), the Nottingham Adjustment Scale-Japanese version (NAS-J), and the European QOL scale (EQ-5D). Additional five factors affecting QOL as identified by MS patients in a focus group interview were also investigated: employment status, change of income, availability of disease information, communication with medical staff, and care received. Disease severity was determined using the Expanded Disability Status Scale (EDSS). There was a strong negative correlation of the subscale scores for mobility, symptoms, emotional well-being, thinking and fatigue, and additional concerns on the FAMS with EDSS score. For the NAS-J, only acceptance of the condition was correlated with disease severity. Among the five additional aspects of the condition identified by patients, employment status, income, and disease information were shown to be important for maintaining QOL in patients with MS. Support for finding employment and having increased or maintained household income and readily available information about the disease contribute to improving QOL in Japanese MS patients.
  • Satoshi Yoshimura, Hirofumi Ochi, Noriko Isobe, Takuya Matsushita, Kyoko Motomura, Takeshi Matsuoka, Motozumi Minohara, Jun-ichi Kira
    MULTIPLE SCLEROSIS JOURNAL 16 (10) 1178 - 1188 1352-4585 2010/10 [Peer-reviewed]
     Scientific journal 
    Objective: To clarify brain-derived neurotrophic factor production by peripheral blood immunocytes and its relationship with clinical parameters in multiple sclerosis. Methods: Serum brain-derived neurotrophic factor levels were measured by conventional enzyme-linked immunosorbent assay while brain-derived neurotrophic factor production by immunocytes was determined by an in situ enzyme-linked immunosorbent assay in 74 multiple sclerosis patients, 32 healthy controls, and 86 patients with other neurological diseases. The tyrosine kinase receptor TrkB expression level in peripheral blood mononuclear cells was measured by real-time polymerase chain reaction. Results: Multiple sclerosis patients showed significantly higher serum brain-derived neurotrophic factor levels than healthy controls and patients with other neurological diseases. Multiple sclerosis patients with high brain-derived neurotrophic factor levels were younger, and showed fewer relapse numbers than those with low brain-derived neurotrophic factor levels. Brain-derived neurotrophic factor production by T cells increased with age in healthy controls, but not in multiple sclerosis patients. Interferon beta induced a significant increase in serum brain-derived neurotrophic factor levels. Brain-derived neurotrophic factor production from T cells and TrkB expression levels in peripheral blood mononuclear cells were significantly enhanced in interferon beta-treated multiple sclerosis patients compared with untreated ones. Conclusions: A high brain-derived neurotrophic factor level is related to early mild disease in young multiple sclerosis patients. Interferon beta potentiates brain-derived neurotrophic factor production and brain-derived neurotrophic factor receptor expression in peripheral blood mononuclear cells, which may act beneficially.
  • Treatment and clinical management of patients with neuromyelitis optica and anti-aquaporin 4 antibody
    Hirofumi Ochi
    Brain and Nerve 62 (9) 945 - 952 1881-6096 2010/09 [Peer-reviewed]
     
    Neuromyelitis optica (NMO) is a unique inflammatory condition characterized by selective involvement of the optic nerves and spinal cord. The cardinal features of NMO and a tendency of recurrence led to the classification of NMO as a subtype of multiple sclerosis (MS) however, it can be distinguished from MS on the basis of clinicoradiological and serological findings. In paticular, NMO is characterized by the presence of spinal cord lesions that are longer than the total length of 3 vertebral segments and presence of anti-aquaporin 4 antibodies. Secondary progression of this condition is usually not observed, and therapy for NMO patients is designed to prevent acute exacerbations and limit irreversible neurological disability. Intravenous administration of a high dose of methylprednisolone is a standard treatment for patients with acute exacerbations of this condition, and patients with refractory cases are often responsive to plasmapher-esis. To reduce the frequency of relapses and severity, standard therapies for MS, such as interferon-beta therapy, are not effective further, a long-term immunosuppressive therapy is required for NMO patients. Immunosuppressive therapies often involve oral administration of prednisolone with or without azathioprine patients who are refractory to the oral therapy may be treated by parental administration of cyclophosphamide, mitoxantrone, or rituximab. At present, there is no cure for NMO early and precise diagnosis is critical to initiate immunosuppressive therapy for prevention of relapse.
  • Masahito Tanaka, Takaaki Ishizu, Hirofumi Ochi, Yuji Kawano, Yasumasa Ohyagi, Jun-ichi Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 275 (1-2) 74 - 77 0022-510X 2008/12 [Peer-reviewed]
     Scientific journal 
    juvenile Muscular atrophy of the distal upper extremity (JMADUE) is associated with airway allergy and hyperIgEaemia, suggesting the involvement of immunological processes. In this study we aimed to clarify the changes in various cytokines/chemokines in cerebrospinal fluid (CSF) from JMADUE patients. We simultaneously measured 17 cytokines/chemokines in sera and CSF from 6 patients with JMADUE before treatment and from 14 patients with cervical spondylosis (CS) as a disease control (mean age at examination 23 +/- 7 and. 57 +/- 16 years, respectively), using a fluorescent bead-based immunoassay. We also assayed CSF from a JMADUE patient before and after plasma exchanges. In sera, only an increase of MIP-1 beta (CCL3) in the JMADUE patients had a marginal significance as compared with the CS patients. In the CSF, IFN-gamma and MIP-1 beta (CCL3) were significantly elevated in JMADUE patients compared with controls (1.5 and 2-fold increases, respectively), while no other cytokines/chemokines showed any significant differences. Moreover, the upregulated cytokines decreased after plasma exchanges in accord with improvement of distal upper limb weakness. The intrathecal upregulation of proinflammatory Th1 cytokines/chemokines, such as IFN-gamma and MIP-1 beta (CCL3), in the CSF of JMADUE patients indicates the possible involvement of intrathecal immunological processes in this condition. (C) 2008 Elsevier B.V. All rights reserved.
  • Hirofumi Ochi, Michal Abraham, Hiroki Ishikawa, Dan Frenkel, Kaiyong Yang, Alexandre Basso, Henry Wu, Mei-Ling Chen, Roopali Gandhi, Ariel Miller, Ruth Maron, Howard L. Weiner
    JOURNAL OF THE NEUROLOGICAL SCIENCES 274 (1-2) 9 - 12 0022-510X 2008/11 [Peer-reviewed]
     Scientific journal 
    One of the major goals for the immunotherapy Of autoimmune diseases is the induction of regulatory T cells that mediate immunologic tolerance. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We have found that oral administration of anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental autoimmune encephalomyelitis both prior to disease induction and at the height of disease. Oral anti-CD3 antibody acts by inducing a unique type of regulatory T cell characterized by latency-associated peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF-beta dependent mechanism. Orally delivered antibody would not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. These findings identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions. (C) 2008 Elsevier B.V. All rights reserved.
  • Takeshi Matsuoka, Takuya Matsushita, Manabu Osoegawa, Hirofumi Ochi, Yuji Kawano, Futoshi Mihara, Yasumasa Ohyagi, Jun-Ichi Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 266 (1-2) 115 - 125 0022-510X 2008/03 [Peer-reviewed]
     Scientific journal 
    There are two distinct subtypes of multiple sclerosis (MS) in Asians: optic-spinal (OSMS) and conventional (CMS). Longitudinally extensive spinal cord lesions (LESCLs) extending over three or more vertebral segments are characteristic of patients with OSMS, yet in Asians, one-fourth of CMS patients also have LESCLs. To clarify the distinction between LESCLs in OSMS and CMS, and to characterize the relationship between the presence of LESCLs and brain magnetic resonance imaging (MRI) findings, we studied 142 patients with clinically definite MS of relapsing-remitting onset and 12 patients with primary progressive MS (PPMS) by MRI of the whole spinal cord and brain. The former was diagnosed by Poser criteria, including 57 with OSMS, 67 with CMS and 18 with brainstem-spinal form of MS, while the latter by McDonald criteria. The presence of LESCLs throughout the entire clinical course was significantly more common in OSMS patients than in CMS patients, while brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) were significantly more common in CMS patients than OSMS patients. LESCLs in OSMS patients most frequently affected the upper to middle thoracic cord, with either holocord or central gray matter involvement. By contrast, 70% of LESCLs in CMS patients predominantly affected the peripheral white matter of the mid-cervical cord. LESCLs in patients with PPMS also showed preferential involvement of the peripheral white matter of the mid-cervical cord. One-third of OSMS patients had neither LESCLs nor Barkhof brain lesions more than 10 years after disease onset, and showed significantly milder disability than OSMS patients with LESCLs. These findings suggest that LESCLs are heterogeneous between OSMS and CMS patients, and that there are distinct subtypes of MS in Japanese, according to clinical and MRI findings. (c) 2007 Elsevier B.V. All rights reserved.
  • Koichi Hagiwara, Hiroyuki Murai, Hirofumi Ochi, Manabu Osoegawa, Hiroshi Shigeto, Yasumasa Ohyagi, Jun-ichi Kira
    INTERNAL MEDICINE 47 (11) 1047 - 1051 0918-2918 2008 [Peer-reviewed]
     Scientific journal 
    We present two patients with primary lateral sclerosis-like upper motor neuron disease accompanying subclinical Sjogren's syndrome. Both patients showed progressive spastic quadriparesis, but neither sensory involvement nor detrusor dysfunction was noted. Lower motor neuron signs were detected only in their late follow-up period. Although sicca symptom was nearly absent, salivary labial gland biopsy revealed marked sialoadenitis in both patients. They also displayed a constellation of findings that suggested an autoimmune etiology closely related to Sjogren's syndrome, including germinal center formation in one patient, and markedly elevated levels of anti-nuclear antibody with abnormal sialography in the other. Both patients showed significant neurological improvement after the initial course of intravenous immunoglobulin therapy. We suggest that the evidence for subclinical Sjogren's syndrome should be sought in patients presenting with selective upper motor neuron involvement.
  • Kiyomi Tsukimori, Hirofumi Ochi, Yasuo Yumoto, Satomi Iwasaki, Satoshi Hojo, Tomoyuki Noguchi, Norio Wake
    CEREBROVASCULAR DISEASES 25 (4) 377 - 380 1015-9770 2008 [Peer-reviewed]
     Scientific journal
  • Upper motor neuron syndrome associated with subclinical Sjögren's syndrome.
    Hagiwara K, Murai H, Ochi H, Osoegawa M, Shigeto H, Ohyagi Y, Kira J
    Internal medicine (Tokyo, Japan) 47 (11) 1047 - 1051 0918-2918 2008 [Peer-reviewed]
  • Hiroki Ishikawa, Hirofumi Ochi, Mei-Ling Chen, Dan Frenkel, Ruth Maron, Howard L. Weiner
    DIABETES 56 (8) 2103 - 2109 0012-1797 2007/08 [Peer-reviewed]
     Scientific journal 
    Anti-CD3 monoclonal antibody (mAb) has been shown to induce tolerance and to be an effective treatment for diabetes both in animal models and in human trials. We have shown that anti-CD3 mAb given orally is biologically active in the gut and suppresses experimental autoimmune encephalitis by the induction of a regulatory T-cell that expresses latency-associated peptide (LAP) on its surface. In the present study, we investigated the effect of oral anti-CD3 mAb on the prevention of autoimmune diabetes in AKR mice in which the low-dose streptozocin (STZ) model induces autoimmunity to the beta-cells of the islets. We found that oral anti-CD3 mAb given at doses of 50 and 250 mu g/feeding suppressed the incidence of diabetes in this model with the best effects seen at the 50 mu g/dose. Associated with suppression, we observed decreased cell proliferation in the spleen and conversion of T-helper (Th)1 responses into Th2/Th3 responses in the periphery, including the pancreatic lymph nodes. Oral anti-CD3 mAb increased the expression of LAP on CD4(+) beta-cells, and these cells could adoptively transfer protection. Protection by oral anti-CD3 was transforming growth factor-beta dependent. Our results demonstrate that oral anti-CD3 is effective in the model of STZ-induced diabetes and may be a useful form of therapy for type 1 diabetes in humans.
  • [Acute myelitis in a patient with ulcerative colitis].
    Hagiwara K, Ochi H, Murai H, Shigeto H, Ohyagi Y, Kira J
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 96 (8) 1703 - 1705 0021-5384 2007/08 [Peer-reviewed]
  • Takeshi Matsuoka, Takuya Matsushita, Yuji Kawano, Manabu Osoegawa, Hirofumi Ochi, Takaaki Ishizu, Motozumi Minohara, Hitoshi Kikuchi, Futoshi Mihara, Yasumasa Ohyagi, Jun-ichi Kira
    BRAIN 130 (Pt 5) 1206 - 1223 0006-8950 2007/05 [Peer-reviewed]
     Scientific journal 
    Opticospinal multiple sclerosis (OSMS) in Asians has similar features to the relapsing-remitting form of neuromyelitis optica (NMO) seen in Westerners. OSMS is suggested to be NMO based on the frequent detection of specific IgG targeting aquaporin-4 (AQP4), designated NMO-IgG. The present study sought to clarify the significance of anti-AQP4 autoimmunity in the whole spectrum of MS. Sera from 113 consecutive Japanese patients with clinically definite MS, based on the Poser criteria, were assayed for anti-AQP4 antibodies by immunofluorescence using GFP-AQP4 fusion protein-transfected HEK-293T cells. Sensitivity and specificity of the anti-AQP4 antibody assay, 83.3 and 100%, respectively, were calculated using serum samples with NMO-IgG status predetermined at the Mayo Clinic. The anti-AQP4 antibody positivity rate was significantly higher in OSMS patients (13/48, 27.1%) than those with CMS (3/54, 5.6%), other neurological diseases (0/52) or healthy controls (0/35). None of the II patients tested with a brainstem-spinal form of MS were positive. Among OSMS patients, the antibody positivity rate was highest in OSMS patients with longitudinally extensive spinal cord lesions (LESCLs) extending over three vertebral segments and brain lesions that fulfilled the Barkhof criteria (5/9, 55.6%). Multiple logistic analyses revealed that emergence of the anti-AQP4 antibody was positively associated only with a higher relapse rate, but not with optic-spinal presentation or LESCLs. Compared with anti-AQP4 antibody-negative CMS patients, anti-AQP4 antibody-positive MS patients showed significantly higher frequencies of severe optic neuritis, acute transverse myelitis and LESCLs while most conditions were also common to anti-AQP4 antibody-negative OSMS patients. The LESCLs in anti-AQP4 antibody-positive patients were located at the upper-to-middle thoracic cord, while those in anti-AQP4 antibody-negative OSMS patients appeared throughout the cervical-to-thoracic cord. On axial planes, the former most frequently showed central grey matter involvement, while holocord involvement was predominant in the latter. In contrast, LESCLs in anti-AQP4 antibody-negative CMS patients preferentially involved the mid-cervical cord presenting a peripheral white matter-predominant pattern, as seen in the short lesions. Anti-AQP4 antibody-positive MS patients fulfilling definite NMO criteria showed female preponderance, higher relapse rate, greater frequency of brain lesions and less frequent responses to interferon beta-Ib than anti-AQP4 antibody-negative OSMS patients with LESCLs. These findings suggested that LESCLs are distinct in anti-AQP4 antibody positivity and clinical phenotypes. There were cases of anti-AQP4 antibody-positive MS/NMO distinct from CMS, and anti-AQP4 antibody-negative OSMS with LESCLs in Japanese. This indicated that the mechanisms producing LESCLs are also heterogeneous in cases with optic-spinal presentation, namely AQP4 autoimmunity-related and -unrelated.
  • Cytokine/chemokine profile in the cerebrospinal fluid from patients with motor neuron disease
    Takahisa Tateishi, Masahito Tanaka, Hitoshi Kikuchi, Hirofumi Ochi, Jun-ichi Kira
    NEUROLOGY 68 (12) A375 - A375 0028-3878 2007/03 [Peer-reviewed]
  • Oral administration of anti-CD3 antibody suppresses experimental allergic encephalomyelitis by inducing CD4(+)CD25(-)LAP(+) regulatory T cells
    Hirofumi Ochi, Michal Abraham, Hiroki Ishikawa, Dan Frenkel, Kaiyong Yang, Alexandre Basso, Henry Wu, Mei-Ling Chen, Roopali Gandhi, Ariel Miller, Ruth Maron, Howard L. Weiner
    JOURNAL OF NEUROIMMUNOLOGY 178 120 - 121 0165-5728 2006/09 [Peer-reviewed]
  • FJ Mei, M Osoegawa, H Ochi, M Minohara, S Nan, H Murai, T Ishizu, T Taniwaki, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 246 (1-2) 71 - 77 0022-510X 2006/07 [Peer-reviewed]
     Scientific journal 
    To address the immune mechanism of the long-term beneficial effects of interferon beta (IFN-beta), we measured the intracellular cytokine production patterns of IFN-gamma, IL-4 and IL-13 in peripheral blood CD4(+) and CD8(+) T cells, which previously displayed alterations during the early course of IFN-beta treatment, in 15 Japanese patients after long-term IFN-beta administration. The patients were treated with IFN-beta-1b 8 X 106 units given subcutaneously every other day for a mean period of 34.5 +/- 5.5 months (range: 26-43 months). During the follow-up period, 6 patients experienced 33 relapses, while the other 9 were relapse-free. The results revealed the following cytokine alterations: (1) type 2 cytokine, such as IL-4 and IL-13, were significantly increased in producing cell percentages in both CD4(+) (p=0.0356 and p=0.0007, respectively) and CD8(+) (p=0.0231 and p=0.0170, respectively) T cells while IFN-gamma, a representative type I cytokine, was significantly decreased in the absolute producing cell numbers (p=0.0125 in CD4(+) T cells and p=0.0022 in CD8(+) T cells) even after approximately 3 years of IFN-beta administration; (2) the intracellular IFN-gamma / IL-4 ratio tended to decrease in both CD4+ and CD8+ T cells (p=0.0535 and p=0.0783, respectively), reflecting a strong downmodulation of type I cytokine producing cells; and importantly (3) alterations such as the decreased intracellular IFN-gamma / IL-4 ratio in CD4(+) T cells and increased percentage of CD8(+) IL-13(+) Tcells compared with the pretreatment levels were only statistically significant in MS patients without relapse during IFN-beta therapy (p=0.0152 and p=0.0078, respectively). Therefore, we consider that cytokine deviation toward the Th2 and Tc2 sides is linked to a long-term favorable response to IFN-beta, while a higher intracellular IFN-gamma / IL-4 ratio is associated with treatment failure. (c) 2006 Elsevier B.V. All rights reserved.
  • XM Zhang, J Reddy, H Ochi, D Frenkel, VK Kuchroo, HL Weiner
    INTERNATIONAL IMMUNOLOGY 18 (4) 495 - 503 0953-8178 2006/04 [Peer-reviewed]
     Scientific journal 
    SJL mice are highly susceptible to proteolipid protein (PLP) 139-151-induced experimental allergic encephalomyelitis (EAE). The disease is characterized by a relapsing-remitting type of paralysis. However, the mechanism by which animals recover from EAE is poorly understood. Here, we investigated the role of regulatory T cells in the recovery from disease. We found that Forkhead box P3-expressing CD4(+)CD25(+) T cells were increased in the blood, draining lymph node and spleen of EAE-recovered SJL mice. These cells were anergic and inhibited proliferation of CD4(+)CD25(-) T cells to PLP 139-151 or anti-CD3 antibody stimulation. Depletion of CD4(+)CD25(+) T cells during the recovery phase exacerbated disease, resulted in the expansion of IA(s)/PLP 139-151-tetramer-positive cells and enhanced IFN-gamma production. In addition, transforming growth factor-beta (TGF-beta) was shown to be involved in the recovery from EAE as the percentage of CD4(+) cells expressing TGF-beta latency-associated peptide (LAP) on the cell surface increased significantly in blood and spleen of EAE-recovered mice as compared with the naive mice and in vivo neutralization of TGF-beta abolished recovery from disease. Taken together, our results demonstrate that both CD4(+)CD25(+) and CD4(+)LAP(+) regulatory T cells mediate recovery from PLP 139-151-induced EAE in SJL mice in which TGF-beta plays an important role.
  • Cortical cerebellar atrophy presenting with central type sleep apnea syndrome
    Jin Qingyu, Takuo Nomura, Hirofumi Ochi, Takayuki Taniwaki, Hirokazu Furuya, Jun-Ichi Kira
    Clinical Neurology 45 (7) 490 - 494 0009-918X 2005/07 [Peer-reviewed]
     Scientific journal 
    The patient was a 55-year-old man who had shown progressive dysarthria and unsteady gait since 48 years of age. Neurologically, pure cerebellar ataxia without either pyramidal or extrapyramidal signs was seen. He had been diagnosed as having cortical cerebellar atrophy (CCA) at age 53. Polysomnography was carried out at June 17 th, 2003, because of snoring and sleep apnea had occurred since January 2003. The results showed central dominant sleep apnea with an apnea index (AI) of 16.6. Apnea occurred during shallow sleep, stages I and II, while the length of REM sleep was almost normal, occupying 17.7% of total sleep time. The rhythm of his sleep was well preserved. Brain MRI showed cerebellar atrophy without any brainstem abnormality. Except for the central type sleep apnea, no other autonomic symptoms were found. We considered that the diagnosis of CCA remained applicable to the patient because of the presence of pure cerebellar symptoms over a 7-year-course, and the absence of brainstem atrophy on MRI. Sleep apnea seen in the present patient was distinct from MSA in which central type sleep apnea dominated, and that the sleeping rhythm including REM was preserved.
  • A case of brachial amyotrophic diplegia accompanied with Sjögren's syndrome presenting good response to immunotherapies in the early course of the disease
    Yuka Takakura, Hiroyuki Murai, Hirokazu Furuya, Hirofumi Ochi, Jun-Ichi Kira
    Clinical Neurology 45 (5) 346 - 350 0009-918X 2005/05 [Peer-reviewed]
     Scientific journal 
    A 74-year-old woman suffered from progressive muscle atrophy and weakness of her arms since she was seventy two years old. Before referral to our department, she was diagnosed as having cervical spondylotic myeloradiculopathy and received spinal fusion. Though spinal decompression was successful, muscle weakness of her upper limbs were progressive even after the surgery. On admission, neurological examinations revealed marked atrophy and weakness of her bilateral upper limbs with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower extremities had normal muscle strength, but fasciculations were seen in her all four limbs. Electrophysiologically, motor nerve conduction velocity was almost normal but the amplitude was remarkably decreased, conduction block was not detected, and electromyography showed neurogenic patterns on her all extremities. Spinal progressive musclar atrophy (SPMA) accompanied with Sjögren's syndrome was the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her serum, we assumed that anterior horn cells were impaired by an autoimmune mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable improvement on her weakness, and the effect lasted for about three months. This is the first case of SPMA with Sjögren's syndrome which showed good response to PE and IVIG in the early course of the disease. We considered that some SPMA-like motor neuron syndrome accompanied with autoimmune features may require immunomodulating therapies.
  • M Osoegawa, R Miyagishi, H Ochi, Nakamura, I, M Niino, S Kikuchi, H Murai, T Fukazawa, M Minohara, K Tashiro, J Kira
    JOURNAL OF NEUROIMMUNOLOGY 161 (1-2) 195 - 198 0165-5728 2005/04 [Peer-reviewed]
     Scientific journal 
    We evaluated the association of the platelet-activating factor receptor (PAFR) gene polymorphism (A224D) with the susceptibility and severity of multiple sclerosis (MS) in a Japanese population. DNA was collected from 162 Japanese patients with clinically definite 'conventional' MS (MS) and 245 healthy controls. The missense mutation A224D that impairs PAF-PAFR signaling was determined by polymerase chain reaction restriction fragment length polymorphism. The frequency of the AD/DD genotypes was significantly higher in MS patients (21.0%) than in healthy controls (13.5%) (p=0.045; odds ratio (OR), 1.71; 95% confidence interval (0), 1.01-2.89). Moreover, the frequency of D allele in MS patients (11.7%) was also significantly higher than those in healthy controls (6.9%) (p=0.019; OR, 1.78; 95% Cl, 1.10-2.89). These findings suggest that the PAFR gene missense mutation has a relation to the susceptibility for MS. (C) 2005 Elsevier B.V. All rights reserved.
  • M Osoegawa, H Ochi, FJ Mei, M Minohara, H Murai, T Taniwaki, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 228 (1) 87 - 92 0022-510X 2005/01 [Peer-reviewed]
     Scientific journal 
    Juvenile muscular atrophy of the distal tipper extremity (JMADUE) is considered to be a type of flexion myelopathy: however,. we recently reported cases of JMADUE associated with airway allergy successfully treated by plasma exchange. To further characterize;he allergo-immunological features of JMADUE, 11 consecutive JMADUE patients in the neurology clinic at Kyushu University Hospital were studied. Past and present together with family histories of common allergic disorders were investigated. Total serum NE was measured by an enzyme linked immunosorbent assay (ELISA) and allergen-specific IgE by a liquid phase enzyme immunoassay. Intracellular interferon (IFN)gamma-, interleukin(IL)-4-, IL-5- and IL-13-producing T cells in peripheral blood were analyzed by flow cytometry. Data from 42 healthy subjects were used as controls for allergological studies. Flow cytometric data from 21 healthy subjects were also used for comparison. The patients exhibited significantly higher frequencies of coexisting airway allergies such as allergic rhinitis (p=0.0057) and pollinosis (p=0.0064), family histories of allergic disorders (p=0.0075). and mite antigen specific IgE (p=0.0361) compared with the healthy subjects. Patients with JMADUE had a significantly higher percentage of IFNgamma(-)IL-4(+)CD4(+) T cells (p=0.0017), but not IL-5- or IL-13-producing CD4(+) T cells. and a reduced intracellular IFNgamma/IL-4 ratio in CD4(+) T cells (p=0.002) compared to the controls. These findings suggest that JMADUE has a significant T helper 2 (Th2) shift, which may in part contribute to the development of spinal cord damage. (C) 2004 Elsevier B.V. All rights reserved.
  • Exacerbation of chronic inflammatory demyelinating polyradiculoneuropathy during interferon beta-1b therapy in a patient with childhood-onset multiple sclerosis
    D Matsuse, H Ochi, K Tashiro, T Nomura, H Murai, T Taniwaki, J Kira
    INTERNAL MEDICINE 44 (1) 68 - 72 0918-2918 2005/01 [Peer-reviewed]
     Scientific journal 
    Interferonbeta-1b (IFNbeta-1b) is commonly used for relapsing-remitting multiple sclerosis (MS). We report a 23-year-old woman with childhood onset relapsing-remitting MS treated with IFNbeta-1b who developed overt chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) immediately after therapy. A baseline conduction study before IFNbeta-1b therapy revealed decreased motor conduction velocities and prolonged F wave latencies in several nerves, but there was no neurological sign indicating neuropathy. The existence of subclinical demyelinating neuropathy before IFNbeta-1b treatment was suggested, although the clinical criteria for CIDP were unfulfilled. Following two months of IFNbeta-1b therapy, numbness of her right upper and lower limbs progressively worsened and all tendon reflexes were depressed. Electrophysiologically, F waves were not evoked in any limbs except for the left ulnar and tibial nerves, which showed marked prolongation of F wave latencies. Moreover, subclinical hyperthyroidism developed in association with high titers of anti-thyroglobulin and antithyroid peroxydase antibodies, which were negative before IFNbeta-1b therapy. These findings indicated that peripheral demyelination worsened at the nerve roots after IFNbeta-1b therapy. In addition to the development of autoimmune thyroid disease, the patient now fulfilled the criteria for probable CIDP. Along with the results of a previous report demonstrating IFNbeta-induced CIDP development in patients with childhood MS, this case underscores IFNbeta as a potential risk factor for CIDP in patients with childhood onset MS.
  • H Murai, H Arahata, M Osoegawa, H Ochi, M Minohara, T Taniwaki, S Tobimatsu, F Mihara, Y Tsuruta, S Inaba, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 227 (1) 39 - 47 0022-510X 2004/12 [Peer-reviewed]
     Scientific journal 
    Objective: A recent nationwide survey of myelitis with atopic diathesis in Japan disclosed that the disease frequently shows a chronic persistent course. A neuropathological study of the spinal cord also revealed chronic active inflammation. Since the effects of various immunotherapies have not been studied extensively in this condition, we evaluated the efficacies of various immunotherapies in patients with myelitis with atopic diathesis. Patients and methods: Forty-two treatments in 26 patients with myelitis with atopic diathesis were retrospectively analyzed. One of the following therapies was administered: (1) corticosteroids (CS) (pulse therapy followed by oral administration with gradual tapering); (2) intravenous immunoglobulin (IVIG) (400 mg/kg/day for 5 consecutive days); (3) plasma exchanges (PE); or (4) PE followed by IVIG or CS (PE+IVIG/CS). The therapeutic efficacies were evaluated by thorough neurological examination and laboratory tests including MRI, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). Results: Objective neurological findings improved in 89% of the PE group and 90% of the PE+IVIG/CS group, compared with only 72% of the CS and 60% of the IVIG groups. Improvement determined by laboratory tests was seen in 57% of the PE and 57% of the PE+IVIG/CS groups, compared with only 15% of the CS and none of the IVIG groups. Thus, the improvement rate determined by laboratory tests was significantly greater for therapies including PE than for those without PE (p=0.0187). Conclusions: These data suggest that immunotherapy is effective in myelitis with atopic diathesis despite a chronic persistent course, and that PE is the most beneficial immunotherapy. (C) 2004 Elsevier B.V. All rights reserved.
  • H Murai, M Osoegawa, H Ochi, JI Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 225 (1-2) 27 - 31 0022-510X 2004/10 [Peer-reviewed]
     Scientific journal 
    Objectives: To investigate the frequency of allergic disorders in myasthenia gravis (MG) patients and characterize the features of MG associated with allergic disorders. Methods: Frequencies of past and present common allergic disorders in 160 MG patients who visited the Department of Neurology, Kyushu University Hospital from April 2000 to July 2003 and in 81 neurological normal controls were studied. Results: Among various allergic disorders, the frequency of allergic conjunctivitis (AC) was significantly higher in MG patients (39/160, 24.4%,p(corr)=0.0112), especially with MG without thymoma (36/123, 29.3%,p(corr)=0.0016), in comparison to the controls (6/81, 7.4%). MG patients with AC showed a significantly higher rate of seronegative MG (43.6% vs. 17.4%, p=0.008) and a higher tendency of ocular MG (43.6% vs. 28.1%, p=0.071). Moreover, MG with AC had significantly lower anti-acetylcholine receptor antibody titers (median 6.8 nmol/l vs. median 23.6 nmol/l, p=0.0359) as well as a lower rate of coexisting thymoma (7.7% vs. 17.4%, p=0.016). The incidence of myasthenic crisis was also lower in MG with AC than without AC, yet the difference was not significant (7.7% vs. 15.7%). Conclusion: There was a significant association of AC with MG especially for ocular or seronegative MG in cases without thymoma. (C) 2004 Elsevier B.V. All rights reserved.
  • HF Ochi, M Feng-Jun, M Osoegawa, M Minohara, H Murai, T Taniwaki, JI Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 222 (1-2) 65 - 73 0022-510X 2004/07 [Peer-reviewed]
     Scientific journal 
    To address the immune mechanism sustaining interferon beta (IFNbeta) efficacy in multiple sclerosis (MS), we longitudinally analyzed expressions of IFN-gamma, IL-4, IL-5 and IL-13 in CD4(+) T cells and CD8(+) T cells in 22 Japanese MS patients (16 patients with conventional MS and 6 with opticospinal MS) undergoing IFNbeta using flow cytometry. During the 48-week observation period, five opticospinal MS patients (83%) relapsed compared to only four conventional MS patients (25%); the frequency of relapsed patients was significantly higher in the former (p = 0.046). The effects of IFNbeta on individual cytokines were time-dependent and altered cytokine productions were particularly evident in CD4(+) rather than CD8(+) T cells. A decreased intracellular IFN-gamma/IL-4 ratio in CD4(+) T cells was thus evident soon after the initiation of therapy, and persisted for the entire 1 year follow-up period, regardless of whether or not the patient relapsed (p < 0.01). IFNbeta treatment resulted in a rapid increase in the percentage of IFN-gamma(-) IL-4(+) and IL-13(+) CD4(+) T cells 1 week after the initiation of therapy and high values were sustained for 6 months but declined to the baseline over 1 year. Later, the percentage of IFN-gamma(+) IL-4(-) CD4(+) T cells decreased significantly from weeks 24 through 48 of therapy (p < 0.01). When comparisons with the pretreatment values were made for each subtype of MS, a significant reduction of IFN-gamma(+) IL-4(-) CD4(+) T cell percentages was shown in conventional MS (p < 0.0001), but not in opticospinal MS. Moreover, when such a comparison was made by the presence or absence of relapse during therapy, a significant reduction of IFN-gamma(+) IL-4(-) CD4(+) T cell percentages was observed in MS patients without relapse (p < 0.01). Thus, a reduction of IFN-gamma(+) IL-4(-) CD4(+) T cell percentages in the late phase of therapy is considered important for reducing relapse in conventional MS. When the expression patterns of IFN-gamma IL-4, IL-5 and IL-13 in CD4(+) T cells and CD8(+) T cells were compared between patients with and without relapse during therapy, the only significant difference was an increase in the IL-13(+) CD4(+) T cell percentages in patients with relapse compared to those without (p < 0.05). The results indicate that in CD4(+) T cells IL-4 was preferentially up-regulated in the early course and IFN-gamma was down-regulated in the late phase of IFNbeta therapy. The net effect of IFNbeta on the immune balance was entirely toward type 2 immune deviation, possibly contributing to its beneficial effects on MS. (C) 2004 Elsevier B.V. All rights reserved.
  • A Watanabe, M Kawajiri, K Ikezoe, M Osoegawa, H Murai, H Ochi, T Taniwaki, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 221 (1-2) 95 - 97 0022-510X 2004/06 [Peer-reviewed]
     Scientific journal 
    Two adult females developed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and psoriasis. Both showed chronic progressive paraparesis and sharply demarcated erythematous scaling plaques on their extremities and trunk. One patient had polymyositis while in the other anti-thyroid antibodies, antinuclear antibodies and SS-A antibody, all autoantibodies, were positive. Both patients were treated by intramuscular injections of interferon-alpha for 2 to 4 weeks, resulting in amelioration of paraparesis. After the therapy psoriasis and polymyositis markedly improved in one patient without any additional therapy, while in the other simultaneous use of topical corticosteroids was effective. This is the first report to describe occurrences of psoriasis in HAM/TSP patients. Although there are several reports indicating interferon-a induces or exacerbates psoriasis, our experience suggests that psoriasis associated with HAM/TSP can be successfully managed even during interferon-a therapy. (C) 2004 Elsevier B.V. All rights reserved.
  • M Osoegawa, M Niino, H Ochi, S Kikuchi, H Murai, T Fukazawa, M Minohara, K Tashiro, J Kira
    JOURNAL OF NEUROIMMUNOLOGY 150 (1-2) 150 - 156 0165-5728 2004/05 [Peer-reviewed]
     Scientific journal 
    We evaluated the association of the plasma platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphism (G(994)-->T) and PAF-AH activity with susceptibility and severity of multiple sclerosis (MS) in Japanese. DNA was collected from 216 patients with clinically definite MS (65 opticospinal MS (OS-MS) and 151 conventional MS (C-MS)) and from 213 healthy controls. The missense mutation G(994)-->T that disrupts the PAF-AH activity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No statistically significant difference in the frequency of genotypes and alleles of the plasma PAF-AH polymorphism was observed among OS-MS patients, C-MS patients and healthy controls. However, the missense mutation tended to be associated with the severity of OS-MS, especially in females (GT/TT genotypes; 51.7% in female rapidly progressive OS-MS vs. 26.6% in female controls, p = 0.0870). Moreover, PAF-AH activities were significantly lower in MS than in controls, irrespective of clinical subtypes, among those carrying the identical polymorphism in terms of nucleotide position 994 of the PAF-AH gene. These findings suggest that the PAF-AH gene missense mutation has no relation to either susceptibility or severity of C-MS, yet its activity is down-regulated, and that the mutation has no relation with susceptibility of OS-MS, yet it may confer the severity of female OS-MS. (C) 2004 Elsevier B.V. All rights reserved.
  • [Neurosyphilis accompanied by Charcot spine].
    Himeno E, Murai H, Ochi H, Kawajiri M, Taniwaki T, Kira J
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 93 (5) 1006 - 1008 0021-5384 2004/05 [Peer-reviewed]
  • T Yamada, Y Ohyagi, N Shinnoh, H Kikuchi, M Osoegawa, H Ochi, J Kira, H Furuya
    JOURNAL OF THE NEUROLOGICAL SCIENCES 218 (1-2) 91 - 97 0022-510X 2004/03 [Peer-reviewed]
     Scientific journal 
    Bone marrow transplantation (BMT) is accepted as an efficient therapy for X-linked adrenoleukodystrophy (ALD). To clarify the mechanisms of this treatment, we examined the effects of hematopoietic cell transplantation (HCT) in an ATP-binding cassette, subfamily D, member 1 (ABCD1) knock out mice and co-culture of ALD patient fibroblasts with normal cells. We treated ABCD I knock out mice with HCT using lacZ-transgenic mice as donors, which enabled us to detect donor-derived cells. We also examined the effects of co-culturing a normal microglia cell line (N9) with ALD fibroblasts. beta-Galactosidase (beta-GAL) activity was higher in spleen, lung and kidney than in liver, brain and spinal cord of the recipient ABCD1 knock out mice. HCT reduced the accumulation of very long chain fatty acid (VLCFA) in those tissues. The reduction of the VLCFA ratio was significant in spleen and lung; tissues with higher beta-GAL activity. ABCD1 was detectable in spleen from HCT mice. Co-culture of ALD fibroblasts with normal fibroblast cells reduced VLCFA accumulation in ALD cells. This effect was not observed when the cells were co-cultured while separated by a filter membrane. Our data suggest that supplying normal cells for ABCD1 knockout mouse by HCT corrects metabolic abnormalities in ALD tissues through a cell-mediated process. The correction requires direct cell-to-cell contact for recovering normal cell function. (C) 2003 Elsevier B.V. All rights reserved.
  • Anterior horn cell involvement in myelitis with atopic diathesis (atopic myelitis).
    Tokunaga H, Osoegawa M, Murai H, Ochi H, Minohara M, Taniwaki T, Kira J
    Fukuoka igaku zasshi = Hukuoka acta medica 95 (2) 36 - 43 0016-254X 2004/02 [Peer-reviewed]
  • H Ochi, M Osoegawa, H Murai, M Minohara, T Taniwaki, J Kira
    INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY 134 (1) 41 - 48 1018-2438 2004 [Peer-reviewed]
     Scientific journal 
    Background: Superantigens are considered to exacerbate autoimmune inflammation through the expansion of autoreactive T cells; however, the immune response to bacterial superantigens has not been extensively studied in any type of myelitis. We recently reported the occurrence of a distinct type of myelitis in patients with atopic diathesis, which in a recent nationwide survey was reported to be widespread in Japan. The aim of this study was to investigate the presence of IgE antibodies to bacterial superantigens and the proportion of IL-13- or IL-5-producing CD4+ or CD8+ T cells in patients with myelitis and atopic diathesis. Methods: Twenty-four myelitic patients with and 12 myelitic patients without hyperlgEemia, 28 patients with multiple sclerosis (MS) and 34 healthy controls were enrolled in this study. IgE antibodies to staphylococcal enterotoxins A ( SEA) and B (SEB) in sera were measured using a liquid-phase enzyme immunoassay, and the intracellular production of IL-5 and IL-13 in peripheral blood CD4+ and CD8+ T cells was measured by flow cytometry. Results: The myelitic patients with hyperlgEemia showed significantly higher positive rates of serum SEA/SEB-specific IgE antibodies (41.7 and 62.5%, respectively) than the healthy controls (5.9 and 8.8%), patients with MS (0 and 21.4%) and those with normolgEemic myelitis (0 and 0%). Moreover, IL-13- producing CD4(+) T cells and CD8(+) T cells increased significantly in the myelitic patients with hyperlgEemia compared to the controls, while IL-5-producing CD4(+) or CD8+ T cells did not. Conclusions: The IgE response to staphylococcal superantigens is heightened in myelitic patients with atopic diathesis, which might contribute to increases in IL-13- producing T cells and thus the development of myelitis. Copyright (C) 2004 S. Karger AG, Basel.
  • [Interferon beta treatment in multiple sclerosis].
    Ochi H
    Nihon rinsho. Japanese journal of clinical medicine 61 (8) 1367 - 1373 0047-1852 2003/08 [Peer-reviewed]
  • M Osoegawa, H Ochi, M Minohara, H Murai, F Umehara, H Furuya, T Yamada, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 209 (1-2) 5 - 11 0022-510X 2003/05 [Peer-reviewed]
     Scientific journal 
    We recently reported the occurrence of myelitis in patients with atopic disorders and its pathology to be eosinophilic inflammation. Because similar cases have been reported, we conducted a nationwide epidemiological survey (NES) of myelitis with atopy in Japan. We compared the clinicolaboratory features of the 30 NES cases with the 49 cases at Kyushu University Hospital (KU). Although the NES cases were distributed throughout Japan, the NES and KU cases shared common characteristics. We therefore combined all of the cases identified. The average onset age was 35.8 +/- 13.4 years, and the male/female ratio was 1:0.65. The onset mode was subacute/chronic in half the patients, and stepwise progression or symptom fluctuation was frequent (69.6%). The most common lesion site was determined clinically and by MRI to be the cervical cord, and paresthesia and/or dysesthesia were the most common symptoms initially (74.7%) and throughout the entire course (83.5%). Cerebrospinal fluid (CSF) abnormalities were infrequent and mild. These findings suggest that myelitis associated with atopy has mild but prolonged symptoms and occurs throughout Japan. (C) 2002 Elsevier Science B.V. All rights reserved.
  • M Osoegawa, H Ochi, H Kikuchi, S Shirabe, T Nagashima, T Tsumoto, Y Tamura, K Yamabe, H Takahashi, T Iwaki, J Kira
    ACTA NEUROPATHOLOGICA 105 (3) 289 - 295 0001-6322 2003/03 [Peer-reviewed]
     Scientific journal 
    Histologically proven eosinophilic myelitis has rarely been reported except in connection with parasitism. To clarify its clinicopathological features, we conducted a nationwide survey of biopsy-proven eosinophilic myelitis of unknown cause throughout Japan. Six such cases were collected and studied immunologically and pathologically. All were young to middle-aged men. All showed a protracted and fluctuating course with mild disability for 3-25 (mean 12.5) months before biopsy. Magnetic resonance imaging revealed localized lesions of T2-high and T1-iso signal intensity with a partial gadolinium enhancement in all cases. Cerebrospinal fluid (CSF) examinations were completely normal except for modest pleocytosis in two cases. Eosinophilia was present in the peripheral blood in two cases but was absent from the CSF of all cases. In spite of the chronic nature of the disease, spinal cord pathology revealed very active lesions with marked cell infiltration consisting mainly of CD8(+) T cells and varying numbers of eosinophils in the perivascular areas and the parenchyma. Both the myelin and axons were severely disrupted in all cases. Moreover, cosinophil cationic protein (ECP), an activated eosinophil product, was heavily deposited in the tissues. All but one case had hyperIgEemia and mite antigen-specific IgE in the sera, and two had accompanying atopic disorders. The present study thus revealed idiopathic eosinophilic myelitis to be a localized and persistent inflammation of the spinal cord. with distinct clinicopathological features, that has a possible link to atopic diathesis.
  • Juvenile muscular atrophy of distal upper extremity associated with airway allergy: Two cases successfully treated by plasma exchange
    H Ochi, H Murai, M Osoegawa, M Minohara, S Inaba, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 206 (1) 109 - 114 0022-510X 2003/01 [Peer-reviewed]
     Scientific journal 
    Juvenile muscular atrophy of the distal upper extremity (JMADUE) is postulated to be a type of flexion myelopathy. However, patients with typical clinical features of JMADUE but without evidence of flexion myelopathy have been reported. We recently reported a significant association of, JMADUE with airway allergy. Here we report the successful treatment by plasma exchange (PE) of two patients with both airway allergy and JMADUE without evidence of flexion myelopathy. Patient 1 had a 5-year history of allergic rhinitis and high titers of mite antigen-specific IgE, and patient 2 had an 8-year history of pollinosis and high titers of cedar pollen-specific IgE. Both patients noted progressive distal muscle atrophy and weakness of the upper extremities: patient I for 3 months and patient 2 for 3 years. Neurologically, both showed asymmetric intrinsic hand muscle atrophy, oblique atrophy of the forearm muscles, and weakness and contraction fasciculation (minipolymyoclonus) of these muscles without any sensory impairment. Neither had any evidence of flexion myelopathy on magnetic resonance imaging (MRI) in a flexed position. Both were subjected to PE three times. Soon after the PEs, both showed improvement of distal muscle weakness of the upper extremities and marked reduction of contraction fasciculation of the forearm muscles. Patient I showed marked reduction in ongoing denervation potentials in the distal muscles on needle electromyography, while patient 2 showed marked improvement of F wave persistence of bilateral median and ulnar nerves. Serum total and allergen-specific IgE decreased after PEs in both patients. PE was thus considered to be effective in these two patients having JMADUE without evidence of flexion myelopathy. These observations may suggest the involvement of an immune-mediated process in the neural damage of JMADUE without evidence of flexion myelopathy, especially in patients with atopic diathesis, and may support the notion that JMADUE is etiologically heterogeneous. (C) 2002 Elsevier Science B.V. All rights reserved.
  • A patient with delayed posthypoxic demyelination: a case report of hyperbaric oxygen treatment
    S Miura, Y Ohyagi, M Ohno, Inoue, I, H Ochi, H Murai, H Furuya, T Yamada, J Kira
    CLINICAL NEUROLOGY AND NEUROSURGERY 104 (4) 311 - 314 0303-8467 2002/09 [Peer-reviewed]
     Scientific journal 
    A 62-year-old man who developed akinetic mutism with delayed white matter demyelination after hypoxia was treated with hyperbaric oxygen (HBO). HBO in the subacute period markedly improved the patient's activity in daily life, cognitive function and organization on EEG. H-1-MRS showed a recovery of aerobic metabolism of the neurons. However, dementia and cerebral atrophy slowly progressed despite HBO treatment. Thus, HBO had a beneficial effect on the activity of depressed neurons but did not improve the prognosis. (C) 2002 Elsevier Science B.V. All rights reserved.
  • Increased IL-13 but not IL-5 production by CD4-positive T cells and CD8-positive T cells in multiple sclerosis during relapse phase
    H Ochi, M Osoegawa, XM Wu, M Minohara, Horiuchi, I, H Murai, H Furuya, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 201 (1-2) 45 - 51 0022-510X 2002/09 [Peer-reviewed]
     Scientific journal 
    In the present study, we flow cytometrically analyzed the intracellular production of interleukin (IL)-5 and IL-13 in peripheral blood CD4(+) and CD8(+) T cells from patients with multiple sclerosis (MS), human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and healthy controls. IL-13-producing T cells were significantly increased in both T cell subsets in MS at relapse, markedly in the conventional form of MS and modestly in the optocospinal form of MS, and returned to normal at remission. However, IL-5-producing T cells did not vary regardless of clinical phase or type. HAM/TSP showed no significant change in the number of IL-5- and IL-13-producing cells. A distinct profile of IL-13 and IL-5 production by disease and by phase of MS suggests an active involvement of these type 2 cytokines in central nervous system (CNS) inflammation. (C) 2002 Elsevier Science B.V. All rights reserved.
  • Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto's encephalopathy
    H Ochi, Horiuchi, I, N Araki, T Toda, T Araki, K Sato, H Murai, M Osoegawa, T Yamada, K Okamura, T Ogino, K Mizumoto, H Yamashita, H Saya, J Kira
    FEBS LETTERS 528 (1-3) 197 - 202 0014-5793 2002/09 [Peer-reviewed]
     Scientific journal 
    Hashimoto's encepbalopathy (HE) is a rare autoimmune disease associated with Hashimoto's thyroiditis (HT). To identify the HE-related autoantigens, we developed a human brain proteome map using two-dimensional electrophoresis and applied it to the immuno-screening of brain proteins that react with autoantibodies in HE patients. After sequential MALDI-TOF-MASS analysis, immuno-positive spots of 48 kDa (pI 7.3-7.8) detected from HE patient sera were identified as a novel autoirnmuno-antigen, alpha-enolase, harboring several modifications. Specific high reaetivities against human a-enolase were significant in HE patients with excellent corticosteroid sensitivity, whereas the patients with fair or poor sensitivity to the corticosteroid treatment showed less reactivities than cut-off level. Although a few HT patients showed faint reactions to a-enolase, 95% of HT patients, patients with other neurological disorders, and healthy subjects tested were all negative. These results suggest that the detection of anti-alpha-enolase antibody is useful for defining HE-related pathology, and this proteomic strategy is a powerful method for identifying autoantigens of various central nervous system diseases with unknown autoimmune etiologies. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
  • High incidence of subclinical peripheral neuropathy in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis): an electrophysiological study.
    Osoegawa M, Ochi H, Yamada T, Horiuchi I, Murai H, Furuya H, Tobimatsu S, Kira J
    Internal medicine (Tokyo, Japan) 41 (9) 684 - 691 0918-2918 2002/09 [Peer-reviewed]
  • Suppression of Cdc2 dephosphorylation at the tyrosine 15 residue during nitrosourea-induced G(2)M phase arrest in glioblastoma cell lines
    A Nakamizo, T Inamura, S Inoha, T Amano, H Ochi, K Ikezaki, M Fukui
    JOURNAL OF NEURO-ONCOLOGY 59 (1) 7 - 13 0167-594X 2002/08 [Peer-reviewed]
     Scientific journal 
    We examined the mechanism of action of nitrosoureas as represented by 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) with respect to p53 and the G(2)M cell cycle checkpoint using two glioblastoma cell lines: U251MG and U373MG, with mutated p53. At log-phase cell growth, fresh medium containing ACNU (final concentration, 3, 10, or 30 mug/ml) was added. After 24 h of incubation, cells were harvested for flow cytometric or Western analysis. In both lines, cell numbers in the G0/G1 phase decreased with ACNU treatment. Cells accumulated in G(2)M and S phases, and the peak was shifted from G(2)M to the S phase in a concentration-dependent manner. In both cell lines, the amount of Cdc2 protein phosphorylated at the tyrosine 15 residue was increased 2- to 6-fold by treatment with ACNU compared with untreated control cells. Expression of cyclin B protein was suppressed in cells treated with 30 mug/ml ACNU. Protein abundance for total Cdc2, Cdc2 phosphorylated at the threonine 161 residue, Wee 1, Myt 1, Chk 1, and 14-3-3sigma was not affected by treatment with ACNU in either cell line. We suggest that a low concentration of ACNU should be used with adjuvant therapies that act upon cells in the G(2)M phase. A high concentration of ACNU should be used with adjuvant therapies that act upon cells in the S phase.
  • Paradoxical lateralization of parasagittal spikes revealed by back averaging of EEG and MEG in a case with epilepsia partialis continua
    A Oishi, S Tobimatsu, H Ochi, Y Ohyagi, T Kubota, T Taniwaki, T Yamamoto, H Furuya, J Kira
    JOURNAL OF THE NEUROLOGICAL SCIENCES 193 (2) 151 - 155 0022-510X 2002/01 [Peer-reviewed]
     Scientific journal 
    Our aim was to localize the generator site of parasagittal epileptiform discharges in a patient with epilepsia partialis continua (EPC) in the right leg. We examined a 32-year-old woman with EPC whose conventional EEG did not show any epileptic discharge. We performed the jerk-locked back averaging (JLA) of EEG and magnetoencephalography (MEG) to localize the dipole source of sharp transients. The myoclonic discharges in the right soleus muscle were used as a trigger pulse. JLA revealed consistent EEG and MEG sharp transients that coincided consistently and constantly preceded the myoclonic jerks. JLA of EEG demonstrated sharp waves paradoxically distributed over the vertex and right hemisphere. However, the estimated dipoles of MEG were localized in a restricted area in the primary leg motor area in the left hemisphere, which was closely located in the abnormal lesion on the brain MRI. JLA of MEG is considered to be a useful noninvasive method for localizing the epileptogenic area in EPC even when paradoxical lateralization of electroencephalographic discharges was noted. (C) 2002 Elsevier Science B.V. All rights reserved.

MISC

  • Masaaki Niino, Takashi Ohashi, Hirofumi Ochi, Ichiro Nakashima, Yuko Shimizu, Makoto Matsui  Clinical and Experimental Neuroimmunology  9-  (4)  235  -243  2018/11  Book review  
    © 2018 Japanese Society for Neuroimmunology A multicenter, randomized, double-blind, placebo-controlled, efficacy and safety study of BG00012 in participants from the Asia–Pacific region and other countries with relapsing–remitting multiple sclerosis (APEX), including Japan, established the efficacy of dimethyl fumarate (DMF) in preventing relapses and disease progression in patients with multiple sclerosis (MS). Consequently, in December 2016, DMF was approved as the second oral disease-modifying drug for MS in Japan. However, the new Japanese guidelines for MS and neuromyelitis optica published in 2017 did not include DMF. Later, after the committee discussed a guideline for DMF, a supplement of the new guidelines for MS and neuromyelitis optica, which included DMF, was published in June 2018; this supplement comprised the following four clinical questions: (i) is DMF effective in preventing relapses in patients with MS?; (ii) is DMF effective in preventing disease progression in patients with MS?; (iii) how to use DMF?; and (iv) what adverse events does DMF possibly cause? Furthermore, the supplement comprised answers to the questions and comments. Overall, this supplement is anticipated to contribute toward the treatment of Japanese MS patients with DMF.
  • 越智博文  Neuroimmunology  23-  (1)  69  -69  2018/09
  • 【神経難病と創薬】 多発性硬化症の創薬の展望
    越智 博文, 藤原 一男  医薬ジャーナル  54-  (7)  1661  -1667  2018/07  
    <文献概要>米国食品医薬品局(FDA)によって承認された多発性硬化症(multiple sclerosis:MS)の疾患修飾薬は,ジェネリック医薬品を含めると既に16種類に上る。一部には進行型MSに対する有効性が確認された薬剤もあるが,そのほとんどは再発寛解型MSに対して有効であっても,進行型MSに対しては無効ないしは十分な治療効果が期待できない。その理由として,再発寛解型MSと進行型MSでは背景にある免疫病理学的な病態が異なることが指摘されている。進行型MSの病態解明は端緒についたばかりであるが,現在,進行型MSに対する新規治療薬や髄鞘再生医薬の開発が進んでいる。
  • 越智博文, 藤原一男  医薬ジャーナル  54-  (7)  1661‐1667  2018/07
  • 越智博文  週刊日本医事新報  (4912)  28‐34  2018/06
  • 【多発性硬化症の診断・治療の進展】 多発性硬化症の病態・疫学
    越智 博文  日本医事新報  (4912)  28  -34  2018/06  
    <Point>▼多発性硬化症(MS)は中枢神経白質を侵す慢性炎症性脱髄疾患である▼若年成人に好発する。世界的に患者数・有病率ともに増加傾向で、特に若年女性での増加が著しい▼中枢神経髄鞘抗原に対するT細胞が介在する自己免疫疾患と考えられているが、真の原因は不明である▼脱髄に伴う中枢神経症候が再発と寛解を繰り返しながら経過(時間的・空間的多発性)し、しだいに慢性進行性の経過となることが多い▼障害は身体機能のみならず高次脳機能にも及び、日常生活や社会生活が大きく制限されることも少なくない(著者抄録)
  • 岡田陽子, 千崎健佑, 越智雅之, 越智博文, 伊賀瀬道也, 大八木保政  Neurosonology  31-  (Supplement)  76  -76  2018/06
  • 尾原麻耶, 松本清香, 田原康玄, 白岡朗, 岡田陽子, 越智雅之, 越智博文, 伊賀瀬道也, 小原克彦, 大八木保政  日本老年医学会雑誌  55-  (Suppl.)  111  -111  2018/05
  • 越智雅之, 白岡朗, 松本清香, 千崎健佑, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  日本老年医学会雑誌  55-  (Suppl.)  158  -158  2018/05
  • 越智博文  Pharma Medica  36-  (3)  45‐51  -51  2018/03
  • 越智博文  日本アフェレシス学会雑誌  37-  (Supplement)  73  2018
  • 越智博文  日本神経学会学術大会プログラム・抄録集  59th-  251  2018
  • 坂井研一, 川井元晴, 鳥居剛, 花山耕三, 三ツ井貴夫, 越智博文, 高橋美枝, 峠哲男, 阿部康二, 下田光太郎  スモンに関する調査研究 平成29年度 総括・分担研究報告書  72‐77  2018
  • 越智雅之, 白岡朗, 松本清香, 千崎健佑, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  日本神経学会学術大会プログラム・抄録集  59th-  395  2018
  • 白岡朗, 越智博文, 越智雅之, 松本清香, 尾原麻耶, 岡田陽子, 伊賀瀬道也, 大八木保政  日本神経学会学術大会プログラム・抄録集  59th-  473  2018
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  8-  (4)  287  -288  2017/11  Report scientific journal  
    Many types of genetic variations have evolved in humans as a result of evolutionary adaptation to malaria. Steri et al. reported that a genetic variant that provided resistance to Plasmodium falciparum or Plasmodium vivax malaria might have increased the susceptibility to multiple sclerosis among Sardinians.
  • 日本人RRMS患者に対するフマル酸ジメチルの安全性 APEX part1+2study 72週中間成績より
    越智 博文, 新野 正明, 鬼塚 康弘, 平松 且稔, 長谷 昌知, Yun Jang, Lin Yan, 鳥居 慎一  神経治療学  34-  (6)  S190  -S190  2017/11
  • 越智博文  Dementia Japan  31-  (4)  539  2017/10
  • 自己免疫性神経疾患と認知症 多発性硬化症と認知症
    越智 博文  Dementia Japan  31-  (4)  539  -539  2017/10
  • 進行型MS克服のための病態理解と挑戦 進行型MSの治療の最新情報
    越智 博文  神経免疫学  22-  (1)  61  -61  2017/10
  • MS・NMO2 多発性硬化症患者におけるCD40/TLR刺激下末梢血B細胞サブセットのIL-10産生の解析
    岡田 洋一郎, 越智 博文, 藤井 ちひろ, 端 祐一郎, 濱谷 美緒, 芦田 真士, 日下 博文, 水野 敏樹, 高橋 良輔, 近藤 誉之  神経免疫学  22-  (1)  115  -115  2017/10
  • 日本人RRMS患者に対する24週間のフマル酸ジメチル療法の安全性 APEX part 1研究(Safety of dimethyl fumarate in Japanese RRMS patients for 24 weeks: the APEX part 1 study)
    越智 博文, 新野 正明, 鬼塚 康弘, 平松 且稔, 長谷 昌知, Jang Yun, Yan Ling, 鳥居 慎一  神経免疫学  22-  (1)  148  -148  2017/10
  • 日本人RRMS患者におけるフマル酸ジメチル療法の安全性 APEX part 2研究の中間分析(Safety of dimethyl fumalate in Japanese RRMS patients: Interim analysis of the APEX part 2 study)
    越智 博文, 新野 正明, 鬼塚 康弘, 平松 且稔, 長谷 昌知, Jang Yun, Yan Ling, 鳥居 慎一  神経免疫学  22-  (1)  150  -150  2017/10
  • 濱谷美緒, 山下博史, 山下博史, 越智博文, 芦田真士, 端祐一郎, 岡田洋一郎, 藤井ちひろ, 水野敏樹, 高橋良輔, 近藤誉之  Neuroimmunology  22-  (1)  122  -122  2017/10
  • 端祐一郎, 岡田洋一郎, 濱谷美緒, 芦田真士, 藤井ちひろ, 越智博文, 水野敏樹, 高橋良輔, 池田昭夫, 近藤誉之  Neuroimmunology  22-  (1)  128  -128  2017/10
  • 越智雅之, 白岡朗, 松本清香, 加藤丈陽, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  日本老年医学会雑誌  54-  (4)  627‐628(J‐STAGE)  -628  2017/10
  • 大八木保政, 加藤丈陽, 越智雅之, 白岡朗, 松本清香, 雑賀徹, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也  日本老年医学会雑誌  54-  (4)  628‐629(J‐STAGE)  -629  2017/10
  • 抗神経抗体陽性のてんかんと扁桃体腫大を伴うてんかんの免疫学的解析(Immunological state of epilepsy with anti-neuronal antibody and epilepsy with amygdala enlargement)
    端 祐一郎, 坂本 光弘, 十川 純平, 岡田 洋一郎, 藤井 ちひろ, 濱谷 美緒, 芦田 真士, 越智 博文, 中川 正法, 水野 敏樹, 下竹 昭寛, 松本 理器, 高橋 良輔, 池田 昭夫, 近藤 誉之  てんかん研究  35-  (2)  434  -434  2017/09
  • 伊賀瀬道也, 岡田陽子, 尾原麻耶, 加藤丈陽, 白岡朗, 松本清香, 千崎健佑, 越智雅之, 越智博文, 大八木保政  愛媛医学  36-  (2)  77‐81  -81  2017/06  
    われわれは2006年から開始している抗加齢ドックのデータを基にした加齢に伴う認知症発症リスクに対する検討を行っている。根本的な治療薬のない現在「可能な限り早期に認知症および認知症予備群を発見して適切な生活への介入を行うこと」が求められている。近年、正常加齢と認知症の境界領域と考えられる軽度認知障害(Mild cognitive impairment:MCI)が注目されており、MCIと関連するファクターを探索し、それらに対する介入を試みることは臨床面からも有用であると考えられる。MCIは65歳以上の高齢者の約5%にみられ、年間約10-15%がADに移行することが知られている。われわれはMCIの診断には「MCI screen」を用いている。このテストを用いて2017年に2本の論文がpublishされた。論文1)高齢者のMCI診断におけるSAFの有用性 AGEs(Accumulation of advanced glycation endproducts)の蓄積と認知症の発症の関連性が示唆されている。しかしながら認知症発症の前段階と考えられるMCI(mild cognitive impairment)とAGEsの関連を検討した報告は少ない。そこで本研究では健常高齢者におけるMCIと皮膚に蓄積したAGEsとの関連について検討した。本研究から非侵襲的なAGEs測定法であるSAFは健常者におけるMCIスクリーニングを行う上で有用なバイオマーカーである可能性が示唆された。論文2)高齢者におけるエクオール産生能と認知機能低下の関連 豆イソフラボン摂取による心血管疾患の予防効果が知られているが、認知機能予防効果については愚論のあるところである。個人差がある原因として大豆イソフラボンの代謝産物である「エクオール」(Equol)産生能の有無が関連している可能性がある。本研究結果からは1)エクオール産生者では有意にタッチパネル式認知機能検査の点数が高い2)エクオール非産生者では有意にMCIの存在率が高い、ことからエクオール産生者では認知機能の予防効果がある可能性がある。(著者抄録)
  • 越智雅之, 白岡朗, 松本清香, 加藤丈陽, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  日本老年医学会雑誌  54-  (Suppl.)  202  -202  2017/05
  • 越智博文  日本アフェレシス学会雑誌  36-  (1)  3‐8  2017/02
  • 【自己免疫性脳炎に対するアフェレシス】 多発性硬化症
    越智 博文  日本アフェレシス学会雑誌  36-  (1)  3  -8  2017/02  
    多発性硬化症(MS)急性増悪期の治療としてのアフェレシスについて概説した。MSの急性増悪期では、できるだけ早期に炎症を沈静化し、神経症候の回復を促進させることが重要である。そのため、できるだけ早期にステロイドパルス療法を行うことが求められる。しかし、ステロイドパルス療法の効果が不十分である症例や合併症や副作用のために副腎皮質ステロイド薬の投与ができない症例に対しては、速やかにアフェレシスを行うことが推奨される。治療法としては、血漿交換療法(PE)、二重濾過血漿分離交換療法(DFPP)、トリプトファンカラムによる免疫吸着療法(IAPP)のいずれかを選択する。
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  8-  33  -39  2017/01  Book review  
    Multiple sclerosis (MS) is a complex immune-mediated disease characterized by recurrent demyelinating episodes of the central nervous system, which typically occurs in young adults. It is the most common disabling neurological disease of young people however, pediatric MS, defined as onset of MS before the age of 18 years, has been increasingly recognized worldwide in the past two decades. Pediatric MS might represent up to 10% of all patients with MS. As in adults, the diagnosis of pediatric MS rests on the demonstration of dissemination of lesions in both space and time, and the exclusion of alternative diagnosis. However, it can be more difficult to distinguish MS accurately from other conditions in children compared with the adult population, because there is considerable overlapping of clinical and magnetic resonance imaging features between pediatric MS and other acquired demyelinating disorders of the central nervous system. In view of therapeutic strategies, although interferon-beta and glatiramer acetate are the most commonly used disease-modifying drugs for pediatric MS so far, none of the current available disease-modifying drugs were tested in pediatric MS by randomized controlled trials, and thus there is limited information regarding the efficacy and safety. The present review article describes the epidemiology, clinical features, consensus definition and treatment strategy of pediatric MS.
  • 岡田洋一郎, 越智博文, 藤井ちひろ, 端祐一郎, 濱谷美緒, 芦田真士, 日下博文, 水野敏樹, 高橋良, 近藤誉之  Neuroimmunology  22-  (1)  115  2017
  • 越智博文  Neuroimmunology  22-  (1)  61  2017
  • 坂井研一, 川井元晴, 鳥居剛, 花山耕三, 三ツ井貴夫, 越智博文, 高橋美枝, 峠哲男, 阿部康二, 下田光太郎  スモンに関する調査研究 平成28年度 総括・分担研究報告書  74‐78  2017
  • 越智雅之, 松本清香, 千崎健佑, 加藤丈陽, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  日本神経学会学術大会プログラム・抄録集  57th-  (Suppl.)  574  -S411  2016/12
  • 尾原麻耶, 加藤丈陽, 田原康玄, 岡田陽子, 越智雅之, 松本清香, 千崎健佑, 越智博文, 伊賀瀬道也, 小原克彦, 大八木保政  日本神経学会学術大会プログラム・抄録集  57th-  (Suppl.)  437  -S288  2016/12
  • 藤井ちひろ, 岡田洋一郎, 端祐一郎, 中川正法, 松本禎之, 高橋良輔, 越智博文, 近藤誉之, 水野敏樹  日本神経学会学術大会プログラム・抄録集  57th-  (Suppl.)  624  -S459  2016/12
  • 端祐一郎, 坂本光弘, 十川純平, 岡田洋一郎, 藤井ちひろ, 越智博文, 中川正法, 水野敏樹, 下竹昭寛, 松本理器, 漆谷真, 池田昭夫, 高橋良輔, 近藤誉之  日本神経学会学術大会プログラム・抄録集  57th-  (Suppl.)  626  -S461  2016/12
  • 岡田洋一郎, 藤井ちひろ, 端祐一郎, 越智博文, 中川正法, 水野敏樹, 松本禎之, 漆谷真, 高橋良輔, 近藤誉之, 近藤誉之  日本神経学会学術大会プログラム・抄録集  57th-  (Suppl.)  624  -S459  2016/12
  • 石川羽津江, 越智雅之, 松本清香, 千崎健佑, 加藤丈陽, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  日本老年医学会雑誌  53-  (4)  463(J‐STAGE)  -463  2016/10
  • 雑賀徹, 加藤丈陽, 白岡朗, 松本清香, 千崎健佑, 尾原麻耶, 岡田陽子, 越智雅之, 越智博文, 伊賀瀬道也, 大八木保政  臨床神経学(Web)  56-  (10)  717(J‐STAGE)  -717  2016/10
  • 松本清香, 越智雅之, 白岡朗, 加藤丈陽, 雑賀徹, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  Neuroimmunology  21-  (1)  156  -156  2016/09
  • 越智雅之, 白岡朗, 松本清香, 加藤丈陽, 雑賀徹, 岡田陽子, 尾原麻耶, 越智博文, 伊賀瀬道也, 大八木保政  Neuroimmunology  21-  (1)  103  -103  2016/09
  • 岡田洋一郎, 藤井ちひろ, 端祐一郎, 越智博文, 中川正法, 松本禎之, 漆谷真, 高橋良輔, 近藤誉之, 近藤誉之  Neuroimmunology  21-  (1)  119  -119  2016/09
  • 越智博文  月刊神経内科  85-  (2)  163‐167  -167  2016/08
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  7-  (3)  260  -271  2016/08  Book review  
    Multiple sclerosis (MS) is a complex immune-mediated disease of the central nervous system. Traditionally, it has been considered to be mediated primarily by T cells, and the contribution of B�cells in the pathogenesis of MS has long been debated. However, clinical trial results of B-cell depletion therapies have established the central role of B�cells in the pathogenesis of MS and their contribution to MS disease activity through antibody-independent pro-inflammatory function. One of the monoclonal antibodies targeting the B-cell surface antigen CD20, ocrelizumab, has shown efficacy in both relapsing–remitting and primary progressive MS in phase�III clinical trials, whereas the potential role of B�cells in compartmentalized central nervous system inflammation that might underlie tissue injury in progressive MS still continues to be debated. Furthermore, the failure of atacicept, which targets the B-cell survival factors and a proliferation-inducing ligand, suggests that B�cells potentially have a dual role in the pathogenesis of MS, and the role of B�cells in MS is highly complex. In the present review, we discuss the role of B�cells in the pathogenesis of MS and review available clinical efficacy data on B-cell-targeted therapy in MS.
  • 越智博文  最新医学  71-  (6)  1149‐1158  -1158  2016/06  
    米国食品医薬品局によって承認された多発性硬化症(MS)に対する疾患修飾薬は,すでに13種類に上る.また,再発寛解型MSを対象とした第III相臨床試験の結果が公表されている薬剤には,ダクリズマブやラキニモド,オクレリズマブがある.さらに,フィンゴリモドより高い受容体サブタイプ選択性を持つ新たな薬剤の開発も進んでいる.今後は,オクレリズマブやビオチンのような進行型MSに対する治療薬の開発も期待されている.(著者抄録)
  • 【多発性硬化症と視神経脊髄炎-基礎から臨床まで-】 多発性硬化症の疾患修飾薬の活用 Induction TherapyとEscalation Therapyをどう使い分けるか
    中辻 裕司, 越智 博文, 吉良 潤一  最新医学  71-  (6)  1083  -1100  2016/06
  • Koji Shinoda, Hiroyuki Murai, Noriko Akutagawa, Hirofumi Ochi, Jun-Ichi Kira  Clinical and Experimental Neuroimmunology  7-  (2)  183  -184  2016/05  Book review
  • 【多発性硬化症の病因・病態から診断・治療まで】 多発性硬化症の病因と病態
    越智 博文  神経治療学  33-  (3)  466  -469  2016/05
  • 高度の脱髄性ニューロパチーと両足関節の変形を合併した筋強直性ジストロフィーの一例
    千崎 健佑, 岡田 陽子, 越智 博文, 松本 清香, 加藤 丈陽, 越智 雅之, 伊賀瀬 道也, 大八木 保政  臨床神経学  56-  (3)  231  -231  2016/03
  • 坂井研一, 川井元晴, 鳥居剛, 花山耕三, 三ツ井貴夫, 越智博文, 高橋美枝, 峠哲男, 阿部康二, 下田光太郎  スモンに関する調査研究 平成27年度総括・分担研究報告書  69‐74  2016
  • 越智博文  神経治療学(Web)  33-  (3)  466‐469(J‐STAGE)  2016
  • 越智博文  月刊メディカル・サイエンス・ダイジェスト  41-  (14)  548  -551  2015/12  
    多発性硬化症(Multiple Sclerosis:MS)の診断は、時間的および空間的多発性を臨床症候によって証明し、かつ他の疾患を十分に除外することが基本である。しかし、近年のMRIの普及によって無症候性病変の鋭敏な検出が可能となり、臨床的には初発の段階であっても、時間的および空間的多発性に関する一定のMRI基準を満たせばMSと診断できるようになった。このため従来よりも早期の診断が可能となり、早期に治療を開始できるようになった。しかし、現在のMRI基準は欧米の典型的なMS患者のデータを基に作成されているため、遺伝的や環境的要因の異なるわが国の患者に適用した場合の妥当性については、今後の検証が必要である。アドヒアランスを良好に保つことは治療効果に直結する重要な問題である。治療の目的と期待される治療効果、予測される有害事象とその対処法など、治療開始前から繰り返し説明することが重要である。(著者抄録)
  • 岡田洋一郎, 藤井ちひろ, 端祐一郎, 越智博文, 中川正法, 水野敏樹, 松本禎之, 漆谷真, 高橋良輔, 近藤誉之, 近藤誉之  Neuroimmunology  20-  (1)  94  -S321  2015/12
  • 藤井ちひろ, 岡田洋一郎, 端祐一郎, 中川正法, 松本禎之, 高橋良輔, 越智博文, 近藤誉之, 水野敏樹  日本神経学会学術大会プログラム・抄録集  56th-  (Suppl.)  384  -S261  2015/12
  • 越智雅之, 越智博文, 七條千佳, 加藤丈陽, 岡田陽子, 尾原麻耶, 永井勅久, 伊賀瀬道也, 小原克彦  日本神経学会学術大会プログラム・抄録集  56th-  (Suppl.)  384  -S261  2015/12
  • 越智博文  神経治療学  32-  (5)  702  2015/09
  • MS基礎 多発性硬化症患者におけるTLR/CD40刺激によるB細胞サイトカインの解析
    岡田 洋一郎, 藤井 ちひろ, 端 祐一郎, 越智 博文, 中川 正法, 水野 敏樹, 松本 禎之, 漆谷 真, 高橋 良輔, 近藤 誉之  神経免疫学  20-  (1)  94  -94  2015/09
  • MS基礎 フィンゴリモド治療下多発性硬化症の再発時における炎症性サイトカイン産生細胞頻度の検討
    藤井 ちひろ, 岡田 洋一郎, 端 祐一郎, 中川 正法, 松本 禎之, 高橋 良輔, 越智 博文, 近藤 誉之, 水野 敏樹  神経免疫学  20-  (1)  95  -95  2015/09
  • 【免疫性神経疾患-基礎・臨床研究の最新知見-】 免疫性中枢神経疾患 多発性硬化症(MS) 多発性硬化症の治療 新規治療薬の開発状況
    越智 博文  日本臨床  73-  (増刊7 免疫性神経疾患)  221  -227  2015/09
  • 多発性硬化症の病因・病態から診断・治療まで 多発性硬化症の病因と病態
    越智 博文  神経治療学  32-  (5)  702  -702  2015/09
  • 藤井ちひろ, 岡田洋一郎, 端祐一郎, 中川正法, 松本禎之, 高橋良輔, 越智博文, 近藤誉之, 水野敏樹  Neuroimmunology  20-  (1)  95  2015
  • 坂井研一, 川井元晴, 鳥居剛, 花山耕三, 三ツ井貴夫, 越智博文, 高橋美枝, 峠哲男, 阿部康二, 下田光太郎  スモンに関する調査研究 平成26年度総括・分担研究報告書  67  -71  2015
  • 岡田洋一郎, 藤井ちひろ, 端祐一郎, 越智博文, 中川正法, 水野敏樹, 松本禎之, 漆谷真, 高橋良輔, 近藤誉之  日本神経学会学術大会プログラム・抄録集  56th-  448  2015
  • 岡田陽子, 加藤丈陽, 山下泰治, 越智雅之, 永井勅久, 越智博文, 伊賀瀬道也, 羽藤高明, 小原克彦  脳卒中  37-  (1)  36-40 (J-STAGE)  -40  2015/01  
    症例は53歳男性、右上肢の感覚障害と脱力発作を繰り返し、脳梗塞を指摘され入院した。本態性血小板血症と診断され、JAK2遺伝子変異を有した。入院後も右上肢の脱力症状を繰り返し、急性期には低用量アスピリンと抗凝固薬の併用を要したが、骨髄抑制療法の効果発現後にはアスピリンが中止可能となった。JAK2遺伝子変異陽性例では、血小板数や機能の異常のみでなく、凝固因子の異常や血管内皮の機能障害を認めることが指摘されており、高齢、血栓塞栓症の既往などに加えて、本態性血小板血症における血栓塞栓症のリスク因子の一つであるといわれる。本症例はアテローム血栓性脳梗塞に類似した臨床経過を呈し、血管内皮の機能障害を背景とした血管壁の血栓易形成性が、脳梗塞発症に関連している可能性を推測した。本疾患における最適な抗血栓療法を検討する上で貴重な症例であると考えられ、報告する。(著者抄録)
  • 千崎健佑, 岡田陽子, 松本清香, 越智雅之, 越智博文, 伊賀瀬道也, 大八木保政  日本栓子検出と治療学会プログラム・抄録集  18th-  86  2015
  • 七條千佳, 岡田陽子, 加藤丈陽, 山下泰治, 越智雅之, 越智博文, 伊賀瀬道也, 小原克彦  臨床神経学(Web)  55-  (1)  50(J‐STAGE)  -50  2015/01
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  5-  (1)  6  -15  2014/12  Book review  
    Multiple sclerosis (MS) is a complex immune mediated disease of the central nervous system. It is characterized by inflammatory and neurodegenerative processes that result in neuroaxonal damage. Its etiology is still unknown, and its pathogenesis is only partly understood. There have been major advances in the treatment of MS in the past two decades, and a wide range of immunomodulagtory and immunosuppressive therapies have been used for the management of MS. More recently, there has been a growing interest in immunotherapeutic strategies with selective actions that target biological molecules involved in MS pathogenesis. Thus, better understanding of the immunopathogenesis of MS is believed to result in the development of more efficacious treatment. However, in contrast to the successful introduced therapies, such as natalizumab and alemtuzumab, there have been a remarkable number of therapeutic failures as well. Despite the convincing immunological concepts and promising results from animal models of MS, some drugs showed no clinical efficacy or even worsened the disease. Clinical trial results of molecular targeted therapy that shed light on the improving understanding of the immunopathogenesis of MS are discussed in the present review. These trials include monoclonal antibodies against leukocyte differentiation molecules (anti-CD3 and anti-CD4 antibodies), tumor necrosis factor-α neutralization, targeting the interleukin (IL)-12/IL-23 pathways, immune cell-depleting ant-CD52 monoclonal antibody and targeting IL-2 receptor signaling.
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  5-  (1)  2  -3  2014/12
  • 藤井ちひろ, 岡田洋一郎, 木村公俊, 笠井高士, 徳田隆彦, 中川正法, 松本禎之, 高橋良輔, 越智博文, 近藤誉之, 水野敏樹  日本神経学会学術大会プログラム・抄録集  55th-  (Suppl.)  632  -S151  2014/12
  • 【多発性硬化症と視神経脊髄炎】 治療 再発抑制の治療 多発性硬化症におけるインターフェロンベータの使用
    越智 博文  日本臨床  72-  (11)  2003  -2009  2014/11
  • 多発性硬化症の環境因子をめぐって
    吉良 潤一, 越智 博文, 新野 正明  MS Frontier: 多発性硬化症の先端情報誌  3-  (2)  71  -77  2014/11
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  5-  (3)  279  -280  2014/10  Book review  
    The autoimmune regulator (Aire) is a key transcription factor that promotes promiscuous expression of tissue-specific antigens by medullary thymic epithelial cells (mTEC), and mediates a role in negative selection of autoreactive T cells. Tagawa et al. reported the central role of Aire in establishing central tolerance to myelin antigen, and its deficiency resulted in spontaneous autoreactivity against central nervous system myelin antigen. The role of mTEC-dependent tolerance in multiple sclerosis must await further study.
  • 越智博文  Brain Nerve  66-  (10)  1201  -1209  2014/10  
    多発性硬化症では最大70%の患者に認知機能障害が認められる。注意や情報処理速度,作業記憶の障害が認められやすく,患者の生活の質や社会生活に大きく影響することも少なくない。多発性硬化症患者の認知機能を正しく評価し,認知機能障害に対して介入することは極めて重要であるが,有効性が確立された対処法がないのが現状である。治療研究の発展が期待される。(著者抄録)
  • 越智博文  老年期認知症研究会誌(Web)  19-  (8)  112-115 (WEB ONLY)  -115  2014/09
  • 藤井ちひろ, 岡田洋一郎, 木村公俊, 中川正法, 松本禎之, 高橋良輔, 越智博文, 近藤誉之, 水野敏樹  Neuroimmunology  19-  (1)  139  -139  2014/09
  • 越智博文  Brain Med  26-  (2)  167  -173  2014/07  
    多発性硬化症治療では、急性増悪期の治療と並んで、早期より再発予防治療を開始し、将来の身体機能障害の進行を抑制することが重要である。この目的で使用される薬剤は病態修飾薬と呼ばれ、わが国では2種類の注射剤のインターフェロンβ製剤と、経口カプセル剤であるフィンゴリモドの合計2剤形3種類の薬剤が使用されている。また、2014年3月には注射剤であるナタリズマブが製策販売承認を受け、現在発売に向けての準備が進んでいる。それぞれの薬剤の特徴を理解したうえで、患者のライフスタイルに合った治療法を選択することが重要である。(著者抄録)
  • Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Katsuhisa Masaki, Shinya Sato, Yuji Kawano, Hirofumi Ochi, Jun Ichi Kira  PLoS ONE  9-  2014/04  
    Background: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. Methodology: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (.0.658). Principal Findings: CSF IgG abnormality was found in 59 of 94 (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1&1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1&0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. Conclusions: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1&1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1&0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative MS, respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status. © 2014 Yoshimura et al.
  • 多発性硬化症を含む神経疾患を診療するために
    越智 博文, 深澤 俊行  Pharma Medica  32-  (1)  57  -60  2014/01
  • 越智博文  日本神経学会学術大会プログラム・抄録集  55th-  333  2014
  • 篠原奈子, 越智雅之, 加藤丈陽, 山下泰治, 尾原麻耶, 岡田陽子, 永井勅久, 越智博文, 伊賀瀬道也, 小原克彦, 三木哲郎  臨床神経学  54-  (1)  74  -74  2014/01
  • Hirofumi Ochi  Clinical and Experimental Neuroimmunology  4-  (3)  251  -252  2013/12  Book review  
    The role of B cells in multiple sclerosis pathogenesis is being increasingly recognized. Although B cells certainly play a critical role in adaptive immunity through antibody secretion, what has received a lot of attention in multiple sclerosis is the antibody-independent B cell functions. © 2013 Japanese Society for Neuroimmunology.
  • Jun-Ichi Kira, Ryo Yamasaki, Satoshi Yoshimura, Toshiyuki Fukazawa, Kazumasa Yokoyama, Kazuo Fujihara, Mieko Ogino, Takanori Yokota, Katsuichi Miyamoto, Masaaki Niino, Kyoichi Nomura, Ryo Tomioka, Masami Tanaka, Izumi Kawachi, Takashi Ohashi, Kenichi Kaida, Makoto Matsui, Yuji Nakatsuji, Hirofumi Ochi, Hikoaki Fukaura, Takashi Kanda, Akiko Nagaishi, Kanae Togo, Hidehiro Mizusawa, Yuji Kawano  Clinical and Experimental Neuroimmunology  4-  (3)  305  -317  2013/12  
    Objectives There has been no large-scale study of methylprednisolone pulse therapy in Asian patients with multiple sclerosis (MS) or neuromyelitis optica (NMO), despite it being widely used for acute relapse. We aimed to clarify treatment response of MS and NMO patients to methylprednisolone pulse therapy and post-pulse oral corticosteroids in real clinical practice in a multicenter study in Japan. Methods Investigators at 28 institutions collected changes in neurological symptoms/signs and Expanded Disability Status Scale (EDSS) scores before and within 1 week of completion of methylprednisolone pulse therapy carried out in 2010, and after post-pulse oral corticosteroids therapy, by retrospective review of medical records. Results In 345 patients (95.1% of all registered patients), 457 series of methylprednisolone pulse therapy were carried out for treatment of acute relapse. EDSS scores improved by 0.8 ± 1.1 (mean ± SD) after the first course. The second and third courses also produced sufficient improvements (by 0.7 and 0.6, respectively), but much smaller improvements were observed thereafter. The target neurological symptoms and signs improved in 79.5% of patients. Improvement rates were 5-20% lower after a course of pulse therapy than after a series of pulse therapy. A half dose (500 mg/day) produced less improvement than a standard dose (1000 mg/day 65.9 vs 79.5%). During post-pulse oral corticosteroid therapy, EDSS scores decreased by 0.6 ± 0.9. No significant adverse effects were observed. Conclusions Methylprednisolone pulse therapy is beneficial in nearly 80% of Japanese MS and NMO patients, and EDSS score improvements after therapy are compatible with those in Western MS patients. © 2013 Japanese Society for Neuroimmunology.
  • 岡田陽子, 小原克彦, 尾原麻耶, 多喜田理絵, 越智雅之, 永井勅久, 越智博文, 伊賀瀬道也, 三木哲郎  日本神経学会学術大会プログラム・抄録集  54th-  (12)  299  -1417  2013/12
  • 越智博文  神経治療学  30-  (6)  742  -750  2013/11
  • 糸山泰人, 藤原一男, 宮本勝一, 清水優子, 中島一郎, 田中正美, 越智博文  神経治療学  30-  (6)  775,777-794  2013/11
  • 日本神経治療学会 標準的神経治療 視神経脊髄炎(NMO)
    糸山 泰人, 藤原 一男, 宮本 勝一, 清水 優子, 中島 一郎, 田中 正美, 越智 博文, 日本神経治療学会治療指針作成委員会  神経治療学  30-  (6)  775  -794  2013/11
  • 抗AQP4抗体陽性脊髄炎患者の画像所見からみた機能予後の推定
    山下 泰治, 山下 夏美, 篠原 奈子, 加藤 丈陽, 岡田 陽子, 越智 雅之, 三木 哲郎, 越智 博文  神経免疫学  18-  (1)  114  -114  2013/11
  • 越智博文  MS Front  2-  (1)  50  2013/05
  • 日常診療におけるMSの機能評価をどのように行うべきか? 総合機能評価
    越智 博文  MS Frontier: 多発性硬化症の先端情報誌  2-  (1)  50  -50  2013/05
  • 岡田陽子, 篠原奈子, 山下泰治, 越智雅之, 永井勅久, 越智博文, 伊賀瀬道也, 小原克彦, 三木哲郎  臨床神経学  53-  (5)  384  -384  2013/05
  • 各種難病の最新治療情報 多発性硬化症の新規治療薬と具体的事例
    越智 博文  難病と在宅ケア  18-  (11)  44  -48  2013/02
  • 越智博文  月刊難病と在宅ケア  18-  (11)  44  -48  2013/02
  • Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Tomomi Yonekawa, Katsuhisa Masaki, Shinya Sato, Yuji Kawano, Jun-Ichi Kira  JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY  84-  (1)  29  -34  2013/01  
    Objective To clarify whether genetic and common infectious backgrounds are distinct, according to anti-aquaporin 4 (AQP4) antibody status in Japanese patients with neuromyelitis optica (NMO). Methods We analysed human leucocyte antigen (HLA)-DRB1 and HLA-DPB1 alleles, and IgG antibodies against Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus and Epstein-Barr virus nuclear antigen (EBNA) in 116 patients with NMO, including 39 patients with neuromyelitis optica spectrum disorder (NMOSD), 145 multiple sclerosis (MS) patients and 367 unrelated healthy controls. 77 NMO/NMOSD patients were seropositive for AQP4 antibody while 39 were seronegative. Results Compared with healthy controls, NMO/NMOSD patients showed a significantly lower frequency of DRB1*0901 and significantly higher frequencies of DRB1*1602 and DPB1*0501, which conferred susceptibility to anti-AQP4 antibody positive NMO/NMOSD, but not antibody negative NMO/NMOSD. DRB1*0901 was a common protective allele, irrespective of the presence or absence of anti-AQP4 antibody. Anti-H pylori and anti-C pneumoniae antibodies were more commonly detected in anti-AQP4 antibody positive NMO/NMOSD patients than healthy controls. Antibody negative NMO/NMOSD patients did not differ from healthy controls regarding the presence of these antibodies. The presence or absence of antibodies against varicella zoster virus and EBNA did not vary among the groups. The frequencies of antibodies against these four pathogens were not significantly different between MS patients and healthy controls. Conclusions Our results suggest that HLA-DRB1*1602 and DPB1*0501 alleles and H pylori and Chlamydia pneumonia infection are risk factors only for anti-AQP4 antibody positive NMO/NMOSD but not for anti-AQP4 antibody negative NMO/NMOSD.
  • 篠原奈子, 岡田陽子, 山下泰治, 越智雅之, 永井勅久, 多喜田理絵, 越智博文, 伊賀瀬道也, 小原克彦, 三木哲郎  臨床神経学  53-  (1)  69  -69  2013/01
  • 小原克彦, 城戸美和子, 宮脇さおり, 田原康玄, 永井勅久, 越智雅之, 岡田陽子, 多喜田理絵, 篠原奈子, 越智博文, 伊賀瀬道也, 三木哲郎  日本神経学会学術大会プログラム・抄録集  53rd-  (12)  253  -1422  2012/12
  • 越智雅之, 小原克彦, 田原康玄, 多喜田理絵, 永井勅久, 篠原奈子, 岡田陽子, 越智博文, 伊賀瀬道也, 三木哲郎  日本神経学会学術大会プログラム・抄録集  53rd-  (12)  394  -1556  2012/12
  • 越智博文  MS Front  1-  (1)  14  -23  2012/11
  • STATE OF THE ART 多発性硬化症の早期治療開始の重要性
    越智 博文  MS Frontier: 多発性硬化症の先端情報誌  1-  (1)  14  -23  2012/11
  • 篠原奈子, 岡田陽子, 山下泰治, 越智雅之, 多喜田理絵, 永井勅久, 越智博文, 伊賀瀬道也, 小原克彦, 三木哲郎  日本神経免疫学会学術集会抄録集  24th-  104  -104  2012/09
  • 越智雅之, 篠原奈子, 山下泰治, 岡田陽子, 永井勅久, 多喜田理絵, 越智博文, 伊賀瀬道也, 小原克彦, 三木哲郎  日本神経免疫学会学術集会抄録集  24th-  94  -94  2012/09
  • 多発性硬化症の新しい治療薬フィンゴリモドについて エキスパートによる処方経験を中心に
    糸山 泰人, 越智 博文, 齋田 孝彦, 河内 泉, 新野 正明  Pharma Medica  30-  (7)  116  -124  2012/07
  • 越智博文  月刊神経内科  76-  (6)  554  -558  2012/06
  • 多発性硬化症の新しい治療戦略 フィンゴリモドへの期待
    近藤 誉之, 越智 博文, 松井 大, 宮本 勝一  Therapeutic Research  33-  (6)  783  -791  2012/06
  • 岡田陽子, 篠原奈子, 越智雅之, 多喜田理絵, 永井勅久, 伊賀瀬道也, 越智博文, 小原克彦, 三木哲郎  臨床神経学  52-  (6)  454  -454  2012/06
  • 多発性硬化症の新しい治療戦略 フィンゴリモドへの期待
    太田 宏平, 越智 博文, 佐藤 滋, 蕨 陽子, 岡本 智子, 大橋 高志  Pharma Medica  30-  (5)  73  -80  2012/05
  • 村上翔, 岡田陽子, 越智博文, 篠原奈子, 越智雅之, 多喜田理絵, 永井勅久, 伊賀瀬道也, 小原克彦, 三木哲郎  臨床神経学  52-  (5)  383  -383  2012/05
  • Taiji Yamashita, Hirohumi Ochi, Naoaki Ishizu, Yasumasa Ohyagi, Jun-ichi Kira, Yasuo Mori, Sou Arahata, Koichi Ohshima  Clinical Neurology  52-  (4)  227  -233  2012  
    We report a 45-year-old man with myositis associated with clonal expansion of γδ T cells. He was referred to our hospital because of slowly progressive (over 10 years) muscle weakness. On neurological examination, weakness and muscle atrophy were noted in the proximal upper and lower limbs. The level of creatinine kinase (CK) was 1,436U/L. Neutropenia and monoclonal gammopathy were found in the peripheral blood. Flow cytometric analysis of peripheral blood and bone marrow revealed proliferation of CD3+CD4-CD8+ and CD3+CD4-CD8- γδ T cells, and Southern blotting demonstrated a clonally rearranged T-cell receptor Jγ gene in peripheral blood and bone marrow. A biopsy of the right quadriceps muscle showed variations in muscle fiber size, and endomysial mononuclear cell infiltration. The expression of MHC Class I antigen was increased on the surfaces of most of muscle fibers, and TCRδ1 positive-lymphocytes invaded nonnecrotic muscle fiber. After starting treatment with cyclosporin A and steroids, his muscle weakness gradually ameliorated, the CK level decreased and neutrophils increased. Although reports of myositis associated with clonal expansion of γδ T cells are extremely rare, the present case suggests that γδ T cells might play a role in mediating myositis. © 2012, Societas Neurologica Japonica. All rights reserved.
  • 越智博文  内科  105-  (5)  778  -782  2010/05  
    NMO-IgG(抗AQP4抗体)の発見により、MSとNMOの免疫病態が異なる疾患であることが明らかとなった。両者の鑑別には、両者の臨床的特徴を理解するとともに抗AQP4抗体の測定が有用である。NMOの急性増悪期にはステロイドパルス療法が行われるが、無効であったり効果が不十分な場合には血液浄化療法が有効である。NMOでは再発予防治療が重要で、経口prednisolone単独やazathioprineとの併用療法が行われることが多い。これらの治療が無効の場合は、さらに強力な免疫抑制治療が行われる。(著者抄録)
  • 多発性硬化症末梢免疫担当細胞におけるbrain-derived neurtrophic factorの産生能
    吉村 怜, 越智 博文, 吉良 潤一  臨床神経学  49-  (12)  1191  -1191  2009/12
  • 土井光, 松下拓也, 磯部紀子, 松岡健, 三野原元澄, 越智博文, 吉良潤一  日本神経学会総会プログラム・抄録集  50th-  (12)  292  -1130  2009/12
  • 内科医のための脳疾患講座 多発性硬化症の治療 新しいガイドラインをふまえて
    越智 博文  Brain Medical  21-  (2)  186  -191  2009/06
  • 菅原三和, 越智博文, 石津尚明, 立石貴久, 河村信利, 大八木保政, 吉良潤一  臨床神経学  49-  (5)  308  -308  2009/05
  • 広岡さとみ, 石津尚明, 立石貴久, 越智博文, 大八木保政, 吉良潤一  臨床神経学  49-  (5)  310  -310  2009/05
  • K. Hagiwara, H. Ochi, S. Suzuki, Y. Shimizu, T. Tokuda, H. Murai, H. Shigeto, Y. Ohyagi, M. Iwata, T. Iwaki, J. -i. Kira  NEUROLOGY  72-  (15)  1358  -1360  2009/04  Others
  • 岩島とも, 越智博文, 石津尚明, 河村信利, 大八木保政, 吉良潤一  臨床神経学  49-  (4)  206  -206  2009/04
  • 山下泰治, 越智博文, 石津尚明, 大八木保政, 荒畑創, 吉良潤一  臨床神経学  49-  (4)  208  -208  2009/04
  • H. Doi, T. Matsushita, N. Isobe, T. Matsuoka, M. Minohara, H. Ochi, J. I. Kira  MULTIPLE SCLEROSIS  15-  (3)  304  -310  2009/03  
    Objective Because Asian patients with opticospinal multiple sclerosis (OSMS) frequently have anti-aquaporin-4 (AQP4) antibody, complement-mediated disruption of astrocyte foot processes is proposed but not yet proven. We aimed to clarify whether complement consumption occurs at relapse in anti-AQP4 antibody-positive patients. Methods We analyzed serum CH50, C3, C4, and C-reactive protein (CRP) levels and their relation to clinical phases in 118 MS patients with or without anti-AQP4 antibody. Serum CH50 levels were higher in 24 patients with anti-AQP4 antibody than in 39 OSMS and 54 conventional form of MS (CMS) patients without anti-AQP4 antibody at relapse (P(corr) < 0.05) but not in remission. The frequency of hypercomplementemia at relapse was also higher in anti-AQP4 antibody-positive patients than in anti-AQP4 antibody-negative CMS patients (70.4% vs 29.0%, P(corr) < 0.05). C3 and C4 levels did not differ significantly among the three groups at relapse. In patients with anti-AQP4 antibody, the coexistence of hypercomplementemia and high CRP values was more common at relapse than in the remission phase (36.0% vs 10.5%, P < 0.05). In patients with extensive central nervous system lesions, hypercomplementemia was significantly more common in anti-AQP4 antibody-positive patients than anti-AQP4 antibody-negative ones (88.9% vs 16.7%, P < 0.01). We consider that hypercomplementemia in anti-AQP4 antibody-positive patients may reflect a systemic inflammatory reaction at relapse. Multiple Sclerosis 2009; 15: 304-310. http://msj.sagepub.com
  • 土井光, 松下拓也, 磯部紀子, 松岡健, 三野原元澄, 越智博文, 吉良潤一  Neuroimmunology  17-  (1)  52  -52  2009/03
  • 吉村怜, 越智博文, 三野原元澄, 吉良潤一  Neuroimmunol  17-  (1)  47  -47  2009/03
  • T. Matsushita, T. Matsuoka, N. Isobe, Y. Kawano, M. Minohara, N. Shi, Y. Nishimura, H. Ochi, J. Kira  TISSUE ANTIGENS  73-  (2)  171  -176  2009/02  
    There are two subtypes of multiple sclerosis (MS) in Asians: the opticospinal (OSMS) form that shows a selective involvement of the optic nerve and the spinal cord and the conventional (CMS) form that has disseminated lesions in the central nervous system including the cerebrum, cerebellum and brainstem. Both show distinct human leukocyte antigen (HLA) class II associations. OSMS has similar features to the relapsing form of neuromyelitis optica (NMO) in Western populations. Recently, it was shown that antibodies to aquaporin-4 (AQP4) are specifically detected in NMO patients and in some Japanese patients with OSMS or recurrent optic neuritis or myelitis. To clarify the immunogenetic background of anti-AQP4 antibody production, we studied HLA-DRB1 and -DPB1 gene polymorphisms in anti-AQP4 antibody-positive and -negative patients with idiopathic demyelinating diseases, such as MS, recurrent optic neuritis and recurrent myelitis. The phenotypic frequency of the HLA-DPB1*0501 allele was significantly increased in anti-AQP4 antibody-positive patients (89.5%, odds ratio = 4.8; 95% confidence interval = 1.6-14.3, n = 38, P(corr) = 0.032) compared with controls (64.0%, n = 125) but not in either anti-AQP4 antibody-negative OSMS (75.0%, n = 32) or CMS (69.2%, n = 52) patients. There was no significant correlation between any HLA-DRB1 allele and the existence of anti-AQP4 antibody. These findings suggest that the emergence of anti-AQP4 antibody is reinforced by the presence of the HLA-DPB1*0501 allele in Japanese.
  • M. Osoegawa, J. Kira, T. Fukazawa, K. Fujihara, S. Kikuchi, M. Matsui, T. Kohriyama, G. Sobue, T. Yamamura, Y. Itoyama, T. Saida, K. Sakata, H. Ochi, T. Matsuoka  MULTIPLE SCLEROSIS  15-  (2)  159  -173  2009/02  
    Background There are two distinct phenotypes of multiple sclerosis (MS) in Asians, manifesting as optic-spinal (OSMS) and conventional (CMS) forms. In Japan, four nationwide surveys of MS have been conducted. The first three were in 1972, 1982, and 1989, and we performed the fourth in 2004. Results The recent survey showed six main findings as follows: (1) a four-fold increase in the estimated number of clinically definite patients with MS in 2003 (9900; crude MS prevalence, 7.7/100,000) compared with 1972; (2) a shift in the peak age at onset from early 30s in 1989 to early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement in clinically definite patients with MS; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after subdivision of the mainland (30-45 degrees North) into northern and southern parts at 37 degrees N, northern-born northern residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern residents (southern patients); (6) among northern patients, the absolute numbers of patients with CMS and those with Barkhof brain lesions rapidly increased with advancing birth year. Conclusions These findings suggest that MS phenotypes are drastically altered by environmental factors, such as latitude and "Westernization." Multiple Sclerosis 2009; 15: 159-173. http://msj.sagepub.com
  • 吉村怜, 越智博文, 吉良潤一  日本神経学会総会プログラム・抄録集  50th-  355  2009
  • 越智博文, 吉良潤一, 大八木保政  食品を介したダイオキシン類等の人体への影響の把握とその治療法の開発等に関する研究 平成18-20年度 総合研究報告書 平成20年度 総括・分担研究報告書  107  -110  2009
  • 吉良潤一, 土井光, 松下拓也, 磯部紀子, 松岡健, 三野原元澄, 越智博文  免疫性神経疾患に関する調査研究班 平成20年度 総括・分担研究報告書  77  -78  2009
  • 小児医学最近の進歩 多発性硬化症における免疫制御
    越智 博文, 吉良 潤一  小児科  49-  (13)  1993  -1999  2008/12
  • 土井光, 松岡健, 松下拓也, 三之原元澄, 越智博文, 河野祐治, 大八木保政, 吉良潤一  日本神経学会総会プログラム・抄録集  49th-  (12)  154  -1075  2008/12
  • 山崎亮, 越智博文, 田中正人, 吉良潤一  日本神経学会総会プログラム・抄録集  49th-  (12)  125  -1048  2008/12
  • 越智博文, 吉良潤一  日本神経学会総会プログラム・抄録集  49th-  (12)  326  -1236  2008/12
  • 吉村怜, 越智博文, 吉良潤一  日本神経学会総会プログラム・抄録集  49th-  (12)  304  -1217  2008/12
  • 越智博文, 吉良潤一  小児科  49-  (13)  1993  -1999  2008/12
  • 特異な自律性呼吸調節障害を認めた一例
    山下 泰治, 越智 博文, 河村 信利, 石津 尚明, 大八木 保政, 吉良 潤一  日本自律神経学会総会プログラム・抄録集  61回-  192  -192  2008/11
  • 菅原三和, 田中正人, 石津尚明, 越智博文, 吉良潤一  日本頭痛学会誌  35-  (2)  120  -120  2008/11
  • M. Tanaka, T. Matsushita, T. Tateishi, H. Ochi, Y. Kawano, F. -J. Mei, M. Minohara, H. Murai, J. -i. Kira  NEUROLOGY  71-  (13)  974  -981  2008/09  
    Background: We reported the emergence of a distinct myelitis in patients with atopic diathesis (atopic myelitis [AM]) by a nationwide survey throughout Japan. Similar cases have recently been reported in Caucasians. Pathologic studies of biopsied spinal cord specimens revealed chronic active inflammation with eosinophilic infiltration. Objective: To clarify the cytokine/chemokine alterations in CSF from patients with AM in comparison to other causes of myelitis. Methods: We measured 27 cytokines, chemokines, and growth factors simultaneously in CSF from 22 patients with AM, 20 with opticospinal multiple sclerosis (OSMS), 11 with HTLV-1 associated myelopathy (HAM), 9 with Sjogren syndrome-related myelitis (SM), and 20 with other noninflammatory neurologic diseases (OND), using a fluorescent bead-based immunoassay. Results: In patients with AM, CCL11 and interleukin (IL)-9 were significantly increased as compared with patients with OND and other myelitis while in patients with OSMS interferon-gamma and granulocyte-colony stimulating factor levels were significantly higher than in patients with OND and other causes of myelitis. Significant increase of IL-17 in comparison to patients with OND was found only in patients with OSMS, irrespective of presence or absence of anti-aquaporin- 4 (AQP4) antibody. In patients with HAM, CXCL10 and CCL5 were higher than in patients with OND and other myelitis. In patients with SM, CCL3 and CCL4 were higher than in patients with OND. In patients with AM, CCL11, IL-9, and IL-1 receptor antagonist (IL-1ra) showed positive correlations with the final Kurtzke Expanded Disability Status Scale scores while IL-1ra and IL-12(p70) had positive correlations with disease duration. Conclusion: Intrathecal upregulation of CCL11 and Th2 cytokines is characteristic of atopic myelitis, which is distinct from interleukin-17/interferon-gamma-related autoimmune condition of opticospinal multiple sclerosis.
  • 磯部紀子, 西口明子, 金ミエ, 立石貴久, 越智博文, 大八木保政, 吉良潤一  Neuroinfection  13-  (2)  92  -92  2008/09
  • 抗アクアポリン4抗体関連神経疾患の病態機序 脊髄炎症性疾患のサイトカイン・ケモカインプロフィール
    田中 正人, 松下 拓也, 松岡 健, 立石 貴久, 河野 祐治, 越智 博文, 吉良 潤一  神経免疫学  16-  (1)  65  -65  2008/04
  • 通常型多発性硬化症の病態機序と治療 多発性硬化症(MS)病態へのbrain derived neurotrophic factor(BDNF)の関与
    吉村 怜, 越智 博文, 松岡 健, 松下 拓也, 河野 祐治, 三野原 元澄, 吉良 潤一  神経免疫学  16-  (1)  81  -81  2008/04
  • 通常型多発性硬化症の病態機序と治療 日本人多発性硬化症患者におけるIFNβ製剤の使用実態に関する全国調査 治療効果に影響を及ぼす因子の検討
    越智 博文, 吉良 潤一  神経免疫学  16-  (1)  82  -82  2008/04
  • 通常型多発性硬化症の病態機序と治療 MS髄液におけるCD4+TNFα+IL2-T細胞サブセット異常
    史 楠, 河野 祐治, 梅 風君, 松岡 健, 三野原 元澄, 越智 博文, 吉良 潤一  神経免疫学  16-  (1)  86  -86  2008/04
  • 田中正人, 松下拓也, 松岡健, 立石貴久, 河野祐治, 越智博文, 吉良潤一  Neuroimmunol  16-  (1)  65  2008/04
  • 吉村怜, 越智博文, 松岡健, 松下拓也, 河野祐治, 三野原元澄, 吉良潤一  Neuroimmunol  16-  (1)  81  2008/04
  • 史楠, 河野祐治, 梅風君, 松岡健, 三野原元澄, 越智博文, 吉良潤一  Neuroimmunol  16-  (1)  86  2008/04
  • 越智博文  月刊メディカル・サイエンス・ダイジェスト  34-  (1)  14  -17  2008/01
  • 【神経と免疫の接点からみた神経難病の病態】 粘膜免疫からみた脱髄 多発性硬化症をモデルとして
    越智 博文  Medical Science Digest  34-  (1)  14  -17  2008/01  
    「経口免疫寛容」とは、古典的には動物にあらかじめ抗原を経口的に投与することにより、その抗原に対する正の免疫応答(細胞増殖や抗体産生など)が抑制される現象として理解される。そのため、食物成分に由来する多種多様な非自己抗原に対して食物アレルギーなどを示さないのは、各抗原に対して「経口免疫寛容」が成立しているからだとされる。最近では、経鼻あるいは経気道的に抗原を投与した場合にも、同様の免疫寛容状態が誘導されることが示されており、「粘膜免疫寛容」と総称されることもある。本稿では、まず腸管免疫と経口免疫寛容について概説し、経口免疫寛容を応用した多発性硬化症(multiple sclerosis:MS)の免疫制御について解説する。(著者抄録)
  • 越智博文, 吉良潤一  免疫性神経疾患に関する調査研究 平成19年度 総括・分担研究報告書  76  -77  2008
  • 越智博文, 三野原元澄, 松下拓也, 松岡健, 河村信利, 吉良潤一  免疫性神経疾患に関する調査研究 平成19年度 総括・分担研究報告書  64  -65  2008
  • 吉良潤一, 田中正人, 立石貴久, 松下拓也, 松岡健, 越智博文  免疫性神経疾患に関する調査研究 平成19年度 総括・分担研究報告書  45  -47  2008
  • 越智博文, 渡邉暁博, 松下拓也, 松岡健, 重藤寛史, 飛松省三, 吉良潤一  免疫性神経疾患に関する調査研究 平成19年度 総括・分担研究報告書  60  -61  2008
  • 越智博文, 吉川弘明, 本村政勝, 藤井義敬, 吉良潤一, 小野寺宏, 荒賀茂, 野村芳子, 村井弘之, 川口直樹, 服部孝道, 渡邊至, 中村好一, 永井正規, 山下夏美  免疫性神経疾患に関する調査研究 平成19年度 総括・分担研究報告書  139  -143  2008
  • 越智博文, 松下拓也, 松岡健, 史楠, 三野原元澄, 河野祐治, 吉良潤一  免疫性神経疾患に関する調査研究 平成19年度 総括・分担研究報告書  58  -59  2008
  • 吉良潤一, 土井光, 松岡健, 松下拓也, 三野原元澄, 越智博文, 河野祐治, 大八木保政  片頭痛に対する画期的治療法の開発に関する研究 平成19年度 総括・分担研究報告書  30  -32  2008
  • 吉良潤一, 田中正人, 河野祐治, 史楠, 小副川学, 越智博文  日本神経学会総会プログラム・抄録集  48th-  (12)  292  -1128  2007/12
  • 小副川学, 越智博文, 坂田清美, 吉良潤一  日本神経学会総会プログラム・抄録集  48th-  (12)  292  -1128  2007/12
  • 立石貴久, 田中正人, 越智博文, 菊池仁志, 吉良潤一  日本神経学会総会プログラム・抄録集  48th-  (12)  218  -1060  2007/12
  • 越智博文, 吉良潤一, WEINER Howard  日本神経学会総会プログラム・抄録集  48th-  (12)  262  -1101  2007/12
  • 萩原綱一, 重藤寛史, 村井弘之, 山下力, 越智博文, 大八木保政, 吉良潤一, 鈴木諭, 岩城徹, 清水優子, 岩田誠, 徳田隆彦  日本神経学会総会プログラム・抄録集  48th-  (12)  344  -1177  2007/12
  • 三野原元澄, 松岡健, 松下拓也, 小副川学, 越智博文, 吉良潤一  日本神経学会総会プログラム・抄録集  48th-  (12)  292  -1128  2007/12
  • 山崎亮, 越智博文, 田中正人, 吉良潤一  日本神経学会総会プログラム・抄録集  48th-  (12)  184  -1029  2007/12
  • 松岡健, 松下拓也, 河野祐治, 小副川学, 越智博文, 吉良潤一  Neuroimmunol  15-  (2)  163  -168  2007/11  
    Clinically definite MS連続113例において抗AQP4抗体と頭部脊髄MRIを評価した。視神経脊髄型(OSMS)で抗AQP4抗体は27.1%、通常型(CMS)で5.6%に認めたが、脳幹脊髄型や対照群では陰性だった。抗体陽性MSは全例女性で、抗体陰性OSMSと同様に抗体陰性CMSに比べて発症年齢が高く、重篤な視神経炎や横断性脊髄炎、長大な脊髄病巣(LESCL)が有意に多かった。LESCLは抗体陽性MSでは主として胸髄灰白質に限局した。一方、抗体陰性OSMSでは頸髄から胸髄に拡がり、灰白質から白質に及んだ。また抗体陽性MSでNMO基準を満たす群は脳病巣やSSA/SSB陽性例が多く、インターフェロンβの効果が乏しい点がLESCLを伴う抗体陰性OSMSと異なった。多変量解析では抗AQP4抗体はLESCLやOSMSには関連がなかった。日本人MSには抗AQP4抗体陽性MSとLESCLを伴う抗体陰性OSMSが存在した。臨床病型と抗AQP4抗体によりLESCLは異なった特徴を呈し、その形成機序はheterogeneousと思われた。(著者抄録)
  • 萩原綱一, 越智博文, 村井弘之, 重藤寛史, 大八木保政, 吉良潤一  日本内科学会雑誌  96-  (8)  1703  -1705  2007/08  
    54歳女、両下肢の痺れを主訴とした。潰瘍性大腸炎(UC)を発症したが治療により寛解状態であった。右前胸部痛と主訴が出現し、入院時、右下肢の筋力低下、両下肢の感覚障害、痙性歩行を認め、脊髄MRIでTh6-7レベルの右後索〜側索にT2延長域を認めた。UCに関連した脊髄炎と診断し、ステロイドパルス療法の後、経口プレドニゾロンを漸減、中止した。筋力の正常化と感覚障害の軽快が得られ、その後も再発なく、6ヵ月後のMRIで病巣の縮小を確認した。
  • 米川智, 越智博文, 村井弘之, 大八木保政, 吉良潤一  臨床神経学  47-  (6)  387  -387  2007/06
  • 山下力, 重藤寛史, 栄信孝, 越智博文, 大八木保政, 吉良潤一  臨床神経学  47-  (6)  387  -387  2007/06
  • 鉾之原敏博, 金森祐治, 越智博文, 谷脇予志秀, 山田猛  月刊神経内科  66-  (5)  477  -479  2007/05  
    Guillain-Barre症候群(GBS)には様々な亜型が存在し、Fisher症候群(FS)、FSとGBSの重複症候群などが含まれる。今回、眼筋麻痺・失調・腱反射消失といったFS様症候と球麻痺症状で発症したが、経過中に四肢筋力低下や呼吸筋麻痺を生じ、最終的にFS/GBSと考えられた症例を経験した。患者は42歳の男性、急性期の血液検査で抗GQ1b抗体と抗GT1a抗体が陽性を示し、両抗体とも症状の改善に伴い陰性化した。FSは通常予後良好とされているが、本例のように病変の範囲が広い場合には重症化しやすいと考えられ、とくに球麻痺を呈する場合には呼吸不全に陥りやすいと思われた。
  • 松岡健, 松下拓也, 小副川学, 河野祐治, 三野原元澄, 越智博文, 吉良潤一  神経治療学  24-  (3)  325  -325  2007/05
  • 小副川学, 越智博文, 坂田清美, 吉良潤一  Neuroimmunol  15-  (1)  97  -97  2007/04
  • 河野祐治, 田中正人, 立石貴久, 史楠, 小副川学, 越智博文, 吉良潤一  Neuroimmunol  15-  (1)  64  -64  2007/04
  • 米川智, 越智博文, 村井弘之, 大八木保政, 吉良潤一  臨床神経学  47-  (4)  197  -197  2007/04
  • 山崎亮, 田中正人, 越智博文, 吉良潤一  Neuroimmunol  15-  (1)  30  -30  2007/04
  • 山下力, 村井弘之, 真崎勝久, 池添浩二, 越智博文, 大八木保政, 吉良潤一, 本村政勝, 白石裕一  臨床神経学  47-  (4)  198  -198  2007/04
  • 松岡健, 松下拓也, 河野祐治, 小副川学, 三野原元澄, 越智博文, 吉良潤一  Neuroimmunol  15-  (1)  50  -50  2007/04
  • 芥川宜子, 村井弘之, 越智博文, 大八木保政, 吉良潤一  Neuroimmunol  15-  (1)  139  -139  2007/04
  • 松岡健, 三野原元澄, 松下拓也, 小副川学, 越智博文, 吉良潤一  Neuroimmunol  15-  (1)  99  -99  2007/04
  • 越智博文, 吉良潤一, HOWARD Weiner  Neuroimmunol  15-  (1)  38  -38  2007/04
  • 萩原綱一, 村井弘之, 小副川学, 越智博文, 大八木保政, 吉良潤一  臨床神経学  47-  (2/3)  128  -128  2007/03
  • 芥川宜子, 村井弘之, 越智博文, 大八木保政, 吉良潤一  臨床神経学  47-  (2/3)  128  -128  2007/03
  • 吉良潤一, 松岡健, 松下拓也, 河野祐治, 小副川学, 三野原元澄, 越智博文  免疫性神経疾患に関する調査研究 平成18年度 総括・分担研究報告書  27  -28  2007
  • 越智博文, 吉良潤一  Curr Insights Neurol Sci  15-  (1)  10  -11  2007/01
  • 村井弘之, 田中正人, 吉良潤一, 河野祐治, 史楠, 小副川学, 越智博文  免疫性神経疾患に関する調査研究 平成18年度 総括・分担研究報告書  79  -80  2007
  • 吉良潤一, 松岡健, 三野原元澄, 松下拓也, 河野祐治, 小副川学, 越智博文  免疫性神経疾患に関する調査研究 平成18年度 総括・分担研究報告書  19  -20  2007
  • 吉良潤一, 菊地誠志, 糸山泰人, 山村隆, 松井真, 郡山達男, 小副川学, 越智博文, 深澤俊行, 藤原一男, 道勇学, 斎田孝彦, 坂田清美, 玉腰暁子, 稲葉裕  免疫性神経疾患に関する調査研究 平成18年度 総括・分担研究報告書  17  -18  2007
  • 2004年MS全国調査結果報告続報 膠原病の合併によるMS病像の違いについて
    越智 博文, 小副川 学, 坂田 清美, 吉良 潤一  臨床神経学  46-  (12)  985  -985  2006/12
  • 小副川学, 越智博文, 坂田清美, 吉良潤一  日本神経学会総会プログラム・抄録集  47th-  (12)  104  -985  2006/12
  • 松瀬大, 村井弘之, 石津尚明, 重藤寛史, 越智博文, 吉良潤一  Neuroinfection  11-  (1)  21  -21  2006/09
  • 米川智, 村井弘之, 越智博文, 大八木保政, 吉良潤一  臨床神経学  46-  (8)  622  -622  2006/08
  • H Ochi, M Abraham, H Ishikawa, D Frenkel, KY Yang, AS Basso, H Wu, ML Chen, R Gandhi, A Miller, R Maron, HL Weiner  NATURE MEDICINE  12-  (6)  627  -635  2006/06  
    A major goal of immunotherapy for autoimmune diseases and transplantation is induction of regulatory T cells that mediate immunologic tolerance. The mucosal immune system is unique, as tolerance is preferentially induced after exposure to antigen, and induction of regulatory T cells is a primary mechanism of oral tolerance. Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We found that orally administered CD3-specific antibody is biologically active in the gut and suppresses autoimmune encephalomyelitis both before induction of disease and at the height of disease. Orally administered CD3-specific antibody induces CD4(+)CD25(-)LAP(+) regulatory T cells that contain latency-associated peptide ( LAP) on their surface and that function in vitro and in vivo through a TGF-beta-dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.
  • 免疫性神経疾患の日本人における特異性 多発性硬化症(MS)2004年全国臨床疫学調査結果報告続報 MRI画像所見からみた日本人MS病像の解析
    小副川 学, 深澤 俊行, 藤原 一男, 松井 真, 郡山 達男, 菊地 誠志, 道勇 学, 糸山 泰人, 斎田 孝彦, 山村 隆, 越智 博文, 坂田 清美, 玉腰 暁子, 稲葉 裕, 吉良 潤一  神経免疫学  14-  (1)  41  -41  2006/03
  • 荒木栄一, 鉾之原敏博, 金森祐治, 越智博文, 谷脇予志秀, 山田猛  脳卒中  28-  (1)  196  -196  2006/03
  • 小副川学, 深沢俊行, 藤原一男, 松井真, 郡山達男, 菊地誠志, 道勇学, 糸山泰人, 斎田孝彦, 山村隆, 越智博文, 坂田清美, 玉腰暁子, 稲葉裕, 吉良潤一  Neuroimmunol  14-  (1)  41  2006/03
  • 多発脳神経麻痺,四肢失調で発症したギラン・バレー症候群(GBS)の1例
    鉾之原 敏博, 金森 祐治, 越智 博文, 谷脇 予志秀, 荒木 栄一, 山田 猛  臨床神経学  46-  (2)  182  -182  2006/02
  • 鉾之原敏博, 金森祐治, 越智博文, 谷脇予志秀, 荒木栄一, 山田猛  臨床神経学  46-  (2)  182  2006/02
  • 吉良潤一, 菊地誠志, 糸山泰人, 山村隆, 松井真, 郡山達男, 小副川学, 越智博文, 深澤俊行, 藤原一男, 道勇学, 斎田孝彦, 坂田清美, 玉腰暁子, 稲葉裕  免疫性神経疾患に関する調査研究 平成17年度 総括・分担研究報告書  151  -152  2006
  • 吉良潤一, 菊地誠志, 糸山泰人, 山村隆, 松井真, 郡山達男, 小副川学, 越智博文, 深澤俊行, 藤原一男, 道勇学, 斎田孝彦, 坂田清美, 玉腰暁子, 稲葉裕  免疫性神経疾患に関する調査研究 平成17年度 総括・分担研究報告書  17  -18  2006
  • 越智博文, 小副川学, 坂田清美, 吉良潤一  日本神経学会総会プログラム・抄録集  47th-  104  2006
  • 2004年多発性硬化症(MS)全国臨床調査成績
    小副川 学, 深澤 俊行, 藤原 一男, 松井 真, 郡山 達男, 菊地 誠志, 道勇 学, 糸山 泰人, 斎田 孝彦, 山村 隆, 越智 博文, 坂田 清美, 玉腰 暁子, 稲葉 裕, 吉良 潤一  臨床神経学  45-  (12)  1013  -1013  2005/12
  • 多発性硬化症(MS)における長期IFNβ-1b投与に伴う末梢血T細胞内サイトカインの変動の意義
    梅 風君, 小副川 学, 越智 博文, 村井 弘之, 吉良 潤一  臨床神経学  45-  (12)  1013  -1013  2005/12
  • JIN Qingyu, 野村拓夫, 越智博文, 谷脇孝恭, 古谷博和, 吉良潤一  臨床神経学  45-  (7)  490  -494  2005/07  
    55歳男.48歳頃より小脳徴候を認めるようになり,53歳時に皮質性小脳萎縮症(CCA)と診断された.タルチレリン水和物療法を開始し経過観察中であったが,睡眠中の呼吸停止,いびきの悪化が指摘されるようになった.終夜ポリグラフを施行した結果,中枢型,閉塞型,混合型,すべての型の無呼吸が確認された.終夜11.6時間の睡眠で合計222回の無呼吸を認め(無呼吸指数17.8),そのうち中枢型無呼吸が188回で,無呼吸指数は16.6であった.その内訳は,中枢型91.7%,閉塞型4.3%,混合型4.0%と,明らかに中枢型優位の無呼吸を示した.無呼吸はいずれも睡眠I,II段階の浅睡眠期に出現しており,レム睡眠の出現率は17.7%と正常で,睡眠リズムは保たれていた.7年の経過で軽度の小脳症候のみで緩徐な経過を呈し,CCAの診断は現時点では妥当と考えられたが,何らかの多系統変性症の過程を捉えている可能性もあることから,今後の注意深い経過観察を要するものと思われた
  • 高倉由佳, 村井弘之, 古谷博和, 越智博文, 吉良潤一  臨床神経学  45-  (5)  346  -350  2005/05  
    74歳女.72歳時より左上肢の進行性筋力低下・筋萎縮を認めるようになった.頸椎症性脊髄根症と診断され前方固定術を施行されたが,左上肢筋力低下は徐々に進行しさらに右上肢の脱力も出現し入院となった.上肢の運動神経伝達速度は正常であったがCMAP振幅は低下し,伝導ブロックは認めず針筋電図ではびまん性に神経原性変化が認められた.以上の所見から,brachial amyotrophic diplegia型の脊髄進行性筋萎縮症と診断した.本症例ではSjoegren症候群の合併が唾液腺造影と唾液腺生検で確認され,ウエスタンブロットにて血清中に約50kDaの脳の蛋白に反応する抗神経抗体が認められた.副腎皮質ステロイド剤パルス療法,血漿交換療法および免疫グロブリン大量静注による免疫療法の施行により,特に後二者が奏効して筋力の著明な改善を認めた.以上より,本症例は神経症状の背景に自己免疫的機序による前角運動ニューロンの障害が推察される極めて貴重な症例であるものと考えられた
  • 多発性硬化症の病型と血漿型PAF-AH/PAF受容体遺伝子多型についての検討
    小副川 学, 宮岸 隆司, 越智 博文, 新野 正明, 中村 一太, 菊地 誠志, 村井 弘之, 深澤 俊行, 三野原 元澄, 田代 邦雄, 吉良 潤一  神経免疫学  13-  (1)  42  -42  2005/03
  • 疫学調査・臨床像からみた日本人MSの特徴 多発性硬化症2004年全国臨床疫学調査結果報告:視神経脊髄型多発性硬化症の現状
    小副川 学, 深澤 俊行, 藤原 一男, 松井 真, 郡山 達男, 菊地 誠志, 道 勇学, 糸山 泰人, 斎田 孝彦, 山村 隆, 越智 博文, 坂田 清美, 玉腰 暁子, 稲葉 裕, 吉良 潤一  神経免疫学  13-  (1)  62  -62  2005/03
  • アトピー素因と神経疾患 アトピー性脊髄炎と寄生虫性脊髄炎:特に髄液における免疫動態の差異について
    小副川 学, 石津 尚明, 梅 風君, 越智 博文, 三野原 元澄, 村井 弘之, 内山 ふくみ, 廣松 賢治, 名和 行文, 吉良 潤一  神経免疫学  13-  (1)  89  -89  2005/03
  • MSの臨床・臨床免疫 多発性硬化症における長期間IFNβ-1b投与に伴う末梢血T細胞内サイトカインの変動の意義
    梅 風君, 小副川 学, 越智 博文, 三野原 元澄, 村井 弘之, 吉良 潤一  神経免疫学  13-  (1)  102  -102  2005/03
  • 小副川学, 宮岸隆司, 越智博文, 新野正明, 中村一太, 菊地誠志, 村井弘之, 深沢俊行, 田代邦雄  Neuroimmunol  13-  (1)  42  2005/03
  • 梅風君, 小副川学, 越智博文, 三野原元澄, 村井弘之, 吉良潤一  Neuroimmunol  13-  (1)  102  2005/03
  • 小副川学, 石津尚明, 梅風君, 越智博文, 三野原元澄, 村井弘之, 内山ふくみ, 広松賢治, 名和行文  Neuroimmunol  13-  (1)  89  2005/03
  • 小副川学, 越智博文, 村井弘之, 玉腰暁子, 坂田清美, 吉良潤一  日本神経学会総会プログラム・抄録集  46th-  102  2005
  • 梅風君, 小副川学, 越智博文, 村井弘之, 吉良潤一  日本神経学会総会プログラム・抄録集  46th-  102  2005
  • 小副川学, 宮岸隆司, 越智博文, 新野正明, 中村一太, 菊地誠志, 村井弘之, 深沢俊行, 田代邦雄  臨床神経学  44-  (12)  1122  -1122  2004/12
  • 姫野恵理, 村井弘之, 越智博文, 川尻真和, 谷脇考恭, 吉良潤一  日本内科学会雑誌  93-  (5)  1006  -1008  2004/05  
    50歳男.残尿感,陰萎,両足底のジンジン感,下肢近位筋の脱力などを主訴とした.神経学的検査でArgyll Robertson瞳孔,右下肢の筋萎縮・脱力,両下肢の腱反射消失・深部覚低下などを認めた.梅毒血清反応はSTSガラス板法,TPHA法,FTA-ABS法の全てが陽性で,髄液検査でもTPHA陽性を認めた.MRIで下部腰椎の骨破壊像と椎間板の異常信号を認め,Charcot spineと診断した.ペニシリンG 1600万単位を1日4回,15日間連日投与し,髄液・血清の梅毒反応には変化が認められなかったが,下肢の症状は軽減した.その後,症状の進行を抑制する目的で外科的に腰椎固定術を行い,現在経過観察中である
  • 小副川学, 越智博文, 中村一太, 村井弘之, 三野原元澄, 吉良潤一  日本神経学会総会プログラム・抄録集  45th-  278  2004/04
  • アトピー素因を伴う脊髄炎(アトピー性脊髄炎)における脊髄前角運動ニューロン障害(Anterior Horn Cell Involvement in Myelitis with Atopic Diathesis (Atopic Myelitis))
    徳永 秀明, 小副川 学, 村井 弘之, 越智 博文, 三野原 元澄, 谷脇 考恭, 吉良 潤一  福岡医学雑誌  95-  (2)  36  -43  2004/02  
    20例のアトピー素因を伴う脊髄炎患者を対象に,神経学的検査,針筋電図,脊髄MRI,運動および体性感覚誘発電位検査を行い,脊髄前角運動ニューロン障害の有無を明らかにした.その結果, 1)明らかな筋萎縮は20例中1例(5%)にのみみられ,他では明らかな下位運動ニューロン障害の所見はなかった. 2)針筋電図では12例(60%)で様々な程度の下位運動ニューロン障害の所見が得られた. 3)線維束性収縮電位,線維性収縮電位,陽性鋭波などのon-goingの脱神経所見は5例で,干渉波形の減少を伴う巨大運動単位電位や多相性運動単位電位などの慢性の神経原性所見は12例でみられた.うち4例では,下位運動ニューロン障害のみられた髄節が脊髄MRIで病巣を認めた髄節以外の部位にあった. 4)2例のon-goingの脱神経所見を呈した患者において血漿交換や免疫グロブリン大量静注療法などの免疫療法を施行したところ,2例とも臨床所見および電気生理学的所見が改善した
  • 萩原綱一, 野村拓夫, 越智博文, 村井弘之, 古谷博和, 吉良潤一  臨床神経学  44-  (2)  123  -123  2004/02
  • 松瀬大, 田代研之, 越智博文, 野村拓夫, 村井弘之, 古谷博和, 吉良潤一  臨床神経学  44-  (2)  124  -124  2004/02
  • 多発性硬化症における血小板活性化因子受容体遺伝子多型についての検討
    小副川 学, 越智 博文, 中村 一太, 村井 弘之, 三野原 元澄, 吉良 潤一  神経免疫学  12-  (1)  27  -27  2004/01
  • 慢性炎症性脱髄性多発神経炎(CIDP)における髄液CD4陽性T細胞内サイトカインの解析
    梅 風君, 村井 弘之, 越智 博文, 小副川 学, 三野原 元澄, 吉良 潤一  神経免疫学  12-  (1)  68  -68  2004/01
  • 村井弘之, 小副川学, 石津尚明, 梅風君, 三野原元澄, 越智博文, 内山ふくみ, 広松賢治, 名和行文  免疫性神経疾患に関する調査研究 平成15年度 総括・分担研究報告書  93  -95  2004
  • 吉良潤一, 小副川学, 越智博文, 村井弘之, 三野原元澄, 新野正明, 菊地誠志, 田代邦雄, 深沢俊行  免疫性神経疾患に関する調査研究 平成15年度 総括・分担研究報告書  26  -28  2004
  • 血漿PAF-AH遺伝子変異は日本人視神経脊髄型多発性硬化症の重症化に関与する
    小副川 学, 新野 正明, 越智 博文, 深澤 俊行, 菊地 誠志, 田代 邦雄, 吉良 潤一  臨床神経学  43-  (12)  1051  -1051  2003/12
  • 越智博文, 小副川学, 村井弘之, 梅風君, 徳永秀明, 吉良潤一  臨床神経学  43-  (12)  1032  -1032  2003/12
  • 小副川学, 新野正明, 越智博文, 深沢俊行, 菊地誠志, 田代邦雄, 吉良潤一  臨床神経学  43-  (12)  1051  2003/12
  • 村井弘之, MEI F‐J, 小副川学, 越智博文, 吉良潤一  末梢神経  14-  (2)  147  -149  2003/12  
    髄液細胞内サイトカイン産生能を測定する系を樹立した.今回,慢性炎症性脱髄性多発根神経炎(CIDP),多発単神経炎の末梢血・髄液でCD4陽性T細胞内サイトカイン産生能を測定し,非炎症性対照疾患(OND)と比較した.また,IVIG治療反応群と治療抵抗群とにおいて髄液細胞内サイトカイン産生能の違いを比較した.CIDPではONDよりも髄液中ではIFNγ+IL-4-細胞%が有意に高く,Th1シフトしていることが示唆された.炎症性ニューロパチーのみならず,ONDでも髄液では末梢血よりもTh1シフトしていることが示された.髄液のIFNγ+IL-4-細胞%が高い群で治療反応性がよく,これがIVIG治療反応性のマーカーになりうる可能性が示唆された
  • 徳永秀明, 小副川学, 越智博文, 村井弘之, 吉良潤一  臨床神経学  43-  (12)  1028  -1028  2003/12
  • 三野原元澄, 朴華, 孫暁嘉, 徳永秀明, 小副川学, 越智博文, 村井弘之, 西村泰治, 吉良潤一  臨床神経学  43-  (12)  1033  -1033  2003/12
  • 梅風君, 村井弘之, 越智博文, 小副川学, 三野原元澄, 吉良潤一  臨床神経学  43-  (12)  1033  -1033  2003/12
  • 皮質性小脳萎縮症の経過中に中枢型睡眠時無呼吸症候群を呈した1例
    金 青玉, 野村 拓夫, 越智 博文, 古谷 博和, 吉良 潤一  日本自律神経学会総会プログラム・抄録集  56回-  92  -92  2003/10
  • 【多発性硬化症 最新の基礎・臨床研究】 臨床研究の進歩 治療(免疫療法) インターフェロン
    越智 博文  日本臨床  61-  (8)  1367  -1373  2003/08
  • 越智博文  日本臨床  61-  (8)  1367  -1373  2003/08
  • 多発性硬化症におけるinterferon beta-1bによる有害事象の検討
    越智 博文, 村井 弘之, 吉良 潤一  神経治療学  20-  (3)  275  -275  2003/05
  • アトピー性脊髄炎の治療効果についての研究
    村井 弘之, 荒畑 創, 越智 博文, 小副川 学, 吉良 潤一  神経治療学  20-  (3)  278  -278  2003/05
  • けいれんを初発とし,皮質下に多発性の点状出血をきたした古典的PNの一例
    古田 興之介, 川尻 真和, 村井 弘之, 越智 博文, 古谷 博和, 吉良 潤一  臨床神経学  43-  (4)  212  -212  2003/04
  • 越智博文, 吉良潤一  最新医学  58-  (2)  308  -317  2003/02
  • 越智博文, 吉良潤一  Annual Review 神経  2003-  221  -233  2003/01
  • 脱髄性疾患 多発性硬化症のprogressive form
    越智 博文, 吉良 潤一  Annual Review神経  2003-  221  -233  2003/01
  • 村井弘之, 梅風君, 小副川学, 越智博文, 三野原元澄, 朴華, 吉良潤一  免疫性神経疾患に関する調査研究 平成14年度総括・分担研究報告書  25  -28  2003
  • 吉良潤一, 越智博文, 小副川学, 梅風君, 徳永秀明  免疫性神経疾患に関する調査研究 平成14年度総括・分担研究報告書  79  -80  2003
  • 吉良潤一, 三野原元澄, 朴華, 孫暁嘉, 徳永秀明, 小副川学, 越智博文, 村井弘之, 西村泰治  免疫性神経疾患に関する調査研究 平成14年度総括・分担研究報告書  45  -46  2003
  • 吉良潤一, 小副川学, 新野正明, 越智博文, 菊地誠志, 深沢俊行, 村井弘之, 田代邦雄  免疫性神経疾患に関する調査研究 平成14年度総括・分担研究報告書  22  -24  2003
  • アトピー性脊髄炎及び多発性硬化症における遺伝学的背景の検討
    小副川 学, 越智 博文, 村井 弘之, 三野原 元澄, 西村 泰治, 吉良 潤一  臨床神経学  42-  (12)  1274  -1274  2002/12
  • 小副川学, 越智博文, 村井弘之, 三野原元澄, 西村泰治, 吉良潤一  臨床神経学  42-  (12)  1274  2002/12
  • 堀内泉, 越智博文, 村井弘之, 吉良潤一, 荒木令江, 佐谷秀行, 戸田年総  臨床神経学  42-  (12)  1411  -1411  2002/12
  • 村井弘之, 越智博文, 小副川学, 吉良潤一, 内山明彦  臨床神経学  42-  (12)  1272  -1272  2002/12
  • 越智博文, 小副川学, 吉良潤一  臨床神経学  42-  (12)  1274  -1274  2002/12
  • 三野原元澄, 朴華, 西村泰治, 堀内泉, 越智博文, 小副川学, 村井弘之, 吉良潤一  臨床神経学  42-  (12)  1322  -1322  2002/12
  • 梅風君, 越智博文, 小副川学, 張昆南, 村井弘之, 吉良潤一  臨床神経学  42-  (12)  1286  -1286  2002/12
  • アトピー素因と末梢の運動神経障害を伴い,平山病類似の一側上肢遠位筋萎縮をきたした一例
    古田 興之介, 川尻 真和, 村井 弘之, 大島 幸子, 越智 博文, 古谷 博和, 吉良 潤一  臨床神経学  42-  (10)  986  -986  2002/10
  • 越智博文, 吉良潤一  からだの科学  (226)  85  -92  2002/09
  • 川野克己, 戸田年総, 堀内泉, 越智博文, 荒木朋洋, 佐谷秀行, 吉良潤一, 荒木令江  生化学  74-  (8)  943  -943  2002/08
  • 乳癌治療後に過眠と小脳失調が改善した傍腫瘍性神経症候群の1例
    河村 信利, 川尻 真和, 大八木 保政, 越智 博文, 村井 弘之, 古谷 博和, 吉良 潤一  臨床神経学  42-  (8)  776  -776  2002/08
  • ステロイド治療が奏効した,高IgE血症をともなう限局性頸部根神経炎の2例
    田中 正人, 川尻 真和, 大八木 保政, 小副川 学, 越智 博文, 古谷 博和, 吉良 潤一  神経治療学  19-  (3)  312  -312  2002/05
  • IFN-α治療が筋脱力と共に乾癬にも奏効したHAMの1例
    川尻 真和, 大八木 保政, 小副川 学, 越智 博文, 古谷 博和, 吉良 潤一  神経治療学  19-  (3)  313  -313  2002/05
  • アトピー性脊髄炎における潜在性末梢神経障害の合併についての検討
    小副川 学, 越智 博文, 山田 猛, 堀内 泉, 村井 弘之, 吉良 潤一  末梢神経  12-  (1)  187  -190  2002/05  
    アトピー性脊髄炎(AM)患者における潜在的な末梢神経障害の有無を検索した.対象はMRIもしくは電気生理学的に病変を認める原因不明の脊髄炎で,アトピー疾患の合併もしくは血清IgE及びダニ特異的IgE高値を認めAMと診断された21名(男13名,女8名,36.0±10.3歳),多発性硬化症(MS)患者28名(男7名,女21名,43.5±13.5歳)を対象とした.AM例ではMS例と比べ感覚神経伝導速度での異常を有意に高率に認め(55.0%対14.3%),運動神経伝導速度もEDSSスコア6.0未満のMS例に比べると異常率が有意に高かった.F波の異常率も有意に高かった.以上よりAM例ではMS例と比べて潜在性末梢神経障害の合併率が有意に高く,アトピー素因に伴って末梢神経系に多発性に炎症性病変を合併しうることが示唆された
  • 越智博文, 吉良潤一  月刊神経内科  56-  (4)  326  -331  2002/04
  • 越智博文  臨床免疫  37-  (4)  493  -498  2002/04
  • MEI F, 越智博文, 小副川学, ZHANG K N, 堀内泉, 三野原元澄, 村井弘之, 吉良潤一  Neuroimmunol  10-  (1)  52  -53  2002/02
  • 越智博文, 小副川学, 村井弘之, 堀内泉, 三原野元澄, 吉良潤一  Neuroimmunol  10-  (1)  128  -129  2002/02
  • 堀内泉, 荒木令江, 戸田年総, 越智博文, 村井弘之, 佐谷秀行, 吉良潤一  Neuroimmunol  10-  (1)  176  -177  2002/02
  • 村井弘之, 小副川学, 越智博文, 堀内泉, 吉良潤一  Neuroimmunol  10-  (1)  82  -83  2002/02
  • 三野原元澄, PIAO H, 堀内泉, 小副川学, 越智博文, 村井弘之, 西村泰治, 吉良潤一  Neuroimmunol  10-  (1)  42  -43  2002/02
  • J. Kira, M. Osoegawa, I. Horiuchi, H. Murai, M. Minohara, Y. Ohyagi, H. Furuya, S. Tobimatsu, K. Yamasaki, H. Ochi  Acta Neurologica Scandinavica  105-  (3)  215  -220  2002  
    Objective - To clarify the association between past and present history of allergic disorders and neurologic diseases. Methods - The past and present history of common allergic disorders together with family history was prospectively studied in all out-patients at the Department of Neurology at Kyushu University Hospital from March 1998 to February 2000. Results - Among 3113 out-patients, 2152 (69.1%) completed a questionnaire. Myelitis showed a statistically significant increase of concomitant atopic dermatitis (P = 0.006) and concomitant and past atopic dermatitis (P = 0.014), as compared with neurologically healthy controls. Moreover, patients with lower motoneuron disease (LMND) had a statistically significant increase of past and concomitant asthma (P = 0.007). None of the other common neurologic diseases showed any increase of allergic disorders when compared with controls. Conclusions - The present study supports the significant association between allergic disorders and such spinal cord diseases as myelitis and LMND in Japanese patients.
  • 脳磁図で棘波の奇異性分布を証明し得た持続部分てんかんの1例
    大石 文芽, 越智 博文, 飛松 省三, 吉良 潤一  臨床脳波  44-  (1)  59  -64  2002/01  
    32歳女.脳波で棘波のない右下肢の持続部分癲癇に対して,病態生理を脳波と脳磁図の逆行性加算平均法(JLA)で検討した.右ヒラメ筋の筋放電をトリガーにした脳波のJLAでは陽性棘波が左頭皮上に,陰性棘波が右頭皮上に認められた.脳磁図のJLAでは左前頭葉下肢運動野に接線方向の棘波の電流双極子が推定された.下肢運動野が半球内側にあるため,脳波のJLAでは棘波が奇異性分布を示した.患者は電気生理学的検査終了後,急性脳症を発症したが,ステロイドパルス療法にて改善した.最終診断は病因不明の自己免疫性脳炎と考えられた.脳磁図のJLAにより棘波の電流源を正確に推定できるため,脳磁図は持続部分癲癇の評価に有用であると思われた
  • 小副川学, 越智博文, 堀内泉, 村井弘之, 吉良潤一  免疫性神経疾患に関する調査研究 平成13年度総括・分担研究報告書  58  -60  2002
  • 大石文芽, 越智博文, 飛松省三, 吉良潤一  臨床脳波  44-  (1)  59  -64  2002/01
  • Horiuchi, I, H Ochi, H Murai, M Osoegawa, M Minohara, H Furuya, J Kira  JOURNAL OF THE NEUROLOGICAL SCIENCES  193-  (1)  49  -52  2001/12  
    To elucidate the T helper 1 (Th1)/T helper 2 (Th2) balance in various inflammatory neuropathies, we measured the ratio of intracellular interferon-gamma (IFN-gamma)-positive to IL-4-positive cells (intracellular IFN-gamma /IL-4 ratio) by flow cytometry in peripheral blood CD4(+) T cells of 14 patients with mononeuritis multiplex (MNM), 12 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 10 patients with Guillain-Barre syndrome (GBS), 23 patients with neurodegenerative disorders and 36 healthy controls by intracellular labeling. The patients with MNM showed a significantly lower intracellular IFN-gamma /IL-4 ratio (P <0.05) and higher IL-4(+)/IFN-gamma (-) cell percentages (P < 0.05) than the controls. The increase of IL-4(+)/IFN-gamma (-) cell percentages was especially prominent in MNM of unknown etiology (P < 0.005). The patients with CIDP also showed significantly higher IL-4(+)/IFN-gamma (-) cell percentages (P < 0.05) than the controls. The IL-4(+)/IFN-gamma (-) cell percentages were increased in some patients with GBS, but the difference was not significant compared with the controls. Thus, our results suggest that a Th2 shift is a characteristic of MNM and may play an important role in the development of the disease. (C) 2001 Elsevier Science B.V. All rights reserved.
  • 越智博文, 吉良潤一  医学のあゆみ  別冊-  (21世紀の神経免疫学-展望)  17  -21  2001/11
  • 村井弘之, 越智博文, 小副川学, 吉良潤一, 内山明彦  神経治療学  18-  (5/6)  521  -521  2001/11
  • 小副川学, 越智博文, 松本省二, 川尻真和, 吉良潤一, 名和行文  神経治療学  18-  (5/6)  497  -497  2001/11
  • 越智博文, 村井弘之, 小副川学, 吉良潤一, 稲葉しょう一  神経治療学  18-  (5/6)  511  -511  2001/11
  • 川尻真和, 越智博文, 堀内泉, 小副川学, 吉良潤一  臨床神経学  41-  (11)  951  -951  2001/11
  • 呉暁牧, 越智博文, 小副川学, 吉良潤一  臨床神経学  41-  (11)  995  -995  2001/11
  • 三野原元澄, 越智博文, 小副川学, 村井弘之, 吉良潤一  臨床神経学  41-  (11)  951  -951  2001/11
  • 村井弘之, 越智博文, 小副川学, 吉良潤一  臨床神経学  41-  (11)  871  -871  2001/11
  • 吉良潤一, 越智博文  臨床神経学  41-  (11)  951  -951  2001/11
  • 大石文芽, 越智博文, 吉良潤一, 谷脇考恭, 飛松省三  臨床神経学  41-  (11)  960  -960  2001/11
  • 越智博文, 三野原元澄, 小副川学, 吉良潤一  臨床神経学  41-  (11)  951  -951  2001/11
  • 小副川学, 越智博文, 山辺和俊, 高橋宏, 調漸, 玉木紀彦, 津本智幸, 田村陽史, 中野今治  臨床神経学  41-  (11)  951  -951  2001/11
  • 越智博文, 吉良潤一  Bio Clin  16-  (11)  1034  -1038  2001/10
  • H Ochi, XM Wu, M Osoegawa, Horiuchi, I, M Minohara, H Murai, Y Ohyagi, H Furuya, J Kira  JOURNAL OF NEUROIMMUNOLOGY  119-  (2)  297  -305  2001/10  
    CD8(+) T cells, like CD4(+) T cells, can differentiate into at least two subsets with distinct cytokine patterns: Tc I cells produce Th I-like cytokines and Tc2 cells produce Th2-like cytokines. To clarify the immunopathological roles of Tc1 and Tc2 cells in central nervous system (CNS) inflammation, we examined intracellular cytokines in CDS' and CD4+ T cells by flow cytometry and analyzed the Tc1/Tc2 balance as well as the Th1/Th2 balance in 80 patients with various CNS inflammatory diseases, including 20 with optico-spinal multiple sclerosis (OS-MS), 21 with conventional MS (C-MS), 22 with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 17 with hyperIgEaemic myelitis. Twenty-two healthy subjects were also examined as controls. Patients with OS-MS showed a significantly higher percentage of INF-gamma +IL-4(-) CD8(+) T cells as well as CD4(+) T cells and a significantly higher intracellular interferon-gamma (IFN-gamma)/interleukin-4 (IL-4) ratio both in CD8 and CD4(+) T cells throughout the relapse and remission phases than the healthy controls. Furthermore, the patients with OS-MS showed a significantly lower percentage of INF-gamma IL-4(+) CD4(+) T cells as well as CD8(+) T cells during the relapse phase than the healthy controls. On the other hand, the patients with C-MS showed a significantly higher percentage of IFN-gamma -IL-4(+) CD8(+) T cells in addition to more IFN-gamma +IL-4(-) CD4(+) T cells during the relapse phase than the healthy controls. The HAM/TSP patients showed a significantly higher percentage of INF-gamma +IL-4(-)CD(8+) T cells and a significantly higher intracellular IFN-gamma /IL-4 ratio in CD8(+) T cells than the healthy controls. In contrast, in C. hyperIgEaemic myelitis, in addition to a significantly lower intracellular IFN-gamma /IL-4 ratio in CD4(+) T cells, a tendency toward a lower intracellular IFN-gamma /IL-4 ratio in CD8(+) T cells in comparison to the healthy controls was observed. These results clarified for the first time the distinct Tc1/Tc2 balance in each disease condition as follows: Tc1 cell response is predominant in OS-MS and HAM/TSP, while Tc2 cell response is predominant in hyperIgEaemic myelitis and at relapse phase of C-MS. Furthermore, our results suggest that CD8(+) T cells play an adjunctive role in disease induction and the clinical course of MS. (C) 2001 Elsevier Science B.V. All rights reserved.
  • クリニカルトピックス アトピー性脊髄炎
    越智 博文, 吉良 潤一  BIO Clinica  16-  (11)  1034  -1038  2001/10
  • 【骨格筋症候群 その他の神経筋疾患を含めて】 炎症性ミオパチー HTLV-1関連ミオパチー
    越智 博文, 吉良 潤一  日本臨床  別冊-  (骨格筋症候群(上))  198  -201  2001/08
  • 越智博文, 吉良潤一  Clin Neurosci  19-  (7)  792  -794  2001/07
  • J Kira, H Ochi  JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY  70-  (6)  798  -801  2001/06  
    Juvenile muscular atrophy of the distal upper Limb (Hirayama disease) is a rare disease predominantly affecting the anterior horn cells of the cervical spinal cord in young men. Although the disease is considered to be a type of cervical myelopathy, the mechanism remains unknown. An immunological study of five consecutive patients with this disorder who were examined in the neurology clinic at Kyushu University Hospital during the past 2 years were performed. Ah developed distal muscular atrophy and weakness of one or both upper limbs in the second decade, and showed forward displacement of the dural sac and passive dilatation of the posterior venus plexus at the lower cervical portion on MRI during neck flexion. Four of the five patients had one or more coexistent airway allergies, such as allergic rhinitis, pollinosis, and asthma, and all five patients had a family history of atopic or allergic disorders in close relatives. Four of the five patients had mild eosinophilia. All five patients commonly had IgE specific to two mite antigens, Dermatophagoides pteronyssinus and Dermatophagoides farinae, whereas three of them also showed a raised total serum IgE concentration. The frequency of mite antigen specific IgE was significantly higher in the present patients with Hirayama disease than in 82 healthy controls (26/82, p <0.005). These findings suggest that atopy may be one of the contributing factors for Hirayama disease.
  • 【最近注目されてきた疾患・病態・治療 内科のトピックスを知る】 アトピー性脊髄炎
    越智 博文, 吉良 潤一  内科  87-  (6)  1454  -1459  2001/06
  • Comments アトピー性脊髄炎とHopkins症候群
    吉良 潤一, 越智 博文, 小副川 学  臨床神経学  41-  (6)  331  -331  2001/06
  • 吉良潤一, 越智博文, 小副川学  臨床神経学  41-  (6)  331  -331  2001/06
  • Reply from the author アトピー性皮膚炎と重症筋無力症
    大八木 保政, 村井 弘之, 甲斐 康稔, 小副川 学, 堀内 泉, 越智 博文, 吉良 潤一  臨床神経学  41-  (4〜5)  207  -207  2001/04
  • M. Osoegawa, S. Matsumoto, H. Ochi, K. Yamasaki, I. Horiuchi, Y. Ohyagi, J. I. Kira, K. Ishiwata, F. Nakamura-Uchiyama, Y. Nawa  Journal of Neurology Neurosurgery and Psychiatry  70-  265  -266  2001/02
  • 村井弘之, 越智博文, 小副川学, 吉良潤一  Neuroimmunol  9-  (1)  76  -77  2001/02
  • 小副川学, 越智博文, 三野原元澄, 村井弘之, 名和行文, 吉良潤一  Neuroimmunol  9-  (1)  154  -155  2001/02
  • 越智博文, 三野原元澄, 小副川学, 村井弘之, 吉良潤一  Neuroimmunol  9-  (1)  152  -153  2001/02
  • 吉良潤一, 越智博文  Neuroimmunol  9-  (1)  150  -151  2001/02
  • WU X‐M, 越智博文, 小副川学, 三野原元澄, MEI F, 村井弘之, 吉良潤一  Neuroimmunol  9-  (1)  54  -55  2001/02
  • H. Ochi, J. Kira  Ryōikibetsu shōkōgun shirīzu  198  -201  2001/01
  • Jun-Ichi Kira, Izumi Horiuchi, Jun Suzuki, Manabu Osoegawa, Shozo Tobimatsu, Hiroyuki Murai, Motozumi Minohara, Masutaka Furue, Hirofumi Ochi  Internal Medicine  40-  (7)  613  -619  2001  
    Objective To clarify the clinical features of myelitis associated with atopic disorders in Japanese patients. Subjects and Methods We retrospectively studied the clinical, immunological and electrophysiological features of 68 consecutive patients with myelitis of acute or subacute onset diagnosed at Kyushu University Hospital during the past 20 years. Results While only 2 of 28 (7% ) patients with myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between 1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and 1998, 19 patients with either AD or BA as well as 21 patients without either disease showed a significantly higher level of serum total IgE, higher frequency of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82 healthy controls. Myelitis patients with AD presenting as persistent paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and abnormalities in upper limb motor evoked potentials but no abnormalities in the cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential involvement of the lower motor neurons clinically and electromyographically. In addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen-specific IgE but neither AD nor BA showed incomplete transverse myelitis with mild motor disability and few CSF abnormalities. Conclusion The clinical features of myelitis associated with atopic disorders were in part distinguished by the type of preceding atopic disorder, and also were different from those of hyperIgEaemic myelitis with no preceding atopic disorders.
  • H Kikuchi, M Osoegawa, H Ochi, H Murai, Horiuchi, I, H Takahashi, K Yamabe, T Iwaki, T Mizutani, M Oda, J Kira  JOURNAL OF THE NEUROLOGICAL SCIENCES  183-  (1)  73  -78  2001/01  
    We report the neuropathological findings of spinal cord specimens obtained from two patients who had localized myelitis with hyperIgEemia and mite antigen specific IgE (atopic myelitis). Both cases showed mild spinal cord dysfunction, and the gadolinium-enhanced area of the isolated spinal cord lesion observed on MRI was biopsied, respectively. Neuropathologically, both cases showed many perivascular lymphocyte cuffings associated with disrupted vessels, and the infiltration of eosinophils in the spinal cord lesions. Both myelin and axons were lost in the lesions, which were associated with astrogliosis. These findings suggest that an allergic mechanism may play a role in this condition. (C) 2001 Elsevier Science B.V. All rights reserved.
  • M. Minohara, H. Ochi, S. Matsushita, A. Irie, Y. Nishimura, J. Kira  Tissue Antigens  57-  (5)  447  -456  2001  
    In Japanese, susceptibility to the conventional form of multiple sclerosis (C-MS) is associated with the HLA-DRB1 *1501-DRB5*0101 haplotype while susceptibility to the opticospinal form of MS (OS-MS) is associated with HLA-DPA1 *0202-DPB1*0501. To clarify the characteristics of T cells autoreactive to myelin proteins in each MS subtype, we established T-cell lines reactive to such myelin antigens as myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) from 5 of 10 OS-MS patients, 6 of 11 C-MS patients and 7 of 13 healthy controls (HCs), and T-cell epitopes and their restriction molecules were determined. We found that (a) intermolecular epitope spreading was found to be significantly more frequent in MS patients than in HCs (P=0.0128), (b) intramolecular epitope spreading also tended to occur more frequently in MS patients than in HCs (P=0.0584), (c) in OS-MS, HLA-DR-restricted and MOG-autoreactive T cells were more frequently established as compared with those reactive to MBP or PLP epitopes and (d) in C-MS, HLA-DQ-restricted and PLP-autoreactive T cells dominated those autoreactive to MBP or MOG epitopes. A DPB1*0501-restricted MBP-reactive T-cell clone from a patient with OS-MS provided evidence that the first HLA class II anchor amino-acid of peptide bound to disease-susceptible DP5 molecule was distinct from that for the DR2 molecule. Taken together, these differences in specificities of myelin-autoreactive T cells between C-MS and OS-MS as well as the difference in the anchor motif of the binding peptides between each MS subtype-susceptible HLA class II molecule may contribute to the development of distinct clinical phenotypes.
  • N. Nakao, T. Ibi, K. Sahashi, Y. Ohyagi, H. Murai, Y. Kai, M. Osoegawa, I. Horiuchi, H. Ochi, J. I. Kira  Clinical Neurology  41-  (4-5)  206  -207  2001  Report scientific journal
  • M. Kawajiri, M. Osoegawa, Y. Ohyagi, H. Ochi, H. Furuya, Y. Nawa, J. Kira  Clinical Neurology  41-  (6)  310  -313  2001  
    A 27-year-old woman was admitted because of pain radiating through her back on neck flexion that had begun a month ago. She frequently ate raw beef liver. General physical examination revealed no abnormal findings, but she showed Lhermitte's sign neurologically. Fecal examination revealed no worm eggs. Blood cell counts showed mild eosinophilia (8.2%). The IgE level was mildly increased to 397IU/ml (normal< 250). Cerebrospinal fluid examination showed 7 cells/μl with 50% eosinophils. A test for anti-Ascaris suum IgG antibody was strongly positive in serum as well as in cerebrospinal fluid. Cervical MRI showed high-intensity areas in the spinal cord extending from the lower medulla to the C4 spine level on the T2-weighted images, and part of the lesion at the C3 spine level was enhanced by gadolinium. Treatment with albendazole 500 mg/day for six weeks ameliorated the Lhermitte's sign and MRI lesions, and reduced the anti-Ascaris suum antibody titers in the serum and cerebrospinal fluid. Larva migrans of Ascaris suum involving the central nervous system is considered to be extremely rare. but such cases showing mild neurologic impairment without systemic symptoms may have been overlooked.
  • 小副川学, 越智博文, 山田猛, 堀内泉, 村井弘之, 吉良潤一  末梢神経  12-  (1)  187  -190  2001
  • 小副川学, 越智博文, 名和行文, 吉良潤一  免疫性神経疾患に関する調査研究班 平成12年度研究報告書  31  -32  2001
  • M. Kawajiri, M. Osoegawa, Y. Ohyagi, H. Ochi, H. Furuya, Y. Nawa, J. Kira  Clinical Neurology  41-  (6)  310  -313  2001  
    A 27-year-old woman was admitted because of pain radiating through her back on neck flexion that had begun a month ago. She frequently ate raw beef liver. General physical examination revealed no abnormal findings, but she showed Lhermitte's sign neurologically. Fecal examination revealed no worm eggs. Blood cell counts showed mild eosinophilia (8.2%). The IgE level was mildly increased to 397IU/ml (normal< 250). Cerebrospinal fluid examination showed 7 cells/μl with 50% eosinophils. A test for anti-Ascaris suum IgG antibody was strongly positive in serum as well as in cerebrospinal fluid. Cervical MRI showed high-intensity areas in the spinal cord extending from the lower medulla to the C4 spine level on the T2-weighted images, and part of the lesion at the C3 spine level was enhanced by gadolinium. Treatment with albendazole 500 mg/day for six weeks ameliorated the Lhermitte's sign and MRI lesions, and reduced the anti-Ascaris suum antibody titers in the serum and cerebrospinal fluid. Larva migrans of Ascaris suum involving the central nervous system is considered to be extremely rare. but such cases showing mild neurologic impairment without systemic symptoms may have been overlooked.
  • 堀内泉, 山崎賢智, 三野原元澄, 小副川学, 越智博文, 菊池仁志, 呉暁牧, 吉良潤一  臨床神経学  40-  (12)  1474  -1474  2000/12
  • 小副川学, 山崎賢智, 堀内泉, 三野原元澄, 越智博文, 吉良潤一  臨床神経学  40-  (12)  1412  -1412  2000/12
  • 呉暁牧, 小副川学, 越智博文, 山崎賢智, 堀内泉, 三野原元澄, 吉良潤一  臨床神経学  40-  (12)  1412  -1412  2000/12
  • 越智博文, 吉良潤一  日本臨床  47  -51  2000/11
  • 【免疫症候群(上巻)】 自己免疫疾患 臓器特異的自己免疫疾患 多発性硬化症
    越智 博文, 吉良 潤一  日本臨床  別冊-  (免疫症候群(上))  47  -51  2000/11
  • ニューロサイエンスのSOMETHING HOT アトピー性脊髄炎
    小副川 学, 越智 博文, 吉良 潤一  脳の科学  22-  (11)  1219  -1223  2000/11
  • 村井弘之, 小副川学, 越智博文, 吉良潤, 稲葉しょう一  日本アフェレシス学会雑誌  19-  (3)  244  -245  2000/10
  • 越智博文, 吉良潤一  月刊神経内科  53-  (4)  342  -346  2000/10
  • アトピー性脊髄炎に対する血漿交換の効果
    村井 弘之, 小副川 学, 越智 博文, 吉良 潤, 稲葉 頌一  日本アフェレシス学会雑誌  19-  (3)  244  -245  2000/10
  • 村井弘之, 野田昌作, 伊藤裕昭, 越智博文  臨床神経学  40-  (10)  1054  -1054  2000/10
  • 越智博文, 小副川学, 吉良潤一  Neuroimmunol  8-  (2)  181  -189  2000/10
  • XM Wu, M Osoegawa, K Yamasaki, Y Kawano, H Ochi, Horiuchi, I, M Minohara, Y Ohyagi, T Yamada, J Kira  JOURNAL OF THE NEUROLOGICAL SCIENCES  177-  (1)  24  -31  2000/08  
    We examined the alterations of memory CD4(+) T cell subsets bearing surface receptors linked to either Th1 or Th2 cytokine production as well as natural killer (NK) cell subsets by three color flow cytometry in the peripheral blood from 36 patients with clinically definite multiple sclerosis (MS), 27 patients with HAM/TSP, 13 patients with hyperIgEaemic myelitis who had mite antigen-specific IgE and 25 healthy controls (HC). The patients with MS were clinically classified into an optico-spinal form of MS (Asian type, MS-A) and the conventional form of MS (Western type, MS-W). MS-A showed a significant increase of CD4(+)CD45RA(-)CCR5(+) cells (Th1 cells) through the relapse and remission phases in comparison to HC, while MS-W showed a significant increase of CD4(+)CD45RO(+)CD62L(-) cells (Th1 cells) only at the relapse phase. HAM/TSP showed a significant increase of CCR5(+) and CD62L(-) memory CD4(+) T cells as well as CD30(+) memory CD4(+) T cells (Th2 cells) in comparison to HC. On the other hand, a selective increase of CD4(+)CD45RO(+)CD30(+) cells was found in hyperIgEaemic myelitis. The percentage of mature NK cells (CD3(-)CD16(+)CD56(+) cells) as well as double negative T cells (CD3(+)CD4(-)CD8(-) cells) decreased significantly in HAM/TSP in comparison to HC. Our findings therefore suggest a flow cytometric analysis of Th1/Th2-associated markers on memory CD4(+) T cells as well as NK cell subsets to be useful for differentiating various inflammatory neurologic conditions. (C) 2000 Elsevier Science B.V. All rights reserved.
  • ブタ回虫感染による脊髄炎の1例
    小副川 学, 松本 省二, 越智 博文, 山崎 賢智, 井上 薫, 山田 猛, 吉良 潤一, 名和 行文  臨床神経学  40-  (8)  865  -865  2000/08
  • 小副川学, 松本省二, 越智博文, 山崎賢智, 井上勲, 山田猛, 吉良潤一, 名和行文  臨床神経学  40-  (8)  865  2000/08
  • LynキナーゼによるCD5,Ly49共受容体を介したB-1細胞におけるB細胞受容体シグナルの負の制御
    128109, 1417-1423-  2000
  • H. Ochi, J. Kira  Ryōikibetsu shōkōgun shirīzu  47  -51  2000/01
  • 越智博文, 渡辺武  日本免疫学会総会・学術集会記録  29-  261  -261  1999/10
  • 越智博文, 吉良潤一  日本臨床  427  -430  1999/07
  • 神経症候群II 脱髄性疾患 中枢性脱髄疾患 進行性多巣性白質脳症
    越智 博文, 吉良 潤一  日本臨床  別冊-  (神経症候群II)  427  -430  1999/07
  • 越智博文, 吉良潤一  日本臨床  444  -447  1999/05
  • 【神経症候群(I)】 炎症性疾患 急性ウイルス感染症 コクサッキーウイルス
    越智 博文, 吉良 潤一  日本臨床  別冊-  (神経症候群I)  444  -447  1999/05
  • 感染症症候群(II) ウイルス感染症 中枢神経系ウイルス感染症 進行性多巣性白質脳症
    越智 博文  日本臨床  別冊-  (感染症症候群II)  65  -68  1999/02
  • 越智博文  日本臨床  65  -68  1999/02
  • 可溶型T cell receptorの作製とEAEの解析
    原 英夫, 越智 博文, 山村 隆, Fazekas Gyorgy, 田平 武, 吉良 潤一  臨床神経学  39-  (1)  131  -131  1999/01
  • 越智博文, 竹下弘道, 西谷授, 本庶佑, 渡辺武  日本免疫学会総会・学術集会記録  28-  (26回抄録集)  77  -77  1998/10
  • 原英夫, 越智博文, 山村隆, FAZEKAS G, 田平武, 渡辺武, 吉良潤一  Neuroimmunol  6-  (1)  36  -37  1998/01
  • 原英夫, 越智博文, 渡辺武, 山村隆, 田平武  日本免疫学会総会・学術集会記録  27-  192  1997/10
  • 遅発性ウイルス感染症 進行性多巣性白質脳症
    長嶋 和郎, 越智 博文  日本臨床  55-  (4)  916  -921  1997/04
  • 症状からみたリウマチ性疾患 鑑別診断と対策 知覚異常
    越智 博文, 原 英夫  リウマチ科  17-  (4)  386  -391  1997/04
  • 長嶋和郎, 越智博文  日本臨床  55-  (4)  916  -921  1997/04
  • 越智博文, 田中公裕, 山下順章  月刊神経内科  46-  (4)  366  -370  1997/04  
    眼症状が先行したdysthyroid orbital myopathyの69歳女を報告した.当初,甲状腺機能が正常で外眼筋炎と思われる症例の中には,遅れて甲状腺機能異常が出現する症例があることに注意し,繰り返し甲状腺機能検査を行うことが重要と考えた
  • K. Nagashima, H. Ochi  Nippon rinsho. Japanese journal of clinical medicine  55-  916  -921  1997/01  
    Progressive multifocal leukoencephalopathy (PML) is the only polyomavirus infection in human caused by JC virus. Clinically PML is diagnosed by neurological signs, supported by MRI and PET, but its pathologic diagnosis at brain biopsy remains to be a confirmative method, although the PCR method, using csf, gives a predictive value. Virological study of the regulatory region of viral genome has suggested that PML-inducing viral type may be derived from the urine-excreted virus (archetype) by mechanisms involving nucleotide deletion and duplication. Viral neurotropism has been shown to be closely related to transcriptional function of the viral promoter-enhancer which cellular proteins bind to and is activate by. Of these, NF-1 binding proteins, glial factor-1, Tst-1 (SCIP, Oct-6) and others should be tested for their specificity to human glial cell.
  • 原英夫, 越智博文, 吉良潤一, 渡辺武, 山村隆, 田平武  免疫性神経疾患調査研究分科会 平成8年度研究報告書  60  -62  1997
  • Eisenmenger症候群に発症した脳膿瘍 脳膿瘍の発症機序とMRIの経時的変化について
    越智 博文, 山下 順章  神経内科  45-  (5)  439  -441  1996/11
  • 上矢状静脈洞血栓症により広汎な脳腫脹を来したと考えられる1例
    越智 博文  臨床神経学  36-  (8)  1040  -1040  1996/08
  • 佐藤澄子, 棟田慎二郎, 小林卓正, 松本勲, 越智博文, 山下順章  日本内科学会雑誌  85-  (8)  1301  -1303  1996/08
  • 越智博文, 由村健夫, 原英夫, 小林卓郎, 浦川学  月刊神経内科  45-  (2)  128  -132  1996/08  
    眩量,平衡障害,複視,及び聴力低下を伴い,再発性発熱及び後頭部拍動性頭痛を訴えた48歳男で,入院時神経学的所見から右内側縦束症候群,聾,及び平衡障害が認められ,血沈は亢進し,C反応性蛋白陽性であった.自己免疫及び補体検査は全て陰性であった.脳脊髄液中細胞数と蛋白の増加を認めた.血清及び脳脊髄液検査により結核や梅毒は除外された.MRIで右中脳梗塞を認めた.脳血管撮影で主幹動脈に著明な壁不整,狭窄,及び拡張,並びに脳底動脈に解離を認めた.プレドニゾロンによる治療後血沈及びC反応性蛋白は正常化した.発熱及び頭痛は消失した.脳脊髄液中細胞数及び蛋白は漸減した
  • Hirofumi Ochi, Takeshi Yamada, Hideo Hara, Takeo Yoshimura, Toru Iwaki, Kazuo Nagashima, Yoshiaki Yogo, Takuro Kobayashi  Clinical Neurology  36-  (7)  858  -863  1996/07  
    We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-1 antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We invesigated cerebral blood flow, glucose and amino acid metabolism in this patient using position emission tomography, and obtained the following three characteristic findings in the lessions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.
  • H. Ochi, T. Kobayashi  Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine  85-  731  -735  1996/05
  • 重要な神経系の感染症 進行性多巣性白質脳症(PML)
    越智 博文, 小林 卓郎  日本内科学会雑誌  85-  (5)  731  -735  1996/05
  • Paramyotonia congenita日本人1家系の遺伝子解析
    小林 卓郎, 越智 博文, 山田 猛  厚生省精神・神経疾患研究委託費研究報告書 筋ジストロフィー及び類縁疾患の病態と治療法に関する研究  平成7年度-  62  -63  1996/03
  • 小林卓郎, 越智博文, 山田猛  筋ジストロフィー及び類縁疾患の病態と治療法に関する研究 平成7年度研究報告書 高木班  62  -63  1996
  • Hirofumi Ochi, Yoriaki Yamashita  Clinical Neurology  36-  (11)  1229  -1233  1996  
    We report a 30-year-old man with adult type adrenoleukodystrophy (ALD) who manifested an acute onset and repeated episodes of ataxic dysarthria. He noticed a moderate dysarthria after a high grade fever in February of 1995 however, two weeks later his symptom disappeared completely. Three months later, he noticed the dysarthria again and he was referred to our hospital for further examination. General physical findings on admission revealed a dark skin color, pigmentation of gingivae and reduced body hair. Neurologically ha was normal except for a moderate ataxic dysarthria. Cranial T2-weighted MRI showed multiple high intensity lesions in the subcortical while matter of frontal lobe, bilateral peritrigonal white matter, splenium of the corpus callosum and bilateral cerebellar white matter. Only cerebellar lesions responsible for his symptom were enhanced on MRI after gadolinium administration. Initially we diagnosed him with multiple sclerosis (MS) based upon the clinical course and MRI findings, and then started corticosteroid treatment. His dysarthria was slightly improved after the treatment and bilateral gadolinium-enhanced lesions of cerebellar white matter on MRI disappeared. Multimodality evoked potentials such as short latency somatosensory evoked potentials, brainstem auditory evoked potentials and pattern-reversal visual evoked potentials, disclosed a prolonged central conduction time associated with bilaterally symmetric individual interpeak latencies. These findings, which supported diffuse and bilateral subclinical demyelinating lesions in the central nervous system, were unusual for MS therefore his plasma very-long-chain fatty acids (VLCFA) were assayed for ALD. Finally, he was diagnosed with adult type ALD because of the high ratio of C26: 0/C22: 0 (0.075 normal < 0.033). It is very difficult to clinically distinguish the early stage of adult type ALD especially in patients like this from MS. Therefore it is useful and important to evaluate not only the level of plasma VLCFA, but also to evaluate multimodality evoked potentials.
  • 骨格筋Na+ channel遺伝子の点変異を認めたparamyotonia congenitaの1家系
    越智 博文, 山田 猛, 原 英夫  臨床神経学  35-  (8)  893  -896  1995/08  
    2症例(42歳女,20歳男)とも反復運動・寒冷刺激により誘発・増強されるmyotoniaと,それに引き続く筋力低下を呈していた.末梢血を用いた遺伝子学的検索では,骨格筋Na+channel遺伝子(SCN4A)の点変異(Thr1313Met)を認めた.本例はSCN4Aの点変異が確認された本邦第1例である
  • Takeshi Yamada, Hirofumi Ochi, Hideo Hara, Takeo Yoshimura, Takuro Kobayashi  Journal of the Neurological Sciences  133-  (1-2)  192  -193  1995
  • H. Ochi, T. Yamada, H. Hara, T. Yoshimura, T. Kobayashi  Clinical Neurology  35-  (8)  893  -896  1995  
    We report here a Japanese family with paramyotonia congenita. The proband was a 42 year-old woman (case 1), who noticed muscle stiffness and weakness in the cold since the age of 7 years. These symptoms were alleviated by warming. Her eldest son (case 2) also experienced similar symptoms, while her younger son and daughter were healthy. Neurological examination in case 1 revealed mild weakness in facial and neck muscles. Cold induced muscle stiffness and weakness were present. Electromyography showed myotonic discharges, intensified by cooling or repetitive exercise. The amplitude of the compound muscle action potentials was also reduced by the repetitive exercise and cooling. Serum chemistry including potassium and CK was normal. Molecular analysis of SCN4A (exon22 24) by SSCP and nucleotide sequencing revealed a C-to-T transition at nucleotide 3,938, causing a substition of 1313methionine for threonine in case 1. This mutation was confirmed by PCR-RFLP with a mismatched primer the proband (case 1) and her eldest son (case 2) had a heterozygous mutation, while the other family members did not. This is the first report that a mutation in SCN4A was identified in a Japanese family with paramyotonia congenita.
  • H. Ochi, H. Aizawa, K. Matsumoto, S. Hashimoto, N. Hara  Japanese Journal of Thoracic Diseases  33-  (5)  576  -582  1995  
    A 31-year-old man was admitted to our hospital because of a sudden onset of thirst, polyposia, and polyuria. Five years previously he had been admitted to our hospital because of a dry cough. On the first admission, the chest X-ray film had shown reticular shadows and bullous changes in both upper lung fields. Histological examination of a transbronchial lung biopsy specimen had revealed that the nodular lesion in the interstitium of the alveolar lesion consisted of an aggregate of many Langerhans cells with pale cytoplasm and partly convoluted nuclei. In addition, immunoperoxidase stain for S-100 protein had been strongly positive in numerous Langerhans cells in a bone biopsy specimen from a left mandibular lesion, which is the same histological appearance as the lung lesion. A diagnosis of pulmonary eosinophilic granuloma had been made. The course after discharge was not progressive without treatment for 5 years, but the patient suddenly began to have thirst, polyposia, and polyuria. Dehydration, vasopressin tests, and the findings of MRI indicated diabetes insipidus due to a pathological change in the pituitary gland. Although diabetes insipidus is known to be a common complication of pulmonary eosinophilic granuloma, only 9 cases have been reported in Japan.
  • H. Ochi, T. Yamada, H. Hara, T. Yoshimura, T. Kobayashi  Clinical Neurology  35-  (8)  893  -896  1995  
    We report here a Japanese family with paramyotonia congenita. The proband was a 42 year-old woman (case 1), who noticed muscle stiffness and weakness in the cold since the age of 7 years. These symptoms were alleviated by warming. Her eldest son (case 2) also experienced similar symptoms, while her younger son and daughter were healthy. Neurological examination in case 1 revealed mild weakness in facial and neck muscles. Cold induced muscle stiffness and weakness were present. Electromyography showed myotonic discharges, intensified by cooling or repetitive exercise. The amplitude of the compound muscle action potentials was also reduced by the repetitive exercise and cooling. Serum chemistry including potassium and CK was normal. Molecular analysis of SCN4A (exon22 24) by SSCP and nucleotide sequencing revealed a C-to-T transition at nucleotide 3,938, causing a substition of 1313methionine for threonine in case 1. This mutation was confirmed by PCR-RFLP with a mismatched primer the proband (case 1) and her eldest son (case 2) had a heterozygous mutation, while the other family members did not. This is the first report that a mutation in SCN4A was identified in a Japanese family with paramyotonia congenita.

Research Grants & Projects

  • Toll様受容体を標的とした制御性B細胞誘導による多発性硬化症の新規治療法の開発
    文部科学省:科学研究費補助金 基盤(C)
    Date (from‐to) : 2018/04 -2020/03 
    Author : 越智 博文
  • スモンに関する調査研究
    厚生労働省:厚生労働科学研究費補助金
    Date (from‐to) : 2014/04 -2019/03 
    Author : 小長谷正明
  • 発性硬化症生体試料バンクを活用したアジア人特有の遺伝子環境因子探索による病態解明
    厚生労働省:厚生労働科学研究委託費(難治世疾患実用化研究事業)
    Date (from‐to) : 2014/04 -2016/03 
    Author : 吉良 潤一
  • 免疫性神経疾患に関する調査研究
    厚生労働省:厚生労働科学研究費補助金
    Date (from‐to) : 2007/04 -2008/03 
    Author : 吉良 潤一
  • TGF-β陽性調節性T細胞を標的とした多発性硬化症の画期的治療法開発に関する研究
    文部科学省:科学研究費補助金 基盤(C)
    Date (from‐to) : 2007/04 -2008/03 
    Author : 越智 博文
  • 遺伝子改変マウスを用いた視神経脊髄型多発性硬化症特異抗原免疫による動物モデルの開発
    文部科学省:科学研究費補助金 基盤(B)
    Date (from‐to) : 2003/04 -2004/03 
    Author : 吉良 潤一
  • 脳プロテオーム解析法による多発性硬化症軸索障害機序の解明
    文部科学省:科学研究費補助金 基盤(C)
    Date (from‐to) : 2003/04 -2004/03 
    Author : 越智 博文
  • 重症筋無力症の発症機序におけるアレルギー反応の関与についての研究
    文部科学省:科学研究費補助金 基盤(C)
    Date (from‐to) : 2001/04 -2002/03 
    Author : 村井 弘之
  • Immunology of multiple sclerosis
    Grant-in-Aid for Scientific Research
    Date (from‐to) : 2002
  • アトピー素因を伴う脊髄炎・ミエロパチーにおける疾患感受性遺伝子の検索
    文部科学省:科学研究費補助金 萌芽研究
    Author : 吉良 潤一
  • 末梢血単球の機能制御による多発性硬化症の新規治療法開発に関する研究
    文部科学省:科学研究費補助金 基盤(C)
    Author : 越智 博文


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