NAKAHARA Jin

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Neurology) Department of Neurology, Keio University School of Medicine （Shinanomachi）

Position

Professor

E-mail Address

E-mail address

Related Websites

External Links
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Profile 【 Display / hide 】

  • - Japanese Society of Neurology
    District Representative
    Delegate
    - Japanese Society of Internal Medicine
    Councilor
    - Japanese Society of Neuroimmunology
    Director
    - Japanese Society of Neurological Therapeutics
    Councilor
    - Japanese Society for Neuroinfectious Diseases
    Councilor
    - Japan Multiple Sclerosis Network
    Director
    - Pan-Asian Congress for Treatment and Research in Multiple Sclerosis (PACTRIMS)
    Central organizing committee member

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Message from the Faculty Member 【 Display / hide 】

  • We aim to develop actual therapeutics by every conceivable means – from advancement of translational research to home care medicine – to improve the quality of life of patients suffering from various neurological diseases.

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Other Affiliation 【 Display / hide 】

  • Keio University Global Research Institute (KGRI), Deputy Director

  • Keio University Hospital Stroke Center, Director

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Career 【 Display / hide 】

  • 2003.04
    -
    2004.03

    慶應義塾大学, COEプログラム（生命科学）, 研究員

  • 2004.04
    -
    2007.03

    独立行政法人日本学術振興会, 特別研究員（DC1）

  • 2007.04
    -
    2008.11

    独立行政法人日本学術振興会, 特別研究員（PD）

  • 2008.12
    -
    2013.03

    慶應義塾大学, 医学部総合医科学研究センター, 特任講師

  • 2013.04
    -
    2018.03

    慶應義塾大学, 医学部内科学教室（神経）, 助教

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Academic Background 【 Display / hide 】

  • 2003.03

    Keio University, School of Medicine

    University, Graduated

  • 2007.03

    Keio University, Graduate School, Division of Medicine, 生理系専攻

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, Coursework, 2007.03

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Licenses and Qualifications 【 Display / hide 】

  • Medical license, 2003.05

  • Certified occupational physician, 2011.09

  • Board certified member of the Japanese Society of Internal Medicine, 2013.09

  • Board certified neurologist, 2014.07

  • Fellow of the Japanese Society of Internal Medicine (FJSIM), 2019.12

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Research Areas 【 Display / hide 】

  • Neurology

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Research Keywords 【 Display / hide 】

  • Oligodendrocyte

  • Multiple sclerosis

  • Neuroimmunology

  • Neurology

  • Neuromyelitis optica spectrum disorder

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Research Themes 【 Display / hide 】

  • 神経治療学の拠点形成, 

    2018
    -
    Present

  • 多発性硬化症の臨床研究, 

    2011
    -
    Present

  • 中枢神経系髄鞘再生療法の開発, 

    1999
    -
    Present

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Books 【 Display / hide 】

  • Visualization of Myelin for the Diagnosis and Treatment Monitoring of Multiple Sclerosis

    Nakahara J., Advances in Experimental Medicine and Biology, 2019

    　View Summary

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) affecting more than two million people worldwide. As the exact etiology of MS remains elusive, the diagnosis of MS is made by referring to the McDonald diagnostic criteria, which utilizes MRI as a tool to identify “demyelinated” MS lesions. In particular, hyperintense lesions on T2-weighted images (T2WI) or so-called “T2-lesions” are considered to represent demyelinated MS lesions. T2WI, however, lacks myelin specificity, and moreover, remyelination could not be depicted by the use of such modality. For the accurate diagnosis and treatment decision-making, or for the future development of remyelination therapeutics, imaging tools to visualize myelin-specific signals are mandatory. In this chapter, the current use and the limitation of imaging modalities in MS diagnosis and treatment will be reviewed, with the introduction of new imaging method, namely q-space Myelin Map (qMM), to be used for visualization of demyelination and remyelination in MS.

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Papers 【 Display / hide 】

  • Meningitis caused by Listeria monocytogenes in a locally advanced cervical cancer patient with pyometra: A case report

    Matoba Y., Nishio H., Sekiguchi K., Uno S., Masuda K., Hiramatsu M., Takahashi M., Oishi M., Uwamino Y., Uchida S., Daté Y., Morisada T., Banno K., Nakahara J., Aoki D.

    Gynecologic Oncology Reports （Gynecologic Oncology Reports)  37 2021.08

    　View Summary

    Locally advanced cervical cancer occasionally induces pyometra, but there have been no reports of meningitis where pyometra is the cause of infection. Here, we report a case of Listeria monocytogenes meningitis related to pyometra during concurrent chemoradiotherapy (CCRT) in a cervical cancer patient. The patient, a 77-year-old woman, was diagnosed with Stage IIB (FIGO 2018) cervical adenocarcinoma, and CCRT was initiated. Pyometra was exacerbated during CCRT, and after her first brachytherapy, she presented at our hospital with fever and decreased consciousness level. After admission to the Intensive Care Unit, the patient lost consciousness and experienced frequent seizures; tracheal intubation was required. Whole-body computed tomography revealed pyometra; therefore, transvaginal removal of the abscess was performed. Laboratory tests and vital signs indicated septic shock, and meropenem was administered. L. monocytogenes was detected in the abscess from the uterine cavity and the blood cultures on the third day of hospitalization. A lumbar puncture was performed on the same day to investigate whether the patient had meningitis. A FilmArray meningitis/encephalitis panel test of the spinal fluid revealed L. monocytogenes. After the diagnosis of meningitis with L. monocytogenes, ampicillin and gentamicin were started, and the blood test results gradually improved. Five months after the initial episode, her consciousness recovered, however she still received mechanical ventilatory support. L. monocytogenes infections can occur in patients undergoing chemotherapy, even without the use of steroids or immunosuppressive agents. In cases with pyometra, intrauterine manipulation can increase the risk of severe infection.

  • Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study

    Kira J.I., Nakahara J., Sazonov D.V., Kurosawa T., Tsumiyama I., Willi R., Zalesak M., Pingili R., Häring D.A., Ramanathan K., Kieseier B.C., Merschhemke M., Su W., Saida T.

    Multiple Sclerosis Journal （Multiple Sclerosis Journal)   2021

    ISSN  13524585

    　View Summary

    Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% (p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

  • Mechanisms of myelin repair, MRI techniques and therapeutic opportunities in multiple sclerosis

    Sommer R.C., Hata J., Rimkus C.d.M., Klein da Costa B., Nakahara J., Sato D.K.

    Multiple Sclerosis and Related Disorders （Multiple Sclerosis and Related Disorders)   2021

    ISSN  22110348

    　View Summary

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The remyelination process requires the activation, migration and differentiation of oligodendrocyte progenitor cells (OPC) in demyelinated areas. The metabolic dysfunction in chronic demyelinating lesions impairs the activation of OPCs, the myelin debris clearance by microglia decreases with age, along with diminished secretion of factors promoting OPC differentiation. Conventional magnetic resonance imaging (MRI) sequences have limited ability to differentiate unmyelinated and remyelinated lesions. Advanced MRI sequences based on magnetization transfer ratio (MTR), myelin water fraction (MWF) and diffusion tensor imaging (DTI) have been used to evaluate remyelination in clinical trials. More recently, the q-space myelin map (qMM) has been used on experimental and exploratory clinical studies. The improvement of myelin-specific MRI sequences with high reliability and standardization among centers will allow a more accurate evaluation of new therapies to improve remyelination. These new remyelination promoting treatments alone or in combination with current options may reduce the risk of long-term disability in MS.

  • Painless thyroiditis presenting with headache

    Takizawa T., Kurihara I., Suzuki N., Nakahara J., Shibata M.

    Internal Medicine （Internal Medicine)  60 （ 16 ） 2693 - 2696 2021

    ISSN  09182918

    　View Summary

    Although headache attributed to hypothyroidism is coded within The International Classification of Headache Disorders, 3rd edition, an association between headache and thyrotoxicosis (hyperthyroidism) is mentioned only in the appendix. Reports on relevant cases are too scarce to establish a causal relationship. A young man with a history of migraine with aura arrived at our headache clinic with a 10-day history of headache and weight loss. Brain MRI revealed normal findings. Blood tests revealed thyrotoxicosis. A test for thyroid-related antibodies was negative. Thus, the patient was diagnosed with painless thyroiditis. The patient's headache resolved as his thyroid hormone levels decreased. To the best of our knowledge, this is the first reported case of headache exaggerated by painless thyrotoxicosis.

  • Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons

    Hatakeyama N., Unekawa M., Murata J., Tomita Y., Suzuki N., Nakahara J., Takuwa H., Kanno I., Matsui K., Tanaka K.F., Masamoto K.

    Journal of Cerebral Blood Flow and Metabolism （Journal of Cerebral Blood Flow and Metabolism)  41 （ 10 ） 2676 - 2689 2021

    ISSN  0271678X

    　View Summary

    A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • ミエリンマップ法を用いた多発性硬化症における髄鞘病理の画像解析

    2018.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 中原　仁, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 髄鞘を標的とした神経変性疾患・脊髄損傷に対する新規治療戦略に関する研究

    2013.04
    -
    2016.03

    文部科学省, Grant-in-Aid for Scientific Research, 中原仁, Principal Investigator

  • 髄鞘の可視化技術による多発性硬化症の病型分類に関する研究

    2013.04
    -
    2016.03

    文部科学省, Grant-in-Aid for Scientific Research, 中原仁, Principal Investigator

  • アストロサイトによるin vivoケトン体生合成機構の解明

    2010.04
    -
    2013.03

    文部科学省, Grant-in-Aid for Scientific Research, 中原仁, Principal Investigator

  • 内在性オリゴデンドロサイト前駆細胞の分化誘導を基盤とする中枢神経系髄鞘再生医薬の開発

    2009.04
    -
    2012.03

    独立行政法人医薬基盤研究所, -, 中原仁, Principal Investigator

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Intellectual Property Rights, etc. 【 Display / hide 】

  • Drug delivery system toward demyelinating lesion and biochemical marker of demyelinating lesions

    Application No.： 8252540  2012.08 

    Registration No.： 8252540  2012.08

    Patent, Joint

  • Medicinal compositions containing Fc receptor γ chain activator

    Application No.： 7901678  2011.03 

    Registration No.： 7901678  2011.03

    Patent, Joint

  • Fc受容体γ鎖活性化物質を含有する医薬組成物

    Application No.： 4214249  2008.11 

    Registration No.： 4214249  2008.11

    Patent, Joint

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Awards 【 Display / hide 】

  • Best Presentation Award

    2017, Sendai Conference

  • MSJ-PACTRIMS investigator award

    2014, Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS)

  • 優秀指導教官賞

    2014, 日本内科学会

  • MSJ-PACTRIMS Investigator Award

    2014, PACTRIMS

  • 優秀指導教官賞

    2014, 内科学サミット2014

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2021

  • INTERNAL MEDICINE: SEMINAR

    2021

  • INTERNAL MEDICINE: PRACTICE

    2021

  • INTERNAL MEDICINE

    2021

  • INTEGRATION OF BASIC SCIENCE AND CLINICAL MEDICINE

    2021

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Memberships in Academic Societies 【 Display / hide 】

  • 日本内科学会

    　

  • 日本神経学会

    　

  • 日本神経免疫学会

    　

  • 日本神経治療学会

    　

  • 日本脳卒中学会

    　

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