2021/12/04 更新

写真a

ニノミヤ イタル
二宮 格
NINOMIYA Itaru
所属
医歯学総合病院 脳神経内科 特任助教
職名
特任助教
外部リンク

学位

  • 博士(医学) ( 2020年3月   新潟大学 )

  • 学士(医学) ( 2008年3月   新潟大学 )

研究キーワード

  • 脳卒中

研究分野

  • ライフサイエンス / 神経内科学

  • ライフサイエンス / 内科学一般

経歴

  • 新潟大学   医歯学総合病院 脳神経内科   特任助教

    2020年4月 - 現在

  • 新潟大学   医歯学総合病院 高次救命災害治療センター   特任助教

    2015年4月 - 2017年3月

 

論文

  • 医学と医療の最前線 脳梗塞に対する細胞療法の最前線

    畠山 公大, 二宮 格, 小野寺 理, 下畑 享良, 金澤 雅人

    日本内科学会雑誌   110 ( 1 )   117 - 123   2021年1月

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    記述言語:日本語   出版者・発行元:(一社)日本内科学会  

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  • Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review. 国際誌

    Yutaka Otsu, Masaki Namekawa, Masafumi Toriyabe, Itaru Ninomiya, Masahiro Hatakeyama, Masahiro Uemura, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

    Journal of the neurological sciences   419   117217 - 117217   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Reperfusion therapies by tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) have ushered in a new era in the treatment of acute ischemic stroke (AIS). However, reperfusion therapy-related HT remains an enigma. AIM: To provide a comprehensive review focused on emerging concepts of stroke and therapeutic strategies, including the use of protective agents to prevent HT after reperfusion therapies for AIS. METHODS: A literature review was performed using PubMed and the ClinicalTrials.gov database. RESULTS: Risk of HT increases with delayed initiation of tPA treatment, higher baseline glucose level, age, stroke severity, episode of transient ischemic attack within 7 days of stroke onset, and hypertension. At a molecular level, HT that develops after thrombolysis is thought to be caused by reactive oxygen species, inflammation, remodeling factor-mediated effects, and tPA toxicity. Modulation of these pathophysiological mechanisms could be a therapeutic strategy to prevent HT after tPA treatment. Clinical mechanisms underlying HT after MT are thought to involve smoking, a low Alberta Stroke Program Early CT Score, use of general anesthesia, unfavorable collaterals, and thromboembolic migration. However, the molecular mechanisms are yet to be fully investigated. Clinical trials with MT and protective agents have also been planned and good outcomes are expected. CONCLUSION: To fully utilize the easily accessible drug-tPA-and the high recanalization rate of MT, it is important to reduce bleeding complications after recanalization. A future study direction could be to investigate the recovery of neurological function by combining reperfusion therapies with cell therapies and/or use of pleiotropic protective agents.

    DOI: 10.1016/j.jns.2020.117217

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  • ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性

    金澤 雅人, 二宮 格, 上村 昌寛, 下畑 享良, 小野寺 理

    臨床神経学   60 ( Suppl. )   S360 - S360   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 脳梗塞に対する低酸素低糖刺激末梢血単核球を用いた細胞療法

    畠山 公大, 金澤 雅人, 二宮 格, 尾前 薫, 木村 泰子, 高橋 哲哉, 小野寺 理, 福島 雅典, 下畑 享良

    脳循環代謝   32 ( 1 )   81 - 81   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本脳循環代謝学会  

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  • ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性の検討

    二宮 格, 金澤 雅人, 上村 昌寛, 小野寺 理

    脳循環代謝   32 ( 1 )   113 - 113   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本脳循環代謝学会  

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  • [Cell Therapy Using Peripheral Mononuclear Cells Preconditioned by Oxygen-Glucose Deprivation for Ischemic Stroke].

    Masahiro Hatakeyama, Itaru Ninomiya, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

    Brain and nerve = Shinkei kenkyu no shinpo   72 ( 10 )   1097 - 1103   2020年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Many studies in recent years have reported cell therapies using embryonic stem cells, induced pluripotent stem cells, and bone marrow-derived mononuclear cells for cerebral ischemia. However, obtaining these cells is challenging, and these cell therapies require complicated procedures to prepare cells for administration. Notably, peripheral blood mononuclear cells (PBMCs) are a useful cell source for clinical applications because cell collection is easier. In this review, we report the therapeutic effects of PBMCs preconditioned by oxygen-glucose deprivation (OGD-PBMCs) on cerebral ischemia. Cell therapies using tissue-protective OGD-PBMCs might be a simple and ideal therapeutic strategy against ischemic stroke.

    DOI: 10.11477/mf.1416201655

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  • 脳梗塞に対する低酸素低糖刺激末梢血単核球療法

    畠山 公大, 二宮 格, 小野寺 理, 下畑 享良, 金澤 雅人

    BRAIN and NERVE: 神経研究の進歩   72 ( 10 )   1097 - 1103   2020年10月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>近年,脳梗塞に対する細胞療法の研究が盛んに行われているが,既存の細胞療法は,投与細胞の採取や調整に複雑な手技を要するため,一般臨床への普及が難しい。われわれは,末梢血単核球に,低酸素低糖刺激という簡便な刺激を加えることにより,脳梗塞に対して治療効果のある細胞を調整できることを証明した。本稿では,われわれの開発した技術と今後の展望について概説する。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J04871&link_issn=&doc_id=20201012210017&doc_link_id=40022380199&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40022380199&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • Cell Therapies under Clinical Trials and Polarized Cell Therapies in Pre-Clinical Studies to Treat Ischemic Stroke and Neurological Diseases: A Literature Review. 国際誌

    Masahiro Hatakeyama, Itaru Ninomiya, Yutaka Otsu, Kaoru Omae, Yasuko Kimura, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata, Masato Kanazawa

    International journal of molecular sciences   21 ( 17 )   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stroke remains a major cause of serious disability because the brain has a limited capacity to regenerate. In the last two decades, therapies for stroke have dramatically changed. However, half of the patients cannot achieve functional independence after treatment. Presently, cell-based therapies are being investigated to improve functional outcomes. This review aims to describe conventional cell therapies under clinical trial and outline the novel concept of polarized cell therapies based on protective cell phenotypes, which are currently in pre-clinical studies, to facilitate functional recovery after post-reperfusion treatment in patients with ischemic stroke. In particular, non-neuronal stem cells, such as bone marrow-derived mesenchymal stem/stromal cells and mononuclear cells, confer no risk of tumorigenesis and are safe because they do not induce rejection and allergy; they also pose no ethical issues. Therefore, recent studies have focused on them as a cell source for cell therapies. Some clinical trials have shown beneficial therapeutic effects of bone marrow-derived cells in this regard, whereas others have shown no such effects. Therefore, more clinical trials must be performed to reach a conclusion. Polarized microglia or peripheral blood mononuclear cells might provide promising therapeutic strategies after stroke because they have pleiotropic effects. In traumatic injuries and neurodegenerative diseases, astrocytes, neutrophils, and T cells were polarized to the protective phenotype in pre-clinical studies. As such, they might be useful therapeutic targets. Polarized cell therapies are gaining attention in the treatment of stroke and neurological diseases.

    DOI: 10.3390/ijms21176194

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  • Elevated serum pentraxin 3 levels might predict the diagnosis of branch atheromatous disease at a very early stage. 査読 国際誌

    Itaru Ninomiya, Masato Kanazawa, Masahiro Umemura, Osamu Onodera

    European journal of neurology   2020年4月

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    記述言語:英語  

    BACKGROUND: Branch atheromatous disease (BAD) is one of the stroke subtypes caused by occlusion at the origin of a deep penetrating artery of the brain and is associated with a microatheroma or a junctional plaque. Patients with BAD often develop progressive worsening of neurologic deficits, although these patients often present minor stroke with clinical characteristics of lacunar syndrome at the onset. Pentraxin 3 (PTX3) is known to be a key molecule involved in the pathogenesis of atherosclerosis. Although a high level of serum PTX3 is observed in patients with acute coronary syndrome, there are no reports on PTX3 levels in patients with BAD. This study aimed to investigate whether serum PTX3 levels can distinguish BAD from other stroke subtypes. METHODS: We investigated 93 patients with ischemic stroke. Serum PTX3 levels on admission were measured using enzyme-linked immunosorbent assay in patients with BAD and those of other stroke subtypes (each n ≥ 20). RESULTS: The median PTX3 levels in patients with BAD (4840 pg/mL) were higher than those with other subtypes of stroke (3397 pg/mL in lacunar stroke, 1298 pg/mL in large artery atherosclerosis, 1470 pg/mL in cardioaortic embolism, and 1006 pg/mL in control) (all p < 0.01). CONCLUSION: Our results suggest that elevated serum pentraxin 3 levels might predict the diagnosis of BAD at a very early stage.

    DOI: 10.1111/ene.14249

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  • Angiogenesis and neuronal remodeling after ischemic stroke. 査読 国際誌

    Masahiro Hatakeyama, Itaru Ninomiya, Masato Kanazawa

    Neural regeneration research   15 ( 1 )   16 - 19   2020年1月

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    記述言語:英語  

    Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke. Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit. In this mini-review, we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia. Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery. Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery. First, new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling. Second, blood vessels are thought to enhance neurogenesis in three stages: 1) Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals, 2) microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen, nutrients, and soluble factors as well as serving as a scaffold for migration, and 3) oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons. Thus, the regions of angiogenesis and surrounding tissue may be coupled, representing novel treatment targets.

    DOI: 10.4103/1673-5374.264442

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  • Publisher Correction: A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation. 査読 国際誌

    Masahiro Hatakeyama, Masato Kanazawa, Itaru Ninomiya, Kaoru Omae, Yasuko Kimura, Tetsuya Takahashi, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata

    Scientific reports   9 ( 1 )   19913 - 19913   2019年12月

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    記述言語:英語  

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    DOI: 10.1038/s41598-019-55308-2

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  • A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation. 査読 国際誌

    Masahiro Hatakeyama, Masato Kanazawa, Itaru Ninomiya, Kaoru Omae, Yasuko Kimura, Tetsuya Takahashi, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata

    Scientific reports   9 ( 1 )   16819 - 16819   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β in vitro, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia in vivo. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both in vitro and in vivo. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.

    DOI: 10.1038/s41598-019-53418-5

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  • Branch Atheromatous Diseaseにおける急性期の血清Lox-1値の検討

    二宮 格, 金澤 雅人, 下畑 享良, 小野寺 理

    臨床神経学   59 ( Suppl. )   S323 - S323   2019年11月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • Apparent diffusion coefficient reduction might be a predictor of poor outcome in patients with posterior reversible encephalopathy syndrome. 査読 国際誌

    Itaru Ninomiya, Masato Kanazawa, Yasuhisa Akaiwa, Takayoshi Shimohata, Kouichirou Okamoto, Osamu Onodera, Masatoyo Nishizawa

    Journal of the neurological sciences   381   1 - 3   2017年10月

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    記述言語:英語  

    It is thought that posterior reversible encephalopathy syndrome (PRES) is both clinically and radiologically reversible. However, its reversible nature has been challenged based on reports of permanent neurological impairments. The factors that predict the development of irreversible neurological impairment are still unclear. In the present study, we investigated clinical manifestations, laboratory findings, and neuroradiological images to identify predictors of functional outcomes in PRES. We investigated 23 PRES patients. Apparent diffusion coefficient (ADC) reduction was observed in 4 patients in the poor outcome group, whereas no patients presented ADC reduction in the favourable outcome group (p<0.01). Further studies are warranted to evaluate the association between ADC reduction and functional outcome after PRES.

    DOI: 10.1016/j.jns.2017.08.002

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  • Microglia and Monocytes/Macrophages Polarization Reveal Novel Therapeutic Mechanism against Stroke. 査読 国際誌

    Masato Kanazawa, Itaru Ninomiya, Masahiro Hatakeyama, Tetsuya Takahashi, Takayoshi Shimohata

    International journal of molecular sciences   18 ( 10 )   2017年10月

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    記述言語:英語  

    Stroke is a leading cause of morbidity and mortality worldwide, and consists of two types, ischemic and hemorrhagic. Currently, there is no effective treatment to increase the survival rate or improve the quality of life after ischemic and hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary to establish therapeutic strategies to facilitate functional recovery in patients with stroke during both phases. Cell-based therapies, using microglia and monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal therapeutic strategy for managing stroke. Microglia and monocytes/macrophages polarize to the classic pro-inflammatory type (M1-like) or alternative protective type (M2-like) by optimal condition. Cell-based therapies using M2-like microglia and monocytes/macrophages might be protective therapeutic strategies against stroke for three reasons. First, M2-like microglia and monocytes/monocytes secrete protective remodeling factors, thus prompting neuronal network recovery via tissue (including neuronal) and vascular remodeling. Second, these cells could migrate to the injured hemisphere through the blood-brain barrier or choroid-plexus. Third, these cells could mitigate the extent of inflammation-induced injuries by suitable timing of therapeutic intervention. Although future translational studies are required, M2-like microglia and monocytes/macrophages therapies are attractive for managing stroke based on their protective functions.

    DOI: 10.3390/ijms18102135

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  • [PRES: Posterior Reversible Encephalopathy Syndrome]. 査読

    Kouichirou Okamoto, Kunio Motohashi, Hidemoto Fujiwara, Tomohiko Ishihara, Itaru Ninomiya, Osamu Onodera, Yukihiko Fujii

    Brain and nerve = Shinkei kenkyu no shinpo   69 ( 2 )   129 - 141   2017年2月

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    記述言語:日本語  

    Posterior reversible encephalopathy syndrome (PRES) is suggested in patients with acute neurological symptoms in the appropriate clinical context, including acute hypertension, blood pressure fluctuations, renal failure, blood transfusion, immunosuppression, autoimmune disorders, and eclampsia. PRES is a clinical syndrome, and refers to a disorder with reversible subcortical vasogenic brain edema caused by endothelial dysfunction, predominantly involving the bilateral parieto-occipital regions. Although the clinical course and prognosis are favorable in most cases, intracranial hemorrhage and/or restricted diffusion similar to acute infarction could be seen in some lesions on brain magnetic resonance imaging (MRI). The spinal cord may be involved in some patients with posterior fossa lesions. Understanding the pathophysiology of PRES is helpful in making the correct early diagnosis and selecting appropriate therapies to improve its clinical course and outcome. Differentiation of PRES from strokes is critical in the setting of a neurological emergency.

    DOI: 10.11477/mf.1416200653

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MISC

  • 脳梗塞に対する低酸素低糖刺激末梢血単核球を用いた細胞療法

    畠山公大, 金澤雅人, 二宮格, 尾前薫, 木村泰子, 高橋哲哉, 小野寺理, 福島雅典, 下畑享良

    脳循環代謝(Web)   32 ( 1 )   2020年

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  • Branch Atheromatous Diseaseにおける急性期の血清Lox-1値の検討

    二宮 格, 金澤 雅人, 下畑 享良, 小野寺 理

    臨床神経学   59 ( Suppl. )   S323 - S323   2019年11月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 血液透析療法下で、脳出血発症後に脳浮腫が急速進行した58歳女性例

    大津 裕, 金山 武史, 二宮 格, 石原 智彦, 保坂 聖子, 忰田 亮平, 成田 一衛, 小野寺 理

    臨床神経学   58 ( 1 )   55 - 55   2018年1月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 血液透析療法下で、脳出血発症後に脳浮腫が急速進行した58歳女性例

    大津 裕, 金山 武史, 二宮 格, 石原 智彦, 保坂 聖子, 忰田 亮平, 成田 一衛, 小野寺 理

    臨床神経学   58 ( 1 )   55 - 55   2018年1月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • リツキシマブが有効であったMAG抗体関連神経障害の67歳男性例

    小出 眞悟, 西田 茉那, 斎藤 奈つみ, 笠原 壮, 二宮 格, 堅田 慎一, 小野寺 理

    臨床神経学   56 ( 12 )   876 - 876   2016年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • リツキシマブが有効であったMAG抗体関連神経障害の67歳男性例

    小出 眞悟, 西田 茉那, 斎藤 奈つみ, 笠原 壮, 二宮 格, 堅田 慎一, 小野寺 理

    臨床神経学   56 ( 12 )   876 - 876   2016年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 担癌患者における再発性脳梗塞の臨床的特徴

    高橋 哲哉, 赤岩 靖久, 上村 昌寛, 二宮 格, 鳥谷部 真史, 金澤 雅人, 西澤 正豊, 下畑 享良

    臨床神経学   56 ( Suppl. )   S512 - S512   2016年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • Posterior reversible encephalopathy syndromeの臨床像・経過に関する検討

    二宮 格, 金澤 雅人, 赤岩 靖久, 下畑 享良, 西澤 正豊

    臨床神経学   56 ( Suppl. )   S514 - S514   2016年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • Activity of Von Willebrand Factor During the Acute Phase of Ischemic Stroke Might Predict Worse Outcome

    Masahiro Uemura, Yasuhisa Akaiwa, Itaru Ninomiya, Hiroaki Arakawa, Masafumi Toriyabe, Takayoshi Shimohata, Masatoyo Nishizawa

    CEREBROVASCULAR DISEASES   36   2 - 3   2013年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:KARGER  

    Web of Science

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