KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2000.05

  -

  2002.04

  慶應義塾大学医学部, 内科学, 研修医

• 2002.05

  -

  2004.05

  慶應義塾大学医学部, 内科学, 専修医

• 2004.06

  -

  2010.01

  慶應義塾大学医学部, 内科学(呼吸器), 助手

• 2007.01

  -

  2010.01

  慶應義塾大学医学部, 微生物学・免疫学, 研究員

• 2008.07

  -

  2010.01

  佐野厚生総合病院, 内科, 医員

display all >>

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2000.03

  Keio University, Faculty of Medicine, 医学科

  University, Graduated

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士, Keio University, Dissertation, 2008.06

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 医師免許, 2000.04

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Respiratory medicine

• Life Science / Infectious disease medicine

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Mycobacteriosis

Books 【 Display / hide 】

Books 【 Display / hide 】

• EBM呼吸器疾患の治療2016-2017

  Nishimura Tomoyasu, 中外医学社, 2016.01

  Scope: Interferon Gamma Release Assayの有用性は？

• 新 呼吸器専門医テキスト

  Nishimura Tomoyasu, 南江堂, 2015.04

  Scope: 肺結核症

• 内科研修マニュアル　改訂第2版

  Nishimura Tomoyasu, 南江堂, 2006.07

  Scope: 市中肺炎/院内肺炎

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study

  Morita A., Yagi K., Asakura T., Namkoong H., Sato Y., Ogawa T., Kusumoto T., Suzuki S., Tanaka H., Lee H., Okamori S., Azekawa S., Nakagawara K., Kaji M., Nagao G., Funatsu Y., Kimizuka Y., Kamata H., Nishimura T., Ishii M., Fukunaga K., Hasegawa N.

  BMC Pulmonary Medicine （BMC Pulmonary Medicine)  23 （ 1 ）  2023.12

  　View Summary

  Background: The long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD. Methods: Overall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study. Data were collected using the St. George’s Respiratory Questionnaire (SGRQ), pulmonary function test (PFT), blood tests, and the 6MWT at registration and at least once after that. The association of the anchors and clinical indicators with the 6MWT parameters was assessed. Results: The median age [interquartile range] of the patients was 67 [63–74] years. The median baseline six-minute walk distance (6MWD) and final Borg scale (FBS) were 413 [361–470] m and 1 [0–2], respectively. In the correlation analysis, ΔSGRQ total/year (yr), Δforced vital capacity (FVC, % predicted)/yr, Δforced expiratory volume in 1 s (FEV1, % predicted)/yr, and Δdiffusing capacity for carbon monoxide (DLCO, % predicted)/yr correlated with both Δ6MWD/yr and ΔFBS/yr in the longitudinal analysis (|Rho| > 0.20). When stratified into three quantiles of changes in each anchor, the 6MWT parameters worsened over time in the bottom 25% group by mixed-effects model. Specifically, Δ6MWD was affected by SGRQ activity, SGRQ impacts, PFT (FVC, FEV1, and DLCO), and C-reactive protein (CRP). ΔFBS was affected by all SGRQ components, total score, and PFT. Anchor scores and variables at baseline that worsened Δ6MWD were higher SGRQ scores, lower FVC (% predicted), lower DLCO (% predicted), higher Krebs von den Lungen-6, old age, and undergoing treatment at registration. Similarly, these clinical parameters and elevated CRP, excluding undergoing treatment at registration, worsened ΔFBS. Conclusions: The decreased walking distance and exacerbation of dyspnea on exertion over time in patients with NTM-PD may reflect a deterioration of health-related quality of life and pulmonary function. Thus, the change in 6MWT over time can be used as an indicator to accurately assess the patient’s condition and tailor their healthcare environment.

  • Access to Document (DOI)

• Inactivation of nontuberculous mycobacteria by gaseous ozone treatment

  Misawa K., Nishimura T., Kashimura S., Hasegawa N.

  Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy)  29 （ 6 ） 628 - 630 2023.06

  ISSN  1341321X

  　View Summary

  Nontuberculous mycobacteria (NTM) are environmental bacteria resistant to many common disinfectants and ultraviolet radiation. Inhalation of aerosols generated from NTM-containing water and soil causes NTM lung disease, especially in people with underlying lung diseases and decreased immunity. To prevent healthcare-acquired NTM infections, it is important to eradicate NTM living in hospital environments. Therefore, we evaluated the efficacy of gaseous ozone for the inactivation of NTM, namely Mycobacterium (M.) avium, M. intracellulare, M. kansasii, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense. Gaseous ozone treatment at 1 ppm for 3 h reduced the bacterial number of all strains by more than 97%. Gaseous ozone treatment could be a practical, effective and convenient disinfection method for NTM living in hospital environments.

  • Access to Document (DOI)

• Characterization of DNA Gyrase Activity and Elucidation of the Impact of Amino Acid Substitution in GyrA on Fluoroquinolone Resistance in Mycobacterium avium

  Thapa J., Chizimu J.Y., Kitamura S., Akapelwa M.L., Suwanthada P., Miura N., Toyting J., Nishimura T., Hasegawa N., Nishiuchi Y., Gordon S.V., Nakajima C., Suzuki Y.

  Microbiology Spectrum （Microbiology Spectrum)  11 （ 3 ）  2023.05

  　View Summary

  Mycobacterium avium, a member of the M. avium complex (MAC), is the major pathogen contributing to nontuberculous mycobacteria (NTM) infections worldwide. Fluoroquinolones (FQs) are recommended for the treatment of macrolide-resistant MACs. The association of FQ resistance and mutations in the quinolone resistance-determining region (QRDR) of gyrA of M. avium is not yet clearly understood, as many FQ-resistant clinical M. avium isolates do not have such mutations. This study aimed to elucidate the role of amino acid substitution in the QRDR of M. avium GyrA in the development of FQ resistance. We found four clinical M. avium subsp. hominissuis isolates with Asp-to-Gly change at position 95 (Asp95Gly) and Asp95Tyr mutations in gyrA that were highly resistant to FQs and had 2- to 32-fold-higher MICs than the wild-type (WT) isolates. To clarify the contribution of amino acid substitutions to FQ resistance, we produced recombinant WT GyrA, GyrB, and four GyrA mutant proteins (Ala91Val, Asp95Ala, Asp95Gly, and Asp95Tyr) to elucidate their potential role in FQ resistance, using them to perform FQ-inhibited DNA supercoiling assays. While all the mutant GyrAs contributed to the higher (1.3- to 35.6-fold) FQ 50% inhibitory concentration (IC50) than the WT, Asp95Tyr was the most resistant mutant, with an IC50 15- to 35.6-higher than that of the WT, followed by the Asp95Gly mutant, with an IC50 12.5- to 17.6-fold higher than that of the WT, indicating that these amino acid substitutions significantly reduced the inhibitory activity of FQs. Our results showed that amino acid substitutions in the gyrA of M. avium contribute to FQ resistance. IMPORTANCE The emergence of fluoroquinolone (FQ) resistance has further compounded the control of emerging Mycobacterium avium-associated nontuberculous mycobacteria infections worldwide. For M. avium, the association of FQ resistance and mutations in the quinolone resistance-determining region (QRDR) of gyrA is not yet clearly understood. Here, we report that four clinical M. avium isolates with a mutation in the QRDR of gyrA were highly resistant to FQs. We further clarified the impact of mutations in the QRDR of GyrA proteins by performing in vitro FQ-inhibited DNA supercoiling assays. These results confirmed that, like in Mycobacterium tuberculosis, mutations in the QRDR of gyrA also strongly contribute to FQ resistance in M. avium. Since many FQ-resistant M. avium isolates do have these mutations, the detailed molecular mechanism of FQ resistance in M. avium needs further exploration.

  • Access to Document (DOI)

• Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity

  Edahiro R., Shirai Y., Takeshima Y., Sakakibara S., Yamaguchi Y., Murakami T., Morita T., Kato Y., Liu Y.C., Motooka D., Naito Y., Takuwa A., Sugihara F., Tanaka K., Wing J.B., Sonehara K., Tomofuji Y., Wang Q.S., Hasegawa T., Saiki R., Hyugaji T., Shimizu E., Katayama K., Kanai M., Naito T., Sasa N., Yamamoto K., Takahashi K., Harada N., Naito T., Hiki M., Matsushita Y., Takagi H., Ichikawa M., Nakamura A., Harada S., Sandhu Y., Kabata H., Masaki K., Kamata H., Ikemura S., Chubachi S., Okamori S., Terai H., Morita A., Asakura T., Sasaki J., Morisaki H., Uwamino Y., Nanki K., Uchida S., Uno S., Nishimura T., Ishiguro T., Isono T., Shibata S., Matsui Y., Hosoda C., Takano K., Nishida T., Kobayashi Y., Takaku Y., Takayanagi N., Ueda S., Tada A., Miyawaki M., Yamamoto M., Yoshida E., Hayashi R., Nagasaka T., Arai S., Kaneko Y., Sasaki K., Tagaya E., Kawana M., Arimura K., Takahashi K., Anzai T., Ito S., Endo A., Uchimura Y., Miyazaki Y., Honda T., Tateishi T., Tohda S., Ichimura N., Sonobe K., Sassa C.T., Nakajima J., Nakano Y., Nakajima Y., Anan R., Arai R., Kurihara Y., Harada Y., Nishio K., Ueda T., Azuma M., Saito R., Sado T.

  Nature Genetics （Nature Genetics)  55 （ 5 ） 753 - 767 2023.05

  ISSN  10614036

  　View Summary

  Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

  • Access to Document (DOI)

• Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine

  Uwamino Y., Yokoyama T., Sato Y., Shibata A., Kurafuji T., Tanabe A., Noguchi M., Arai T., Ohno A., Yokota H., Namkoong H., Nishimura T., Kosaki K., Hasegawa N., Wakui M., Murata M., Matsushita H.

  Vaccine （Vaccine)  41 （ 9 ） 1545 - 1549 2023.02

  ISSN  0264410X

  　View Summary

  Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose. UMIN Clinical Trials Registry ID: UMIN000043340.

  • Access to Document (DOI)

display all >>

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

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

• Measures against COVID-19 at Keio University

  Nishimura, Tomoyasu

  学事振興資金研究成果実績報告書 （慶應義塾大学)  2021

• Measures against COVID-19 at Keio University

  Nishimura, Tomoyasu

  学事振興資金研究成果実績報告書 （慶應義塾大学)  2020

• Elucidation of the host immune response to nontuberculous mycobacterial cell wall lipids

  Nishimura, Tomoyasu

  科学研究費補助金研究成果報告書 2018

• Elucidation of miRNA-mediated pathophysiology of MAC pulmonary disease

  Nishimura, Tomoyasu

  科学研究費補助金研究成果報告書 2018

• Measures against mycobacteriosis at Keio University

  Nishimura, Tomoyasu

  学事振興資金研究成果実績報告書 （慶應義塾大学)  2018

display all >>

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• 外国人留学生を対象とした結核感染調査

  西村知泰，森正明，牧野伸司，広瀬寛，和井内由充子，横山裕一，武田彩乃，畔上達彦，後藤伸子，河邊博史

  第116回日本内科学会総会・講演会 (名古屋) , 

  2019.04

  , 

  Poster presentation

• 肺MAC症の新規検査法

  Nishimura Tomoyasu

  第101回日本細菌学会関東支部総会 (東京) , 

  2018.11

  , 

  Symposium, workshop panel (nominated)

• アスペルギルス沈降抗体陽性である肺Mycobacterium avium complex症患者の臨床的特徴

  鈴木翔二, 朝倉崇徳, 南宮湖, 岡森慧, 八木一馬, 鎌田浩史, 舩津洋平, 中野泰, 西村知泰, 石井誠, 海老原全, 別役智子, 長谷川直樹．

  第58回日本呼吸器学会学術講演会 (大阪) , 

  2018.04

  , 

  Poster presentation

• 大学生における先天性心疾患の管理状況

  牧野伸司, 和井内由充子, 武田彩乃, 畔上達彦, 広瀬寛, 西村知泰, 横山裕一, 河邊博史, 森正明．

  第115回日本内科学会年次学術講演会 (京都) , 

  2018.04

  , 

  Poster presentation

• 当大学医学部留学生に対するImmunization Recordの運用と考察

  武藤志保, 横山裕一, 弦巻美保, 齋藤圭美, 西村知泰, 森正明, 河邊博史．

  第55回全国大学保健管理研究集会 (宜野湾) , 

  2017.11

  , 

  Poster presentation

display all >>

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

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

• 肺MAC症の新規治療法開発に向けた菌細胞壁脂質の解析

  2023.04

  -

  2026.03

  文部科学省・日本学術振興会, 科学研究費補助金, Research grant, Principal investigator

• 肺非結核性抗酸菌症患者の宿主疾患感受遺伝子の機能解析による新規治療基盤の創出

  2023.04

  -

  2026.03

  文部科学省・日本学術振興会, 科学研究費補助金, Research grant, Coinvestigator(s)

• 個細胞空間的degradome解析に基づくプロテアーゼを介したがん免疫制御の解明

  2022.04

  -

  2026.03

  文部科学省・日本学術振興会, 科学研究費補助金, Research grant, Coinvestigator(s)

• 末梢気道病変に着目した肺NTM症の新たな治療標的の創出

  2022.04

  -

  2025.03

  国立研究開発法人日本医療研究開発機構, 新興・再興感染症研究基盤創生事業, Commissioned ｒesearch, Coinvestigator(s)

• ムチン異常集積に着目した肺非結核性抗酸菌症の病態解明

  2021.10

  -

  2024.03

  文部科学省・日本学術振興会, 科学研究費補助金, Research grant, Coinvestigator(s)

display all >>

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• MEDICINE IN MODERN SOCIETY 1

  2024

• INFECTIOUS DISEASES

  2024

• MEDICINE IN MODERN SOCIETY 2

  2023

• INFECTIOUS DISEASES

  2023

• INFECTIOUS DISEASES

  2022

display all >>

Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 感染症学

  Keio University

  2018.04

  -

  2019.03

  , 

  Full academic year, Other, Lecture, Lecturer outside of Keio

• 現代社会と医学Ⅱ

  Keio University

  2018.04

  -

  2019.03

  , 

  Full academic year, Other, Lecture, Within own ｆaculty

Social Activities 【 Display / hide 】

Social Activities 【 Display / hide 】

• 平成27年度外務省巡回医師団

  2016.02

  -

  2016.03

• 平成26年度外務省巡回医師団

  2015.01

  -

  2015.02

Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本免疫学会

  　

• 日本内科学会

  　

• 日本呼吸器学会

  　

• 日本呼吸器内視鏡学会

  　

• 日本感染症学会

  　

display all >>

Committee Experiences 【 Display / hide 】

Committee Experiences 【 Display / hide 】

• 2016.04

  -

  Present

  評議員, 日本感染症学会