Fukunaga, Koichi

写真a

Affiliation

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

Position

Professor
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Other Affiliation 【 Display / hide 】

  • School of Medicine, 内科学(呼吸器), Associate Professor

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Career 【 Display / hide 】

  • 1994.04
    -
    Present

    慶應義塾大学医学部, 内科学教室, 研修医

  • 2000.01
    -
    Present

    東京大学大学院, 生化学分子細胞生物学講座, 研究員

  • 2001.07
    -
    Present

    独立行政法人国立病院機構南横浜病院, 内科, 医員

  • 2002.08
    -
    Present

    ハーバード大学医学部Brigham Women’s Hospital, Post Doctoral fellow

  • 2005.11
    -
    Present

    慶應義塾大学医学部, 内科学呼吸器内科, 臨床助手

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Academic Background 【 Display / hide 】

  • 1994.03

    慶應義塾大学, 医学部

    University, Graduated

  • 2002.04

    慶應義塾大学, 臨床系呼吸循環器内科学

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, 慶應義塾大学, Coursework, 2002.04

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Licenses and Qualifications 【 Display / hide 】

  • 日本医師会産業認定医

  • 臨床研修指導医

  • 日本感染症学会　ICD（インフェクション・コントロールドクター）

  • 日本がん治療認定医機構　認定医

  • 日本アレルギー学会　専門医・指導医

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Research Areas 【 Display / hide 】

  • Life Science / Respiratory medicine

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Research Keywords 【 Display / hide 】

  • アレルギー

  • 喘息

  • 睡眠時無呼吸症候群

  • 脂質メディエーター

  • 自然免疫

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Research Themes 【 Display / hide 】

  • 睡眠時無呼吸症候群における合併症と新たな診断法の解明, 

    2010.04
    -
    Present

  • 難治性喘息における病態解明, 

    2000.04
    -
    Present

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Books 【 Display / hide 】

  • 進行性非小細胞肺癌に対する併用化学療法におけるDocetaxel投与量の影響

    YAMAGUCHI KAZUHIRO, 2003.12

  • ヒト気管支平滑筋細胞におけるトロンボキサンA2の作用

    Suzuki Yuusuke, Asano Kouichirou, Nakajima Takeshi, Yamaguchi Kazuhiro, Fukunaga Kouichi, Shiomi Tetsuya, 2003.02

  • ヒト気管支平滑筋細胞におけるトロンボキサンA2の作用

    YAMAGUCHI KAZUHIRO, 2003

  • 喘息の薬理遺伝学，副腎皮質ステロイド薬―グルココルチコイド受容体遺伝子変異と喘息治療の可能性―

    Fukunaga Kouichi, Yamaguchi Kazuhiro, 2002.04

  • ロイコトリエンC4合成酵素遺伝子多型とロイコトリエン受容体拮抗薬pranlukastの臨床効果

    Asano Kouichirou，Hasegawa Naoki，Nakamura Hidetoshi，Fukunaga Kouichi，Shiomi Tetsuya，Suzuki Yuusuke，Kanazawa Minoru，Yamaguchi Kazuhiro, 2002.02

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Papers 【 Display / hide 】

  • Author's reply: Atrial fibrillation and sleep apnea: A chicken and egg situation

    Kimura, T., Kohno, T., Fukunaga, K., Yamasawa, W., Fujisawa, T., Fukuoka, R., Nakajima, K., Kashimura, S., Kunitomi, A., Katsumata, Y., Nishiyama, T., Nishiyama, N., Aizawa, Y., Fukuda, K. and Takatsuki, S.

    Int J Cardiol 270   187 2018.11

    ISSN  1874-1754

  • Intermittent Exposure to Cigarette Smoke Increases Lung Tumors and the Severity of Emphysema More than Continuous Exposure

    Kameyama, N., Chubachi, S., Hegab, A. E., Yasuda, H., Kagawa, S., Tsutsumi, A., Fukunaga, K., Shimoda, M., Kanai, Y., Soejima, K. and Betsuyaku, T.

    Am J Respir Cell Mol Biol 59 （ 2 ） 179 - 188 2018.08

    ISSN  1535-4989

    　View Summary

    Lung cancer and chronic obstructive pulmonary disease are leading causes of morbidity and mortality worldwide, and cigarette smoking is a main risk factor for both. The presence of emphysema, an irreversible lung disease, further raises the risk of lung cancer in patients with chronic obstructive pulmonary disease. The mechanisms involved in smoke-induced tumorigenesis and emphysema are not fully understood, attributable to a lack of appropriate animal models. Here, we optimized a model of cigarette smoke (CS)-induced lung cancer and emphysema in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent carcinogen. We investigated whether variations in CS exposure patterns with the same total amount and duration of exposure affect tumorigenesis and/or development of emphysema. Continuous CS exposure for 3 months significantly suppressed 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced development of adenomas and adenocarcinomas; however, emphysema independently developed during this period. Surprisingly, intermittent CS exposure increased the severity of emphysema and resulted in a higher incidence of adenocarcinomas. Furthermore, intermittent CS exposure elicited a marked increase in M2-polarized macrophages within and near the developed tumors. By employing a CS exposure protocol with repeated cycles of cessation and relapse, we provide evidence that intermittent CS exposure enhances tumorigenesis and emphysema progression more than that of continuous CS exposure.

  • Development of Necrotizing Myopathy Following Interstitial Lung Disease with Anti-signal Recognition Particle Antibody

    Kusumoto, T., Okamori, S., Masuzawa, K., Asakura, T., Nishina, N., Chubachi, S., Naoki, K., Fukunaga, K. and Betsuyaku, T.

    Intern Med 57 （ 14 ） 2045 - 2049 2018.07

    ISSN  1349-7235

    　View Summary

    A 72-year-old man was admitted due to dyspnea on exertion with interstitial shadows and elevated serum creatinine kinase (CK). Despite a close examination, which included magnetic resonance imaging (MRI), we could not diagnose myopathy. Prednisolone was administered and gradually tapered. One year later, anti-signal recognition particle (SRP) antibody was confirmed and he was re-admitted for hypoxemia with elevated CK. MRI revealed muscle edema and a histopathological examination of a muscle biopsy specimen showed necrotizing myopathy. Prednisolone, cyclosporine, and intravenous immunoglobulin were administered. Physicians should carefully monitor muscle symptoms and serum CK levels in cases of interstitial lung disease with anti-SRP antibodies.

  • Prevalence and clinical characteristics of obstructive- and central-dominant sleep apnea in candidates of catheter ablation for atrial fibrillation in Japan

    Kohno, T., Kimura, T., Fukunaga, K., Yamasawa, W., Fujisawa, T., Fukuoka, R., Nakajima, K., Kashimura, S., Kunitomi, A., Katsumata, Y., Nishiyama, T., Nishiyama, N., Aizawa, Y., Fukuda, K. and Takatsuki, S.

    Int J Cardiol 260   99 - 102 2018.06

    ISSN  1874-1754

    　View Summary

    INTRODUCTION: We aimed to study the prevalence and types of sleep apnea (SA) as well as their clinical characteristics in atrial fibrillation (AF) ablation candidates in Japan. METHODS: Before catheter ablation, 197 consecutive AF patients (age: 60+/-9years, body mass index; 25.0+/-3.0) were evaluated with portable polygraphy. We compared the clinical characteristics, according to the severity of SA as well as its types, as defined by the presence of obstruction and the mixed vs. central apnea indices. RESULTS: The mean apnea-hypopnea index (AHI) was 17.7+/-11.9, with 135 AF patients having an AHI >/=10 (68.5%). Patients with an AHI >/=10 had a significantly higher body mass index, plasma brain natriuretic peptide (BNP) level, prevalence of hypertension, and larger left atrial size. Among patients with an AHI >/=10, the incidence of obstructive-dominant SA was 60.9% and that of central-dominant SA was 7.6%. The prevalence of hypertension was significantly higher in obstructive-dominant SA patients (obstructive vs. central: 48.3% vs. 20.0%, P=0.038). The obstructive apnea index correlated with plasma BNP level and age, but the central and mixed apnea indices did not. CONCLUSIONS: The prevalence of SA was common in AF ablation candidates, even without an obesity epidemic, and the SA type was predominantly obstructive. Portable polygraphy was useful for detecting undiagnosed SA patients in AF ablation candidates.

  • 12-OH-17,18-Epoxyeicosatetraenoic acid alleviates eosinophilic airway inflammation in murine lungs

    Mochimaru, T., Fukunaga, K., Miyata, J., Matsusaka, M., Masaki, K., Kabata, H., Ueda, S., Suzuki, Y., Goto, T., Urabe, D., Inoue, M., Isobe, Y., Arita, M. and Betsuyaku, T.

    Allergy 73 （ 2 ） 369 - 378 2018.02

    ISSN  1398-9995

    　View Summary

    BACKGROUND: Asthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega-6 fatty acid, is metabolized into cysteinyl leukotriene with pro-inflammatory properties for allergic inflammation, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti-inflammatory effects. In this study, we investigated the mechanism underlying the counter-regulatory roles of EPA in inflamed lungs. METHODS: Male C57BL6 mice were sensitized and challenged by ovalbumin (OVA). After EPA treatment, we evaluated the cell count of Bronchoalveolar lavage fluid (BALF), mRNA expressions in the lungs by q-PCR, and the amounts of lipid mediators by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics. We investigated the effect of the metabolite of EPA by in vivo and in vitro studies. RESULTS: Eicosapentaenoic acid treatment reduced the accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA-derived metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12-OH-17,18-EpETE attenuated airway eosinophilic inflammation through downregulation of C-C chemokine motif 11 (CCL11) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin-4. CONCLUSION: These results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12-OH-17,18-EpETE is a potential therapeutic target for the management of asthma.

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

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Presentations 【 Display / hide 】

  • 進行性非小細胞癌に対する併用化学療法におけるドセタキセル投与量の影響

    YAMAGUCHI KAZUHIRO

    第137回日本肺癌学会関東地方会 (東京) , 

    2003.06
    , 

    Oral presentation (general)

  • The usefulness monitoring serum concentrations of pulmonary epithelial markers KL6 and SPD during 18 months chemotherapy for patients with pulmonary Mycobacteria avium complex infection.

    YAMAGUCHI KAZUHIRO

    2003 ATS International Conference (Seattle) , 

    2003.05
    , 

    Poster presentation

  • 一次性肺MAC（Mycobacterium avium complex）症に対するクラリスロマイシン800mgを含む4剤治療の効果

    Hasegawa Naoki, Ooya Sumire, Fukunaga Kouichi, Takeshita Kei, Kou Hidefumi, Shimizu Mie, Yamada Wakako, Fujishima Seitarou, Ishizaka Akitoshi, Komatsu Hikotarou, Ishii Masamichi, Yamaguchi Kazuhiro

    43回日本呼吸器学会総会, 

    2003.03
    , 

    Oral presentation (general)

  • 血小板活性化因子（PAF）受容体遺伝子多型のヒト好中球機能に及ぼす影響

    Nakajima Takeshi, Asano Kouichirou, Fukunaga Kouichi, Suzuki Yuusuke, Shiomi Tetsuya, Yamaguchi Kazuhiro

    43回日本呼吸器学会総会, 

    2003.03
    , 

    Oral presentation (general)

  • Effects of thromboxane A2 mimetic on proliferation of human bronchial smooth muscle cells

    YAMAGUCHI KAZUHIRO

    2003 American Thoracic Society International Conference ('Seattle, Washington, USA') , 

    2003
    , 

    Poster presentation

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

  • Novel therapeutic strategy for refractory asthma using immunophenotyping

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

  • ヒト腸内細菌移植マウスを用いた肥満合併重症喘息の解明

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • steroid resistance of upper and lower airways

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

    　View Summary

    In conducting our research regarding steroid resistance of upper and lower airways, we collected　eosinophils and Group 2 innate lymphoid cells (ILC 2s) from surgical specimens of chronic eosinophilic sinusitis and peripheral blood of severe asthmatic patients and examined them. First, we established a method to collect each cell stably from the specimen and blood. Especially, ILC2s with small number in blood was examined using single cell analysis method which can analyze from one cell. As a result, the difference between the healthy subjects and the patient's phenotype (proliferative ability and cytokine production capacity) has become clear. In addition, eosinophils were also examined using comprehensive analysis and revealed differences in productivity of enzymes and mediators as compared to healthy subjects. We are currently investigating the resistance of steroids of these cells and will continue to conduct current research.

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Courses Taught 【 Display / hide 】

  • SYMPTOMATOLOGY

    2024

  • PHARMACOLOGY

    2024

  • ORIENTAL MEDICINE

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (PULMONOLOGY)

    2024

  • KAMPO MEDICINE: SEMINAR

    2024

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