Updated on 2022/06/24

写真a

 
TAKAHASHI Ken
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
Profile

Ken is currently a Research Associate Professor at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences in Japan. He directs research groups focused on organ-on-a-chip, cardiovascular regenerative medicine, ischemia-reperfusion injury, and space medicine/biology. His interests also extend to physics simulation including finite element analysis and molecular dynamics. In these endeavors he has been privileged to act as a mentor for many international students. At the Harvard Medical School, Ken had developed a model of ischemia-reperfusion injury using the organ-on-a-chip technology.

Ken received his Ph.D. in Medicine from Nagoya University. He is a member of the Cellular Biology of the Heart Working Group in European Society of Cardiology, and a councilor of the Physiological Society of Japan. He serves on the Editorial Boards of journals including AIMS Biophysics, Mechanobiology, Hearts, and Biology and Medicine. He received several awards such as Award for Outstanding Research Achievement and Award for Outstanding Contribution to Education. Ken is also running a joint research about space medicine with PD AeroSpace, Ltd. He is a finisher of an Ironman Triathlon race.

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Degree

  • Ph. D. (Medicine) ( 2006.1   Nagoya University )

Research Interests

  • organ on a chip

  • Regenerative Medicine

  • Physiology

  • Mechanobiology

  • ischemia-reperfusion injury

  • Biophysics

  • Cardiovascular diseases

  • myocardial infarction

  • Space Medicine

  • Biomedical Engineering

Research Areas

  • Life Science / Biomaterials  / Biomedical Engineering

  • Life Science / Biomedical engineering  / Biomedical Engineering

  • Natural Science / Biophysics, chemical physics and soft matter physics  / Biophysics

  • Life Science / Physiology  / Space Medicine

  • Life Science / Physiology  / Physiology

  • Life Science / Clinical pharmacy  / Physiology

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Education

  • Nagoya University   医学系研究科   細胞情報医学専攻 神経性調節分野

    - 2006.1

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    Country: Japan

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Research History

  • Okayama University   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences   Research Associate Professor

    2020

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    Country:Japan

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  • Harvard University   Wyss Institute for Biologically Inspired Engineering   Visiting Scholar

    2018 - 2019

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  • Okayama University   Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Assistant Professor

    2010 - 2020

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    Country:Japan

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  • Nagoya University   Graduate School of Medicine   Assistant Professor

    2007 - 2010

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  • Nagoya University   Graduate School of Medicine   Research Assistant

    2006 - 2007

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  • Nagoya University   Graduate School of Medicine   Researcher

    2006

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  • The Japan Foundation for Aging and Health   Research Redident

    2003.6 - 2005.3

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Professional Memberships

  • Physiological Society of Japan

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  • Japanese Society for Medical and Biological Engineering

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  • European Society of Cardiology

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  • O-NECUS Interview Board

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  • The Japanese Society for Comparative Physiology and Biochemistry

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  • The Biophysical Society of Japan

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  • Japan Society of Aerospace and Environmental Medicine

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Committee Memberships

  • Hearts   Editorial Board  

    2020.1   

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    Committee type:Academic society

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  • Okayama University Clinical Research Review Expert Committee   Committee member  

    2019.12   

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    Committee type:Other

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  • AIMS Biophysics   Editorial Board  

    2013.9   

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    Committee type:Academic society

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  • The Physiological Society of Japan   Councilor  

    2011   

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    Committee type:Academic society

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  • Okayama University Department of Medicine   Member, Curriculum Committee  

    2021.4   

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    Committee type:Other

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  • The BME Society of Okayama Prefecture   Secretary General  

    2021.1   

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    Committee type:Academic society

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  • Pathophysiology   Editorial Board  

    2020.10   

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  • Heart and Mind (published by Wolters Kluwer)   Reviewer  

    2020.7   

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    Committee type:Academic society

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  • Biology and Medicine   Editorial Board  

    2020.1   

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  • Mechanobiology Journal   Associate Editor  

    2019.9   

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  • Asia Pacific Society for Biology and Medical Sciences   Academic Advisory Board  

    2018.10   

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    Committee type:Academic society

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  • European Society of Cardiology   Council, Basic Cardiovascular Science  

    2014   

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    Committee type:Academic society

    European Society of Cardiology

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  • Okayama University   Okayama University-North East China Universities Platform Student Exchange Program (O-NECUS)  

    2014 - 2018   

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    Committee type:Other

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  • International Symposium on Mechanobiology   Secretary General  

    2012.12 - 2014.5   

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Papers

  • Live imaging of nitric oxide release in vascular endothelial cells in response to mechanical stimuli on an organ chip (accepted) Reviewed International journal

    Takahashi K, Liu Y, Wang M, Liang Y, Naruse K

    European Heart Journal   43 ( Supplement_1 )   2022.10

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (international conference proceedings)  

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  • Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells Reviewed International journal

    Liu, Y, Wang, M, Liang, Y, Naruse, K, Takahashi, K

    European Heart Journal   42 ( Supplement_1 )   2021.10

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1093/eurheartj/ehab724.3190

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  • Meta-Analysis-Assisted Detection of Gravity-Sensitive Genes in Human Vascular Endothelial Cells Reviewed International journal

    Yin Liang, Mengxue Wang, Yun Liu, Chen Wang, Ken Takahashi, Keiji Naruse

    Frontiers in Cell and Developmental Biology   9   689662   2021.8

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Gravity affects the function and maintenance of organs, such as bones, muscles, and the heart. Several studies have used DNA microarrays to identify genes with altered expressions in response to gravity. However, it is technically challenging to combine the results from various microarray datasets because of their different data structures. We hypothesized that it is possible to identify common changes in gene expression from the DNA microarray datasets obtained under various conditions and methods. In this study, we grouped homologous genes to perform a meta-analysis of multiple vascular endothelial cell and skeletal muscle datasets. According to the t-distributed stochastic neighbor embedding (t-SNE) analysis, the changes in the gene expression pattern in vascular endothelial cells formed specific clusters. We also identified candidate genes in endothelial cells that responded to gravity. Further, we exposed human umbilical vein endothelial cells (HUVEC) to simulated microgravity (SMG) using a clinostat and measured the expression levels of the candidate genes. Gene expression analysis using qRT-PCR revealed that the expression level of the prostaglandin (PG) transporter gene <italic>SLCO2A1</italic> decreased in response to microgravity, consistent with the meta-analysis of microarray datasets. Furthermore, the direction of gravity affected the expression level of <italic>SLCO2A1</italic>, buttressing the finding that its expression was affected by gravity. These results suggest that a meta-analysis of DNA microarray datasets may help identify new target genes previously overlooked in individual microarray analyses.

    DOI: 10.3389/fcell.2021.689662

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  • Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress Reviewed

    Chen Wang, Jian Chen, Mengxue Wang, Keiji Naruse, Ken Takahashi

    Biochemical and Biophysical Research Communications   566   190 - 196   2021.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.bbrc.2021.03.077

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  • Optimization of the cardiac differentiation of human pluripotent stem cells International journal

    Liu Y, Wang M, Naruse K, Takahashi K

    The Journal of Physiological Sciences   71 ( S1 )   168   2021.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1186/s12576-021-00809-x

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    Other Link: https://link.springer.com/article/10.1186/s12576-021-00809-x/fulltext.html

  • Establishing an artificial heart model on a chip by using cardiomyocytes differentiated from human induced pluripotent stem cells International journal

    Wang M, Liu Y, Naruse K, Takahashi K

    The Journal of Physiological Sciences   71 ( S1 )   162   2021.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1186/s12576-021-00809-x

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    Other Link: https://link.springer.com/article/10.1186/s12576-021-00809-x/fulltext.html

  • Kidney-on-a-chip model using human renal proximal tubular epithelial cells and human umbilical vein endothelial cells International journal

    Yin Liang, Mengxue Wang, Keiji Naruse, Ken Takahashi

    The Journal of Physiological Sciences   71 ( S1 )   166   2021.8

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1186/s12576-021-00809-x

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    Other Link: https://link.springer.com/article/10.1186/s12576-021-00809-x/fulltext.html

  • Production of TRPM4 knockout cell line using rat cardiomyocyte H9c2 Reviewed International journal

    Chen Wang, Masakazu Maeda, Jian Chen, Mengxue Wang, Keiji Naruse, Ken Takahashi

    MethodsX   8   101404   2021.5

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.mex.2021.101404

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  • The Mechanisms of the Development of Atherosclerosis in Prediabetes Reviewed International journal

    Yin Liang, Mengxue Wang, Chen Wang, Yun Liu, Keiji Naruse, Ken Takahashi

    International Journal of Molecular Sciences   22 ( 8 )   4108 - 4108   2021.4

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Lifestyle changes, such as overeating and underexercising, can increase the risk of prediabetes. Diabetes is one of the leading causes of atherosclerosis, and recently it became clear that the pathophysiology of atherosclerosis progresses even before the onset of diabetic symptoms. In addition to changes in platelets and leukocytes in the hyperglycemic state and damage to vascular endothelial cells, extracellular vesicles and microRNAs were found to be involved in the progression of prediabetes atherosclerosis. This review discusses the cellular and molecular mechanisms of these processes, with an intention to enable a comprehensive understanding of the pathophysiology of prediabetes and atherosclerosis.

    DOI: 10.3390/ijms22084108

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  • Systematic Understanding of Pathophysiological Mechanisms of Oxidative Stress-Related Conditions—Diabetes Mellitus, Cardiovascular Diseases, and Ischemia–Reperfusion Injury Reviewed International journal

    Mengxue Wang, Yun Liu, Yin Liang, Keiji Naruse, Ken Takahashi

    Frontiers in Cardiovascular Medicine   8   2021.4

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Reactive oxygen species (ROS) plays a role in intracellular signal transduction under physiological conditions while also playing an essential role in diseases such as hypertension, ischemic heart disease, and diabetes, as well as in the process of aging. The influence of ROS has some influence on the frequent occurrence of cardiovascular diseases (CVD) in diabetic patients. In this review, we considered the pathophysiological relationship between diabetes and CVD from the perspective of ROS. In addition, considering organ damage due to ROS elevation during ischemia–reperfusion, we discussed heart and lung injuries. Furthermore, we have focused on the transient receptor potential (TRP) channels and L-type calcium channels as molecular targets for ROS in ROS-induced tissue damages and have discussed about the pathophysiological mechanism of the injury.

    DOI: 10.3389/fcvm.2021.649785

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  • Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia Reviewed International journal

    Yun Liu, Mengxue Wang, Yin Liang, Chen Wang, Keiji Naruse, Ken Takahashi

    International Journal of Molecular Sciences   22 ( 4 )   1729 - 1729   2021.2

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    A thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia–reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.

    DOI: 10.3390/ijms22041729

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  • Gravity sensing in plant and animal cells Reviewed International journal

    Ken Takahashi, Hideyuki Takahashi, Takuya Furuichi, Masatsugu Toyota, Makoto Furutani-Seiki, Takeshi Kobayashi, Haruko Watanabe-Takano, Masahiro Shinohara, Takuro Numaga-Tomita, Asako Sakaue-Sawano, Atsushi Miyawaki, Keiji Naruse

    npj Microgravity   7 ( 1 )   2   2021.2

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Gravity determines shape of body tissue and affects the functions of life, both in plants and animals. The cellular response to gravity is an active process of mechanotransduction. Although plants and animals share some common mechanisms of gravity sensing in spite of their distant phylogenetic origin, each species has its own mechanism to sense and respond to gravity. In this review, we discuss current understanding regarding the mechanisms of cellular gravity sensing in plants and animals. Understanding gravisensing also contributes to life on Earth, e.g., understanding osteoporosis and muscle atrophy. Furthermore, in the current age of Mars exploration, understanding cellular responses to gravity will form the foundation of living in space.

    DOI: 10.1038/s41526-020-00130-8

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    Other Link: http://www.nature.com/articles/s41526-020-00130-8

  • Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes Reviewed International journal

    Liu Y, Liang Y, Wang M, Wang C, Wei H, Naruse K, Takahashi K

    Journal of Visualized Experiments   159   e61104   2020.5

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3791/61104

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  • Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1. Reviewed International journal

    Takashi Ohtsuki, Akira Shinaoka, Kanae Kumagishi-Shinaoka, Keiichi Asano, Omer Faruk Hatipoglu, Junko Inagaki, Ken Takahashi, Toshitaka Oohashi, Keiichiro Nishida, Keiji Naruse, Satoshi Hirohata

    Experimental cell research   383 ( 2 )   111556 - 111556   2019.10

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    The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1β and tumor necrosis factor (TNF)-α-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.

    DOI: 10.1016/j.yexcr.2019.111556

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  • Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells Reviewed International journal

    Heng Wei, Chen Wang, Rui Guo, Ken Takahashi, Keiji Naruse

    Biochemical and Biophysical Research Communications   520 ( 3 )   600 - 605   2019.10

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2019.09.119

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  • L-type calcium channel modulates mechanosensitivity of the cardiomyocyte cell line H9c2. Reviewed International journal

    Ken Takahashi, Shogo Hayashi, Mari Miyajima, Marei Omori, Jing Wang, Keiko Kaihara, Masatoshi Morimatsu, Chen Wang, Jian Chen, Gentaro Iribe, Keiji Naruse, Masahiro Sokabe

    Cell Calcium   79   68 - 74   2019.5

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    The application of mechanical stimuli to cells often induce increases in intracellular calcium, affecting the regulation of a variety of cell functions. Although the mechanism of mechanotransduction-induced calcium increases has not been fully resolved, the involvement of mechanosensitive ion channels in the plasma membrane and the endoplasmic reticulum has been reported. Here, we demonstrate that voltage-gated L-type calcium channels play a critical role in the mechanosensitive calcium response in H9c2 rat cardiomyocytes. The intracellular calcium level in H9c2 cells increased in a reproducible dose-dependent manner in response to uniaxial stretching. The stretch-activated calcium response (SICR) completely disappeared in calcium-free medium, whereas thapsigargin and cyclopiazonic acid, inhibitors of sarcoendoplasmic reticulum calcium ATPase, partially reduced the SICR. These findings suggest that both calcium influx across the cell membrane and calcium release from the sarcoendoplasmic reticulum are involved in the SICR. Nifedipine, diltiazem, and verapamil, inhibitors of L-type calcium channels, reduced the SICR in a dose-dependent manner. Furthermore, small interfering RNA against the L-type calcium channel α1c subunit diminished the SICR dramatically. Nifedipine also diminished the mechanosensitivity of Langendorff-perfused rat heart. These results suggest that the SICR in H9c2 cardiomyocytes involves the activation of L-type calcium channels and subsequent calcium release from the sarcoendoplasmic reticulum.

    DOI: 10.1016/j.ceca.2019.02.008

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  • Human gingival fibroblast feeder cells promote maturation of induced pluripotent stem cells into cardiomyocytes Reviewed International journal

    Matsuda Y, Takahashi K, Kamioka H, Naruse K

    Biochem Biophys Res Commun   503 ( 3 )   1798 - 1804   2018.9

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.bbrc.2018.07.116

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  • Role of the TRPM4 Channel in Cardiovascular Physiology and Pathophysiology Invited Reviewed International journal

    Wang C, Naruse K, Takahashi K

    Cells   7 ( 6 )   62   2018.6

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/cells7060062

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  • TRPC3 participates in angiotensin II type 1 receptor-dependent stress-induced slow increase in intracellular Ca2+ concentration in mouse cardiomyocytes Reviewed

    Yohei Yamaguchi, Gentaro Iribe, Toshiyuki Kaneko, Ken Takahashi, Takuro Numaga-Tomita, Motohiro Nishida, Lutz Birnbaumer, Keiji Naruse

    Journal of Physiological Sciences   68 ( 2 )   153 - 164   2018.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Tokyo  

    When a cardiac muscle is held in a stretched position, its [Ca2+] transient increases slowly over several minutes in a process known as stress-induced slow increase in intracellular Ca2+ concentration ([Ca2+]i) (SSC). Transient receptor potential canonical (TRPC) 3 forms a non-selective cation channel regulated by the angiotensin II type 1 receptor (AT1R). In this study, we investigated the role of TRPC3 in the SSC. Isolated mouse ventricular myocytes were electrically stimulated and subjected to sustained stretch. An AT1R blocker, a phospholipase C inhibitor, and a TRPC3 inhibitor suppressed the SSC. These inhibitors also abolished the observed SSC-like slow increase in [Ca2+]i induced by angiotensin II, instead of stretch. Furthermore, the SSC was not observed in TRPC3 knockout mice. Simulation and immunohistochemical studies suggest that sarcolemmal TRPC3 is responsible for the SSC. These results indicate that sarcolemmal TRPC3, regulated by AT1R, causes the SSC.

    DOI: 10.1007/s12576-016-0519-3

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  • Effect of dimensional factor of cell culture on cardiac differentiation of human induced pluripotent stem cells International journal

    Tada C, Takahashi K, Naruse K

    The Journal of Physiological Sciences   68 ( S1 )   S73   2018.3

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s12576-018-0610-z

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    Other Link: http://link.springer.com/article/10.1007/s12576-018-0610-z/fulltext.html

  • TRPM4 channel is involved in cellular damage caused by simulated ischemia-reperfusion injury: study of human iPSC-derived cardiomyocytes International journal

    Wang C, Wei H, Naruse K, Takahashi K

    The Journal of Physiological Sciences   68 ( S1 )   S90   2018.3

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    Authorship:Last author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s12576-018-0610-z

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    Other Link: http://link.springer.com/article/10.1007/s12576-018-0610-z/fulltext.html

  • Cellular model of ischemic heart disease using human induced pluripotent stem cells International journal

    Wei H, Wang C, Takahashi K, Naruse K

    The Journal of Physiological Sciences   68 ( S1 )   S141   2018.3

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/s12576-018-0610-z

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    Other Link: http://link.springer.com/article/10.1007/s12576-018-0610-z/fulltext.html

  • Simultaneous mapping of multiple proteins in heart using matrix-assisted laser desorption/ionization imaging mass spectrometry Reviewed International journal

    Takahashi K, Naruse K

    European Heart Journal   38 ( Suppl 1 )   ehx501.45   2017.8

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (international conference proceedings)  

    DOI: 10.1093/eurheartj/ehx501.45

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  • Effect of Oxidative Stress on Cardiovascular System in Response to Gravity Invited Reviewed International journal

    Ken Takahashi, Hiroki Okumura, Rui Guo, Keiji Naruse

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 ( 7 )   E1426   2017.7

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Long-term habitation in space leads to physiological alterations such as bone loss, muscle atrophy, and cardiovascular deconditioning. Two predominant factors-namely space radiation and microgravity-have a crucial impact on oxidative stress in living organisms. Oxidative stress is also involved in the aging process, and plays important roles in the development of cardiovascular diseases including hypertension, left ventricular hypertrophy, and myocardial infarction. Here, we discuss the effects of space radiation, microgravity, and a combination of these two factors on oxidative stress. Future research may facilitate safer living in space by reducing the adverse effects of oxidative stress.

    DOI: 10.3390/ijms18071426

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  • Imaging of Cell Mechanics under High Gravity by Rotational Microscope International journal

    Masatoshi Morimatsu, Ken Takahashi, Ayano Fujita, Keiji Naruse

    BIOPHYSICAL JOURNAL   112 ( 3 )   271A - 272A   2017.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:CELL PRESS  

    DOI: 10.1016/j.bpj.2016.11.1471

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  • メカノストレスによる歯周組織リモデリング機構の解明

    藤田 彩乃, 森松 賢順, 高橋 賢, 高柴 正悟, 成瀬 恵治

    日本生理学雑誌   79 ( 1 )   44 - 44   2017.2

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    Language:Japanese   Publisher:(一社)日本生理学会  

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  • Optimization of manufacturing of planar patch clamp electrode

    Masuda S, Takahashi K, Naruse K

    The Journal of Physiological Sciences   67 ( S1 )   S154   2017.1

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (international conference proceedings)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/bf03405812

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    Other Link: http://link.springer.com/article/10.1007/BF03405812/fulltext.html

  • Effect of vascular endothelial cells on cardiac differentiation of iPS cells International journal

    Tada C, Takahashi K, Naruse K

    The Journal of Physiological Sciences   67 ( S1 )   S173   2017.1

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    DOI: 10.1007/bf03405812

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    Other Link: http://link.springer.com/article/10.1007/BF03405812/fulltext.html

  • Dynamic Remodeling of the Heart and Blood Vessels: Implications of Health and Disease Reviewed

    Ken Takahashi, Hulin Piao, Keiji Naruse

    Mechanobiology: Exploitation for Medical Benefit   175 - 189   2016.11

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Part of collection (book)   Publisher:wiley  

    Long-term exposure to pressure/volume overload of the heart due to hypertension or aortic stenosis induces pathological hypertrophy and remodeling, and eventually causes heart failure. This process accompanies pathological phenomena such as inflammation, apoptosis, and arrhythmia. On the other hand, physical exercise promotes physiological hypertrophy and remodeling of the heart, thereby enhancing cardiac performance. Interestingly, recent research has suggested that enhancement of heart function is a result not only of physiological hypertrophy of pre-existing cardiomyocytes, but also of cardiac stem cell activation and myocyte formation. Furthermore, exercise improves exacerbated cardiac function in heart diseases, including dilated cardiomyopathy (DCM) and myocardial infarction (MI). The suggested mechanisms of action of exercise remedies for these diseases include angiogenesis, cardiac resynchronization, and inhibition of inflammatory cytokines. However, excessive exercise can cause arrhythmogenic remodeling and sudden death. In this chapter, we elaborate the mechanisms of hypertrophy and remodeling under physiological and pathological conditions and discuss future directions for coping with pathological hypertrophy and remodeling.

    DOI: 10.1002/9781118966174.ch11

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  • Innovation of vascular engineering by mechanomedicine Reviewed

    Ken Takahashi, Keiji Naruse

    Vascular Engineering: New Prospects of Vascular Medicine and Biology with a Multidiscipline Approach   283 - 296   2016.1

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Part of collection (book)   Publisher:Springer Japan  

    This article describes how physical forces contribute to development, physiology, and pathology of vascular cells, focusing on endothelial cells and vascular smooth muscle cells. Based on these basic understandings of the mechanobiology, we discuss mechanomedicine, an application of the mechanobiology to medicine. Basic knowledge about cellular responses, such as cellular signal transduction pathway, gene expression, and cytoskeletal remodeling, to mechanical stimuli is important for understanding the pathology of vascular diseases including atherosclerosis. Introducing the knowledge of the vascular mechanobiology will not only contribute to the development of regenerative medicine using pluripotent stem cells but also provide a way to prevent diseases caused by thromboembolisms, such as myocardial and cerebral infarctions.

    DOI: 10.1007/978-4-431-54801-0_15

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  • Mechanosensitive ion channels Invited Reviewed

    Ken Takahashi, Yusuke Matsuda, Keiji Naruse

    AIMS Biophysics   3 ( 1 )   63 - 74   2016

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    Cell surface receptors are involved in numerous important biological processes including embryogenesis, tissue differentiation, and cellular homeostasis. Among them, mechanosensitive ion channels play an essential role in cellular functions of every cell including neurons, cardiomyocytes, and osteocytes. Here, we discuss types, roles, structures, and biophysical factors that affect the functions of mechanosensitive ion channels.

    DOI: 10.3934/biophy.2016.1.63

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  • Mechanical Stretch on Human Skin Equivalents Increases the Epidermal Thickness and Develops the Basement Membrane Reviewed

    Eijiro Tokuyama, Yusuke Nagai, Ken Takahashi, Yoshihiro Kimata, Keiji Naruse

    PLOS ONE   10 ( 11 )   e0141989   2015.11

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    All previous reports concerning the effect of stretch on cultured skin cells dealt with experiments on epidermal keratinocytes or dermal fibroblasts alone. The aim of the present study was to develop a system that allows application of stretch stimuli to human skin equivalents (HSEs), prepared by coculturing of these two types of cells. In addition, this study aimed to analyze the effect of a stretch on keratinization of the epidermis and on the basement membrane. HSEs were prepared in a gutter-like structure created with a porous silicone sheet in a silicone chamber. After 5-day stimulation with stretching, HSEs were analyzed histologically and immunohistologically. Stretch-stimulated HSEs had a thicker epidermal layer and expressed significantly greater levels of laminin 5 and collagen IV/VII in the basal layer compared with HSEs not subjected to stretch stimulation. Transmission electron microscopy revealed that the structure of the basement membrane was more developed in HSEs subjected to stretching. Our model may be relevant for extrapolating the effect of a stretch on the skin in a state similar to an in vivo system. This experimental system may be useful for analysis of the effects of stretch stimuli on skin properties and wound healing and is also expected to be applicable to an in vitro model of a hypertrophic scar in the future.

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  • Transient Receptor Potential Melastatin-4 Is Involved in Hypoxia-Reoxygenation Injury in the Cardiomyocytes Reviewed

    Hulin Piao, Ken Takahashi, Yohei Yamaguchi, Chen Wang, Kexiang Liu, Keiji Naruse

    PLOS ONE   10 ( 4 )   e0121703   2015.4

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    Ischemic heart disease still remains the most common cause of cardiac death. During ischemia-reperfusion (I/R), reactive oxygen species (ROS) are produced in excess in cardiac tissue, where they induce cell death. Our previous study showed that 9-phenanthrol (9-Phe), a specific inhibitor of the TRPM4 channel, preserves cardiac contractile function and protects the heart from I/R injury-related infarction in the excised rat heart. Accordingly, we hypothesized that TRPM4 channels are involved in the 9-Phe-mediated cardioprotection against ROS-induced injury. In rats, intravenous 9-Phe mitigated the development of myocardial infarction caused by the occlusion of the left anterior descending artery. Immunohistochemical analysis indicated that TRPM4 proteins are expressed in ventricular myocytes susceptible to I/R injury. Hydrogen peroxide (H2O2) is among the main ROS overproduced during I/R. In the cardiomyocyte cell line H9c2, pretreatment with 9-Phe prevented cell death induced by conditions mimicking I/R, namely 200 mu M H2O2 and hypoxia-reoxygenation. Gene silencing of TRPM4 preserved the viability of H9c2 cardiomyocytes exposed to 200 mu M H2O2. These results suggest that the cardioprotective effects of 9-Phe are mediated through the inhibition of the TRPM4 channels.

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  • Planar Patch Clamp System Capable of Recording Mechanosensitive Activity of Ion Channels

    Ken Takahashi, Keiji Naruse

    Biophysical Journal   108 ( 2 )   584A   2015.1

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  • Contractile function of reconstituted cardiac tissue is facilitated by mechanical stretch

    Sakai N, Takahashi K, Naruse K

    The Journal of Physiological Sciences   65 ( S1 )   S165   2015.1

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    DOI: 10.1007/bf03405845

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  • 9-Phenanthrol, a TRPM4 Inhibitor, protects rat hearts from ischemia-reperfusion injury

    Takahashi K, Piao H, Wang J, Naruse K

    J Physiol Sci   64 ( Suppl 1 )   S55   2014

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    DOI: 10.1007/BF03405834

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  • Coarse-grained molecular dynamics simulations of biomolecules Invited Reviewed

    Ken Takahashi, Takayuki Oda, Keiji Naruse

    AIMS Biophysics   1 ( 1 )   1 - 15   2014

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    Coarse-grained molecular dynamics (CGMD) simulations are increasingly being used to analyze the behaviors of biological systems. When appropriately used, CGMD can simulate the behaviors of molecular systems several hundred times faster than elaborate all-atom molecular dynamics simulations with similar accuracy. CGMD parameters for lipids, proteins, nucleic acids, and some artificial substances such as carbon nanotubes have been suggested. Here we briefly discuss a method for CGMD system configuration and the types of analysis and perturbations that can be performed with CGMD simulations. We also describe specific examples to show how CGMD simulations have been applied to various situations, and then describe experimental results that were used to validate the simulation results. CGMD simulations are applicable to resolving problems for various biological systems.

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  • 心臓・血管の組織工学と再生医療 Invited

    高橋賢, 成瀬恵治

    人工臓器   43 ( 3 )   206 - 209   2014

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    DOI: 10.11392/jsao.43.206

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  • Fabrication of a simple and compact patch clamp system for high-throughput recording

    Takahashi K, Fukasawa T, Kuniyasu K, Naruse K

    Trans JSMBE   51 ( Suppl )   R-149   2013.9

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    DOI: 10.11239/jsmbe.51.R-149

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  • Developing a small, inexpensive planar patch-clamp device

    Kuniyasu K, Fukasawa T, Takahashi K, Naruse K

    Trans JSMBE   51 ( Suppl )   R-14   2013.9

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    DOI: 10.11239/jsmbe.51.R-14

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  • 9-Phenanthrol, a TRPM4 Inhibitor, Protects Isolated Rat Hearts from Ischemia-Reperfusion Injury Reviewed

    Jing Wang, Ken Takahashi, Hulin Piao, Peng Qu, Keiji Naruse

    PLOS ONE   8 ( 7 )   e70587   2013.7

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    Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4. Isolated Langendorff-perfused rat hearts were pretreated with Krebs-Henseleit (K-H) solution (control), 9-phenanthrol, or 5-hydroxydecanoate (5-HD, a blocker of the ATP-sensitive potassium channel) and then subjected to global ischemia followed by reperfusion with the K-H solution. To evaluate the extent of heart damage, lactate dehydrogenase (LDH) activity in the effluent solution was measured, and the size of infarcted area of the heart was measured by 2,3,5-triphenyltetrazolium chloride staining. In controls, cardiac contractility decreased, and LDH activity and the infarcted area size increased. In contrast, in hearts pretreated with 9-phenanthrol, contractile function recovered dramatically, and the infarcted area size significantly decreased. The cardioprotective effects of 9-phenanthrol was not completely blocked by 5-HD. These findings show that 9-phenanthrol exerts a cardioprotective effect against ischemia in the isolated rat heart and suggest that its mechanism of action is largely independent of ATP-sensitive potassium channels.

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  • Mechanobiology in cardiac physiology and diseases Invited Reviewed

    Ken Takahashi, Yoshihide Kakimoto, Kensaku Toda, Keiji Naruse

    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE   17 ( 2 )   225 - 232   2013.2

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    Mechanosensitivity is essential for heart function just as for all other cells and organs in the body, and it is involved in both normal physiology and diseases processes of the cardiovascular system. In this review, we have outlined the relationship between mechanosensitivity and heart physiology, including the FrankStarling law of the heart and mechanoelectric feedback. We then focused on molecules involved in mechanotransduction, particularly mechanosensitive ion channels. We have also discussed the involvement of mechanosensitivity in heart diseases, such as arrhythmias, hypertrophy and ischaemic heart disease. Finally, mechanobiology in cardiogenesis is described with regard to regenerative medicine.

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  • Deformation and pressure propagation in deep tissue during mechanical painful pressure stimulation Reviewed

    Sara Finocchietti, Ken Takahashi, Kaoru Okada, Yasuharu Watanabe, Thomas Graven-Nielsen, Kazue Mizumura

    MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING   51 ( 1-2 )   113 - 122   2013.2

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    Manual palpation or pressure stimulation is often used for pain sensitivity assessment. The aim of the current study was to define a method for investigating the relation between pressure pain sensitivity and pressure propagation in soft or harder muscles. Three-dimensional finite-element computer-models were developed to simulate the tissue stress and strain distribution during pressure stimulation on the tibialis anterior and gastrocnemius muscles. Four cases were modelled representing females and males who were trained and untrained. The model geometry was based on MR images of the lower leg during pressure stimulation. Stress and strain were extracted from the models at pressure intensity levels equivalent to the pressure pain threshold. The principal strain peaked in the adipose tissue at 0.30 and 0.14 for stimulation on the gastrocnemius and tibialis anterior muscle, respectively. The principal strain in the muscle was higher for four models of the stimulation on the gastrocnemius muscle (0.22-0.30) compared with the four models of stimulation on the tibialis anterior muscle (0.11-0.14). Average pressure pain thresholds were significantly lower for the tibialis anterior compared with the gastrocnemius muscle (319 vs. 432 kPa) These data show different pressure propagation profiles in soft and hard muscle at the same pressure pain sensation level. This new approach is relevant as the clinical routine assesses all muscles equally. This results in a different exposure to pressure in relation to the muscle evaluated which may affect the outcome of the examination.

    DOI: 10.1007/s11517-012-0974-9

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  • Development of planar patch clamp system with stretchable resin

    Fukasawa T, Takahashi K, Naruse K

    J Physiol Sci   63 ( Suppl 1 )   S193   2013

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  • Molecular basis for mechanosensitivity of ion channels — coarse grained molecular dynamics simulation study

    Takahashi K, Toda K, Saruwatari K, Yokoyama T, Naruse K, Sokabe M

    The Journal of Physiological Sciences   2013

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  • Stretch-activated BK channel and heart function Invited Reviewed

    Ken Takahashi, Keiji Naruse

    PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY   110 ( 2-3 )   239 - 244   2012.10

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    The heart is an organ that is exposed to extreme dynamic mechanical stimuli. From birth till death, the heart indefinitely repeats periodic contraction and dilation, i.e., shortening and elongation of cardiomyocytes. Mechanical stretch elicits a change in heart rate and may cause arrhythmia if it is excessive. Thus, mechanosensitivity is crucial to heart function. The molecule that is substantially involved in mechanosensitivity is a stretch-activated ion channel. Among several ion channels believed to be activated by stretch in the heart, the stretch-activated K-Ca (SAKCA) channel, a member of the group of large conductance (Big Potassium, BK) channels, shows a mechanosensitive (MS) response to membrane stretch. As BK channels respond to voltage and intracellular calcium concentration with large conductance, they are considered to be involved in repolarization after depolarization. Some BK channels are known to be activated by stretch and are expressed in a number of cells, including human osteoblasts and guinea pig intestinal neurons. The SAKCA channel was found to be sensitive to stretch in the chick heart. Given that the cardiomyocyte is unremittingly exposed to contraction and dilation and that it generates action potential and its contractility is modulated by intracellular calcium concentration, the SAKCA channel, which is dependent voltage and calcium, may be involved in action potential generation. It was recently reported that a BK channel is involved in the modulation of heart rate in the mouse. Further studies regarding the role of MS BK channels, including SAKCA, in the modulation of heart rate and contractility are expected. (C) 2012 Elsevier Ltd. All rights reserved.

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  • Aberrant Calcium Handling Inhibits Functional Maturation and Excitation in Factors-based Human Cardiomyocytes Differentiation Reviewed

    Suguru Tarui, Junko Kobayashi, Masataka Hirata, Ken Takahashi, Gentaro Iribe, Keiji Naruse, Shingo Kasahara, Shunji Sano, Hidemasa Ou

    JOURNAL OF CARDIAC FAILURE   18 ( 10 )   S146 - S146   2012.10

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    DOI: 10.1016/j.cardfail.2012.08.116

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  • The potential role of L‐type voltage‐gated channels in rat cardiac mechanosensitivity

    Wang J, Takahashi K

    J Hypertens   30 ( 892 )   2012.9

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  • L-type voltage gated calcium channel is involved with the mechanosensitivity of the rat heart. The 89th Annual Meeting of the Physiological Society of Japan

    Takahashi K, Fujii S, Hattori M, Omori M, Naruse K, Sokabe M

    J Physiol Sci   62 ( Suppl 1 )   S50   2012

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  • Painful muscle stimulation preferentially activates emotion-related brain regions compared to painful skin stimulation Reviewed

    Ken Takahashi, Toru Taguchi, Satoshi Tanaka, Norihiro Sadato, Yunhai Qiu, Ryusuke Kakigi, Kazue Mizumura

    NEUROSCIENCE RESEARCH   70 ( 3 )   285 - 293   2011.7

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    Skin pain and muscle pain are categorically distinct from each other. While skin pain is a sharp, spatially localized sensation, muscle pain is a dull, poorly localized and more unpleasant one. We hypothesized that there are specific brain regions preferentially activated by muscle pain compared to skin pain. To test this hypothesis, brain responses were recorded from 13 normal male subjects in response to repeated painful electrical stimulation of the muscle and skin of the left leg, using 3-T magnetic resonance imaging scanner. The common brain regions that responded to painful stimulations of both skin and muscle were the thalamus, anterior cingulate cortex, bilateral insula, contralateral primary and secondary somatosensory cortices, and ipsilateral cerebellum. Brain regions specifically activated by muscle stimulation were the midbrain, bilateral amygdala, caudate, orbitofrontal cortex, hippocampus, parahippocampus and superior temporal pole, most of which are related to emotion. Regions except the midbrain showed contralateral preference. These results suggest that dull sensation, which is characteristic of muscular pain, is related with processing in these brain regions. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/j.neures.2011.04.001

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  • Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells Reviewed

    Etsushi Matsushita, Naoya Asai, Atsushi Enomoto, Yoshiyuki Kawamoto, Takuya Kato, Shinji Mii, Kengo Maeda, Rei Shibata, Shun Hattori, Minako Hagikura, Ken Takahashi, Masahiro Sokabe, Yoshiki Murakumo, Toyoaki Murohara, Masahide Takahashi

    MOLECULAR BIOLOGY OF THE CELL   22 ( 6 )   736 - 747   2011.3

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    Continued exposure of endothelial cells to mechanical/shear stress elicits the unfolded protein response (UPR), which enhances intracellular homeostasis and protect cells against the accumulation of improperly folded proteins. Cells commit to apoptosis when subjected to continuous and high endoplasmic reticulum (ER) stress unless homeostasis is maintained. It is unknown how endothelial cells differentially regulate the UPR. Here we show that a novel Girdin family protein, Gipie (78 kDa glucose-regulated protein [GRP78]-interacting protein induced by ER stress), is expressed in endothelial cells, where it interacts with GRP78, a master regulator of the UPR. Gipie stabilizes the interaction between GRP78 and the ER stress sensor inositol-requiring protein 1 (IRE1) at the ER, leading to the attenuation of IRE1-induced c-Jun N-terminal kinase (JNK) activation. Gipie expression is induced upon ER stress and suppresses the IRE1-JNK pathway and ER stress-induced apoptosis. Furthermore we found that Gipie expression is up-regulated in the neointima of carotid arteries after balloon injury in a rat model that is known to result in the induction of the UPR. Thus our data indicate that Gipie/GRP78 interaction controls the IRE1-JNK signaling pathway. That interaction appears to protect endothelial cells against ER stress-induced apoptosis in pathological contexts such as atherosclerosis and vascular endothelial dysfunction.

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  • Coarse grained molecular dynamics simulation of a mechanically gated ion channel

    Takahashi K, Sokabe M

    J Physiol Sci   61 ( Suppl 1 )   S125   2011

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  • ANTI-CHOLESTEROL DRUG STATINS AFFECT STRETCH-INDUCED CALCIUM INFLUX IN THE CARDIOMYOCYTE CELL LINE H9c2

    Ken Takahashi, Marei Omori, Masahiro Sokabe

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59 ( Suppl 1 )   170 - 170   2009

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  • STRETCH-ACTIVATED CALCIUM RESPONSE OF A RAT CARDIOMYOCYTE CELL LINE H9c2

    Ken Takahashi, Mari Hattori, Masahiro Sokabe

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59 ( Suppl 1 )   241 - 241   2009

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  • Alteration of peripheral afferent fibers in persistently inflamed rats hypersensitive to cold Reviewed

    Ken Takahashi, Jun Sato, Kazue Mizumura

    COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY   145 ( 3-4 )   422 - 422   2006.11

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    DOI: 10.1016/j.cbpb.2006.10.090

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  • 筋痛によって活動する脳部位の特定

    高橋 賢, 田口 徹, 田中 悟志, 定藤 規弘, 柿木 隆介, 水村 和枝

    J Physiol Sci   56 ( Suppl 1 )   S89   2006

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  • Influence of surface anesthesia on the pressure pain threshold measured with different-sized probes Reviewed

    K Takahashi, T Taguchi, K Itoh, K Okada, K Kawakita, K Mizumura

    SOMATOSENSORY AND MOTOR RESEARCH   22 ( 4 )   299 - 305   2005.12

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    Transcutaneous pressure with pressure probes of arbitrary diameters have been commonly used for measuring the threshold and magnitude of muscle pain, yet this procedure lacks scientific validation. To examine the valid probe dimensions, we conducted physiological experiments using 34 human subjects. Pin-prick pain, pressure pain threshold (PPT) to pressure probes of various diameters, heat pain threshold, and electrical pain threshold of deep tissues were measured before and after application of surface lidocaine anesthesia to the skin surface over the brachioradial muscle in a double-blinded manner. The anesthesia neither affected PPT with larger probes (diameters: 1.6 and 15 mm) nor increased electric pain threshold of deep structures, whereas it diminished pain count in pin-prick test and PPT with a 1.0 mm diameter probe, suggesting that mechanical pain thresholds measured with 1.6 and 15 mm probes reflect the pain threshold of deep tissues, possibly muscle. Pain thresholds to heat did not change after application of the anesthesia. These results suggest that larger pressure probes can give a better estimation of muscular pain threshold.

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  • [Adjuvant-induced arthritis]. Reviewed

    Takahashi K, Okumura S, Sato J, Mizumura K

    Nihon rinsho. Japanese journal of clinical medicine   63 Suppl 1   51 - 54   2005.1

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  • Artificially produced meteorological changes aggravate pain in adjuvant-induced arthritic rats Reviewed

    J Sato, M Aoyama, M Yamazaki, S Okumura, K Takahashi, M Funakubo, K Mizumura

    NEUROSCIENCE LETTERS   354 ( 1 )   46 - 49   2004.1

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    To examine the effects of change in meteorological parameters on pain-related behaviors in a simulated arthritic condition, rats with an injection of complete Freund's adjuvant into the tibio-tarsal joint were exposed to low barometric pressure (20 mmHg below the natural atmospheric pressure) and low ambient temperature (7 degreesC lower than 22 degreesC) in a climate-controlled room. When the arthritic rats were exposed to these environments, the already increased number of hindpaw withdrawals in response to noxious mechanical stimulation (hyperalgesia) was further increased, and a hindpaw withdrawal response to innocuous mechanical stimulation (allodynia) began to occur. Such exposures did not influence any of the pain-related behaviors of the control rats. These results show that lowering barometric pressure and ambient temperature within the range of natural environmental fluctuation intensify pain in arthritic rats. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

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  • Hyperalgesia to cold in persistently inflamed rats: Changes in C-fiber-receptor activities and cold-sensitive ion channel expression Reviewed

    K Mizumura, K Takahashi, J Sato

    HYPERALGESIA: MOLECULAR MECHANISMS AND CLINICAL IMPLICATIONS   30   71 - 86   2004

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  • Responses of C-fiber low threshold mechanoreceptors and nociceptors to cold were facilitated in rats persistently inflamed and hypersensitive to cold Reviewed

    K Takahashi, J Sato, K Mizumura

    NEUROSCIENCE RESEARCH   47 ( 4 )   409 - 419   2003.12

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    Cold allodynia is an annoying symptom in conditions of chronic inflammation such as rheumatoid arthritis. To examine whether primary afferent nerve activities are changed in association with hypersensitivity to cold, we recorded single nerve activities from the sural nerve in persistently inflamed rats in vivo. Inflammation was induced by an injection of complete Freund's adjuvant (CFA) solution into the tibio-tarsal joint. Inflamed rats showed an increased number of paw shakes to paw immersion in 25degreesC water (pre-inflammation: 1.15 +/- 0.58, 2-week inflammation: 4.70 +/- 1.15). We also recorded cutaneous C-fiber activities under pentobarbital anesthesia and studied their responses to thermal and mechanical stimuli. The response of C-low threshold mechanoreceptors to cooling (total discharges between 27 and 23degreesC) increased 1.8-fold (control group: 5.17 +/- 1.04 impulses, inflamed group: 9.38 +/- 1.47 impulses). In addition, the proportion of C-nociceptor units responding to cold down to 2degreesC was significantly greater in the inflamed group (9 out of 18 units; threshold: 10.0 +/- 2.6degreesC) than in the intact group (1 out of 14 units; threshold: 4.0degreesC). These results suggest that the facilitated responses of these primary afferents are associated with cold hypersensitivity in chronically inflamed conditions. (C) 2003 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.

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  • Increased C-fiber Activities to Cold in Adjuvant-monoarthritic Rats was not Accompanied by Increased Expression of TREK1 and CMR1 mRNAs Reviewed

    TAKAHASHI Ken, KATANOSAKA Kimiaki, KOZAKI Yasuko, SATO Jun, MIZUMURA Kazue

    Environmental medicine   46 ( 1/2 )   122   2002.12

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  • Adjuvant Monoarthritis at the Tibio-Tarsal Joint in the Rat: A Model for Investigating the Mechanism of Pain in Chronic Inflammation Reviewed

    Takahashi K, Sato J, Mizumura K

    Environmental Medicine   45 ( 2 )   86 - 89   2001

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Books

  • Dynamic remodeling of the heart and blood vessels: implications of health and disease

    Takahashi K, Piao H, Naruse K( Role: Joint author)

    Wiley-Blackwell  2016.12  ( ISBN:9781118966143

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    DOI: 10.1002/9781118966174.ch11

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  • Innovation of vascular engineering by mechano-medicine

    Takahashi K, Naruse K( Role: Joint author)

    Springer Japan  2016  ( ISBN:9784431548

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  • Guyton and Hall Textbook of Medical Physiology, 11th Edition

    Takahashi K, Sokabe M( Role: Joint translator)

    Elsevier Japan  2010  ( ISBN:9784860347246

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  • Hyperalgesia to cold in persistently inflamed rats: changes in C-fiber-receptor activities and cold-sensitive ion channel expression

    Mizumura K, Takahashi K, Sato J( Role: Joint author)

    IASP press  2004  ( ISBN:9780931092503

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  • 寒冷に対する痛覚過敏の末梢神経機構の解析

    水村 和枝, 佐藤 純, 高橋 賢( Role: Joint author)

    2003  ( ISBN:9784880037172

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MISC

  • Cellular mechanism of gravity sensing Invited

    Takahashi K, Sasanami M, Osada H, Naruse K

    69 ( 2 )   106 - 109   2018.4

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    DOI: 10.11477/mf.2425200769

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  • Application of mechanobiological engineering to regenerative and reproductive medicine Invited

    Takahashi K, Oh H, Iribe G, Matsuura K, Naruse K

    Trans JSMBE   55 ( 4PM-Abstract )   340   2017

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  • Response to mechanical stimulus and cardiovascular homeostasis Invited Reviewed

    Takahashi K, Naruse K

    Clinical Calcium   26 ( 12 )   1671 - 1676   2016.11

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  • 力学刺激に応答する循環器系の恒常性 Invited

    高橋賢, 成瀬恵治

    Clinical Calcium   26 ( 12 )   21 - 26   2016

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  • 書評「メカノバイオロジー」 Invited

    高橋賢

    生物物理   56 ( 1 )   54 - 54   2016

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  • Mechanosensor Invited

    Takahashi K

    128 ( 1 )   61 - 62   2016

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.4044/joma.128.61

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  • iPS治療とメカニカルストレス Invited Reviewed

    高橋賢, 成瀬恵治

    ファルマシア   51 ( 11 )   1038 - 1041   2015

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  • 筋肉の痛みの脳イメージング

    高橋 賢

    ペインクリニック   34 ( 12 )   1613 - 1619   2013

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  • Brain imaging of muscle pain

    Ken Takahashi

    Pain Clinic   34 ( 12 )   1613 - 1619   2013

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  • Factors-based Human Cardiomyocytes Differentiation Exhibits Defective Maturation and Excitation Through Aberrant Calcium Handling Proteins

    Suguru Tarui, Junko Kobayashi, Masataka Hirata, Ken Takahashi, Gentaro Iribe, Keiji Naruse, Shingo Kasahara, Shunji Sano, Hidemasa Oh

    CIRCULATION   126 ( 21 )   2012.11

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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  • Patient-specific Induced Pluripotent Stem Cells For Modeling Hypoplastic Left Heart Syndrome

    Junko Kobayashi, Masashi Yoshida, Suguru Tarui, Masataka Hirata, Ken Takahashi, Shingo Kasahara, Keiji Naruse, Hiroshi Ito, Shunji Sano, Hidemasa Oh

    CIRCULATION   126 ( 21 )   2012.11

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    Web of Science

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  • 細胞伸展培養

    高橋 賢, 成瀬 恵治

    Surgery Frontier   18 ( 2 )   59 - 63   2011

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  • 筋肉痛に応ずる脳部位

    高橋 賢, 水村 和枝

    神経内科   67 ( 5 )   404 - 408   2007

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  • Kチャネルの比較生物学 Invited

    高橋 賢, 曽我部 正博

    生体の科学   57 ( 5 )   472 - 473   2006.12

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.11477/mf.2425100317

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  • 経皮的圧刺激によって筋肉内に生じる応力の3次元有限要素解析 Invited

    高橋 賢, 水村 和枝

    名古屋大学情報連携基盤センターニュース   5 ( 1 )   13 - 15   2006.2

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  • Brain regions that distinguish muscle pain from skin pain

    Takahashi Ken, Taguchi Toru, Tanaka Satoshi, Sadato Norihiro, Kakigi Ryusuke, Mizumura Kazue

    Proceedings of Annual Meeting of the Physiological Society of Japan   2006 ( 0 )   89 - 89   2006

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    Publisher:PHYSIOLOGICAL SOCIETY OF JAPAN  

    CiNii Article

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  • アジュバント関節炎

    高橋 賢, 奥村 聡, 佐藤 純, 水村 和枝

    日本臨牀   63 ( Suppl 1 )   51 - 54   2005

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  • 皮膚表面麻酔下における圧痛閾値変化の解析

    高橋 賢, 水村 和枝

    Painres   19 ( 2 )   71   2004

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  • 経皮的圧刺激によって皮膚・筋に生じる応力の3次元有限要素解析

    高橋 賢, 水村 和枝

    Jpn J Physiol   54 ( Suppl )   S175   2004

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  • 経皮的に圧刺激を与えたときの組織内応力の3次元有限要素法を用いた推定

    高橋 賢, 水村 和枝

    Painres   19 ( 2 )   72   2004

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  • TREK-1とCMR1のmRNA発現量は, アジュバント単関節炎ラットにおけるC線維の冷応答増強時に増加していない

    高橋 賢, 片野坂 公明, 小崎 康子, 佐藤 純, 水村 和枝

    Jpn J Physiol   53 ( Suppl )   S240   2003

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  • 慢性炎症における冷痛覚過敏には, 末梢神経の変化が関与する

    高橋 賢, 佐藤 純, 水村 和枝

    J J Aerospace Env Med   39 ( 4 )   198   2002

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  • 冷痛覚過敏を生じたアジュバント関節炎ラットでは, C-一次求心神経の冷刺激に対する反応も増大している

    高橋 賢, 佐藤 純, 水村 和枝

    Jpn J Physiol   52 ( Suppl )   S153   2002

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  • アジュバント単関節炎ラットにおけるC-一次求心神経の冷応答の増強

    高橋 賢, 佐藤 純, 水村 和枝

    Jpn J Biometeor   39 ( 3 )   S64   2002

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  • 慢性炎症時における冷アロディニアの末梢機構の解析

    高橋 賢, 佐藤 純, 水村 和枝

    Painres   17 ( 3 )   136   2002

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  • アジュバント関節炎ラットの機械刺激に対する痛覚過敏は低気圧・低温曝露により増悪する

    高橋 賢, 佐藤 純, 水村 和枝

    Jpn J Biometeor   38 ( 2 )   S59   2001

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  • 低温・低圧刺激は慢性炎症による痛覚過敏を増悪させる

    高橋 賢, 奥村 聡, 佐藤 純, 水村 和枝

    J J Aerospace Env Med   38 ( 4 )   167   2001

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Presentations

  • Live imaging of nitric oxide release in vascular endothelial cells in response to mechanical stimuli on an organ chip International conference

    Takahashi K, Liu Y, Wang M, Liang Y, Naruse K

    ESC Congress 2022  2022.8.26  European Society of Cardiology

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    Event date: 2022.8.26 - 2022.8.29

    Language:English   Presentation type:Poster presentation  

    Venue:Barcelona  

    Background
    Nitric oxide (NO), released from vascular endothelial cells in response to mechanical stimuli, regulates cardiac contractility and are also involved in the prevention of the development of cardiac hypertrophy.

    Purpose
    To establish an experimental system for live observation of NO release in response to mechanical stimuli on an organ chip.

    Methods
    Organ chips, which we used for the development of a heart-on-a-chip in the previous study [1], were used.
    We seeded 300,000 human umbilical vein endothelial cells on a stretchable elastic membrane coated with Matrigel of a chip channel. Shear stress was applied to the cells by increasing flow rate of a peristaltic pump connected to the chip channel (Figure 1A). Pressure stimulus was applied by hydrostatic pressure. Stretch stimulus was applied by suction to the side ports of a chip using an electric syringe pump (Figure 1B). Cells were stained with 10 μM 4,5-diaminofluorescein diacetate for fluorescent live NO imaging.

    Results
    Monolayers of the endothelial cells formed intercellular junctions confirmed by CD31 staining (Figure 1C, yellow). Apparent permeability, which was measured by Texas red dye (MW 3000), was maintained at a low level of ~3 x 10^-6 cm/s until day 30, suggested the formation of robust intercellular junction.
    When the endothelial cells were subjected to a pressure stimulus of 60 mmHg for 60 s, NO release was observed that lasted for >2 minutes (Figure 2A). A peak value of 1.46 ± 1.08 (mean ± standard deviation) times the baseline was observed 271 s after the beginning of the pressure stimulus (n = 251 cells). When the cells were subjected to a 1% stretch for 60 s, a peak value of 1.29 ± 0.33 times the baseline was observed 105 s after the beginning of the stretch stimulus (Figure 2B). A shear stress of 0.01 dyn/cm² hardly increased NO release (1.20 ± 0.27 times the baseline, Figure 2C).

    Conclusion
    The system for live NO imaging in vascular endothelial cells in response to mechanical stimuli was established using organ-on-a-chip. The heart-on-a-chip with endothelial cells will be useful in elucidating the effects of mechanical stimulus such as hypertension on the contractile function and the remodeling of the heart.

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  • Mechanical stretch facilitates cardiomyocyte differentiation of human-induced pluripotent stem cells co-cultured with human gingival fibroblasts Invited International conference

    Ken Takahashi, Harumi Idei, Mengxue Wang, Yusuke Matsuda, Hiroshi Kamioka, Keiji Naruse

    9th World Congress of Biomechanics 2022 Taipei  2022.7.14 

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    Event date: 2022.7.10 - 2022.7.14

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Taipei (hybrid)  

    Mechanical stretch facilitates cardiomyocyte differentiation of human-induced pluripotent stem cells co-cultured with human gingival fibroblasts

    Introduction
    Although regenerative medicine using induced pluripotent stem cells (iPSCs) has been studied in cardiovascular medicine, scalability and efficiency of cardiomyocyte differentiation need to be improved. We hypothesized that mechanical stimulus could increase the efficiency and maturity of iPS-derived cardiomyocytes (iPS-CMs).

    Methods
    On a 2 × 2 cm elastic silicone chamber, we co-cultured human iPSCs with human gingival fibroblasts to promote differentiation of iPSCs into iPS-CMs and applied cyclic stretch (30 cycles/min) stimulus. We started a 72-h-long 2% stretch on the 15th day of cardiomyocyte differentiation protocol.

    Results
    Gene expression analysis using quantitative polymerase chain reaction revealed that expression levels of the mesoderm (Nkx2.5) and cardiomyocyte markers (cTnT) in the stretch group were significantly higher than those in the control group, suggesting that the stretch stimulus facilitated cardiomyocyte differentiation of iPSCs. Furthermore, expression levels of pluripotent markers (Sox2 and Oct4) tended to be lower in the stretch group than those in the control group. Furthermore, transmission electron microscopy revealed that the sarcomere length of iPS-CMs in the stretch group was significantly larger than that in the control group, suggesting that the stretch stimulus facilitated the maturation of iPS-CMs. Video-based contractility analysis suggested that the contractility of iPS-CMs tended to be larger in the stretch group than that in the control group.

    Discussion
    These results suggest that the mechanical stretch facilitates cardiomyocyte differentiation of iPSCs co-cultured with fibroblasts. The protocol of the stretch stimulus should be optimized in future studies.

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  • Effect of gravity on aging Invited

    Takahashi K

    61st Annual Conference of Japanese Society for Medical and Biological Engineering  2022.6.29 

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    Event date: 2022.6.28 - 2022.6.30

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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  • Development of a human heart-on-a-chip model using induced pluripotent stem cells, fibroblasts and endothelial cells International conference

    Liu Y, Wang M, Liang Y, Naruse K, Takahashi K

    ESC Congress 2021  2021.8  European Society of Cardiology

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    Event date: 2021.8.27 - 2021.8.30

    Language:English   Presentation type:Poster presentation  

    Venue:Online  

    Background
    The use of animal models in cardiovascular research is associated with two serious, intrinsic problems:
    inaccuracy in the extrapolation of data obtained from animals such as rodents due to different cardiac physiology
    and animal ethics.
    Purpose
    To develop an artificial human heart model for cardiovascular research using organ-on-a-chip technology and
    human cells
    Methods
    Organ chips made of silicone (polydimethylsiloxane) that have two microfluidic channels, a top channel and a
    bottom channel, separated by a 50-μm thick membrane with 7-μm pores hexagonally packed at 40-μm intervals
    (Figure 1), were used in this study.
    We seeded 10,000 human umbilical vein endothelial cells on the membrane surface in the bottom channel to
    mimic the vasculature. Next, we seeded a mixture of 100,000 human-induced pluripotent stem cells (hiPSCs) and
    50,000 human gingival fibroblasts on the membrane surface in the top channel (Figure 1). Human gingival
    fibroblasts facilitate cardiac differentiation of hiPSCs [1]. We performed the cardiac differentiation of hiPSCs
    using a previously described protocol [1]. Culture medium was perfused at a constant rate of 60 μl/h to maintain
    the culture.
    Results
    We observed spontaneous contraction of hiPSC-derived cardiomyocytes 20–26 days after the start of the
    differentiation protocol. Simultaneously, we conducted live intracellular calcium imaging using a fluorogenic
    calcium-sensitive dye, Cal-520 AM (5 μM in the culture medium). hiPSC-derived cardiomyocytes exhibited a
    periodic, coordinated pattern of calcium influx synchronised with their contraction under fluorescence
    microscopy (Figure 2A). Moreover, we found that the β-adrenergic agonist noradrenaline elevated the heart rate
    of hiPSC-derived cardiomyocytes on the organ chips in a dose-dependent manner (Figures 2A, B).
    After observing the contraction and intracellular calcium influx of hiPSC-derived cardiomyocytes, we performed
    immunocytochemistry. Confocal microscopy indicated that the fluorescent signal obtained from anti-cardiac
    troponin T antibody staining in the top channel exhibited a typical striated pattern with 1.56 ± 0.12-μm interval
    that reflected sarcomere structure (Figure 2C, yellow). Moreover, the fluorescent signal obtained from anti-CD31
    antibody staining in the bottom channel exhibited a typical pattern at the boundary between cells, which is
    expected at the cell–cell junction of endothelial cells.
    Conclusion
    We developed a human heart-on-a-chip model that was confirmed by the functional response to noradrenaline
    and the histological evidence of sarcomere structure and vasculature, with a capability of live imaging. We expect
    that this model would be useful for examining the physiological function and for the pharmacological analysis of
    not only the normal heart but also the heart that reflects specific patient’s pathophysiology using patientderived
    hiPSCs.

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  • Development and functional characterization of a model of human heart using organ-on-a-chip Invited

    Takahashi K

    The 3rd International Conference of Microfluidics, Nanofluidics and Lab-on-a-Chip  2021.7.4 

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    Event date: 2021.7.2 - 2021.7.4

    Language:English   Presentation type:Oral presentation (invited, special)  

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  • Development of a model of human heart using organ-on-a-chip

    Takahashi K

    The 60th Annual Conference of Japanese Society for Medical and Biological Engineering  2021.6.16 

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    Event date: 2021.6.15 - 2021.6.17

    Language:English   Presentation type:Oral presentation (general)  

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  • Evaluation of organ function using human organ-on-a-chip Invited

    Takahashi K

    Chem-Bio Informatics Society Annual Meeting 2020  2020.10.27  The Chem-Bio Informatics Society

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    Event date: 2020.10.27 - 2020.10.30

    Presentation type:Symposium, workshop panel (nominated)  

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  • Development of microfluidic cell culture system in preparation for human organ on a chip

    Takahashi K, Wang M, Liu Y, Liang Y, Wang C, Naruse K

    59th Annual Conference of Japanese Society for Medical and Biological Engineering  2020.5.26 

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    Event date: 2020.5.25 - 2020.5.27

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  • "All-JAPAN Medical School Physiology Quiz" framed completely new effective system of basic-medicine education in Japan

    Yuki Otsuka, Ken Takahashi

    The 48th Annual Meeting of the Japan Society for Medical Education  2016 

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    Event date: 2016.7.29 - 2016.7.30

    Language:Japanese   Presentation type:Poster presentation  

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  • Cancer-on-a-chip: Development of tumor-monocyte communication model using fluorescent exosome technology and microfluidic chip

    Yamamoto Y, Takahashi K, Okamoto K, Eguchi T

    SCRP Japan National Team Selection Tournament  2022.8 

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  • Functional analysis of a kidney-on-a-chip using human renal proximal tubular epithelial cells and human umbilical vein endothelial cells

    Yin Liang, Mengxue Wang, Yun Liu, Keiji Naruse, Ken Takahashi

    The 99th Annual Meeting of The Physiological Society of Japan  2022.3.18  The Physiological Society of Japan

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    Venue:Sendai (hybrid)  

    The kidney is an important organ that controls the reabsorption and excretionof substances such as glucose, urea nitrogen, and creatinine. To develop amodel of human kidney, we used human renal proximal tubular epithelialcells (RPTECs) and human umbilical vein endothelial cells (HUVECs) torecapitulate the renal proximal tubule of the nephron. RPTECs and HUVECswere seeded on a two-channel microfluidic chip connected to a peristalticpump. To evaluate the barrier integrity of the cell layers, we measuredpermeability using Texas Red-conjugated dextran (MW: 3000). The apparentpermeability of the RPTEC-HUVEC bilayer was ~2 × 10
    cm/s, suggestingsufficient barrier integrity. Next, we performed functional analysis of thekidney chip using urea nitrogen as an index. The concentration of ureanitrogen was ~0.7 mg/dl in the RPTEC channel, while it was ~0.3 mg/dl in theHUVEC channel, suggesting transport of urea nitrogen from the microvascularendothelial side to the kidney epithelial tubular side was active. However, theconcentration of glucose was ~110 mg/dl in the RPTEC channel, while it was~110 mg/dl in the HUVEC channel, suggesting no significant transport ofglucose. These results suggest that medium composition should be optimizedto assess the renal function of the kidney-on-a-chip.

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  • 臓器チップを用いたヒト臓器モデルの開発 Invited

    高橋 賢

    日本生体医工学会関西支部 講演会  2021.12.4 

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  • International Collaboration Invited

    Takahashi K

    Brainstorming 2021  2021.8.28  Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

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    Venue:Online  

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  • Development of human organ model using organ-on-a-chip and its application Invited

    Takahashi K

    The 124th Seminar of the BME Society of Okayama Prefecture  2021.6.25  The BME Society of Okayama Prefecture

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    Venue:Online  

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  • Establishing an artificial heart model on a chip by using cardiomyocytes differentiated from human induced pluripotent stem cells

    Wang M, Liu Y, Naruse K, Takahashi K

    The 98th Annual Meeting of The Physiological Society of Japan  2021.3.30 

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  • Kidney-on-a-chip model using human renal proximal tubular epithelial cells and human umbilical vein endothelial cells

    Yin Liang, Mengxue Wang, Keiji Naruse, Ken Takahashi

    The 98th Annual Meeting of The Physiological Society of Japan  2021.3.30 

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  • Optimization of the cardiac differentiation of human pluripotent stem cells

    Liu Y, Wang M, Naruse K, Takahashi K

    The 98th Annual Meeting of The Physiological Society of Japan  2021.3.30 

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  • Roles of the TRPM4 channel in mitochondrial function, ROS generation, and calcium release in myocardial ischemia–reperfusion injury

    Wang C, Chen J, Naruse K, Takahashi K

    The 97th Annual Meeting of the Physiological Society of Japan  2020.3.18 

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  • Roles of the TRPM4 channel in mitochondrial function, ROS generation, and calcium release in myocardial ischemia–reperfusion injury International conference

    Wang C, Naruse K, Takahashi K

    2019 International Conference for Leading and Young Medical Scientists  2019.12.22 

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  • Ischemia-reperfusion injury Invited International conference

    TAKAHASHI K

    2019 International Conference for Leading and Young Medical Scientists  2019.12.22 

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    Language:English   Presentation type:Oral presentation (keynote)  

    Venue:Taipei  

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  • Mechanobiology and its application to medical problem solving Invited International conference

    Takahashi K

    2019 International Conference on Biology and Medical Sciences  2019.3.2  Asia Pacific Society for Biology and Medical Sciences

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    Venue:Okinawa  

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  • TRPM4 channel is involved in cellular damage caused by simulated ischemia-reperfusion injury: study of human iPSC-derived cardiomyocytes

    Wang C, Wei H, Naruse K, Takahashi K

    The 95th Annual Meeting of the Physiological Society of Japan  2018.3.30  Physiological Society of Japan

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    Venue:Takamatsu, Japan  

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  • Cellular model of ischemic heart disease using human induced pluripotent stem cells

    Wei H, Wang C, Takahashi K, Naruse K

    The 95th Annual Meeting of the Physiological Society of Japan  2018.3.29  Physiological Society of Japan

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    Venue:Takamatsu, Japan  

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  • Effect of dimensional factor of cell culture on cardiac differentiation of human induced pluripotent stem cells

    Tada C, Takahashi K, Naruse K

    The 95th Annual Meeting of the Physiological Society of Japan  2018.3.28  Physiological Society of Japan

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    Venue:Takamatsu, Japan  

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  • Coarse grained molecular dynamics simulation of mammalian mechanosensitive ion channel TRPV2 Invited International conference

    Takahashi K

    3rd International Symposium on Mechanobiology  2017.12.14  International Symposium on Mechanobiology

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Singapore  

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  • ヒトiPS細胞を用いた虚血性心疾患モデルの構築

    魏恒, 王晨, 高橋賢, 成瀬恵治

    第69回日本生理学会中国・四国地方会  2017.10.28  日本生理学会中国・四国地方会

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    Venue:徳島  

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  • Simultaneous mapping of multiple proteins in heart using matrix-assisted laser desorption/ionization imaging mass spectrometry International conference

    Takahashi K, Naruse K

    ESC Congress 2017  2017.8.26  European Society of Cardiology

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    Venue:Barcelona, Spain  

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  • Optimization of manufacturing of planar patch clamp electrode

    Masuda S, Takahashi K, Naruse K

    The 94th Annual Meeting of the Physiological Society of Japan  2017.5.30  Physiological Society of Japan

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    Venue:Hamamatsu, Japan  

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  • Effect of vascular endothelial cells on cardiac differentiation of iPS cells

    Tada C, Takahashi K, Naruse K

    The 94th Annual Meeting of the Physiological Society of Japan  2017.5.30  Physiological Society of Japan

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    Venue:Hamamatsu, Japan  

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  • Application of mechanobiological engineering to regenerative and reproductive medicine Invited

    Takahashi K, Oh H, Iribe G, Matsuura K, Naruse K

    The 56th Annual Conference of Japanese Sociely for Medical and Biogical Engineering  2017.5.4  Japanese Sociely for Medical and Biogical Engineering

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    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:Sendai, Japan  

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  • Imaging of Cell Mechanics under High Gravity by Rotational Microscope International conference

    Morimatsu M, Takahashi K, Fujita A, Naruse K

    Biophysical Society 61st Annual Meeting  2017.2.13  Biophysical Society

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    Language:English   Presentation type:Poster presentation  

    Venue:New Orleans, USA  

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  • Effects of Mechanical Stress on Remodeling of Periodontal Ligament International conference

    Fujita A, Morimatsu M, Takahashi K, Takashiba S, Naruse K

    ASCB 2016 Annual Meeting  2016.12.6  The American Society for Cell Biology

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    Language:English   Presentation type:Poster presentation  

    Venue:San Francisco  

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  • High hydrostatic pressure induces cytoskeletal organization and signal transduction International conference

    Morimatsu M, Fujita A, Takahashi K, Naruse K

    ASCB 2016 Annual Meeting  2016.12.4  The American Society for Cell Biology

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    Venue:San Francisco  

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  • High Hydrostatic Pressure Induces Signal Transduction of the MAPK Pathway International conference

    Morimatsu M, Fujita A, Takahashi K, Naruse K

    Mechanobiology of Disease  2016.9.28  Biophysical Society

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    Venue:Singapore  

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  • 機械刺激による歯根膜線維芽細胞への影響

    藤田 彩乃, 森松 賢順, 高橋 賢, 高柴 正悟, 成瀬恵治

    生体医工学シンポジウム  2016.9.18  日本生体医工学会

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:旭川  

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  • TRPM4: new molecular target for cardiac ischemia–reperfusion injury Invited International conference

    Takahashi K

    BIT's 6th World Gene Convention  2015.11.14  BIT Life Science

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    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Qingdao, China  

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  • A Search for Scaffold Condition Suitable for Inducing Cardiac Differentiation of Induced Pluripotent Stem Cells International conference

    Matsuda Y, Sakai N, Takahashi K, orresponding, Naruse K

    The 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society  2015.8.29  IEEE Engineering in Medicine and Biology Society

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    Language:English   Presentation type:Poster presentation  

    Venue:Milan, Italy  

    Cellular scaffold is extremely important for cellular differentiation. To find efficient method to induce cardiac differentiation of stem cells, we tested several scaffold proteins using two dimensional (2D) and three dimensional (3D) cell culture systems. It is suggested that specific proteins such as vitronectin are necessary for 2D adhesion of stem cells and their cardiac differentiation. Also suggested is that fibroblast may play an essential role in forming 3D structure of cardiac tissue.

    SaBPoT7.14

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  • TRPM4: new molecular target for cardiac ischemia–reperfusion injury International conference

    TAKAHASHI Ken

    NIPS International Workshop TRPs and SOCs -Unconventional Ca2+ Physiology-  2015.6.4  NIPS

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    Language:English   Presentation type:Poster presentation  

    Venue:Okazaki, Japan  

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  • Contractile function of reconstituted cardiac tissue is facilitated by mechanical stretch

    The 92nd Annual Meeting of the Physiological Society of Japan  2015 

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  • Planar patch clamp system capable of recording mechanosensitive responses of ion channels

    第59回米国生物物理学会  2015 

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  • Implication of TRPM4 channel in ischemia-reperfusion injury International conference

    Takahashi K, Naruse K

    ASCB 2014 Annual Meeting  2014.12.7  The American Society for Cell Biology

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    Language:English   Presentation type:Poster presentation  

    Venue:Philadelphia, USA  

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  • 筋痛の中枢神経メカニズム Invited

    高橋賢

    岡山脳研究セミナー  2014.7.12  日本神経科学会

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    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:岡山  

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  • Conformational changes of ion channels in response to bilayer stretch ? A coarse grained molecular dynamics simulation study Invited International conference

    Takahashi K

    International Symposium on Mechanobiology 2014  2014.5.23  International Symposium on Mechanobiology

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Okayama, Japan  

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  • L-type calcium channel modulates mechanosensitive response of rat cardiomyocytes Invited International conference

    Takahashi K, Naruse K, Sokabe K

    International Symposium on Mechanobiology 2014  2014.5.21  International Symposium on Mechanobiology

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Okayama, Japan  

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  • 9-Phenanthrol, a TRPM4 Inhibitor, protects rat hearts from ischemia-reperfusion injury Invited

    Takahashi K, Piao H, Wang J, Naruse K

    The 91st Annual Meeting of the Physiological Society of Japan  2014  Physiological Society of Japan

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Kagoshima, Japan  

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  • 粗視化分子動力学シミュレーションで何ができるか? Invited

    高橋 賢

    第2回スーパーコンピュータ「京」と生命科学  2013.7.19  岡山大学

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    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:岡山  

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  • TRPM4阻害薬9-phenanthrolはラット摘出心臓の虚血再灌流障害を抑制する

    高橋 賢, 朴 虎林, 王 静, 成瀬 恵治

    第9回TRPチャネル研究会  2013.6  生理学研究所

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:岡崎  

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  • How do proteins sense force? — a coarse grained molecular dynamics simulation study Invited International conference

    Takahashi K

    BIT Life Sciences' 6th Annual Protein & Peptide Conference  2013.3.23  BIT Life Science

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    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Suzhou, China  

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  • 痛覚刺激時のfMRI Invited

    高橋 賢

    第35回日本疼痛学会  2013  日本疼痛学会

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    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:大宮  

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  • Development of planar patch clamp system with stretchable resin

    第90回 日本生理学会大会  2013 

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  • Developing a small, inexpensive planar patch-clamp device

    The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society  2013 

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  • TRPM4チャネル阻害薬9-Phenanthrolはラット心臓を虚血再灌流障害から保護する

    朴 虎林, 王 静, 高橋 賢, 成瀬 恵治

    第65回日本生理学会中国四国地方会  2013  日本生理学会中国四国支部会

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:倉敷  

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  • Fabrication of a simple and compact patch clamp system for high-throughput recording

    The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society  2013 

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  • TRPC channels may possibly be involved with the mechanosensitivity of the heart

    Takahashi K, Fujii S, Hattori M, Omori M, Wang J, Naruse K, Sokabe M

    The 8th TRP Channel Conference  2012.6.14 

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    Language:Japanese   Presentation type:Oral presentation (general)  

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  • L-type voltage gated calcium channel is involved with the mechanosensitivity of the rat heart Invited

    Takahashi K, Fujii S, Hattori M, Omori M, Naruse K

    The 89th Annual Meeting of the Physiological Society of Japan  2012.3.30  Physiological Society of Japan

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

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  • Conformational change of membrane proteins in response to membrane tension — a coarse grained molecular dynamics simulation study Invited International conference

    Takahashi K, Toda K, Saruwatari K, Yokoyama T, Naruse K, Sokabe M

    BIT Life Sciences' 5th Annual Protein & Peptide Conference  2012.3.25  BIT Life Science

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    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Beijing, China  

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  • Mechanical stretch promotes reprogramming of human cardiac progenitors into functional cardiomyocytes by defined factors

    Tarui S, Kobayashi J, Hirata M, Yoshida M, Kasahara S, Takahashi K, Nagai Y, Ito H, Naruse K, Sano S, Oh H

    The 76th Annual Scientific Meeting of the Japanese Circulation Society  2012.3.18 

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  • Patient-specific induced pluripotent stem cells from cardiac progenitors recapitulate the models for cardiac chamber disorders

    European Society for Cardiology Congress 2012  2012 

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  • Tissue deformation and pressure propagation in human tissue during mechanical painful stimulation: comparison of tibialis anterior and gastrocnemius medialis

    14th World Congress on Pain  2012 

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  • 平面膜パッチクランプ法の実用化

    異分野融合先端研究コア シンポジウム-2012  2012 

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  • Finite element analysis for mechanical environment of the human body

    2012 

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  • Fabrication and characterization of planar patch clamp electrode of stretchable resin

    2012 

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  • Molecular basis for mechanosensitivity of ion channels — coarse grained molecular dynamics simulation study

    第89回 日本生理学会大会  2012 

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  • Fabrication and characterization of planar patch clamp electrode of stretchable resin

    第89回 日本生理学会大会  2012 

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  • Molecular basis for mechanosensitivity of ion channels -- coarse grained molecular dynamics simulation study

    The 89th Annual Meeting of the Physiological Society of Japan  2012 

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  • Fabrication and characterization of planar patch clamp electrode of stretchable resin

    The 89th Annual Meeting of the Physiological Society of Japan  2012 

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  • 小型・安価な平面パッチクランプ装置の開発

    第35回日本生体医工学会大会中国四国支部大会  2012 

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  • 生体内の力学環境の有限要素解析

    第51回日本生体医工学会大会  2012 

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  • Tissue deformation and pressure propagation in human tissue during mechanical painful stimulation: comparison of tibialis anterior and gastrocnemius medialis

    14th World Congress on Pain  2012 

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  • The potential role of L‐type voltage‐gated channels in rat cardiac mechanosensitivity

    24th Scientific Meeting of the International Society of Hypertension  2012 

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  • 伸展可能な樹脂製平面パッチクランプ電極の作製と評価

    第51回日本生体医工学会大会  2012 

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  • Novel planar patch clamp system for recording of mechanosensitive ion channels Invited International conference

    Takahashi K, Fukasawa T, Matsuura K, Wakimoto S, Naruse K

    2011 Scientific Research Publishing Workshop  2011.10.21 

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

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  • Coarse grained molecuIar dynamics simulation of a mechanically gated ion channel

    The 88th Annual Meeting of the PhysiologicaI Society of Japan  2011 

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  • 伸展可能な平面パッチクランプ装置の開発

    アクチュエータシンポジウム  2011 

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  • 伸展可能樹脂製平面パッチクランプ法の開発

    第50回日本生体医工学会大会  2011 

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  • How Do We Know Force Inside the Body? – Finite Element Stress Analysis Invited International conference

    Takahashi K, Mizumura K

    BIT Life Sciences' 2nd Annual BioSoft-2010  2010.6.24 

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    Language:English   Presentation type:Oral presentation (invited, special)  

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  • Mechanosensitive ion channels in a rat cardiomyocyte cell line H9c2

    2010 

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  • 伸展可能樹脂製平面パッチクランプ法の開発

    第33回日本生体医工学会中国四国支部大会  2010 

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  • Mechanosensitive ion channels in a rat cardiomyocyte cell line H9c2

    第62回日本生理学会中国四国地方会  2010 

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  • Coarse-grained Molecular Dynamics Simulation of Membrane Proteins Invited International conference

    Takahashi K

    BIT Life Sciences' 2nd Annual Protein and Peptide Conference  2009.4.3 

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    Language:English   Presentation type:Oral presentation (invited, special)  

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  • Stretch-activated calcium response of a rat cardiomyocyte cell line H9c2

    XXXVI International Congress of Physiological Sciences  2009 

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  • Anti-cholesterol drug statins affect stretch-induced calcium influx in the cardiomyocyte cell line H9c2

    XXXVI International Congress of Physiological Sciences  2009 

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  • Does a non-mechanosensitive ion channel really not open by mechanical force? – A corase grained molecular dynamics simulation study

    The 47th Annual Meeting of the Biophysical Society of Japan  2009 

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  • Stretch-induced Ca response of cardiomyocyte cell line H9c2

    第85回日本生理学会  2008 

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  • Does the subcutaneous fat alleviate deep pressure pain? A simulation study Invited International conference

    Takahashi K, Mizumura K

    IASP Research Symposium 2007, Fundamentals of Musculoskeletal Pain  2007.5.7 

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    Language:English   Presentation type:Oral presentation (invited, special)  

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  • 生体内に生じる応力の有限要素解析 Invited

    高橋 賢

    LS-DYNAセミナー2007  2007.2.9  富士通

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    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:幕張  

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  • Brain regions specifically activated by painful muscle stimulation

    IASP Research Symposium 2007, Fundamentals of Musculoskeletal Pain  2007 

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  • 筋肉痛に応ずる脳部位 Invited

    高橋 賢

    第36回日本臨床神経生理学会  2006.11.29 

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    Language:English   Presentation type:Oral presentation (invited, special)  

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  • Low barometric pressure and low ambient temperature exacerbate mechanical pain in arthritic rats Invited International conference

    Takahashi K, Sato J, Mizumura K

    6th International Head-Out Water Immersion Symposium: From Bathing to Space  2005.9.21 

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    Language:English   Presentation type:Oral presentation (invited, special)  

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  • Artificially produced meteorological changes aggravate mechanical allodynia in adjuvant-arthritis rats. Society for Neuroscience International conference

    Takahashi K, Okumura S, Sato J, Mizumura K

    Neuroscience 2001  2001.11.13  Society for Neuroscience

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    Language:English   Presentation type:Poster presentation  

    Venue:San Diego, USA  

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Industrial property rights

  • Method for producing cardiomyocytes

    Ken Takahashi, Harumi Idei, Keiji Naruse

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    Applicant:Okayama University

    Application no:特願2020-084982  Date applied:2020.5.14

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  • Preventive/therapeutic reagent for ischemic heart diseases

    Takahashi K, Wang J, Naruse K

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    Application no:特願2012-278633  Date applied:2012.12.20

    Announcement no:特開2014-122174  Date announced:2014.7.3

    Patent/Registration no:特許第6073125号  Date issued:2017.1.13

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  • Centrifugal microscope

    Naruse K, Takahashi K, Morimatsu M

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    Applicant:Okayama University

    Application no:特願2016-043814  Date applied:2016.3.7

    Announcement no:特開2017-161608  Date announced:2017.9.14

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  • Cell incubator

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    Application no:特願2012-512445  Date applied:2012.4.26

    Patent/Registration no:特許第6074860号  Date issued:2017.1.20

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Works

  • 中央西日本メディカル・イノベーション

    高橋 賢

    2018.1

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    てんかん・不整脈の創薬スクリーニングに向けた平面パッチクランプ装置の開発

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  • 第13回国際バイオテクノロジー展/技術会議

    高橋 賢

    2014.5

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    低価格平面パッチクランプシステムの開発

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  • 岡山メディカルイノベーション

    高橋 賢

    2014.3

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    小型・安価な平面パッチクランプ装置

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  • BIO tech 2014

    2014

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  • Bio Japan 2012 World Business Forum

    2012.10

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  • 第11回国際バイオテクノロジー展/技術会議

    高橋 賢, 深澤太郎, 成瀬恵治

    2012.4

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    機械刺激応答を記録可能な平面パッチクランプ装置の開発

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  • BIO tech 2012

    2012

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  • Innovation Japan 2009

    Takahashi K

    2009.9.17

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    Finite element analysis simulation of stress in human body

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Awards

  • Award for Outstanding Research Achievement and Contribution

    2019.12   Asia Pacific Society for Biology and Medical Sciences  

    TAKAHASHI K

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    Award type:Award from international society, conference, symposium, etc.  Country:Taiwan, Province of China

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  • Award for Outstanding Research Achievement

    2019.3   Asia Pacific Society for Biology and Medical Sciences  

    Ken Takahashi

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  • Award for Outstanding Contribution to Education

    2018.6   Okayama Medical Association   Contribution to internationalization

    Ken Takahashi

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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  • Best Teacher Award

    2017.3   Okayama University, Department of Medicine  

    Cardiovascular, Physiology Lab

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  • Young Investor Award

    2004   Polymodal Club  

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    Country:Japan

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Research Projects

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Other research activities

  • Tokyo 2020 Olympics - Torchbearer

    2020.01
    -
    2021.08

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  • Ironman Triathlete

    2006.12

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    Finished an Ironman Triathlon race (Western Australia, 2006)

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  • JAXA有人閉鎖実験 完遂

    2004.02

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    2004年2月25日から3月5日までつくば宇宙センターで行われた第2回JAXA有人閉鎖実験に被験者として参加し、完遂

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Class subject in charge

  • Research Projects and Practicals: Cardiovascular Physiology I (2021academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Physiology I (2021academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Physiology II (2021academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Physiology II (2021academic year) special  - その他

  • Human Physiology (2021academic year) Concentration  - その他

  • Lecture: Myocardial Infarction (2021academic year) special  - その他

  • Physiology (2) (2021academic year) special  - その他

  • Practice in Physiology (2) (2021academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Physiology I (2020academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Physiology I (2020academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Physiology II (2020academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Physiology II (2020academic year) special  - その他

  • Human Physiology (2020academic year) Concentration  - その他

  • Physiology (2) (2020academic year) special  - その他

  • Practice in Physiology (2) (2020academic year) special  - その他

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Social Activities

  • Robotic Project of Elementary School Students

    Role(s):Advisor, Informant

    Elementary School at Westford, MA, USA  2018.11

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    Audience: Schoolchildren

    Type:Research consultation

    Mentoring elementary school students (Westford, MA) for a robotic project about a solution to muscle atrophy in space.

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  • Seminar: How does space environment change your body?

    Role(s):Lecturer

    Takatsuki High School/Junior High School, The Biophysical Society of Japan  Takatsuki High School/Junior High School  2018.1.31

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    Audience: Junior students, High school students

    Type:Visiting lecture

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  • Obesity, cancer, and thin tube - health and disease controlled by blood vessel

    Role(s):Lecturer

    Frompage; Japanese Ministry of Education, Culture, Sports, Science and Technology  2015 Dream Navigator Lecture live  Intex Osaka  2015.6.20

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    Audience: High school students

    Type:Lecture

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  • Publons Reviewer

    Role(s):Advisor, Report writing

    Clarivate Analytics  2014

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    Audience: Researchesrs, Scientific

    Type:Newspaper, magazine

    Our mission is to speed up research by harnessing the power of peer review.

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  • JAXAリーダーズセミナー

    Role(s):Lecturer

    JAXA  名古屋市・大同工業大学  2007.11.13 - 2007.11.14

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    Audience: Teachers, General

    Type:Seminar, workshop

    東海地区の宇宙教育リーダーを対象とした「JAXAリーダーズセミナー」に参加、「宇宙教育の理念」と「宇宙と人間の身体」の2題を講演

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Media Coverage

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Academic Activities