AnatomyⅠ

秦 龍二

hata ryuji

基本情報

所属
藤田医科大学 医学部 医学科 解剖学Ⅰ 教授
学位
医学博士(大阪大学)

J-GLOBAL ID
200901089408235951
researchmap会員ID
1000307116

研究キーワード

 3

論文

 15
  • Yahata N, Matsumoto Y, Omi M, Yamamoto N, Hata R
    Scientific reports 8(1) 4683 2018年3月  査読有り
  • Naoki Yahata, Yuji Matsumoto, Minoru Omi, Naoki Yamamoto, Ryuji Hata
    SCIENTIFIC REPORTS 7(1) 15557 2017年11月  査読有り
    Induced pluripotent stem cells (iPSCs) are suitable for studying mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations. Here, we generated iPSCs from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with the m.13513G>A mutation. The patient's dermal fibroblasts were reprogrammed, and we established two iPSC clones with and without mutant mtDNA. Furthermore, we tried to decrease mutant mtDNA level in iPSCs using transcription activator-like effector nucleases (TALENs). We originally engineered platinum TALENs, which were transported into mitochondria, recognized the mtDNA sequence including the m.13513 position, and preferentially cleaved G13513A mutant mtDNA (G13513A-mpTALEN). The m.13513G>A heteroplasmy level in MELAS-iPSCs was decreased in the short term by transduction of G13513A-mpTALEN. Our data demonstrate that this mtDNA-targeted nuclease would be a powerful tool for changing the heteroplasmy level in heteroplasmic iPSCs, which could contribute to elucidation of the pathological mechanisms of mitochondrial diseases caused by mtDNA mutations.
  • Kazuyoshi Sakai, Takao Senda, Ryuji Hata, Makoto Kuroda, Midori Hasegawa, Masao Kato, Masato Abe, Kazunori Kawaguchi, Shigeru Nakai, Yoshiyuki Hiki, Yukio Yuzawa, Nobuya Kitaguchi
    JOURNAL OF ALZHEIMERS DISEASE 51(4) 997-1002 2016年  査読有り
    As a proof of concept that removal of blood amyloid-beta (A beta) can reduce A beta deposition in the brains of patients with Alzheimer's disease, cortices of patients who had undergone hemodialysis (HD), which removes A beta from the blood, were histochemically analyzed; postmortem brain sections were stained with anti-A beta antibodies. Brains from patients who had undergone HD had significantly fewer senile plaques than those of patient who had not undergone HD. This significant difference was also confirmed by silver staining. Our findings suggest that removal of blood A beta by hemodialysis results in lower accumulation of A beta in the brain.
  • Masahiro Sakanaka, Pengxiang Zhu, Bo Zhang, Tong-Chun Wen, Fang Cao, Yong-Jie Ma, Keiichi Samukawa, Noriaki Mitsuda, Junya Tanaka, Makoto Kuramoto, Hidemitsu Uno, Ryuji Hatai
    JOURNAL OF NEUROTRAUMA 24(6) 1037-1054 2007年6月  査読有り
    Red ginseng root (Panax Ginseng CA Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of Red ginseng root is ginsenoside Rb-1 (gRb1). Previously, we showed that intravenous infusion of gRb1 ameliorated ischemic brain damage through upregulation of an anti-apoptotic factor, BCI-X-L and that topical application of gRb1 to burn wound lesion facilitated wound healing through upregulation of vascular endothelial growth factor (VEGF). In the present study, we produced dihydroginsenoside Rb1 (dgRb1), a stable chemical derivative of gRb1, and showed that intravenous infusion of dgRb1 improved spinal cord injury (SCI) as well as ischemic brain damage. As we expected, the effective dose of dgRb1 was ten times lower than that of gRb1. Intravenous infusion of dgRb1 at this effective dose did not affect brain temperature, blood pressure or cerebral blood flow, suggesting that dgRb1 rescued damaged neurons without affecting systemic parameters. In subsequent in vitro studies that focused on dgRb1-induced expression of gene products responsible for neuronal death or survival, we showed that dgRb1 could upregulate the expression of not only BCI-XL, but also a potent angiogenic and neurotrophic factor, VEGF. We also showed that dgRb1-induced expression of bcl-X-L and VEGF mRNA was HRE (hypoxia response element) and STRE (signal transducers and activators of transcription 5 (Stat5) response element) dependent, respectively.
  • Kensuke Fujita, Nobuhiro Hakuba, Ryuji Hata, Isao Morizane, Tadashi Yoshida, Masachika Shudou, Masahiro Sakanaka, Kiyofumi Gyo
    NEUROSCIENCE LETTERS 415(2) 113-117 2007年3月  査読有り
    The effects of transient cochlear ischemia on spiral ganglion cells (SGCs) were studied in Mongolian gerbils. Ischemic insult was induced by occluding the bilateral vertebral arteries of gerbils for 15 min. Seven days after ischemia, the percentage of SGCs decreased to 67.5% from the preischemic baseline in the basal turn. Evaluation with immunohistochemical staining showed TUNEL-positive reactions in the SGCs with fragmented nuclei. In addition, we investigated the protective effects of ginsenoside Rb1 (gRb1) against ischemic injury to SGCs. Seven days after ischemia, the auditory brainstem response threshold shift was significantly reduced and the percentage of SGCs decreased to 90.2% from the preischemic baseline in the basal turn in the gRb1-treated group. These findings suggest that Rb1 prevented hearing loss caused by ischemic injury to SGCs in Mongolian gerbils. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

MISC

 11
  • Taro Takagi, Tadashi Yoshida, Masahiro Okada, Ryuji Hata, Naohito Hato, Kiyofumi Gyo, Nobuhiro Hakuba
    NEUROREPORT 25(11) 807-813 2014年8月  査読有り
    Bone marrow mononuclear cells (BMMCs) are known to enhance recovery from ischemic insults by secreting angiogenic factors and inducing the expression of angiogenic factors from host tissues. Therefore, the transplantation of BMMCs is considered a potential approach to promoting the repair of ischemic damaged organs. Here, we investigated the influence of BMMCs on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries immediately before their entry into the transverse foramen of the cervical vertebra. An intravenous injection of BMMCs prevented ischemia-induced hair cell degeneration and ameliorated hearing impairment. A tracking study showed that BMMCs injected into the femoral vein were limited in the spiral artery of the cochlea, suggesting that, although transplanted BMMCs were retained within the spiral ganglion area of the cochlea, they were neither transdifferentiated into cochlear cells nor fused with the injured hair cells and supporting cells in the organ of Corti to restore their functions. We also showed that the protein level of neurotrophin-3 and glial cell line-derived neurotrophic factor in the organ of Corti was upregulated after treatment with BMMCs. These results suggested that BMMCs have therapeutic potential possibly through paracrine effects. Thus, we propose the use of BMMCs as a potential new therapeutic strategy for hearing loss. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
  • Takayuki Kondo, Masashi Asai, Kayoko Tsukita, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada, Keiko Imamura, Naohiro Egawa, Naoki Yahata, Keisuke Okita, Kazutoshi Takahashi, Isao Asaka, Takashi Aoi, Akira Watanabe, Kaori Watanabe, Chie Kadoya, Rie Nakano, Dai Watanabe, Kei Maruyama, Osamu Hori, Satoshi Hibino, Tominari Choshi, Tatsutoshi Nakahata, Hiroyuki Hioki, Takeshi Kaneko, Motoko Naitoh, Katsuhiro Yoshikawa, Satoko Yamawaki, Shigehiko Suzuki, Ryuji Hata, Shu-ichi Ueno, Tsuneyoshi Seki, Kazuhiro Kobayashi, Tatsushi Toda, Kazuma Murakami, Kazuhiro Irie, William L. Klein, Hiroshi Mori, Takashi Asada, Ryosuke Takahashi, Nobuhisa Iwata, Shinya Yamanaka, Haruhisa Inoue
    CELL STEM CELL 12(4) 487-496 2013年4月  査読有り
    Oligomeric forms of amyloid-beta peptide (A beta) are thought to play a pivotal role in the pathogenesis of Alzheimer's disease (AD), but the mechanism involved is still unclear. Here, we generated induced pluripotent stem cells (iPSCs) from familial and sporadic AD patients and differentiated them into neural cells. A beta oligomers accumulated in iPSC-derived neurons and astrocytes in cells from patients with a familial amyloid precursor protein (APP)-E693 Delta mutation and sporadic AD, leading to endoplasmic reticulum (ER) and oxidative stress. The accumulated A beta oligomers were not proteolytically resistant, and docosahexaenoic acid (DHA) treatment alleviated the stress responses in the AD neural cells. Differential manifestation of ER stress and DHA responsiveness may help explain variable clinical results obtained with the use of DHA treatment and suggests that DHA may in fact be effective for a subset of patients. It also illustrates how patient-specific iPSCs can be useful for analyzing AD pathogenesis and evaluating drugs.
  • Pengxiang Zhu, Ryuji Hata, Masahito Ogasawara, Fang Cao, Kenji Kameda, Kohei Yamauchi, Alfred H. Schinkel, Kazutaka Maeyama, Masahiro Sakanaka
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 32(10) 1897-1908 2012年10月  査読有り
    The organic cation transporters OCT1, 2, and 3 (SLC22A1-3) have been implicated in the elimination of biogenic amines such as histamine. Among them, OCT3 was identified as an uptake-2 transporter, responsible for clearance of histamine. Because increasing evidence suggests the involvement of histamine in cerebral ischemia, we investigated the effects of targeted disruption of organic cation transporter-3 (Oct3) on the severity of ischemic brain damage. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery (MCA) of homozygous Oct3-deficient mice and their wild-type (Wt) littermates. Although targeted disruption of Oct3 did not affect physiological parameters after MCA occlusion, this disruption significantly increased histamine content in the ischemic cortex and significantly reduced the infarct volume after cerebral ischemia. Furthermore, targeted disruption of Oct3 prevented the reduction of regulatory T-cell proportion after cerebral ischemia while this disruption did not affect Th1 and Th2 cells proportions after ischemia. Since repeated administration of L-histidine (a precursor of histamine) to Wt mice also showed the same effects, our observations suggested that OCT3 is the molecule responsible for clearance of ischemia-induced histamine in the brain and targeted disruption of Oct3 ameliorated ischemic brain damage through an increase in regulatory T cells. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1897-1908; doi:10.1038/jcbfm.2012.92; published online 27 June 2012
  • Naomi Sonobe, Ryuji Hata, Tomohisa Ishikawa, Kantaro Sonobe, Teruhisa Matsumoto, Yasutaka Toyota, Takaaki Mori, Ryuji Fukuhara, Kenjiro Komori, Shu-ichi Ueno, Satoshi Tanimukai, Manabu Ikeda
    INTERNATIONAL PSYCHOGERIATRICS 23(5) 772-779 2011年6月  査読有り
    Background: Memory impairment has been proposed as the most common early sign of Alzheimer's disease (AD). The aims of this work were to evaluate the risk of progression from mild memory impairment / no dementia (MMI/ND) to clinically diagnosable AD in a community-based prospective cohort and to establish the risk factors for progression from MMI/ND to AD in the elderly. Methods: Elderly subjects aged over 65 years were selected from the participants in the first Nakayama study. MMI/ND was defined as memory deficit on objective memory assessment, without dementia, impairment of general cognitive function, or disability in activities of daily living. A total of 104 MMI/ND subjects selected from 1242 community-dwellers were followed longitudinally for five years. Results: During the five-year follow-up, 11 (10.6%) subjects were diagnosed with AD, five (4.8%) with vascular dementia (VaD), and six (5.8%) with dementia of other etiology. Logistic regression analysis revealed that diabetes mellitus (DM) and a family history of dementia (within third-degree relatives) were positively associated with progression to AD, while no factor was significantly associated with progression to VaD or all types of dementia. Conclusions: DM and a family history of dementia were significant risk factors for progression from MMI/ND to clinically diagnosable AD in the elderly in a Japanese community.
  • Akihiko Taguchi, Pengxiang Zhu, Fang Cao, Akie Kikuchi-Taura, Yukiko Kasahara, David M. Stern, Toshihiro Soma, Tomohiro Matsuyama, Ryuji Hata
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 31(3) 855-867 2011年3月  査読有り
    Circulating bone marrow-derived immature cells, including endothelial progenitor cells, have been implicated in homeostasis of the microvasculature. Decreased levels of circulating endothelial progenitor cells, associated with aging and/or cardiovascular risk factors, correlate with poor clinical outcomes in a range of cardiovascular diseases. Herein, we transplanted bone marrow cells from young stroke-prone spontaneously hypertensive rats (SHR-SP) into aged SHR-SP, the latter not exposed to radiation or chemotherapy. Analysis of recipient peripheral blood 28 days after transplantation revealed that 5% of circulating blood cells were of donor origin. Cerebral infarction was induced on day 30 posttransplantation. Animals transplanted with bone marrow from young SHR-SP displayed an increase in density of the microvasculature in the periinfarction zone, reduced ischemic brain damage and improved neurologic function. In vitro analysis revealed enhanced activation of endothelial nitric oxide synthase and reduced activation p38 microtubule-associated protein (MAP) kinase, the latter associated with endothelial apoptosis, in cultures exposed to bone marrow-derived mononuclear cells from young animals versus cells from aged counterparts. Our findings indicate that partial rejuvenation of bone marrow from aged rats with cells from young animals enhances the response to ischemic injury, potentially at the level of endothelial/vascular activation, providing insight into a novel approach ameliorate chronic vascular diseases. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 855-867; doi:10.1038/jcbfm.2010.165; published online 22 September 2010

所属学協会

 1

教育内容・方法の工夫(授業評価等を含む)

 1
  • 件名
    講義資料に図表を多く取り入を学生の理解を深めるように、努めた。
    開始年月日
    2012
    概要
    授業評価にて平成25年度Teacher of the year賞を取得した。

その他教育活動上特記すべき事項

 1
  • 件名
    学生指導委員会委員