論文 - 久原　真

Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis.

Yusei Miyazaki, Masaaki Niino, Eri Takahashi, Masako Suzuki, Masanori Mizuno, Shin Hisahara, Toshiyuki Fukazawa, Itaru Amino, Fumihito Nakano, Masakazu Nakamura, Sachiko Akimoto, Naoya Minami, Naoto Fujiki, Shizuki Doi, Shun Shimohama, Yasuo Terayama, Seiji Kikuchi

Clinical immunology (Orlando, Fla.)   187   95 - 101  2018年02月  [国際誌]

　概要を見る

Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease.

DOI PubMed

修正型電気けいれん療法(mECT)施行後、著明なparkinsonismの改善を認めた重度精神症状合併Parkinson病の2例

大橋 一慶, 鈴木 秀一郎, 山本 大輔, 松村 晃寛, 松下 隆司, 久原 真, 川又 純, 下濱 俊, 石田 智隆, 松山 清治, 河西 千秋, 柏木 智則

臨床神経学 ( (一社)日本神経学会 )  57 ( 12 ) 815 - 815  2017年12月  [査読有り]

尿閉が先行し、経過中に網膜電図異常を伴う視力低下を認めた孤発性神経核内封入体病(NIID)の1例

廣瀬 文吾, 土谷 円花, 宮永 怜, 眞部 建郎, 山本 大輔, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 久原 真, 川又 純, 上杉 春雄, 今井 富裕, 下濱 俊, 曽根 淳, 祖父江 元

臨床神経学 ( (一社)日本神経学会 )  57 ( 12 ) 815 - 815  2017年12月

Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis

Daisuke Yamamoto, Tomihiro Imai, Emiko Tsuda, Takayoshi Hozuki, Rika Yamauchi, Shin Hisahara, Jun Kawamata, Shun Shimohama

CLINICAL NEUROPHYSIOLOGY ( ELSEVIER IRELAND LTD )  128 ( 11 ) 2309 - 2317  2017年11月  [査読有り]

　概要を見る

Objective: The ice-pack test is a convenient diagnostic testing procedure for myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack test performed on bilateral masseters.& para;& para;Methods: We performed trigeminal repetitive nerve stimulation (RNS), excitation-contraction (E-C) coupling assessment (lmai's method) and bite force measurement before and after cooling of the masseters in MG patients and normal controls. After placing the ice-pack on the masseters for 3 min, serial recordings of the three tests were performed at various time intervals during 10 min after cooling.& para;& para;Results: The bite force increased significantly after cooling in ice-pack-positive MG patients. The acceleration and acceleration ratio (acceleration at a given time to baseline acceleration) of jaw movement increased significantly after cooling of the masseters in ice-pack-positive MG patients compared to ice-pack-negative patients and normal controls. The prolonged effect of cooling continued until the end of recording even though decremental response to RNS had returned to baseline value.& para;& para;Conclusions: Cooling of myasthenic muscle may induce two effects. One is relatively short effect on electrical synaptic transmission at the endplate, and another is prolonged effect on E-C coupling in the muscle.& para;& para;Significance: The ice-pack test induces a prolonged effect of ameliorating impaired E-C coupling in MG. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

DOI PubMed

急性硬膜下血腫開頭術後に発症した硬膜動静脈瘻の1例

大橋 一慶, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 宮田 圭, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  57 ( 6 ) 324 - 324  2017年06月

四肢腱反射が亢進し、病的反射が陽性であったギランバレー症候群の1例

倉内 麗徳, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  57 ( 6 ) 321 - 321  2017年06月

末梢神経障害を伴った強皮症の1例

山田 稔, 津田 笑子, 鈴木 秀一郎, 松村 晃寛, 村原 貴史, 松下 隆司, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  57 ( 6 ) 322 - 322  2017年06月

Role of Suppressor of Cytokine Signaling 3 (SOCS3) in Altering Activated Microglia Phenotype in APPswe/PS1dE9 Mice.

Naotoshi Iwahara, Shin Hisahara, Jun Kawamata, Akihiro Matsumura, Kazuki Yokokawa, Taro Saito, Mai Fujikura, Tatsuo Manabe, Hiromi Suzuki, Takashi Matsushita, Syuuichirou Suzuki, Shun Shimohama

Journal of Alzheimer's disease : JAD   55 ( 3 ) 1235 - 1247  2017年  [国際誌]

　概要を見る

In response to changes of the central nervous system environment, microglia are capable of acquiring diverse phenotypes for cytotoxic or immune regulation and resolution of injury. Alzheimer's disease (AD) pathology also induces several microglial activations, resulting in production of pro-inflammatory cytokines and reactive oxygen species or clearance of amyloid-β (Aβ) through phagocytosis. We previously demonstrated that microglial activation and increase in oxidative stress started from the middle age in APPswe/PS1dE9 mice, and hypothesized that M1 activation occurs in middle-aged AD mice by Aβ stimulation. In the present study, we analyzed in vivo expressions of pro-inflammatory cytokines (M1 microglial markers), M2 microglial markers, and suppressor of cytokine signaling (SOCS) family, and examined the microglial phenotypic profile in APPswe/PS1dE9 mice. Then we compared the in vitro gene expression patterns of Aβ- and lipopolysaccharide (LPS)-stimulated primary-cultured microglia. Microglia in APPswe/PS1dE9 mice exhibited an M1-like phenotype, expressing tumor necrosis factor α (TNFα) but not interleukin 6 (IL6). Aβ-stimulated primary-cultured microglia also expressed TNFα but not IL6, whereas LPS-stimulated primary-cultured microglia expressed both pro-inflammatory cytokines. Furthermore, both microglia in APPswe/PS1dE9 mice and Aβ-stimulated primary-cultured microglia expressed SOCS3. Reduction of SOCS3 expression in Aβ-challenged primary-cultured microglia resulted in upregulation of IL6 expression. Our findings indicate that SOCS3 suppresses complete polarization to M1 phenotype through blocking IL6 production, and Aβ-challenged primary-cultured microglia replicate the in vivo gene expression pattern of microglia in APPswe/PS1dE9 mice. Aβ may induce the M1-like phenotype through blocking of IL6 by SOCS3.

PubMed

右正中神経前腕部で伝導ブロックを呈し、多巣性運動ニューロパチーが疑われた1例

倉内 麗徳, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  56 ( 11 ) 801 - 801  2016年11月

FUS/TLS R521L変異を認めた家族性筋萎縮性側索硬化症(FALS)の1家系

大橋 一慶, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 松下 隆司, 村原 貴史, 津田 笑子, 齊藤 正樹, 久原 真, 川又 純, 鈴木 昭治, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  56 ( 11 ) 803 - 803  2016年11月

下垂足を呈し末梢神経障害との鑑別を要した胸髄症の1例

池田 和奈, 石田 智隆, 蒲生 直希, 山本 大輔, 鈴木 秀一郎, 津田 笑子, 久原 真, 村原 貴史, 松下 隆司, 松村 晃寛, 齊藤 正樹, 川又 純, 下濱 俊, 今井 富裕

臨床神経学 ( (一社)日本神経学会 )  56 ( 11 ) 802 - 802  2016年11月

けいれん重積を来したAngiomyxomatous tumorの一例

横川 和樹, 池田 和奈, 越智 龍太郎, 村原 貴史, 臼井 桂子, 松下 隆司, 松村 晃寛, 津田 笑子, 鈴木 秀一郎, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊, 江夏 怜, 三國 信啓, 杉田 真太朗, 長谷川 匡

臨床神経学 ( (一社)日本神経学会 )  56 ( 11 ) 802 - 802  2016年11月

肥厚性硬膜炎様の頭部MRI所見を呈したびまん性大細胞型B細胞リンパ腫の1例

蒲生 直希, 池田 和奈, 鈴木 秀一郎, 津田 笑子, 村原 貴史, 松下 隆司, 松村 晃寛, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  56 ( 11 ) 804 - 804  2016年11月

首下がりで発症した重症筋無力症の1例

山田 稔, 倉内 麗徳, 村原 貴史, 津田 笑子, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 久原 真

日本老年医学会雑誌 ( (一社)日本老年医学会 )  53 ( 4 ) 441 - 441  2016年10月

ANCA-negative granulomatosis with polyangiitis presenting with orbital apex syndrome and recurrent pachymeningitis: A case report.

Shin Hisahara, Minoru Yamada, Yousuke Matsuura, Emiko Tsuda, Yukinori Akiyama, Masaki Saitoh, Jun Kawamata, Nobuhiro Mikuni, Shun Shimohama

Journal of the neurological sciences   368   175 - 7  2016年09月  [国際誌]

DOI PubMed

Fingolimod suppresses bone resorption in female patients with multiple sclerosis.

Yusei Miyazaki, Masaaki Niino, Ippei Kanazawa, Masako Suzuki, Masanori Mizuno, Shin Hisahara, Toshiyuki Fukazawa, Eri Takahashi, Itaru Amino, Ryutaro Ochi, Masakazu Nakamura, Sachiko Akimoto, Naoya Minami, Naoto Fujiki, Shizuki Doi, Shun Shimohama, Yasuo Terayama, Seiji Kikuchi

Journal of neuroimmunology   298   24 - 31  2016年09月  [国際誌]

　概要を見る

Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the inflammatory activity of multiple sclerosis (MS), and has been shown to suppress osteoporosis in mouse models. In this study, levels of bone turnover markers were quantified in serum and urine samples from MS patients treated with fingolimod. Compared with untreated MS patients and healthy controls, fingolimod-treated MS patients had a significantly lower level of the bone resorption marker type I collagen cross-linked N-telopeptide in urine. This finding was prominent in female but was not seen in male subjects. Our results suggest that fingolimod may have a beneficial effect on bone mass loss in female MS patients.

DOI PubMed

Oxidation and interaction of DJ-1 with 20S proteasome in the erythrocytes of early stage Parkinson's disease patients.

Yoshiro Saito, Yoko Akazawa-Ogawa, Akihiro Matsumura, Kazumasa Saigoh, Sayoko Itoh, Kenta Sutou, Mayuka Kobayashi, Yuichiro Mita, Mototada Shichiri, Shin Hisahara, Yasuo Hara, Harutoshi Fujimura, Hiroyuki Takamatsu, Yoshihisa Hagihara, Yasukazu Yoshida, Takao Hamakubo, Susumu Kusunoki, Shun Shimohama, Noriko Noguchi

Scientific reports   6   30793 - 30793  2016年07月  [国際誌]

　概要を見る

Parkinson's disease (PD) is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1, the product of the causative gene of a familial form of PD, plays a significant role in anti-oxidative defence to protect cells from oxidative stress. DJ-1 undergoes preferential oxidation at the cysteine residue at position 106 (Cys-106) under oxidative stress. Here, using specific antibodies against Cys-106-oxidized DJ-1 (oxDJ-1), it was found that the levels of oxDJ-1 in the erythrocytes of unmedicated PD patients (n = 88) were higher than in those of medicated PD patients (n = 62) and healthy control subjects (n = 33). Elevated oxDJ-1 levels were also observed in a non-human primate PD model. Biochemical analysis of oxDJ-1 in erythrocyte lysates showed that oxDJ-1 formed dimer and polymer forms, and that the latter interacts with 20S proteasome. These results clearly indicate a biochemical alteration in the blood of PD patients, which could be utilized as an early diagnosis marker for PD.

DOI PubMed

MFN2遺伝子点変異を有するシャルコー・マリー・トゥース病の1例

横川 和樹, 池田 和奈, 村原 貴史, 齊藤 正樹, 鈴木 秀一郎, 津田 笑子, 林 貴士, 久原 真, 川又 純, 下濱 俊, 外山 祐一郎

臨床神経学 ( (一社)日本神経学会 )  56 ( 6 ) 453 - 453  2016年06月

ネフローゼ症候群、潰瘍性大腸炎、再生不良性貧血を合併した抗MuSK抗体陽性重症筋無力症の1例

安食 さえ子, 横川 和樹, 津田 笑子, 久原 真, 鈴木 秀一郎, 林 貴士, 齊藤 正樹, 川又 純, 今井 富裕, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  56 ( 6 ) 452 - 452  2016年06月

肛門周囲の感覚障害で発症し、前立腺生検にて診断に至った血管内リンパ腫(IVL)の1例

齋藤 太郎, 中村 祐貴, 鈴木 秀一郎, 津田 笑子, 林 貴士, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊, 村瀬 和幸, 高田 弘一

臨床神経学 ( (一社)日本神経学会 )  56 ( 6 ) 451 - 451  2016年06月