Ishii, Makoto

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Pulmonary Medicine) (Shinanomachi)

Position

Associate Professor

External Links

Career 【 Display / hide

  • 1996.04
    -
    1998.03

    慶應義塾大学医学部研修医(内科学)

  • 1998.04
    -
    2002.03

    慶應義塾大学医学部専修医(内科学)

  • 1998.05
    -
    1999.04

    北里研究所メディカルセンター病院 内科

  • 1999.05
    -
    2000.05

    済生会宇都宮病院 内科

  • 2000.06
    -
    2004.06

    慶應義塾大学医学部 内科学(呼吸器)

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Academic Background 【 Display / hide

  • 1996.03

    Keio University

    University, Graduated

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, 2005.05

Licenses and Qualifications 【 Display / hide

  • 医師免許, 1996.05

 

Research Areas 【 Display / hide

  • Respiratory organ internal medicine (呼吸器感染症学、呼吸器再生学)

  • Infectious disease medicine

Research Keywords 【 Display / hide

  • エピジェネティクス

  • 呼吸器再生医学

  • 呼吸器感染症 

  • 感染免疫

 

Papers 【 Display / hide

  • Exposure to Cigarette Smoke Enhances the Stemness of Alveolar Type 2 Cells

    A Tsutsumi, M Ozaki, S Chubachi, H Irie, M Sato, N Kameyama, M Sasaki, ...

    American Journal of Respiratory Cell and Molecular Biology (American journal of respiratory cell and molecular biology)  63 ( 3 ) 293 - 305 2020.09

     View Summary

    Chronic exposure to cigarette smoke (CS) causes chronic inflammation, oxidative stress, and apoptosis of epithelial cells, which results in destruction of the lung matrix. However, the mechanism by which the lung fails to repair the CS-induced damage, thereby succumbing to emphysema, remains unclear. Alveolar type 2 (AT2) cells comprise the stem cells of the alveolar compartments and are responsible for repairing and maintaining lung tissues. In this study, we examined the effect of chronic CS on AT2 stem cells. Adult mice expressing GFP in their AT2 cells were exposed to CS for > 3 months. Histological assessment showed that CS not only induced emphysematous changes but also increased the number of AT2 cells compared with that of air-exposed lungs. Assessment of sorted GFP+/AT2 cells via the stem cell three-dimensional organoid/colony-forming assay revealed that the number and size of the colonies formed by the CS-exposed AT2 stem cells were significantly higher than those of air-exposed control AT2 cells. Although CS-exposed lungs had more apoptotic cells, examination of the surviving AT2 stem cells in two-dimensional in vitro culture revealed that they developed a higher ability to resist apoptosis. Microarray analysis of CS-exposed AT2 stem cells revealed the upregulation of genes related to circadian rhythm and inflammatory pathways. In conclusion, we provide evidence that AT2 stem cells respond to chronic CS exposure by activating their stem cell function, thereby proliferating and differentiating faster and becoming more resistant to apoptosis. Disturbances in expression levels of several circadian rhythm-related genes might be involved in these changes.

  • Clinical significance of anti-glycopeptidolipid-core IgA antibodies in patients newly diagnosed with Mycobacterium avium complex lung disease

    Matsuda S., Asakura T., Morimoto K., Suzuki S., Fujiwara K., Furuuchi K., Osawa T., Namkoong H., Ishii M., Kurashima A., Tatsumi K., Ohta K., Hasegawa N., Sasaki Y.

    Respiratory Medicine (Respiratory Medicine)  171 2020.09

    ISSN  09546111

     View Summary

    © 2020 Elsevier Ltd Background: Although recent studies have identified anti-glycopeptidolipid (GPL)-core IgA antibodies as a serodiagnostic test for Mycobacterium avium complex lung disease (MAC-LD), this test shows insufficient sensitivity. This study aimed to determine the clinical utility of these antibodies in assessing disease progression and the clinical characteristics of MAC-LD patients with negative antibody results. Methods: We retrospectively reviewed the medical records of consecutive newly diagnosed, untreated MAC-LD patients in two referral hospitals. We evaluated the association of anti-GPL-core IgA antibody results with disease progression requiring treatment and the factors associated with negative antibody results. Results: In total, 229 patients (161 females; median age, 71 years; 185 with nodular/bronchiectatic disease phenotype; 69 with cavitary lesions) were enrolled; 146 patients (64%) were anti-GPL-core IgA antibody-positive. Radiological severity scores were associated with anti-GPL-core IgA antibody titers. During the median 364-day follow-up, 114 patients (49.8%) required treatment. Multivariate Cox proportional hazards analysis showed that positive anti-GPL-core IgA antibody results, a younger age, the absence of malignancy, and the presence of cavitary lesions were associated with disease progression requiring treatment. Multivariate logistic analysis revealed that significant factors related to the negative antibody results included underlying pulmonary disease, lower radiological scores, chronic sinusitis, and macrolide monotherapy. Conclusion: In addition to cavitary lesions, anti-GPL-core IgA antibody positivity was associated with disease progression requiring treatment. Physicians should carefully use anti-GPL-core IgA antibody results for the diagnosis of patients with underlying pulmonary disease, chronic sinusitis, macrolide monotherapy, and lower radiological severity.

  • Coronavirus disease 2019-associated rapidly progressive organizing pneumonia with fibrotic feature: Two case reports

    Okamori S., Lee H., Kondo Y., Akiyama Y., Kabata H., Kaneko Y., Ishii M., Hasegawa N., Fukunaga K.

    Medicine (Medicine)  99 ( 35 )  2020.08

     View Summary

    INTRODUCTION: Pneumonia is one of the most important characteristics of coronavirus disease 2019 (COVID-19) and imaging findings of COVID-19 pneumonia are diverse and change over disease course. However, the detailed clinical course of organizing pneumonia (OP) caused by COVID-19 has not been clarified. PATIENT CONCERNS: A 60-year-old man and a 61-year-old woman diagnosed with mild COVID-19 were admitted to our hospital. Their respiratory symptoms were deteriorating even after initiating treatment with antiviral drugs. DIAGNOSIS: Chest X-rays and computed tomography scan showed a rapid progression of linear consolidation with reversed halo sign, distributed in subpleural and peri-bronchial regions. They also presented with pulmonary fibrosis findings, including traction bronchiectasis and marked lung volume reduction. They were diagnosed with rapidly progressing OP. INTERVENTIONS: They were treated with systemic corticosteroids. OUTCOMES: The patients' imaging findings and respiratory conditions improved rapidly without any adverse effects. CONCLUSION: Physicians should carefully monitor patients with COVID-19, as they can develop rapidly progressive and fibrotic OP, which respond to corticosteroids.

  • ADAM17 protects against elastase-induced emphysema by suppressing CD62L<sup>+</sup> leukocyte infiltration in mice

    Suzuki S., Ishii M., Asakura T., Namkoong H., Okamori S., Yagi K., Kamata H., Kusumoto T., Kagawa S., Hegab A.E., Yoda M., Horiuchi K., Hasegawa N., Betsuyaku T.

    American journal of physiology. Lung cellular and molecular physiology (American journal of physiology. Lung cellular and molecular physiology)  318 ( 6 ) L1172 - L1182 2020.06

     View Summary

    Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation. In the present study, we aimed to investigate the potential role of ADAM17 and CD62L in the development of elastase-induced emphysema. Control and Adam17flox/flox/Mx1-Cre (Adam17ΔMx1) mice (8-10 wk old) were intratracheally injected with 5 units of porcine pancreas elastase and monitored for 35 days after injection. Lung alveolar destruction was evaluated by analyzing the mean linear intercepts of lung tissue specimens and by histopathological examination. Mean linear intercepts data indicated that the degree of elastase-induced emphysema was significantly more severe in Adam17ΔMx1 mice. Furthermore, flow cytometry showed that CD62L+ neutrophil, CD62L+ macrophage, and CD62L+ B lymphocyte numbers were significantly increased in Adam17ΔMx1 mice. Moreover, the pharmacological depletion of CD62L+ cells with a CD62L-neutralizing antibody ameliorated the extent of emphysema in Adam17ΔMx1 mice. Collectively, these results suggest that ADAM17 possibly suppresses the progression of emphysema by proteolytically processing CD62L in immune cells and that ADAM17 and CD62L could be novel therapeutic targets for treating pulmonary emphysema.

  • DISTINCT EXPRESSION OF COINHIBITORY MOLECULES ON ALVEOLAR T CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS- AND IDIOPATHIC INFLAMMATORY MYOPATHIES-ASSOCIATED INTERSTITIAL LUNG DISEASE

    Nakazawa M., Suzuki K., Takeshita M., Inamo J., Kamata H., Ishii M., Oyamada Y., Oshima H., Takeuchi T.

    ANNALS OF THE RHEUMATIC DISEASES 79   232 - 233 2020.06

    ISSN  0003-4967

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

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Reviews, Commentaries, etc. 【 Display / hide

  • 嗅神経芽細胞腫がACTH産生腫瘍へ形質転換し、小細胞癌と鑑別を要したノカルジア肺炎の一例

    小林 慧悟, 朝倉 崇徳, 石井 誠

    感染症学雑誌 ((一社)日本感染症学会)  94 ( 臨増 ) 274 - 274 2020.03

    ISSN  0387-5911

  • ハイインパクトペーパーシンポジウム 呼吸器感染症の病態解明に向けた基礎研究からのアプローチ

    石井 誠

    感染症学雑誌 ((一社)日本感染症学会)  94 ( 臨増 ) 167 - 167 2020.03

    ISSN  0387-5911

  • 感染と免疫の分子機構 増加する肺非結核性抗酸菌症の臨床研究から得られた最近の知見

    石井 誠

    日本細菌学雑誌 (日本細菌学会)  75 ( 1 ) 7 - 7 2020.01

    ISSN  0021-4930

  • 呼吸器内視鏡が開く感染症学との接点 気道被覆液中の抗微生物薬濃度のPharmacokinetics

    舩津 洋平, 藤原 宏, 浅見 貴弘, 西村 智泰, 石井 誠, 南宮 湖, 八木 一馬, 黄 英文, 長谷川 直樹

    気管支学 ((NPO)日本呼吸器内視鏡学会)  41 ( Suppl. ) S157 - S157 2019.06

    ISSN  0287-2137

  • 呼吸器の修復・再生機序を探る 直接リプログラミングにより誘導した肺上皮様細胞による呼吸器修復・再生

    石井 誠

    日本呼吸器学会誌 ((一社)日本呼吸器学会)  8 ( 増刊 ) 42 - 42 2019.03

    ISSN  2186-5876

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Presentations 【 Display / hide

  • ラット肺虚血再潅流傷害に対するJNK阻害剤の効果

    YAMAGUCHI KAZUHIRO

    第44回日本呼吸器学会総会 (東京) , 2004.03, Poster (general)

  • Ovalbumin(OA)感作気道炎症ラットモデルの肺微小循環におけるVCAM-1依存性リンパ球動態異常

    YAMAGUCHI KAZUHIRO

    第44回日本呼吸器学会総会 (東京) , 2004.03, Poster (general)

  • Protection of hypercapnic acidosis against endotoxin-induced pulmonary endothelial cell injury.

    YAMAGUCHI KAZUHIRO

    第44回日本呼吸器学会総会 (東京) , 2004.03, Oral Presentation(general)

  • 肺血管内皮細胞障害に対するエダラボンの抑制効果とその機序

    YAMAGUCHI KAZUHIRO

    第44回日本呼吸器学会総会 (東京) , 2004.03, Poster (general)

  • Intracellular signal transduction and cytokine production in hyperoxia-exposed human alveolar macrophages.

    YAMAGUCHI KAZUHIRO

    2003 ATS International Conference (Seattle) , 2003.05, Poster (general)

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

  • AMED再生医療実現拠点ネットワークプログラム(技術開発個別課題<トランスレーショナルリサーチ1> 研究開発代表者

    2019.09
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    2022.03

    国立研究開発法人 日本医療研究開発機構(AMED), 石井誠, Research grant, Principal Investigator

  • COVID-19症例の急性増悪/重症化に至る予測マーカーの探索と数理的定量化

    2020.07
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    2021.03

    慶應義塾 KGRI 2020年度新型コロナウイルス危機研究補助金, 石井誠

  • 直接リプログラミングによるヒト肺上皮細胞の誘導と新たな治療法の開発

    2020.04
    -
    2021.03

    慶應義塾 福沢基金 研究助成

  • 呼吸器と腸管をつなぐ粘膜上皮インターフェースを制御する分子基盤の解明

    2020.04
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    2021.03

    慶應義塾次世代研究プロジェクト推進プログラム, 木村俊介, Research grant, Co-investigator

  • 肺非結核性抗酸菌症の疾患感受性遺伝子の同定・機能解析

    2019.04
    -
    2020.03

    慶應義塾 学事振興資金 共同研究(代表), Principal Investigator

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Awards 【 Display / hide

  • 第67回日本感染症学会東日本地方会 最優秀賞

    2019.02

    Type of Award: Awards of National Conference, Council and Symposium

  • AMED橋渡し研究 シーズA

    2018

  • JKiC(JSR・慶應義塾大学 医学化学イノベーションセンター)学術開発プロジェクト

    2018

    Type of Award: Other Awards

  • 財団法人武田科学振興財団 2017年度 医学系研究奨励 継続助成

    2017

  • AMED橋渡し研究 シーズA

    2017

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Courses Taught 【 Display / hide

  • LECTURE SERIES, INTERNAL MEDICINE (PULMONOLOGY)

    2020

  • LECTURE SERIES, INTERNAL MEDICINE

    2020

  • CASE STUDIES OF INTERNAL MEDICINE

    2020

  • CASE STUDIES OF INTERNAL MEDICINE

    2019

  • LECTURE SERIES, INTERNAL MEDICINE

    2019

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Courses Previously Taught 【 Display / hide

  • 内科学(呼吸器)

    慶應義塾大学医学部, 2019, Major subject, Lecture, Lecturer outside of Keio

  • 内科学(呼吸器)

    慶應義塾大学医学部, 2018, Major subject, Lecture, Lecturer outside of Keio

  • 内科学(呼吸器)

    慶應義塾大学医学部, 2017, Major subject, Lecture, Lecturer outside of Keio

  • 内科学(呼吸器)

    慶應義塾大学医学部, 2016, Major subject, Lecture, Lecturer outside of Keio

  • 内科学(呼吸器)

    Keio University, 2015

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Educational Activities and Special Notes 【 Display / hide

  • 慶應義塾大学内科専門研修プログラム管理委員会委員長

    2015
    -
    Present

    , Device of Educational Contents

  • ハワイ大学PBL教育ワークショップ 参加

    2011
    -
    Present

    , Special Affairs

 

Social Activities 【 Display / hide

  • 日本学術振興会 科学研究費一次審査委員

    2015.04
    -
    2017.03
  • 日本学術振興会 科学研究費一次審査委員 二次審査委員

    2018.04
    -
    2020.03
  • NPO法人 NTM-JRC 理事

    2015.04
    -
    Present

Memberships in Academic Societies 【 Display / hide

  • American Thoracic Society

     
  • 日本内科学会(認定医・専門医・指導医)

     
  • 日本呼吸器学会(専門医・指導医)

     
  • 日本呼吸器内視鏡学会(専門医・指導医)

     
  • 日本感染症学会(専門医・指導医), 

    2003.12
    -
    Present

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Committee Experiences 【 Display / hide

  • 2015.09
    -
    Present

    慶應義塾大学内科専門研修プログラム管理委員会委員長, 日本内科学会/慶應義塾大学病院

  • 2019.04
    -
    Present

    第94回日本感染症学会学術集会プログラム委員, 日本感染症学会

  • 2011.04
    -
    Present

    慶應義塾大学病院 保険委員会(副委員長) 

  • 2020.04
    -
    Present

    財務委員会 委員, 日本呼吸器学会 

  • 2017
    -
    Present

    臨床研究推進委員会 委員, 日本感染症学会

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