Researchers Database

tanaka ryouta

    Professor
Last Updated :2021/11/23

Researcher Information

J-Global ID

Research Interests

  • 脳梗塞と免疫   認知症   血圧変動   起立性低血圧   パーキンソン病   脳梗塞と糖代謝異常   脳梗塞の再生治療   オリゴデンドロサイト前駆細胞   神経幹細胞   脳保護薬の開発   脳梗塞の病態   脳卒中   

Research Areas

  • Life sciences / Neurology

Academic & Professional Experience

  • 2018/04 - Today  Jichi Medical University脳卒中センター/内科学講座神経内科学部門教授
  • 2011/04 - 2017/03  Juntendo UniversityFaculty of Medicine准教授
  • 2008/10 - 2011/03  Juntendo UniversityFaculty of Medicine准教授
  • 2008/04 - 2008/09  Juntendo UniversityFaculty of Medicine助手
  • 2006/09 - 2008/03  Juntendo UniversityFaculty of Medicine助手
  • 2006/01 - 2006/08  Juntendo UniversityFaculty of Medicine助手
  • 2005/05 - 2005/12  Juntendo UniversityFaculty of Medicine助手
  • 2003/05 - 2005/04  カルガリー大学医学部細胞生物学・解剖学(Prof. Samuel Weiss)博士研究員
  • 2000/04 - 2003/03  Juntendo University神経学講座大学院生
  • 1996/04 - 2000/03  Juntendo UniversityDepartment of Neurology

Education

  •        - 1996/03  Juntendo University  Medical

Association Memberships

  • 日本頭痛学会   日本パーキンソン病・運動障害疾患学会   日本脳血管・認知症学会   日本神経治療学会   日本栓子検出と治療学会   THE JAPAN ACADEMY OF NEUROSONOLOGY   JAPAN EPILEPSY SOCIETY   International Society of Cerebral Blood Flow & Metabolism   Japanese society of cerebral blood flow and metabolism   THE JAPANESE SOCIETY OF INTERNAL MEDICINE   THE JAPAN STROKE SOCIETY   JAPANESE SOCIETY OF NEUROLOGY   

Published Papers

  • Andrea Pilotto, Alberto Romagnolo, Andrea Scalvini, Mario Masellis, Yasushi Shimo, Laura Bonanni, Richard Camicioli, Lily L Wang, Alok K Dwivedi, Katherine Longardner, Federico Rodriguez-Porcel, Mark DiFrancesco, Joaquin A Vizcarra, Elisa Montanaro, Simona Maule, Alessandro Lupini, Carmen Ojeda-López, Sandra E Black, Stefano Delli Pizzi, Myrlene Gee, Ryota Tanaka, Kazuo Yamashiro, Taku Hatano, Barbara Borroni, Roberto Gasparotti, Maria C Rizzetti, Nobutaka Hattori, Leonardo Lopiano, Irene Litvan, Alberto J Espay, Alessandro Padovani, Aristide Merola
    Neurology 97 (8) e814-e824  2021/08 
    OBJECTIVE: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales. RESULTS: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72). CONCLUSIONS: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.
  • Kosuke Matsuzono, Tomoya Yagisawa, Keisuke Ohtani, Yohei Ishishita, Takashi Yamaguchi, Takafumi Mashiko, Tadashi Ozawa, Reiji Koide, Ryota Tanaka, Kensuke Kawai, Shigeru Fujimoto
    The Journal of international medical research 49 (8) 3000605211035197 - 3000605211035197 2021/08 
    Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma, but its diagnosis is challenging in some cases. A brain biopsy is the gold standard for diagnosing PCNSL, but its invasiveness can be problematic. Thus, noninvasive imaging examinations have been developed for the pre-surgical diagnosis of PCNSL, including gadolinium-enhanced magnetic resonance imaging (MRI), 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (123I-IMP SPECT), and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET). Here, we report the case of a 71-year-old woman with negative imaging findings for PCNSL, but who was diagnosed with PCNSL by a brain biopsy and histological analysis. Her imaging results were negative for gadolinium-enhanced cranial MRI, with low uptake in 123I-IMP SPECT and hypometabolism in 18F-FDG PET. However, a stereotactic brain biopsy from an abnormal lesion revealed that many round cells had infiltrated into the brain. Moreover, many infiltrating cells were positive for cluster of differentiation (CD)20 and CD79a, and proliferation marker protein Ki-67-positive cells accounted for nearly 80% of all cells. Based on these results, our final pathological diagnosis was PCNSL. The present case highlights the possibility of a PCNSL diagnosis even when all imaging-related examinations display negative results.
  • Kosuke Matsuzono, Masayuki Suzuki, Kumiko Miura, Tadashi Ozawa, Takafumi Mashiko, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2021/07 
    BACKGROUND: Although the relationship between amyotrophic lateral sclerosis (ALS) and cervical spondylotic myelopathy (CSM) is important, data relating to CSM complications in ALS remain lacking. PURPOSE: We aimed to investigate and validate the spinal cord conditions of ALS patients. MATERIALS AND METHODS: We recruited all patients diagnosed with ALS, Parkinson's disease (PD), or chronic inflammatory demyelinating polyneuropathy (CIDP) who were admitted to our department from April 1, 2017, to March 31, 2020. We analyzed the cervical or thoracolumbar magnetic resonance imaging (MRI) scans of these 128 patients. Data relating to spondylosis, cord compression, spinal canal diameter, spinal cord diameter, and the closest distance between the cervical spinal canal and cord were validated using MRI. RESULTS: Of the 128 patients, 52 had ALS, 48 had PD, and 28 had CIDP. The proportions of both cervical spondylosis and cervical cord compression were highest in the ALS group compared with the other patient groups (p < 0.05). The proportion of cervical spondylosis in ALS patients reached 38.3%, and that of cervical cord compression reached 53.2%. The closest distance between the cervical spinal canal and cord was also significantly smaller in ALS patients compared with CIDP patients (p < 0.05). In contrast to the cervical cord findings, there were no significant differences in the thoracolumbar cord between ALS patients and the other patient groups. CONCLUSIONS: Of the three disease groups, the proportion of CSM was highest in ALS patients. Furthermore, cervical cord conditions were significantly more crowded in the ALS patients than in the other patient groups.
  • Masayuki Suzuki, Shigeru Fujimoto, Ryota Tanaka
    Journal of atherosclerosis and thrombosis 28 (7) 789 - 790 2021/07
  • Junya Aoki, Yasuyuki Iguchi, Takao Urabe, Hiroshi Yamagami, Kenichi Todo, Shigeru Fujimoto, Koji Idomari, Nobuyuki Kaneko, Takeshi Iwanaga, Tadashi Terasaki, Ryota Tanaka, Nobuaki Yamamoto, Akira Tsujino, Koichi Nomura, Koji Abe, Masaaki Uno, Yasushi Okada, Hideki Matsuoka, Sen Yamagata, Yasumasa Yamamoto, Toshiro Yonehara, Takeshi Inoue, Yoshiki Yagita, Kazumi Kimura
    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 89 216 - 222 2021/07 
    BACKGROUND AND PURPOSE: In this post-hoc analysis using acute dual study dataset, the impacts of cerebral microbleeds (MBs) after mild stroke on clinical outcome were investigated. METHODS: The number of MBs on admission was categorized as 1) no MBs, 2) MBs 1-4, 3) MBs 5-9, and 4) MBs ≥ 10. The efficacy outcome was defined as neurological deterioration and stroke recurrence within 14 days. Safety outcomes included ICH and/or SAH as well as extracranial hemorrhages. RESULTS: Of the 1102 patients, 780 (71%) had no MBs on admission, while 230 (21%) had MBs 1-4, 48 (4%) had MBs 5-9, and 44 (4%) had MBs ≥ 10. The number of MBs was not associated with the neurological deterioration and/or stroke recurrence (p = 0.934), ICH and/or SAH (p = 0.743), and extracranial hemorrhage (p = 0.205). Favorable outcome was seem in 84% in the No MBs group, 83% in the MBs 1-4, 94% in the MBs 5-9, and 85% in the MBs ≥ 10 (p = 0.304). Combined cilostazol and aspirin therapy did not alter any rates of efficacy and safety outcomes among the no MBs, MBs 1-4, MBs 5-9, and MBs ≥ 10 groups compared to aspirin alone (all p > 0.05). By multivariate regression analysis, a history of ICH and diastolic blood pressure were the independent parameters to all of the MBs criteria (presence, MBs ≥ 5, and MBs ≥ 10). CONCLUSIONS: MBs did not alter the clinical outcome at 3 months of onset. Elevated diastolic blood pressure and a history of ICH were the essential parameters related to the MBs.
  • Sho Nakajima, Ryota Tanaka, Kazuo Yamashiro, Asako Chiba, Daisuke Noto, Toshiki Inaba, Naohide Kurita, Nobukazu Miyamoto, Takuma Kuroki, Hideki Shimura, Yuji Ueno, Takao Urabe, Sachiko Miyake, Nobutaka Hattori
    Journal of the American Heart Association 2021/03 [Refereed]
     
    Background

    Mucosal‐associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. Methods and Results

    We used MR1 knockout C57BL/6 (MR1 −/− ) mice and wild‐type littermates (MR1 +/+ ). After performing a transient middle cerebral artery occlusion (tMCAO), we evaluated the association with inflammation and prognosis in the acute cerebral ischemia. Furthermore, we analyzed the tMCAO C57BL/6 mice administered with the suppressive MR1 ligand and the vehicle control. We also evaluated the infiltration of MAIT cells into the ischemic brain by flow cytometry. Results showed a reduction of infarct volume and an improvement of neurological impairment in MR1 −/− mice (n=8). There was a reduction in the number of infiltrating microglia/macrophages (n=3–5) and in their activation (n=5) in the peri‐infarct area of MR1 −/− mice. The cytokine levels of interleukin‐6 and interleukin‐17 at 24 hours after tMCAO (n=3–5), and for interleukin‐17 at 72 hours after tMCAO (n=5), were lower in the MR1 −/− mice. The administration of the suppressive MR1 ligand reduced the infarct volume and improved functional impairment (n=5). Flow cytometric analysis demonstrated there was a reduction of MAIT cells infiltrating into the ischemic brain at 24 hours after tMCAO (n=17). Conclusions

    Our results showed that MAIT cells play an important role in neuroinflammation after focal cerebral ischemia and the use of MAIT cell regulation has a potential role as a novel neuroprotectant for the treatment of acute ischemic stroke.

  • Junya Aoki, Yasuyuki Iguchi, Takao Urabe, Hiroshi Yamagami, Kenichi Todo, Shigeru Fujimoto, Koji Idomari, Nobuyuki Kaneko, Takeshi Iwanaga, Tadashi Terasaki, Ryota Tanaka, Nobuaki Yamamoto, Akira Tsujino, Koichi Nomura, Koji Abe, Masaaki Uno, Yasushi Okada, Hideki Matsuoka, Sen Yamagata, Yasumasa Yamamoto, Toshiro Yonehara, Takeshi Inoue, Yoshiki Yagita, Kazumi Kimura
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 30 (2) 105494 - 105494 2021/02 
    BACKGROUND: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. METHODS: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). RESULTS: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030). CONCLUSIONS: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.
  • Kosuke Matsuzono, Takafumi Mashiko, Tadashi Ozawa, Kumiko Miura, Masayuki Suzuki, Kohei Furuya, Misato Ozawa, Yuhei Anan, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Tomoaki Kameda, Shigeru Fujimoto
    Journal of Thrombosis and Thrombolysis 51 (2) 522 - 529 0929-5305 2021/02 [Refereed]
     
    The treatment of ischemic stroke has recently witnessed dramatic developments. However, there are limited data on ischemic stroke characteristics in aged patients. As part of the South Tochigi Acute Ischemic Stroke Registry, we prospectively enrolled 636 consecutive acute ischemic stroke patients (within 7 days after the onset) who were ≥ 60 years of age and who were admitted to two independent institutes from April 1, 2016 to February 28, 2019. We analyzed three groups divided by age: early-aged (60-69 years), middle-aged (70-79 years), and oldest-aged (≥ 80 years). From the 636 subjects, 194 were early-aged, 215 were middle-aged, and 227 were oldest-aged. There were significant differences in the ischemic stroke subtypes in each aging group (p < 0.01). The proportion of cardioembolism was 22.2% in early-aged, 27.4% in middle-aged, and 41.4% in the oldest-aged patients. The proportion of patients with a modified Rankin Scale of 0-2 at 1 year after onset decreased to 42.2% in middle-aged and 17.8% in oldest-aged with cardioembolic ischemic stroke. The proportion of patients receiving anticoagulation therapy before admission was 25.6% (36.7% of atrial fibrillation [AF]) in early-aged, 39.0% (52.3% of AF) in middle-aged, and 18.1% (21.0% of AF) in oldest-aged patients (p < 0.001). Our study reports characteristics of clinical ischemic stroke in an aging population. The assessment of cardiogenic embolism is important for an aging population.
  • Kosuke Matsuzono, Theerawat Kumutpongpanich, Kana Kubota, Takafumi Okuyama, Kohei Furuya, Tomoya Yagisawa, Akie Horikiri, Takeshi Igarashi, Kumiko Miura, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Hayato Shimizu, Yasushi Imai, Kazuomi Kario, Ichizo Nishino, Shigeru Fujimoto
    Internal Medicine 0918-2918 2021 [Refereed]
  • Hiroshi Hasegawa, Kenji Yatomi, Yumiko Mitome-Mishima, Nobukazu Miyamoto, Ryota Tanaka, Hidenori Oishi, Hajime Arai, Nobutaka Hattori, Takao Urabe
    Neuroscience Research 0168-0102 2020/12 [Refereed]
  • 心房細動合併脳梗塞急性期患者における大動脈弓部複合粥腫病変(CAPs)併存に関する研究
    鈴木 雅之, 小澤 美里, 三浦 久美子, 小澤 忠嗣, 松薗 構佑, 益子 貴史, 小出 玲爾, 藤本 茂, 田中 亮太
    脳循環代謝 (一社)日本脳循環代謝学会 32 (1) 86 - 86 0915-9401 2020/11
  • Ryota Tanaka, Kazuo Yamashiro, Takashi Ogawa, Genko Oyama, Kenya Nishioka, Atsushi Umemura, Yasushi Shimo, Nobutaka Hattori
    PLOS ONE 15 (10) e0240491 - e0240491 2020/10 [Refereed]
     
    Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). While OH is usually diagnosed based on an orthostatic blood pressure drop, the association between the heart rate response and cognitive impairment remains unclear. We retrospectively analyzed 143 cases of clinically diagnosed PD to determine the association between the absence of a heart rate response and cognitive impairment in PD with OH. Among the patients with OH, neurogenic OH was diagnosed in cases without a heart rate increase, while all other patients were diagnosed with non-neurogenic OH. Dementia was found in 23 of 143 PD cases (16.1%) in this cohort. The presence of OH was an independent risk factor for dementia in PD in addition to the disease severity, years of education and beta-blockers use. Neurogenic OH was significantly associated with dementia compared to the no OH group (hazard ratio [HR] 7.3, 95% confidence interval [CI] 2.2-24.6, P<0.01), an association that was preserved after adjusting for age, gender and other covariant factors. However, no such association was observed for non-neurogenic OH (HR 2.9, 95%CI 0.8-10.9, P = 0.12). While the cognitive impairment was significantly worse in the neurogenic OH group than the no-OH group, the groups were otherwise similar. The blood pressure decrease was significantly lower in both OH groups than in the no-OH group, despite no significant differences between the OH groups. Our finding showed that OH without a heart rate response was an important predictor of cognitive impairment in PD.
  • Yu Kono, Yuka Terasawa, Kenichiro Sakai, Yasuyuki Iguchi, Yasuhiro Nishiyama, Chikako Nito, Satoshi Suda, Kazumi Kimura, Takao Kanzawa, Ichiro Imafuku, Takahiro Nakayama, Masayuki Ueda, Takeshi Iwanaga, Tomoyuki Kono, Kazuo Yamashiro, Ryota Tanaka, Seiji Okubo, Makoto Nakajima, Nobuhito Nakajima, Masahiro Mishina, Hiroshi Yaguchi, Hisayoshi Oka, Masahiko Suzuki, Masato Osaki, Nobuyuki Kaneko, Kazuo Kitagawa, Sadahisa Okamoto, Koichi Nomura, Mineo Yamazaki, Takehiko Nagao, Yoshitaka Murakami
    Journal of the Neurological Sciences 417 117068 - 117068 0022-510X 2020/10 [Refereed]
     
    PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.
  • Tameto Naoi, Mitsuya Morita, Koki Kosami, Takafumi Mashiko, Tomoaki Kameda, Shunich Okada, Yuka Hayashi, Tadataka Kawakami, Ryota Tanaka, Shigeru Fujimoto
    Journal of Stroke and Cerebrovascular Diseases 29 (10) 105183 - 105183 1052-3057 2020/10 [Refereed]
  • Yohsuke Sugiyama, Takaaki Tsuchiya, Ryota Tanaka, Aiko Ouchi, Arata Motoyama, Takeshi Takamoto, Natsumi Hara, Yoshitaka Yanagawa
    Journal of Clinical Neuroscience 79 30 - 32 0967-5868 2020/09 [Refereed]
  • Kosuke Matsuzono, Kohei Furuya, Takafumi Mashiko, Tadashi Ozawa, Kumiko Miura, Masayuki Suzuki, Misato Ozawa, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Journal of the Neurological Sciences 415 116924 - 116924 0022-510X 2020/08 [Refereed]
     
    OBJECTIVES: Magnetic resonance angiography (MRA), three-dimensional computed tomography angiography, and cerebral angiography may be used to assess intracranial vertebrobasilar stenosis. However, these examinations cannot be performed at patients' bedsides. Our purpose was to develop a new bedside method to assess intracranial vertebrobasilar arterial stenosis. METHODS: We developed the new method using carotid duplex ultrasonography combined with the head-up test. A total of 141 subjects admitted between June 1, 2017 and March 31, 2019 were enrolled in this study. We calculated vertebral arterial peak systolic velocities (PSVs), end-diastolic velocities (EDVs), and mean velocities (MVs) at 0°, 16°, and 30° head-up angles. Vertebrobasilar arterial stenosis was confirmed using MRA. RESULTS: We excluded 28 subjects and included data for 113 subjects and 226 vessels in the final analysis. Cervical vertebral arterial PSV, EDV, and MV gradually decreased from 0° to 30° only in stenotic intracranial vertebral arteries. Sensitivity (probability of detection) was 75.5% and specificity (true negative rate) was 79.7% when EDV at the 30° head-up angle decreased ≥19.5% from the initial 0° head-up angle. Specificity was better (86.4%; sensitivity: 69.4%) when EDV was <9.1 cm/s at the 30° head-up angle. CONCLUSION: This new method easily detects intracranial vertebrobasilar arterial stenosis.
  • Hikaru Watanabe, Reiji Koide, Misato Yokose Ozawa, Younhee Kim, Kumiko Miura, Tadashi Ozawa, Kosuke Matsuzono, Takafumi Mashiko, Ryota Tanaka, Yusuke Amano, Katsuya Nagatani, Kojiro Sato, Shigeru Fujimoto
    Otology & Neurotology 41 (7) e889 - e890 1531-7129 2020/08 [Refereed]
  • 高齢社会における脳梗塞の実態と課題
    松薗 構佑, 益子 貴史, 小澤 忠嗣, 三浦 久美子, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 亀田 知明, 藤本 茂
    日本老年医学会雑誌 (一社)日本老年医学会 57 (Suppl.) 70 - 70 0300-9173 2020/07
  • Kosuke Matsuzono, Kohei Furuya, Takeshi Igarashi, Akie Horikiri, Takamasa Murosaki, Daekwan Chi, Yuichi Toyama, Kumiko Miura, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Journal of Thrombosis and Thrombolysis 49 (4) 681 - 684 0929-5305 2020/05 [Refereed]
  • Kazuo Yamashiro, Ryota Tanaka, Naohide Kurita, Yuji Ueno, Nobukazu Miyamoto, Kenichiro Hira, Sho Nakajima, Takao Urabe, Nobutaka Hattori
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 (4) 104650 - 104650 2020/04 [Refereed][Not invited]
     
    BACKGROUND: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ischemic stroke and AF. METHODS: We retrospectively examined consecutive patients with acute ischemic stroke and AF who underwent brain gradient-echo T2*-weighted magnetic resonance imaging. The number and distribution (lobar, deep or infratentorial, and mixed) of CMBs were assessed. Kidney function was assessed according to the estimated glomerular filtration rate (eGFR), which was calculated using a modified version of the Modification of Diet in Renal Disease equation. RESULTS: Of the 357 included patients, 105 (29.4%) had CMBs. CKD (eGFR < 60 mL/min/1.73 m2) was found in 131 (36.7%) patients. Patients with CKD showed a higher prevalence of any form of CMB (41.2% versus 22.6%, P < .001), deep or infratentorial CMBs (19.9% versus 9.3%, P < .01), and mixed CMBs (14.5% versus 5.3%, P < .01) than those without CKD. After adjusting for age and other confounding factors, CKD was found to be independently associated with the presence of any form of CMB (odds ratio 1.89, P = .02) and mixed CMBs (odds ratio 3.10, P < .01). Moreover, moderate to severe CKD (eGFR < 45 mL/min/1.73 m2) was independently associated with the presence of multiple CMBs (odds ratio 2.31, P = .04). CONCLUSIONS: CMBs and CKD are common in acute ischemic stroke patients with AF, and CKD may be a risk factor for CMBs. Further longitudinal studies are needed to evaluate whether maintaining kidney function can prevent the development of CMBs.
  • Kosuke Matsuzono, Kohei Furuya, Azusa Karube, Akie Horikiri, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Journal of the neurological sciences 411 116708 - 116708 2020/01 [Refereed][Not invited]
  • Yuri Shojima, Yuji Ueno, Ryota Tanaka, Kazuo Yamashiro, Nobukazu Miyamoto, Kenichiro Hira, Naohide Kurita, Sho Nakajima, Takao Urabe, Nobutaka Hattori
    Journal of atherosclerosis and thrombosis 2020/01 [Refereed][Not invited]
     
    AIMS: The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) is related to major adverse events and death in cardiovascular diseases. The association between long-term prognosis of ischemic stroke and EPA/AA ratio has not been clarified. METHODS: Acute ischemic stroke patients who had undergone blood examinations for polyunsaturated fatty acids were enrolled. Major cardiovascular events, including recurrence of ischemic stroke, occurrence of cardiovascular and peripheral artery diseases and hemorrhagic stroke, and death, were analyzed, retrospectively. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, laboratory data including EPA/AA ratio, and treatments associated with major cardiovascular events and death. RESULTS: A total of 269 patients (mean age, 70±13 years; 179 men) were enrolled. During follow-up (mean, 2.3 ±1.0 years), 64 patients exhibited major cardiovascular events and death (annualized rate, 10.5% per person-year). Multivariate Cox analysis revealed that EPA/AA ratio (hazard ratio, 0.26; 95% confidence interval, 0.07- 0.99; p=0.048) and statin therapy (hazard ratio, 0.43; 95% confidence interval, 0.25-0.73; p=0.002) correlated inversely with major cardiovascular events and death. In the Kaplan-Meier analysis, cumulative event-free rates were significantly lower among patients with EPA/AA ratio <0.33 and patients without statin therapy (p=0.006). CONCLUSIONS: Low EPA/AA ratio at baseline and treatment without statins could predict mortality, recurrent ischemic stroke, cardiovascular and peripheral artery diseases, and hemorrhagic stroke among patients with acute ischemic stroke. The combination of baseline EPA/AA ratio and statin therapy could be critical in predicting the long-term prognosis of ischemic stroke patients.
  • Kosuke Matsuzono, Takafumi Mashiko, Tadashi Ozawa, Kumiko Miura, Masayuki Suzuki, Kohei Furuya, Misato Ozawa, Yuhei Anan, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Psychiatry and clinical neurosciences 74 (4) 279 - 280 2020/01 [Refereed][Not invited]
  • Naohide Kurita, Kazuo Yamashiro, Takuma Kuroki, Ryota Tanaka, Takao Urabe, Yuji Ueno, Nobukazu Miyamoto, Masashi Takanashi, Hideki Shimura, Toshiki Inaba, Yuichiro Yamashiro, Koji Nomoto, Satoshi Matsumoto, Takuya Takahashi, Hirokazu Tsuji, Takashi Asahara, Nobutaka Hattori
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 271678X19899577  2020/01 [Refereed][Not invited]
  • Masayuki Suzuki, Kohei Furuya, Misato Ozawa, Kumiko Miura, Tadashi Ozawa, Kosuke Matsuzono, Takafumi Mashiko, Reiji Koide, Shigeru Fujimoto, Ryota Tanaka
    Journal of Atherosclerosis and Thrombosis 1340-3478 2020 [Refereed]
     
    AIM: Aortic arch atherosclerosis, particularly complex aortic arch plaques (CAPs), is an important source of cerebral emboli. CAPs and atrial fibrillation (AF) often co-exist; however, the prevalence and risk of CAPs in acute ischemic stroke patients with AF is unclear. METHODS: In patients with acute ischemic stroke with non-valvular AF admitted to Jichi Medical University Hospital during April 2016 to September 2019, we retrospectively evaluated the presence of CAPs on transesophageal echocardiography (TEE). RESULTS: CAPs were observed in 41 (38.7 %) of 106 patients with non-valvular AF. Older age, diabetes mellitus, chronic kidney disease, low high-density lipoprotein cholesterol (HDL-C) levels, higher levels of glycohemoglobin A1c (HbA1c), higher CHADS2 and CHA2DS2-VASc scores, and intracranial or carotid artery stenosis were more frequently observed in CAPs-positive than in CAPs-negative patients. In multivariable analyses, older age (odds ratio [OR]: 1.2 per year increase; 95% confidence interval [CI]: 1.07-1.24; P<0.0001), diabetes mellitus (OR: 4.7; 95%CI: 1.27-17.35; P<0.05), and low HDL-C (OR: 0.95 per 1 mg/dl increase; 95%CI: 0.92-0.99; P <0.01) were independent risk factors for CAPs. The prevalence of CAPs was age-dependent, and there was a significantly higher risk in patients aged either 75-84 years or >84 years than in those aged <65 (OR: 7.6; 95%CI: 1.50-38.62, and OR: 32.1; 95%CI: 5.14-200.11, respectively). CONCLUSIONS: Even in patients with ischemic stroke with non-valvular AF, concomitant CAPs should be considered in older individuals and those who have diabetes or low HDL-C.
  • SLEの経過中に可逆性両側内頸動脈病変を呈し脳梗塞に至った46歳女性例
    薄井 美由, 益子 貴史, 鈴木 雅之, 松薗 構佑, 小澤 忠嗣, 三浦 久美子, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経学 (一社)日本神経学会 60 (1) 80 - 80 0009-918X 2020/01 [Refereed][Not invited]
  • Tadashi Ozawa, Ryota Tanaka, Risa Nagaoka, Yuhei Anan, Younhee Kim, Kosuke Matsuzono, Takafumi Mashiko, Reiji Koide, Haruo Shimazaki, Keisuke Ohtani, Yusuke Amano, Kensuke Kawai, Shigeru Fujimoto
    Data in brief 27 104648 - 104648 2019/12 [Refereed][Not invited]
     
    Data presented in this article are related to our article entitled "Unilateral posterior reversible encephalopathy syndrome: A case report" [1]. Cases of Posterior Reversible Encephalopathy Syndrome (PRES) involving unilateral lesions are very rare. We searched the PubMed database using keywords such as PRES, unilateral, and asymmetric and found a small number of cases to include in our review. We summarized the characteristics of these reported cases of unilateral PRES, including our case.
  • 脳梗塞急性期のLDLコレステロール値とスタチン使用の急性期再発への影響
    横瀬 美里, 三浦 久美子, 古谷 浩平, 鈴木 雅之, 阿南 悠平, 小澤 忠嗣, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経学 (一社)日本神経学会 59 (Suppl.) S250 - S250 0009-918X 2019/11
  • 脳梗塞患者における大動脈弓部プラークおよび心房細動と急性期脳卒中再発との関連
    阿南 悠平, 小澤 忠嗣, 横瀬 美里, 古谷 浩平, 鈴木 雅之, 三浦 久美子, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経学 (一社)日本神経学会 59 (Suppl.) S324 - S324 0009-918X 2019/11
  • 時間で追う脳虚血の病態と治療:(1)急性期 脳梗塞急性期におけるMAIT細胞制御と新規治療法に関する研究
    中島 翔, 田中 亮太, 山城 一雄, 千葉 麻子, 能登 大介, 志村 秀樹, 栗田 尚英, 平 健一郎, 宮元 伸和, 上野 祐司, 卜部 貴夫, 三宅 幸子, 服部 信孝
    脳循環代謝 (一社)日本脳循環代謝学会 31 (1) 59 - 59 0915-9401 2019/11
  • 心房細動を伴う虚血性脳卒中患者の脳微小出血における腎機能の影響
    山城 一雄, 田中 亮太, 栗田 尚英, 上野 祐司, 宮元 伸和, 平 健一郎, 中島 翔, 卜部 貴夫, 服部 信孝
    脳循環代謝 (一社)日本脳循環代謝学会 31 (1) 102 - 102 0915-9401 2019/11
  • 脳梗塞急性期のLDLコレステロール値とスタチン使用の急性期再発への影響
    横瀬 美里, 三浦 久美子, 古谷 浩平, 鈴木 雅之, 阿南 悠平, 小澤 忠嗣, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経学 (一社)日本神経学会 59 (Suppl.) S250 - S250 0009-918X 2019/11 [Refereed][Not invited]
  • 脳梗塞患者における大動脈弓部プラークおよび心房細動と急性期脳卒中再発との関連
    阿南 悠平, 小澤 忠嗣, 横瀬 美里, 古谷 浩平, 鈴木 雅之, 三浦 久美子, 松薗 構佑, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経学 (一社)日本神経学会 59 (Suppl.) S324 - S324 0009-918X 2019/11 [Refereed][Not invited]
  • Ueno Y, Miyamoto N, Yamashiro K, Tanaka R, Hattori N
    International journal of molecular sciences 20 (22) 5549 - 5549 2019/11 [Refereed][Not invited]
     
    Stroke is a major leading cause of death and disability worldwide. N-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid and docosahexaenoic acid have potent anti-inflammatory effects, reduce platelet aggregation, and regress atherosclerotic plaques. Since the discovery that the Greenland Eskimo population, whose diet is high in marine n-3 PUFAs, have a lower incidence of coronary heart disease than Western populations, numerous epidemiological studies to explore the associations of dietary intakes of fish and n-3 PUFAs with cardiovascular diseases, and large-scale clinical trials to identify the benefits of treatment with n-3 PUFAs have been conducted. In most of these studies the incidence and mortality of stroke were also evaluated mainly as secondary endpoints. Thus, a systematic literature review regarding the association of dietary intake of n-3 PUFAs with stroke in the epidemiological studies and the treatment effects of n-3 PUFAs in the clinical trials was conducted. Moreover, recent experimental studies were also reviewed to explore the molecular mechanisms of the neuroprotective effects of n-3 PUFAs after stroke.
  • 42歳で3回目の再発発作を認めた難治頻回部分発作重積型急性脳炎の女性例
    松薗 構佑, 古谷 浩平, 三浦 久美子, 小澤 忠嗣, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    日本老年医学会雑誌 (一社)日本老年医学会 56 (4) 575 - 575 0300-9173 2019/10
  • 虚血性脳卒中急性期に治療介入したせん妄及び不眠に関する検討
    松薗 構佑, 益子 貴史, 小澤 忠嗣, 三浦 久美子, 鈴木 雅之, 古谷 浩平, 小澤 美里, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    Dementia Japan (一社)日本認知症学会 33 (4) 559 - 559 1342-646X 2019/10
  • Tadashi Ozawa, Ryota Tanaka, Risa Nagaoka, Yuhei Anan, Younhee Kim, Kosuke Matsuzono, Takafumi Mashiko, Reiji Koide, Haruo Shimazaki, Keisuke Ohtani, Yusuke Amano, Kensuke Kawai, Shigeru Fujimoto
    Clinical neurology and neurosurgery 185 105493 - 105493 0303-8467 2019/10 [Refereed][Not invited]
  • Junya Aoki, Yasuyuki Iguchi, Takao Urabe, Hiroshi Yamagami, Kenichi Todo, Shigeru Fujimoto, Koji Idomari, Nobuyuki Kaneko, Takeshi Iwanaga, Tadashi Terasaki, Ryota Tanaka, Nobuaki Yamamoto, Akira Tsujino, Koichi Nomura, Koji Abe, Masaaki Uno, Yasushi Okada, Hideki Matsuoka, Sen Yamagata, Yasumasa Yamamoto, Toshiro Yonehara, Takeshi Inoue, Yoshiki Yagita, Kazumi Kimura
    Journal of the American Heart Association 8 (15) e012652  2019/08 
    Background The aim of the present study was to investigate the efficacy and safety of antiplatelet (aspirin plus cilostazol) dual therapy for patients with noncardioembolic stroke within 48 hours of symptom onset. Methods and Results The ADS (Acute Aspirin Plus Cilostazol Dual Therapy for Non-Cardiogenic Stroke Patients Within 48 Hours of Symptom Onset ) study is an investigator-initiated, prospective, multicenter (34 hospitals in Japan), randomized, open-label, and aspirin-controlled trial. Acute stroke patients with noncardioembolic stroke within 48 hours of onset were studied. The subjects were randomly allocated to combination therapy with aspirin 81 to 200 mg plus cilostazol 200 mg (dual group) and single therapy with aspirin 81 to 200 mg (aspirin group) for 14 days. After the 14 days, all patients took the cilostazol 200 mg for 3 months. A primary efficacy outcome was defined as any one of the following occurring (neurological deterioration, symptomatic stroke recurrence, or transient ischemic attack) within 14 days. A primary safety outcome included intracerebral hemorrhage and subarachnoid hemorrhage. Between May 2011 and June 2017, 1201 patients (796 [66%] men; median age, 69 [61-77] years) randomized 1:1 to either the dual group or the aspirin group were analyzed. Initial National Institutes of Health Stroke Scale score was 2 (1-4) in both groups (P=0.830). A primary efficacy outcome was observed in 11% in the dual group and 11% in the aspirin group (P=0.853). A primary safety outcome occurred in 2 (0.3%) in the dual group and in 1 (0.2%) in the aspirin group (P=0.624). Conclusions Dual antiplatelet therapy using cilostazol and aspirin was safe but did not reduce the rate of short-term neurological worsening. Clinical Trial Registration URL: umin.ac.jp/ctr/index/htm. Unique identifier: UMIN000004950.
  • Sugiyama M, Ueno Y, Kamo H, Edahiro Y, Miyamoto N, Yamashiro K, Tanaka R, Shimo Y, Komatsu N, Hattori N
    Journal of neurology 266 (8) 1869 - 1878 0340-5354 2019/08 [Refereed][Not invited]
     
    BACKGROUND: JAK2 V617F mutation increases the risk of thrombosis, and both ischemic and hemorrhagic strokes can occur in essential thrombocythemia (ET). The mechanisms underlying ischemic stroke in ET are diverse, and hemorrhagic stroke has rarely been reported in ET. METHODS: Among 627 stroke patients, those identified as having ET were investigated retrospectively. A comprehensive systemic literature search of the PubMed database was also conducted. RESULTS: Two cases were extracted with the diagnosis of ET who developed SAH and then ischemic stroke. In Case 1, a 47-year-old woman developed SAH in the left high convexity. Eleven hours later, acute cerebellar infarction suddenly developed due to right vertebral artery dissection. In Case 2, a 70-year-old woman developed SAH in the right high convexity. Magnetic resonance angiography showed multifocal stenotic changes in intracranial arteries. Three days later, she developed acute brain infarcts in the right middle cerebral artery territory. Eight weeks later, multifocal stenotic lesions improved. The literature review revealed 5 patients with hemorrhagic stroke and 40 patients with ischemic stroke associated with ET. Age at onset varied, female gender predominated, and the frequency of JAK2 V617F mutation was high. Atherosclerotic vascular risk factors were more common in ischemic stroke, but not in hemorrhagic stroke. CONCLUSIONS: The current study describes rare cases of SAH accompanied by ischemic stroke secondary to ET along with a review of the current literature, implying specific mechanisms for cerebral artery disorders associated with JAK2 V617F mutation.
  • パーキンソン病における脳微小出血と血圧調節障害
    山城 一雄, 田中 亮太, 下 泰司, 大山 彦光, 小川 崇, 梅村 淳, 服部 信孝
    パーキンソン病・運動障害疾患コングレスプログラム・抄録集 Movement Disorder Society of Japan (MDSJ) 13回 107 - 107 2019/07 [Refereed][Not invited]
  • パーキンソン病におけるneurogenic orthostatic hypotensionと認知機能低下の関係について
    田中 亮太, 山城 一雄, 小川 崇, 大山 彦光, 西岡 健弥, 梅村 淳, 下 泰司, 服部 信孝
    パーキンソン病・運動障害疾患コングレスプログラム・抄録集 Movement Disorder Society of Japan (MDSJ) 13回 108 - 108 2019/07 [Refereed][Not invited]
  • 破傷風治療中にタコツボ心筋症様の壁運動異常を合併した75歳女性例
    堀切 映江, 松薗 構佑, 古谷 浩平, 小澤 忠嗣, 益子 貴史, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経学 (一社)日本神経学会 59 (7) 469 - 469 0009-918X 2019/07 [Refereed][Not invited]
  • Miyu Usui, Takafumi Mashiko, Masuko Tsuda, Masayuki Suzuki, Kosuke Matsuzono, Tadashi Ozawa, Yonhee Kim, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (7) e98-e99 - e99 1052-3057 2019/07 [Refereed][Not invited]
     
    Isolated vertigo is an important symptom of posterior circulation stroke. It has been reported that 11.3% of patients with isolated vertigo have a stroke and that most lesions are located in the cerebellum, particularly in the posterior inferior cerebellar artery. We report the case of a 63-year-old man with multiple atherosclerotic risk factors and atrial fibrillation who showed repeated episodes of isolated vertigo. His repeated vertigo was short-lasting and was often triggered by body position, mimicking benign paroxysmal positional vertigo. Cranial computed tomography on the third hospital day showed left cerebellar infarction within the territory of the posterior inferior cerebellar artery. The vertigo was ameliorated on the fifth hospital day and warfarin was prescribed for secondary prevention. Clinicians should pay special attention to cases in which a patient presents isolated vertigo, even if it shows transient recurrence or is triggered by a positional change, especially in patients with multiple cerebrovascular risk factors.
  • Kamo H, Ueno Y, Sugiyama M, Miyamoto N, Yamashiro K, Tanaka R, Yokoyama K, Hattori N
    Journal of neuroimmunology 330 19 - 22 0165-5728 2019/05 [Refereed][Not invited]
  • Magami S, Miyamoto N, Ueno Y, Hira K, Tanaka R, Yamashiro K, Oishi H, Arai H, Urabe T, Hattori N
    Neuroscience 406 167 - 175 0306-4522 2019/05 [Refereed][Not invited]
  • 片側優位の可逆性後頭葉白質脳症(PRES)の1例
    長岡 理沙, 阿南 悠平, 小澤 忠嗣, 三浦 久美子, 松薗 構佑, 益子 貴史, 小出 玲爾, 田中 亮太, 藤本 茂
    日本内科学会関東地方会 日本内科学会-関東地方会 649回 68 - 68 2019/03 [Refereed][Not invited]
  • Kosuke Matsuzono, Kohei Furuya, Akie Horikiri, Kumiko Miura, Younhee Kim, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Journal of the neurological sciences 397 31 - 33 0022-510X 2019/02 [Refereed][Not invited]
  • Kurita Naohide, Yamashiro Kazuo, Kuroki Takuma, Tanaka Ryota, Ueno Yuji, Urabe Takao, Yamashiro Yuichiro, Hattori Nobutaka
    STROKE 50 0039-2499 2019/02 [Refereed][Not invited]
  • Kamo H, Ueno Y, Sugiyama M, Miyamoto N, Yamashiro K, Tanaka R, Hattori N
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (2) 389 - 391 1052-3057 2019/02 [Refereed][Not invited]
  • 急性脳血管症候群における悪性腫瘍合併症例の検討
    中島 翔, 山城 一雄, 上野 祐司, 田中 亮太, 宮元 伸和, 平 健一郎, 栗田 尚英, 服部 信孝
    臨床神経学 (一社)日本神経学会 58 (Suppl.) S281 - S281 0009-918X 2018/12
  • Capsular Warning Syndromeを呈した2例の臨床的特徴の検討
    大谷 花, 宮元 伸和, 加茂 晃, 田中 亮太, 服部 信孝
    臨床神経学 (一社)日本神経学会 58 (Suppl.) S458 - S458 0009-918X 2018/12
  • 脳虚血におけるインクレチン(GLP-1)の役割と脳保護作用
    田中 亮太, 黒木 卓馬, 寺本 紳一郎, 山城 一雄, 宮元 伸和, 上野 祐司, 新井 一, 服部 信孝, 卜部 貴夫
    臨床神経学 (一社)日本神経学会 58 (Suppl.) S92 - S92 0009-918X 2018/12 [Refereed][Not invited]
  • 心停止と呼吸停止を主徴とする孤発性成人発症型ネマリンミオパチーの1例
    八木澤 伯耶, 松薗 構佑, 古谷 浩平, 金 蓮姫, 小澤 忠嗣, 益子 貴史, 小出 玲爾, 田中 亮太, 西野 一三, 藤本 茂
    日本内科学会関東地方会 日本内科学会-関東地方会 646回 47 - 47 2018/11 [Refereed][Not invited]
  • 鈴木 雅之, 桧垣 鮎帆, 難波 克成, 松薗 構佑, 古谷 浩平, 五十嵐 丈之, 金 蓮姫, 小澤 忠嗣, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    神経治療学 (一社)日本神経治療学会 35 (6) S218 - S218 0916-8443 2018/11 [Refereed][Not invited]
  • Kamo H, Miyamoto N, Otani H, Kurita N, Nakajima S, Ueno Y, Yamashiro K, Tanaka R, Hattori N
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 27 (11) 3095 - 3099 1052-3057 2018/11 [Refereed][Not invited]
  • Kosuke Matsuzono, Masayuki Suzuki, Kohei Furuya, Dan Tomomasa, Younhee Kim, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto
    Journal of the neurological sciences 393 113 - 115 0022-510X 2018/10 [Refereed][Not invited]
  • Kensuke Daida, Ryota Tanaka, Kazuo Yamashiro, Takashi Ogawa, Genko Oyama, Kenya Nishioka, Yasushi Shimo, Atsushi Umemura, Nobutaka Hattori
    Journal of the neurological sciences 393 39 - 44 0022-510X 2018/10 [Refereed][Not invited]
     
    BACKGROUND: Cerebral microbleeds (CMBs) are often observed in Parkinson's disease (PD); however, their association with cognitive decline has been unclear. We performed a retrospective analysis of 124 cases of clinically diagnosed PD to determine the association between the presence of CMBs and cognitive decline. RESULTS: Of the 124 participants, 21 (16.9%) was diagnosed as PDD in this cohort. CMBs were observed significantly more frequently in the PDD than in the PD (47.6% vs 7.8%, P < .001). The presence of both deep/infratentorial (40% vs 14.9%, P < .05) and strictly lobar (75% vs 12.9%, P < .001) CMBs were associated with PDD. The values of cognitive scales such as Mini-Mental State Examination and the Hasegawa Dementia Scale-revised, were also significantly lower in the presence of each type of CMB. A multivariable logistic regression analysis showed the presence of strictly lobar CMBs as well as a male gender, orthostatic hypotension, periventricular hyperintensity on magnetic resonance imaging were significantly associated with PDD in this cohort. CONCLUSIONS: This study showed the presence of CMBs, especially strictly lobar type, was strongly associated with PDD. We suspect that the burden of small vessel disease and cerebral amyloid angiopathy may be related to the development of cognitive decline in PD, and a prospective study enrolling more cases is warranted.
  • パーキンソン病におけるneurogenic orthostatic hypotensionと認知機能低下の関係について
    田中 亮太, 山城 一雄, 小川 崇, 大山 彦光, 西岡 健弥, 梅村 淳, 下 泰司, 服部 信孝
    脳循環代謝 (一社)日本脳循環代謝学会 30 (1) 132 - 132 0915-9401 2018/10 [Refereed][Not invited]
  • 松薗 構佑, 古谷 浩平, 五十嵐 丈之, 八木澤 伯耶, 金 蓮姫, 小澤 忠嗣, 益子 貴史, 嶋崎 晴雄, 小出 玲爾, 田中 亮太, 藤本 茂
    臨床神経生理学 (一社)日本臨床神経生理学会 46 (5) 408 - 408 1345-7101 2018/10 [Refereed][Not invited]
  • Yamashiro K, Kurita N, Tanaka R, Ueno Y, Miyamoto N, Hira K, Nakajima S, Urabe T, Hattori N
    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 28 (6) 1773 - 1780 1052-3057 2018/10 [Refereed][Not invited]
  • Hira K, Ueno Y, Tanaka R, Miyamoto N, Yamashiro K, Inaba T, Urabe T, Okano H, Hattori N
    Stroke 49 (10) 2483 - 2494 0039-2499 2018/10 [Refereed][Not invited]
  • Kono Y, Nishioka K, Li Y, Komatuzaki Y, Ito Y, Yoshino H, Tanaka R, Iguchi Y, Hattori N
    Clinical neurology and neurosurgery 172 174 - 176 0303-8467 2018/09 [Refereed][Not invited]
     
    The term cerebral small vessel disease (SVD) refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. SVD occurs in approximately 5% of patients. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL),a recessive form of heritable SVD, is caused by a mutation in the high temperature requirement A serine peptidase (HTRA1) gene. Recently, heterozygous mutations in HTRA1 were identified in patients with symptomatic SVD. We identified two families harboring HTRA1 (p.S284 N and p.V216 M) heterozygous mutations with symptoms that mimicked common symptoms of CARASIL.
  • Fumi Nakano, Yuji Ueno, Akimitsu Suda, Masashi Takanashi, Atsushi Yamashita, Yoshiyuki Abe, Takayuki Kon, Nobukazu Miyamoto, Kazuo Yamashiro, Ryota Tanaka, Toshio Naito, Takashi Yao, Naoto Tamura, Nobutaka Hattori
    Journal of the Neurological Sciences 391 22 - 24 1878-5883 2018/08 [Refereed][Not invited]
  • Ueno Y, Tanaka R, Yamashiro K, Miyamoto N, Hira K, Kurita N, Sakurai M, Urabe T, Shimada K, Miyazaki T, Daida H, Hattori N
    Journal of atherosclerosis and thrombosis 25 (7) 593 - 605 1340-3478 2018/07 [Refereed][Not invited]
  • Sakiko Miyazaki, Katsumi Miyauchi, Hidemori Hayashi, Ryota Tanaka, Shuko Nojiri, Tadashi Miyazaki, Masataka Sumiyoshi, Satoru Suwa, Yuji Nakazato, Takao Urabe, Nobutaka Hattori, Hiroyuki Daida
    Journal of Cardiology 71 (6) 590 - 596 1876-4738 2018/06 [Refereed][Not invited]
     
    Background: The management of atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs), but data on their clinical effectiveness and safety outside clinical trial settings are limited. Method: The RAFFINE registry is an observational, multicenter, prospective registry of Japanese patients with AF, designed to follow clinical events over 3 years. Patient enrollment was conducted from 2013 to 2015 at university hospitals, general hospitals, and private clinics to ensure inclusion of a broad spectrum of representative AF patients. The primary outcome events in this study will be ischemic stroke, systemic embolism, and major bleeding. Result: We enrolled 3901 ambulatory patients with AF from 4 university hospitals and 50 general hospitals/clinics in Japan. The mean patient age was 72.6 years and 68.5% were male. The type of AF was paroxysmal in 37.8%, persistent in 9.3%, and permanent in 51.7%. Major coexisting diseases were hypertension (72.7%), diabetes mellitus (30.3%), congestive heart failure (23.8%), history of ischemic stroke or transient ischemic attack (15.1%), and coronary artery disease (13.7%). Of the entire cohort, 44.6% were treated with warfarin and 43.0% were treated with DOACs. The prescription of DOACs exceeded that of warfarin in the general hospitals and clinics. Risk scores such as CHADS2 score, CHA2DS2-VASc score, and HAS-BLED score were higher in patients at university hospitals than in patients at general hospitals or clinics. Conclusion: The RAFFINE registry at baseline described the current status of anticoagulation therapy in Japan and long-term follow-up data will identify how outcomes vary between stratified groups in patients with AF in the DOAC era (UMIN Clinical Trials Registry UMIN000009617).
  • Yoshiaki Shimada, Hideki Shimura, Ryota Tanaka, Kazuo Yamashiro, Masato Koike, Yasuo Uchiyama, Takao Urabe, Nobutaka Hattori
    PLoS ONE 13 (5) e0198039  1932-6203 2018/05 [Refereed][Not invited]
     
    Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.
  • Kazuo Yamashiro, Ryota Tanaka, Yasushi Shimo, Genko Oyama, Takashi Ogawa, Atsushi Umemura, Nobutaka Hattori
    eNeurologicalSci 10 5 - 11 2018/03 [Refereed][Not invited]
     
    Blood pressure abnormalities are frequently observed in patients with Parkinson's disease (PD), and are associated with cerebrovascular diseases such as white matter hyperintensities and carotid atherosclerosis. We assessed the relationship between blood pressure abnormalities and cerebral microbleeds (CMBs), a marker of cerebral small vessel disease, in 128 patients with PD. We examined supine and orthostatic blood pressures and used 24-hour ambulatory blood pressure monitoring to assess the presence or absence of orthostatic hypotension (OH), supine hypertension (SH), nocturnal hypertension (NH), and loss of nocturnal blood pressure dips (non-dipping). CMBs were found in 13 (10.2%) patients, and the median number of CMBs was 1 (range: 1 to 10). Six of these patients had deep or infratentorial CMBs, six had strictly lobar CMBs, and one had mixed CMBs. Linear regression analysis indicated that presence of both OH and SH was independently associated with greater numbers of CMBs in deep or infratentorial regions, independent of age, sex, cardiovascular risk factors, and white matter hyperintensities. NH and non-dipping were not associated with CMBs in deep or infratentorial regions, and there was no association between blood pressure and CMBs in lobar regions. Our results suggest that the presence of both OH and SH may be related to deep or infratentorial CMBs in patients with PD.
  • Ryota Tanaka, Yasushi Shimo, Kazuo Yamashiro, Takashi Ogawa, Kenya Nishioka, Genko Oyama, Atsushi Umemura, Nobutaka Hattori
    Parkinsonism & related disorders 46 24 - 29 1353-8020 2018/01 [Refereed][Not invited]
     
    BACKGROUND: Circadian blood pressure alterations are frequently observed in Parkinson's disease, but the association between these changes and dementia in the condition remains unclear. Here, we assess the relationship between abnormal nocturnal blood pressure profiles and dementia in Parkinson's disease. METHODS: We enrolled 137 patients with Parkinson's disease, who underwent 24 h ambulatory blood pressure monitoring, following cognitive and clinical assessment. RESULTS: Twenty-seven patients (19.7%) were diagnosed with dementia in this cohort. We observed significant associations of dementia with age, male gender, Hoehn-Yahr (H-Y) stage, diabetes mellitus, history of stroke, presence of cerebrovascular lesions on MRI, and orthostatic hypotension. Univariate logistic regression analysis showed that among the patterns of nocturnal blood pressure profiles, the riser pattern was significantly associated with dementia (OR 11.6, 95%CI: 2.14-215.0, P < 0.01), and this trend was observed after adjusting for all confounding factors except orthostatic hypotension (OR 19.2, 95%CI: 1.12-1960.3, P = 0.04). However, coexistence of a riser pattern and orthostatic hypotension was related to a higher prevalence of dementia (45.2%) than was a riser pattern alone (9.5%). Furthermore, coexistence of a riser pattern and orthostatic hypotension was significantly more associated with dementia than was a riser pattern alone, even after adjusting for confounders (OR 1625.1, 95%CI: 21.9-1343909.5, P < 0.01). CONCLUSIONS: Our results suggest a relationship between a riser pattern coexisting with orthostatic hypotension and dementia in Parkinson's disease. Further prospective studies are warranted to investigate whether abnormal nocturnal blood pressure profiles predict dementia in Parkinson's disease.
  • Kensuke Daida, Nobukazu Miyamoto, Hiromi Takagi, Yuji Ueno, Kazuo Yamashiro, Ryota Tanaka, Nobutaka Hattori
    Journal of Stroke and Cerebrovascular Diseases 27 (9) e219 - e220 1532-8511 2018 [Refereed][Not invited]
     
    A 75-year-old woman presented with consciousness disturbance accompanied by hematemesis. Brain imaging revealed ischemia in the bilateral caudate nuclei and right cerebral watershed area due to stenosis of the right anterior cerebral artery (ACA) and bilateral internal carotid arteries (ICA), and hypoperfusion in the right caudate nucleus. The patient's only symptom was abulia, which gradually resolved. Further brain scans showed that the ICA stenosis had improved, although the right ACA stenosis persisted. This was a rare case of bilateral caudate nucleus infarctions with a hemodynamic etiology.
  • Takashi Ogawa, Yuji Ueno, Hikaru Kamo, Nobukazu Miyamoto, Kazuo Yamashiro, Ryota Tanaka, Yasushi Shimo, Nobutaka Hattori
    Journal of Stroke and Cerebrovascular Diseases 27 (9) e221 - e223 1532-8511 2018 [Refereed][Not invited]
     
    Conjugate eye deviation (CED) is defined as a sustained shift in horizontal gaze toward 1 side, together with gaze failure to the other side, caused by lesions in the brainstem, basal ganglia, or cortical frontal eye fields. To date, very few reports have described CED in patients with medullary infarction. A 76-year-old woman presented with sudden onset of vertigo and right hemiparesis, accompanied by CED to the right with gaze palsy to the left. Her brain magnetic resonance imaging showed left upper medial medullary infarction involving the left nucleus prepositus hypoglossi (NPH) and adjacent to the left inferior olivary nucleus (ION). After treatments with 200 mg of aspirin and 60 mg of edaravone daily, symptoms gradually improved. The NPH and ION constitute NPH-ION-floccus-vestibular nucleus loop and contribute to the inhibitory mechanisms for horizontal eye movements. In addition, NPH projects excitatory neurons to the contralateral vestibular nucleus. In our case, disorders of the NPH and ION might have dysregulated inhibitory and excitatory projections, and thereby cause CED to the right with gaze palsy to the left. This represents a rare case showing CED to the contralesional side in upper medial medullary infarction.
  • Nobukazu Miyamoto, Ryota Tanaka, Yuji Ueno, Masao Watanabe, Naohide Kurita, Kenichiro Hira, Yoshiaki Shimada, Takuma Kuroki, Kazuo Yamashiro, Takao Urabe, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 (12) 2834 - 2839 1052-3057 2017/12 [Refereed][Not invited]
     
    Background: Early neurological worsening is associated with increased mortality and long-term functional disability. We developed the WORSEN score for predicting whether patients with stroke will deteriorate during the week after stroke onset and investigated its usefulness. Patients and Methods: We retrospectively investigated the cases of 478 patients who were admitted to Juntendo University Hospital between April 2007 and March 2009. Neurological deterioration was defined as a worsening of 4 points or higher on the National Institute of Health Stroke Scale score within 1 week of admission. Based on a previous study, we developed the WORSEN score, which was derived from the following factors: wrong (poor) blood sugar control (W), old myocardial infarction (O), radiological findings (R), infarct size (S), elevated low-density lipoprotein cholesterol (E), and neurological findings (N). Next, we investigated the utility of this scoring system in 456 other patients who were admitted to Juntendo University Hospital and Juntendo Urayasu Hospital between October 2013 and December 2014. Results: First, we checked the utility of the WORSEN score for detecting worsening in cases of stroke. In the first patient group, deterioration was noted in 32.5% of the patients with scores higher than 3 points (sensitivity:.704 and specificity:.744). For checking reproductivity on using the second group, deterioration was detected in 36.1% of the patients with WORSEN scores higher than 3 points (sensitivity:.740 and specificity:.835). Conclusions: Careful attention should be paid to patients with acute stroke with high WORSEN scores. The WORSEN score might become a valuable tool for detecting the neurological deterioration of ischemic stroke.
  • Hideki Shimura, Ryota Tanaka, Yoshiaki Shimada, Kazuo Yamashiro, Nobutaka Hattori, Takao Urabe
    BMC BIOCHEMISTRY 18 (1) 14  1471-2091 2017/11 [Refereed][Not invited]
     
    Background: Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, beta-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. Results: We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly- Gly- His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Conclusion: Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.
  • Daisuke Taniguchi, Yutaka Oji, Yuji Ueno, Shunki Hirayama, Mariko Fukui, Nobukazu Miyamoto, Kazuo Yamashiro, Ryota Tanaka, Kenji Suzuki, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 (10) E197 - E198 1052-3057 2017/10 [Refereed][Not invited]
     
    We report a case of limb-shaking transient ischemic attack (TIA) caused by a dissection of the middle cerebral artery (MCA) following lung surgery under general anesthesia. An 81-year-old male patient who underwent lobectomy for lung cancer suddenly developed transient shaking movements of the neck and the left upper distal limb on postoperative day 1. On the basis of the double-barrel appearance of the right M1 segment of the MCA, a diagnosis of MCA dissection was made. Physicians should be aware that limb-shaking TIA is sometimes caused by MCA dissection and could be precipitated by any condition, including lung surgery under general anesthesia.
  • Kenya Nishioka, Toyoyoshi Uchida, Chie Usui, Ryota Tanaka, Takashi Matsushima, Yoshifuji Matsumoto, Ikuro Nakamura, Kusuki Nishioka, Nobutaka Hattori
    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES 20 (6) 685 - 690 1756-1841 2017/06 [Refereed][Not invited]
     
    Aim: Fibromyalgia syndrome (FMS) is defined as chronic widespread pain that cannot be accounted for by any other medical disorder. Our aim was to explore the prevalence of thyroid autoimmunity in patients with FMS. Methods: For determining thyroid function in 207 FMS patients, we tested for the titers of free tri-iodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) and anti-TSH receptor antibody (TRAb). Results: Twenty-five patients who had either subclinical hyper-or hypothyroidism, or overt hypothyroidism were excluded. Sixty-nine FMS patients with autoimmune thyroid diseases (AITD) (37.9%, 69/182) were identified. The prevalence of positivity for TRAb, TgAb and TPOAb was 20.3% (n = 37), 16.5% (n = 30) and 13.2% (n = 24), respectively. Compared to control populations in previous studies, the prevalence of TRAb positivity was high, and titers of TRAb were low (1.0-1.5 IU/L). The prevalence of TPOAb and TgAb positivity was not significantly higher than that reported in FMS patients in previous studies. Clinical symptom profiles were identical for FMS patients with and without AITD. Conclusion: We found a high prevalence of AITD among 207 patients with clinically defined FMS, with TRAb being especially prominent among these patients. Further study is needed to evaluate changes in thyroid function among FMS patients with AITD.
  • Rintaro Fukuda, Nobukazu Miyamoto, Arisa Hayashida, Yuji Ueno, Kazuo Yamashiro, Ryota Tanaka, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 (6) E119 - E121 1052-3057 2017/06 [Refereed][Not invited]
     
    We report a case of bilateral hearing loss caused by decreased vascular flow in the anterior inferior cerebellar artery (AICA) territory. A 74-year-old man who experienced right hearing loss 5 months ago presented with bilateral deafness and right cerebellar ataxia; however, no ischemic lesion was detected in the bilateral AICA area. After stroke treatment, hearing loss was improved. One month later, we obtained blood flow improvement in the left AICA territory on single-photon-emission computed tomography and vertebral artery stenosis on magnetic resonance angiography. Therefore, clinicians should recognize that bilateral hearing loss may be related to stroke in the vertebrobasilar artery area.
  • Kazuo Yamashiro, Ryota Tanaka, Takao Urabe, Yuji Ueno, Yuichiro Yamashiro, Koji Nomoto, Takuya Takahashi, Hirokazu Tsuji, Takashi Asahara, Nobutaka Hattori
    PLOS ONE 12 (4) 1932-6203 2017/04 [Refereed][Not invited]
  • Takashi Matsushima, Silvio Conedera, Ryota Tanaka, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Aya Ikeda, Yuka Hosaka, Ayame Okuzumi, Yoshiaki Shimada, Kazuo Yamashiro, Yumiko Motoi, Kenya Nishioka, Nobutaka Hattori
    NEUROBIOLOGY OF AGING 50 169.e7 - 169.e14 0197-4580 2017/02 [Refereed][Not invited]
     
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by cerebral infarction related to mutations in the notch homolog protein 3 (NOTCH3). We enrolled 10 patients whose brain magnetic resonance imaging (MRI) fluid-attenuated inversion recovery images showed hyperintensities (HIs) in the deep white matter and the external capsule. We then investigated the mutations in NOTCH3 using direct sequencing within the region of intron-exon boundaries in exons 2-24 of NOTCH3. Eight patients harboring NOTCH3 mutations (8 of 10) were identified, including a novel mutation, p.C162Y, and 3 cases with a sporadic form. Seven patients with cysteine replacement showed HI in the anterior part of the temporal lobes (ATLs), whereas these changes were not detected in 1 patient without cysteine replacement, p.R75P. Reviewing previous reports, we conclude that the patients can clearly be divided in 2 groups: those with cysteine replacement who showed HI in the ATL and those without cysteine replacement who showed no HI in the ATL. Our findings expand the understanding of genotypeephenotype correlations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. (C) 2016 Elsevier Inc. All rights reserved.
  • Kazuo Yamashiro, Ryota Tanaka, Takao Urabe, Yuji Ueno, Yuichiro Yamashiro, Koji Nomoto, Takuya Takahashi, Hirokazu Tsuji, Takashi Asahara, Nobutaka Hattori
    PLOS ONE 12 (2) e0171521  1932-6203 2017/02 [Refereed][Not invited]
     
    The role of metabolic diseases in ischemic stroke has become a primary concern in both research and clinical practice. Increasing evidence suggests that dysbiosis is associated with metabolic diseases. The aim of this study was to investigate whether the gut microbiota, as well as concentrations of organic acids, the major products of dietary fiber fermentation by the gut microbiota, are altered in patients with ischemic stroke, and to examine the association between these changes and host metabolism and inflammation. We analyzed the composition of the fecal gut microbiota and the concentrations of fecal organic acids in 41 ischemic stroke patients and 40 control subjects via 16S and 23S rRNA-targeted quantitative reverse transcription (qRT)-PCR and high-performance liquid chromatography analyses, respectively. Multivariable linear regression analysis was subsequently performed to evaluate the relationships between ischemic stroke and bacterial counts and organic acid concentrations. Correlations between bioclinical markers and bacterial counts and organic acids concentrations were also evaluated. Although only the bacterial counts of Lactobacillus ruminis were significantly higher in stroke patients compared to controls, multivariable analysis showed that ischemic stroke was independently associated with increased bacterial counts of Atopobium cluster and Lactobacillus ruminis, and decreased numbers of Lactobacillus sakei subgroup, independent of age, hypertension, and type 2 diabetes. Changes in the prevalence of Lactobacillus ruminis were positively correlated with serum interleukin-6 levels. In addition, ischemic stroke was associated with decreased and increased concentrations of acetic acid and valeric acid, respectively. Meanwhile, changes in acetic acid concentrations were negatively correlated with the levels of glycated hemoglobin and low density lipoprotein cholesterol, whereas changes in valeric acid concentrations were positively correlated with the level of high sensitivity C-reactive protein and with white blood cell counts. Together, our findings suggest that gut dysbiosis in patients with ischemic stroke is associated with host metabolism and inflammation.
  • Kenya Nishioka, Motoki Fujimaki, Kazuaki Kanai, Yuta Ishiguro, Tomoko Nakazato, Ryota Tanaka, Kazumasa Yokoyama, Nobutaka Hattori
    INTERNAL MEDICINE 56 (1) 101 - 104 0918-2918 2017 [Refereed][Not invited]
     
    Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patient's symptoms drastically improved over the course of one year. The patient's neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome.
  • Kensuke Daida, Kenya Nishioka, Yuanzhe Li, Sho Nakajima, Ryota Tanaka, Nobutaka Hattori
    INTERNAL MEDICINE 56 (18) 2507 - 2512 0918-2918 2017 [Refereed][Not invited]
     
    We herein report the case of a 47-year-old female with the colony-stimulating factor 1 receptor (CSF1R) mutation p. G589R, which is related to hereditary leukoencephalopathy with axonal spheroid (HDLS). The patient presented with an early-onset cognitive decline and progressive aphasia. Brain magnetic resonance imaging revealed HDLS-related alterations. In addition, brain computed tomography revealed interspersed spotty calcifications in the frontal and parietal subcortical white matter, while a characteristic "stepping stone" appearance was observed in the frontal pericallosal regions. Our findings emphasize the importance of calcification appearances in establishing an HDLS diagnosis and in screening for CSF1R mutations.
  • 起立性低血圧と夜間血圧上昇の存在とパーキンソン病における認知症合併のリスク
    小川 崇, 田中 亮太, 山城 一雄, 大山 彦光, 下 泰司, 梅村 淳, 服部 信孝
    臨床神経学 (一社)日本神経学会 56 (Suppl.) S409 - S409 0009-918X 2016/12 [Refereed][Not invited]
  • Kenya Nishioka, Yasunobu Hoshino, Kauzuaki Kanai, Shinichi Ueno, Tomoko Nakazato, Masashi Takanashi, Ryota Tanaka, Kazumasa Yokoyama, Kimiyoshi Arimura, Satoshi Kuwabara, Nobutaka Hattori
    Clinical and Experimental Neuroimmunology 7 (4) 369 - 372 1759-1961 2016/11 [Refereed][Not invited]
     
    The anti-paraneoplastic (Ma2/Ta) antibody is related to testicular, lung and ovarian cancers, and might cause paraneoplastic neurological disorders. We present a 25-year-old woman presenting various neurological symptoms of myokymia, chronic widespread pain, tremor, excessive daytime sleepiness, impaired eye of movements, and seizures and autonomic symptoms related to anti-Ma2/Ta antibodies. Needle electromyography showed spontaneous multiplet and myokymic discharges in the left vestus lateralis. Thus, we diagnosed her as Morvan syndrome. After initiation of steroids, plasma exchange and dantrolene, her symptoms partially improved with decreasing intensity of the antigen of anti-Ma2/Ta antibodies, from moderate strong to borderline. The present case expands the clinical spectrum of anti-Ma2/Ta antibodies-related disorders to include the existence of neuroimmune activation and Morvan syndrome.
  • パーキンソン病における24時間血圧測定と認知症合併に関する研究
    田中 亮太, 山城 一雄, 小川 崇, 西岡 健弥, 大山 彦光, 下 泰司, 梅村 淳, 服部 信孝
    脳循環代謝 (一社)日本脳循環代謝学会 28 (1) 200 - 200 0915-9401 2016/11 [Refereed][Not invited]
  • Haruka Takeshige, Yuji Ueno, Koji Kamagata, Fuyuko Sasaki, Kazuo Yamashiro, Ryota Tanaka, Shigeki Aoki, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 25 (11) 2575 - 2579 1052-3057 2016/11 [Refereed][Not invited]
     
    Background: Midbrain infarction shows diverse patterns of ophthalmoplegia; however, the association of ophthalmoplegia with a precise microanatomy has not been fully studied. Here, we report a patient with characteristic ophthalmoplegia and explore the associated pathologic fiber tracts using diffusion-tensor imaging (DTI). Methods: A 21-year-old woman with an 11-year history of mixed connective tissue disease (MCTD) abruptly developed bilateral internuclear ophthalmoplegia (INO) with upward gaze and convergence palsies. Plasma levels of U1-ribonucleoprotein, double-stranded-DNA antibodies, and cerebrospinal fluid interleukin-6 were all increased. Diffusion-weighted imaging showed an acute ischemic lesion in the periaqueductal gray matter. Results: DTI exhibited a reduction of fractional anisotropy and an increase of apparent diffusion coefficient values in the tract involving the left medial longitudinal fasciculus (MLF) in the midbrain to the posterior commissure (PC) when compared to the right-sided tract in the midbrain and to the bilateral MLF in the upper pontine levels. Antiplatelet and immunosuppressant therapies dramatically improved her symptoms. Conclusions: We believe this is the first case of a patient with juvenile MCTD presenting with bilateral INO with an upward gaze and convergence palsies caused by midbrain infarction associated with vasculitis. It is suggested that DTI might identify the pathologic fiber tract connecting the left MLF in the midbrain to the PC.
  • Yuji Ueno, Kazuo Yamashiro, Ryota Tanaka, Takuma Kuroki, Kenichiro Hira, Naohide Kurita, Takao Urabe, Nobutaka Hattori
    STROKE 47 (11) 2714 - 2721 0039-2499 2016/11 [Refereed][Not invited]
     
    Background and Purpose Underlying embolic causes diagnosed by transesophageal echocardiography could be implicated in mechanisms of embolic stroke of undetermined source. We aimed to explore factors, including underlying embolic causes, related to recurrent vascular events in embolic stroke of undetermined source. Methods Patients who fulfilled the diagnostic criteria for embolic stroke of undetermined source and whose potential embolic sources were examined by transesophageal echocardiography were included. Recurrent vascular events, including ischemic stroke, cardiovascular and peripheral artery diseases, and vascular death, were retrospectively analyzed. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, embolic causes on transesophageal echocardiography, and the Calcification in the Aortic Arch, Age, Multiple Infarction score (CAM), based on the degree of aortic arch calcification on chest radiograph (0-3 points), age (70 years; 1 point), and multiple infarctions on magnetic resonance imaging (multiple infarcts in 1, 2, or 3 territories of large intracranial arteries, 1, 2, or 3 points) associated with recurrent vascular events. Results A total of 177 patients (age, 64.114.2 years; 127 men) were enrolled. Thirty-one patients had recurrent vascular events (follow-up, 3.5 +/- 2.7 years; annualized rate, 5.0% per person-year). Among embolic causes on transesophageal echocardiography, incidence of recurrent vascular events was high in patients with large aortic arch plaques (7.5% per person-year). Diabetes mellitus (hazard ratio, 2.56; 95% confidence interval, 1.23-5.32; P=0.012) and CAM score grade (hazard ratio, 2.29; 95% confidence interval, 1.11-4.72; P=0.026) predicted recurrent vascular events. Conclusions History of diabetes mellitus and the CAM score could be novel risk factors for recurrent vascular events in embolic stroke of undetermined source.
  • Yasunobu Hoshino, Kenya Nishioka, Kauzuaki Kanai, Ryota Tanaka, Masanori Nagaoka, Satoshi Kuwabara, Nobutaka Hattori
    JOURNAL OF THE NEUROLOGICAL SCIENCES 367 361 - 362 0022-510X 2016/08 [Refereed][Not invited]
  • Takuma Kuroki, Ryota Tanaka, Yoshiaki Shimada, Kazuo Yamashiro, Yuji Ueno, Hideki Shimura, Takao Urabe, Nobutaka Hattori
    STROKE 47 (5) 1328 - 1335 0039-2499 2016/05 [Refereed][Not invited]
     
    Background and Purpose Admission hyperglycemia is an independent risk factor for poor outcome of ischemic stroke. Amelioration of hyperglycemia by insulin has not been shown to improve the poststroke outcome. Glucagon-like peptide 1 receptor agonists, which modulate glucose levels by stimulating insulin secretion, have been shown to exert cytoprotective effects by inhibiting inflammation and oxidative stress. This study aimed to evaluate whether the glucagon-like peptide 1 receptor agonist exendin-4 could reduce glucose levels and exert protective effects after acute focal ischemia in hyperglycemic mice. Methods Hyperglycemia was induced by intraperitoneal injection of dextrose 15 minutes before transient middle cerebral artery occlusion was performed for 60 minutes using an intraluminal thread. We assessed 4 groups: (1) normal glucose (vehicle control), (2) induced hyperglycemia, (3) induced hyperglycemia with insulin treatment, and (4) induced hyperglycemia with exendin-4 treatment. Neurovascular injuries in brains from each group were evaluated 24 hours and 7 days post ischemia. Results Hyperglycemia significantly increased infarct volume (36.31.20 versus 26.9 +/- 1.28; P<0.001), brain edema (P<0.05), and hemorrhagic transformation compared with control (P<0.001). This increase in infarct volume was associated with increased blood-brain barrier disruption and matrix metalloproteinase-9 activation. Exendin-4, but not insulin, attenuated matrix metalloproteinase-9 activation, proinflammatory cytokine (tumor necrosis factor-) release, and biomarkers of oxidative stress and showed significant inhibition of infarct growth at 24 hours (23.6 +/- 0.97 versus 36.3 +/- 1.20; P<0.001) and at 7 days after ischemia (21.0 +/- 0.92 versus 29.3 +/- 1.41; P<0.001). Conclusions Treatment with exendin-4 could be a potentially useful therapeutic option for treatment of acute ischemic stroke with transient hyperglycemia.
  • Ueno Yuji, Yamashiro Kazuo, Tanaka Ryota, Kuroki Takuma, Hira Kenichiro, Kurita Naohide, Urabe Takao, Hattori Nobutaka
    STROKE 47 0039-2499 2016/02 [Refereed][Not invited]
  • Takashi Matsushima, Kenya Nishioka, Ryota Tanaka, Kazumasa Yokoyama, Nobutaka Hattori
    NEUROCASE 22 (1) 103 - 108 1355-4794 2016/01 [Refereed][Not invited]
     
    We report a 19-year-old female presenting with fever, drooling, anarthria, and voluntary facial movement disruption, characteristic of anterior opercular syndrome (AOS). Serological examination revealed Epstein-Barr virus (EBV) infection following acute encephalitis with severe ataxia. A single-photon emission computerized tomography (SPECT) examination indicated hypoperfusion in the left perisylvian region, bilateral thalamus, occipital lobe, and cerebellum. This is the first report of AOS related to EBV encephalitis. SPECT was a useful method for detecting the damaged region of the operculum. In addition, AOS is a clinically distinct entity that may help us understand the mechanisms of language circuits within the operculum.
  • Kenya Nishioka, Tetsuo Hayashi, Michimasa Suzuki, Yuanzhe Li, Sachiko Nakayama, Takashi Matsushima, Chie Usui, Nobuto Shibata, Yumiko Motoi, Ryota Tanaka, Kusuki Nishioka, Nobutaka Hattori
    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES 19 (1) 21 - 29 1756-1841 2016/01 [Refereed][Not invited]
     
    AimFibromyalgia syndrome (FMS) is an extremely rare complication of neurocognitive disorders (NCDs). We experienced seven such cases, and we discuss their clinical manifestation and pathomechanisms. MethodsSeven patients with FMS as a complication of NCD were enrolled. We used the patients' medical records to identify clinical manifestations and obtain experimental data, such as pain questionnaire scores, cognitive tests, genetics and radiological imaging of the brain. ResultsThe seven patients were clinically diagnosed with frontotemporal NCD (n=3) or Alzheimer's disease (n=4). No patient presented with any organic disorder that would explain their chronic pain. Through their courses, they experienced refractory widespread pain continuously despite analgesics. Brain magnetic resonanceimaging revealed moderate or severe atrophic changes in the temporal lobes and hippocampus. Three-dimensional stereotactic surface projection (3D-SSP) analysis of brain single photon emission computed tomography (SPECT), indicated severe hypoperfusion on the right side of the medial temporal lobe, both sides of the anterior corpus callosum, anterior cingulate gyrus, and primary sensory area. Genetic analysis uncovered no pathogenic mutations. ConclusionsNeurodegenerative disorders are rarely complicated by FMS, which is associated with relatively severe pain. Central sensitization may be a possible risk factor of widespread pain in elderly patients with NCD.
  • アルツハイマー病患者におけるガランタミンの効果と、有効症例の特徴の検討
    須田 晃充, 中山 茶千子, 佐々木 芙悠子, 森 聡生, 中島 明日香, 田中 亮太, 久保 紳一郎, 本井 ゆみ子, 服部 信孝
    臨床神経学 (一社)日本神経学会 55 (Suppl.) S368 - S368 0009-918X 2015/12
  • Yuji Ueno, Ryota Tanaka, Kazuo Yamashiro, Yoshiaki Shimada, Takuma Kuroki, Kenichiro Hira, Takao Urabe, Nobutaka Hattori
    JOURNAL OF THE NEUROLOGICAL SCIENCES 359 (1-2) 287 - 292 0022-510X 2015/12 [Refereed][Not invited]
     
    Background: Clinical characteristics are important for determining the etiologies of embolic stroke, including patent foramen ovale and complex aortic plagues demonstrated on transesophageal echocardiography (TEE). This study sought to analyze the clinical signs of cryptogenic stroke (CS) without such embolic etiologies and to examine the association between CS and brain natriuretic peptide (BNP), which is currently unknown. Methods: Patients with CS after routine examinations who underwent TEE were included in this single-center observational study. Patients were classified into the potential embolic sources (PES) group (patients having PES on TEE) and the no potential embolic source (NPES) group. Patients were also categorized according to the tertile of BNP. Results: A total of 158 patients (age, 64.0 +/- 13.9 years; 119 males) with CS were enrolled. The PES group had 108 (68%) patients, and the NPES group had 50 (32%). Hypertension was more common, and glucose, D-dimer, and BNP were higher in the NPES than in the PES group (p < 0.05). NPES was independently associated with high-BNP tertile (OR: 5.61; 95% CI: 1.91 to 16.44; p = 0.002). Conclusions: BNP, an indicator of cardioembolism, was closely associated with NPES. Cardiogenic mechanisms may be implicated in the etiology of CS without potential embolic etiologies on TEE. (C) 2015 Elsevier B.V. All rights reserved.
  • Kazuo Yamashiro, Ryota Tanaka, Yasunobu Hoshino, Taku Hatano, Kenya Nishioka, Nobutaka Hattori
    PARKINSONISM & RELATED DISORDERS 21 (9) 1076 - 1081 1353-8020 2015/09 [Refereed][Not invited]
     
    Introduction: Cerebral microbleeds (CMBs) are frequently observed in patients with cerebrovascular disease and Alzheimer's disease. CMBs that are located in the deep or infratentorial regions and those that are present strictly in the lobar regions reflect hypertensive vasculopathy and cerebral amyloid angiopathy, respectively. The development of CMBs can be accelerated by clinical factors. Orthostatic hypotension (OH) has been reported to be associated with cerebral small vessel disease, such as white matter lesions in Parkinson's disease (PD). We investigated the prevalence, location and risk factors, including OH, for CMBs in patients with PD. Methods: We conducted a retrospective chart review of consecutive patients with PD who were admitted to the Department of Neurology, Juntendo University School of Medicine between January 2010 and July 2014. One hundred and sixty-seven patients with PD who underwent gradient echo T2*-weighted magnetic resonance imaging of the brain were included in the present study. A multivariate logistic regression analysis was performed to investigate the associations between risk factors and the presence of CMBs. Results: CMBs were detected in 29 (17.4%) patients. Among the patients with CMBs, 19 (65.5%) had deep or infratentorial CMBs and 10(34.5%) had strictly lobar CMBs. Hypertension, OH and a history of ischemic stroke were independently associated with deep or infratentorial CMBs, whereas antiplatelet use was independently associated with strictly lobar CMBs. Conclusions: In patients with PD, deep or infratentorial CMBs were more frequent than strictly lobar CMBs, and were associated with hypertension, OH and a history of ischemic stroke. (C) 2015 Elsevier Ltd. All rights reserved.
  • Manami Kobayashi, Ryota Tanaka, Kazuo Yamashiro, Yuji Ueno, Etsuro Kato, Seiji Miura, Hiroyuki Daida, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (6) E161 - E163 1052-3057 2015/06 [Refereed][Not invited]
     
    Background: Early recurrence of an embolism is rarely observed in patients with stroke treated with intravenous thrombolysis. Pre-existing cardiac thrombus is thought as a risk factor for recurrent embolism, although the relationship remains unclear. Methods: The present patient was a 30-year-old man with acute ischemic stroke. Transthoracic echocardiography performed before thrombolysis demonstrated an intraventricular mobile thrombus, and the patient was treated with intravenous thrombolysis 183 minutes after the onset of stroke. During thrombolysis, he suffered from a peripheral artery embolism, without further signs of neurologic deterioration. Repeated transthoracic echocardiography showed the disappearance of the intraventricular thrombus. However, follow-up magnetic resonance imaging disclosed new ischemic lesions at the splenium of the corpus callosum, and body computed tomography showed infarction of the spleen and kidney. The peripheral artery embolism improved spontaneously without further evidence of recurrent embolism. Results: This is the first report to provide findings of an intracardiac mobile thrombus before thrombolysis and to demonstrate the acceleration of detachment of the thrombus during thrombolysis. Conclusions: Because there are currently no guidelines for the use of intravenous thrombolysis for acute ischemic stroke associated with a pre-existing intracardiac thrombus with respect to the efficacy and safety, physicians should pay special attention to similar cases.
  • Yuji Ueno, Kazuo Yamashiro, Yasutaka Tanaka, Masao Watanabe, Nobukazu Miyamoto, Yoshiaki Shimada, Takuma Kuroki, Ryota Tanaka, Katsumi Miyauchi, Hiroyuki Daida, Nobutaka Hattori, Takao Urabe
    ATHEROSCLEROSIS 239 (2) 476 - 482 0021-9150 2015/04 [Refereed][Not invited]
     
    Objective: Large atheromatous aortic plaques (AAPs) have been associated with ischemic stroke. There is little evidence to guide the therapeutic strategy for ischemic stroke associated with large AAPs. This study sought to analyze the temporal profile of AAPs after rosuvastatin therapy in Japanese patients with acute ischemic stroke. Methods: The Efficacy of Post-stroke Intensive Rosuvastatin Treatment for aortogenic Embolic stroke (EPISTEME) trial was a prospective, randomized, open-label study. Acute ischemic stroke patients with dyslipidemia and AAPs >= 4-mm-thick on transesophageal echocardiography (TEE) were enrolled and randomly allocated to either the group treated with 5 mg/day rosuvastatin or the control group. The primary endpoint was the changes in volume and composition of AAPs on repeat TEE after 6 months. High-echoic plaque area was analyzed using binary images. Results: A total of 24 Japanese patients (rosuvastatin 12; control 12) were included in the primary analysis. Rosuvastatin substantially reduced low-density lipoprotein cholesterol (LDL-C) compared to control (-42.1% vs. 1.4%, P < 0.001). Percent changes of high-echoic plaque areas were significantly increased in the rosuvastatin group, while they were decreased in the control group (65.8% vs - 14.7%, P < 0.001). There was a significant linear correlation between percent increase in high-echoic plaque area and LDL-C decrease (r = 0.434, P = 0.002). Conclusion: Treatment with 5-mg rosuvastatin for 6 months might induce atheromatous aortic plaque stabilization together with marked LDL-C reduction in Japanese patients with ischemic stroke, which could provide evidence on which to base the therapeutic strategy for aortogenic brain embolism. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
  • Y. Yatomi, R. Tanaka, Y. Shimada, K. Yamashiro, M. Liu, Y. Mitome-Mishima, N. Miyamoto, Y. Ueno, T. Urabe, N. Hattori
    Neuroscience 289 214 - 223 1873-7544 2015/03 [Refereed][Not invited]
     
    Diabetes mellitus (DM) is a major risk factor for stroke and it exacerbates tissue damage after ischemic insult. Diabetes is one of the important causes of the progression of white matter lesion, however, the pathological mechanisms remain unclear. The present study evaluated the influences of type 2 DM on ischemic subcortical white matter injury and the recruitment of oligodendrocyte progenitor cells (OPCs) under chronic cerebral hypoperfusion using type 2 diabetic (db/. db) mice. After bilateral common carotid artery stenosis (BCAS), the rarefaction in the white matter was more severe in db/. db mice than in db/+ mice, and the number of glutathione S-transferase-pi (GST-pi)-positive mature oligodendrocytes (OLG) was lower in db/. db mice than in db/+ mice at 4 and 8 weeks after ischemia. There were no significant differences in the number of single-stranded DNA (ssDNA)-positive apoptotic cells in the deep white matter between the db/. db and db/+ mice. We found a transient increase in the platelet-derived growth factor receptor-α (PDGFRα)-positive OPCs in white matter lesions after ischemia. However, significantly fewer PDGFRα-positive OPCs were detected in db/. db than db/+ mice from 4. weeks after BCAS. The number of Ki67-positive proliferating cells in the deep white matter was significantly lower in db/. db mice than in db/+ mice from 4 to 8. weeks after BCAS. Most of the Ki67-positive cells were PDGFRα-positive OPCs. Finally, we assessed the survival of 5-bromo-2'-deoxyuridine (BrdU)-positive proliferating cells in ischemic white matter, and found significantly poorer survival of BrdU/PDGFRα-positive OPCs or BrdU/GST-pi-positive OLGs in the db/. db mice compared to the db/+ mice in the white matter after BCAS. Our findings suggest that the type 2 DM mice exhibited more severe white matter injury 8 weeks after chronic ischemia. Decreased proliferation and survival of OPCs may play an important role in the progression of white matter lesions after ischemia in diabetics.
  • Yuji Ueno, Masato Koike, Yoshiaki Shimada, Hideki Shimura, Kenichiro Hira, Ryota Tanaka, Yasuo Uchiyama, Nobutaka Hattori, Takao Urabe
    Journal of Perinatology 35 (3) 382 - 391 1476-5543 2015/03 [Refereed][Not invited]
     
    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.
  • Yuji Ueno, Masato Koike, Yoshiaki Shimada, Hideki Shimura, Kenichiro Hira, Ryota Tanaka, Yasuo Uchiyama, Nobutaka Hattori, Takao Urabe
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 35 (3) 382 - 391 0271-678X 2015/03 [Refereed][Not invited]
     
    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent With a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapannycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.
  • Miyamoto Nobukazu, Tanaka Ryota, Ueno Yuji, Watanabe Masao, Tanaka Yasutaka, Shimada Yoshiaki, Kuroki Takuma, Yamashiro Kazuo, Hattori Nobutaka, Urabe Takao
    STROKE 46 0039-2499 2015/02 [Refereed][Not invited]
  • Yasutaka Tanaka, Yuji Ueno, Yoshiaki Shimada, Kazuo Yamashiro, Ryota Tanaka, Takao Urabe, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 24 (2) E55 - E57 1052-3057 2015/02 [Refereed][Not invited]
     
    Kimura disease (KD) is an uncommon chronic inflammatory disease presenting as subcutaneous lymphadenopathy with eosinophilia. To date, only a single case of brain embolism caused by fibroblastic endocarditis associated with KD has been reported. Watershed infarction was seen in patients with episodes of severe hypotension or cardiac surgery. We here report a young case of KD who developed ischemic stroke and showed multiple small infarcts in the border zones between the territories of major cerebral arteries, mimicking watershed infarction. Transesophageal echocardiography revealed patent foramen ovale and atrial septal aneurysm. Concurrently, deep venous thrombus in the femoral vein was found on duplex ultrasonography. Our case supports the notion that paradoxical brain embolism associated with KD can cause multiple small embolisms and mimic watershed infarction. (C) 2015 by National Stroke Association
  • Kazuo Yamashiro, Sayaka Funabe, Ryota Tanaka, Yuki Fukumura, Masashi Takanashi, Takashi Yao, Nobutaka Hattori
    NEUROLOGY 84 (7) 755 - 756 0028-3878 2015/02 [Refereed][Not invited]
     
    A 64-year-old woman with an aortic mass experienced repeated recurrences of stroke (figure 1) and died 8 months later. The postmortem examination showed the tumor to almost completely obstruct the aortic lumen, while extending to the intracranial arteries without parenchymal invasion (figure 2). The pathologic diagnosis was undifferentiated aortic intimal sarcoma. Primary aortic sarcoma is a rare and aggressive tumor, with clinical symptoms including acute arterial embolism and disseminated metastasis.(1) Although arch atheroma is sometimes identified as a cause of cerebral emboli,(2) this case shows that primary aortic sarcoma should be included in the differential diagnosis of aortic arch diseases.
  • Ryota Tanaka, Kazuo Yamashiro, Yasuyuki Okuma, Hideki Shimura, Shinichiro Nakamura, Yuji Ueno, Yasutaka Tanaka, Nobukazu Miyamoto, Yuji Tomizawa, Toshiki Nakahara, Yoshiaki Furukawa, Hirotaka Watada, Ryuzo Kawamori, Nobutaka Hattori, Takao Urabe
    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 22 (12) 1305 - 1316 1340-3478 2015 [Refereed][Not invited]
     
    Aim: Prediabetes is an independent risk factor for future stroke. However, no effective treatment has yet been established for the recurrence of stroke in patients with prediabetes. Here we investigated the effects of pioglitazone, a potent peroxisome proliferator-activated receptor-gamma agonist, for the reduction of recurrent stroke in patients with prediabetes. Methods: Participants were patients who had a symptomatic ischemic stroke or transient ischemic attack (TIA) without a history of type 2 diabetes mellitus and who were diagnosed to have IGT or newly diagnosed diabetes by a 75-g oral glucose tolerance test. These patients were randomized to either receive or not receive pioglitazone. The primary endpoint was a recurrence of ischemic stroke. Results: A total of 120 patients were enrolled in the study. Sixty-three patients received pioglitazone and 57 were enrolled in the control group that did not receive pioglitazone. The majority of patients (68.3%) were prescribed 15 mg of pioglitazone, while the remaining patients (31.7%) were treated with 30 mg of pioglitazone. Over a median follow-up period of 2.8 years, treatment with pioglitazone was found to be associated with a lower rate of the primary endpoint (recurrence of stroke) than that observed in the control group [event rate = 4.8% pioglitazone vs 10.5% control, hazard ratio = 0.62, 95% confidence interval 0.13-2.35, p = 0.49]. However, differences were not statistically significant. Conclusions: While this study was too underpowered to determine the effect of pioglitazone, the result failed to show beneficial effects in patients of ischemic stroke or TIA with impaired glucose tolerance and newly diagnosed diabetes.
  • Kenya Nishioka, Ryota Tanaka, Hideki Shimura, Kazuoki Hirano, Taku Hatano, Koichi Miyakawa, Heii Arai, Nobutaka Hattori, Takao Urabe
    JOURNAL OF NEURAL TRANSMISSION 121 (11) 1405 - 1410 0300-9564 2014/11 [Refereed][Not invited]
     
    Patients with advanced-stage Parkinson's disease (PD) occasionally experience refractory depression or catatonic stupor. Electroconvulsive therapy (ECT) has been reported as a successful procedure for both severe psychosis and motor symptoms in patients with PD. Four patients with PD who were receiving ECT were quantitatively evaluated using the Unified PD Rating scale part III, Hoehn and Yahr scale, Barthel index, Neuropsychiatric Inventory, mini-mental state examination, Revised Hasegawa's Dementia scale, Beck's Depression Inventory, and Hamilton Rating Scale for Depression-17. We adopted the "half-age" method, which is an age-based stimulus-dosing method. The patients showed improvement in symptoms of psychosis and motor symptoms without any adverse effects. The interval of improvement after ECT varied among patients. Of note, a decrease in psychiatric symptoms successfully alleviated the burden of caregivers. ECT may be useful to treat parkinsonism with refractory psychosis, major depression, or catatonic stupor, within the limitations of the patients enrolled.
  • Takuma Kuroki, Kazuo Yamashiro, Ryota Tanaka, Kazuoki Hirano, Yoshiaki Shimada, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 (10) E441 - E443 1052-3057 2014/11 [Refereed][Not invited]
     
    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal cystic disease, and it is associated with various extrarenal manifestations, including vascular complications, such as intracranial aneurysms, and aortic root dilatation and aneurysms. However, intracranial arterial dissection has rarely been reported. We herein report the cases of 2 patients with ADPKD who developed a vertebral artery (VA) dissection. Dissection was also observed on the other side of the VA and in the internal carotid artery in the first and second patient, respectively. Both patients also had a history of hypertension, which is frequently accompanied by ADPKD, and their serum creatinine levels were normal. Our report supports the importance of considering ADPKD as one of the possible pathogenic factors in arterial dissection.
  • Y. Shimada, R. Tanaka, H. Shimura, K. Yamashiro, T. Urabe, N. Hattori
    Neuroscience 278 113 - 121 1873-7544 2014/10 [Refereed][Not invited]
     
    Heat shock protein 27 (HSP27) exerts cytoprotection against many cellular insults including cerebral ischemia. We previously indicated that intravenous injection of HSP27 purified from human lymphocytes (hHSP27) significantly reduced infarct volume following cerebral ischemia-reperfusion injury, while recombinant HSP27 (rHSP27) was less effective. Phosphorylation is important for HSP27 function, and hHSP27 was more highly phosphorylated than rHSP27. We hypothesized that MAPKAP kinase 2 in vitro-phosphorylated rHSP27 (prHSP27) might increase its brain protection. Mice underwent transient 1-h middle cerebral artery occlusion (MCAO), and then received tail-vein injections of one of the following 1h after reperfusion: hHSP27 as positive control, rHSP27, prHSP27, or bovine serum albumin (BSA) as control. We measured infarct volume, neurological deficits, neurological severity, physiological parameters, cell-death, oxidative stress, and inflammatory response. Compared with BSA controls (30.7±3.1mm3, n=5), infarct volume was reduced by 67% in the hHSP27 positive-control group (10.1±4.6mm3, P< 0.001, n=5), 17% following rHSP27 (25.4±3.6mm3, P< 0.05, n=5), and 46% following prHSP27 (16.5±4.0mm3, P< 0.001, n=9). Compared to the rHSP27 and BSA-treated groups, prHSP27 also reduced functional deficits, and significantly suppressed apoptosis, oxidative stress, and inflammatory responses. Here, we showed the superior neuroprotective effects of phosphorylated HSP27 by administering prHSP27. prHSP27 may be a useful therapeutic agent to protect against acute cerebral ischemic stroke.
  • Yamashiro K, Tanaka R, Okuma Y, Shimura H, Ueno Y, Miyamoto N, Urabe T, Hattori N
    Cerebrovascular diseases extra 4 (3) 212 - 220 2014/09 [Refereed][Not invited]
  • Kenya Nishioka, Ryota Tanaka, Satoshi Tsutsumi, Kazuo Yamashiro, Mariko Nakahara, Hideki Shimura, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 (7) 1985 - 1987 1052-3057 2014/08 [Refereed][Not invited]
     
    We report a case of cerebral venous thrombosis (CVT) associated with a giant adenomyosis. At admission, the patient demonstrated generalized seizures and consciousness disturbance. Brain fluid-attenuated inversion recovery magnetic resonance imaging revealed a localized, high-intensity region in the left frontal lobe. Subsequent brain angiography showed that right internal carotid angiograms display abrupt termination of the anterior half of the superior sagittal sinus and a filling defect in the lateral part of the left transverse sinus. The patient complicated with iron deficiency anemia (IDA) and adenomyosis with higher levels of serum carbohydrate antigen 125 (CA125) and D-dimer. After 1 year from onset, intermittent severe menalgia and headache persisted, and blood examination revealed abnormal values; the patient was receiving oral medications. Finally, adenomyosis resection was performed with a favorable outcome, and no recurrence was observed during the 2-year follow-up period. We conclude that IDA and increased CA125 levels may have promoted hypercoagulability and CVT. This report emphasizes the possible relationship between CVT and adenomyosis.
  • K. Yamashiro, R. Tanaka, Y. Tanaka, N. Miyamoto, Y. Shimada, Y. Ueno, T. Urabe, N. Hattori
    European Journal of Neurology 21 (4) 667 - 673 1351-5101 2014/04 [Refereed][Not invited]
     
    Background and purpose: Obesity is associated with the risk of coronary artery disease and stroke. Visceral fat plays a significant role in the atherogenic effects of obesity. Whether visceral fat accumulation, as measured by computed tomography (CT), is an independent risk factor for the presence of cerebral small vessel disease (SVD) was investigated. Methods: This study comprised 506 Japanese subjects 35-74 years of age (mean 55.3 years) without a history of symptomatic cerebrovascular disease who underwent health screening tests, including brain magnetic resonance imaging, carotid echography and measurements of the visceral fat area (VFA) and subcutaneous fat area (SFA) on abdominal CT. Visceral fat accumulation was defined as VFA ≥ 100 cm2. Logistic regression analysis was performed to examine the associations between visceral fat accumulation and cerebral SVD such as white matter lesions (WMLs) and silent lacunar infarction (SLI). Results: The prevalence of WMLs and SLI but not carotid plaque were significantly higher in subjects with VFA ≥ 100 cm2 than those with VFA < 100 cm2. A VFA ≥ 100 cm2 was associated with WMLs and SLI independent of age, cardiovascular risk factors and other measurements of obesity, such as waist circumference and body mass index. A large waist circumference was independently associated with SLI. SFA, the combination of VFA and SFA, and body mass index were not associated with WMLs or SLI. Conclusions: Visceral fat accumulation was independently associated with the presence of cerebral SVD in subjects without a history of symptomatic cerebrovascular disease. © 2014 EFNS.
  • Sayaka Funabe, Ryota Tanaka, Akito Hayashi, Kazuo Yamashiro, Hideki Shimura, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 (4) 785 - 787 1052-3057 2014/04 [Refereed][Not invited]
     
    We report a rare case of transient "dropped head syndrome'' (DHS) after acute ischemic stroke. A 64-year-old man noticed a sudden onset of mild weakness in his left hand and also difficulty in preventing his head from dropping onto his chest without weakness of the neck extensor muscles. Magnetic resonance images showed acute ischemic changes at the right putamen and caudate nucleus. Surface electromyography (EMG) performed 3 days after the stroke showed that both trapeziuses were hypertonic at rest, whereas the activity of the sternocleidomastoids was gradually increased on passive head lifting, indicating dystonia of the neck muscles. His dropped head fully improved by 9 days after the stroke. Re-examination by surface EMG 30 days after the stroke showed no hypertonic activity in the neck muscles. DHS is characterized by an abnormal ante-fixed posture of the neck, usually observed in patients with neurodegenerative disorders such as multiple system atrophy and Parkinson disease. This is the first case of reversible DHS after acute ischemic stroke, and the accumulation of similar cases will be important to elucidate the mechanisms underlying the development of DHS and stroke-associated movement disorders.
  • Kazuo Yamashiro, Ryota Tanaka, Yasuyuki Okuma, Yuji Ueno, Yasutaka Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 (3) 433 - 440 1052-3057 2014/03 [Refereed][Not invited]
     
    The association of the presence of cerebral microbleeds with antiplatelet use remains controversial. Long durations of antiplatelet use and vascular risk factors may have a greater impact on the development of cerebral microbleeds than short durations. The aim of this study was to determine whether the durations of antiplatelet use and vascular risk factors were associated with the presence of cerebral microbleeds in patients with ischemic cerebrovascular disease, who are frequently treated with antiplatelet agents. Two hundred twenty outpatients with ischemic cerebrovascular lesions (eg, cerebral infarcts and/or white matter lesions) detected by magnetic resonance imaging were examined. Patients with a history of cerebral hemorrhage were excluded. Cerebral microbleeds were observed in 71 (32.3%) patients. Deep or infratentorial microbleeds and strictly lobar microbleeds were observed in 53 (24.1%) patients and 18 (8.2%) patients, respectively. Aspirin use (odds ratio, 2.14; 95% confidence interval [CI], 1.02-4.73; P = .04) and a long duration (>= 10 years) of aspirin use (odds ratio, 3.75; 95% CI, 1.31-10.86; P = .01) were significantly associated with deep or infratentorial microbleeds in the crude analysis, but this became nonsignificant after adjustment for hypertension and other confounding factors. The prevalence of antiplatelet use was significantly higher in the patients with hypertension than in those without hypertension (72.5% versus 49.1%, P = .002). Hypertension (odds ratio, 2.50; 95% CI, 1.11-6.41; P = .04) was significantly associated with the development of deep or infratentorial microbleeds even after adjustment for confounding factors and the association increased with the duration of hypertension. In conclusion, we found a significant association between aspirin use and deep or infratentorial microbleeds, but this association may reflect the presence of hypertension as a confounding factor.
  • Yuji Tomizawa, Ryota Tanaka, Kiyoshi Sekiguchi, Yutaka Oji, Yasutaka Tanaka, Kazuo Yamashiro, Nobutaka Hattori
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 (2) 393 - 394 1052-3057 2014/02 [Refereed][Not invited]
     
    Our objective is to report a rare coexistence of Parry-Romberg disease and ischemic stroke. Here, we report the case of a 34-year-old woman with Parry-Romberg syndrome who developed cerebral infarction. This patient developed sudden left-sided weakness and was admitted to our hospital. Magnetic resonance imaging revealed acute cerebral infarction in the posterior limb of the right internal capsule. The patient had been diagnosed with Parry-Romberg syndrome at the age of 12, and she had a history of migraine without aura. Transesophageal echocardiography revealed a patent foramen ovale, but no atrial septal aneurysm or deep vein thrombosis was observed in the lower extremities. She was treated with 200 mg of aspirin and 10 mg of atorvastatin. Her symptoms gradually improved, and she was discharged 10 days after admission. Parry-Romberg syndrome is a rare disease of progressive hemifacial atrophy with unknown etiology. The potential risk factors for ischemic stroke in Parry-Romberg syndrome include ipsilateral cerebrovascular abnormality or migraine. In addition, patent foramen ovale was identified as a concomitant risk factor in our case.
  • Yuji Ueno, Kazuo Yamashiro, Yasutaka Tanaka, Masao Watanabe, Yoshiaki Shimada, Takuma Kuroki, Nobukazu Miyamoto, Masao Daimon, Ryota Tanaka, Katsumi Miyauchi, Hiroyuki Daida, Nobutaka Hattori, Takao Urabe
    CARDIOVASCULAR DRUGS AND THERAPY 28 (1) 79 - 85 0920-3206 2014/02 [Refereed][Not invited]
     
    Background Large atheromatous aortic plaques (AAPs) are associated with stroke recurrence. Rosuvastatin is a potent lipid-lowering agent and suppresses carotid and coronary artery atherosclerosis. It is unclear whether rosuvastatin has anti-atherogenic effects against AAPs in stroke patients. We designed a clinical trial in stroke patients to analyze changes in AAPs after rosuvastatin treatment using repeated transesophageal echocardiography (TEE). This trial is a prospective randomized open label study. Inclusion criteria were patients were ischemic stroke with hypercholesterolemia and AAPs a parts per thousand yen4 mm in thickness. The patients are randomly assigned to either a group treated with 5 mg/day rosuvastatin or a control group. Primary endpoint is the changes in volume and composition of AAPs after 6 months using transesophageal echocardiography (TEE). Biochemical findings are analyzed. By using repeated TEE and binary image analysis, we will be able to compare the dynamic changes in plaque composition of AAPs before and after therapy in the two groups. The EPISTEME trial will provide information on the changes in plaque volume and composition achieved by improvement of lipid profiles with rosuvastatin therapy in stroke patients with aortic atherosclerosis. The results of the study may provide evidence for a therapeutic strategy for aortogenic brain embolism. This study is registered with UMIN-CTR (UMIN000010548).
  • Hiroki Hongo, Yasutaka Tanaka, Yoshiaki Shimada, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 23 (1) 182 - 183 1052-3057 2014/01 [Refereed][Not invited]
     
    A 61-year-old man who experienced a sudden onset of unstable gait followed by nuchal pain was admitted to our department. The neurologic examination revealed right-sided limb ataxia, right partial ptosis, and decreased sensation to 50% of the normal side to pinprick and temperature stimuli on the left side below the level of the T-6 dermatome. A lateral medullary infarction caused by spontaneous vertebral artery dissection was diagnosed by magnetic resonance imaging and computed tomography angiography. In conclusion, lateral medullary infarction is an important entity to consider in the differential diagnosis of dermatomal sensory manifestations.
  • Yuji Ueno, Ayami Okuzumi, Masao Watanabe, Yasutaka Tanaka, Yoshiaki Shimada, Kazuo Yamashiro, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 21 (10) 1011 - 1021 1340-3478 2014 [Refereed][Not invited]
     
    Aim: Aortic arch calcification (AoAC) on chest X-rays represents systemic atherosclerosis and it is associated with ischemic cardiovascular diseases. However, the relationship between ischemic stroke and AoAC has yet to be fully elucidated. Methods: Patients with acute ischemic stroke who were undergoing chest X-ray, blood, and brain magnetic resonance imaging (MRI) examinations were prospectively studied. The extent of AoAC on chest X-ray was divided into four grades (0-3). Clinical characteristics, biochemical findings, white matter lesions on MRI, and AoAC extent were assessed in each stroke subtype, and the factors associated with AoAC were investigated. Results: A total of 175 patients (age, 70 +/- 13 years; 115 men) were enrolled in the study. According to the Trial of Org 10172 in Acute Stroke Treatment classification with minor modification, 33 patients (19%) had small artery occlusion (SAO), 42 (24%) had large artery atherosclerosis, 49 (28%) had cardioembolism, 24 (14%) had stroke with other determined etiologies, and 27 (17%) had stroke with undetermined etiologies. Compared to other stroke subtypes, the extent of AoAC was independently correlated with SAO (all p<0.05). Age (odds ratio [OR]: 1.14, 95% confidence interval [CI]: 1.08 to 1.19, p<0.001), hypertension, (OR: 3.44, 95% CI: 1.23 to 9.66, p=0.019), diabetes mellitus (OR: 2.19, 95% CI: 0.99 to 4.85, p=0.054), white matter lesions (OR: 1.54, 95% CI: 1.00 to 2.36, p=0.048), and SAO (OR: 1.38, 95% CI: 1.02 to 1.89, p=0.040) were significantly associated with AoAC. Conclusions: Age, hypertension, cerebral small artery disease, and possibly diabetes mellitus appear to be closely associated with AoAC in patients with acute ischemic stroke.
  • Yumiko Mitome-Mishima, Nobukazu Miyamoto, Ryota Tanaka, Tatsuo Shimosawa, Hidenori Oishi, Hajime Arai, Nobutaka Hattori, Takao Urabe
    BIOMED RESEARCH INTERNATIONAL 2014 861632  2314-6133 2014 [Refereed][Not invited]
     
    Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. Here, we examine whether adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion. Adrenomedullin heterozygous, wild-type young/aged mice were subjected to prolonged hypoperfusion. Prolonged cerebral hypoperfusion followed by immunohistochemical analysis was used to evaluate white matter injury. After prolonged hypoperfusion, white matter damage progressed in a time-dependent manner in AM(+/-) group compared with the wild-type group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM(+/-) group (p < 0.05). Oxidative stress was detected in oligodendrocytes, with a larger increase in theAM(+/-) group (p < 0.05). Aged mice showed the same tendency, butwhite matter damage was worse, especially in the aged AM(+/-) group. Our results demonstrated that white matter injury was increased in adrenomedullin deficiency, which induced oxidative stress. White matter injury was more exacerbated because of hyperglycemia in aged AM(+/-) group. Adrenomedullin may be an important target in the control of ischemic white matter injury.
  • Ran Tomomasa, Kazuo Yamashiro, Ryota Tanaka, Nobutaka Hattori
    Journal of Stroke and Cerebrovascular Diseases 22 (8) e650 - e652 1052-3057 2013/11 [Refereed][Not invited]
     
    A 41-year-old male with a history of human immunodeficiency virus (HIV) infection developed motor aphasia, dysarthria, and right hemiparesis. A magnetic resonance imaging scan of the brain revealed a cerebral infarction in the territory of the left middle cerebral artery. The laboratory data showed decreased levels of protein S and protein C. Transesophageal contrast-enhanced echocardiography revealed a patent foramen ovale (PFO). Prothrombotic states, such as protein S and C deficiency, have been reported in HIV-infected patients. In addition, previous studies have reported prothrombotic states to be risk factors for PFO-related cerebral infarction. An association between combined protein S and C deficiency caused by HIV infection and PFO-related cerebral infarction was suggested in our patient. © 2013 Elsevier B.V. All rights reserved.
  • Kazuo Yamashiro, Ryota Tanaka, Yuanzhe Li, Michitaka Mikasa, Nobutaka Hattori
    JOURNAL OF NEUROLOGY 260 (10) 2653 - 2655 0340-5354 2013/10 [Refereed][Not invited]
  • Ryota Tanaka, Yuji Ueno, Nobukazu Miyamoto, Kazuo Yamashiro, Yasutaka Tanaka, Hideki Shimura, Nobutaka Hattori, Takao Urabe
    JOURNAL OF THE NEUROLOGICAL SCIENCES 332 (1-2) 45 - 50 0022-510X 2013/09 [Refereed][Not invited]
     
    Objective: We aimed to explore the association between abnormal glucose metabolism such as diabetes, prediabetes, and short-term prognosis in patients with acute ischemic stroke. Methods: Of 242 consecutive acute ischemic stroke patients, a 75-g oral glucose tolerance test was administered to 116 patients without previously diagnosed diabetes. One hundred forty patients were classified into diabetes, 52 patients were prediabetes (impaired glucose tolerance or impaired fasting glucose or both), and 50 patients were normal glucose tolerance (NGT). The association between each glycemic status and early neurological deterioration (END; increase in the NIH Stroke Scale (NIHSS) of >= 2 points during the first 14 days after admission) or poor short-term outcome (30-day modified Ranking Scale [mRS] score 2-6) was evaluated. Results: In multivariable analysis, the risk of END was significantly higher in the diabetes group than in the NGT group (ORs = 11354; 95% CI, 1.492-86.415; p = 0.019), even after adjustment for possible confounding factors (ORs = 12.769; 95% Cl, 1.361-119.763; p = 0.026). Similar but insignificant associations were observed between prediabetes and NGT groups (ORs = 6.369; 95% Cl, 0.735-55.177; p = 0.093). The risk of poor outcome (30-day mRS 2-6) was significantly higher in the diabetes group (ORs = 3.667; 95% CI, 1.834-7.334; p < 0.001) than in the NGT group, even after adjusting for confounding factors (ORs = 3.340; 95% Cl, 1.361-8.195; p = 0.008). Similar but insignificant associations were observed between prediabetes and NGT groups (ORs = 2.058; 95% Cl, 0.916-4.623; p = 0.08). Conclusion: In our patient population, both diabetes and prediabetes were associated with a poor early prognosis after acute ischemic stroke. (C) 2013 Elsevier B.V. All rights reserved.
  • Y. Yatomi, R. Tanaka, H. Shimura, N. Miyamoto, K. Yamashiro, M. Takanashi, T. Urabe, N. Hattori
    Neuroscience 244 113 - 121 0306-4522 2013/08 [Refereed][Not invited]
     
    Glutamate plays a central role in brain physiology and pathology. The involvement of excitatory amino acid transporters (EAATs) in neurodegenerative disorders including acute stroke has been widely studied, but little is known about the role of glial glutamate transporters in white matter injury after chronic cerebral hypoperfusion. The present study evaluated the expression of glial (EAAT1 and EAAT2) and neuronal (EAAT3) glutamate transporters in subcortical white matter and cortex, before and 3-28. days after the ligation of bilateral common carotid arteries (LBCCA) in rat brain. K-B staining showed a gradual increase of demyelination in white matter after ischemia, while there was no cortical involvement. Between 3 and 7. days after LBCCA, a significant increase in EAAT2 protein levels was observed in the ischemic brain and the number of EAAT2-positive cells also significantly increased both in the cortical and white matter lesions. EAAT2 was detected in glial-fibrillary acidic protein (GFAP)-positive astrocytes in both the cortex and white matter, but not in neuronal and oligodendroglial cells. EAAT1 was slightly elevated after ischemia only in the white matter, but EAAT3 was at almost similar levels both in the cortex and white matter after ischemia. A significant increase in EAAT2 expression level was also noted in the deep white matter of chronic human ischemic brain tissue compared to the control group. Our findings suggest important roles for up-regulated EAAT2 in chronic brain ischemia especially in the regulation of high-affinity of extracellular glutamate and minimization of white matter damage. © 2013 IBRO.
  • Shinichiro Teramoto, Hideki Shimura, Ryota Tanaka, Yoshiaki Shimada, Nobukazu Miyamoto, Hajime Arai, Takao Urabe, Nobutaka Hattori
    PLOS ONE 8 (6) e66001  1932-6203 2013/06 [Refereed][Not invited]
     
    Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27) is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27) from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of ab-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27), which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.
  • Taiki Kambe, Hideki Shimura, Yuji Ueno, Kenya Nishioka, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    PSYCHOSOMATICS 54 (3) 284 - 285 0033-3182 2013/05 [Refereed][Not invited]
  • Nobukazu Miyamoto, Yasutaka Tanaka, Yuji Ueno, Miyako Kawamura, Yoshiaki Shimada, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 22 (3) 205 - 210 1052-3057 2013/04 [Refereed][Not invited]
     
    One-third of patients with acute ischemic stroke develop early neurologic worsening, which is associated with increased mortality and long-term functional disability. We investigated the predictive factors for neurologic deterioration in patients with acute ischemic stroke within 1 week of onset. We retrospectively investigated 643 patients who were admitted within 2 days of acute ischemic stroke between April 2007 and March 2010. Neurologic deterioration was defined as an increase of 4 points or more in the National Institutes of Health Stroke Scale (NIHSS) score within 1 week of admission. We retrieved data on demographic and clinical characteristics, medications, and stroke subtypes. Out of 537 patients, deterioration was noted in 64 patients (11.9%; deterioration group). Multivariate analysis identified history of myocardial infarction (P < .001), NIHSS score >= 8 at onset (P < .001), high leukocyte count (P = .035), low-density lipoprotein cholesterol >= 140 mg/dL (P = .002), and hemoglobin A1c >= 7% (P = .006) as significant factors associated with deterioration. Branch atheromatous disease was more frequent in the deterioration group, and >90% of patients with deterioration either were discharged to nursing home care or died. Multivariate analysis of magnetic resonance imaging findings identified internal carotid/middle cerebral artery occlusion (each P < .001), striate capsular infarction (P = .030), pontine infarction (P = .047), and lesion size of 15-30 mm (P = .011) as independent factors associated with deterioration. Stroke patients with a high low-density lipoprotein level, high hemoglobin A1c level on admission, a history of myocardial infarction, and high NIHSS score are at high risk for neurologic deterioration. Patients with multiple risk factors for deterioration can benefit most from intensive monitoring.
  • Yumiko Mitome-Mishima, Nobukazu Miyamoto, Ryota Tanaka, Hidenori Oishi, Hajime Arai, Nobutaka Hattori, Takao Urabe
    NEUROSCIENCE RESEARCH 75 (4) 340 - 348 0168-0102 2013/04 [Refereed][Not invited]
     
    Phosphodiesterase (PDE) exists in the cardiovascular system, adipose tissue and platelets, and its inhibition increases the cellular levels of cAMP, which could activate cAMP-responsive element binding protein (pCREB). The present study was designed to map the expression of PDE3A/B in the forebrain and define the time course of PDE3 expression in the ischemic boundary zone after ischemia. The number of PDE3A-positive cells (neurons and endothelial cells) remained unchanged, while PDE3B-positive cells gradually increased after ischemia/reperfusion. In the corpus callosum, PDE3B was expressed in oligodendrocytes, oligodendrocyte progenitor cells, and astrocytes. PDE3B-expressing astrocytes showed gradual increase after ischemia/reperfusion. In the cortex, the majority of PDE3B-expressing cells before ischemia were neurons, though few were astrocytes. Ischemic insult resulted in gradual increase in PDE3B-expressing astrocytes and neurons, with larger increase in astrocytes. Expression of brain derived neurotrophic factor (BDNF) and B-cell leukemia/lymphoma 2 protein (Bcl-2) was detected in pCREB-positive cells, not in PDE3B-positive cells. Our results demonstrated that ischemic insult increased PDE3B expression, but not PDE3A, and changed the number and type of cells in a time-dependent manner. The variation of PDE3B-expression in the brain might play a crucial pathophysiological role, and regulation of PDE3B production might protect against ischemic brain damage. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
  • Ayami Okuzumi, Yuji Ueno, Yoshiaki Shimada, Yasutaka Tanaka, Nobukazu Miyamoto, Kazuo Yamashiro, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF THE NEUROLOGICAL SCIENCES 326 (1-2) 83 - 88 0022-510X 2013/03 [Refereed][Not invited]
     
    The ratio of low- (LDL-C) to high- (HDL-C) density lipoprotein cholesterol serves as a positive predictor of atherosclerosis including coronary artery disease. We assessed the contribution of the LDL-C/HDL-C ratio to atheromatous aortic plaques (AAPs) in patients with unexplained ischemic stroke. One hundred thirty-seven patients (age, 65 +/- 14 years; 87 male) with ischemic stroke underwent transesophageal echocardiography (TEE) and enrolled to the study. Patients were classified based on TEE findings: (1) AAPs<4 mm in thickness; (2) AAPs >= 4 mm; and (3) mobile or ulcerated aortic plaques (MUAPs). We assessed clinical characteristics and biochemical findings, and investigated the relationship between AAPs and the LDL-C/HDL-C ratio of stroke patients. 84 (61%) patients had AAPs<4 mm, 29 (21%) had AAPs >= 4 mm, and 24 (18%) had MUAPs. Older age (OR: 1.18; 95% CI: 1.08 to 130; p = 0.001), and LDL-C/HDL-C ratio (OR: 2.94; 95% CI: 1.10 to 7.87; p = 0.032) were significantly associated with MUAPs. The incidence of MUAPs substantially increased in patients with LDL-C/HDL-C ratios of >223 (p<0.001) when the ratios were divided into quartiles. The LDL-C/HDL-C ratio was closely associated with MUAPs. An elevated LDL-C/HDL-C ratio could be a positive predictor of aortogenic brain embolism. (c) 2013 Elsevier B.V. All rights reserved.
  • Yamashiro Kazuo, Tanaka Ryota, Okuma Yasuyuki, Ueno Yuji, Tanaka Yasutaka, Hattori Nobutaka, Urabe Takao
    STROKE 44 (2) 0039-2499 2013/02 [Refereed][Not invited]
  • Tanaka Ryota, Yamashiro Kazuo, Tanaka Yasutaka, Miyamoto Nobukazu, Ueno Yuji, Watanabe Masao, Okuma Yasuyuki, Nakamura Shinichiro, Furukawa Yoshiaki, Watada Hirotaka, Kawamori Ryuzo, Hattori Nobutaka, Urabe Takao
    STROKE 44 (2) 0039-2499 2013/02 [Refereed][Not invited]
  • Tanaka Ryota, Yamashiro Kazuo, Tanaka Yasutaka, Miyamoto Nobukazu, Ueno Yuji, Watanabe Masao, Okuma Yasuyuki, Nakamura Shinichiro, Furukawa Yoshiaki, Watada Hirotaka, Hattori Nobutaka, Urabe Takao
    CEREBROVASCULAR DISEASES 36 32  1015-9770 2013 [Refereed][Not invited]
  • Yamashiro Kazuo, Tanaka Ryota, Tanaka Yasutaka, Miyamoto Nobukazu, Ueno Yuji, Hattori Nobutaka, Urabe Takao
    CEREBROVASCULAR DISEASES 36 46  1015-9770 2013 [Refereed][Not invited]
  • Yasutaka Tanaka, Yuji Ueno, Nobukazu Miyamoto, Yoshiaki Shimada, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF NEUROLOGY 260 (1) 189 - 196 0340-5354 2013/01 [Refereed][Not invited]
     
    The purpose of the present study was to evaluate the contributions of embolic etiologies, patent foramen ovale (PFO) and atrial septal aneurysm (ASA) to the pathogenesis of ischemic stroke in patients with antiphospholipid syndrome (APS). We performed transesophageal echocardiography (TEE) examination for consecutive stroke patients who had been diagnosed with APS (APS group) to detect potential embolic sources. APS was diagnosed based on the modified Sapporo criteria. The control stroke group comprised age- and sex-matched cryptogenic stroke patients undergoing TEE. We assessed and compared the clinical characteristics and TEE findings between stroke patients with APS and control stroke groups. Among 582 patients, nine patients (nine women; mean age, 50 +/- A 18 years) were classified into the APS group. In 137 patients undergoing TEE, 41 age-matched female stroke patients were recruited to the control stroke group. Prevalences of PFO and ASA were significantly higher in the APS group than in the control stroke group (89 vs. 41 %, p = 0.027; 67 vs. 20 %, p = 0.015, respectively). Multiple logistic regression analysis showed that PFO (odds ratio (OR), 13.71; 95 % confidence interval (CI), 1.01-185.62; p = 0.049) and ASA (OR, 8.06; 95 % CI, 1.17-55.59; p = 0.034) were independently associated with the APS group. PFO and ASA were strongly associated with the APS group, and could thus represent potential embolic sources in ischemic stroke patients with APS.
  • Youichi Yanagawa, Keiichiro Ohara, Yasutaka Tanaka, Ryota Tanaka
    Journal of Emergencies, Trauma and Shock 6 (1) 53 - 55 0974-2700 2013/01 [Refereed][Not invited]
     
    We herein report the fourth case of cerebral infarction, concomitant with hemorrhagic shock, in English literature. A 33-year-old male, who had been diagnosed with schizophrenia and given a prescription for Olanzapine, was discovered with multiple self-inflicted bleeding cuts on his wrist. On arrival, he was in hemorrhagic shock without verbal responsiveness, but his vital signs were normalized following infusion of Lactate Ringer's solution. The neuroradiological studies revealed multiple cerebral ischemic lesions without any vascular abnormality. He was diagnosed with speech apraxia, motor aphasia, and dysgraphia, due to multiple cerebral infarctions. As there was no obvious causative factor with regard to the occurrence of cerebral infarction in the patient, the hypoperfusion due to hemorrhagic shock, and the thromboembolic tendency due to Olanzapine, might have acted together to lead to the patient's cerebral ischemia.
  • Yoshiaki Shimada, Yuji Ueno, Yasutaka Tanaka, Ayami Okuzumi, Nobukazu Miyamoto, Kazuo Yamashiro, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    CEREBROVASCULAR DISEASES 35 (3) 282 - 290 1015-9770 2013 [Refereed][Not invited]
     
    Background: Mobile or ulcerated aortic plaques (MUAPs) on transesophageal echocardiography (TEE) can cause aortogenic brain embolism. Aortic arch calcification (AoAC) on chest X-ray represents systemic atherosclerosis. This study focused on AoAC on chest X-ray and its link with atheromatous aortic plaques (AAPs) on TEE in stroke patients. The aim of the present study was to assess the relationship between AoAC and AAPs in unexplained stroke patients. Methods: A total of 178 patients (mean age: 64 +/- 15 years; 115 males) with ischemic stroke who underwent TEE were enrolled. The patients were classified based on TEE findings: (1) AAPs <4 mm; (2) AAPs >= 4 mm, and (3) MUAPs. The extent of AoAC on chest X-ray was divided into 4 grades (0-3). Clinical characteristics including AoAC were compared among the 3 groups. Multiple logistic regression analysis was performed to identify the independent factors associated with MUAPs. An original diagnostic criterion was defined as a potential indicator of MUAPs in unexplained stroke patients. Results: 104 (58%) patients had AAPs <4 mm, 46 (26%) had AAPs >= 4 mm, and 28 (16%) had MUAPs. Older age (OR: 1.14; 95% CI: 1.06-1.24; p = 0.001), AoAC (OR: 2.35; 95% CI: 1.30-4.24; p = 0.005), and multiple infarctions in multiple vascular territories (VTs) demonstrated on diffusion-weighted imaging (DWI) (OR: 2.58; 95% CI: 1.35-4.92; p = 0.004) were independently associated with MUAPs. The CAM score was defined as consisting of the degree of AoAC (0-3 points), age (= 70 years: 1 point), and DWI findings (multiple infarctions in 1 VT: 1 point; 2 VTs: 2 points; more than 3 VTs: 3 points). The prevalence of MUAPs was substantially increased in patients with medium risk (CAM score 3-4, OR: 7.68; 95% CI: 2.89-20.44; p < 0.001) and high risk (CAM score 5-7, OR: 20.63; 95% CI: 5.12-83.06; p < 0.001). Conclusions: Older age, advanced AoAC, and multiple infarctions in multiple VTs are associated with aortogenic brain embolism. The CAM score can be useful for the diagnosis of aortogenic brain embolism. Copyright (C) 2013 S. Karger AG, Basel
  • Nishioka K, Tanaka R, Tsutsumi S, Shimura H, Oji Y, Saeki H, Yasumoto Y, Ito M, Hattori N, Urabe T
    Case reports in neurological medicine 2013 305670  2090-6668 2013 [Refereed][Not invited]
  • Kazuo Yamashiro, Ryota Tanaka, Kenya Nishioka, Yuji Ueno, Hideki Shimura, Yasuyuki Okuma, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 21 (8) 910.e1 - 5 1052-3057 2012/11 [Refereed][Not invited]
     
    Cerebral infarcts associated with hypercoagulability in malignant tumors have been well recognized. However, reports on cerebral infarcts in patients with a benign gynecologic tumor, such as adenomyosis, are extremely limited. We report the cases of 4 patients with adenomyosis and cerebral infarcts, all without obvious evidence of conventional causes of cerebral infarcts. Brain magnetic resonance imaging revealed multiple cerebral infarcts in both cortical and subcortical areas in all the patients and in different arterial territories in 3 patients. Two patients also had systemic embolism in the fingers or kidneys. One patient had thrombi in the brachiocephalic trunk and left subclavian artery. The levels of coagulation markers were elevated in the acute phase of cerebral infarcts. Although cerebral infarcts might be uncommon in adenomyosis patients, these patients might be potentially at risk of developing cerebral infarcts associated with hypercoagulability related to increased mucinous tumor marker levels, menstruation-related coagulopathy, or increased tissue factor expression levels. Additional study is required to determine the mechanism underlying the development of cerebral infarcts in adenomyosis; however, physicians need to pay particular attention to those who have hypercoagulability with adenomyosis among middle-aged women.
  • Ryota Tanaka, Yoshiaki Shimada, Hideki Shimura, Hideki Oizumi, Nobutaka Hattori, Shigeki Tanaka
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 21 (6) 509 - 511 1052-3057 2012/08 [Refereed][Not invited]
     
    Cerebral air embolism (CAE) is a rare neurologic complication that can occur in patients undergoing various medical procedures or trauma. CAE can sometimes result in death caused by severe brain edema. In spite of these implications, the pathophysiologic mechanisms and radiologic features of fatal CAE remain to be elucidated. In this case report, a patient with carcinomatous pleuritis lost consciousness and developed quadriplegia and had generalized seizures during intrathoracic lavage. Serial computed tomography (CT) revealed the presence of air in intracranial blood vessels following severe brain edema; these are typically observed on the CT scans of patients with fatal CAE. Diffusion-weighted imaging (DWI) of the brain obtained at 24 hours after the onset of CAE revealed scattered cortical gyriform high signal intensity often observed in CAE cases, whereas the apparent diffusion coefficient and T2-weighted imaging revealed diffuse hyperintensity in the subcortical deep white matter, indicating vasogenic edema. Our case showed predominant vasogenic edema rather than cortical ischemic changes in the subcortical deep white matter area. These findings indicate that diffuse subcortical vasogenic edema could be the main cause of mortality in fatal CAE.
  • Nobukazu Miyamoto, Yasutaka Tanaka, Yuji Ueno, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 21 (5) 363 - 368 1052-3057 2012/07 [Refereed][Not invited]
     
    Background: There is a general agreement that the stroke prevention benefit of antihypertensive agents is mainly based on their blood pressure lowering properties. The aim of this retrospective study was to assess the benefits of angiotensin type 1 receptor blockers (ARBs) used before the onset of ischemic stroke. Methods: Data were obtained between April 2007 and March 2009 using the discharge statistics of the neurologic service at Juntendo hospital. We retrieved the demographic and clinical characteristics of stroke patients and functional status upon discharge assessed by the modified Rankin Scale (mRS) and Barthel index (BI). Results: We enrolled 151 patients. Patients treated with ARBs were less often treated with a calcium channel blocker (CaB)/angiotensin-converting enzyme inhibitor (ACEI). They often had diabetes and showed better outcomes than the non-ARB group. Logistic regression analysis indicated that in patients with a mRS score of 0 to 2, older age (P < .007) was associated with severe outcomes, while the factor of pretreatment with ARB (P < .014) was associated with better outcomes. For patients with BI scores of more than 75, older age (P < .015) and large artery atherosclerosis (P < .035) were associated with severe outcomes. Logistic regression analysis identified the factor of pretreatment with ARB (P < .020) to be associated with better outcomes. Conclusions: ARB is widely used in patients with hypertension and cardiovascular disease, and our results further support this indication.
  • Hideki Shimura, Ryota Tanaka, Takao Urabe, Shigeki Tanaka, Nobutaka Hattori
    JOURNAL OF NEUROLOGY 259 (5) 879 - 881 0340-5354 2012/05 [Refereed][Not invited]
     
    In Parkinson's disease (PD), nonmotor symptoms manifest before motor symptoms. In this report, we present a remarkable case of a semiprofessional painter with PD whose painting style dramatically changed from abstract painting to realism before he developed motor, psychiatric, and autonomic nerve disorders. This case suggests that certain types of visual creativity may be impaired in the very early, presymptomatic stages of PD.
  • Ryota Tanaka, Tadaaki Kawanabe, Yoshiya Yamauchi, Hideki Shimura, Yasutaka Tanaka, Nobukazu Miyamoto, Yuji Ueno, Takao Urabe, Nobutaka Hattori, Shigeki Tanaka
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 21 (2) 155 - 157 1052-3057 2012/02 [Refereed][Not invited]
     
    Economy class stroke syndrome is a cardiovascular complication associated with long periods of travel, only a few cases have been reported after long drives, however. The patient, a 62-year-old professional driver, had driven a truck for 2 days with minimal rest. While driving, he noted left foot paresis and numbness, along with geographical disorientation. Magnetic resonance imaging of the brain revealed multiple cerebral embolisms in the bilateral cerebral hemisphere. The only complications representing a stroke risk in this patient were a patent foramen ovale and an anterior septal aneurysm, as detected by transesophageal echocardiography. The patient was diagnosed with paradoxical cerebral embolism following his long drive. This case report examines the paradoxical cerebral emboli documented in a patient following a long period of driving.
  • Tanaka Ryota, Ueno Yuji, Miyamoto Nobukazu, Yamashiro Kazuo, Tanaka Yasutaka, Shimura Hideki, Hattori Nobutaka, Urabe Takao
    CEREBROVASCULAR DISEASES 34 25  1015-9770 2012 [Refereed][Not invited]
  • Yamashiro Kazuo, Tanaka Ryota, Okuma Yasuyuki, Ueno Yuji, Tanaka Yasutaka, Hattori Nobutaka, Urabe Takao
    CEREBROVASCULAR DISEASES 34 43  1015-9770 2012 [Refereed][Not invited]
  • 急性期脳梗塞におけるPDEIIIA/IIIB受容体の経時的変化の検討
    三島 有美子, 田中 亮太, 宮元 伸和, 大石 英則, 新井 一, 服部 信孝, 卜部 貴夫
    脳循環代謝 (一社)日本脳循環代謝学会 23 (1) 134 - 134 0915-9401 2011/11
  • Ryota Tanaka, Kumi Sasaki-Ikesawa, Hideki Shimura, Kenya Nishioka, Nobutaka Hattori, Shigeki Tanaka
    Journal of Neurology 258 (11) 2083 - 2085 0340-5354 2011/11 [Refereed][Not invited]
  • Tadaaki Kawanabe, Ryota Tanaka, Yohei Sakaguchi, Osamu Akiyama, Hideki Shimura, Yukimasa Yasumoto, Masanori Ito, Nobutaka Hattori, Shigeki Tanaka
    NEUROLOGIA MEDICO-CHIRURGICA 51 (8) 582 - 585 0470-8105 2011/08 [Refereed][Not invited]
     
    A 57-year-old woman suffered sudden onset of thunderclap headache after exposure to phenylpropanolamine (PPA), and subsequently developed posterior reversible encephalopathy syndrome (PRES) complicated by occipital intracranial hemorrhage (ICH) with cerebral vasoconstriction. PPA is well known to be associated with ICH and vasoconstriction, but this case illustrates the association with PRES. The danger of exposure to PPA and subsequent adverse events is quite low at present, but we must consider the possibility of exposure to medical agents in patients with repeated severe headache who have no organic disorder.
  • Miyamoto Nobukazu, Tanaka Yasutaka, Ueno Yuji, Tanaka Ryota, Hattori Nobutaka, Urabe Takao
    STROKE 42 (3) E308  0039-2499 2011/03 [Refereed][Not invited]
  • 頭部MRIにて両側大脳辺縁系・基底核病変を伴い、脳生検によりgliomatosis cerebriと診断し得た73歳女性例
    平 健一郎, 川鍋 伊晃, 田中 亮太, 志村 秀樹, 田中 茂樹
    臨床神経学 (一社)日本神経学会 51 (1) 77 - 77 0009-918X 2011/01
  • Hideki Oizumi, Ryota Tanaka, Hideki Shimura, Kumi Sasaki, Hiroyuki Koike, Nobutaka Hattori, Shigeki Tanaka
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 20 (1) 79 - 81 1052-3057 2011/01 [Refereed][Not invited]
     
    Cardiac tumor is a rare, but clinically important source of cerebral embolism. We report a case of metastatic chondrosarcoma in the left atrium with multiple cerebral emboli. A computed tomography scan of the chest revealed a large mass in the left atrium and pulmonary vein. The patient underwent heart surgery to remove the metastatic chondrosarcoma in the left atrium, to prevent the formation of further systemic emboli and possible sudden death. The cardiac tumor resection was successful, and the patient was discharged from the hospital without any handicap. This is a rare case of metastatic cardiac tumor that was a source of emboli into the brain and was eradicated.
  • Y. Tanaka, R. Tanaka, M. Liu, N. Hattori, T. Urabe
    Neuroscience 171 (4) 1367 - 1376 0306-4522 2010/12 [Refereed][Not invited]
     
    Evidence suggests that neurogenesis occurs in the adult mammalian brain, and that various stimuli, for example, ischemia/hypoxia, enhance the generation of neural progenitor cells in the subventricular zone (SVZ) and their migration into the olfactory bulb. In a mouse stroke model, focal ischemia results in activation of neural progenitor cells followed by their migration into the ischemic lesion. The present study assessed the in vivo effects of cilostazol, a type 3 phosphodiesterase inhibitor known to activate the cAMP-responsive element binding protein (CREB) signaling, on neurogenesis in the ipsilateral SVZ and peri-infarct area in a mouse model of transient middle cerebral artery occlusion. Mice were divided into sham operated (n=12), vehicle- (n=18) and cilostazol-treated (n=18) groups. Sections stained for 5-bromodeoxyuridine (BrdU) and several neuronal and a glial markers were analyzed at post-ischemia days 1, 3 and 7. Cilostazol reduced brain ischemic volume (P< 0.05) and induced earlier recovery of neurologic deficit (P< 0.05). Cilostazol significantly increased the density of BrdU-positive newly-formed cells in the SVZ compared with the vehicle group without ischemia. Increased density of doublecortin (DCX)-positive and BrdU/DCX-double positive neural progenitor cells was noted in the ipsilateral SVZ and peri-infarct area at 3 and 7 days after focal ischemia compared with the vehicle group (P< 0.05). Cilostazol increased DCX-positive phosphorylated CREB (pCREB)-expressing neural progenitor cells, and increased brain derived neurotrophic factor (BDNF)-expressing astrocytes in the ipsilateral SVZ and peri-infarct area. The results indicated that cilostazol enhanced neural progenitor cell generation in both ipsilateral SVZ and peri-infarct area through CREB-mediated signaling pathway after focal ischemia. © 2010 IBRO.
  • Nobukazu Miyamoto, Yasutaka Tanaka, Yuji Ueno, Ryota Tanaka, Nobutaka Hattori, Takao Urabe
    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 19 (5) 393 - 397 1052-3057 2010/09 [Refereed][Not invited]
     
    Background: The aim of this study was to identify the relevant clinical backgrounds for anterior circulation territory infarctions (ACTI) and posterior circulation territory infarctions (PCTI). Methods: Data were obtained from April 1995 to May 2005 discharge statistics of the neurologic service in our hospital. The infarctions were divided into anterior circulation territory and posterior circulation territory by computed tomography and magnetic resonance imaging, and we examined clinical backgrounds for small vessel disease, large artery disease, and cardioembolism (CE). Results: A total of 1089 cases were ACTI and 430 were PCTI. Male/female ratio was 1.75 for ACTI and 2.67 for PCTI (P <.05). The mean age was 69.1 years for ACTI and 65.9 years for PCTI (P <.001). Multiple logistic regression analysis showed that significant contributed clinical backgrounds for small vessel disease were age and hyperlipidemia in ACTI. Those for large artery disease were male sex and history of cerebrovascular disease in PCTI. Those for CE were age and atrial fibrillation in ACTI; and diabetes, hypertension, hyperlipidemia, and smoking in PCTI. Those for all cerebral infarctions were age and atrial fibrillation in ACTI; and male sex, diabetes, and hypertension in PCTI. Conclusion: This study showed differences in clinical backgrounds between ACTI and PCTI. Moreover, PCTI were closely related to the conventional vascular risk factors even in CE.
  • Nobukazu Miyamoto, Ryota Tanaka, Hideki Shimura, Terubumi Watanabe, Hideo Mori, Masafumi Onodera, Hideki Mochizuki, Nobutaka Hattori, Takao Urabe
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 30 (2) 299 - 310 0271-678X 2010/02 [Refereed][Not invited]
     
    Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris water-maze task, immunohistochemistry for bromodeoxyuridine, as well as serial neuronal and glial markers were analyzed until 28 days after hypoperfusion. There was a significant increase in the number of oligodendrocyte progenitor cells in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. The oligodendrocyte progenitor cells subsequently underwent cell death and the number of oligodendrocytes decreased. In the rat model, treatment with a phosphodiesterase III inhibitor prevented cell death, markedly increased the mature oligodendrocytes, and promoted restoration of white matter and recovery of cognitive decline. These effects were cancelled by using protein kinase A/C inhibitor in the phosphodiesterase III inhibitor group. The results of our study indicate that the mammalian brain white matter tissue has the capacity to regenerate after ischemic injury. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 299-310; doi: 10.1038/jcbfm.2009.210; published online 14 October 2009
  • Yuji Ueno, Yoshiaki Shimada, Ryota Tanaka, Nobukazu Miyamoto, Yasutaka Tanaka, Nobutaka Hattori, Takao Urabe
    CEREBROVASCULAR DISEASES 30 (1) 15 - 22 1015-9770 2010 [Refereed][Not invited]
     
    Background: The purpose of the present study was to assess the contribution of embolic etiologies, patent foramen ovale (PFO) and atrial septal aneurysm (ASA), to cerebral white matter lesions (WMLs) in ischemic stroke patients. Methods: Patients with acute ischemic stroke who underwent transesophageal echocardiography were prospectively studied to investigate the relationships between the prevalence of PFO and ASA and the degree of WMLs. The patients were classified into four groups based on transesophageal echocardiography findings: (1) the PFO group (patients having PFO but not ASA); (2) the ASA group (patients having ASA but not PFO); (3) the PFO-ASA group (patients having both PFO and ASA), and (4) the non-septal abnormalities group (non-SA group, patients with neither PFO nor ASA). Based on MRI findings, the patients were also subdivided into grades 0, 1, 2, and 3 according to the Fazekas classification. Results: 115 patients (age, 69 +/- 11 years; 41 females) were enrolled; 49 (43%) were in the PFO group, 4 (3%) were in the ASA group, 23 (20%) were in the PFO-ASA group, and 39 (34%) were in the non-SA group. The PFO-ASA group had significantly increased WMLs compared to the other three groups (p = 0.004). On multiple logistic regression analysis, the coexistence of PFO and ASA was significantly associated with the degree of WMLs (odds ratio: 2.40; 95% confidence interval: 1.11-5.17; p = 0.026) when the PFO-ASA and non-SA groups were compared. Conclusions: The coexistence of PFO with ASA could play an important pathogenic role in WML severity. Copyright (c) 2010 S. Karger AG, Basel
  • パーキンソン病の精神症状及び運動症状に対するm-ECT著効例
    大泉 英樹, 佐々木 久実, 川鍋 伊晃, 田中 亮太, 志村 秀樹, 田中 茂樹
    臨床神経学 (一社)日本神経学会 49 (12) 1094 - 1094 0009-918X 2009/12
  • Nobukazu Miyamoto, Ryota Tanaka, Tatsuo Shimosawa, Yutaka Yatomi, Toshiro Fujita, Nobutaka Hattori, Takao Urabe
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 29 (11) 1769 - 1779 0271-678X 2009/11 [Refereed][Not invited]
     
    This study was designed to examine the effect of adrenomedullin deficiency on cerebral infarction and the relationship between adrenomedullin and cyclic AMP-protein kinase A pathway in regulating reactive oxygen species (ROS). Adrenomedullin heterozygous and wild-type mice were subjected to 60-mins focal ischemia. We used adrenomedullin heterozygous mice because adrenomedullin homozygotes die in utero. Infarct volume, neurologic deficit scores, and immunohistochemical analyses were evaluated at several time points after ischemia. The infarct volume and neurologic deficit scores were significantly worse in adrenomedullin heterozygous mice. Significant accumulation of inducible nitric oxide, oxidative DNA damage, and lipid peroxidation was noted after reperfusion in adrenomedullin heterozygous mice. Treatment of wild-type mice with H89, a protein kinase A inhibitor, resulted in increased infarct size, and worsening of neurologic deficit score and other parameters to levels comparable to those of adrenomedullin heterozygous mice. In contrast, cilostazol, which increases cyclic AMP, rescued neurologic deficit and ROS accumulation in adrenomedullin heterozygous mice. This study showed that adrenomedullin downregulation results in increase in ROS after transient focal ischemia in mice. The results also indicated that adrenomedullin has an important function against ischemic injury through the cyclic AMP-protein kinase A pathway. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1769-1779; doi:10.1038/jcbfm.2009.92; published online 1 July 2009
  • N. Miyamoto, R. Tanaka, N. Zhang, H. Shimura, M. Onodera, H. Mochizuki, N. Hattori, T. Urabe
    Neuroscience 162 (2) 525 - 536 0306-4522 2009/08 [Not refereed][Not invited]
     
    Various stimuli, such as ischemia/hypoxia enhance newborn cell survival in the subventricular zone and their migration tangentially in chains toward the olfactory bulb. The present study assessed the fate of newborn neurons from subventricular zone to olfactory bulb under conditions of chronic cerebral hypoperfusion, and examined the role of cAMP-responsive element binding protein signaling on the survival of these neurons by using cilostazol, a potent inhibitor of type III phosphodiesterase. Rats underwent bilateral common carotid artery ligation. They were divided into sham-operated (n=70), vehicle- (n=70), and type III phosphodiesterase inhibitor-treated (n=70) groups. Immunohistochemically-stained section for 5-bromodeoxyuridine and a series of neuronal and glial markers were analyzed at days 7, 14, 21 and 28 after hypoperfusion. The reduction of olfactory bulb size gradually progressed in the vehicle group (P< 0.05), but not in the sham-operated and type III phosphodiesterase inhibitor-treated group. The subventricular zone of the vehicle-treated rats contained significantly larger numbers of newborn neuroblasts after hypoperfusion, compared with sham-operated rats (P< 0.05), but significantly lower numbers in the rostral migratory stream and olfactory bulb (P< 0.05). Treatment of rats with type III phosphodiesterase inhibitor increased the number of neuroblasts and enhanced the survival and differentiation of cells (P< 0.05). Phosphorylated cAMP-responsive element binding protein within neuroblasts was markedly decreased in the subventricular zone, rostral migratory stream, and olfactory bulb of vehicle-treated rats (P< 0.05), but treatment with type III phosphodiesterase inhibitor resulted in recovery of this expression throughout hypoperfusion, leading to enhanced neurogenesis (P< 0.05). These effects were abrogated by protein kinase A and C inhibitor. Our results indicated that cAMP-responsive element binding protein signaling is a key mediator of neurogenesis after prolonged hypoperfusion and provide the basis for new regenerative therapies for ischemic brain injury. © 2009 IBRO.
  • Y. Ueno, N. Zhang, N. Miyamoto, R. Tanaka, N. Hattori, T. Urabe
    Neuroscience 162 (2) 317 - 327 0306-4522 2009/08 [Not refereed][Not invited]
     
    A multicenter randomized clinical trial demonstrated that acute ischemic stroke patients treated with edaravone, a scavenger of hydroxyl radicals, had significant functional improvement. We tested the hypothesis that edaravone has protective effects against white matter lesions (WML) and endothelial injury, using a rat chronic hypoperfusion model. Adult Wistar rats underwent ligation of bilateral common carotid artery (LBCCA) and were divided into the edaravone group (injected once only immediately after LBCCA [n=39, ED1] and injected on three consecutive days [n=39, ED3]), the vehicle group (n=39), and the sham group (n=15). Cerebral blood flow, Morris water maze performance, footprint test for locomotor function, immunohistochemical analyses and Western blot analysis were performed before and after LBCCA. The ED3 group upregulated endothelial nitric oxide synthase and attenuated Evans Blue extravasation at day 3 after LBCCA (P< 0.05). Edaravone markedly suppressed accumulation of 4-hydroxy-2-nonenal-modified protein and 8-hydroxy-deoxyguanosine (P< 0.01), and loss of oligodendrocytes (P< 0.05) in the cerebral white matter at days 3, 7, 14, 21 and 28 after LBCCA. These results were more evident in the ED3 group. Moreover, at day 21 after LBCCA, spatial memory but not motor function, and axonal damage were significantly improved by three-time treatment of edaravone (P< 0.05). Our results indicated that 3-day treatment with edaravone provides protection against WML through endothelial protection and free radical scavenging and suggested that edaravone is potentially useful for the treatment of cognitive impairment. © 2009 IBRO.
  • Kumi Sasaki, Hideki Shimura, Masako Itaya, Ryota Tanaka, Hideo Mori, Yoshikuni Mizuno, Kenneth S. Kosik, Shigeki Tanaka, Nobutaka Hattori
    FEBS Letters 583 (13) 2194 - 2200 0014-5793 2009/07 [Refereed][Not invited]
     
    Phosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies. Structured summary: MINT-7148349, MINT-7148361:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by pull-down (MI:0096). MINT-7148372, MINT-7148384:TAU (uniprotkb:P10636) physically interacts (MI:0914) with EAAT2 (uniprotkb:P43004) by anti bait coimmunoprecipitation (MI:0006). © 2009 Federation of European Biochemical Societies.
  • Kumi Sasaki, Hideki Shimura, Masako Itaya, Ryota Tanaka, Hideo Mori, Yoshikuni Mizuno, Kenneth S. Kosik, Shigeki Tanaka, Nobutaka Hattori
    FEBS LETTERS 583 (13) 2194 - 2200 1873-3468 2009/07 [Refereed][Not invited]
     
    Phosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies. Structured summary: MINT-7148349, MINT-7148361: TAU (uniprotkb: P10636) physically interacts (MI: 0914) with EAAT2 (uniprotkb: P43004) by pull-down (MI: 0096) MINT-7148372, MINT-7148384: TAU (uniprotkb: P10636) physically interacts (MI: 0914) with EAAT2 (uniprotkb: P43004) by anti bait coimmunoprecipitation (MI: 0006) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
  • 弱毒性麻疹風疹ワクチン接種後に抗神経細胞抗体陽性脳炎を発症した18歳男性例
    山内 芳也, 川鍋 伊晃, 田中 亮太, 志村 秀樹, 田中 茂樹
    臨床神経学 (一社)日本神経学会 49 (6) 384 - 384 0009-918X 2009/06
  • Takao Urabe, Hirotaka Watada, Yasuyuki Okuma, Ryota Tanaka, Yuji Ueno, Nobukazu Miyamoto, Yasutaka Tanaka, Nobutaka Hattori, Ryuzo Kawamori
    STROKE 40 (4) 1289 - 1295 0039-2499 2009/04 [Refereed][Not invited]
     
    Background and Purpose-The purpose was to assess the prevalence of disorders of glucose metabolism and insulin resistance in Japanese ischemic stroke patients with no history of diabetes by performing 75-gram oral glucose tolerance test (OGTT). Methods-We recruited 427 ischemic stroke patients (atherothrombotic infarction, n = 220; lacunar infarction, n = 125; cardioembolic infarction, n = 82). OGTT was used to evaluate disorders of glucose metabolism in stroke patients without previously known diabetes (n=113). We investigated the relationships among the prevalence of abnormal glucose metabolism, ischemic stroke subtypes, and the prevalence of insulin resistance using homeostasis model assessment for insulin resistance and immunoreactive insulin at 120 minutes after glucose loading (IRI(120)). Results-OGTT identified the presence of disorders of glucose metabolism in 62.8% of ischemic stroke patients without previously known diabetes, including diabetes (24.8%) and impaired glucose tolerance (lone impaired glucose tolerance and impaired fasting glucose plus impaired glucose tolerance, 34.5%). The prevalence of newly diagnosed diabetes and impaired glucose tolerance was the highest in the atherothrombotic infarction group (68.9%). The highest values of homeostasis model assessment for insulin resistance and immunoreactive insulin at 120 minutes after glucose loading were found in atherothrombotic infarction patients with abnormal glucose tolerance. Conclusions-In this study, a significantly large percentage of Japanese patients with ischemic stroke and no history of diabetes were found to have disorders of glucose metabolism by OGTT. Impaired glucose tolerance and insulin resistance could play an important pathogenic role in the development of atherothrombotic infarction. (Stroke. 2009;40:1289-1295.)
  • N. Zhang, N. Miyamoto, R. Tanaka, H. Mochizuki, N. Hattori, T. Urabe
    Neuroscience 158 (2) 665 - 672 0306-4522 2009/01 [Not refereed][Not invited]
     
    Pneumonia is a common complication with the highest attributable proportion of deaths in patients with stroke. Cilostazol is a potent type III phosphodiesterase inhibitor, approved as an anti-platelet aggregation agent. The present study was designed to determine the protective mechanism of cilostazol against post-stroke pneumonia using a rat chronic cerebral hypoperfusion model. Rats were subjected to bilateral common carotid artery ligation (LBCCA) and divided randomly into the vehicle group (n=72) and cilostazol group (n=72). Rats of each group were sacrificed at baseline and at days 14, 28 and 42 after LBCCA. Cilostazol significantly improved the swallowing reflex by shortening the latency to elicited swallowing and increasing the numbers of swallows (P< 0.05) at 14 days of hypoperfusion. It also decreased the numbers of bacterial colonies grown in cultures from homogenized lungs. Cilostazol markedly upregulated cyclic AMP responsive element binding protein (CREB) phosphorylation, increased tyrosine hydroxylase (TH) expression in the substantial nigra, and maintained dopamine (84.7±2.3 vs. 79.2±4.1% control P=0.0512) and substance P levels (86.6±7.9 vs. 73.9±6.5% control P< 0.05) in the striatum, compared with the vehicle group. Our results indicate that cilostazol improves the swallowing reflex by enhancing the expression of TH through the CREB phosphorylation signaling pathway, and suggest that cilostazol could be useful in preventing pneumonia in the chronic stage of stroke. © 2009 IBRO.
  • Sayaka Funabe, Ryota Tanaka, Takao Urabe, Seiji Kawasaki, Keiko Kobayashi, Nobutaka Hattori
    Clinical Neurology 49 (9) 571 - 575 0009-918X 2009 [Refereed][Not invited]
     
    Adult-onset type II citrullinemia (CTLN2) is a hereditary metabolic disorder characterized by highly elevated plasma citrulline and ammonia. Recent studies have identified the "citrin gene" (SLC25A13) as the causative gene for CTLN2. Various neurobehavioral symptoms seen in this disease, such as unconsciousness, disorientation, abnormal behavior, and epilepsy, are thought to be caused by encephalopathy mostly due to hyperammonemia. A 47-year-old woman presented with repeated unconsciousness and abnormal behavior. The high plasma anmonia level was not always associated with her neurobehavioral symptoms (unconsciousness, disorientation, abnormal behavior, and epilepsy), but paroxysmal EEG discharges were invariably associated with these symptoms. Her symptoms and abnormal EEG discharges were sometimes treated with diazepam simultaneously. Based on these findings, we considered that her symptoms were caused by nonconvulsive status epilepticus (NCSE). Until date, neurobehavioral symptoms of CTLN2 are considered to be caused by hyperammonemia or other metabolic factors. We suggest that encephalopathy of CTLN2 is caused not only by hyperammonemia but also by NCSE. Therefore, repeated EEG monitoring is recommended in the follow up of patients with CTLN2.
  • Nobukazu Miyamoto, Ning Zhang, Ryota Tanaka, Meizi Liu, Nobutaka Hattori, Takao Urabe
    NEUROSCIENCE RESEARCH 61 (3) 249 - 256 0168-0102 2008/07 [Refereed][Not invited]
     
    This study assessed the time course of angiotensin (Ang) II type 1 and type 2 receptor expression after 60 min of ischemia/reperfusion in mice treated with a nonhypotensive dose of valsartan, an angiotensin II type 1 receptor antagonist. We also examined the potential neuroprotective mechanisms mediated by angiotensin II type 2 receptor. Mice were divided into two groups (n = 64, each): valsartan-treated and control, vehicle groups. Infarct volume and neurological deficit scores were evaluated at several time points after ischemia, while immunohistochemical analyses were performed at serial time points after reperfusion. Valsartan significantly reduced the infarct volume and improved the neurological deficit scores (P < 0.05). Both angiotensin II type 1 and type 2 receptors were upregulated at 24 h and peaked at 72 h with type I receptors dominating in the ischemic penumbra of the vehicle group. Interestingly, angiotensin II type 2 receptor expression levels were significantly higher in the valsartan group than vehicle controls (P < 0.001). Moreover, angiotensin II type 2 receptor upregulated phosphosignal transducer and activator of transcription-3, and B-cell lymphoma protein-2 (P < 0.05). Our results indicated that angiotensin II type 2 receptor has antiapoptotic activity by activating the B-cell lymphoma protein-2 via the janus kinase/signal transducer and activator of transcription signaling pathway. (c) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
  • Ueno Yuji, Zhang Ning, Miyamoto Nobukazu, Tanaka Ryota, Tanaka Yasutaka, Hattori Nobutaka, Urabe Takao
    STROKE 39 (2) 667  0039-2499 2008/02 [Refereed][Not invited]
  • T Watanabe, N Zhang, MZ Liu, R Tanaka, Y Mizuno, T Urabe
    STROKE 37 (6) 1539 - 1545 0039-2499 2006/06 [Refereed][Not invited]
     
    Background and Purpose - White matter lesions contribute to cognitive impairment in poststroke patients. The present study was designed to assess the neuroprotective mechanisms of cilostazol, a potent inhibitor of type III phosphodiesterase, through signaling pathways that lead to activation of transcription factor cAMP-responsive element binding protein (CREB) phosphorylation using rat chronic cerebral hypoperfusion model. Methods - Rats underwent bilateral common carotid artery ligation. They were divided into the cilostazol group (n = 80) and the vehicle (control) group (n = 80). Performance at the Morris water maze task and immunohistochemistry for 4-hydroxy-2-nonenal (HNE), glutathione-S-transferase-pi (GST-pi), ionized calcium-binding adaptor molecule 1, phosphorylated CREB (p-CREB), Bcl-2, and cyclooxygenase-2 (COX-2) were analyzed at baseline and at 3, 7, 14, 21, and 28 days after hypoperfusion. Result - Cilostazol significantly improved spatial learning memory (6.8 +/- 2.3 seconds; P < 0.05) at 7 days after hypoperfusion. Cilostazol markedly suppressed accumulation of HNE-modified protein and loss of GST-pi-positive oligodendrocytes in the cerebral white matter during the early period after hypoperfusion (P < 0.05). Cilostazol upregulated p-CREB and Bcl-2 (P < 0.05), increased COX-2 expression, and reduced microglial activation in the early period of hypoperfusion. Conclusion - Our results indicate that cilostazol exerts a brain- protective effect through the CREB phosphorylation pathway leading to upregulation of Bcl-2 and COX-2 expressions and suggest that cilostazol is potentially useful for the treatment of cognitive impairment in poststroke patients.
  • M Komine-Kobayashi, N Zhang, MZ Liu, R Tanaka, H Hara, A Osaka, H Mochizuki, Y Mizuno, T Urabe
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 26 (3) 402 - 413 0271-678X 2006/03 [Refereed][Not invited]
     
    Cerebral ischemia induces the expression of several growth factors and cytokines, which protect neurons against ischemic insults. Recent studies showed that granulocyte colony-stimulating factor (G-CSF) has a neuroprotective effect through the signaling pathway for the antiapoptotic cascade. The current study was designed to assess the neuroprotective mechanisms of G-CSF in ischemia/reperfusion injury using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). Mice were subjected to ischemia/reperfusion and divided into two groups: those treated with G-CSF (G-CSF group) and vehicle (control group) (n=35 in each group). Immunohistochemistry and immunoblotting for antiapoptotic protein, nitrotyrosine, and inducible nitrate oxide synthase ( iNOS) were performed. G-CSF significantly reduced stroke volume (34%, P < 0.006). G-CSF upregulated Stat3, pStat3, and Bcl-2 (P < 0.05), and suppressed iNOS and nitrotyrosine expression. In EGFP chimera mice, G-CSF decreased the migration of Iba-1/EGFP-positive bone marrow-derived monocytes/macrophages and increased intrinsic microglia/macrophages at ischemic penumbra (P < 0.05), suggesting that bone marrow-derived monocytes/macrophages are not involved in GCSF-induced reduction of ischemic injury size. Our study indicated that G-CSF exerts a neuroprotective effect through the direct activation of antiapoptotic pathway, and suggested that G-CSF is important for expansion of the therapeutic time window in patients with cerebral ischemia.
  • Kazuo Yamashiro, Terubumi Watanabe, Ryota Tanaka, Miki Komine-Kobayashi, Yoshikuni Mizuno, Takao Urabe
    CEREBROVASCULAR DISEASES 22 (5-6) 432 - 438 1015-9770 2006 [Refereed][Not invited]
     
    Background: The purpose of this study was to assess the influence of clusters of risk factors on the incidence of echolucent carotid plaque in stroke patients. Methods: A retrospective analysis of 413 stroke patients who had undergone carotid ultrasonography was performed. High-resolution B-mode ultrasonography was used to evaluate the characteristics of carotid plaque. We investigated the relationships between the incidence of echolucent carotid plaque and clustering of risk factors (hypertension, diabetes mellitus and hyperlipidemia) and stroke subtypes and transient ischemic attack (TIA). Results: Echolucent plaques were present in 10.5% of patients free of risk factors, in 18.8% with a single risk factor (NS), in 27.7% with two risk factors (p < 0.01) and in 50.0% with three risk factors (p < 0.001), and were significantly more common in patients with multiple risk factors (odds ratio 1.79; 95% CI, 1.05-3.06; p = 0.045). Echolucent plaques were observed in 41.2% of patients with atherothrombotic infarction, in 17.6% with lacunar infarction, in 11.5% with cardioembolic stroke, and in 25.0% with TIA, and were significantly more common in patients with atherothrombotic infarction than in those with lacunar infarction or cardioembolic stroke (p < 0.001), or in those with TIA (p < 0.05). Conclusions: The clustering of risk factors increased the incidence of echolucent carotid plaque. Patients with multiple risk factors were at increased risk of echolucent plaque, and these had a significant relationship with atherothrombotic infarction compared with other stroke subtypes and TIA. Copyright (c) 2006 S. Karger AG, Basel.
  • N Zhang, M Komine-Kobayashi, R Tanaka, MZ Liu, Y Mizuno, T Urabe
    STROKE 36 (10) 2220 - 2225 0039-2499 2005/10 [Refereed][Not invited]
     
    Background and Purpose - Oxidative stress contributes to ischemia/reperfusion neuronal damage in a consecutive 2-phase pattern: an immediate direct cytotoxic effect and subsequent redox-mediated inflammatory insult. The present study was designed to assess the neuroprotective mechanisms of edaravone, a novel free radical scavenger, through antioxidative and anti-inflammatory pathways, from the early period to up to 7 days after ischemia/reperfusion in mice. Methods - Mice were subjected to 60-minute ischemia followed by reperfusion. They were divided into the edaravone group (n = 72; with different schedules for first administration) and the vehicle (control) group (n = 36). Infarct volume and neurological deficit scores were evaluated at several time points after ischemia. Immunohistochemical analysis for 4-hydroxy-2-nonenal (HNE), 8-hydroxy-deoxyguanosine (8- OHdG), ionized calcium-binding adapter molecule 1 (Iba-1), inducible NO synthase (iNOS), and nitrotyrosine were performed at 24 hours, 72 hours, or 7 days after reperfusion. Result - Edaravone, even when administrated 6 hours after onset of ischemia/ reperfusion, significantly reduced the infarct volume (68.10 +/- 6.24%; P < 0.05) and improved the neurological deficit scores (P < 0.05) at 24 hours after reperfusion. Edaravone markedly suppressed the accumulation of HNE-modified protein and 8- OHdG at the penumbra area during the early period after reperfusion (P < 0.05) and reduced microglial activation, iNOS expression, and nitrotyrosine formation at the late period. Conclusion - Our results indicated that edaravone exerts an early neuroprotective effect through the early free radicals scavenging pathway and a late anti-inflammatory effect and suggested that edaravone is important for expansion of the therapeutic time window in stroke patients.
  • R Tanaka, K Yamashiro, H Mochizuki, N Cho, M Onodera, Y Mizuno, T Urabe
    STROKE 35 (6) 1454 - 1459 0039-2499 2004/06 [Refereed][Not invited]
     
    Background and Purpose-Neurogenesis has been observed in the dentate gyrus of the adult hippocampus; however, the mechanisms involved in this process are still only partly understood. In this study, we visualized the proliferation, migration, and differentiation of neuronal progenitor cells in the dentate gyrus induced by ischemic stress using improved retroviral vector. Methods-Improved retroviral vector expressing enhanced green fluorescent protein (EGFP) as a transgene was injected into the dentate gyrus of adult Mongolian gerbils. After 48 hours, transient global ischemia (TGI) was induced by bilateral common carotid artery occlusion for 5 minutes using aneurysm clips. The morphological and immunohistological features of newly-generated cells in the dentate gyrus were analyzed at various times thereafter. Results-At 48 hours after viral injection, almost all EGFP-positive dividing cells were found in the subgranule layer (SGL). These cells proliferated and migrated to the granule cell layer (GCL), expressing the developing neuronal markers polysialic acid and doublecortin, and differentiated to neuronal nuclei-positive or calbindin-positive mature granule cells at 30 days after TGI or sham-operation. The number of GFP-positive cells in the GCL was significantly higher (P<0.05) in the ischemic animals at 30 days than in sham-operated gerbils. Conclusions-We saw neurogenesis in the adult dentate gyrus. Furthermore, we showed that ischemic stress promoted the proliferation and normal development of neurons at this site.
  • T Furuya, R Tanaka, T Urabe, J Hayakawa, M Migita, T Shimada, Y Mizuno, H Mochizuki
    NEUROREPORT 14 (4) 629 - 631 0959-4965 2003/03 [Refereed][Not invited]
     
    Chimeric mice stably reconstituted with bone marrow cells represent a good model for analysis of the mechanism of bone marrow cell infiltration in the brain. However, in preparing chimeric mice, irradiation of the recipient mice is necessary to kill their own bone marrow before transplantation, which induces gliosis and inflammatory response by activation of astrocytes and microglia in the brain. Here, we determined the most suitable dose of irradiation associated with the least brain damage before transplantation for reconstitution of chimeric mice, using FACS analysis. Our mouse model of 10 Gy body/5Gy head irradiation should be useful for investigating the mechanism(s) of microglial activation in various neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease.
  • R Tanaka, M Komine-Kobayashi, H Mochizuki, M Yamada, T Furuya, M Migita, T Shimada, Y Mizuno, T Urabe
    NEUROSCIENCE 117 (3) 531 - 539 0306-4522 2003 [Not refereed][Not invited]
     
    Brain ischemia induces a marked response of resident microglia and hematopoietic cells including monocytes/macrophages. The present study was designed to assess the distribution of microglia/macrophages in cerebral ischemia using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). At 24 h after middle cerebral artery occlusion (MCAO), many round-shaped EGFP-positive cells migrated to the ischemic core and peri-infarct area. At 48-72 h after MCAO, irregular round-or oval-shaped EGFP/ionized calcium-binding adapter molecule 1 (Iba 1)-positive cells increased in the transition zone, while many amoeboid-shaped or large-cell-body EGFP/Iba I-positive cells were increased in number in the innermost area of ischemia. At 7 days after MCAO, many process-bearing ramified shaped EGFP/Iba 1-positive cells were detected in the transition to the peri-infarct area, while phagocytic cells were distributed in the transition to the core area of the infarction. The distribution of these morphologically variable EGFP/Iba 1-positive cells was similar up to 14 days from MCAO. The present study directly showed the migration and distribution of bone marrow-derived monocytes/macrophages and the relationship between resident microglia and infiltrated hematogenous element in ischemic mouse brain. It is important to study the distribution of intrinsic and extrinsic microglia/macrophage in ischemic brain, since such findings may allow the design of appropriate gene-delivery system using exogenous microglia/macrophages to the ischemic brain area. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.
  • T Kobayashi, H Mori, Y Okuma, DW Dickson, N Cookson, Y Tsuboi, Y Motoi, R Tanaka, N Miyashita, M Anno, H Narabayashi, Y Mizuno
    JOURNAL OF NEUROLOGY 249 (6) 669 - 675 0340-5354 2002/06 [Refereed][Not invited]
     
    Association between clinical characteristics and types of the tau gene mutation has been observed in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). P301L mutation seldom causes parkinsonism as a leading symptom; instead it usually causes personality changes with aggressiveness and disinhibition. We experienced two patients of FTDP-17 from separate families (designated as patient I from family I and patient 2 from family 2). They had P301L mutation in common. However, their phenotypes were distinct from each other. Aggressive behaviors and disinhibition were the main symptoms in patient 1, whereas parkinsonism was the most prominent feature in patient 2. Their genotypes of the tau gene were different at three sites, i.e. in exon 6, in intron segment before exon 10, and in exon 13, though they do not bring amino acid change. Patient 1 had more prevalent C/C, C/C, and rare T/C respectively. Patient 2 had less prevalent T/T, A/A, and more prevalent T/T respectively. These findings suggest two things. Firstly, they do not share a common founder for P301L mutation. Secondly, either of the two less prevalent genotypes observed in patient 2 may be the factor to modify the phenotype of P301L mutation into those unusual clinical features with prominent parkinsonism. Accumulation of information as to phenotype-genotype association will settle this hypothesis.
  • T Urabe, R Tanaka, K Noda, Y Mizuno
    JOURNAL OF THROMBOSIS AND THROMBOLYSIS 13 (3) 155 - 160 0929-5305 2002/06 [Refereed][Not invited]
     
    Background: Argatroban is a selective thrombin inhibitor used for the treatment of atherothrombotic infarction. We evaluated its therapeutic effect using coagulation markers in 30 patients with cardioembolic infarction and 30 patients with atherothrombotic infarction during the immediate period after ischemic stroke. Methods: Argatroban therapy was initiated within 24 hours of the onset of stroke and the course was followed until 7 days after the start of treatment. Neurological evaluation was performed using the Hemispheric Stroke Scale (HSS). We also monitored the serial changes in activated partial thromboplastin time, prothrombin time, thrombin-antithrombin complex (TAT), and prothrombin fragments 1 + 2 (F1 + 2). Results: Both groups of patients showed significant improvement of HSS after 7 days of argatroban therapy ( p 0 05). Hemorrhagic infarction developed in 8 of patients with cardioembolic infarction, but no worsening of symptoms was noted in any of these patients. There was no significant prolongation of activated partial thromboplastin time or prothrombin time after 7 days, while levels of both TAT and F1 + 2 were significantly decreased from day 2. Conclusion: The decrease in TAT and F1 + 2 during argatroban therapy suggested improvement of hypercoagulability, which might explain how this drug prevents the recurrence of both ATI and CEI in the acute stage. Our findings also suggested that TAT and F1 + 2 might be useful indices for evaluation of argatroban efficacy.
  • R Tanaka, H Mochizuki, A Suzuki, N Katsube, R Ishitani, YU Mizuno, T Urabe
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 22 (3) 280 - 288 0271-678X 2002/03 [Refereed][Not invited]
     
    Glyceraldehyde- 3 -phosphate dehydrogenase (GAPDH), a glycolytic enzyme, has been recently identified to be involved in the initiation of neuronal apoptosis. To investigate the serial changes and cellular localization of GAPDH expression, and its role in ischemia/reperfusion-induced neuronal apoptosis, the authors analyzed immunohistochemically brain areas of rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Nuclear overexpression of GAPDH was noted in the ischemic core area after 2 hours of MCAO without reperfusion. During the subsequent reperfusion, nuclear accumulation of GAPDH in this area decreased in a time-dependent manner. However, cytoplasmic and nuclear GAPDH immunoreactivity was detected in neurons of the penumbra area of the parietal cortex, in rats subjected to 2-hour MCAO followed by 3-hour reperfusion. The increase of nuclear GAPDH immunoreactivity was persistently noted up to 48 hours of reperfusion, Whereas cytoplasmic immunoreactivity correlated inversely With the duration of reperfusion. Moreover. double staining revealed colocalization of nuclear GAPDH and TUNEL in the penumbra area, The authors' study demonstrated that overexpression of GAPDH and nuclear translocation occurred in both the ischemic core and penumbra area soon after focal ischemia. These processes could be viewed as an early marker of ischemia/reperfusion-induced apoptotic neuronal death. The results suggest that GAPDH may play a critical role in the progression and spread of ischemic neuronal damage.
  • H Mochizuki, H Hayakawa, M Migita, M Shibata, R Tanaka, A Suzuki, Y Shimo-Nakanishi, T Urabe, M Yamada, K Tamayose, T Shimada, M Miura, Y Mizuno
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 98 (19) 10918 - 10923 0027-8424 2001/09 [Refereed][Not invited]
     
    Adeno-associated virus (AAV) vector delivery of an Apaf-1-dominant negative inhibitor was tested for its antiapoptotic effect on degenerating nigrostriatal neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. The wildtype caspase recruitment domain of Apaf-1 was used as a dominant negative inhibitor of Apaf-1 (rAAV-Apaf-1-DN-EGFP). An AAV virus vector was used to deliver it into the striatum of C57 black mice, and the animals were treated with MPTP. The number of tyrosine hydroxylase-positive neurons in the substantia nigra was not changed on the rAAV-Apaf-1-DN-EGFP injected side compared with the noninjected side. We also examined the effect of a caspase 1 C285G mutant as a dominant negative inhibitor of caspase 1 (rAAV-caspase-1-DN-EGFP) in the same model. However, there was no difference in the number of tyrosine hydroxylase-positive neurons between the rAAV-caspase-1-DN-EGFP injected side and the noninjected side. These results indicate that delivery of Apaf-1-DN by using an AAV vector system can prevent nigrostriatal degeneration in MPTP mice, suggesting that it could be a promising therapeutic strategy for patients with Parkinson's disease. The major mechanism of dopaminergic neuronal death triggered by MPTP seems to be the mitochondrial apoptotic pathway.
  • Y Okuma, R Tanaka, K Fujishima, T Kobayashi, Y Mizuno
    EUROPEAN NEUROLOGY 45 (3) 193 - 194 0014-3022 2001 [Refereed][Not invited]

Books etc

  • 日本臨牀増刊号 パーキンソン病(第2版)
    田中亮太 (Joint work血管障害性パーキンソニズム)
    日本臨牀社 2018/03
  • 脳卒中病態学のススメ
    田中亮太 (Joint work局所脳虚血の病態~アポトーシスとネクローシス~)
    南山堂 2018/02
  • 特集 脳血管病変と脳疾患
    田中亮太 (Joint work慢性期脳血管障害の病態と治療)
    神経治療 2017
  • 神経内科 Clinical Qestion & Pearls 脳血管障害
    田中亮太 (Joint work脳卒中急性期での頭部CTおよびCT血管撮影の有用性、問題点について)
    中外医学社 2016
  • Modern Physician 5 神経内科検査のみかたー脳のイメージングを中心に
    田中亮太 (Joint work神経内科のトピックス 新しい経口抗凝固薬の使い方)
    2013
  • 脳卒中診療の最前線
    田中亮太 (Joint work再発予防の治療戦略:抗血栓療法と危険因子管理ポイント)
    順天堂医学 2009
  • 脳卒中クリニカルパス実例集
    田中亮太 (Joint work順天堂大学医学部附属順天堂医院におけるクリニカルパス)
    メディカルレビュー社 2006

MISC

  • Kosuke Matsuzono, Kohei Furuya, Takeshi Igarashi, Akie Horikiri, Takamasa Murosaki, Daekwan Chi, Yuichi Toyama, Kumiko Miura, Tadashi Ozawa, Takafumi Mashiko, Haruo Shimazaki, Reiji Koide, Ryota Tanaka, Shigeru Fujimoto  Journal of Thrombosis and Thrombolysis  49-  (4)  681  -684  2020/05  [Refereed][Not invited]
     
    Cerebral amyloid angiopathy-related inflammation is a syndrome of reversible encephalopathy with cerebral amyloid angiopathy, however the pathology is not well understood. We clear a part of the pathology through the first case of an 80-year-old man with cerebral amyloid angiopathy-related inflammation induced by relapsing polychondritis (RP) analysis. An 80-year-old man was diagnosed with RP by auricular cartilage biopsy. Almost no abnormality including intracranial microbleeding was detected by cranial magnetic resonance image (MRI) at diagnosis. However, he developed a headache and hallucination after five months. Seven-month cranial MRI showed novel, multiple, intracranial microbleeding, especially in the bilateral but asymmetry posterior, temporal, and parietal lobes. 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow in the bilateral posterior lobes. After treatment, both of his neurological symptoms and increased cerebral blood flow improved to mild. Photon emission computed tomography using Pittsburgh compound B (PiB) for evaluation of brain amyloidosis at 12 months after onset showed an amyloid deposit in the bilateral frontal lobes, but a lack of uptake corresponded to the RP lesions. Our case suggests that inflammation coupled with an amyloid deposit, induced the multiple intracranial bleeding, and resulted in the lack of PiB uptake. Findings from our case show that inflammation including excess blood flow coupled with an amyloid deposit synergistically facilitate intracranial bleeding.
  • 脳虚血におけるインクレチン(GLP-1)の役割と脳保護作用
    田中 亮太, 黒木 卓馬, 寺本 紳一郎, 山城 一雄, 宮元 伸和, 上野 祐司, 新井 一, 服部 信孝, 卜部 貴夫  臨床神経学  58-  (Suppl.)  S92  -S92  2018/12  [Not refereed][Not invited]
  • 急性脳血管症候群における悪性腫瘍合併症例の検討
    中島 翔, 山城 一雄, 上野 祐司, 田中 亮太, 宮元 伸和, 平 健一郎, 栗田 尚英, 服部 信孝  臨床神経学  58-  (Suppl.)  S281  -S281  2018/12  [Not refereed][Not invited]
  • 脳梗塞急性期におけるMAIT細胞制御と脳保護効果
    中島 翔, 田中 亮太, 山城 一雄, 千葉 麻子, 能登 大介, 志村 秀樹, 栗田 尚英, 平 健一郎, 宮元 伸和, 上野 祐司, 卜部 貴夫, 三宅 幸子, 服部 信孝  脳循環代謝  30-  (1)  137  -137  2018/10  [Not refereed][Not invited]
  • 腸内細菌異常による腸管透過性の亢進はLPSを介した急性期脳梗塞の組織障害進展に関与する
    栗田 尚英, 山城 一雄, 黒木 卓馬, 田中 亮太, 上野 祐司, 宮元 伸和, 卜部 貴夫, 山城 雄一郎, 服部 信孝  脳循環代謝  30-  (1)  138  -138  2018/10  [Not refereed][Not invited]
  • 【パーキンソン病(第2版)-基礎・臨床研究のアップデート-】 検査・診断 関連疾患 血管障害性パーキンソニズム
    田中 亮太, 服部 信孝  日本臨床  76-  (増刊4 パーキンソン病)  371  -374  2018/05  [Not refereed][Not invited]
  • 【パーキンソン病(第2版)-基礎・臨床研究のアップデート-】 治療 再生療法 骨髄間葉系幹細胞
    田中 亮太, 服部 信孝  日本臨床  76-  (増刊4 パーキンソン病)  540  -543  2018/05  [Not refereed][Not invited]
  • 上野 祐司, 卜部 貴夫, 田中 亮太, 服部 信孝  脳卒中  40-  (2)  100  -104  2018/03  [Not refereed][Not invited]
     
    潜因性脳梗塞の頻度は稀ではなく、その病態は多岐にわたる。潜因性脳梗塞はcryptogenic strokeとして提言され、心エコー検査を主体とした塞栓源診断で卵円孔開存や弓部大動脈プラークの発症機序への関与が明らかにされてきた。特に、経食道心エコー(transthoracic echocardiography:TEE)は半侵襲的な検査であるが、これらの塞栓源の検出には有用である。近年では、潜因性脳梗塞に対してembolic stroke of undetermined source(ESUS)という新たな概念が提唱された。ESUSは診断の標準化という立場から、半侵襲的な検査であるTEEによる塞栓源診断は必須ではない。しかし、逆説的にいえば、ESUSはTEEで診断される種々の塞栓源疾患が含まれる。我々は、ESUSの診断基準を満たしTEEを実施した症例を対象に、脳梗塞再発や心血管イベント発症の有無を後方視的に調査し、塞栓源疾患や臨床的特徴と予後の関連性を検討した。(著者抄録)
  • 新しい時代の抗凝固療法に注目した日本人心房細動患者のレジストリ RAFFINEレジストリにおける1年間の追跡調査(Registry of Japanese Patients with Atrial Fibrillation Focused on Anticoagulant Therapy in the New Era: 1-Year Follow-up of the RAFFINE Registry)
    宮内 克己, 宮崎 彩記子, 林 英守, 田中 亮太, 野尻 宗子, 諏訪 哲, 住吉 正孝, 中里 祐二, 卜部 貴夫, 服部 信孝, 代田 浩之  日本循環器学会学術集会抄録集  82回-  LBCS1  -3  2018/03  [Not refereed][Not invited]
  • 新しい時代の抗凝固療法に注目した日本人心房細動患者のレジストリ RAFFINEレジストリにおける1年間の追跡調査(Registry of Japanese Patients with Atrial Fibrillation Focused on Anticoagulant Therapy in the New Era: 1-Year Follow-up of the RAFFINE Registry)
    宮内 克己, 宮崎 彩記子, 林 英守, 田中 亮太, 野尻 宗子, 諏訪 哲, 住吉 正孝, 中里 祐二, 卜部 貴夫, 服部 信孝, 代田 浩之  日本循環器学会学術集会抄録集  82回-  LBCS1  -3  2018/03  [Not refereed][Not invited]
  • 脳梗塞後における軸索再生と機能回復
    上野 祐司, 田中 亮太, 卜部 貴夫, 服部 信孝  脳循環代謝  30-  (1)  65  -69  2018  [Not refereed][Not invited]
     
    脳梗塞後の軸索再生は、損傷後の組織再構築において重要な役割を担い、機能回復とも関連する。筆者は、ラット中大脳動脈閉塞モデルのperi-infarct areaにおいて、7日後の急性期に脱落した軸索や樹状突起は56日後の慢性期では再生していることを確認した。In vitroでは、虚血後軸索の再生にはphosphatase tensin homolog deleted on chromosome 10/Akt/Glycogen synthase kinase 3βシグナルが関わることを報告した。ラット慢性脳低灌流モデルでは、L-carnitine経口投与により脳白質において軸索再生とoligodendrocyteの再生によるミエリンの増強が生じ、慢性脳虚血ラットの認知機能障害が改善した。脳梗塞後の軸索再生、機能回復のメカニズムは多岐にわたり、今後軸索再生を目的とした脳梗塞新規治療薬の開発、実用化が期待される。(著者抄録)
  • パーキンソン病におけるcerebral microbleeds(CMBs)と認知症の関係について
    田中 亮太, 山城 一雄, 大山 彦光, 梅村 淳, 下 泰司, 服部 信孝  脳循環代謝  29-  (1)  161  -161  2017/11  [Not refereed][Not invited]
  • 腸内細菌叢の異常に伴う高LPS血症は急性期脳梗塞の組織障害進展に関与する
    栗田 尚英, 山城 一雄, 黒木 卓馬, 田中 亮太, 上野 祐司, 卜部 貴夫, 山城 雄一郎, 野本 康二, 松本 敬, 高橋 琢也, 辻 浩和, 朝原 崇, 服部 信孝  脳循環代謝  29-  (1)  222  -222  2017/11  [Not refereed][Not invited]
  • マウス慢性脳虚血モデル初期のBBB破綻に対する酸化ストレス抑制効果の検討
    宮元 伸和, Pham Loc-Duyen D, 眞木 崇州, 田中 亮太, 卜部 貴夫, Lo Eng H, 荒井 健, 服部 信孝  脳循環代謝  29-  (1)  218  -218  2017/11  [Not refereed][Not invited]
  • レベチラセタムによる白質病変後の認知機能改善効果
    稲葉 俊東, 島田 佳明, 志村 秀樹, 渡邊 雅男, 宮元 伸和, 田中 亮太, 卜部 貴夫  脳循環代謝  29-  (1)  223  -223  2017/11  [Not refereed][Not invited]
  • Wernicke脳症の発症にメトロニダゾールの関与が疑われた83歳女性例
    井関 賛, 石黒 雄太, 森 聡生, 波田野 琢, 田中 亮太, 服部 信孝  臨床神経学  57-  (4)  196  -196  2017/04  [Not refereed][Not invited]
  • 新時代の抗凝固療法に焦点を当てた日本人心房細動患者のレジストリ RAFFINE試験(Registry of Japanese Patients with Atrial Fibrillation Focused on Anticoagulant Therapy in New Era: The RAFFINE Study)
    宮崎 彩記子, 宮内 克己, 田渕 晴名, 林 英守, 野尻 宗子, 田中 亮太, 代田 浩之  日本循環器学会学術集会抄録集  81回-  PJ  -345  2017/03  [Not refereed][Not invited]
  • 田中 亮太, 服部 信孝  神経治療学  34-  (1)  24  -30  2017/01  [Not refereed][Not invited]
  • パーキンソン病における脳微小出血は血圧調節障害と関連する
    山城 一雄, 田中 亮太, 波田野 琢, 西岡 健弥, 服部 信孝  脳循環代謝  28-  (1)  199  -199  2016/11  [Not refereed][Not invited]
  • 脳血管障害の新たな病態 急性期脳梗塞における腸内細菌の関与
    栗田 尚英, 山城 一雄, 黒木 卓馬, 上野 祐司, 田中 亮太, 山城 雄一郎, 野本 康二, 高橋 琢也, 辻 裕和, 朝原 崇, 卜部 貴夫, 服部 信孝  脳循環代謝  28-  (1)  152  -152  2016/11  [Not refereed][Not invited]
  • 脳虚血後の軸索再生とSemaphorin 3Aの発現に関する検討
    平 健一郎, 上野 祐司, 黒木 卓馬, 島田 佳明, 山城 一雄, 田中 亮太, 卜部 貴夫, 服部 信孝  脳循環代謝  28-  (1)  238  -238  2016/11  [Not refereed][Not invited]
  • オリゴデンドロサイト新生に対するAKAP12の重要性
    宮元 伸和, 眞木 崇州, Seo Ji Hae, 田中 亮太, Gelman Irwin, Lo Eng H, 荒井 健, 卜部 貴夫  脳循環代謝  28-  (1)  196  -196  2016/11  [Not refereed][Not invited]
  • 2型糖尿病マウスにおける発症前運動習慣と脳保護効果
    中島 翔, 田中 亮太, 平 健一郎, 栗田 尚英, 宮元 伸和, 上野 祐司, 山城 一雄, 服部 信孝  脳循環代謝  28-  (1)  233  -233  2016/11  [Not refereed][Not invited]
  • T. Urabe, Y. Mitome-Mishima, N. Miyamoto, R. Tanaka, H. Oishi, H. Arai, N. Hattori  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  36-  503  -504  2016/06  [Not refereed][Not invited]
  • R. Tanaka, Y. Shimada, H. Shimura, K. Yamashiro, M. Koike, Y. Uchiyama, T. Urabe, N. Hattori  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  36-  269  -270  2016/06  [Not refereed][Not invited]
  • K. Yamashiro, T. Kuroki, R. Tanaka, Y. Ueno, T. Urabe, N. Hattori  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  36-  480  -481  2016/06  [Not refereed][Not invited]
  • Kazuo Yamashiro, Ryota Tanaka, Yasunobu Hoshino, Taku Hatano, Kenya Nishioka, Nobutaka Hattori  MOVEMENT DISORDERS  31-  S84  -S84  2016/03  [Not refereed][Not invited]
  • 虚血性脳卒中患者における腸内細菌叢(Gut microbiota in patients with ischemic stroke)
    山城 一雄, 田中 亮太, 上野 祐司, 卜部 貴夫, 山城 雄一郎, 野本 康二, 高橋 琢也, 辻 浩和, 朝原 崇, 服部 信孝  臨床神経学  55-  (Suppl.)  S219  -S219  2015/12  [Not refereed][Not invited]
  • 発症前糖尿病治療と脳梗塞急性期の予後について
    栗田 尚英, 田中 亮太, 山城 一雄, 上野 祐司, 島田 佳明, 黒木 卓馬, 平 健一郎, 卜部 貴夫, 服部 信孝  臨床神経学  55-  (Suppl.)  S244  -S244  2015/12  [Not refereed][Not invited]
  • 心房細動合併脳梗塞/TIA患者におけるNOAC登場前後の発症前抗血栓薬の服用状況の推移
    中島 翔, 田中 亮太, 山城 一雄, 栗田 尚英, 島田 佳明, 黒木 卓馬, 上野 祐司, 服部 信孝  臨床神経学  55-  (Suppl.)  S303  -S303  2015/12  [Not refereed][Not invited]
  • 自己免疫性自律神経節障害の臨床的多様性(Clinical heterogeneity of autoimmune autonomic ganglionopathy)
    小川 崇, 西岡 健弥, 須田 晃充, 林 徹生, 森 聡生, 中根 俊成, 樋口 理, 松尾 秀徳, 田中 亮太, 横山 和正, 卜部 貴夫, 服部 信孝  臨床神経学  55-  (Suppl.)  S450  -S450  2015/12  [Not refereed][Not invited]
  • 急性期脳梗塞における腸内細菌の関与
    栗田 尚英, 山城 一雄, 黒木 卓馬, 上野 祐司, 田中 亮太, 山城 雄一郎, 野本 康二, 高橋 琢也, 辻 浩和, 朝原 崇, 服部 信孝  脳循環代謝  27-  (1)  187  -187  2015/10  [Not refereed][Not invited]
  • 脳梗塞急性期における高血糖の影響とその治療介入の意義
    黒木 卓馬, 田中 亮太, 上野 祐司, 山城 一雄, 服部 信孝, 卜部 貴夫  脳循環代謝  27-  (1)  189  -189  2015/10  [Not refereed][Not invited]
  • 脳虚血後peri-infarct areaにおけるSemaphorin 3Aと神経再生に関する検討
    平 健一郎, 上野 祐司, 黒木 卓馬, 島田 佳明, 山城 一雄, 田中 亮太, 卜部 貴夫, 服部 信孝  脳循環代謝  27-  (1)  204  -204  2015/10  [Not refereed][Not invited]
  • tPA投与前に心腔内壁在血栓を有し、その後全身性塞栓症を発症した心原性脳塞栓症の30歳男性例
    小林 愛美, 田中 亮太, 林 徹生, 大山 彦光, 山城 一雄, 上野 祐司, 代田 浩之, 服部 信孝  臨床神経学  55-  (10)  766  -766  2015/10  [Not refereed][Not invited]
  • 発症前糖尿病治療と脳梗塞急性期の予後について
    田中 亮太, 栗田 尚英, 山城 一雄, 上野 祐司, 島田 佳明, 黒木 卓馬, 平 健一郎, 服部 信孝  神経治療学  32-  (5)  833  -833  2015/09  [Not refereed][Not invited]
  • Cryptogenic strokeにおけるCHADS2スコアとBNPの意義
    上野 祐司, 田中 亮太, 山城 一雄, 島田 佳明, 黒木 卓馬, 平 健一郎, 卜部 貴夫, 服部 信孝  Neurosonology  28-  (増刊)  111  -111  2015/06  [Not refereed][Not invited]
  • 2型糖尿病における虚血性白質障害進行のメカニズム オリゴ前駆細胞の動員とその生存
    田中 亮太, 矢富 裕子, 山城 一雄, 島田 佳明, 三島 有美子, 宮元 伸和, 上野 祐司, 卜部 貴夫, 服部 信孝  脳循環代謝  26-  (1)  211  -211  2014/11  [Not refereed][Not invited]
  • 高血糖と急性期脳梗塞の病態に関する研究
    黒木 卓馬, 上野 祐司, 山城 一雄, 田中 亮太, 卜部 貴夫  脳循環代謝  26-  (1)  222  -222  2014/11  [Not refereed][Not invited]
  • 腹部内臓脂肪測定を用いたメタボリックシンドロームと脳梗塞の急性期予後について
    西岡 健弥, 田中 亮太, 山城 一雄, 上野 祐司, 渡邉 雅男, 田中 康貴, 志村 秀樹, 服部 信孝, 卜部 貴夫  臨床神経学  53-  (12)  1600  -1600  2013/12  [Not refereed][Not invited]
  • 糖代謝異常を有する脳梗塞患者におけるピオグリタゾンの再発予防効果(J-SPIRIT研究)
    田中 亮太, 山城 一雄, 田中 康貴, 宮元 伸和, 上野 祐司, 渡邉 雅男, 大熊 泰之, 中村 真一郎, 古川 芳明, 綿田 裕孝, 河盛 隆造, 服部 信孝, 卜部 貴夫  臨床神経学  53-  (12)  1601  -1601  2013/12  [Not refereed][Not invited]
  • HSP27蛋白質の経静脈的投与はマウス脳梗塞モデルにおいて虚血巣を縮小する
    志村 秀樹, 寺本 紳一郎, 田中 亮太, 宮元 伸和, 島田 佳明, 新井 一, 卜部 貴夫, 服部 信孝  臨床神経学  53-  (12)  1477  -1477  2013/12  [Not refereed][Not invited]
  • 脳保護効果を有する合成HSP27の開発について
    島田 佳明, 志村 秀樹, 田中 亮太, 宮元 伸和, 寺本 紳一郎, 新井 一, 卜部 貴夫, 服部 信孝  臨床神経学  53-  (12)  1539  -1539  2013/12  [Not refereed][Not invited]
  • 脳保護効果を有する合成HSP27の開発について
    島田 佳明, 志村 秀樹, 田中 亮太, 寺本 紳一郎, 新井 一, 卜部 貴夫, 服部 信孝  脳循環代謝  25-  (1)  170  -170  2013/11  [Not refereed][Not invited]
  • 糖代謝異常を有する脳梗塞患者におけるピオグリタゾンの再発予防効果(J-SPIRIT試験)
    田中 亮太, 山城 一雄, 田中 康貴, 宮元 伸和, 上野 祐司, 渡邊 雅夫, 志村 秀樹, 大熊 泰之, 中村 真一郎, 古川 芳明, 綿田 裕孝, 河盛 隆造, 服部 信孝, 卜部 貴夫  神経治療学  30-  (5)  677  -677  2013/09  [Not refereed][Not invited]
  • Rosuvastatinの大動脈弓部粥状動脈硬化病変に対するプラーク安定効果
    上野 祐司, 渡邉 雅男, 田中 康貴, 山城 一雄, 田中 亮太, 志村 秀樹, 宮内 克己, 服部 信孝, 卜部 貴夫  神経治療学  30-  (5)  677  -677  2013/09  [Not refereed][Not invited]
  • 志村 秀樹, 田中 亮太, 寺本 紳一郎, 島田 佳明, 宮元 伸和, 新井 一, 卜部 貴夫, 服部 信孝  神経治療学  30-  (5)  641  -641  2013/09  [Not refereed][Not invited]
  • HIV感染症治療中に発症した脳底動脈狭窄を伴う脳幹梗塞の一例
    黒木 卓馬, 島田 佳明, 田中 康貴, 上野 祐司, 田中 亮太, 卜部 貴夫  分子脳血管病  12-  (1)  114  -115  2013/01  [Not refereed][Not invited]
  • 虚血脳組織におけるKv2.1チャンネルの発現
    三橋 立, 志村 秀樹, 田中 亮太, 荻野 郁子, 新井 一  順天堂医学  58-  (6)  544  -544  2012/12  [Not refereed][Not invited]
  • 糖代謝異常を有する脳梗塞症例の再発に関する検討
    黒木 卓馬, 田中 亮太, 山城 一雄, 上野 祐司, 宮元 伸和, 服部 信孝, 卜部 貴夫  臨床神経学  52-  (12)  1490  -1490  2012/12  [Not refereed][Not invited]
  • 糖尿病、耐糖能異常を有する脳梗塞症例の急性期予後に関する検討
    田中 亮太, 上野 祐司, 宮元 伸和, 山城 一雄, 田中 康貴, 服部 信孝, 卜部 貴夫  臨床神経学  52-  (12)  1490  -1490  2012/12  [Not refereed][Not invited]
  • 虚血性脳血管障害における大動脈弓部粥腫病変とLDL/HDL比との関連性
    奥住 文美, 上野 祐司, 島田 佳明, 田中 康貴, 宮元 伸和, 田中 亮太, 卜部 貴夫, 服部 信孝  臨床神経学  52-  (12)  1567  -1567  2012/12  [Not refereed][Not invited]
  • 脳卒中急性期におけるHMG-CoA還元酵素阻害剤投与による機能予後の比較検討
    島田 佳明, 田中 亮太, 田中 康貴, 宮元 伸和, 山城 一雄, 上野 祐司, 服部 信孝, 卜部 貴夫  臨床神経学  52-  (12)  1571  -1571  2012/12  [Not refereed][Not invited]
  • Cerebral microbleedsと血管性危険因子の罹患期間および抗血小板薬の内服期間との関連について
    山城 一雄, 田中 亮太, 田中 康貴, 島田 佳明, 上野 祐司, 卜部 貴夫, 大熊 泰之, 服部 信孝  臨床神経学  52-  (12)  1572  -1572  2012/12  [Not refereed][Not invited]
  • 急性期脳梗塞におけるPDEIIIの経時的変化の検討
    三島 有美子, 田中 亮太, 宮元 伸和, 大石 英則, 新井 一, 卜部 貴夫, 服部 信孝  順天堂医学  58-  (6)  544  -544  2012/12  [Not refereed][Not invited]
  • Dabigatran投与患者における安全性に関する調査
    山城 一雄, 田中 亮太, 田中 康貴, 島田 佳明, 黒木 卓馬, 上野 祐司, 卜部 貴夫, 服部 信孝  神経治療学  29-  (5)  634  -634  2012/09  [Not refereed][Not invited]
  • アンジオテンシンII1型受容体拮抗薬(ARB)の脳梗塞発症前内服は退院時転帰を改善する
    黒木 卓馬, 宮元 伸和, 田中 康貴, 上野 祐司, 田中 亮太, 卜部 貴夫, 服部 信孝  臨床神経学  51-  (12)  1246  -1246  2011/12  [Not refereed][Not invited]
  • 急性期脳塞栓症患者における大動脈弓部プラークの傾向についての検討
    田中 康貴, 島田 佳明, 上野 祐司, 宮元 伸和, 田中 亮太, 卜部 貴夫  Neurosonology  24-  (増刊)  64  -64  2011/06  [Not refereed][Not invited]
  • 中大脳動脈閉塞をきたした薬物中毒患者
    島田 佳明, 上野 祐司, 久保 紳一郎, 大垣 光太郎, 田中 亮太, 宮元 伸和, 田中 康貴, 卜部 貴夫, 服部 信孝  分子脳血管病  9-  (1)  130  -131  2010/01  [Not refereed][Not invited]
  • TANAKA RYOTA  Juntendo medical journal  55-  (4)  416  -425  2009/12
  • 脳白質病変とPFOとの関連性について
    島田 佳明, 上野 祐司, 田中 亮太, 平山 喬, 宮元 伸和, 田中 康貴, 卜部 貴夫, 服部 信孝  臨床神経学  49-  (12)  1043  -1043  2009/12  [Not refereed][Not invited]
  • 脳梗塞における新規糖代謝異常とインスリン抵抗性の関与
    卜部 貴夫, 大熊 泰之, 田中 亮太, 上野 祐司, 宮元 伸和, 田中 康貴, 服部 信孝  臨床神経学  49-  (12)  1122  -1122  2009/12  [Not refereed][Not invited]
  • N. Miyamoto, Y. Tanaka, K. Yatomi, Y. Ueno, R. Tanaka, N. Hattori, T. Urabe  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  29-  S262  -S263  2009/10  [Not refereed][Not invited]
  • Y. Tanaka, N. Miyamoto, R. Tanaka, N. Hattori, T. Urabe  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  29-  S547  -S547  2009/10  [Not refereed][Not invited]
  • T. Urabe, N. Zhang, N. Miyamoto, T. Watanabe, Y. Ueno, Y. Tanaka, R. Tanaka, N. Nattori  JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM  29-  S428  -S428  2009/10  [Not refereed][Not invited]
  • Nobukazu Miyamoto, Ryota Tanaka, Ning Zhang, Nobutaka Hattori, Takao Uralbe  STROKE  40-  (4)  E171  -E172  2009/04  [Not refereed][Not invited]
  • 一般健康成人における内臓脂肪蓄積と無症候性ラクナ梗塞、頸動脈プラークに関する検討
    田中 亮太, 宮元 伸和, 田中 康貴, 上野 祐司, 卜部 貴夫, 服部 信孝  臨床神経学  48-  (12)  1059  -1059  2008/12  [Not refereed][Not invited]
  • 慢性脳低灌流モデルの白質障害に対するL-カルニチンの治療効果
    上野 祐司, 張 寧, 宮元 伸和, 田中 亮太, 田中 康貴, 卜部 貴夫, 服部 信孝  臨床神経学  48-  (12)  1181  -1181  2008/12  [Not refereed][Not invited]
  • 慢性脳低灌流モデルでの白質障害に対するL-カルニチンの有効性
    上野 祐司, 張 寧, 宮元 伸和, 田中 亮太, 田中 康貴, 卜部 貴夫, 服部 信孝  脳循環代謝  20-  (1)  108  -108  2008/11  [Not refereed][Not invited]
  • 抗リン脂質抗体症候群に合併した奇異性脳塞栓症の一例
    田中 康貴, 宮元 伸和, 上野 祐司, 田中 亮太, 卜部 貴夫, 服部 信孝  分子脳血管病  7-  (4)  484  -485  2008/10  [Not refereed][Not invited]
  • 宮元 伸和, 田中 亮太, 上野 祐司, 卜部 貴夫, 服部 信孝  順天堂医学  54-  (3)  2008/09  [Not refereed][Not invited]
  • 張 寧, 宮元 伸和, 田中 亮太, 望月 秀樹, 服部 信孝, 卜部 貴夫  順天堂医学  54-  (3)  411  -412  2008/09  [Not refereed][Not invited]
  • Edaravoneの脳白質保護効果
    上野 祐司, 張 寧, 宮元 伸和, 田中 亮太, 田中 康貴, 服部 信孝, 卜部 貴夫  脳卒中  30-  (2)  297  -297  2008/03  [Not refereed][Not invited]
  • ラット慢性脳低灌流モデルにおける嚥下障害に対するシロスタゾールの治療効果
    卜部 貴夫, 張 寧, 田中 亮太, 上野 祐司, 宮元 伸和, 服部 信孝  脳卒中  30-  (2)  297  -297  2008/03  [Not refereed][Not invited]
  • Nobukazu Miyamoto, Ryota Tanaka, Ning Zhang, Nobutaka Hattori, Takao Urabe  STROKE  39-  (2)  684  -684  2008/02  [Not refereed][Not invited]
  • エダラボンのラット慢性脳虚血モデルにおける検討
    上野 祐司, 張 寧, 宮元 伸和, 田中 亮太, 服部 信孝, 卜部 貴夫  Pharma Medica  26-  (2)  178  -179  2008/02  [Not refereed][Not invited]
  • 当院での経食道心エコーによる脳梗塞患者の塞栓源診断
    上野 祐司, 田中 康隆, 宮元 伸和, 田中 亮太, 山城 一雄, 卜部 貴夫, 服部 信孝  臨床神経学  47-  (12)  1007  -1007  2007/12  [Not refereed][Not invited]
  • 慢性脳低灌流モデルにおけるドパミン合成に対するシロスタゾールの治療効果
    卜部 貴夫, 張 寧, 田中 亮太, 上野 祐司, 宮元 伸和, 服部 信孝  臨床神経学  47-  (12)  1122  -1122  2007/12  [Not refereed][Not invited]
  • 慢性脳虚血におけるOligodendrogenesisについての検討
    宮元 伸和, 田中 亮太, 上野 祐司, 張 寧, 服部 信孝, 卜部 貴夫  脳循環代謝  19-  (2)  102  -102  2007/10  [Not refereed][Not invited]
  • 慢性脳虚血モデルにおける神経前駆細胞とpCREBの活性化についての検討
    田中 亮太, 宮元 伸和, 張 寧, 上野 祐司, 卜部 貴夫, 服部 信孝  脳循環代謝  19-  (2)  114  -114  2007/10  [Not refereed][Not invited]
  • 宮元 伸和, 張 寧, 柳 美子, 田中 亮太, 卜部 貴夫, 服部 信孝  順天堂医学  53-  (3)  2007/09  [Not refereed][Not invited]
  • 脳卒中における糖代謝異常に対するインスリン抵抗性改善薬の治療効果の検討
    卜部 貴夫, 田中 亮太, 山城 一雄, 上野 祐司, 宮元 伸和, 田中 康貴, 服部 信孝  脳卒中  29-  (2)  247  -247  2007/03  [Not refereed][Not invited]
  • 慢性虚血における嗅球の細胞死と再生についての検討
    宮元 伸和, 田中 亮太, 張 寧, 上野 祐司, 卜部 貴夫  脳卒中  29-  (2)  429  -429  2007/03  [Not refereed][Not invited]
  • 脳梗塞急性期における経口抗血小板薬の選択
    卜部 貴夫, 田中 亮太, 山城 一雄, 上野 祐司, 宮元 伸和, 田中 康貴  脳循環代謝  18-  (3)  97  -97  2006/11  [Not refereed][Not invited]
  • K Yamashiro, T Watanabe, R Tanaka, M Komine-Kobayashi, T Urabe, Y Mizuno  JOURNAL OF THE NEUROLOGICAL SCIENCES  238-  S495  -S495  2005/11  [Not refereed][Not invited]
  • T Urabe, N Zhang, M Komine-Kobayashi, R Tanaka, MZ Liu, Y Mizuno  JOURNAL OF THE NEUROLOGICAL SCIENCES  238-  S448  -S449  2005/11  [Not refereed][Not invited]
  • A Suzuki, R Tanaka, H Mochizuki, R Ishitani, Y Mizuno, T Urabe  STROKE  35-  (6)  E251  -E251  2004/06  [Not refereed][Not invited]
  • K Yamashiro, R Tanaka, H Mochizuki, N Cho, M Onodera, Y Mizuno, T Urabe  STROKE  35-  (6)  E253  -E253  2004/06  [Not refereed][Not invited]
  • 田中 亮太, 卜部 貴夫, 山城 一雄, 張 寧, 望月 秀樹, 水野 美邦  順天堂医学  49-  (3)  379  -379  2003/09  [Not refereed][Not invited]
  • 小林 美紀, 卜部 貴夫, 田中 亮太, 張 寧, 望月 秀樹, 水野 美邦  順天堂医学  49-  (3)  379  -379  2003/09  [Not refereed][Not invited]
  • 田中 亮太, 小林 美紀, 卜部 貴夫, 望月 秀樹, 古谷 剛, 水野 美邦, 山田 正典, 右田 真, 島田 隆  順天堂医学  48-  (3)  419  -419  2002/12  [Not refereed][Not invited]
  • 急性期ラクナ梗塞における抗血栓療法の選択に関する検討
    上野 祐司, 卜部 貴夫, 田中 亮太, 水野 美邦  臨床神経学  41-  (11)  981  -981  2001/11  [Not refereed][Not invited]
  • 虚血性脳血管障害急性期における尿中8-Hydroxy 2'-deoxyguanosine(8-OHdG)の検討
    田中 亮太, 卜部 貴夫, 佐藤 栄人, 服部 信孝, 水野 美邦  臨床神経学  40-  (12)  1330  -1330  2000/12  [Not refereed][Not invited]
  • パーキンソン病(PD)における尿中8-OHdGの検討
    佐藤 栄人, 服部 信孝, 田中 亮太, 卜部 貴夫, 水野 美邦  臨床神経学  40-  (12)  1339  -1339  2000/12  [Not refereed][Not invited]
  • R Tanaka, T Kobayashi, Y Motoi, M Anno, Y Mizuno, H Mori  JOURNAL OF NEUROLOGY  247-  (9)  705  -707  2000/09  [Not refereed][Not invited]
  • パーキンソン病(PD)における尿中8-OHdGの検討
    佐藤 栄人, 服部 信孝, 田中 亮太, 卜部 貴夫, 水野 美邦  順天堂医学  46-  (1)  122  -122  2000/06  [Not refereed][Not invited]

Awards & Honors

  • 順天堂大学 順天堂大学医師会賞
     
    受賞者: 田中亮太

Research Grants & Projects

  • The role of MAIT cell and its feasibility for the treatment of human acute ischemic stroke
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2021/04 -2024/03 
    Author : 田中 亮太
  • 脳梗塞におけるMAIT細胞制御と新規治療法に関する研究
    日本学術振興会;科学研究費助成事業:基盤研究C
    Date (from‐to) : 2016/04 -2018/03 
    Author : 田中亮太
  • HSP27による新規脳保護療法の臨床実用化に向けた研究
    日本学術振興会;科学研究費助成事業:基盤研究C
    Date (from‐to) : 2013/04 -2016/03 
    Author : 田中亮太
  • HSP27蛋白質による新規脳梗塞治療法の開発
    日本学術振興会;科学研究費助成事業:挑戦的萌芽研究
    Date (from‐to) : 2012/04 -2013/03 
    Author : 志村秀樹
  • 慢性脳虚血におけるオリゴデンドロサイトの再生と機能回復の役割に関する研究
    日本学術振興会;科学研究費助成事業:若手研究B
    Date (from‐to) : 2007/04 -2008/03 
    Author : 田中亮太


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.