論文 - 久原　真

A case of Charcot-Marie-Tooth disease type 2Z caused by MORC2 S87L mutation mimicking spinal muscular atrophy

Daisuke Yamamoto, Ryosuke Oda, Shin Hisahara, Aki Ishikawa, Tomoo Ogi, Shun Shimohama

Clinical Neurology ( Societas Neurologica Japonica )  61 ( 4 ) 262 - 264  2021年

　概要を見る

A 33-year-old man with an unremarkable family history has had limb muscle weakness, joint contracture and skeleton deformation from early childhood. He was diagnosed with spinal muscular atrophy (SMA) by a pediatrician. He needed assistance and used orthoses in his daily life. There was no subjective sensory disturbance. However, physical examination showed slight sensory impairment, and nerve conduction study indicated sensory motor axonal neuropathy. This finding suggested Charcot-Marie-Tooth disease (CMT). Gene analysis detected MORC2 S87L mutation, leading to a diagnosis of CMT type 2Z. Patients with MORC2 S87L mutation are known to exhibit a severe phenotype, and may mimic SMA. It is important to demonstrate subclinical sensory neuropathy in patients with MORC2 S87L mutation mimicking SMA.

DOI PubMed

Hyperemesis-induced Wernicke-Korsakoff Syndrome due to Hypergastrinemia during Long-term Treatment with Proton Pump Inhibitors.

Rei Miyanaga, Shin Hisahara, Ikkei Ohhashi, Daisuke Yamamoto, Akihiro Matsumura, Syuuichirou Suzuki, Katsumasa Tanimoto, Masahiro Hirakawa, Jun Kawamata, Junji Kato, Shun Shimohama

Internal medicine (Tokyo, Japan)   59 ( 21 ) 2783 - 2787  2020年11月  [国内誌]

　概要を見る

We herein report a patient with Wernicke-Korsakoff syndrome (WKS) who had neither a history of alcoholism or of history of gastric surgery. A 56-year-old woman was transferred to our hospital because of the loss of consciousness and she was diagnosed to have Wernicke encephalopathy. She showed proton pump inhibitor-induced refractory hypergastrinemia with the subsequent development of hyperemesis and a vitamin B1 deficiency.

DOI PubMed

Severe mononeuritis multiplex due to rheumatoid vasculitis in rheumatoid arthritis in sustained clinical remission for decades

Masanobu Tanemoto, Shin Hisahara, Bungo Hirose, Kazuna Ikeda, Takashi Matsushita, Shuichiro Suzuki, Tatsuo Manabe, Tomihiro Imai, Shun Shimohama

Internal Medicine ( Japanese Society of Internal Medicine )  59 ( 5 ) 705 - 710  2020年03月

　概要を見る

Rheumatoid vasculitis (RV) usually occurs in patients with refractory rheumatoid arthritis (RA). An 80-year-old woman was transferred to our hospital because of muscle weakness and paresthesia in all 4 limbs. She had been diagnosed with RA 30 years ago and achieved sustained clinical remission. At presentation, polyarthritis and drop foot were observed, and rheumatoid factor was prominently elevated. A peripheral nerve conduction test revealed mononeuritis multiplex in her limbs. We suspected that RV had developed rapidly despite RA having been stable for many years and started immunosuppression therapy with steroids combined with azathioprine. The treatment prevented worsening of muscle weakness and paresthesia.

DOI PubMed

16SrRNA解析と膿瘍培養でFusobacterium nucleatumとStreptococcus intermediusの感染が判明した脳膿瘍の一例

真部 建郎, 種本 真将, 小田 亮介, 松村 晃寛, 久原 真, 下濱 俊

日本病院総合診療医学会雑誌 ( (一社)日本病院総合診療医学会 )  16 ( 臨増1 ) 65 - 65  2020年02月

16SrRNA解析と膿瘍培養でFusobacterium nucleatumとStreptococcus intermediusの感染が判明した脳膿瘍の一例

曹 博, 種本 真将, 廣瀬 文吾, 池田 和奈, 津田 玲子, 真部 建郎, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 久原 真, 高橋 聡, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  60 ( 1 ) 94 - 94  2020年01月

神経変性疾患に対する脳血流123I-IMP-SPECTにおけるCIScore解析の検証

松村 晃寛, 浅沼 治, 横川 和樹, 齋藤 太郎, 藤倉 舞, 岩原 直敏, 眞部 建郎, 津田 玲子, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 臼井 桂子, 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 )  59 ( Suppl. ) S266 - S266  2019年11月

神経変性疾患に対する脳血流123I-IMP-SPECTにおけるCIScore解析の検証

松村 晃寛, 浅沼 治, 横川 和樹, 齋藤 太郎, 藤倉 舞, 岩原 直敏, 眞部 建郎, 津田 玲子, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 臼井 桂子, 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 )  59 ( Suppl. ) S266 - S266  2019年11月

孤発性神経核内封入体病(NIID)の1例

廣瀬 文吾, 松下 隆司, 鈴木 秀一郎, 久原 真, 上杉 春雄, 川又 純, 今井 富裕, 曽根 淳, 祖父江 元, 下濱 俊

日本老年医学会雑誌 ( (一社)日本老年医学会 )  56 ( 4 ) 545 - 545  2019年10月

Transplantation of Mesenchymal Stem Cells Improves Amyloid-β Pathology by Modifying Microglial Function and Suppressing Oxidative Stress.

Yokokawa K, Iwahara N, Hisahara S, Emoto MC, Saito T, Suzuki H, Manabe T, Matsumura A, Matsushita T, Suzuki S, Kawamata J, Sato-Akaba H, Fujii HG, Shimohama S

Journal of Alzheimer's disease : JAD   72 ( 3 ) 867 - 884  2019年10月  [査読有り]  [国際誌]

　概要を見る

Mesenchymal stem cells (MSC) are increasingly being studied as a source of cell therapy for neurodegenerative diseases, and several groups have reported their beneficial effects on Alzheimer's disease (AD). In this study using AD model mice (APdE9), we found that transplantation of MSC via the tail vein improved spatial memory in the Morris water maze test. Using electron paramagnetic resonance imaging to evaluate the in vivo redox state of the brain, we found that MSC transplantation suppressed oxidative stress in AD model mice. To elucidate how MSC treatment ameliorates oxidative stress, we focused on amyloid-β (Aβ) pathology and microglial function. MSC transplantation reduced Aβ deposition in the cortex and hippocampus. Transplantation of MSC also decreased Iba1-positive area in the cortex and reduced activated ameboid shaped microglia. On the other hand, MSC transplantation accelerated accumulation of microglia around Aβ deposits and prompted microglial Aβ uptake and clearance as shown by higher frequency of Aβ-containing microglia. MSC transplantation also increased CD14-positive microglia in vivo, which play a critical role in Aβ uptake. To confirm the effects of MSC on microglia, we co-cultured the mouse microglial cell line MG6 with MSC. Co-culture with MSC enhanced Aβ uptake by MG6 cells accompanied by upregulation of CD14 expression. Additionally, co-culture of MG6 cells with MSC induced microglial phenotype switching from M1 to M2 and suppressed production of proinflammatory cytokines. These data indicate that MSC treatment has the potential to ameliorate oxidative stress through modification of microglial functions, thereby improving Aβ pathology in AD model mice.

DOI PubMed

脊髄梗塞と鑑別を要しステロイドパルス療法で改善が得られた急性脊髄炎の1例

種本 真将, 鈴木 秀一郎, 廣瀬 文吾, 池田 和奈, 久原 真, 下濱 俊

神経治療学 ( (一社)日本神経治療学会 )  36 ( 6 ) S282 - S282  2019年10月

Early administration of galantamine from preplaque phase suppresses oxidative stress and improves cognitive behavior in APPswe/PS1dE9 mouse model of Alzheimer's disease.

Saito T, Hisahara S, Iwahara N, Emoto MC, Yokokawa K, Suzuki H, Manabe T, Matsumura A, Suzuki S, Matsushita T, Kawamata J, Sato-Akaba H, Fujii HG, Shimohama S

Free radical biology & medicine   145   20 - 32  2019年09月  [査読有り]

DOI PubMed

悪性リンパ腫に合併した抗アクアポリン4抗体陽性散在性脳白質病変の1例

山田 稔, 津田 玲子, 山本 大輔, 松村 晃寛, 岩原 直敏, 松下 隆司, 鈴木 秀一郎, 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 )  59 ( 6 ) 391 - 391  2019年06月

Evaluation of Mitochondrial Oxidative Stress in the Brain of a Transgenic Mouse Model of Alzheimer's Disease by in vitro Electron Paramagnetic Resonance Spectroscopy.

Manabe T, Matsumura A, Yokokawa K, Saito T, Fujikura M, Iwahara N, Matsushita T, Suzuki S, Hisahara S, Kawamata J, Suzuki H, Emoto MC, Fujii HG, Shimohama S

Journal of Alzheimer's disease : JAD   67 ( 3 ) 1079 - 1087  2019年  [査読有り]

DOI PubMed

CD14 and Toll-Like Receptor 4 Promote Fibrillar Aβ42 Uptake by Microglia Through A Clathrin-Mediated Pathway.

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

Journal of Alzheimer's disease : JAD   68 ( 1 ) 323 - 337  2019年  [国際誌]

　概要を見る

We previously demonstrated that microglia play an essential role in clearance of amyloid-β (Aβ) in Alzheimer's disease (AD)-like pathology. Our prior work also showed that several receptors expressed on microglia participated in Aβ phagocytosis. However, clathrin-mediated endocytosis (CME), which is associated with production and release of Aβ in neurons, has received much less attention in the context of microglial Aβ uptake. To elucidate the detailed mechanisms of microglial Aβ uptake pathways, we focused on CD14 and Toll-like receptor 4 (TLR4), which have been shown to mediate fibrillar Aβ1 - 42 (fAβ42) phagocytosis in microglia. CD14 has also been known to control lipopolysaccharide-induced internalization of TLR4 in a clathrin-dependent manner. However, it remains unclear whether CD14 and TLR4 engage in CME in microglial fAβ42 uptake, including whether CD14 interacts with TLR4 in the process. In the present study, we found that CD14-positive microglia increased in an age-dependent manner in the cortex of AD model mice. Immunostaining showed that CD14 interacted with TLR4 to internalize fAβ42 in the mouse microglial cell line MG6. Knock-down of CD14 and TLR4 in MG6 cells significantly reduced intracellular fAβ42, showing their involvement in fAβ42 uptake. We also found that clathrin participated in fAβ42 uptake by MG6 cells. Furthermore, CD14 and TLR4 mediated fAβ42 uptake via clathrin-dependent mechanisms. These results indicate that CD14 and TLR4 participate not only in phagocytosis but also in clathrin-dependent fAβ42 internalization in microglia. These findings provide novel molecular understanding of microglial fAβ42 uptake, which could be of therapeutic relevance for AD.

DOI PubMed

筋力低下を主訴とした孤発性成人発症型ネマリンミオパチーの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, 齊藤 正樹, 久原 真, 川又 純, 下濱 俊

日本老年医学会雑誌 ( (一社)日本老年医学会 )  55 ( 4 ) 698 - 698  2018年10月

Arterial spin labelingが早期診断に貢献した進行性多巣性白質脳症の一例

松下 隆司, 中村 祐貴, 齋藤 太郎, 津田 玲子, 山本 大輔, 松村 晃寛, 鈴木 秀一郎, 津田 笑子, 久原 真, 川又 純, 菅原 太郎, 杉田 真太朗, 中道 一生, 下濱 俊

NEUROINFECTION ( 日本神経感染症学会 )  23 ( 2 ) 225 - 225  2018年10月

脳血流IMP-SPECTにおけるCIScore解析によるDLB・AD鑑別の検証

松村 晃寛, 浅沼 治, 蒲生 直希, 横川 和樹, 齋藤 太郎, 藤倉 舞, 岩原 直敏, 真部 建郎, 津田 玲子, 山本 大輔, 松下 隆司, 鈴木 秀一郎, 臼井 桂子, 齊藤 正樹, 久原 真, 川又 純, 今井 富裕, 下濱 俊

Dementia Japan ( (一社)日本認知症学会 )  32 ( 3 ) 452 - 452  2018年09月

[Sporadic adult-onset neuronal intranuclear inclusion disease with abnormal electroretinogram, nerve conduction studies and somatosensory evoked potential].

Bungo Hirose, Shin Hisahara, Haruo Uesugi, Jun Sone, Gen Sobue, Shun Shimohama

Rinsho shinkeigaku = Clinical neurology   58 ( 6 ) 407 - 410  2018年06月  [国内誌]

　概要を見る

A 70-year-old man, a urinary retention of unknown origin from 10 years ago, decreased cognitive function from 4 years ago, vision impairment advanced a year ago. Brain MRI with DWI showed high intensity erea in the cortico-medullary junction. We diagnosed as intranuclear inclusion body disease (NIID) because of p62-positive intranuclear inclusion bodies by skin biopsy. Electroretinogram revealed amplitude reduction in the cone response superiority. Nerve conduction test showed mild conduction velocity reduction. Furthermore, in the somatosensory evoked potential of the lower limb, latency of the first cortical component was prolonged. These electrophysiological abnormalities were considered to be associated with the pathological features of NIID.

DOI PubMed

網膜電図、末梢神経伝導検査、体性感覚誘発電位異常を伴った孤発性神経核内封入体病の1例

廣瀬 文吾, 久原 真, 上杉 春雄, 曽根 淳, 祖父江 元, 下濱 俊

臨床神経学 ( (一社)日本神経学会 )  58 ( 6 ) 407 - 410  2018年06月

　概要を見る

症例は70歳の男性、10年前より原因不明の尿閉、4年前より認知機能低下、1年前より視力障害が進行した。頭部MRI拡散強調画像で皮質下皮髄境界に弧状の高信号を、皮膚生検で神経核内封入体を認めたため神経核内封入体病(neuronal intranuclear inclusion disease;NIID)と診断した。神経伝導検査では軽度の伝導速度低下を、下肢体性感覚誘発電位では早期皮質潜時の延長が見られた。視力低下の原因精査で行った網膜電図では錐体応答優位に振幅低下を認めていた。これらの所見は他に明らかな原因がなくNIIDに伴う異常と考えられた。視力低下は臨床徴候として知られておらず詳細な文献的考察は少ない。症例の集積が必要であると考えられる。(著者抄録)

Non-HIV-PMLの診断後2年以上生存した1症例

中村 祐貴, 齋藤 太郎, 津田 玲子, 山本 大輔, 松下 隆司, 松村 晃寛, 鈴木 秀一郎, 津田 笑子, 久原 真, 川又 純, 下濱 俊, 菅原 太郎, 杉田 真太朗, 中道 一生

臨床神経学 ( (一社)日本神経学会 )  58 ( 5 ) 358 - 358  2018年05月