研究者業績

桑原 聡

クワバラ サトシ  (Satoshi Kuwabara)

基本情報

所属
千葉大学 大学院医学研究院脳神経内科学 教授 (教授)
学位
医学博士(1993年3月 千葉大学)

J-GLOBAL ID
200901033727459280
researchmap会員ID
1000200574

論文

 938
  • Sawai S, Mori M, Kuwabara S
    Neurology 83(24) 2314; discussion 2314-5 2014年12月  査読有り
  • Hiroki Masuda, Masahiro Mori, Akiyuki Uzawa, Saeko Masuda, Mayumi Muto, Tomohiko Uchida, Satoshi Kuwabara
    Clinical and Experimental Neuroimmunology 5(1) 52-53 2014年12月1日  査読有り
  • Masahiro Mori, Satoshi Kuwabara
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 85(11) 1180-1180 2014年11月  査読有り
  • Shunsuke Koga, Ayako Kojima, Chieko Ishikawa, Satoshi Kuwabara, Kimihito Arai, Yasumasa Yoshiyama
    NEUROBIOLOGY OF DISEASE 71 180-192 2014年11月  査読有り
    The number of patients with Alzheimer's disease (AD) is increasing worldwide, and available drugs have shown limited efficacy. Hence, preventive interventions and treatments for presymptomatic AD are currently considered very important. Obesity rates have also been increasing dramatically and it is an independent risk factor of AD. Therefore, for the prevention of AD, it is important to elucidate the pathomechanism between obesity and AD. We generated high calorie diet (HCD)-induced obese tauopathy model mice (PS19), which showed hyperleptinemia but limited insulin resistance. HCD enhanced tau pathology and glial activation. Conversely, voluntary exercise with a running wheel normalized the serum leptin concentration without reducing body weight, and restored the pathological changes induced by HCD. Thus, we speculated that persistent hyperleptinemia played an important role in accelerating pathological changes in PS19 mice. Leptin primarily regulates food intake and body weight via leptin receptor b (LepRb). Interestingly, the nuclear staining for p-STAT3, which was activated by LepRb, was decreased in hippocampal neurons in HCD PS19 mice, indicating leptin resistance. Meanwhile, astroglial activation and the astrocytic expression of a short LepR isoform, LepRa, were enhanced in the hippocampus of HCD PS19 mice. Real-time PCR analysis demonstrated that leptin increased mRNA levels for pro-inflammatory cytokines including IL-1 beta and TNF-alpha in primary cultured astrocytes from wild type and LepRb-deficient mice. These observations suggest that persistent hyperleptinemia caused by obesity induces astrocytic activation, astrocytic leptin hypersensitivity with enhanced LepRa expression, and enhanced inflammation, consequently accelerating tau pathology in PS19 mice. (C) 2014 The Authors. Published by Elsevier Inc.
  • Nobuyuki Araki, Masato Asahina, Hiroshi Arai, Akira Katagiri, Anupama Poudel, Yoshikatsu Fujinuma, Yoshitaka Yamanaka, Satoshi Kuwabara
    MOVEMENT DISORDERS 29 S41-S42 2014年11月  
  • A. Uzawa, M. Mori, J. Taniguchi, S. Kuwabara
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY 178(2) 245-252 2014年11月  査読有り
    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Bradykinin is the end-product of the kallikrein/kinin system, which has been recognized as an endogenous target for combating CNS inflammation. Angiotensin-converting enzyme (ACE) inhibitors influence the kallikrein/kinin system and reportedly have immunomodulatory characteristics. The objectives of this study were to determine whether bradykinin is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and whether bradykinin control by the ACE inhibitor could be a therapeutic target in MS. The ACE inhibitor enalapril (1.0 or 0.2 mg/kg/day) was administered orally to EAE mice and the serum levels of bradykinin and cytokines in EAE mice were analysed. As a result, the administration of enalapril increased serum bradykinin levels, decreased the clinical and pathological severity of EAE and attenuated interleukin-17-positive cell invasion into the CNS. Additionally, bradykinin receptor antagonist administration reduced the favourable effects of enalapril. Our results suggest that bradykinin is involved in the pathomechanism underlying CNS inflammation in EAE, possibly through inhibiting cell migration into CNS. Control of the kallikrein/kinin system using ACE inhibitors could be a potential therapeutic strategy in MS.
  • Sagiri Isose, Sonoko Misawa, Masahiro Sonoo, Toshio Shimuzu, Chizuko Oishi, Kazumoto Shibuya, Saiko Nasu, Yukari Sekiguchi, Satsuki Mitsuma, Minako Beppu, Shigeki Omori, Tetsuo Komori, Norito Kokubun, Akira Inaba, Fumiko Hirashima, Satoshi Kuwabara
    JOURNAL OF CLINICAL NEUROPHYSIOLOGY 31(5) 441-443 2014年10月  査読有り
    Purpose:In current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy, the cutoff values of distal compound muscle action potential (DCMAP) duration are defined using electromyogram low-cut filter setting of 20 Hz. We aimed to assess effects of low-cut filter on DCMAP duration (10 vs. 20 Hz).Methods:We prospectively measured DCMAP duration in 130 normal controls and 42 patients, fulfilling diagnostic criteria for typical chronic inflammatory demyelinating polyneuropathy by European Federation of Neurological Societies/Peripheral Nerve Society.Results:Distal compound muscle action potential duration was significantly shortened with 20-Hz than 10-Hz filtering. When the cutoff values were defined as the upper limit of normal (ULN, mean + 2.5SD), the sensitivity/specificity was 67%/95% in 10-Hz recordings, and 69%/95% in 20-Hz recordings. This diagnostic accuracy was similar to that defined by receiver operating characteristic analyses.Conclusions:Distal compound muscle action potential duration significantly affected by the low-cut electromyogram filter setting, but with at least 10 and 20 Hz, the diagnostic accuracy is similar.
  • Johannes Brettschneider, Kimihito Arai, Kelly Del Tredici, Jon B. Toledo, John L. Robinson, Edward B. Lee, Satoshi Kuwabara, Kazumoto Shibuya, David J. Irwin, Lubin Fang, Vivianna M. Van Deerlin, Lauren Elman, Leo McCluskey, Albert C. Ludolph, Virginia M. -Y. Lee, Heiko Braak, John Q. Trojanowski
    ACTA NEUROPATHOLOGICA 128(3) 423-437 2014年9月  査読有り
    We examined the phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) inclusions as well as neuronal loss in full-length spinal cords and five selected regions of the central nervous system from 36 patients with amyotrophic lateral sclerosis (ALS) and 10 age-matched normal controls. The most severe neuronal loss and pTDP-43 lesions were seen in lamina IX motor nuclei columns 4, 6, and 8 of lower cervical segments and in columns 9-11 of lumbosacral segments. Severity of pTDP-43 pathology and neuronal loss correlated closely with gray and white matter oligodendroglial involvement and was linked to onset of disease, with severe involvement of columns 4, 6, and 8 of upper extremity onset cases and severe involvement of columns of 9, 10, and 11 in cases with lower extremity onset. Severe TDP-43 lesions and neuronal loss were observed in stage 4 cases and sometimes included Onuf's nucleus. Notably, three cases displayed pTDP-43 aggregates in the midbrain oculomotor nucleus, which we had not seen previously even in cases with advanced (i.e., stage 4) pathology. pTDP-43 aggregates were observed in neurons of Clarke's column in 30.6 % of cases but rarely in the intermediolateral nucleus (IML). Gray matter oligodendroglial pTDP-43 inclusions were present in areas devoid of neuronal pTDP-43 aggregates and neuronal loss. Taken together, our findings indicate that (1) the dorsolateral motor nuclei columns of the cervical and lumbosacral anterior horn may be the earliest foci of pTDP-43 pathology in the spinal cord, (2) gray matter oligodendroglial involvement is an early event in the ALS disease process that possibly heralds subsequent involvement of neurons by pTDP-43 pathology, and (3) in some very advanced cases, there is oculomotor nucleus involvement, which may constitute an additional neuropathological stage (designated here as stage 5) of pTDP-43 pathology in ALS.
  • Atsuhiko Sugiyama, Masato Asahina, Yusuke Takeda, Toshiaki Shiojiri, Kenji Sano, Shu-ichi Ikeda, Satoshi Kuwabara
    AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS 21(3) 218-220 2014年9月  査読有り
  • S. Mitsuma, P. Van den Bergh, M. Sonoo, Y. Rajabally, A. Inaba, N. Kokubun, T. Komori, T. Shimizu, S. Misawa, S. Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 19(3) 275-275 2014年9月  
  • Yu Sekiguchi, S. Misawa, K. Shibuya, S. Mitsuma, Y. Iwai, K. Watanabe, M. Beppu, S. Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 19(3) 280-280 2014年9月  
  • Bae JS, Yuki N, Kuwabara S, Kim JK, Vucic S, Lin CS, Kiernan MC
    Journal of neurology, neurosurgery, and psychiatry 85(8) 905-911 2014年8月  査読有り
  • Shunsuke Segawa, Setsu Sawai, Shota Murata, Motoi Nishimura, Minako Beppu, Kazuyuld Sogawa, Masaharu Watanabe, Mamoru Satoh, Tomoo Matsutani, Masayoshi Kobayashi, Yasuo Iwadate, Satoshi Kuwabara, Naokatsu Saeki, Fumio Nomura
    CLINICA CHIMICA ACTA 435 59-61 2014年8月  査読有り
    Background: Bacterial meningitis is a neurological emergency. Early diagnosis and rapid initiation of antimicrobial therapy are vital. Methods: Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is increasingly used as a rapid and accurate microbial diagnostic method for species identification of pathogens. Although this technology requires a growth step to obtain bacterial colonies for the acquisition of substantial spectra in most cases, it can also be used to analyze clinical specimens such as urine and cerebrospinal fluid for direct bacterial identification. There are very few reports describing the use of MALDI-TOF MS for the direct detection of microorganisms causing bacterial meningitis. Results: We describe a case of bacterial meningitis caused by Klebsiella pneumoniae in which MALDI-TOF MS provided a rapid bacteriological diagnosis, thus enabling early and appropriate treatment. Conclusions: Identification of microbes based on MALDI-TOF MS is now an important technology in clinical microbiology laboratories that are required to provide a rapid diagnosis of bacterial meningitis. (C) 2014 Elsevier B.V. All rights reserved.
  • Fumitaka Shimizu, Setsu Sawai, Yasuteru Sano, Minako Beppu, Sonoko Misawa, Hideaki Nishihara, Michiaki Koga, Satoshi Kuwabara, Takashi Kanda
    PLOS ONE 9(8) e104205 2014年8月  査読有り
    Objective: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype. Methods: We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs). Results: The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion. Conclusions: Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.
  • T. Uchiyama, T. Yamamoto, C. Shibata-Yamaguchi, K. Kaga, M. Fuse, Y. Watanabe, Y. Awa, T. Kamai, T. Yamanishi, R. Sakakibara, S. Kuwabara, K. Hirata
    NEUROUROLOGY AND URODYNAMICS 33(6) 839-839 2014年8月  
  • Sawai S, Satoh M, Mori M, Misawa S, Sogawa K, Kazami T, Ishibashi M, Beppu M, Shibuya K, Ishige T, Sekiguchi Y, Noda K, Sato K, Matsushita K, Kodera Y, Nomura F, Kuwabara S
    Neurology 83(2) 113-117 2014年7月8日  査読有り
  • Shahrizaila N, Kokubun N, Sawai S, Umapathi T, Chan YC, Kuwabara S, Hirata K, Yuki N
    Neurology 83(2) 118-124 2014年7月  査読有り
  • Kenichi Yasui, Ichiro Yabe, Kunihiro Yoshida, Kazuaki Kanai, Kimihito Arai, Mizuki Ito, Osamu Onodera, Shigeru Koyano, Eiji Isozaki, Setsu Sawai, Yoshiki Adachi, Hidenao Sasaki, Satoshi Kuwabara, Takamichi Hattori, Gen Sobue, Hidehiro Mizusawa, Shoji Tsuji, Masatoyo Nishizawa, Kenji Nakashima
    ORPHANET JOURNAL OF RARE DISEASES 9 118 2014年7月  査読有り
    Background: Only a few prospective studies have determined which clinical symptoms and factors are associated with the disease severity of spinocerebellar ataxia type 6 (SCA6). A multicenter longitudinal cohort study was conducted to clarify both the natural history of SCA6 in Japan and the factors influencing disease progression. Methods: Patients were consecutively recruited between 2007 and 2008. Scores from the Scale for the Assessment and Rating of Ataxia (SARA) and Barthel Index (BI) were collected prospectively each year. Additionally, data from the Japan intractable diseases research (IDR) registry were collected both retrospectively, from 2003 to 2006, and prospectively, from 2007 to 2010. As a result, we were able to collect 3 years of retrospective data and 4 years of prospective data during the course of 3 yearly visits. Results: Forty-six patients were registered. The follow-up rate of the third year was 93%. The SARA scores worsened significantly each year. Over 3 years, the decline of the SARA scores was 1.33 +/- 1.40 points/year. The results of multivariate analysis of the decline of the SARA score were not significant. The IDR scores correlated well with the SARA and BI scores. Kaplan-Meier curves of 7 years of data from the IDR registry illustrated the correlation between the ability to walk and the time course of the disease. Conclusions: Information regarding the progression of ataxia and the decline in the activities of daily living (ADL) in patients with SCA6 was obtained by a 3-year cohort study and a 7-year IDR study. The decline of the SARA score of patients with SCA6 was 1.33 +/- 1.40 points/year. The results elucidate the natural history of SCA6, factors influencing disease severity, and utility of data from the IDR registry of Japan.
  • Tatsuya Yamamoto, Ryuji Sakakibara, Tomoyuki Uchiyama, Chiharu Yamaguchi, Sayaka Ohno, Fumio Nomura, Mitsuru Yanagisawa, Takamichi Hattori, Satoshi Kuwabara
    NEUROUROLOGY AND URODYNAMICS 33(5) 516-523 2014年6月  査読有り
    Aims Because time-dependent changes and gender differences in urinary dysfunction in patients with multiple system atrophy (MSA) are yet unknown, we aimed to determine these parameters through a combination of urodynamic examination and the results of a questionnaire on urinary symptoms. Methods We retrospectively reviewed 66 patients with MSA who responded to a urinary symptoms questionnaire and underwent urodynamic examination more than twice. The participants' mean age was 62 years and mean disease duration at the first urodynamic examination was 3.2 years. Mean duration between the first and second urodynamic examination was 441 days. Results With regard to overall (both genders) time-dependent change, none of the urinary symptoms showed significant differences. In the urodynamic examination there were significant differences in reduced urine flow, increased post-void residuals, and decreased detrusor contractility at the second examination. With regard to gender differences, at the first examination, night-time urinary frequency, and voiding symptoms were significantly more severe in male than in female patients; however, at the second examination, except for urinary urgency, gender differences were not observed for any other symptoms. In urodynamic examination, the degree of detrusor contraction was significantly less in male patients at the first examination. However, no significant differences were found in urodynamic examination at the second examination. Conclusions The present study indicates that voiding dysfunction progressed without significant worsening of voiding symptoms. In addition, gender differences are important in evaluating urinary dysfunction being basically less severe in female than in male patients, at least during the early stage. Neurourol. Urodynam. 33:516-523, 2014. (c) 2013 Wiley Periodicals, Inc.
  • Junko Taniguchi, Chie Seki, Hiroyuki Takuwa, Hiroshi Kawaguchi, Yoko Ikoma, Masayuki Fujinaga, Iwao Kanno, Ming-Rong Zhang, Satoshi Kuwabara, Hiroshi Ito
    MOLECULAR IMAGING AND BIOLOGY 16(3) 395-402 2014年6月  査読有り
    Rho is a small molecular weight GTP-binding protein and works as a molecular shuttling switch between an active (GTP-bound) and inactive (GDP-bound) state. Rho is known to be involved in cell motility, cell adhesion, and cytokinesis through actin cytoskeleton reorganization. The GTP-bound form of Rho interacts with its specific downstream target, triggering intracellular signaling cascades. Rho effectors such as Rho-kinases have been isolated on the basis of their selective binding to the GTP-bound form of Rho. Rho-kinase is thought to have an important role in the pathogenesis of a variety of neurological diseases because activation of the Rho/Rho-kinase pathway has been observed in various central nervous system disorders. Previous histochemical studies have shown multiple molecular mechanisms for the regulation of Rho-kinase. Neuroimaging of Rho/Rho-kinase has rarely been studied because of a lack of appropriate radiotracers. Recently, N-[C-11]methyl-hydroxyfasudil, a new radiotracer for positron emission tomography (PET), has been introduced to measure Rho-kinase activity. In this study, the regional distribution and kinetics of N-[C-11]methyl-hydroxyfasudil were investigated in the brains of mice. A 90-min dynamic scan was performed following intravenous infusion of N-[C-11]methyl-hydroxyfasudil. The uptake of N-[C-11]methyl-hydroxyfasudil reached a maximum within 5 min and gradually decreased in all organs. The standard uptake values (SUVs) in the brain, liver, and kidney on average between 30 to 60 min were 0.17 +/- 0.03, 0.76 +/- 0.18, and 0.62 +/- 0.18 and from 60 to 90 min were 0.15 +/- 0.01, 0.69 +/- 0.33, and 0.64 +/- 0.17, respectively. N-[C-11]Methyl-hydroxyfasudil showed a widespread distribution throughout the brain, with low levels of radioactivity. Radioactivity concentration in plasma at 90 min after injection of N-[C-11]methyl-hydroxyfasudil resulted in SUVs in the control and fasudil pretreatment of 0.0013 and 0.0023 +/- 0.0008, respectively. Compared to normal control mice, about twofold higher radioactivity concentration was observed in fasudil-pretreated mice. In a cold brain injury mouse model, accumulation of N-[C-11]methyl-hydroxyfasudil was slightly higher at the injury site than that at the control site, and the difference was statistically significant in the "24 h after injury" group (P < 0.05). These results suggest that following brain injury, N-[C-11]methyl-hydroxyfasudil binds to the active form of Rho-kinase. PET imaging using N-[C-11]methyl-hydroxyfasudil could provide new insights into the pathophysiology of a variety of neurological disorders including stroke, inflammatory diseases, demyelinating diseases, Alzheimer's disease, and neuropathic pain.
  • Shunsuke Koga, Ayako Kojima, Satoshi Kuwabara, Yasumasa Yoshiyama
    NEUROSCIENCE LETTERS 571 11-16 2014年6月  査読有り
    Accumulating evidence indicates that obesity is an independent risk factor for developing Alzheimer disease (AD). Recent studies have shown that diet-induced obesity (DIO) enhances AD-related pathologies in transgenic mouse models of the disease. DIO increases amyloid beta (A beta) deposition in amyloidogenic transgenic mice and enhances tau phosphorylation in tau transgenic mice. However, it remains unclear whether DIO also enhances AD-related pathological processes in wild-type (WT) mice. In this study, we examined the effects of DIO on A beta and tau pathology in WT mice using immunohistochemistry. In addition, we evaluated the protective effect of voluntary exercise on the DIO-induced pathological changes. DIO caused tau phosphorylation and astroglial activation in the hippocampus in WT mice. Interestingly, these changes were associated with enhanced astrocytic leptin receptor (LepR) expression and mild microgliosis, but not A beta accumulation. Although phosphorylated tau staining was only observed in the hippocampus, astrogliosis and microgliosis were present in both the amygdala and hippocampus. However, no apparent neuronal loss was observed. Voluntary exercise prevented these DIO-induced pathological changes. Our results demonstrate for the first time that DIO causes tau phosphorylation and that astrocytic LepR might be involved in the pathological process in WT mouse hippocampus. Our findings also suggest that physical exercise is a promising strategy for the prevention of AD in patients with obesity. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
  • Akiyuki Uzawa, Masahiro Mori, Junko Taniguchi, Saeko Masuda, Mayumi Muto, Tomohiko Uchida, Hiroki Masuda, Satoshi Kuwabara
    MULTIPLE SCLEROSIS JOURNAL 20(7) 908-909 2014年6月  
  • S. Masuda, M. Mori, A. Uzawa, M. Muto, T. Uchida, H. Masuda, S. Kuwabara
    MULTIPLE SCLEROSIS JOURNAL 20(7) 939-939 2014年6月  
  • Masahiro Mori, Mayumi Muto, Takaki Hiwasa, Akiyuki Uzawa, Saeko Masuda, Tomohiko Muto, Hiroki Masuda, Satoshi Kuwabara
    MULTIPLE SCLEROSIS JOURNAL 20(7) 910-911 2014年6月  
  • Satoshi Kuwabara, Kazumoto Shibuya, Sonoko Misawa
    CLINICAL NEUROPHYSIOLOGY 125(5) 872-873 2014年5月  査読有り
  • Akiyuki Hiraga, Satoshi Kuwabara
    CLINICAL NEUROLOGY AND NEUROSURGERY 120 142-142 2014年5月  査読有り
  • Hiroki Masuda, Masahiro Mori, Shoichi Ito, Toshiyuki Yagishita, Satoshi Kuwabara
    Case reports in neurology 6(2) 166-70 2014年5月  査読有り
    BACKGROUND: When a neuropsychiatric symptom due to encephalopathy develops in a patient with anti-thyroid antibodies, especially when the symptom is steroid-responsive, Hashimoto's encephalopathy (HE) needs to be included in the differential diagnosis of the patient. Although HE is an elusive disease, it is thought to cause various clinical presentations including seizures, myoclonus, and epilepsia partialis continua (EPC). CASE REPORT: We present the case of a 33-year-old Japanese woman who acutely developed EPC in the right hand as an isolated manifestation. A thyroid ultrasound showed an enlarged hypoechogenic gland, and a thyroid status assessment showed euthyroid with high titers of thyroid antibodies. A brain MRI revealed a nodular lesion in the left precentral gyrus. Corticosteroid treatment resulted in a cessation of the symptom. CONCLUSIONS: A precentral nodular lesion can be responsible for steroid-responsive EPC in a patient with anti-thyroid antibodies and may be caused by HE. The serial MRI findings of our case suggest the presence of primary demyelination, with ischemia possibly due to vasculitis around the demyelinating lesion.
  • H. Shimada, S. Hirano, H. Shinotoh, S. Furukawa, Y. Eguchi, K. Takahata, Y. Kimura, Y. Ikoma, M. Yamada, M. -R. Zhang, H. Ito, M. Higuchi, S. Kuwabara, T. Suhara
    MOVEMENT DISORDERS 29 S95-S95 2014年5月  
  • T. Yamamoto, M. Asahina, T. Uchiyama, S. Hirano, Y. Yamanaka, A. Sugiyama, M. Yanagisawa, R. Sakakibara, S. Kuwabara
    MOVEMENT DISORDERS 29 S132-S132 2014年5月  
  • S. Furukawa, H. Shimada, H. Shinotoh, S. Hirano, M. Yamada, H. Kawaguchi, H. Ito, S. Nishida, M. Kobayashi, T. Sasai, M. Nakamura, S. Kuwabara, Y. Inoue, T. Suhara
    MOVEMENT DISORDERS 29 S291-S291 2014年5月  
  • M. Koide, S. Isose, K. Ito, Y. Yoshiyama, K. Arai, A. Uzawa, S. Kuwabara
    EUROPEAN JOURNAL OF NEUROLOGY 21 165-165 2014年5月  
  • T. Uchiyama, Z. Liu, T. Yamamoto, C. Shibata-Yamaguchi, Y. Watanabe, K. Hashimoto, H. Tateno, Y. Higuchi, T. Shingo, M. Yanagisawa, M. Fuse, T. Yamanishi, R. Sakakibara, S. Kuwabara, K. Hirata
    MOVEMENT DISORDERS 29 S570-S570 2014年5月  
  • M. Koide, S. Isose, K. Ito, Y. Yoshiyama, K. Arai, A. Uzawa, S. Kuwabara
    JOURNAL OF NEUROLOGY 261 S116-S116 2014年5月  
  • K. Arai, M. Koide, S. Isose, K. Itoh, Y. Yoshiyama, S. Kuwabara, K. Kanai, H. Tomiyama, N. Hattori
    MOVEMENT DISORDERS 29 S373-S374 2014年5月  
  • A. Uzawa, N. Kawaguchi, K. Himuro, T. Kanai, S. Kuwabara
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY 176(2) 232-237 2014年5月  査読有り
    Myasthenia gravis (MG) is an autoimmune-mediated inflammatory disease of the neuromuscular junction. Previous studies of animal MG models have suggested important roles of cytokines in MG pathogenesis, but adequate studies on cytokines in human MG are lacking. Using a multiplex suspension array system, we measured the serum levels of 27 cytokines/chemokines in 47 anti-acetylcholine receptor antibody-positive patients with MG and 20 normal controls (NC) to investigate the contribution of cytokines/chemokines toward MG pathogenesis. Correlations between clinical parameters and cytokine/chemokine levels in patients with MG were also examined. The serum levels of interleukin (IL)-15 (mean +/- standard deviation: 6 center dot 85 +/- 6 center dot 97 pg/ml) and vascular endothelial growth factor (VEGF) (96 center dot 21 +/- 71 center dot 60 pg/ml) significantly increased, whereas IL-4 levels (3 center dot 57 +/- 0 center dot 86 pg/ml) decreased in patients with MG compared with NC (IL-15: 4 center dot 42 +/- 1 center dot 55 pg/ml; VEGF: 63 center dot 51 +/- 32 center dot 95 pg/ml; IL-4: 4 center dot 15 +/- 0 center dot 81 pg/ml, P < 0 center dot 05). In addition, eight cytokines (IL-4, IL-8, IL-15, eotaxin, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, VEGF and IL-1b) were significantly changed among MG patients with thymoma, MG patients without thymoma and NC (P < 0 center dot 05). Some cytokines, such as IL-4, IL-15, and VEGF, may play roles in the pathogenesis of MG.
  • Mori T, Shimada H, Shinotoh H, Hirano S, Eguchi Y, Yamada M, Fukuhara R, Tanimukai S, Zhang MR, Kuwabara S, Ueno S, Suhara T
    Journal of neurology, neurosurgery, and psychiatry 85(4) 449-455 2014年4月  査読有り
  • Tadahiro Yonezu, Shoichi Ito, Masahiro Mori, Yoshitsugu Ogawa, Takahiro Makino, Akiyuki Uzawa, Satoshi Kuwabara
    MULTIPLE SCLEROSIS JOURNAL 20(3) 331-337 2014年3月  査読有り
    Background: Spinal magnetic resonance imaging (MRI) finding of longitudinally extensive spinal cord lesions (LESCL) extending over three vertebral segments and involvements of spinal central gray matter have been reported in patients with neuromyelitis optica (NMO). Objectives: We aimed to review spinal MRI findings in NMO and multiple sclerosis (MS), and to determine whether the "bright spotty lesions" (BSLs) are a discriminative finding of NMO. Methods: For this study, 24 consecutive patients with NMO and 34 patients with MS were enrolled. BSLs were defined as very hyperintense spotty lesions on axial T2WI. We also studied the length, distribution, signal homogeneity, size, and presence of contrast-enhanced lesions. Results: BSLs were more frequently found in patients with NMO (54%) than in those with MS (3%; p < 0.01). LESCL were found in 67% of the NMO patients. BSLs were seen in 63% of the patients without LESCL. BSLs or LESCL were found in 88% of the NMO patients. Inhomogeneous lesions, transversally extensive lesions, and central lesions were more frequently seen in NMO than in MS. Conclusions: BSLs are a newly defined spinal MRI finding specifically seen in NMO. In combination with LESCL, BSLs can help differentiate patients with NMO from those with MS with higher sensitivity than LESCL alone.
  • Jun-Ichiro Shimada, Masahiro Yasaka, Yoshiyuki Wakugawa, Toshiyasu Ogata, Noriko Makihara, Shoichi Ito, Satoshi Kuwabara, Yasushi Okada
    CIRCULATION JOURNAL 78(3) 738-742 2014年3月  査読有り
    Background: The features of acute aortogenic embolic stroke on magnetic resonance diffusion-weighted imaging (DWI) have not been fully elucidated, so we compared patients with acute aortogenic embolic stroke and those with acute cardioembolic stroke. Methods and Results: This study included 40 consecutive patients with acute aortogenic embolic stroke, and 40 age- and sex-matched patients with acute cardioembolic stroke. The diagnosis of aortogenic embolic stroke was made when patients met 5 criteria: (1)acute neurologic event lasting >24h; (2) positive signals on DWI; (3) atherosclerotic lesions >= 3.5-mm thick at the aortic arch on transesophageal echocardiography; (4) neuroradiologic features suggesting embolic stroke, such as lesions involving the brain cortex or the re-opening phenomenon of previously occluded vessels on Magnetic Resonance Angiography (MRA); and (5) absence of other embolic sources, including heart disease and carotid stenosis. The number, site, and maximal diameter of the infarct lesions on DWI were compared between the aortogenic and cardiogenic groups. The aortogenic patients more frequently had >= 3 lesions (25.0% vs. 2.5%, P<0.01), lesions with a maximal diameter <30 mm (77.5% vs. 20.0%, P< 0.001), and vertebrobasilar system lesions (55.0% vs. 10.0%, P< 0.001) than the cardiogenic patients. Conclusions: Acute aortogenic embolic stroke is characterized by multiple (>= 3) and small lesions, and involvement of the vertebrobasilar system.
  • Ai Miyashiro, Naoko Matsui, Yoshimitsu Shimatani, Hiroyuki Nodera, Yuishin Izumi, Satoshi Kuwabara, Tomihiro Imai, Masayuki Baba, Tetsuo Komori, Masahiro Sonoo, Takahiro Mezaki, Jun Kawamata, Takefumi Hitomi, Nobuo Kohara, Kimiyoshi Arimura, Shuji Hashimoto, Kokichi Arisawa, Susumu Kusunoki, Ryuji Kaji
    MUSCLE & NERVE 49(3) 357-361 2014年3月  査読有り
    Introduction: Our objective was to do an epidemiologic survey of patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan. Methods: In this retrospective study, we examined 46 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) and the revised El Escorial criteria. The efficacy of intravenous immunoglobulin (IVIg) was also taken into consideration in the diagnosis of MMN. Results: The ratio of MMN to ALS patients (0-0.10) varied among the centers, but mostly converged to 0.05. The prevalence was estimated to be 0.29 MMN patients and 6.63 ALS patients per 100,000 population. Conclusions: The frequency of MMN patients was around 1 out of 20 ALS patients, and MMN was possibly underdiagnosed in some centers. Muscle Nerve49:357-361, 2014
  • Saiko Nasu, Sonoko Misawa, Chiaki Nakaseko, Kazumoto Shibuya, Sagiri Isose, Yukari Sekiguchi, Satsuki Mitsuma, Shigeki Ohmori, Yuta Iwai, Minako Beppu, Naomi Shimizu, Chikako Ohwada, Yusuke Takeda, Yumi Fujimaki, Satoshi Kuwabara
    CLINICAL NEUROPHYSIOLOGY 125(2) 381-387 2014年2月  査読有り
    Objective: Bortezomib is a proteasome inhibitor with high efficacy for multiple myeloma but with severe peripheral neurotoxicity, leading to dose modification and severe neurological disability. This study aimed to investigate the pathophysiology of bortezomib-induced neuropathy. Methods: Threshold tracking was used to assess the excitability of sensory and motor axons. Measurements were sequentially performed before and after bortezomib treatment in nine patients with newly diagnosed multiple myeloma. Results: In total, 67% of patients finally developed symptomatic neuropathy. Changes in sensory axonal excitability indices readily occurred after the first course of administration. Patterns of changes in excitability indices suggest membrane depolarization (decreased superexcitability, P < 0.001; decreased depolarizing threshold electrotonus 90-100 ms, P = 0.02). Abnormalities in nerve conduction parameters suggestive of axonal degeneration appeared after the second course of treatment. Conclusions: Bortezomib induces a depolarizing shift in resting membrane potential prior to the development of neuropathy. Membrane depolarization could be associated with impairment of electrogenic Na+-K+-ATPase-dependent pump caused by toxic effects of bortezomib on mitochondria. Significance: Axonal depolarization and hyperexcitability might enhance neurodegeneration in bortezomib-induced neuropathy. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Akiyuki Hiraga, Ikuo Kamitsukasa, Satoshi Kuwabara
    CLINICAL NEUROLOGY AND NEUROSURGERY 117 51-54 2014年2月  査読有り
    Background: Cases of transient myoclonus without other neurological manifestations in the elderly have very rarely been reported. Objective: To report clinical features of elderly people with isolated transient myoclonus. Methods: Clinical and laboratory features of 11 consecutive patients with isolated transient myoclonus (six men and five women; mean age, 75 years) were reviewed. Transient myoclonus was defined as an acute onset of tremulous myoclonus with/without asterixis in adults without other neurological symptoms. Results: Preceding infections were recorded in five patients (pneumonia, two; upper respiratory tract infection, two; and septic arthritis of the shoulder, one). Myoclonus predominantly affected the head and/or neck (n = 10) and upper extremities (n = 11), compared with the trunk (n =2) and lower extremities (n = 6). Asterixis was observed in six patients. Laboratory testing, neuroimaging, and electroencephalograms revealed no specific abnormalities. With or without treatment using benzodiazepines, myoclonus in all patients resolved completely within 1-4 days, although five had recurrence 2-19 months after their first episodes. Among these five patients, the accompanying asterixis patterns (presence or not) in four were different in the first and subsequent episodes. Conclusions: Isolated transient myoclonus with or without asterixis may be more common than generally believed, and it could be a clinical entity or disease spectrum. Transient myoclonus is a benign condition in the elderly, but can be under-reported or misdiagnosed. Therefore, it is important to recognize that the elderly may have this syndrome. (C) 2013 Elsevier B.V. All rights reserved.
  • T. Yamamoto, T. Uchiyama, R. Sakakibara, J. Taniguchi, S. Kuwabara
    NEUROSCIENCE 259 43-52 2014年2月  査読有り
    Aims: Not all the mechanisms by which subthalamic nucleus deep brain stimulation (STN-DBS) alleviates parkinsonian symptoms have been clarified as yet. The levels of striatal monoamine and the subthalamic beta activity might contribute to its efficacy. However, their direct relationship is unclear. We aimed to examine the correlation between the striatal monoamine and the STN beta activity induced by STN-DBS. Experimental procedures: Experiments were performed under urethane anesthesia in normal (n = 4) and 6-hydroxydopamine hemi-lesioned Parkinson's disease (PD) model rats (n = 5). STN-DBS was applied to the left STN, and local field potential (LFP) was recorded before and after STN-DBS. Striatal extracellular fluid was collected before, during, and after STN-DBS. Spectral analysis of STN-LFP was performed, and the levels of monoamine were measured. Results: The levels of 3-4-dihydroxyphenylacetic acid (DOPAC) were significantly decreased after the cessation of stimulation in PD model rats. The levels of none of the monoamines were significantly affected in normal rats. The STN beta power was significantly elevated after the cessation of stimulation in normal rats but was significantly decreased in PD model rats. Results: The STN beta power and the levels of DOPAC and 5-HT was positively correlated in PD model rats, whereas the levels of dopamine and 5-HT showed positive correlation and the levels of DOPAC and Homovanillic acid (HVA) showed negative correlation in normal rats. Conclusion: STN-DBS could decrease the levels of DOPAC and the STN beta power in a PD model rat. The STN beta power and the levels of striatal monoamine might be differentially correlated between normal and PD model rats. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
  • Satoshi Kuwabara, Yukari Sekiguchi, Sonoko Misawa
    CLINICAL NEUROPHYSIOLOGY 125(1) 213-214 2014年1月  査読有り
  • Akiyuki Uzawa, Masahiro Mori, Satoshi Kuwabara
    JOURNAL OF CLINICAL NEUROSCIENCE 21(1) 12-21 2014年1月  査読有り
    Neuromyelitis optica (NMO) is an inflammatory disorder of the central nervous system (CNS) that predominantly affects the optic nerves and spinal cord. Previously, it has been considered to be a severe variant of multiple sclerosis (MS), especially common in Asia. However, the finding that most NMO patients have autoantibodies against aquaporin-4 (AQP4) has improved our knowledge of its pathogenesis and led to the concept that NMO is a disease distinct from MS. Although the 2006 NMO revised criteria are useful for diagnosing NMO, their usefulness in the diagnosis of early-stage NMO is limited. Hence, there is an urgent need for new and more precise diagnostic methods. Interleukin-6 may play important roles in NMO pathogenesis, as it is involved in the survival of plasmablasts that produce anti-AQP4 antibody in the peripheral circulation and in the enhancement of inflammation in the CNS. Severe blood-brain barrier disruption in NMO allows the anti-AQP4 antibody to access the astrocytic endfeet. The anti-AQP4 antibody causes astrocytic damage through complement activation. Thus, NMO is an astrocytopathic, rather than a demyelinating, disease. Some brain lesions specific to NMO have recently been reported. Significant advances in the understanding of NMO pathogenesis are beginning to improve existing treatment strategies and will help develop new treatments. This review focuses on the current advances in NMO research and its clinical characteristics, immunological findings, neuroimaging and pathophysiology. (C) 2013 Elsevier Ltd. All rights reserved.
  • Teruhiko Sekiguchi, Tadashi Kanouchi, Kazumoto Shibuya, Yu-ichi Noto, Yohsuke Yagi, Akira Inaba, Keisuke Abe, Sonoko Misawa, Satoshi Orimo, Takayoshi Kobayashi, Tomoyuki Kamata, Masanori Nakagawa, Satoshi Kuwabara, Hidehiro Mizusawa, Takanori Yokota
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 85(1) 85-91 2014年1月  査読有り
    Objective To investigate whether or not the lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation in the rostrocaudal direction along the spinal cord, as has been hypothesised (the 'single seed and simple propagation' hypothesis). Methods Subjects included 36 patients with sporadic ALS and initial symptoms in the bulbar, respiratory or upper limb regions. Abnormal spontaneous activities in needle electromyography (nEMG)-that is, fibrillation potentials, positive sharp waves (Fib/PSWs) or fasciculation potentials (FPs)-were compared among the unilateral muscles innervated by different spinal segments, especially between the T10 and L5 paraspinal muscles, and between the vastus medialis and biceps femoris. Axon length and the proportion of muscle fibre types, which are both related to motoneuronal vulnerability in ALS, are similar in the paired muscles. Results Fourteen of 36 patients showed a non-contiguous distribution of nEMG abnormalities from the onset site, with skipping of intermediate segments. In eight of them, the non-contiguous pattern was evident between paired muscles with the same motoneuronal vulnerability. The non-contiguously affected lumbosacral lesions involved motoneuron columns horizontally or radially proximate to one another, appearing to form a cluster in four of the eight patients. FPs, known to precede Fib/PSWs, were shown more frequently than Fib/PSWs in all the lumbosacral segments but L5, suggesting that 2nd hits occur at L5 and then spread to other lumbosacral segments. Conclusions In sporadic ALS, the distribution of lower motoneuron involvement cannot be explained by the 'single seed and simple propagation' hypothesis alone. We propose a 'multifocal hits and local propagation' hypothesis instead.
  • Atsuhiko Sugiyama, Masahiro Mori, Naruhiko Ishiwada, Keiichi Himuro, Satoshi Kuwabara
    JOURNAL OF THE NEUROLOGICAL SCIENCES 336(1-2) 263-264 2014年1月  査読有り
    Helicobacter cinaedi, a gram-negative spiral bacillus that inhabits the intestinal tracts of rodents and primates, is associated with gastroenteritis in humans. H. cinaedi infection has been commonly reported in immunocompromised individuals such as human immunodeficiency virus-infected patients, but rarely in immunocompetent individuals. Prior contact with animals has attracted attention as a possible Source of H. cinaedi infection. We report a case of meningitis in an immunocompetent 34-year-old woman who had daily contact with a kitten for a month. She developed acute headaches, fevers, and chills. Neurological examination revealed neck stiffness and her cerebrospinal fluid (CSF) exhibited polymorphonudear pleocytosis and a decreased concentration of glucose. Blood and CSF cultures were negative; however, the pathogen responsible for her condition was identified as H. cinaedi by polymerase chain reaction in CSF. This is the first adult case of meningitis caused by H. cinaedi. Thus, this bacillus should be considered a possible causative agent of bacterial meningitis in healthy adults. (C) 2013 Published by Elsevier B.V.
  • Atsuhiko Sugiyama, Shoichi Ito, Shigeki Hirano, Masahiro Mori, Satoshi Kuwabara
    CLINICAL NEUROLOGY AND NEUROSURGERY 116 87-89 2014年1月  査読有り
  • Akiyuki Uzawa, Mori Masahiro, Satoshi Kuwabara
    BRAIN PATHOLOGY 24(1) 67-73 2014年1月  査読有り
    Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extensive transverse myelitis. The discovery of an NMO-specific autoantibody to the aquaporin-4 (AQP4) water channel has improved knowledge of NMO pathogenesis. Many studies have focused on inflammatory and pathological biomarkers of NMO, including cytokines and chemokines. Increased concentrations of T helper (Th)17- and Th2-related cytokines and chemokines may be essential factors for developing NMO inflammatory lesions. For example, interleukin-6 could play important roles in NMO pathogenesis, as it is involved in the survival of plasmablasts that produce anti-AQP4 antibody in peripheral circulation and in the enhancement of inflammation in the central nervous system. Therefore, assessment of these useful biomarkers may become a supportive criterion for diagnosing NMO. Significant advances in the understanding of NMO pathogenesis will lead to the development of novel treatment strategies. This review focuses on the current advances in NMO immunological research, particularly that of cytokines and chemokines.
  • Masato Asahina, Christopher J. Mathias, Akira Katagiri, David A. Low, Ekawat Vichayanrat, Yoshikatsu Fujinuma, Yoshitaka Yamanaka, Satoshi Kuwabara
    JOURNAL OF PARKINSONS DISEASE 4(3) 385-393 2014年  査読有り
    Background: According to Braak staging of Parkinson's disease (PD), detection of autonomic dysfunction would help with early diagnosis of PD. Objective: To determine whether the autonomic nervous system is involved in the early stage of PD, we evaluated cardiovascular and sudomotor function in early untreated PD patients. Methods: Orthostatic blood pressure regulation, heart rate variability, skin vasomotor function, and palmar sympathetic sweat responses were examined in 50 early untreated PD patients and 20 healthy control subjects. Results: The mean decrease in systolic blood pressure during head-up tilt in PD patients was mildly but significantly larger than in controls (p = 0.0001). There were no differences between the 2 groups in heart rate variability, with analysis of low frequency (LF; mediated by baroreflex feedback), and high frequency (HF; mainly reflecting parasympathetic vagal) modulation. However, LF/HF, an index of sympatho-parasympathetic balance, was lower in the PD group than in controls (p = 0.02). Amplitudes of palmar sweat responses to deep inspiration (p = 0.004), mental arithmetic (p = 0.01), and exercise (p = 0.01) in PD patients were lower than in controls, with negative correlations with motor severity. Amplitudes of palmar skin vasomotor reflexes in PD patients did not differ from controls. Conclusions: Our study indicates impairment of sympathetic cardiovascular and sudomotor function with orthostatic dysregulation of blood pressure control, reduced LF/HF and reduction in palm sweat responses even in early untreated PD patients.
  • Hayashida N, Masuda M, Pearce Y, Kuwabara S
    Annals of vascular diseases 7(1) 17-20 2014年  査読有り

MISC

 1029

書籍等出版物

 77

講演・口頭発表等

 84

担当経験のある科目(授業)

 3

共同研究・競争的資金等の研究課題

 64