Kamata, Hirofumi



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



Academic Background 【 Display / hide

  • 2003

    Keio University, 医学部

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, 2011


Papers 【 Display / hide

  • 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 AE, 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 2020.03

    ISSN  1040-0605

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    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.

  • Sitafloxacin-containing regimen for the treatment of refractory mycobacterium avium complex lung disease

    Asakura T., Suzuki S., Fukano H., Okamori S., Kusumoto T., Uwamino Y., Ogawa T., So M., Uno S., Namkoong H., Yoshida M., Kamata H., Ishii M., Nishimura T., Hoshino Y., Hasegawa N.

    Open Forum Infectious Diseases (Open Forum Infectious Diseases)  6 ( 4 ) ofz108 2019.04

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    © The Author(s) 2019. Background. Sitafloxacin (STFX) exhibits potent activity against Mycobacterium avium complex (MAC) in both in vitro and in vivo experiments. However, limited data are available for the clinical efficacy and adverse effects of STFX and the susceptibility of refractory MAC lung disease (MAC-LD) to the drug. Therefore, this study was aimed at evaluating the clinical efficacy and safety of an STFX-containing regimen for the treatment of refractory MAC-LD. Methods. We retrospectively evaluated treatment outcomes of 31 patients with refractory MAC-LD, who received an STFXcontaining regimen for ≥4 weeks between January 2010 and July 2017. Refractory MAC-LD was defined as persistent positive sputum cultures for >6 months of macrolide-based standard therapy. Results. Clarithromycin resistance (minimum inhibitory concentration [MIC] ≥32 μg/mL) was identified in 15 patients (48%). Twelve months after receiving the STFX-containing regimen, 26% and 19% of patients showed symptomatic and radiological responses, respectively. Although STFX-associated adverse effects were noted in 9 patients, their severity was grade 1 (National Cancer Institute Common Terminology Criteria); only 1 patient discontinued STFX because of suspected gastrointestinal disturbance. Negative sputum culture conversion was achieved in 7 patients (23%). Both univariate and multivariate logistic regression analyses revealed that surgery, low STFX MIC (≤1 μg/mL), and macrolide resistance were significant predictors of negative sputum culture conversion. Conclusions. Our results demonstrate that STFX may be effective in one-fourth of patients with refractory MAC-LD. Prospective larger studies that include the analyses of MAC are needed to determine the clinical efficacy of STFX against refractory MAC-LD.

  • Development of lung cancer in patients with nontuberculous mycobacterial lung disease

    Kusumoto T., Asakura T., Suzuki S., Okamori S., Namkoong H., Fujiwara H., Yagi K., Kamata H., Ishii M., Betsuyaku T., Hasegawa N.

    Respiratory Investigation (Respiratory Investigation)  57 ( 2 ) 157 - 164 2019.03

    ISSN  22125345

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    © 2018 The Japanese Respiratory Society Background: As lung cancer development in patients with nontuberculous mycobacterial lung disease (NTM-LD) has never been reported, we investigated its incidence and clinical characteristics. Methods: Prospective observational cohort registry (from June 2012 to June 2017), and retrospective identification by the International Classification of Diseases, tenth revision (between March 2010 and March 2018), were used to identify NTM-LD patients aged ≥20 years who developed lung cancer. Results: Eight patients (two men and six women, one with smoking history), having Mycobacterium avium complex lung disease (MAC-LD) were identified. Four were identified from retrospective chart reviews and four from the prospective observational cohort registry (n = 361, 289 women; 311 never-smokers). All patients underwent chest computed tomography (CT) at least once a year. The incidence rate of lung cancer developing in NTM-LD patients was 124.6 per 100,000 patient-years, which was higher than the lung cancer rate in Japan. The mean age at diagnosis of MAC-LD and lung cancer was 63.6 and 74.4 years, respectively. The most common lung cancer types were adenocarcinoma (six patients) followed by squamous cell carcinoma (two patients). Lung cancer was diagnosed at early and advanced clinical stages in seven and one patients, respectively. Outcomes were favorable, except in two patients: one with advanced stage disease, and another with poor performance status. Conclusions: We identified the clinical characteristics of eight MAC-LD patients who developed lung cancer. NTM-LD may be a risk factor for lung cancer development. Periodic follow-up with chest CT might contribute to early diagnosis and curative therapy for lung cancer.

  • Quantitative assessment of erector spinae muscles in patients with Mycobacterium avium complex lung disease

    Asakura T., Yamada Y., Suzuki S., Namkoong H., Okamori S., Kusumoto T., Niijima Y., Ozaki A., Hashimoto M., Yagi K., Kamata H., Funatsu Y., Ishii M., Jinzaki M., Betsuyaku T., Hasegawa N.

    Respiratory Medicine (Respiratory Medicine)  145   66 - 72 2018.12

    ISSN  09546111

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    © 2018 Elsevier Ltd Background and objective: No reports exist regarding skeletal muscle involvement in patients with Mycobacterium avium complex lung disease (MAC-LD). The cross-sectional area of the erector spinae muscles (ESMCSA) reflects physical activity and can be assessed by computed tomography (CT). We investigated the relationship between ESMCSA and physiological parameters and prognosis in MAC-LD patients. Material and methods: In this prospective observational study, the ESMCSA was measured on single-slice axial CT images. MAC-LD patients and sex- and age-matched controls (non-MAC-LD participants) were evaluated. We evaluated the relationship between the ESMCSA and physiological parameters and prognosis. Results: A total of 260 patients (209 female; median age, 69 years; 190 with nodular/bronchiectatic disease; 74 with cavitary lesions) were enrolled. The ESMCSA was not different between MAC-LD patients and controls. In MAC-LD patients, the ESMCSA was significantly associated with age, body mass index (BMI), pulmonary function, CT severity, and health-related quality of life (HRQL). Multivariate Cox proportional hazards analyses revealed that an ESMCSA < −1 standard derivation (hazards ratio [HR], 2.76; P = 0.047) was significantly associated with all-cause mortality, along with BMI < 18.5 kg/m2 (HR, 3.67; P = 0.02) and presence of cavitary lesions (HR, 5.84; P = 0.001). However, the ESMCSA was not significantly associated with all-cause mortality when current treatment status, % predicted functional vital capacity, and forced expiratory volume in 1 s were added to the analyses. Conclusions: Although the prognostic impact was limited, ESMCSA was significantly associated with HRQL and prognostic physiological parameters, such as BMI and pulmonary function.

  • Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b <sup>+</sup> Gr-1 <sup>+</sup> cell expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine pulmonary emphysema

    Asakura T., Ishii M., Namkoong H., Suzuki S., Kagawa S., Yagi K., Komiya T., Hashimoto T., Okamori S., Kamata H., Tasaka S., Kihara A., Hegab A., Hasegawa N., Betsuyaku T.

    Mucosal Immunology (Mucosal Immunology)  11 ( 6 ) 1606 - 1620 2018.11

    ISSN  19330219

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    © 2018, Society for Mucosal Immunology. Sphingolipids play a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, little is known about the precise roles of sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, and its receptor modulation in COPD. In this study, we demonstrated that the S1P receptor modulator ONO-4641 induced the expansion of lung CD11b + Gr-1 + cells and lymphocytopenia in naive mice. ONO-4641-expanded CD11b + Gr-1 + cells showed higher arginase-1 activity, decreased T cell proliferation, and lower IFN-γ production in CD3 + T cells, similar to the features of myeloid-derived suppressor cells. ONO-4641 treatment decreased airspace enlargement in elastase-induced and cigarette smoke-induced emphysema models and attenuated emphysema exacerbation induced by post-elastase pneumococcal infection, which was also associated with an increased number of lung CD11b + Gr-1 + cells. Adoptive transfer of ONO-4641-expanded CD11b + Gr-1 + cells protected against elastase-induced emphysema. Lymphocytopenia observed in these models likely contributed to beneficial ONO-4641 effects. Thus, ONO-4641 attenuated murine pulmonary emphysema by expanding lung CD11b + Gr-1 + cell populations and inducing lymphocytopenia. The S1P receptor might be a promising target for strategies aimed at ameliorating pulmonary emphysema progression.

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

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

  • 肺炎球菌性肺炎においてSectm1aが好中球の肺への集積に及ぼす影響と機序の解明


    文部科学省・日本学術振興会, 科学研究費助成事業, 鎌田浩史, 基盤研究(C), Principal Investigator

  • 肺炎球菌性肺炎においてSectm1aが肺の感染免疫機構へ及ぼす作用の解明


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 鎌田 浩史, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • The contribution of a novel epithelial-derived cytokine to the host defense against pneumococcal pneumonia


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 鎌田 浩史, Grant-in-Aid for Young Scientists (B), Principal Investigator


Courses Taught 【 Display / hide