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  2. 桑原 聡

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

研究キーワード

 5

研究分野

 1

経歴

 3

委員歴

 12
もっとみる

論文

 903
  • Yamagishi Y, Suzuki H, Sonoo M, Kuwabara S, Yokota T, Nomura K, Chiba A, Kaji R, Kanda T, Kaida K, Ikeda SI, Mutoh T, Yamasaki R, Takashima H, Matsui M, Nishiyama K, Sobue G, Kusunoki S
    Journal of the peripheral nervous system : JPNS 22(4) 433-439 2017年12月  査読有り
  • Akiyuki Hiraga, Satoshi Kuwabara
    CEPHALALGIA 37(13) 1310-1310 2017年11月  査読有り
  • Shingo Suzuki, Sonoko Misawa, Takahiro Ota, Yu Li, Satoshi Kuwabara, Masatomi Ikusaka
    AMERICAN JOURNAL OF MEDICINE 130(11) E491-E492 2017年11月  査読有り
  • Keisuke Suzuki, Yasuyuki Okuma, Tomoyuki Uchiyama, Masayuki Miyamoto, Ryuji Sakakibara, Yasushi Shimo, Nobutaka Hattori, Satoshi Kuwabara, Toshimasa Yamamoto, Yoshiaki Kaji, Shigeki Hirano, Ayaka Numao, Koichi Hirata
    PARKINSONISM & RELATED DISORDERS 44 18-22 2017年11月  査読有り
    Background: We investigated the prevalence and impact of restless legs syndrome (RLS) and leg motor restlessness (LMR) in patients with Parkinson's disease (PD) in a multicenter study.Methods: A total of 436 PD patients and 401 age- and sex-matched controls were included in this study. RLS was diagnosed based on four essential features. LMR was diagnosed when a participant exhibited the urge to move his or her legs but did not meet the four essential features of RLS.Results: The RLS prevalence did not differ between PD patients and controls (3.4% vs. 2.7%), while LMR prevalence was significantly higher in PD patients than in controls (12.8% vs. 4.5%). PD patients with RLS or LMR had a higher prevalence of excessive daytime sleepiness (EDS) (50.7%, vs. 6.9%), probable REM sleep behavior disorder (38.0% vs. 3.4%) and PD-related sleep problems (49.3% vs. 20.7%) than controls with RLS or LMR. RLS/LMR preceding PD onset was related to an older age of PD onset.Conclusion: Our study revealed an increased prevalence of LMR but not RLS in PD patients. LMR could be an early manifestation of PD; however, whether LMR is within the range of RLS or whether LMR and RLS constitute different entities in PD requires further studies. (C) 2017 Elsevier Ltd. All rights reserved.
  • Keisuke Suzuki, Yasuyuki Okuma, Tomoyuki Uchiyama, Masayuki Miyamoto, Ryuji Sakakibara, Yasushi Shimo, Nobutaka Hattori, Satoshi Kuwabara, Toshimasa Yamamoto, Yoshiaki Kaji, Shigeki Hirano, Taro Kadowaki, Koichi Hirata
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 88(11) 953-959 2017年11月  査読有り
    Objectives To investigate the impact of sleep disturbances on Parkinson's disease (PD) clinical motor subtypes and disease-related disability in a multicentre setting.Methods We report a cross-sectional relationship between sleep-related symptoms and clinical motor subtypes (tremor dominant (TD); intermediate; postural instability and gait disturbances (PIGDs)) identified in a multicentre study, including 436 patients with PD and 401 age-matched controls. PD-related sleep problems (PD-SP), excessive daytime sleepiness (EDS) and probable REM sleep behaviour disorder (pRBD) were evaluated using the PD sleep scale (PDSS)-2, Epworth Sleepiness Scale (ESS) and RBD screening questionnaire-Japanese version (RBDSQ-J), respectively.Results PD-SP (PDSS-2 >= 18; 35.1% vs 7.0%), EDS (ESS >= 10; 37.8% vs 15.5%) and pRBD (RBDSQ-J >= 5; 35.1% vs 7.7%) were more common in patients with PD than in controls. The prevalence of restless legs syndrome did not differ between patients with PD and controls (3.4% vs 2.7%). After adjusting for age, sex, disease duration and Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) part III score, the PIGD group had higher PDSS-2 and ESS scores than the TD group. The RBDSQ-J scores did not differ among the TD, intermediate and PIGD groups. A stepwise regression model predicting the MDS-UPDRS part II score identified the Hoehn and Yahr stage, followed by the number of sleep-related symptoms (PD-SP, EDS and pRBD), disease duration, MDS-UPDRS part III score, PIGD subtype, depression and MDS-UPDRS part IV score as significant predictors.Conclusion Our study found a significant relationship between sleep disturbances and clinical motor subtypes. An increased number of sleep-related symptoms had an impact on disease-related disability.
  • Tetsuya Kanai, Akiyuki Uzawa, Yasunori Sato, Shigeaki Suzuki, Naoki Kawaguchi, Keiichi Himuro, Fumiko Oda, Yukiko Ozawa, Jin Nakahara, Norihiro Suzuki, Yuko K. Takahashi, Satoru Ishibashi, Takanori Yokota, Takashi Ogawa, Kazumasa Yokoyama, Nobutaka Hattori, Shoko Izaki, Satoru Oji, Kyoichi Nomura, Juntaro Kaneko, Kazutoshi Nishiyama, Ichiro Yoshino, Satoshi Kuwabara
    ANNALS OF NEUROLOGY 82(5) 841-849 2017年11月  査読有り
    ObjectiveMyasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis. MethodsWe studied 393 patients with MG who underwent thymectomy at 6 tertiary centers in Japan (275 patients for derivation and 118 for validation). Clinical characteristics, such as gender, age at onset and operation, body mass index, disease duration, MG subtype, severity, symptoms, preoperative therapy, operative data, and laboratory data, were reviewed retrospectively. A multivariate logistic regression with LASSO penalties was used to determine the factors associated with postoperative myasthenic crisis, and a score was assigned. Finally, the predictive score was evaluated using bootstrapping technique in the derivation and validation groups. ResultsMultivariate logistic regression identified 3 clinical factors for predicting postoperative myasthenic crisis risk: (1) vital capacity<80%, (2) disease duration<3 months, and (3) bulbar symptoms immediately before thymectomy. The postoperative myasthenic crisis predictive score, ranging from 0 to 6 points, had areas under the curve of 0.84 (0.66-0.96) in the derivation group and 0.80 (0.62-0.95) in the validation group. InterpretationA simple scoring system based on 3 preoperative clinical characteristics can predict the possibility of postoperative myasthenic crisis. Ann Neurol 2017;82:841-849
  • Atsuhiko Sugiyama, Daichi Sone, Noriko Sato, Yukio Kimura, Miho Ota, Norihide Maikusa, Tomoko Maekawa, Mikako Enokizono, Madoka Mori-Yoshimura, Yasushi Ohya, Satoshi Kuwabara, Hiroshi Matsuda
    PLOS ONE 12(11) e0187343 2017年11月  査読有り
    This study aimed to investigate abnormalities in structural covariance network constructed from gray matter volume in myotonic dystrophy type 1 (DM1) patients by using graph theoretical analysis for further clarification of the underlying mechanisms of central nervous system involvement. Twenty-eight DM1 patients (4 childhood onset, 10 juvenile onset, 14 adult onset), excluding three cases from 31 consecutive patients who underwent magnetic resonance imaging in a certain period, and 28 age-and sex-matched healthy control subjects were included in this study. The normalized gray matter images of both groups were subjected to voxel based morphometry (VBM) and Graph Analysis Toolbox for graph theoretical analysis. VBM revealed extensive gray matter atrophy in DM1 patients, including cortical and subcortical structures. On graph theoretical analysis, there were no significant differences between DM1 and control groups in terms of the global measures of connectivity. Betweenness centrality was increased in several regions including the left fusiform gyrus, whereas it was decreased in the right striatum. The absence of significant differences between the groups in global network measurements on graph theoretical analysis is consistent with the fact that the general cognitive function is preserved in DM1 patients. In DM1 patients, increased connectivity in the left fusiform gyrus and decreased connectivity in the right striatum might be associated with impairment in face perception and theory of mind, and schizotypal-paranoid personality traits, respectively.
  • A. Sugiyama, N. Sato, Y. Kimura, T. Maekawa, M. Enokizono, Y. Saito, Y. Takahashi, H. Matsuda, S. Kuwabara
    AMERICAN JOURNAL OF NEURORADIOLOGY 38(11) 2100-2104 2017年11月  査読有り
    Neuronal intranuclear inclusion disease is a neurodegenerative disorder pathologically characterized by eosinophilic hyaline intranuclear inclusions. A high-intensity signal along the corticomedullary junction on DWI has been described as a specific MR imaging finding of the cerebrum in neuronal intranuclear inclusion disease. However, MR imaging findings of the cerebellum in neuronal intranuclear inclusion disease have not been fully evaluated. Here, we review MR imaging findings of the cerebellum in a series of 8 patients with pathologically confirmed neuronal intranuclear inclusion disease. The MR imaging results showed cerebellar atrophy (8/8 patients) and high-intensity signal on FLAIR images in the medial part of the cerebellar hemisphere right beside the vermis (the "paravermal area") (6/8) and in the middle cerebellar peduncle (4/8). The paravermal abnormal signals had a characteristic distribution, and they could be an indicator of the diagnosis of neuronal intranuclear inclusion disease even when using the results of past MR imaging examinations in which DWI findings were not examined.
  • Nobusada Funabashi, Sonoko Misawa, Hiroyuki Takaoka, Koya Ozawa, Satoshi Kuwabara, Yoshio Kobayashi
    CIRCULATION 136 2017年11月  
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  • Atsuta N, Yokoi D, Nakamura R, Watanabe H, Hayashi N, Ito M, Watanabe H, Katsuno M, Izumi Y, Morita M, Taniguchi A, Oda M, Abe K, Mizoguchi K, Kano O, Kuwabara S, Aoki M, Hattori N, Kaji R, Sobue G
    JOURNAL OF THE NEUROLOGICAL SCIENCES 381 103-103 2017年10月15日  
  • Yokoi D, Atsuta N, Hirakawa A, Nakamura R, Watanabe H, Hayashi N, Ito M, Watanabe H, Katsuno M, Izumi Y, Morita M, Taniguchi A, Oda M, Abe K, Mizoguchi K, Kano O, Kuwabara S, Kaji R, Sobue G
    JOURNAL OF THE NEUROLOGICAL SCIENCES 381 720-721 2017年10月15日  
  • Akiyuki Hiraga, Yuya Aotsuka, Kyosuke Koide, Satoshi Kuwabara
    CEPHALALGIA 37(11) 1102-1105 2017年10月  査読有り
    Background Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by segmental vasospasm. Vasoactive agents and childbirth have been reported as precipitating factors for RCVS; however, RCVS induced by altitude change or air travel has rarely been reported. Case We present a case of a 74-year-old woman who presented with thunderclap headache during airplane descent. Magnetic resonance angiography demonstrated segmental vasoconstriction that improved 9 days after onset. Conclusion These findings indicate that airplane descent may be a trigger of RCVS. The time course of headache in the present case was similar to that of prolonged headache attributed to airplane travel, indicating that RCVS during air travel may have previously been overlooked and that some headache attributed to airplane travel cases may represent a milder form of RCVS.
  • Tatsuya Yamamoto, Masato Asahina, Yoshitaka Yamanaka, Tomoyuki Uchiyama, Shigeki Hirano, Miki Fuse, Yasuko Koga, Ryuji Sakakibara, Satoshi Kuwabara
    JOURNAL OF THE NEUROLOGICAL SCIENCES 381 230-234 2017年10月  査読有り
    Objective: It is difficult to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD) at least in the early stage. Urodynamic study (UDS) is useful in differentiating MSA from PD. We aimed to clarify which UDS parameter was useful in differentiating MSA from PD.Methods: We retrospectively reviewed 273 cases and performed UDS and external anal sphincter electromyography (EAS-EMG) in patients with MSA (n = 182) and PD (n = 91). We analyzed the utility of UDS parameters, including postvoid residuals (PVR), detrusor overactivity (DO), degree of bladder contraction, and mean duration of motor unit potentials (MUPs) in EAS-EMG, for differentiating MSA from PD.Results: PVR > 150 ml during free-flow study strongly indicated MSA rather than PD (OR 8.723, 95% CI 2.612-29.130, p < 0.001). 'Weak detrusor' also suggested MSA, but it was not a statistically significant indicator (OR 10.598, 95% CI 0.359-312.473, p = 0.172). DO and neurogenic changes in EAS-EMG (mean duration of MUPs > 10 ms). did not significantly contribute to the differentiation of MSA from PD.Conclusions: PVR > 150 ml during free-flow study might be more useful than other UDS parameters in clinically differentiating MSA from PD.
  • Satoshi Kuwabara, Masahiro Mori, Sonoko Misawa, Miki Suzuki, Kazutoshi Nishiyama, Tatsuro Mutoh, Shizuki Doi, Norito Kokubun, Mikiko Kamijo, Hiroo Yoshikawa, Koji Abe, Yoshihiko Nishida, Kazumasa Okada, Kenji Sekiguchi, Ko Sakamoto, Susumu Kusunoki, Gen Sobue, Ryuji Kaji
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 88(10) 832-838 2017年10月  査読有り
    Objective Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. Methods This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. Results At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. Conclusions Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors.
  • Ryuji Sakakibara, Fuyuki Tateno, Masahiko Kishi, Yohei Tsuyusaki, Yosuke Aiba, Hitoshi Terada, Tsutomu Inaoka, Setsu Sawai, Satoshi Kuwabara, Fumio Nomura
    JOURNAL OF MOVEMENT DISORDERS 10(3) 116-122 2017年9月  査読有り
    Objective Diagnosis of sporadic cerebellar ataxia is a challenge for neurologists. A wide range of potential causes exist, including chronic alcohol use, multiple system atrophy of cerebellar type (MSA-C), and sporadic late cortical cerebellar atrophy. Recently, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was identified in a cohort of patients with non-MSA-C sporadic cerebellar ataxia. The aim of this study is to genetically screen genes involved in SCA in a Japanese single-hospital cohort.Methods Over an 8-year period, 140 patients with cerebellar ataxia were observed. There were 109 patients with sporadic cerebellar ataxia (no family history for at least four generations, 73 patients with MSA-C, and 36 patients with non-MSA-C sporadic cerebellar ataxia) and 31 patients with familial cerebellar ataxia. We performed gene analysis comprising SCA1, 2, 3, 6, 7, 8, 12, 17, 31, and dentatorubro-pallidoluysian atrophy (DRPLA) in 28 of 31 non-MSA-C sporadic patients who requested the test. Familial patients served as a control.Results Gene abnormalities were found in 57% of non-MSA-C sporadic cerebellar ataxia cases. Among patients with sporadic cerebellar ataxia, abnormalities in SCA6 were the most common (36%), followed by abnormalities in SCA1 (7.1%), SCA2 (3.6%), SCA3 (3.6%), SCA8 (3.6%), and DRPLA (3.6%). In contrast, gene abnormalities were found in 75% of familial cerebellar ataxia cases, with abnormalities in SCA6 being the most common (29%). For sporadic versus familial cases for those with SCA6 abnormalities, the age of onset was older (69 years vs. 59 years, respectively), and CAG repeat length was shorter (23 vs. 25, respectively) in the former than in the latter (not statistically significant).Conclusion Autosomal-dominant mutations in SCA genes, particularly in SCA6, are not rare in sporadic cerebellar ataxia. The reason for the frequency of mutations in SCA6 remains unclear; however, the reason may reflect a higher age at onset and variable penetrance of SCA6 mutations.
  • S. Isose, K. Watanabe, S. Omori, Y. Sekiguchi, M. Beppu, K. Shibuya, H. Amino, T. Suichi, S. Misawa, S. Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 22(3) 305-305 2017年9月  
  • Y. Yamagishi, H. Suzuki, Masahiro Sonoo, Satoshi Kuwabara, Takanori Yokota, Kyoichi Nomura, Atsuro Chiba, Ryuji Kaji, Takashi Kanda, Kenichi Kaida, Shuichi Ikeda, Tatsuro Mutoh, Junichi Kira, Hiroshi Takashima, Makoto Matsui, Gen Sobue, Kazutoshi Nishiyama, S. Kusunoki
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 22(3) 412-412 2017年9月  
  • T. Suichi, S. Misawa, Y. Sato, M. Beppu, Y. Sekiguchi, K. Shibuya, K. Watanabe, H. Amino, S. Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 22(3) 390-390 2017年9月  
  • Keisuke Suzuki, Yasuyuki Okuma, Tomoyuki Uchiyama, Masayuki Miyamoto, Ryuji Sakakibara, Yasushi Shimo, Nobutaka Hattori, Satoshi Kuwabara, Toshimasa Yamamoto, Koichi Hirata
    CEPHALALGIA 37 228-229 2017年9月  
  • S. Kuwabara, S. Misawa, Y. Sekiguchi, Susumu Kusunoki
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 22(3) 323-323 2017年9月  
  • S. Misawa, Y. Sato, K. Katayama, Y. Sekiguchi, H. Amino, T. Suichi, S. Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 22(3) 342-342 2017年9月  
  • H. Amino, S. Misawa, Y. Sekiguchi, K. Shibuya, K. Watanabe, T. Suichi, S. Kuwabara
    JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 22(3) 235-235 2017年9月  
  • Omori S, Isose S, Misawa S, Watanabe K, Sekiguchi Y, Shibuya K, Beppu M, Amino H, Kuwabara S
    Neuroscience research 121 43-48 2017年8月  査読有り
  • Masahiro Mori, Akiyuki Uzawa, Satoshi Kuwabara
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 88(8) 620-620 2017年8月  
  • Tatsuya Yamamoto, Tomoyuki Uchiyama, Yoshinori Higuchi, Masato Asahina, Shigeki Hirano, Yoshitaka Yamanaka, Liu Weibing, Satoshi Kuwabara
    JOURNAL OF THE NEUROLOGICAL SCIENCES 379 18-21 2017年8月  査読有り
    Introduction: We aimed to examine temporal changes in health-related quality of life (HRQOL) and its relationship with motor and cognitive functions in patients with Parkinson's disease (PD) after subthalamic nucleus deep brain stimulation (STN-DBS). Methods: In total, 31 patients with PD were enrolled in this study (mean age: 66.7 +/- 0.9 years; mean disease duration: 11.6 +/- 3.7 years). Participants completed the Unified Parkinson's Disease Rating Scale and the Parkinson's Disease Questionnaire-39. Cognitive function was assessed using the Mini Mental State Examination, the Frontal Assessment Battery, and the Montreal Cognitive Assessment. Postoperative evaluation was performed at three months, one year, three years, and five years after surgery; temporal changes in the correlation between HRQOL and motor and cognitive functions were evaluated at all follow-up periods. Results: All patients completed postoperative clinical evaluations after three months, after one year. Of the 31 participants, twelve completed postoperative clinical evaluations after three years and seven after five years. Motor functions showed significant improvement over the five-year follow-up period. The mobility subdomain of the HRQOL worsened whereas the total score did not change significantly over years. Cognitive functions were not significantly impaired during follow-up periods. HRQOL was basically not significantly correlated with motor and cognitive functions during the follow-up period. Conclusions: The mobility subdomain of the HRQOL worsened after surgery, and the improvement in motor functions was basically not correlated with HRQOL after STN-DBS in patients with PD. Cognitive functions were not significantly impaired during follow-up periods. (C) 2017 Published by Elsevier B.V.
  • Hiroki Masuda, Shigeki Hirano, Nobuyoshi Takahashi, Etsuko Hatsugano, Akiyuki Uzawa, Tomohiko Uchida, Ryohei Ohtani, Satoshi Kuwabara, Masahiro Mori
    PLOS ONE 12(8) e0184012 2017年8月  査読有り
    Objective Brain regions responsible for cognitive dysfunction in MS and neuromyelitis optica spectrum disorder (NMOSD) are not known. Our aim of this study was to investigate whether cognitive function and brain volume differed between MS and NMOSD in Japanese patients. Methods Brain MRI and neuropsychological tests including the Wechsler Adult Intelligence Scale-III (WAIS-III), Wechsler Memory Scale-Revised (WMS-R), Trail Making Test (TMT) and Clinical Assessment for Attention (CAT) were performed. Parametric grey matter (GM) and white matter (WM) volumes determined from lesion-filled T1-weighted images using wholebrain voxel-based morphometry (VBM) were compared by two-tailed t test. Results Twenty relapsing-remitting MS and sixteen NMOSD patients were included. MS patients were younger than NMOSD patients. Processing speed intelligence quotient (IQ), general memory, verbal memory and delayed recall were significantly worse in MS patients than in NMOSD patients. Furthermore, left superior temporal gyrus (STG) GM volume was smaller in MS patients than in NMOSD patients (P &lt; 0.05, family-wise error [FWE] corrected, Zmax = 4.97, 62 voxel). The left STG GM volume tended to be positively correlated with delayed recall in MS patients. Conclusions Despite being younger, MS patients demonstrated worse performance in certain cognitive variables than NMOSD patients, which might be associated with left STG GM volume loss.
  • Tomohiko Uchida, Masahiro Mori, Akiyuki Uzawa, Hiroki Masuda, Mayumi Muto, Ryohei Ohtani, Satoshi Kuwabara
    MULTIPLE SCLEROSIS JOURNAL 23(8) 1072-1084 2017年7月  査読有り
    Background: Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood-brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown. Objective: We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO. Methods: The concentrations 9 MMPs, 4 TIMPs, and 14 cytokines were measured by multiplex assay in CSF and serum samples from 29 NMO patients, 29 relapsing-remitting multiple sclerosis (MS) patients, and 27 patients with other neurological disorders. We also performed immunohistochemistry for MMP-2 and TIMP-1 expression in post-mortem brain tissues from NMO patients. Results: NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF/serum albumin ratio, an index of BBB permeability, was most strongly correlated with CSF MMP-2 concentration, which in turn correlated with CSF interleukin-6 levels. Immunohistochemistry revealed MMP-2- and TIMP-1-positive cells surrounding vessels in NMO lesions. Conclusion: In NMO, increased CSF MMP-2, likely induced by interleukin-6 signaling, may disrupt the BBB and enable serum anti-AQP-4 antibodies migration into the central nervous system (CNS).
  • Uncini A, Ippoliti L, Shahrizaila N, Sekiguchi Y, Kuwabara S
    Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 128(7) 1176-1183 2017年7月  査読有り
  • T. Yamamoto, M. Asahina, Y. Yamanaka, T. Uchiyama, S. Hirano, M. Fuse, Y. Koga, R. Sakakibara, S. Kuwabara
    NEUROUROLOGY AND URODYNAMICS 36 S510-S512 2017年7月  
  • T. Uchiyama, T. Yamamoto, Y. Higuchi, K. Suzuki, T. Kadowaki, H. Fujita, Y. Watanabe, K. Kaga, T. Yamanishi, R. Sakakibara, K. Hirata, S. Kuwabara
    NEUROUROLOGY AND URODYNAMICS 36 S484-S484 2017年7月  
  • Hirotaka Yokouchi, Takayuki Baba, Sonoko Misawa, Masayasu Kitahashi, Toshiyuki Oshitari, Satoshi Kuwabara, Shuichi Yamamoto
    BRITISH JOURNAL OF OPHTHALMOLOGY 101(6) 786-790 2017年6月  査読有り
    Aims To determine the changes in the subfoveal choroidal thickness (CT), the foveal thickness (FT) and the serum level of vascular endothelial growth factor (VEGF) after thalidomide treatment in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. Methods We studied 13 left eyes of 13 treatment-naive patients with POEMS syndrome. The subfoveal CT and FT were determined by enhanced depth imaging optical coherence tomography, and the serum level of VEGF was determined by ELISA at the baseline and at 6 months after thalidomide treatment. The correlations in the serum level of VEGF and the subfoveal CT or the FT at the baseline and at 6 months after treatment were determined. Results Together with the reduction in the serum level of VEGF, the subfoveal CT was also reduced significantly from 439.1 +/- 66.5 mm at the baseline to 307.2 +/- 75.4 mm at 6 months (p=0.001). The mean FT at the baseline was 236.4 +/- 30.7 mm which did not change significantly at 6 months at 228.1 +/- 33.1 mm (p&gt;0.05). The change in the subfoveal CT was significantly and linearly correlated with the change in the serum level of VEGF at 6 months after treatment (r=0.67, p=0.011). Conclusions The significant correlation between the CT and the serum level of VEGF may offer clues on the pathogenesis of ocular diseases of POEMS syndrome and on the role of serum VEGF on the choroid.
  • T. Yamamoto, M. Asahina, Y. Yamanaka, T. Uchiyama, S. Hirano, M. Fuse, Y. Koga, R. Sakakibara, S. Kuwabara
    MOVEMENT DISORDERS 32(1) e0169405 2017年6月  査読有り
  • Akiyuki Uzawa, Masahiro Mori, Hiroki Masuda, Ryohei Ohtani, Tomohiko Uchida, Setsu Sawai, Satoshi Kuwabara
    CLINICA CHIMICA ACTA 469 144-149 2017年6月  査読有り
    Background: Elevation of cerebrospinal fluid (CSF) interleukin (IL)-6 has been reported in various neurological disorders but has never been systematically analyzed. Our main objectives are to compare the CSF IL-6 levels among various neurological disorders and to evaluate the significance of CSF IL-6 measurements for the diagnosis of neuromyelitis optica (NMO). Methods: We retrospectively investigated the IL-6 levels of 572 consecutive CSF samples in patients with various neurological disorders. Additionally, the associations between clinical manifestations in NMO patients and CSF IL-6 levels were closely investigated. Results: Among the neurological disorders, patients with NMO had the highest CSF IL-6 level. Receiver operating characteristic analysis found the optimal cutoff CSF IL-6 value for diagnosing NMO as 7.8 pg/ml, and the sensitivity and specificity were 0.7317 and 0.7694, respectively. In NMO, CSF IL-6 levels were correlated with the length of the spinal cord lesion and anti-aquaporin-4 antibody-positivity and decreased after treatment. Conclusion: CSF IL-6 can be high in various inflammatory and non-inflammatory CNS disorders, but its upregulation appears to be the most remarkable in NMO. (C) 2017 Elsevier B.V. All rights reserved.
  • Satoshi Kuwabara, Sonoko Misawa, Masahiro Mori
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 88(6) 459-459 2017年6月  
  • Bart C. Jacobs, Bianca van den Berg, Christine Verboon, Govindsinh Chavada, David R. Cornblath, Kenneth C. Gorson, Thomas Harbo, Hans-Peter Hartung, Richard A. C. Hughes, Susumu Kusunoki, Pieter A. van Doorn, Hugh J. Willison, the IGOS Consortium, B. C. Jacobs, R. A.C. Hughes, D. R. Cornblath, K. C. Gorson, H. P. Hartung, S. Kusunoki, P. A. van Doorn, H. J. Willison, M. van Woerkom, B. van den Berg, C. Verboon, J. Roodbol, B. C. Jacobs, R. C. Reisin, S. W. Reddel, Z. Islam, B. Islam, Q. D. Mohammad, P. van den Bergh, T. E. Feasby, Y. Z. Wang, T. Harbo, Y. Péréon, H. P. Hartung, H. C. Lehmann, E. Dardiotis, E. Nobile-Orazio, S. Kusunoki, N. Shahrizaila, B. C. Jacobs, B. van den Berg, C. Verboon, K. Bateman, I. Illa, L. A. Querol, S. T. Hsieh, H. J. Willison, G. Chavada, A. Davidson, K. C. Gorson, J. M. Addington, S. Ajroud-Driss, H. Andersen, G. Antonini, S. Attarian, U. Badrising, F. A. Barroso, L. Benedetti, A. Beronio, M. Bianco, D. Binda, C. Briani, J. Bürmann, I. R. Bella, T. E. Bertorini, R. Bhavaraju-Sanka, T. H. Brannagan, M. Busby, S. Butterworth, M. Campagnolo, C. Casasnovas, G. Cavaletti, C. S. Chao, S. Chen, S. Chetty, K. G. Claeys, J. A. Cohen, M. E. Conti, J. S. Cosgrove, M. C. Dalakas, M. M. Dimachkie, U. Dillmann, C. Domínguez González, K. Doppler, C. Dornonville de la Cour, A. Echaniz-Laguna, F. Eftimov, C. G. Faber, R. Fazio, C. Fokke, T. Fujioka, E. A. Fulgenzi, G. Galassi, T. Garcia, M. Garnero, M. P.J. Garssen, C. J. Gijsbers, J. M. Gilchrist, H. J. Gilhuis, J. M. Goldstein, N. Goyal, V. Granit, A. Grapperon, G. Gutiérrez Gutiérrez, L. Gutmann, R. D.M. Hadden, J. V. Holbech, J. K.L. Holt, C. Homedes Pedret, M. Htut, K. Jellema, I. Jericó Pascual, K. Kaida, S. Karafiath, H. D. Katzberg, L. Kiers, B. C. Kieseier, K. Kimpinski, R. P. Kleyweg, N. Kokubun, N. A. Kolb, K. Kuitwaard, S. Kuwabara, J. Y. Kwan, S. S. Ladha, L. Landschoff Lassen, V. Lawson, D. Ledingham, L. Léon Cejas, C. A. Luciano, S. T. Lucy, M. P.T. Lunn, A. Magot, H. Manji, C. Marchesoni, G. A.M. Marfia, C. Márquez Infante, E. Martinez Hernandez, G. Mataluni, M. Mattiazi, C. J. McDermott, G. D. Meekins, J. Miller, M. S. Monges, M. C.J. Montero, G. Morís de la Tassa, C. Nascimbene, C. Neumann, R. J. Nowak, P. Orizaola Balaguer, M. Osei-Bonsu, E. B.L. Pan, J. Pardo Fernandez, M. Pasnoor, M. T. Pulley, Y. A. Rajabally, S. Rinaldi, C. Ritter, R. C. Roberts, I. Rojas-Marcos, S. A. Rudnicki, G. M. Sachs, J. P.A. Samijn, L. Santoro, D. S. Saperstein, A. Savransky, H. Schneider, A. Schenone, M. J. Sedano Tous, Y. Sekiguchi, K. A. Sheikh, N. J. Silvestri, S. H. Sindrup, C. L. Sommer, B. Stein, A. M. Stino, A. Spyropoulos, J. Srinivasan, H. Suzuki, S. W. Taylor, H. Tankisi, D. Tigner, P. T. Twydell, F. Valzania, P. van Damme, A. J. van der Kooi, G. W. van Dijk, T. van der Ree, R. van Koningsveld, J. D. Varrato, F. H. Vermeij, J. J.G.M. Verschuuren, L. H. Visser, M. V. Vytopil, W. Waheed, M. Wilken, C. Wilkerson, P. W. Wirtz, Y. Yamagishi, E. M. Yiu, L. Zhou, S. Zivkovic
    Journal of the Peripheral Nervous System 22(2) 68-76 2017年6月1日  査読有り
    Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multicenter cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within 2 weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course, and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1,000 patients with a follow-up of 1–3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1,400 participants from 143 active centers in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modeling, treatment effects, and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS.
  • T. Uchiyama, T. Yamamoto, K. Suzuki, T. Kadowaki, A. Numao, H. Fujita, Y. Watanabe, T. Matsubara, M. Miyamoto, K. Kaga, T. Yamanishi, R. Sakakibara, S. Kuwabara, K. Hirata
    MOVEMENT DISORDERS 32 2017年6月  
  • Hiroki Masuda, Masahiro Mori, Tomohiko Uchida, Akiyuki Uzawa, Ryohei Ohtani, Satoshi Kuwabara
    JOURNAL OF NEUROIMMUNOLOGY 305 102-107 2017年4月  査読有り
    Soluble CD40 ligand (sCD4OL) is reported to disrupt the blood-brain barrier (BBB). Cerebrospinal fluid (CSF) and serum sCD4OL levels were measured in 29 multiple sclerosis (MS), 29 neuromyelitis optica spectrum disorder (NMOSD), and 27 disease control (DC) patients. In MS, serum sCD4OL levels were higher than in DCs and positively correlated with the CSF/serum albumin ratio (Qalb). In NMOSD, CSF sCD4OL levels were significantly increased compared to DCs, and were correlated to Qalb, CSF cell counts, protein concentrations, and interleukin-6 levels. sCD4OL could be involved in BBB disruption in MS, whereas it may contribute to CNS inflammation in NMOSD. (C) 2017 Elsevier B.V. All rights reserved.
  • Mayumi Muto, Masahiro Mori, Jia Liu, Akiyuki Uzawa, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Kazuo Sugimoto, Satoshi Kuwabara
    JOURNAL OF NEUROIMMUNOLOGY 305 131-134 2017年4月  査読有り
    Previously, we identified anti-Talin-1 antibodies in the serum of MS. In this case, we measured the serum soluble Talin-1 (sTalin-1) levels by enzyme-linked immunosorbent assay. The serum sTalin-1 levels were significantly higher in 40 patients with MS than in 43 normal controls and in the acute phase of disease than in the remission phase. Interestingly, serum sTalin-1 levels were associated with a sustained increase in disability after MS attack but not with serum anti-Talin-1 antibody levels. sTalin-1 may be a biomarker for the acute phase of MS and may be used for the short-term prognosis of MS. (C) 2017 Elsevier B.V. All rights reserved.
  • Satoshi Kuwabara, Akiyuki Uzawa, Masahiro Mori
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 88(4) 283-283 2017年4月  
  • Antonino Uncini, Nortina Shahrizaila, Satoshi Kuwabara
    JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 88(3) 266-271 2017年3月  査読有り
    In 2016, we have seen a rapid emergence of Zika virus-associated Guillain-Barre syndrome (GBS) since its first description in a French-Polynesian patient in 2014. Current evidence estimates the incidence of GBS at 24 cases per 100 000 persons infected by Zika virus. This will result in a sharp rise in the number of GBS cases worldwide with the anticipated global spread of Zika virus. A better understanding of the pathogenesis of Zika-associated GBS is crucial to prepare us for the current epidemic. In this review, we evaluate the existing literature on GBS in association with Zika and other flavivirus to better define its clinical subtypes and electrophysiological characteristics, demonstrating a demyelinating subtype of GBS in most cases. We also recommend measures that will help reduce the gaps in knowledge that currently exist.
  • Tomoya Muto, Chikako Ohwada, Koji Takaishi, Yusuke Isshiki, Yuhei Nagao, Nagisa Hasegawa, Chika Kawajiri-Manako, Emi Togasaki, Ryoh Shimizu, Shokichi Tsukamoto, Shio Sakai, Yusuke Takeda, Naoya Mimura, Masahiro Takeuchi, Emiko Sakaida, Sonoko Misawa, Naomi Shimizu, Tohru Iseki, Satoshi Kuwabara, Chiaki Nakaseko
    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 23(2) 361-363 2017年2月  査読有り
    Although autologous stem cell transplantation can achieve excellent responses in patients with POEMS syndrome, the optimal regimen for peripheral blood stem cell (PBSC) collection is still controversial. We retrospectively investigated the safety and efficacy of 41 PBSC collecting procedures in 37 patients with POEMS syndrome. PBSC mobilization was performed using cyclophosphamide + granulocyte colony-stimulating factor (G-CSF) (CG, n = 14) or G-CSF alone (G, n = 27). Twelve (85.7%) patients in the CG group and all (100%) patients in the G group received induction chemotherapy before PBSC collection. The proportions of good mobilizers &gt;= 2.0 x 10(6) CD34(+) cells/kg) were comparable between the 2 groups (CG versus G: 78.6% versus 70.4%, P=.71). Two (14.3%) patients in the CG group developed severe capillary leak symptoms during the PBSC mobilization period, whereas no patient in the G group experienced severe adverse events. Appropriate induction therapies followed by the G-CSF monotherapy compose an optimal strategy for PBSC collection. (C) 2017 American Society for Blood and Marrow Transplantation.
  • T. Kanai, A. Uzawa, N. Kawaguchi, K. Himuro, F. Oda, Y. Ozawa, S. Kuwabara
    EUROPEAN JOURNAL OF NEUROLOGY 24(2) 270-275 2017年2月  査読有り
    Background and purposeA single, oral dose of 3 mg/day tacrolimus, approved for myasthenia gravis (MG) treatment in Japan, was shown to reduce steroid dose and anti-acetylcholine receptor (AChR) antibody titers as well as to improve MG symptoms. However, no studies have investigated the association between tacrolimus concentration and its clinical efficacy in MG. In this study, we aimed to determine the optimal tacrolimus concentration for MG treatment. MethodsThe trough tacrolimus concentration in 51 patients with MG (positive for anti-AChR antibody, n = 48; negative for anti-AChR and anti-muscle-specific tyrosine kinase antibodies, n = 3) who received 3 mg/day tacrolimus for more than 1 year was measured using a chemiluminescent enzyme immunoassay. The clinical characteristics of patients with MG as well as the dose of prednisolone used before and after tacrolimus treatment were evaluated retrospectively. ResultsThe median trough tacrolimus concentration was 5.4 (range, 2.9-7.6) ng/mL, which was correlated with minimal manifestation or better status' (P = 0.0190, r = 0.3273) and the reduction in anti-AChR antibody 1 year after tacrolimus initiation (P = 0.0170, r = 0.3465). When the cut-off value for tacrolimus was defined as 4.8 ng/mL using a receiver operating characteristic curve, patients with adequate tacrolimus concentration (4.8 ng/mL) showed more reduction in anti-AChR antibody titers and more improvement in MG-related activities in daily life scores. More patients with adequate tacrolimus concentration achieved minimal manifestation or better status' compared with those with low tacrolimus concentration. ConclusionsAn adequate tacrolimus concentration is required for better MG prognosis.
  • Masayuki Homma, Akiyuki Uzawa, Hitoshi Tanaka, Naoki Kawaguchi, Tetsuya Kanai, Kenji Nakajima, Masakuni Narita, Yukio Hara, Hideya Maruyama, Yasumasa Ogawa, Keiichi Himuro, Satoshi Kuwabara
    NEUROTHERAPEUTICS 14(1) 191-198 2017年1月  査読有り
    Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient-derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG.
  • Satoshi Kuwabara, Yukari Sekiguchi, Sonoko Misawa
    CLINICAL NEUROPHYSIOLOGY 128(1) 215-219 2017年1月  
    Fisher syndrome (FS), a variant of Guillain-Barre syndrome (GBS), is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia. The lesion sites for these unique clinical features include the oculomotor nerves and group 1a neurons in the dorsal root ganglion, and the presence of FS is determined by the expression of ganglioside GQ1b in the human nervous system. Neurophysiological findings suggest that ataxia and areflexia are due to an impaired proprioceptive afferent system. Typically, the soleus H-reflex is absent and a body-sway analysis using posturography shows a 1-Hz peak, which indicates proprioception dysfunction. Sensory nerve action potentials and somatosensory-evoked potentials are abnormal in approximately 30% of FS patients, indicating the occasional involvement of cutaneous (group 2) afferents. During the disease course, approximately 15% of FS patients suffer an overlap of axonal GBS with nerve conduction abnormalities that reflect axonal dysfunction. This review summarizes electro-physiological abnormalities and their clinical significance in FS. (C) 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Beppu M, Sawai S, Misawa S, Mori M, Ito S, Sogawa K, Nishimura M, Matsushita K, Nomura F, Kuwabara S
    Journal of neuroimmunology 302 20-22 2017年1月  査読有り
  • Shimada H, Kitamura S, Shinotoh H, Endo H, Niwa F, Hirano S, Kimura Y, Zhang MR, Kuwabara S, Suhara T, Higuchi M
    Alzheimer's & dementia (Amsterdam, Netherlands) 6 11-20 2017年  査読有り
  • Masuda H, Mori M, Iwai Y, Kuwabara S
    Internal medicine (Tokyo, Japan) 56(7) 879-880 2017年  査読有り
  • Atsuhiko Sugiyama, Makoto Kobayashi, Ayaka Daizo, Miyako Suzuki, Hirotoshi Kawashima, Shin-ichiro Kagami, Hiroaki Tanaka, Yoshio Suzuki, Takashi Matsunaga, Satoshi Kuwabara
    INTERNAL MEDICINE 56(13) 1715-1718 2017年  査読有り
    An 87-year-old woman presented with a 3-month history of fever, edema of the lower legs, and gait disturbance. A laboratory examination revealed high serum levels of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA). Although microscopic polyangiitis was initially suspected and treated, the patient subsequently developed transient hemiparesis and disturbed consciousness. Brain magnetic resonance imaging/angiography revealed infarct-like lesions, pachymeningeal involvement, and diffuse cerebral vasoconstriction. A random skin biopsy confirmed the histological diagnosis of intravascular lymphoma. Diffuse cerebral vasoconstriction and a high serum MPO-ANCA level have rarely been reported in patients with intravascular lymphoma. Endothelial damage due to immune-mediated mechanisms, tumor derived factors, or the direct interaction of lymphoma cells with endothelial cells may commonly predispose patients to both cerebral vasoconstriction and the development of ANCAs.
  • Marie Murakawa, Kazumoto Shibuya, Yukari Sekiguchi, Satoshi Kuwabara
    INTERNAL MEDICINE 56(13) 1747-1748 2017年  査読有り
  • Akiyuki Hiraga, Satoshi Kuwabara
    INTERNAL MEDICINE 56(21) 2865-2869 2017年  査読有り
    Objective The differences in the frequency and clinical features of malignant syndrome (MS) and serotonin syndrome (SS) in same population have only rarely been reported. To report the frequency and clinical features of MS and SS in a general hospital setting. Methods The clinical and laboratory features of patients with MS and those with SS, who were consecutively admitted to Chiba Rosai Hospital, during the past 4.5 years were reviewed. Results Of the 2005 patients admitted, MS was observed in 16 patients (0.8%) and SS in 2 (0.1%). In the 16 patients with MS, the underlying disorder included depression (n = 5), and dementia or parkinsonism (n = 11). The underlying etiology of the 2 patients with SS was depression. In 5 patients, MS was difficult to distinguish from SS because of overlapping symptoms and signs and/or treatments with both neuroleptic and serotoninergic drugs. Of the 16 patients with MS, 1 died, 1 remained wheelchair-bound, 4 were able to walk with assistance, and 10 regained their ability to ambulate independently. The 2 patients with SS recovered after cyproheptadine therapy and were discharged on foot. Conclusion MS occurs more frequently than SS in the general hospital setting. Underlying aetiologies in patients with MS were more common due to dementia or parkinsonism than in patients with psychiatric disorders. The differential diagnosis of MS and SS is often difficult and the diagnostic sensitivities largely differ for each of the diagnostic criteria. As a result, the establishment of new diagnostic criteria that specifically focus on distinguishing MS from SS is therefore required.

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