2024/04/04 更新

写真a

イシイ マコト
石井 誠
ISHII Makoto
所属
大学院医学系研究科 総合医学専攻 病態内科学 教授
大学院担当
大学院医学系研究科
学部担当
医学部 医学科
職名
教授
連絡先
メールアドレス
プロフィール
1996年3月 慶應義塾大学医学部卒業
1996年4月 慶應義塾大学医学部 研修医(内科学)
1998年5月 北里研究所メディカルセンター病院(現北里大学メディカルセンター) 内科
1999年5月 済生会宇都宮病院 内科
2000年6月 慶應義塾大学医学部 内科学(呼吸器) 助手
2004年7月 さいたま市立病院内科(呼吸器内科)
2006年8月 米国ミシガン大学医学部 病理学教室免疫プログラム Steven Kunkel教授研究室ポストドクトラルフェロー
2009年9月 慶應義塾大学医学部 呼吸器内科 助教
2010年10月 慶應義塾大学医学部 呼吸器内科 専任講師
2019年10月 慶應義塾大学医学部 呼吸器内科 准教授/診療副部長
2020年10月 慶應義塾大学病院 医療保険指導部 部長(兼任)
2022年6月 名古屋大学 大学院医学系研究科 総合医学専攻 病態内科学講座 呼吸器内科学 教授
現在に至る。

学位 1

  1. 博士(医学) ( 2004年11月   慶應義塾大学 ) 

研究キーワード 5

  1. 呼吸器感染症学

  2. 感染免疫学

  3. 呼吸器再生学

  4. エピジェネティクス

  5. 呼吸器感染症

研究分野 1

  1. ライフサイエンス / 呼吸器内科学  / 呼吸器感染症学

現在の研究課題とSDGs 1

  1. 炎症性肺疾患の病態解明と新規治療法の開発

経歴 1

  1. 国立大学法人 東海国立大学機構 名古屋大学   大学院医学系研究科 総合医学専攻 病態内科学講座 呼吸器内科学   教授

    2022年6月 - 現在

学歴 1

  1. 慶應義塾大学

    - 1996年3月

所属学協会 11

  1. 日本禁煙学会(認定指導者)

  2. 米国胸部疾患学会

    2000年 - 現在

  3. 日本臨床腫瘍学会

  4. 日本肺癌学会

  5. 日本結核病学会(認定医,指導医)

  6. 日本感染症学会(専門医・指導医)

  7. 日本呼吸器学会(専門医・指導医)

  8. 日本呼吸器内視鏡学会(専門医・指導医)

  9. 日本化学療法学会(認定医、指導医)

  10. 日本再生医療学会

  11. 日本アレルギー学会(専門医・指導医)

▼全件表示

委員歴 7

  1. 慶應義塾大学病院 保険指導部 (部長)  

    2021年4月 - 2022年5月   

  2. 国民保険東京都審査委員(公益代表)  

    2013年4月 - 2022年5月   

  3. 日本呼吸器学会   財務委員会 委員  

    2020年4月 - 現在   

  4. 日本感染症学会   第94回日本感染症学会学術集会プログラム委員  

    2019年4月 - 2020年4月   

  5. 日本感染症学会 評議員  

    2018年4月 - 現在   

  6. 日本呼吸器学会 代議員  

    2018年4月 - 現在   

  7. 日本感染症学会   臨床研究推進委員会 委員  

    2017年 - 現在   

▼全件表示

受賞 24

  1. 国民健康保険中央会 診療報酬審査 永年表彰

    2021年8月  

  2. 2021年大樹生命財団 第54回医学研究助成(代表)

    2021年7月   新型コロナウイルス感染後の肺及び他臓器の長期後遺症の実態解明

  3. 慶應義塾大学医学部呼吸器内科同門会 最優秀論文(臨床研究部門)

    2021年7月  

  4. 大和証券ヘルス財団 令和2年度 新型コロナウイルス感染症(COVID-19) に関する調査研究助成

    2021年1月   公益財団法人 大和証券ヘルス財団  

  5. 平成30年度 日本感染症学会 東日本地方会 最優秀賞

    2019年2月  

  6. 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年  

  7. 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年  

  8. ファイザー独立教育グラント (Pfizer Independent Grants for Learning & Change (IGL&C)

    2017年  

  9. 公益財団法人 日本呼吸器財団 平成29年度研究助成

    2017年  

  10. 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

    2017年  

  11. 公益財団法人金原一郎記念医学医療振興財団 第30回基礎医学医療研究助成

    2015年  

  12. 第42回大和証券ヘルス財団調査研究助成

    2015年  

  13. 財団法人武田科学振興財団 2014年度 医学系研究奨励 助成

    2014年  

  14. 第51回日本呼吸器学会学術講演会 International Session Award

    2011年4月  

  15. 慶應義塾大学医学部三四会(医学部同窓会)奨励賞

    2010年11月  

  16. 第25回日本Shock学会総会 会長賞

    2010年5月  

  17. 財団法人武田科学振興財団 2010年度 医学系研究奨励 助成

    2010年  

  18. 大山健康財団学術研究助成

    2010年  

  19. Kyorin Respiratory Research Award

    2009年11月  

  20. 第6回東京呼吸器リサーチフォーラム 最優秀奨励賞

    2009年11月  

  21. 第13回呼吸器病態研究会 優秀奨励賞

    2009年11月  

  22. 上原記念生命科学財団 海外留学助成リサーチフェローシップ

    2008年   マクロファージのエピジェネティック制御

  23. 第36回 かなえ医薬振興財団 海外留学助成

    2006年  

  24. 慶應義塾大学医学部呼吸循環器内科同窓会 最優秀論文

    2004年12月  

▼全件表示

 

論文 332

  1. Durvalumab plus carboplatin-etoposide treatment in a patient with small-cell lung cancer on hemodialysis: a case report and literature review.

    Ushijima F, Hase T, Yamashita Y, Kim H, Shimokata T, Kondo C, Sato T, Baba T, Watanabe S, Futamura K, Ando Y, Mizuno M, Ishii M

    International cancer conference journal   13 巻 ( 2 ) 頁: 88 - 92   2024年4月

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    記述言語:英語  

    DOI: 10.1007/s13691-023-00640-8

    PubMed

  2. Integrated assessment of computed tomography density in pectoralis and erector spinae muscles as a prognostic biomarker for coronavirus disease 2019

    Nakagawara K., Shiraishi Y., Chubachi S., Tanabe N., Maetani T., Asakura T., Namkoong H., Tanaka H., Shimada T., Azekawa S., Otake S., Fukushima T., Watase M., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    Clinical Nutrition   43 巻 ( 3 ) 頁: 815 - 824   2024年3月

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    記述言語:英語   出版者・発行元:Clinical Nutrition  

    Background & aims: Muscle quantification using chest computed tomography (CT) is a useful prognostic biomarker for coronavirus disease 2019 (COVID-19). However, no studies have evaluated the clinical course through comprehensive assessment of the pectoralis and erector spinae muscles. Therefore, we compared the impact of the areas and densities of these muscles on COVID-19 infection outcome. Methods: This multicenter retrospective cohort study was conducted by the COVID-19 Task Force. A total of 1410 patients with COVID-19 were included, and data on the area and density of the pectoralis and erector spinae muscles on chest CT were collected. The impact of each muscle parameter on the clinical outcome of COVID-19 was stratified according to sex. The primary outcome was the percentage of patients with severe disease, including those requiring oxygen supplementation and those who died. Additionally, 167 patients were followed up for changes in muscle parameters at three months and for the clinical characteristics in case of reduced CT density. Results: For both muscles, low density rather than muscle area was associated with COVID-19 severity. Regardless of sex, lower erector spinae muscle density was associated with more severe disease than pectoralis muscle density. The muscles were divided into two groups using the receiver operating characteristic curve of CT density, and the population was classified into four (Group A: high CT density for both muscles, Group B: low CT density for pectoralis and high for erector spinae muscle. Group C: high CT density for pectoralis and low for erector spinae muscle, Group D: low CT density for both muscles). In univariate analysis, Group D patients exhibited worse outcomes than Group A (OR: 2.96, 95% CI: 2.03–4.34 in men; OR: 3.02, 95% CI: 2.66–10.4 in women). Multivariate analysis revealed that men in Group D had a significantly more severe prognosis than those in Group A (OR: 1.82, 95% CI: 1.16–2.87). Moreover, Group D patients tended to have the highest incidence of other complications due to secondary infections and acute kidney injury during the clinical course. Longitudinal analysis of both muscle densities over three months revealed that patients with decreased muscle density over time were more likely to have severe cases than those who did not. Conclusions: Muscle density, rather than muscle area, predicts the clinical outcomes of COVID-19. Integrated assessment of pectoralis and erector spinae muscle densities demonstrated higher accuracy in predicting the clinical course of COVID-19 than individual assessments.

    DOI: 10.1016/j.clnu.2024.02.004

    Scopus

    PubMed

  3. Rapidly progressive interstitial lung disease with positive anti-MDA5 antibody as an immune-related complication of nivolumab: A case report

    Kato S., Sakamoto K., Sato T., Kobayashi T., Shindo Y., Morise M., Iwama S., Arima H., Ishii M.

    Respiratory Investigation   62 巻 ( 2 ) 頁: 313 - 316   2024年3月

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    記述言語:英語   出版者・発行元:Respiratory Investigation  

    Clinically amyopathic dermatomyositis (CADM) with a positive anti-MDA5 antibody titer is often associated with lethal rapidly progressive interstitial lung disease (RP-ILD). Despite the widespread use of immune checkpoint inhibitors (ICIs) in practice, there is no report of CADM with positive anti-MDA5 antibodies as their immune-related complication. We present a case of malignant mesothelioma who developed RP-ILD accompanied by distinct skin manifestations following the administration of nivolumab. Postmortem assessment of stored samples revealed a pre-existing positive titer of anti-MDA5 antibody, further augmented following ICI use, suggesting the possible value of serum screening for better risk stratification of this lethal complication.

    DOI: 10.1016/j.resinv.2024.01.009

    Scopus

    PubMed

  4. Cluster analysis of long COVID in Japan and association of its trajectory of symptoms and quality of life.

    Ito F, Terai H, Kondo M, Takemura R, Namkoong H, Asakura T, Chubachi S, Masuzawa K, Nakayama S, Suzuki Y, Hashiguchi M, Kagyo J, Shiomi T, Minematsu N, Manabe T, Fukui T, Funatsu Y, Koh H, Masaki K, Ohgino K, Miyata J, Kawada I, Ishii M, Sato Y, Fukunaga K

    BMJ open respiratory research   11 巻 ( 1 )   2024年2月

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    記述言語:英語  

    DOI: 10.1136/bmjresp-2023-002111

    PubMed

  5. Real-time ultrasound-guided thoracentesis simulation using an optical see-through head-mounted display: a proof-of-concept study.

    Okachi S, Matsui T, Sakurai M, Ito T, Morise M, Imaizumi K, Ishii M, Fujiwara M

    Journal of ultrasonography   24 巻 ( 96 ) 頁: 20240012   2024年2月

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    記述言語:英語  

    DOI: 10.15557/jou.2024.0012

    PubMed

  6. Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study.

    Matsubara Y, Kiyohara H, Mikami Y, Nanki K, Namkoong H, Chubachi S, Tanaka H, Azekawa S, Sugimoto S, Yoshimatsu Y, Sujino T, Takabayashi K, Hosoe N, Sato T, Ishii M, Hasegawa N, Okada Y, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Fukunaga K, Kanai T, Japan COVID-19 Task Force

    Journal of gastroenterology     2024年1月

     詳細を見る

    記述言語:英語  

    DOI: 10.1007/s00535-023-02071-x

    PubMed

  7. Epicardial adipose tissue measured from analysis of adipose tissue area using chest CT imaging is the best potential predictor of COVID-19 severity

    Fukushima T., Maetani T., Chubachi S., Tanabe N., Asakura T., Namkoong H., Tanaka H., Shimada T., Azekawa S., Otake S., Nakagawara K., Watase M., Shiraishi Y., Terai H., Sasaki M., Ueda S., Kato Y., Harada N., Suzuki S., Yoshida S., Tateno H., Yamada Y., Jinzaki M., Hirai T., Okada Y., Koike R., Ishii M., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    Metabolism: Clinical and Experimental   150 巻   頁: 155715   2024年1月

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    記述言語:英語   出版者・発行元:Metabolism: Clinical and Experimental  

    Background: Computed tomography (CT) imaging is widely used for diagnosing and determining the severity of coronavirus disease 2019 (COVID-19). Chest CT imaging can be used to calculate the epicardial adipose tissue (EAT) and upper abdominal visceral adipose tissue (Abd-VAT) areas. The EAT is the main source of inflammatory cytokines involved in chest inflammatory diseases; thus, the EAT area might be a more useful severity predictor than the Abd-VAT area for COVID-19. However, to the best of our knowledge, there are no large-scale reports that sufficiently consider this issue. In addition, there are no reports on the characteristics of patients with normal body mass index (BMI) and high adipose tissue. Aim: The purpose of this study was to analyze whether the EAT area, among various adipose tissues, was the most associated factor with COVID-19 severity. Using a multicenter COVID-19 patient database, we analyzed the associations of chest subcutaneous, chest visceral, abdominal subcutaneous, and Abd-VAT areas with COVID-19 outcomes. In addition, the clinical significance of central obesity, commonly disregarded by BMI, was examined. Methods: This retrospective cohort study evaluated patients with COVID-19 aged ≥18 years In Japan. Data including from chest CT images collected between February 2020 and October 2022 in four hospitals of the Japan COVID-19 Task Force were analyzed. Patient characteristics and COVID-19 severity were compared according to the adipose tissue areas (chest and abdominal subcutaneous adipose tissue [Chest-SAT and Abd-SAT], EAT, and Abd-VAT) calculated from chest CT images. Results: We included 1077 patients in the analysis. Patients with risk factors of severe COVID-19 such as old age, male sex, and comorbidities had significantly higher areas of EAT and Abd-VAT. High EAT area but not high Abd-VAT area was significantly associated with COVID-19 severity (adjusted odds ratio (aOR): 2.66, 95 % confidence interval [CI]: 1.19–5.93). There was no strong correlation between BMI and VAT. Patients with high VAT area accounted for 40.7 % of the non-obesity population (BMI < 25 kg/m2). High EAT area was also significantly associated with COVID-19 severity in the non-obesity population (aOR: 2.50, 95 % CI: 1.17–5.34). Conclusions: Our study indicated that VAT is significantly associated with COVID-19 severity and that EAT is the best potential predictor for risk stratification in COVID-19 among adipose tissue areas. Body composition assessment using EAT is an appropriate marker for identifying obesity patients overlooked by BMI. Considering the next pandemic of the global health crisis, our findings open new avenues for implementing appropriate body composition assessments based on CT imaging.

    DOI: 10.1016/j.metabol.2023.155715

    Scopus

    PubMed

  8. Upper Respiratory Symptoms as Long COVID: Insight from a Multicenter Cohort Study 査読有り 国際誌

    Masahiko Okada, Noriyuki Ishida, Sho Kanzaki, Ichiro Kawada, Kengo Nagashima, Hideki Terai, Gaku Hiruma, Ho Namkoong, Takanori Asakura, Katsunori Masaki, Keiko Ohgino, Jun Miyata, Shotaro Chubachi, Nobuhiro Kodama, Shunsuke Maeda, Satoshi Sakamoto, Masaki Okamoto, Yoji Nagasaki, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Kazuhiro Minami, Rie Hagiwara, Makoto Ishii, Yasunori Sato, Koichi Fukunaga

    OTO Open   8 巻 ( 1 ) 頁: e120   2024年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OTO Open  

    Objective: This study aimed to investigate the clinical features of long COVID cases presenting with upper respiratory symptoms, a topic not yet fully elucidated. Study Design: Prospective cohort study. Setting: A multicenter study involving 26 medical facilities in Japan. Methods: Inclusion criteria were patients aged ≥18 years old with a confirmed COVID-19 diagnosis via severe acute respiratory syndrome coronavirus 2 polymerase chain reaction or antigen testing, who were hospitalized at the participating medical facilities. Analyzing clinical information and patient-reported outcomes from 1009 patients were analyzed. The outcome measured the degree of initial symptoms for taste or olfactory disorders and assessed the likelihood of these symptoms persisting as long COVID, as well as the impact on quality of life if the upper respiratory symptoms persisted as long COVID. Results: Patients with high albumin, low C-reactive protein, and low lactate dehydrogenase in laboratory tests tended to experience taste or olfactory disorders as part of long COVID. Those with severe initial symptoms had a higher risk of experiencing residual symptoms at 3 months, with an odds ratio of 2.933 (95% confidence interval [CI], 1.282-6.526) for taste disorders and 3.534 (95% CI, 1.382-9.009) for olfactory disorders. Presence of upper respiratory symptoms consistently resulted in lower quality of life scores. Conclusion: The findings from this cohort study suggest that severe taste or olfactory disorders as early COVID-19 symptoms correlate with an increased likelihood of persistent symptoms in those disorders as long COVID.

    DOI: 10.1002/oto2.120

    Scopus

    PubMed

  9. Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease

    Sato T., Furukawa T., Teramachi R., Fukihara J., Yamano Y., Yokoyama T., Matsuda T., Kataoka K., Kimura T., Sakamoto K., Ishii M., Kondoh Y.

    Thorax     2024年

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    記述言語:英語   出版者・発行元:Thorax  

    Background: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. Methods: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. Results: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 20<MPAP<25 mm Hg, and ≥25 mm Hg were 26.2%, 60.4% and 86.4%, respectively. In Cox proportional hazards analyses with adjustment for ILD-Gender, Age and Physiology Index, PVR but not MPAP was associated with a higher mortality rate (HR 1.37, 95% CI 1.23 to 1.52, p<0.0001; HR 0.98, 95% CI 0.96 to 1.01, p=0.1671, respectively). PVR>2 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. Conclusions: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

    DOI: 10.1136/thorax-2023-220179

    Scopus

    PubMed

  10. Characteristics of patients with COVID-19 who have deteriorating chest X-ray findings within 48 h: a retrospective cohort study 国際誌

    Kusumoto T., Chubachi S., Namkoong H., Tanaka H., Lee H., Otake S., Nakagawara K., Fukushima T., Morita A., Watase M., Asakura T., Masaki K., Kamata H., Ishii M., Hasegawa N., Harada N., Ueda T., Ueda S., Ishiguro T., Arimura K., Saito F., Yoshiyama T., Nakano Y., Mutoh Y., Suzuki Y., Edahiro R., Murakami K., Sato Y., Okada Y., Koike R., Kitagawa Y., Tokunaga K., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    Scientific Reports   13 巻 ( 1 ) 頁: 22054 - 22054   2023年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    The severity of chest X-ray (CXR) findings is a prognostic factor in patients with coronavirus disease 2019 (COVID-19). We investigated the clinical and genetic characteristics and prognosis of patients with worsening CXR findings during early hospitalization. We retrospectively included 1656 consecutive Japanese patients with COVID-19 recruited through the Japan COVID-19 Task Force. Rapid deterioration of CXR findings was defined as increased pulmonary infiltrates in ≥ 50% of the lung fields within 48 h of admission. Rapid deterioration of CXR findings was an independent risk factor for death, most severe illness, tracheal intubation, and intensive care unit admission. The presence of consolidation on CXR, comorbid cardiovascular and chronic obstructive pulmonary diseases, high body temperature, and increased serum aspartate aminotransferase, potassium, and C-reactive protein levels were independent risk factors for rapid deterioration of CXR findings. Risk variant at the ABO locus (rs529565-C) was associated with rapid deterioration of CXR findings in all patients. This study revealed the clinical features, genetic features, and risk factors associated with rapid deterioration of CXR findings, a poor prognostic factor in patients with COVID-19.

    DOI: 10.1038/s41598-023-49340-6

    Scopus

    PubMed

  11. High-performance glass filters for capturing and culturing circulating tumor cells and cancer-associated fibroblasts 査読有り

    Tanaka H., Iwata D., Shibata Y., Hase T., Onoshima D., Yogo N., Shibata H., Sato M., Ishikawa K., Nagasawa I., Hasegawa Y., Ishii M., Baba Y., Hori M.

    Scientific Reports   13 巻 ( 1 ) 頁: 4130   2023年12月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Various liquid biopsy methods have been developed for the non-invasive and early detection of diseases. In particular, the detection of circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) in blood has been receiving a great deal of attention. We have been developing systems and materials to facilitate such liquid biopsies. In this study, we further developed glass filters (with various patterns of holes, pitches, and non-adhesive coating) that can capture CTCs, but not white blood cells. We optimized the glass filters to capture CTCs, and demonstrated that they could be used to detect CTCs from lung cancer patients. We also used the optimized glass filters for detecting CAFs. Additionally, we further developed a system for visualizing the captured cells on the glass filters. Finally, we demonstrated that we could directly culture the captured cells on the glass filters. Based on these results, our high-performance glass filters appear to be useful for capturing and culturing CTCs and CAFs for further examinations.

    DOI: 10.1038/s41598-023-31265-9

    Scopus

    PubMed

  12. Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations.

    Nakagawara K, Morita A, Namkoong H, Terai H, Chubachi S, Asakura T, Tanaka H, Ito F, Matsuyama E, Kaji M, Saito A, Takaoka H, Okada M, Sunata K, Watase M, Yagi K, Ohgino K, Miyata J, Kamata H, Kawada I, Kobayashi K, Hirano T, Inoue T, Kagyo J, Shiomi T, Otsuka K, Miyao N, Odani T, Baba R, Arai D, Nakachi I, Ueda S, Funatsu Y, Koh H, Ishioka K, Takahashi S, Nakamura M, Sato T, Hasegawa N, Kitagawa Y, Kanai T, Ishii M, Fukunaga K

    Vaccine: X   15 巻   頁: 100381   2023年12月

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    記述言語:英語  

    DOI: 10.1016/j.jvacx.2023.100381

    PubMed

  13. Clinical features of Japanese patients with gastrointestinal long-COVID symptoms 国際誌

    Yagi K., Asakura T., Terai H., Ohgino K., Masaki K., Namkoong H., Chubachi S., Miyata J., Kawada I., Kodama N., Sakamoto S., Umeda A., Ishiguro T., Ishii M., Fukunaga K.

    JGH Open   7 巻 ( 12 ) 頁: 998 - 1002   2023年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JGH Open  

    DOI: 10.1002/jgh3.13006

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    PubMed

  14. Estimating gene-level false discovery probability improves eQTL statistical fine-mapping precision 国際誌

    Wang Q.S., Edahiro R., Namkoong H., Hasegawa T., Shirai Y., Sonehara K., Kumanogoh A., Ishii M., Koike R., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K., Okada Y.

    NAR Genomics and Bioinformatics   5 巻 ( 4 ) 頁: lqad090   2023年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NAR Genomics and Bioinformatics  

    Statistical fine-mapping prioritizes putative causal variants from a large number of candidate variants, and is widely used in expression quantitative loci (eQTLs) studies. In eQTL fine-mapping, the existence of causal variants for gene expression is not guaranteed, since the genetic heritability of gene expression explained by nearby (cis-) variants is limited. Here we introduce a refined fine-mapping algorithm, named Knockoff-Finemap combination (KFc). KFc estimates the probability that the causal variant(s) exist in the cis-window of a gene through construction of knockoff genotypes (i.e. a set of synthetic genotypes that resembles the original genotypes), and uses it to adjust the posterior inclusion probabilities (PIPs). Utilizing simulated gene expression data, we show that KFc results in calibrated PIP distribution with improved precision. When applied to gene expression data of 465 genotyped samples from the Japan COVID-19 Task Force (JCTF), KFc resulted in significant enrichment of a functional score as well as reporter assay hits in the top PIP bins. When combined with functional priors derived from an external fine-mapping study (GTEx), KFc resulted in a significantly higher proportion of hematopoietic trait putative causal variants in the top PIP bins. Our work presents improvements in the precision of a major fine-mapping algorithm.

    DOI: 10.1093/nargab/lqad090

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    PubMed

  15. Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial

    Matsuzawa R., Morise M., Ito K., Hataji O., Takahashi K., Koyama J., Kuwatsuka Y., Goto Y., Imaizumi K., Itani H., Yamaguchi T., Zenke Y., Oki M., Ishii M.

    eClinicalMedicine   66 巻   頁: 102303   2023年12月

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    記述言語:英語   出版者・発行元:eClinicalMedicine  

    Background: Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however, no prospective clinical trials of docetaxel (DTX) plus ramucirumab (RAM) following first-line ICI plus platinum-based chemotherapy has been reported. Methods: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients with NSCLC from eight centres in Japan. Patients with metastatic NSCLC with disease progression after platinum-based chemotherapy plus ICI were eligible for the study. Patients were intravenously treated with 60 mg/m2 of DTX and 10 mg/kg of RAM on day 1 with a strong recommendation of pegfilgrastim administration on day 2 every 3 weeks. The primary end point was objective response rate (ORR) in efficacy analysis population. Safety was assessed in all patients treated at least one dose. The ORR of the null and alternative hypotheses were 10% and 30%, with α error of 0.1 and β error of 0.1. This trial is registered with the Japan Registry for Clinical Trials, jCRTs041190077. Findings: Between 16 January, 2020, and 24 August, 2021, 33 patients (median age 66 [range 42–79] years) were enrolled. Thirteen patients (41%) had Eastern Cooperative Oncology Group performance status of 1. Twenty-five patients (78%) had an interval of <60 days after the last administration of ICI. In the efficacy analysis population (n = 32), the primary endpoint was met as 11 patients achieved partial response (PR), with ORR of 34.4% (80% CI, 23.1–47.2). Grade ≥3 anaemia and febrile neutropenia were observed in 2 (6%) and 3 (9%) patients, respectively. No treatment-related deaths and no new safety signals were observed. Interpretation: DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have progressed on front-line ICIs plus platinum-based chemotherapy. The results of this trial can be a helpful reference in conducting further phase III trials of new second-line treatment options. Funding: Eli Lilly Japan K.K.

    DOI: 10.1016/j.eclinm.2023.102303

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  16. Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study 国際誌

    Sunata K., Miyata J., Terai H., Matsuyama E., Watase M., Namkoong H., Asakura T., Masaki K., Chubachi S., Ohgino K., Kawada I., Harada N., Sasano H., Nakamura A., Kusaka Y., Ohba T., Nakano Y., Nishio K., Nakajima Y., Suzuki S., Yoshida S., Tateno H., Ishii M., Fukunaga K.

    Allergology International     2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Allergology International  

    Background: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. Methods: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. Results: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. Conclusions: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

    DOI: 10.1016/j.alit.2023.11.003

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    PubMed

  17. Calcium channel blockers may reduce the development of long COVID in females 国際誌

    Ozawa T., Kimura R., Terai H., Takemura R., Namkoong H., Kondo M., Fukuda K., Yagi K., Asakura T., Masaki K., Chubachi S., Miyata J., Ohgino K., Kawada I., Kagyo J., Odani T., Kuwahara N., Nakachi I., Ishii M., Sato Y., Fukunaga K.

    Hypertension Research     2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Hypertension Research  

    With the rising numbers of patients infected with severe acute respiratory syndrome coronavirus 2, long coronavirus disease 2019 (COVID-19)—a sequelae of COVID-19—has become a major problem. Different sexes and age groups develop different long COVID symptoms, and the risk factors for long COVID remain unclear. Therefore, we performed subgroup analyses of patients with COVID-19, classifying them into different groups. In this multicenter cohort study, using an original questionnaire, we examined patients (≥18 years old) diagnosed with COVID-19 from November 2020 to March 2022 and hospitalized at participating medical facilities. In total, 1066 patients were registered (361 female, 620 male). Hypertension was the most common comorbidity (n = 344; 32.5%). Females with hypertension were significantly less likely to develop long COVID symptoms than those without hypertension (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27–0.98; p = 0.043). In females, Ca channel blocker administration, rather than having hypertension, was significantly associated with reductions in the frequency of alopecia (OR 0.14, 95% CI 0.03–0.67, p = 0.015), memory impairment (OR 0.14, 95% CI 0.02–0.82, p = 0.029), sleeping disorders (OR 0.17, 95% CI 0.04–0.67, p = 0.012), tinnitus (OR 0.23, 95% CI 0.05–0.98, p = 0.047), sputum (OR 0.31, 95% CI 0.10–0.92, p = 0.035), and fever (OR 0.33, 95% CI 0.12–0.93, p = 0.036). Several long COVID symptoms, including alopecia, were significantly negatively associated with Ca channel-blocker administration in female patients with long COVID. [Figure not available: see fulltext.].

    DOI: 10.1038/s41440-023-01501-w

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    PubMed

  18. Cough and sputum in long COVID are associated with severe acute COVID-19: a Japanese cohort study 国際誌

    Watase M., Miyata J., Terai H., Sunata K., Matsuyama E., Asakura T., Namkoong H., Masaki K., Yagi K., Ohgino K., Chubachi S., Kawada I., Mochimaru T., Satomi R., Oyamada Y., Kobayashi K., Hirano T., Inoue T., Lee H., Sugihara K., Omori N., Sayama K., Mashimo S., Makino Y., Kaido T., Ishii M., Fukunaga K.

    Respiratory Research   24 巻 ( 1 ) 頁: 283 - 283   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respiratory Research  

    Background: Multiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID. Methods: Hospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. Results: At the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan–Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months. Conclusions: In a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.

    DOI: 10.1186/s12931-023-02591-3

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  19. 特集 呼吸器感染症のアンメットニーズを探る Ⅰ.病態理論に基づく治療戦略 ウイルス性肺炎の病態機序

    石井 誠

    呼吸器ジャーナル   71 巻 ( 4 ) 頁: 460 - 467   2023年11月

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    出版者・発行元:株式会社 医学書院  

    DOI: 10.11477/mf.1437200680

    CiNii Research

  20. Clinical utilization of artificial intelligence-based COVID-19 pneumonia quantification using chest computed tomography - a multicenter retrospective cohort study in Japan.

    Tanaka H, Maetani T, Chubachi S, Tanabe N, Shiraishi Y, Asakura T, Namkoong H, Shimada T, Azekawa S, Otake S, Nakagawara K, Fukushima T, Watase M, Terai H, Sasaki M, Ueda S, Kato Y, Harada N, Suzuki S, Yoshida S, Tateno H, Yamada Y, Jinzaki M, Hirai T, Okada Y, Koike R, Ishii M, Hasegawa N, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K

    Respiratory research   24 巻 ( 1 ) 頁: 241   2023年10月

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    記述言語:英語  

    DOI: 10.1186/s12931-023-02530-2

    PubMed

  21. 縦隔リンパ節腫大を呈するラテックスアレルギー患者に対してバルーン非使用下にEBUS-TBNAを施行し確定診断が得られた2例

    松澤 令子, 伊藤 貴康, 今泉 和良, 石井 あずさ, 伊藤 克樹, 二村 圭祐, 岡地 祥太郎, 森瀬 昌宏, 若原 恵子, 石井 誠

    気管支学   45 巻 ( 5 ) 頁: 339 - 344   2023年9月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    <p><b>背景.</b>超音波気管支鏡ガイド下針生検(EBUS-TBNA)の際,バルーン非使用下で穿刺可能な病変についての報告は少ない.<b>症例1.</b>70代,女性.ゴム手袋にアレルギーあり.ぶどう膜炎の精査中に多発リンパ節(#4R,#7)腫大を指摘された.<b>症例2.</b>40代,男性.ゴム手袋にアレルギーあり.肺腺癌の術後経過観察目的に撮像したCTで縦隔リンパ節(#7)の腫大を指摘された.<b>結果.</b>症例1,2ともに,バルーン非使用下に腫大した縦隔リンパ節に対してEBUS-TBNAを施行した.症例1は#7が短径10 mm,#4Rが短径15 mm,症例2は#7が短径17 mmと腫大しておりバルーン非使用下でも十分に病変の描出・穿刺が可能であった.症例1はサルコイドーシス,症例2は肺腺癌術後再発と診断した.<b>結論.</b>バルーン非使用下にEBUS-TBNAを行う際,標的病変の穿刺難易度を検査前に評価しアプローチが比較的容易と考えられる病変を選択するなど十分に準備した上で検査に望むことが重要である.</p>

    DOI: 10.18907/jjsre.45.5_339

    CiNii Research

  22. A second update on mapping the human genetic architecture of COVID-19

    Kanai M., Andrews S.J., Cordioli M., Stevens C., Neale B.M., Daly M., Ganna A., Pathak G.A., Iwasaki A., Karjalainen J., Mehtonen J., Pirinen M., Chwialkowska K., Trankiem A., Balaconis M.K., Veerapen K., Wolford B.N., Ahmad H.F., Andrews S., von Hohenstaufen Puoti K.A., Boer C., Boua P.R., Butler-Laporte G., Cadilla C.L., Colombo F., Douillard V., Dueker N., Dutta A.K., El-Sherbiny Y.M., Eltoukhy M.M., Esmaeeli S., Faucon A., Fave M.J., Cadenas I.F., Francescatto M., Francioli L., Franke L., Fuentes M., Durán R.G., Cabrero D.G., Harry E.N., Jansen P., Szentpéteri J.L., Kaja E., Kanai M., Kirk C., Kousathanas A., Krieger J.E., Patel S.K., Lemaçon A., Limou S., Lió P., Marouli E., Marttila M.M., Medina-Gómez C., Michaeli Y., Migeotte I., Mondal S., Moreno-Estrada A., Moya L., Nakanishi T., Nasir J., Pasko D., Pearson N.M., Pereira A.C., Priest J., Prijatelj V., Prokic I., Teumer A., Várnai R., Romero-Gómez M., Roos C., Rosenfeld J., Ruolin L., Schulte E.C., Schurmann C., Sedaghati-khayat B., Shaheen D., Shivanathan I., Sipeky C., Sirui Z., Striano P., Tanigawa Y., Remesal A.U., Vadgama N., Vallerga C.L., van der Laan S., Verdugo R.A., Wang Q.S., Wei Z., Zainulabid U.A., Zárate R.N., Auton A., Shelton J.F., Shastri A.J., Weldon C.H., Filshtein-Sonmez T., Coker D., Symons A.

    Nature   621 巻 ( 7977 ) 頁: E7 - E26   2023年9月

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    出版者・発行元:Nature  

    DOI: 10.1038/s41586-023-06355-3

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  23. Erratum to: Mapping the human genetic architecture of COVID-19 (Nature, (2021), 600, 7889, (472-477), 10.1038/s41586-021-03767-x)

    Niemi M.E.K., Karjalainen J., Liao R.G., Neale B.M., Daly M., Ganna A., Pathak G.A., Andrews S.J., Kanai M., Veerapen K., Fernandez-Cadenas I., Schulte E.C., Striano P., Marttila M., Minica C., Marouli E., Karim M.A., Wendt F.R., Savage J., Sloofman L., Butler-Laporte G., Kim H.N., Kanoni S., Okada Y., Byun J., Han Y., Uddin M.J., Smith G.D., Willer C.J., Buxbaum J.D., Mehtonen J., Finucane H., Cordioli M., Martin A.R., Zhou W., Pasaniuc B., Julienne H., Aschard H., Shi H., Yengo L., Polimanti R., Ghoussaini M., Schwartzentruber J., Dunham I., Chwialkowska K., Francescatto M., Trankiem A., Balaconis M.K., Davis L., Lee S., Priest J., Renieri A., Sankaran V.G., Van Heel D., Deelen P., Richards J.B., Nakanishi T., Biesecker L., Kerchberger V.E., Baillie J.K., Mari F., Bernasconi A., Ceri S., Canakoglu A., Wolford B., Faucon A., Dutta A.K., Schurmann C., Harry E., Birney E., Nguyen H., Nasir J., Kaunisto M., Solomonson M., Dueker N., Vadgama N., Limou S., Rahmouni S., Mbarek H., Darwish D., Uddin M.M., Albertos R., Pérez-Tur J., Li R., Folkersen L., Moltke I., Koelling N., Teumer A., Kousathanas A., Utrilla A., Verdugo R.A., Zárate R., Medina-Gómez C., Gómez-Cabrero D., Carnero-Montoro E., Cadilla C.L., Moreno-Estrada A., Garmendia A., Moya L., Sedaghati-Khayat B.

    Nature   621 巻 ( 7977 ) 頁: E7 - E26   2023年9月

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    出版者・発行元:Nature  

    DOI: 10.1093/1476-4687

    Scopus

  24. Association between ABO blood group/genotype and COVID-19 in a Japanese population.

    Kusumoto T, Chubachi S, Namkoong H, Tanaka H, Lee H, Azekawa S, Otake S, Nakagawara K, Fukushima T, Morita A, Watase M, Sakurai K, Asakura T, Masaki K, Kamata H, Ishii M, Hasegawa N, Harada N, Ueda T, Ueda S, Ishiguro T, Arimura K, Saito F, Yoshiyama T, Nakano Y, Mutoh Y, Suzuki Y, Edahiro R, Sano H, Sato Y, Okada Y, Koike R, Kitagawa Y, Tokunaga K, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K

    Annals of hematology     2023年8月

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    記述言語:英語  

    DOI: 10.1007/s00277-023-05407-y

    PubMed

  25. Clinical characteristics of patients with COVID-19 harboring detectable intracellular SARS-CoV-2 RNA in peripheral blood cells.

    Tanaka H, Namkoong H, Chubachi S, Irie S, Uwamino Y, Lee H, Azekawa S, Otake S, Nakagawara K, Fukushima T, Watase M, Kusumoto T, Masaki K, Kamata H, Ishii M, Okada Y, Takano T, Imoto S, Koike R, Kimura A, Miyano S, Ogawa S, Kanai T, Sato TA, Fukunaga K, Japan COVID-19 Task Force

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases     2023年8月

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    記述言語:英語  

    DOI: 10.1016/j.ijid.2023.07.030

    PubMed

  26. Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study 国際誌

    Morita Atsuho, Yagi Kazuma, Asakura Takanori, Namkoong Ho, Sato Yasunori, Ogawa Takunori, Kusumoto Tatsuya, Suzuki Shoji, Tanaka Hiromu, Lee Ho, Okamori Satoshi, Azekawa Shuhei, Nakagawara Kensuke, Kaji Masanori, Nagao Genta, Funatsu Yohei, Kimizuka Yoshifumi, Kamata Hirofumi, Nishimura Tomoyasu, Ishii Makoto, Fukunaga Koichi, Hasegawa Naoki

    BMC PULMONARY MEDICINE   23 巻 ( 1 ) 頁: 247 - 247   2023年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Pulmonary Medicine  

    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.

    DOI: 10.1186/s12890-023-02528-y

    Web of Science

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    PubMed

  27. Propensity-Score Matched Analysis of the Effectiveness of Baricitinib in Patients With Coronavirus Disease 2019 (COVID-19) Using Nationwide Real-World Data: An Observational Matched Cohort Study From the Japan COVID-19 Task Force.

    Tanaka H, Chubachi S, Namkoong H, Sato Y, Asakura T, Lee H, Azekawa S, Otake S, Nakagawara K, Fukushima T, Watase M, Sakurai K, Kusumoto T, Kondo Y, Masaki K, Kamata H, Ishii M, Kaneko Y, Hasegawa N, Ueda S, Sasaki M, Izumo T, Inomata M, Miyazawa N, Kimura Y, Suzuki Y, Harada N, Ichikawa M, Takata T, Ishikura H, Yoshiyama T, Kokuto H, Murakami K, Sano H, Ueda T, Kuwahara N, Fujiwara A, Ogura T, Inoue T, Asami T, Mutoh Y, Nakachi I, Baba R, Nishi K, Tani M, Kagyo J, Hashiguchi M, Oguma T, Asano K, Nishikawa M, Watanabe H, Okada Y, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K

    Open forum infectious diseases   10 巻 ( 7 ) 頁: ofad311   2023年7月

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    記述言語:英語  

    DOI: 10.1093/ofid/ofad311

    PubMed

  28. Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review

    Futamura Keisuke, Hase Tetsunari, Tanaka Akihito, Sakai Yoshinori, Okachi Shotaro, Shibata Hirofumi, Ushijima Futoshi, Hashimoto Takahiko, Nakashima Kuniya, Ito Katsuki, Yamamoto Takanori, Numaguchi Atsushi, Inden Yasuya, Ishii Makoto

    INTERNATIONAL CANCER CONFERENCE JOURNAL   12 巻 ( 4 ) 頁: 299 - 304   2023年6月

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  29. Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents

    Takeshita Masaru, Fukuyama Hidehiro, Kamada Katsuhiko, Matsumoto Takehisa, Makino-Okamura Chieko, Lin Qingshun, Sakuma Machie, Kawahara Eiki, Yamazaki Isato, Uchikubo-Kamo Tomomi, Tomabechi Yuri, Hanada Kazuharu, Hisano Tamao, Moriyama Saya, Takahashi Yoshimasa, Ito Mutsumi, Imai Masaki, Maemura Tadashi, Furusawa Yuri, Yamayoshi Seiya, Kawaoka Yoshihiro, Shirouzu Mikako, Ishii Makoto, Saya Hideyuki, Kondo Yasushi, Kaneko Yuko, Suzuki Katsuya, Fukunaga Koichi, Takeuchi Tsutomu, Keio Donner Project the Keio Donner

    ISCIENCE   26 巻 ( 6 ) 頁: 106955   2023年6月

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    記述言語:英語   出版者・発行元:iScience  

    Several antibody therapeutics have been developed against SARS-CoV-2; however, they have attenuated neutralizing ability against variants. In this study, we generated multiple broadly neutralizing antibodies from B cells of convalescents, by using two types of receptor-binding domains, Wuhan strain and the Gamma variant as bait. From 172 antibodies generated, six antibodies neutralized all strains prior to the Omicron variant, and the five antibodies were able to neutralize some of the Omicron sub-strains. Structural analysis showed that these antibodies have a variety of characteristic binding modes, such as ACE2 mimicry. We subjected a representative antibody to the hamster infection model after introduction of the N297A modification, and observed a dose-dependent reduction of the lung viral titer, even at a dose of 2 mg/kg. These results demonstrated that our antibodies have certain antiviral activity as therapeutics, and highlighted the importance of initial cell-screening strategy for the efficient development of therapeutic antibodies.

    DOI: 10.1016/j.isci.2023.106955

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  30. Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis

    Yamamoto Takafumi, Mizuno Kazuyuki, Ito Takanori, Yokoyama Shinya, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Ishikawa Takuya, Kanamori Akira, Yasuda Satoshi, Toyoda Hidenori, Yokota Kenji, Hase Tetsunari, Nishio Naoki, Maeda Osamu, Ishii Makoto, Sone Michihiko, Ando Yuichi, Akiyama Masashi, Ishigami Masatoshi, Kawashima Hiroki

    INVESTIGATIONAL NEW DRUGS   41 巻 ( 3 ) 頁: 512 - 521   2023年6月

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    記述言語:英語   出版者・発行元:Investigational New Drugs  

    Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics.

    DOI: 10.1007/s10637-023-01366-3

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  31. Rebound mortality rate of Legionella pneumonia in Japan.

    Yamasue M, Komiya K, Kinjo T, Ito A, Yamaguchi T, Iwanaga N, Ishii M, Tateda K, Kawakami K

    Respiratory investigation   61 巻 ( 4 ) 頁: 487 - 489   2023年5月

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    記述言語:英語  

    DOI: 10.1016/j.resinv.2023.04.005

    PubMed

  32. Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan.

    Fukutani E, Wakahara K, Nakamura S, Yokoi E, Yoshimi A, Miyazaki M, Nakamura M, Shindo Y, Sakamoto K, Okachi S, Tanaka I, Hamajima N, Noda Y, Hashimoto N, Ishii M

    The Journal of asthma : official journal of the Association for the Care of Asthma     頁: 1 - 18   2023年5月

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    記述言語:英語  

    DOI: 10.1080/02770903.2023.2209173

    PubMed

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

    Edahiro Ryuya, Shirai Yuya, Takeshima Yusuke, Sakakibara Shuhei, Yamaguchi Yuta, Murakami Teruaki, Morita Takayoshi, Kato Yasuhiro, Liu Yu-Chen, Motooka Daisuke, Naito Yoko, Takuwa Ayako, Sugihara Fuminori, Tanaka Kentaro, Wing James B., Sonehara Kyuto, Tomofuji Yoshihiko, Namkoong Ho, Tanaka Hiromu, Lee Ho, Fukunaga Koichi, Hirata Haruhiko, Takeda Yoshito, Okuzaki Daisuke, Kumanogoh Atsushi, Okada Yukinori, Wang Qingbo S., Edahiro Ryuya, Namkoong Ho, Hasegawa Takanori, Shirai Yuya, Sonehara Kyuto, Tanaka Hiromu, Lee Ho, Saiki Ryunosuke, Hyugaji Takayoshi, Shimizu Eigo, Katayama Kotoe, Kanai Masahiro, Naito Tatsuhiko, Sasa Noah, Yamamoto Kenichi, Kato Yasuhiro, Morita Takayoshi, Takahashi Kazuhisa, Harada Norihiro, Naito Toshio, Hiki Makoto, Matsushita Yasushi, Takagi Haruhi, Ichikawa Masako, Nakamura Ai, Harada Sonoko, Sandhu Yuuki, Kabata Hiroki, Masaki Katsunori, Kamata Hirofumi, Ikemura Shinnosuke, Chubachi Shotaro, Okamori Satoshi, Terai Hideki, Morita Atsuho, Asakura Takanori, Sasaki Junichi, Morisaki Hiroshi, Uwamino Yoshifumi, Nanki Kosaku, Uchida Sho, Uno Shunsuke, Nishimura Tomoyasu, Ishiguro Takashi, Isono Taisuke, Shibata Shun, Matsui Yuma, Hosoda Chiaki, Takano Kenji, Nishida Takashi, Kobayashi Yoichi, Takaku Yotaro, Takayanagi Noboru, Ueda Soichiro, Tada Ai, Miyawaki Masayoshi, Yamamoto Masaomi, Yoshida Eriko, Hayashi Reina, Nagasaka Tomoki, Arai Sawako, Kaneko Yutaro, Sasaki Kana, Tagaya Etsuko, Kawana Masatoshi, Arimura Ken, Takahashi Kunihiko, Anzai Tatsuhiko, Ito Satoshi, Endo Akifumi, Uchimura Yuji, Miyazaki Yasunari, Honda Takayuki, Tateishi Tomoya, Tohda Shuji, Ichimura Naoya, Sonobe Kazunari, Sassa Chihiro Tani, Nakajima Jun, Nakano Yasushi, Nakajima Yukiko, Anan Ryusuke, Arai Ryosuke, Kurihara Yuko, Harada Yuko, Nishio Kazumi, Ueda Tetsuya, Azuma Masanori, Saito Ryuichi, Sado Toshikatsu, Miyazaki Yoshimune, Sato Ryuichi, Haruta Yuki, Nagasaki Tadao, Yasui Yoshinori, Hasegawa Yoshinori, Mutoh Yoshikazu, Kimura Tomoki, Sato Tomonori, Takei Reoto, Hagimoto Satoshi, Noguchi Yoichiro, Yamano Yasuhiko, Sasano Hajime, Ota Sho, Nakamori Yasushi, Yoshiya Kazuhisa, Saito Fukuki, Yoshihara Tomoyuki, Wada Daiki, Iwamura Hiromu, Kanayama Syuji, Maruyama Shuhei, Yoshiyama Takashi, Ohta Ken, Kokuto Hiroyuki, Ogata Hideo, Tanaka Yoshiaki, Arakawa Kenichi, Shimoda Masafumi, Osawa Takeshi, Tateno Hiroki, Hase Isano, Yoshida Shuichi, Suzuki Shoji, Kawada Miki, Horinouchi Hirohisa, Saito Fumitake, Mitamura Keiko, Hagihara Masao, Ochi Junichi, Uchida Tomoyuki, Baba Rie, Arai Daisuke, Ogura Takayuki, Takahashi Hidenori, Hagiwara Shigehiro, Nagao Genta, Konishi Shunichiro, Nakachi Ichiro, Murakami Koji, Yamada Mitsuhiro, Sugiura Hisatoshi, Sano Hirohito, Matsumoto Shuichiro, Kimura Nozomu, Ono Yoshinao, Baba Hiroaki, Suzuki Yusuke, Nakayama Sohei, Masuzawa Keita, Namba Shinichi, Shiroyama Takayuki, Noda Yoshimi, Niitsu Takayuki, Adachi Yuichi, Enomoto Takatoshi, Amiya Saori, Hara Reina, Yamaguchi Yuta, Murakami Teruaki, Kuge Tomoki, Matsumoto Kinnosuke, Yamamoto Yuji, Yamamoto Makoto, Yoneda Midori, Tomono Kazunori, Kato Kazuto, Hirata Haruhiko, Takeda Yoshito, Koh Hidefumi, Manabe Tadashi, Funatsu Yohei, Ito Fumimaro, Fukui Takahiro, Shinozuka Keisuke, Kohashi Sumiko, Miyazaki Masatoshi, Shoko Tomohisa, Kojima Mitsuaki, Adachi Tomohiro, Ishikawa Motonao, Takahashi Kenichiro, Inoue Takashi, Hirano Toshiyuki, Kobayashi Keigo, Takaoka Hatsuyo, Watanabe Kazuyoshi, Miyazawa Naoki, Kimura Yasuhiro, Sado Reiko, Sugimoto Hideyasu, Kamiya Akane, Kuwahara Naota, Fujiwara Akiko, Matsunaga Tomohiro, Sato Yoko, Okada Takenori, Hirai Yoshihiro, Kawashima Hidetoshi, Narita Atsuya, Niwa Kazuki, Sekikawa Yoshiyuki, Nishi Koichi, Nishitsuji Masaru, Tani Mayuko, Suzuki Junya, Nakatsumi Hiroki, Ogura Takashi, Kitamura Hideya, Hagiwara Eri, Murohashi Kota, Okabayashi Hiroko, Mochimaru Takao, Nukaga Shigenari, Satomi Ryosuke, Oyamada Yoshitaka, Mori Nobuaki, Baba Tomoya, Fukui Yasutaka, Odate Mitsuru, Mashimo Shuko, Makino Yasushi, Yagi Kazuma, Hashiguchi Mizuha, Kagyo Junko, Shiomi Tetsuya, Fuke Satoshi, Saito Hiroshi, Tsuchida Tomoya, Fujitani Shigeki, Takita Mumon, Morikawa Daiki, Yoshida Toru, Izumo Takehiro, Inomata Minoru, Kuse Naoyuki, Awano Nobuyasu, Tone Mari, Ito Akihiro, Nakamura Yoshihiko, Hoshino Kota, Maruyama Junichi, Ishikura Hiroyasu, Takata Tohru, Odani Toshio, Amishima Masaru, Hattori Takeshi, Shichinohe Yasuo, Kagaya Takashi, Kita Toshiyuki, Ohta Kazuhide, Sakagami Satoru, Koshida Kiyoshi, Hayashi Kentaro, Shimizu Tetsuo, Kozu Yutaka, Hiranuma Hisato, Gon Yasuhiro, Izumi Namiki, Nagata Kaoru, Ueda Ken, Taki Reiko, Hanada Satoko, Kawamura Kodai, Ichikado Kazuya, Nishiyama Kenta, Muranaka Hiroyuki, Nakamura Kazunori, Hashimoto Naozumi, Wakahara Keiko, Koji Sakamoto, Omote Norihito, Ando Akira, Kodama Nobuhiro, Kaneyama Yasunari, Maeda Shunsuke, Kuraki Takashige, Matsumoto Takemasa, Yokote Koutaro, Nakada Taka-Aki, Abe Ryuzo, Oshima Taku, Shimada Tadanaga, Harada Masahiro, Takahashi Takeshi, Ono Hiroshi, Sakurai Toshihiro, Shibusawa Takayuki, Kimizuka Yoshifumi, Kawana Akihiko, Sano Tomoya, Watanabe Chie, Suematsu Ryohei, Sageshima Hisako, Yoshifuji Ayumi, Ito Kazuto, Takahashi Saeko, Ishioka Kota, Nakamura Morio, Masuda Makoto, Wakabayashi Aya, Watanabe Hiroki, Ueda Suguru, Nishikawa Masanori, Chihara Yusuke, Takeuchi Mayumi, Onoi Keisuke, Shinozuka Jun, Sueyoshi Atsushi, Nagasaki Yoji, Okamoto Masaki, Ishihara Sayoko, Shimo Masatoshi, Tokunaga Yoshihisa, Kusaka Yu, Ohba Takehiko, Isogai Susumu, Ogawa Aki, Inoue Takuya, Fukuyama Satoru, Eriguchi Yoshihiro, Yonekawa Akiko, Kan-o Keiko, Matsumoto Koichiro, Kanaoka Kensuke, Ihara Shoichi, Komuta Kiyoshi, Inoue Yoshiaki, Chiba Shigeru, Yamagata Kunihiro, Hiramatsu Yuji, Kai Hirayasu, Asano Koichiro, Oguma Tsuyoshi, Ito Yoko, Hashimoto Satoru, Yamasaki Masaki, Kasamatsu Yu, Komase Yuko, Hida Naoya, Tsuburai Takahiro, Oyama Baku, Takada Minoru, Kanda Hidenori, Kitagawa Yuichiro, Fukuta Tetsuya, Miyake Takahito, Yoshida Shozo, Ogura Shinji, Abe Shinji, Kono Yuta, Togashi Yuki, Takoi Hiroyuki, Kikuchi Ryota, Ogawa Shinichi, Ogata Tomouki, Ishihara Shoichiro, Kanehiro Arihiko, Ozaki Shinji, Fuchimoto Yasuko, Wada Sae, Fujimoto Nobukazu, Nishiyama Kei, Terashima Mariko, Beppu Satoru, Yoshida Kosuke, Narumoto Osamu, Nagai Hideaki, Ooshima Nobuharu, Motegi Mitsuru, Umeda Akira, Miyagawa Kazuya, Shimada Hisato, Endo Mayu, Ohira Yoshiyuki, Watanabe Masafumi, Inoue Sumito, Igarashi Akira, Sato Masamichi, Sagara Hironori, Tanaka Akihiko, Ohta Shin, Kimura Tomoyuki, Shibata Yoko, Tanino Yoshinori, Nikaido Takefumi, Minemura Hiroyuki, Sato Yuki, Yamada Yuichiro, Hashino Takuya, Shinoki Masato, Iwagoe Hajime, Takahashi Hiroshi, Fujii Kazuhiko, Kishi Hiroto, Kanai Masayuki, Imamura Tomonori, Yamashita Tatsuya, Yatomi Masakiyo, Maeno Toshitaka, Hayashi Shinichi, Takahashi Mai, Kuramochi Mizuki, Kamimaki Isamu, Tominaga Yoshiteru, Ishii Tomoo, Utsugi Mitsuyoshi, Ono Akihiro, Tanaka Toru, Kashiwada Takeru, Fujita Kazue, Saito Yoshinobu, Seike Masahiro, Watanabe Hiroko, Matsuse Hiroto, Kodaka Norio, Nakano Chihiro, Oshio Takeshi, Hirouchi Takatomo, Makino Shohei, Egi Moritoki, Omae Yosuke, Nannya Yasuhito, Ueno Takafumi, Takano Tomomi, Katayama Kazuhiko, Ai Masumi, Kumanogoh Atsushi, Sato Toshiro, Hasegawa Naoki, Tokunaga Katsushi, Ishii Makoto, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    NATURE GENETICS   55 巻 ( 5 ) 頁: 753 - +   2023年5月

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    出版者・発行元:Nature Genetics  

    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.

    DOI: 10.1038/s41588-023-01375-1

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  34. Serum KL-6 levels predict clinical outcomes and are associated with MUC1 polymorphism in Japanese patients with COVID-19 国際誌

    Azekawa Shuhei, Chubachi Shotaro, Asakura Takanori, Namkoong Ho, Sato Yasunori, Edahiro Ryuya, Lee Ho, Tanaka Hiromu, Otake Shiro, Nakagawara Kensuke, Fukushima Takahiro, Watase Mayuko, Sakurai Kaori, Kusumoto Tatsuya, Masaki Katsunori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    BMJ OPEN RESPIRATORY RESEARCH   10 巻 ( 1 )   2023年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMJ Open Respiratory Research  

    Background Krebs von den Lungen-6 (KL-6) is a known biomarker for diagnosis and monitoring of interstitial lung diseases. However, the role of serum KL-6 and the mucin 1 (MUC1) variant (rs4072037) in COVID-19 outcomes remains to be elucidated. We aimed to evaluate the relationships among serum KL-6 levels, critical outcomes and the MUC1 variant in Japanese patients with COVID-19. Methods This is a secondary analysis of a multicentre retrospective study using data from the Japan COVID-19 Task Force collected from February 2020 to November 2021, including 2226 patients with COVID-19 whose serum KL-6 levels were measured. An optimal serum KL-6 level cut-off to predict critical outcomes was determined and used for multivariable logistic regression analysis. Furthermore, the relationship among the allele dosage of the MUC1 variant, calculated from single nucleotide polymorphism typing data of genome-wide association studies using the imputation method, serum KL-6 levels and COVID-19 critical outcomes was evaluated. Results Serum KL-6 levels were significantly higher in patients with COVID-19 with critical outcomes (511±442 U/mL) than those without (279±204 U/mL) (p<0.001). Serum KL-6 levels ≥304 U/mL independently predicted critical outcomes (adjusted OR (aOR) 3.47, 95% CI 2.44 to 4.95). Moreover, multivariable logistic regression analysis with age and sex indicated that the MUC1 variant was independently associated with increased serum KL-6 levels (aOR 0.24, 95% CI 0.28 to 0.32) but not significantly associated with critical outcomes (aOR 1.11, 95% CI 0.80 to 1.54). Conclusion Serum KL-6 levels predicted critical outcomes in Japanese patients with COVID-19 and were associated with the MUC1 variant. Therefore, serum KL-6 level is a potentially useful biomarker of critical COVID-19 outcomes.

    DOI: 10.1136/bmjresp-2023-001625

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  35. Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study. 国際誌

    Nakagawara K, Kamata H, Chubachi S, Namkoong H, Tanaka H, Lee H, Otake S, Fukushima T, Kusumoto T, Morita A, Azekawa S, Watase M, Asakura T, Masaki K, Ishii M, Endo A, Koike R, Ishikura H, Takata T, Matsushita Y, Harada N, Kokutou H, Yoshiyama T, Kataoka K, Mutoh Y, Miyawaki M, Ueda S, Ono H, Ono T, Shoko T, Muranaka H, Kawamura K, Mori N, Mochimaru T, Fukui M, Chihara Y, Nagasaki Y, Okamoto M, Amishima M, Odani T, Tani M, Nishi K, Shirai Y, Edahiro R, Ando A, Hashimoto N, Ogura S, Kitagawa Y, Kita T, Kagaya T, Kimura Y, Miyazawa N, Tsuchida T, Fujitani S, Murakami K, Sano H, Sato Y, Tanino Y, Otsuki R, Mashimo S, Kuramochi M, Hosoda Y, Hasegawa Y, Ueda T, Takaku Y, Ishiguro T, Fujiwara A, Kuwahara N, Kitamura H, Hagiwara E, Nakamori Y, Saito F, Kono Y, Abe S, Ishii T, Ohba T, Kusaka Y, Watanabe H, Masuda M, Watanabe H, Kimizuka Y, Kawana A, Kasamatsu Y, Hashimoto S, Okada Y, Takano T, Katayama K, Ai M, Kumanogoh A, Sato T, Tokunaga K, Imoto S, Kitagawa Y, Kimura A, Miyano S, Hasegawa N, Ogawa S, Kanai T, Fukunaga K, Japan COVID-19 Task Force

    BMC pulmonary medicine   23 巻 ( 1 ) 頁: 146 - 146   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12890-023-02418-3

    PubMed

  36. Characteristics and clinical effectiveness of COVID-19 vaccination in hospitalized patients in Omicron-dominated epidemic wave - a nationwide study in Japan. 国際誌

    Tanaka H, Chubachi S, Asakura T, Namkoong H, Azekawa S, Otake S, Nakagawara K, Fukushima T, Lee H, Watase M, Sakurai K, Kusumoto T, Masaki K, Kamata H, Ishii M, Hasegawa N, Okada Y, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   132 巻   頁: 84 - 88   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.ijid.2023.04.399

    PubMed

  37. Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device.

    Onoshima D, Hase T, Kihara N, Kuboyama D, Tanaka H, Ozawa N, Yukawa H, Sato M, Ishikawa K, Hasegawa Y, Ishii M, Hori M, Baba Y

    ACS measurement science au   3 巻 ( 2 ) 頁: 113 - 119   2023年4月

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    記述言語:英語  

    DOI: 10.1021/acsmeasuresciau.2c00057

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  38. Use of the neutrophil-to-lymphocyte ratio and an oxygen requirement to predict disease severity in patients with COVID-19. 国際誌

    Ozawa T, Asakura T, Chubachi S, Namkoong H, Tanaka H, Lee K, Fukushima T, Otake S, Nakagawara K, Watase M, Masaki K, Kamata H, Ishii M, Hasegawa N, Harada N, Ueda T, Ueda S, Ishiguro T, Arimura K, Saito F, Yoshiyama T, Nakano Y, Mutoh Y, Suzuki Y, Edahiro R, Murakami K, Okada Y, Koike R, Kitagawa Y, Tokunaga K, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K, Japan COVID-19 Task Force

    Respiratory investigation   61 巻 ( 4 ) 頁: 454 - 459   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.resinv.2023.03.007

    PubMed

  39. Diagnostic significance of secondary bacteremia in patients with COVID-19 査読有り

    Nakagawara K., Kamata H., Chubachi S., Namkoong H., Tanaka H., Lee H., Otake S., Fukushima T., Kusumoto T., Morita A., Azekawa S., Watase M., Asakura T., Masaki K., Ishii M., Endo A., Koike R., Ishikura H., Takata T., Matsushita Y., Harada N., Kokutou H., Yoshiyama T., Kataoka K., Mutoh Y., Miyawaki M., Ueda S., Ono H., Ono T., Shoko T., Muranaka H., Kawamura K., Mori N., Mochimaru T., Fukui M., Chihara Y., Nagasaki Y., Okamoto M., Amishima M., Odani T., Tani M., Nishi K., Shirai Y., Edahiro R., Ando A., Hashimoto N., Ogura S., Kitagawa Y., Kita T., Kagaya T., Kimura Y., Miyazawa N., Tsuchida T., Fujitani S., Murakami K., Sano H., Sato Y., Tanino Y., Otsuki R., Mashimo S., Kuramochi M., Hosoda Y., Hasegawa Y., Ueda T., Takaku Y., Ishiguro T., Fujiwara A., Kuwahara N., Kitamura H., Hagiwara E., Nakamori Y., Saito F., Kono Y., Abe S., Ishii T., Ohba T., Kusaka Y., Watanabe H., Masuda M., Watanabe H., Kimizuka Y., Kawana A., Kasamatsu Y., Hashimoto S., Okada Y., Takano T., Katayama K., Ai M., Kumanogoh A., Sato T., Tokunaga K., Imoto S., Kitagawa Y., Kimura A., Miyano S., Hasegawa N., Ogawa S., Kanai T., Fukunaga K.

    Journal of Infection and Chemotherapy   29 巻 ( 4 ) 頁: 422 - 426   2023年4月

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    記述言語:英語   出版者・発行元:Journal of Infection and Chemotherapy  

    Objectives: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. Results: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97–39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. Conclusions: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

    DOI: 10.1016/j.jiac.2023.01.006

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  40. Multi-center, phase II study of docetaxel (DTX) plus ramucirumab (RAM) following platinum-based chemotherapy plus ICIs in patients with NSCLC: SCORPION study

    Matsuzawa R., Morise M., Ito K., Hataji O., Takahashi K., Kuwatsuka Y., Goto Y., Imaizumi K., Itani H., Yamaguchi T., Zenke Y., Oki M., Ishii M.

    JOURNAL OF THORACIC ONCOLOGY   18 巻 ( 4 ) 頁: S68 - S68   2023年4月

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  41. Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma 査読有り

    Ebisudani Toshiki, Hamamoto Junko, Togasaki Kazuhiro, Mitsuishi Akifumi, Sugihara Kai, Shinozaki Taro, Fukushima Takahiro, Kawasaki Kenta, Seino Takashi, Oda Mayumi, Hanyu Hikaru, Toshimitsu Kohta, Emoto Katsura, Hayashi Yuichiro, Asakura Keisuke, Johnson Todd A., Terai Hideki, Ikemura Shinnosuke, Kawada Ichiro, Ishii Makoto, Hishida Tomoyuki, Asamura Hisao, Soejima Kenzo, Nakagawa Hidewaki, Fujii Masayuki, Fukunaga Koichi, Yasuda Hiroyuki, Sato Toshiro

    CELL REPORTS   42 巻 ( 3 ) 頁: 112212   2023年3月

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  42. Omalizumab ameliorates extra-respiratory symptoms in patients with aspirin-exacerbated respiratory disease. 査読有り

    Hayashi H, Fukutomi Y, Mitsui C, Kajiwara K, Watai K, Tomita Y, Kamide Y, Tsuburai T, Sekiya K, Ishii M, Hasegawa Y, Taniguchi M

    The Journal of allergy and clinical immunology     2023年3月

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    記述言語:英語  

    DOI: 10.1016/j.jaci.2023.03.014

    PubMed

  43. The Application of Mixed Reality in Bronchoscopy Simulation Training: A Feasibility Study 査読有り

    Okachi Shotaro, Sakurai Manami, Matsui Toshinori, Ito Takayasu, Matsuzawa Reiko, Morise Masahiro, Wakahara Keiko, Ishii Makoto, Fujiwara Michitaka

    SURGICAL INNOVATION     2023年3月

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    担当区分:最終著者   出版者・発行元:Surgical Innovation  

    DOI: 10.1177/15533506231160201

    Web of Science

    Scopus

  44. COVID-19 トランスレーショナルリサーチ 日本人COVID-19患者において血清KL-6値は重症化を予測する

    阿瀬川 周平, 中鉢 正太郎, 石井 誠, 朝倉 崇徳, 南宮 湖, 佐藤 泰憲, 岡田 随象, 枝廣 龍哉, 田中 拓, 李 昊, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 176 - 176   2023年3月

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  45. COVID-19 バイオマーカー 日本人COVID-19において入院時の好中球/リンパ球比(NLR)と酸素需要の組み合わせは重症化を予測する

    小澤 拓矢, 朝倉 崇徳, 中鉢 正太郎, 南宮 湖, 田中 拓, 李 昊, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 金井 隆典, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 205 - 205   2023年3月

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  46. COVID-19 バイオマーカー 血糖異常を示す日本人COVID-19患者のアウトカムの統合解析

    福島 貴大, 中鉢 正太郎, 南宮 湖, 朝倉 崇徳, 田中 拓, 李 昊, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 楠本 竜也, 櫻井 香, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 205 - 205   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  47. COVID-19 後遺症 COVID-19罹患後症状の大規模日本人コホート研究 診断12ヵ月後データ解析

    寺井 秀樹, 竹村 亮, 南宮 湖, 舘野 博喜, 上田 壮一郎, 仲地 一郎, 朝倉 崇徳, 正木 克宜, 中鉢 正太郎, 石井 誠, 佐藤 泰憲, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 202 - 202   2023年3月

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  48. COVID-19 後遺症 重症患者でのCOVID-19罹患後症状における咳嗽・喀痰の遷延

    渡瀬 麻友子, 宮田 純, 朝倉 崇徳, 中鉢 正太郎, 寺井 秀樹, 加行 淳子, 小山田 吉孝, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 202 - 202   2023年3月

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  49. COVID-19後遺症における呼吸困難の危険因子に関する考察

    松山 笑子, 宮田 純, 大竹 史朗, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 寺井 秀樹, 宮崎 直己, 岩崎 俊樹, 長島 健吾, 牧野 靖, 高橋 左枝子, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  50. COVID-19患者における呼吸器感染症を除く細菌感染合併症例の臨床的特徴の検討

    中川原 賢亮, 鎌田 浩史, 中鉢 正太郎, 南宮 湖, 朝倉 崇徳, 大竹 史朗, 田中 拓, 福島 貴大, 李 昊, 渡瀬 麻友子, 楠本 竜也, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 348 - 348   2023年3月

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  51. COVID-19罹患後症状が健康関連QOLに与える影響に関する考察

    八木 一馬, 寺井 秀樹, 田中 拓, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 近藤 雅大, 竹村 亮, 中野 泰, 鈴木 雄介, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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  52. Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force 査読有り

    Watase Mayuko, Masaki Katsunori, Chubachi Shotaro, Namkoong Ho, Tanaka Hiromu, Lee Ho, Fukushima Takahiro, Otake Shiro, Nakagawara Kensuke, Kusumoto Tatsuya, Asakura Takanori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Oyamada Yoshitaka, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Edahiro Ryuya, Sano Hirohito, Sato Yasunori, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Tokunaga Katsushi, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES   128 巻   頁: 121 - 127   2023年3月

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  53. COVID-19罹患後症状である倦怠感の危険因子に関する考察

    砂田 啓英也, 宮田 純, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 寺井 秀樹, 吉山 崇, 原田 紀宏, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 231 - 231   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  54. COVID-19罹患後症状における高血圧を含む併存症との関係

    小澤 拓矢, 寺井 秀樹, 木村 流星, 竹村 亮, 福田 桂太郎, 中川原 賢亮, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 黄 英文, 石黒 卓, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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  55. 日本人COVID-19患者における気道症状と臨床的予後との関連

    中川原 賢亮, 中鉢 正太郎, 南宮 湖, 大竹 史朗, 阿瀬川 周平, 田中 拓, 福島 貴大, 李 昊, 渡瀬 麻友子, 楠本 竜也, 朝倉 崇徳, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 347 - 347   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  56. 第1波から第5波までのCOVID-19入院患者の特徴

    李 昊, 中鉢 正太郎, 南宮 湖, 朝倉 崇徳, 田中 拓, 楠本 竜也, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 347 - 347   2023年3月

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  57. 第1波から第3波までのCOVID-19罹患後症状の比較

    高岡 初誉, 川田 一郎, 阿瀬川 周平, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 寺井 秀樹, 比留間 岳, 石田 典之, 長島 健吾, 井上 卓, 岡元 昌樹, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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  58. 消化器系COVID-19罹患後症状を呈する患者の頻度および臨床的特徴

    八木 一馬, 寺井 秀樹, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 宮尾 直樹, 桑原 直太, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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  59. 日本人COVID-19患者のリアルワールドデータを用いたバリシチニブの有効性評価

    田中 拓, 中鉢 正太郎, 南宮 湖, 佐藤 泰憲, 朝倉 崇徳, 李 昊, 楠本 竜也, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 348 - 348   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  60. COVID-19 トランスレーショナルリサーチ 日本人COVID-19患者において血清KL-6値は重症化を予測する

    阿瀬川 周平, 中鉢 正太郎, 石井 誠, 朝倉 崇徳, 南宮 湖, 佐藤 泰憲, 岡田 随象, 枝廣 龍哉, 田中 拓, 李 昊, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 176 - 176   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  61. 第1波から第5波までのCOVID-19入院患者の特徴

    李 昊, 中鉢 正太郎, 南宮 湖, 朝倉 崇徳, 田中 拓, 楠本 竜也, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 347 - 347   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  62. 消化器系COVID-19罹患後症状を呈する患者の頻度および臨床的特徴

    八木 一馬, 寺井 秀樹, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 宮尾 直樹, 桑原 直太, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  63. 日本人COVID-19患者のリアルワールドデータを用いたバリシチニブの有効性評価

    田中 拓, 中鉢 正太郎, 南宮 湖, 佐藤 泰憲, 朝倉 崇徳, 李 昊, 楠本 竜也, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 348 - 348   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  64. 日本人COVID-19患者における気道症状と臨床的予後との関連

    中川原 賢亮, 中鉢 正太郎, 南宮 湖, 大竹 史朗, 阿瀬川 周平, 田中 拓, 福島 貴大, 李 昊, 渡瀬 麻友子, 楠本 竜也, 朝倉 崇徳, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 347 - 347   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  65. COVID-19罹患後症状における高血圧を含む併存症との関係

    小澤 拓矢, 寺井 秀樹, 木村 流星, 竹村 亮, 福田 桂太郎, 中川原 賢亮, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 黄 英文, 石黒 卓, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  66. COVID-19罹患後症状である倦怠感の危険因子に関する考察

    砂田 啓英也, 宮田 純, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 寺井 秀樹, 吉山 崇, 原田 紀宏, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 231 - 231   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  67. COVID-19患者における呼吸器感染症を除く細菌感染合併症例の臨床的特徴の検討

    中川原 賢亮, 鎌田 浩史, 中鉢 正太郎, 南宮 湖, 朝倉 崇徳, 大竹 史朗, 田中 拓, 福島 貴大, 李 昊, 渡瀬 麻友子, 楠本 竜也, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 348 - 348   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  68. COVID-19後遺症における呼吸困難の危険因子に関する考察

    松山 笑子, 宮田 純, 大竹 史朗, 朝倉 崇徳, 南宮 湖, 中鉢 正太郎, 寺井 秀樹, 宮崎 直己, 岩崎 俊樹, 長島 健吾, 牧野 靖, 高橋 左枝子, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 232 - 232   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  69. COVID-19 後遺症 重症患者でのCOVID-19罹患後症状における咳嗽・喀痰の遷延

    渡瀬 麻友子, 宮田 純, 朝倉 崇徳, 中鉢 正太郎, 寺井 秀樹, 加行 淳子, 小山田 吉孝, 石井 誠, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 202 - 202   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  70. COVID-19 後遺症 COVID-19罹患後症状の大規模日本人コホート研究 診断12ヵ月後データ解析

    寺井 秀樹, 竹村 亮, 南宮 湖, 舘野 博喜, 上田 壮一郎, 仲地 一郎, 朝倉 崇徳, 正木 克宜, 中鉢 正太郎, 石井 誠, 佐藤 泰憲, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 202 - 202   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  71. COVID-19 バイオマーカー 血糖異常を示す日本人COVID-19患者のアウトカムの統合解析

    福島 貴大, 中鉢 正太郎, 南宮 湖, 朝倉 崇徳, 田中 拓, 李 昊, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 楠本 竜也, 櫻井 香, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 205 - 205   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  72. COVID-19 バイオマーカー 日本人COVID-19患者とABO血液型/遺伝子型の関連

    楠本 竜也, 中鉢 正太郎, 南宮 湖, 田中 拓, 李 昊, 阿瀬川 周平, 大竹 史朗, 中川原 賢亮, 福島 貴大, 渡瀬 麻友子, 櫻井 香, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 金井 隆典, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 205 - 205   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  73. COVID-19 バイオマーカー 日本人COVID-19において入院時の好中球/リンパ球比(NLR)と酸素需要の組み合わせは重症化を予測する

    小澤 拓矢, 朝倉 崇徳, 中鉢 正太郎, 南宮 湖, 田中 拓, 李 昊, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 金井 隆典, 福永 興壱

    日本呼吸器学会誌   12 巻 ( 増刊 ) 頁: 205 - 205   2023年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  74. EBUS-GS TBBに加えてPeriView FLEXを用いたGS-TBNAが肺放線菌症の診断に有用であった1例 査読有り

    篠原 由佳, 伊藤 貴康, 岡地 祥太郎, 下山 芳江, 福谷 衣里子, 松澤 令子, 森瀬 昌宏, 若原 恵子, 石井 誠

    気管支学   45 巻 ( 1 ) 頁: 37 - 42   2023年1月

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    担当区分:最終著者   記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    <p><b>背景.</b>肺放線菌症確定診断のためのガイドシース併用気管支腔内超音波断層法(endobronchial ultrasonography with a guide sheath:EBUS-GS)を用いた診断能は不十分である.病巣深部からの検体採取が肝要と報告されている.<b>症例.</b>52歳女性.胸部異常陰影を契機に胸部CTにて右S<sup>6</sup>に結節影を認めた.約2年間で軽度増大し,当科に紹介された.<b>結果.</b>EBUS-GSを用いて,EBUSでwithinから生検を行ったが,炎症性細胞浸潤などの非特異的所見のみであった.PeriView FLEXを用いた穿刺吸引針生検により,壊死性変化を認め,悪性所見は認めなかった.さらに生検検体の組織培養で<i>Actinomyces odontolyticus</i>を認め,肺放線菌症と診断した.抗菌薬加療で病変の改善を認めた.<b>結論.</b>肺放線菌症の診断のため,病巣深部からサンプリングを行う際,ガイドシース併用経気管支穿刺吸引針生検は有用である.</p>

    DOI: 10.18907/jjsre.45.1_37

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  75. Comparison of antibiotic use and antibiotic resistance between a community hospital and tertiary care hospital for evaluation of the antimicrobial stewardship program in Japan.

    Morosawa M, Ueda T, Nakajima K, Inoue T, Toyama M, Ogasiwa H, Doi M, Nozaki Y, Murakami Y, Ishii M, Takesue Y

    PloS one   18 巻 ( 4 ) 頁: e0284806   2023年

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    記述言語:英語  

    DOI: 10.1371/journal.pone.0284806

    PubMed

  76. Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer

    Hatta T., Hase T., Hara T., Kimura T., Kojima E., Abe T., Horio Y., Goto Y., Ozawa N., Yogo N., Shibata H., Shimokata T., Oguri T., Yamamoto M., Yanagisawa K., Ando M., Ando Y., Kondo M., Ishii M., Hasegawa Y.

    Cancer Medicine     2023年

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    記述言語:英語   出版者・発行元:Cancer Medicine  

    Background: The Cockcroft–Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. Methods: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin–pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. Results: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76–1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65–1.17; p = 0.363), with higher grade 3–4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20–0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23–0.82; p = 0.010). Conclusions: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.

    DOI: 10.1002/cam4.6235

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  77. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment?

    Yonezawa Toshiyuki, Suzuki Atsushi, Fukumitsu Kensuke, Katano Takuma, Kako Hisashi, Ishii Makoto, Niimi Akio, Imaizumi Kazuyoshi, Sakamoto Koji, Omote Norihito, Yamaguchi Etsuro

    RESPIRATORY MEDICINE CASE REPORTS   43 巻   頁: 101857   2023年

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    記述言語:英語   出版者・発行元:Respiratory Medicine Case Reports  

    We present a case of 79-year-old female with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) developed an acute exacerbation (AE) triggered by coronavirus disease 2019 (COVID-19). The patient was unresponsive to a combination therapy of remdesivir, dexamethasone, and tocilizumab. Given that a recent multicenter cohort study reported ILD as a poor prognostic contributor in patients with RA and COVID-19, there may be potentially a certain number of patients with AE of RA-ILD triggered by COVID-19. This case highlights the need for a discussion how to treat these patients in a daily clinical practice.

    DOI: 10.1016/j.rmcr.2023.101857

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  78. Prognostic significance of hypertension history and blood pressure on admission in Japanese patients with coronavirus disease 2019: integrative analysis from the Japan COVID-19 Task Force

    Sakurai K., Chubachi S., Asakura T., Namkoong H., Tanaka H., Azekawa S., Shimada T., Otake S., Nakagawara K., Fukushima T., Lee H., Watase M., Kusumoto T., Masaki K., Kamata H., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Kanai T., Fukunaga K.

    Hypertension Research     2023年

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    記述言語:英語   出版者・発行元:Hypertension Research  

    The effect of preexisting hypertension on coronavirus disease 2019 (COVID-19) prognosis remains controversial. Additionally, no studies have compared the association between blood pressure (BP) indices on admission and COVID-19 outcomes using preexisting hypertension status. Therefore, this study aimed to investigate the association between preexisting hypertension and COVID-19 outcomes in Japanese patients with COVID-19 and assess the impact of BP indices on admission on clinical outcomes in patients with and without preexisting hypertension. Preexisting hypertension presence was confirmed based on the patient’s clinical history. Critical outcomes were defined as high-flow oxygen use, non-invasive and invasive positive-pressure ventilation, extracorporeal membrane oxygenation, or death during hospitalization. Preexisting hypertension was observed in 64.6% of the patients. Multivariable logistic regression analysis of severe COVID-19 risk factors indicated that preexisting hypertension was independently associated with critical outcomes [adjusted odds ratio (OR): 1.35; 95% confidence interval (CI): 1.05–1.73]. Low or high BP and high pulse pressure on admission were associated with critical outcomes in patients without preexisting hypertension [OR for systolic BP < 100 mmHg: 2.13, 95% CI: 1.21–3.75; OR for high BP stage 2 (160–179 systolic and/or 100–109 mmHg diastolic BP): 2.13, 95% CI: 1.27–3.58; OR for pulse pressure ≥60 mmHg: 1.68, 95% CI: 1.14–2.48]. Preexisting hypertension is a risk factor for critical outcomes in Japanese patients with COVID-19. BP indices are useful biomarkers for predicting COVID-19 outcomes, particularly in patients without preexisting hypertension. Thus, hypertension history, systolic BP, and pulse pressure should be assessed to predict severe COVID-19 outcomes. [Figure not available: see fulltext.]

    DOI: 10.1038/s41440-023-01490-w

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  79. Effectiveness of remdesivir-based therapy for moderate COVID-19: comparison of Omicron and other variant phases

    Suzuki A., Fukumitsu K., Fukihara J., Katano T., Kako H., Maeda Y., Ishii M., Niimi A., Imaizumi K., Yamaguchi E.

    Journal of Chemotherapy     頁: 1 - 6   2023年

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    記述言語:英語   出版者・発行元:Journal of Chemotherapy  

    Remdesivir is an antiviral drug for the treatment of coronavirus disease 2019 (COVID-19), and the sustained antiviral activity against Omicron variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported. In this single-center retrospective study, we first compared the clinical effectiveness of remdesivir-based therapy between Omicron and other variant phases of moderate COVID-19 in a real-world setting. Between Dec 2020 and July 2022, a total of 406 patients with COVID-19 pneumonia were treated with remdesivir-based therapy on admission. The oxygen deterioration rate after initiation of treatment significantly decreased in the Omicron variant phase compared to the alpha and delta variant phases. In an adjusted multivariate Cox proportional hazards model, Omicron variant phase was significantly associated with delayed oxygen deterioration and early recovery from hypoxia. These favorable outcomes during the Omicron variant phase, compared to previous variant phases, might be due to the attenuation and the popularization of vaccination.

    DOI: 10.1080/1120009X.2023.2289268

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  80. Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models 査読有り

    Takeshita Masaru, Fukuyama Hidehiro, Kamada Katsuhiko, Matsumoto Takehisa, Makino-Okamura Chieko, Uchikubo-Kamo Tomomi, Tomabechi Yuri, Hanada Kazuharu, Moriyama Saya, Takahashi Yoshimasa, Ishigaki Hirohito, Nakayama Misako, Nguyen Cong Thanh, Kitagawa Yoshinori, Itoh Yasushi, Imai Masaki, Maemura Tadashi, Furusawa Yuri, Ueki Hiroshi, Iwatsuki-Horimoto Kiyoko, Ito Mutsumi, Yamayoshi Seiya, Kawaoka Yoshihiro, Shirouzu Mikako, Ishii Makoto, Saya Hideyuki, Kondo Yasushi, Kaneko Yuko, Suzuki Katsuya, Fukunaga Koichi, Takeuchi Tsutomu

    ISCIENCE   25 巻 ( 12 ) 頁: 105596   2022年12月

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  81. Characteristics of hospitalized patients with COVID-19 during the first to fifth waves of infection: a report from the Japan COVID-19 Task Force 査読有り

    Lee Ho, Chubachi Shotaro, Namkoong Ho, Asakura Takanori, Tanaka Hiromu, Otake Shiro, Nakagawara Kensuke, Morita Atsuho, Fukushima Takahiro, Watase Mayuko, Kusumoto Tatsuya, Masaki Katsunori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Murakami Koji, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    BMC INFECTIOUS DISEASES   22 巻 ( 1 ) 頁: 935   2022年12月

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    記述言語:英語   出版者・発行元:BMC infectious diseases  

    BACKGROUND: We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. METHODS: We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. RESULTS: Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9]) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p < 0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p < 0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. CONCLUSIONS: We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.

    DOI: 10.1186/s12879-022-07927-w

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  82. 【新型コロナウイルスと闘う最前線】パンデミック下における臨床研究の進め方

    石井 誠, 南宮 湖, 福永 興壱

    BIO Clinica   37 巻 ( 13 ) 頁: 1178 - 1182   2022年12月

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    記述言語:日本語   出版者・発行元:(株)北隆館  

    新型コロナウイルス感染症(COVID-19)のパンデミック下で臨床研究を推進することは,最前線で診療にあたる臨床医や患者にとって負担が大きく,容易なことではない。筆者は,COVID-19の流行初期よりCOVID-19診療チームのサブリーダーとして診療に携わる一方で,このパンデミック下において,多くの臨床医や基礎研究者のサポートを得ながら,チームとしてCOVID-19の各種の多施設共同臨床研究にたずさわってきた。本稿では,筆者が関わってきたこれらの研究に関して紹介したい。(著者抄録)

  83. Impact of upper and lower respiratory symptoms on COVID-19 outcomes: a multicenter retrospective cohort study 査読有り

    Nakagawara Kensuke, Chubachi Shotaro, Namkoong Ho, Tanaka Hiromu, Lee Ho, Azekawa Shuhei, Otake Shiro, Fukushima Takahiro, Morita Atsuho, Watase Mayuko, Sakurai Kaori, Kusumoto Tatsuya, Asakura Takanori, Masaki Katsunori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Edahiro Ryuya, Murakami Koji, Sato Yasunori, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Tokunaga Katsushi, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    RESPIRATORY RESEARCH   23 巻 ( 1 ) 頁: 315   2022年11月

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    記述言語:英語   出版者・発行元:Respiratory Research  

    Background: Respiratory symptoms are associated with coronavirus disease 2019 (COVID-19) outcomes. However, the impacts of upper and lower respiratory symptoms on COVID-19 outcomes in the same population have not been compared. The objective of this study was to characterize upper and lower respiratory symptoms and compare their impacts on outcomes of hospitalized COVID-19 patients. Methods: This was a multicenter, retrospective cohort study; the database from the Japan COVID-19 Task Force was used. A total of 3314 COVID-19 patients were included in the study, and the data on respiratory symptoms were collected. The participants were classified according to their respiratory symptoms (Group 1: no respiratory symptoms, Group 2: only upper respiratory symptoms, Group 3: only lower respiratory symptoms, and Group 4: both upper and lower respiratory symptoms). The impacts of upper and lower respiratory symptoms on the clinical outcomes were compared. The primary outcome was the percentage of patients with poor clinical outcomes, including the need for oxygen supplementation via high-flow oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation or death. Results: Of the 3314 COVID-19 patients, 605, 1331, 1229, and 1149 were classified as Group 1, Group 2, Group 3, and Group 4, respectively. In univariate analysis, patients in Group 2 had the best clinical outcomes among all groups (odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.11–0.39), while patients in Group 3 had the worst outcomes (OR: 3.27, 95% CI: 2.43–4.40). Group 3 patients had the highest incidence of pneumonia, other complications due to secondary infections, and thrombosis during the clinical course. Conclusions: Upper and lower respiratory tract symptoms had vastly different impacts on the clinical outcomes of COVID-19.

    DOI: 10.1186/s12931-022-02222-3

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  84. Differences in lung and lobe volumes between supine and upright computed tomography in patients with idiopathic lung fibrosis 査読有り

    Chubachi Shotaro, Okamori Satoshi, Yamada Yoshitake, Yamada Minoru, Yokoyama Yoichi, Niijima Yuki, Kamata Hirofumi, Ishii Makoto, Fukunaga Koichi, Jinzaki Masahiro

    SCIENTIFIC REPORTS   12 巻 ( 1 ) 頁: 19408   2022年11月

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  85. 【肺炎の最近の動向-感染症から特殊な肺炎まで】COVID-19

    福永 興壱, 武藤 義和, 石井 誠

    カレントテラピー   40 巻 ( 11 ) 頁: 1104 - 1112   2022年11月

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    記述言語:日本語   出版者・発行元:(株)ライフメディコム  

  86. DOCK2 is involved in the host genetics and biology of severe COVID-19 査読有り

    Namkoong Ho, Edahiro Ryuya, Takano Tomomi, Nishihara Hiroshi, Shirai Yuya, Sonehara Kyuto, Tanaka Hiromu, Azekawa Shuhei, Mikami Yohei, Lee Ho, Hasegawa Takanori, Okudela Koji, Okuzaki Daisuke, Motooka Daisuke, Kanai Masahiro, Naito Tatsuhiko, Yamamoto Kenichi, Wang Qingbo S., Saiki Ryunosuke, Ishihara Rino, Matsubara Yuta, Hamamoto Junko, Hayashi Hiroyuki, Yoshimura Yukihiro, Tachikawa Natsuo, Yanagita Emmy, Hyugaji Takayoshi, Shimizu Eigo, Katayama Kotoe, Kato Yasuhiro, Morita Takayoshi, Takahashi Kazuhisa, Harada Norihiro, Naito Toshio, Hiki Makoto, Matsushita Yasushi, Takagi Haruhi, Aoki Ryousuke, Nakamura Ai, Harada Sonoko, Sasano Hitoshi, Kabata Hiroki, Masaki Katsunori, Kamata Hirofumi, Ikemura Shinnosuke, Chubachi Shotaro, Okamori Satoshi, Terai Hideki, Morita Atsuho, Asakura Takanori, Sasaki Junichi, Morisaki Hiroshi, Uwamino Yoshifumi, Nanki Kosaku, Uchida Sho, Uno Shunsuke, Nishimura Tomoyasu, Ishiguro Takashi, Isono Taisuke, Shibata Shun, Matsui Yuma, Hosoda Chiaki, Takano Kenji, Nishida Takashi, Kobayashi Yoichi, Takaku Yotaro, Takayanagi Noboru, Ueda Soichiro, Tada Ai, Miyawaki Masayoshi, Yamamoto Masaomi, Yoshida Eriko, Hayashi Reina, Nagasaka Tomoki, Arai Sawako, Kaneko Yutaro, Sasaki Kana, Tagaya Etsuko, Kawana Masatoshi, Arimura Ken, Takahashi Kunihiko, Anzai Tatsuhiko, Ito Satoshi, Endo Akifumi, Uchimura Yuji, Miyazaki Yasunari, Honda Takayuki, Tateishi Tomoya, Tohda Shuji, Ichimura Naoya, Sonobe Kazunari, Sassa Chihiro Tani, Nakajima Jun, Nakano Yasushi, Nakajima Yukiko, Anan Ryusuke, Arai Ryosuke, Kurihara Yuko, Harada Yuko, Nishio Kazumi, Ueda Tetsuya, Azuma Masanori, Saito Ryuichi, Sado Toshikatsu, Miyazaki Yoshimune, Sato Ryuichi, Haruta Yuki, Nagasaki Tadao, Yasui Yoshinori, Hasegawa Yoshinori, Mutoh Yoshikazu, Kimura Tomoki, Sato Tomonori, Takei Reoto, Hagimoto Satoshi, Noguchi Yoichiro, Yamano Yasuhiko, Sasano Hajime, Ota Sho, Nakamori Yasushi, Yoshiya Kazuhisa, Saito Fukuki, Yoshihara Tomoyuki, Wada Daiki, Iwamura Hiromu, Kanayama Syuji, Maruyama Shuhei, Yoshiyama Takashi, Ohta Ken, Kokuto Hiroyuki, Ogata Hideo, Tanaka Yoshiaki, Arakawa Kenichi, Shimoda Masafumi, Osawa Takeshi, Tateno Hiroki, Hase Isano, Yoshida Shuichi, Suzuki Shoji, Kawada Miki, Horinouchi Hirohisa, Saito Fumitake, Mitamura Keiko, Hagihara Masao, Ochi Junichi, Uchida Tomoyuki, Baba Rie, Arai Daisuke, Ogura Takayuki, Takahashi Hidenori, Hagiwara Shigehiro, Nagao Genta, Konishi Shunichiro, Nakachi Ichiro, Murakami Koji, Yamada Mitsuhiro, Sugiura Hisatoshi, Sano Hirohito, Matsumoto Shuichiro, Kimura Nozomu, Ono Yoshinao, Baba Hiroaki, Suzuki Yusuke, Nakayama Sohei, Masuzawa Keita, Namba Shinichi, Suzuki Ken, Naito Yoko, Liu Yu-Chen, Takuwa Ayako, Sugihara Fuminori, Wing James B., Sakakibara Shuhei, Hizawa Nobuyuki, Shiroyama Takayuki, Miyawaki Satoru, Kawamura Yusuke, Nakayama Akiyoshi, Matsuo Hirotaka, Maeda Yuichi, Nii Takuro, Noda Yoshimi, Niitsu Takayuki, Adachi Yuichi, Enomoto Takatoshi, Amiya Saori, Hara Reina, Yamaguchi Yuta, Murakami Teruaki, Kuge Tomoki, Matsumoto Kinnosuke, Yamamoto Yuji, Yamamoto Makoto, Yoneda Midori, Kishikawa Toshihiro, Yamada Shuhei, Kawabata Shuhei, Kijima Noriyuki, Takagaki Masatoshi, Sasa Noah, Ueno Yuya, Suzuki Motoyuki, Takemoto Norihiko, Eguchi Hirotaka, Fukusumi Takahito, Imai Takao, Fukushima Munehisa, Kishima Haruhiko, Inohara Hidenori, Tomono Kazunori, Kato Kazuto, Takahashi Meiko, Matsuda Fumihiko, Hirata Haruhiko, Takeda Yoshito, Koh Hidefumi, Manabe Tadashi, Funatsu Yohei, Ito Fumimaro, Fukui Takahiro, Shinozuka Keisuke, Kohashi Sumiko, Miyazaki Masatoshi, Shoko Tomohisa, Kojima Mitsuaki, Adachi Tomohiro, Ishikawa Motonao, Takahashi Kenichiro, Inoue Takashi, Hirano Toshiyuki, Kobayashi Keigo, Takaoka Hatsuyo, Watanabe Kazuyoshi, Miyazawa Naoki, Kimura Yasuhiro, Sado Reiko, Sugimoto Hideyasu, Kamiya Akane, Kuwahara Naota, Fujiwara Akiko, Matsunaga Tomohiro, Sato Yoko, Okada Takenori, Hirai Yoshihiro, Kawashima Hidetoshi, Narita Atsuya, Niwa Kazuki, Sekikawa Yoshiyuki, Nishi Koichi, Nishitsuji Masaru, Tani Mayuko, Suzuki Junya, Nakatsumi Hiroki, Ogura Takashi, Kitamura Hideya, Hagiwara Eri, Murohashi Kota, Okabayashi Hiroko, Mochimaru Takao, Nukaga Shigenari, Satomi Ryosuke, Oyamada Yoshitaka, Mori Nobuaki, Baba Tomoya, Fukui Yasutaka, Odate Mitsuru, Mashimo Shuko, Makino Yasushi, Yagi Kazuma, Hashiguchi Mizuha, Kagyo Junko, Shiomi Tetsuya, Fuke Satoshi, Saito Hiroshi, Tsuchida Tomoya, Fujitani Shigeki, Takita Mumon, Morikawa Daiki, Yoshida Toru, Izumo Takehiro, Inomata Minoru, Kuse Naoyuki, Awano Nobuyasu, Tone Mari, Ito Akihiro, Nakamura Yoshihiko, Hoshino Kota, Maruyama Junichi, Ishikura Hiroyasu, Takata Tohru, Odani Toshio, Amishima Masaru, Hattori Takeshi, Shichinohe Yasuo, Kagaya Takashi, Kita Toshiyuki, Ohta Kazuhide, Sakagami Satoru, Koshida Kiyoshi, Hayashi Kentaro, Shimizu Tetsuo, Kozu Yutaka, Hiranuma Hisato, Gon Yasuhiro, Izumi Namiki, Nagata Kaoru, Ueda Ken, Taki Reiko, Hanada Satoko, Kawamura Kodai, Ichikado Kazuya, Nishiyama Kenta, Muranaka Hiroyuki, Nakamura Kazunori, Hashimoto Naozumi, Wakahara Keiko, Sakamoto Koji, Omote Norihito, Ando Akira, Kodama Nobuhiro, Kaneyama Yasunari, Maeda Shunsuke, Kuraki Takashige, Matsumoto Takemasa, Yokote Koutaro, Nakada Taka-Aki, Abe Ryuzo, Oshima Taku, Shimada Tadanaga, Harada Masahiro, Takahashi Takeshi, Ono Hiroshi, Sakurai Toshihiro, Shibusawa Takayuki, Kimizuka Yoshifumi, Kawana Akihiko, Sano Tomoya, Watanabe Chie, Suematsu Ryohei, Sageshima Hisako, Yoshifuji Ayumi, Ito Kazuto, Takahashi Saeko, Ishioka Kota, Nakamura Morio, Masuda Makoto, Wakabayashi Aya, Watanabe Hiroki, Ueda Suguru, Nishikawa Masanori, Chihara Yusuke, Takeuchi Mayumi, Onoi Keisuke, Shinozuka Jun, Sueyoshi Atsushi, Nagasaki Yoji, Okamoto Masaki, Ishihara Sayoko, Shimo Masatoshi, Tokunaga Yoshihisa, Kusaka Yu, Ohba Takehiko, Isogai Susumu, Ogawa Aki, Inoue Takuya, Fukuyama Satoru, Eriguchi Yoshihiro, Yonekawa Akiko, Kan-o Keiko, Matsumoto Koichiro, Kanaoka Kensuke, Ihara Shoichi, Komuta Kiyoshi, Inoue Yoshiaki, Chiba Shigeru, Yamagata Kunihiro, Hiramatsu Yuji, Kai Hirayasu, Asano Koichiro, Oguma Tsuyoshi, Ito Yoko, Hashimoto Satoru, Yamasaki Masaki, Kasamatsu Yu, Komase Yuko, Hida Naoya, Tsuburai Takahiro, Oyama Baku, Takada Minoru, Kanda Hidenori, Kitagawa Yuichiro, Fukuta Tetsuya, Miyake Takahito, Yoshida Shozo, Ogura Shinji, Abe Shinji, Kono Yuta, Togashi Yuki, Takoi Hiroyuki, Kikuchi Ryota, Ogawa Shinichi, Ogata Tomouki, Ishihara Shoichiro, Kanehiro Arihiko, Ozaki Shinji, Fuchimoto Yasuko, Wada Sae, Fujimoto Nobukazu, Nishiyama Kei, Terashima Mariko, Beppu Satoru, Yoshida Kosuke, Narumoto Osamu, Nagai Hideaki, Ooshima Nobuharu, Motegi Mitsuru, Umeda Akira, Miyagawa Kazuya, Shimada Hisato, Endo Mayu, Ohira Yoshiyuki, Watanabe Masafumi, Inoue Sumito, Igarashi Akira, Sato Masamichi, Sagara Hironori, Tanaka Akihiko, Ohta Shin, Kimura Tomoyuki, Shibata Yoko, Tanino Yoshinori, Nikaido Takefumi, Minemura Hiroyuki, Sato Yuki, Yamada Yuichiro, Hashino Takuya, Shinoki Masato, Iwagoe Hajime, Takahashi Hiroshi, Fujii Kazuhiko, Kishi Hiroto, Kanai Masayuki, Imamura Tomonori, Yamashita Tatsuya, Yatomi Masakiyo, Maeno Toshitaka, Hayashi Shinichi, Takahashi Mai, Kuramochi Mizuki, Kamimaki Isamu, Tominaga Yoshiteru, Ishii Tomoo, Utsugi Mitsuyoshi, Ono Akihiro, Tanaka Toru, Kashiwada Takeru, Fujita Kazue, Saito Yoshinobu, Seike Masahiro, Watanabe Hiroko, Matsuse Hiroto, Kodaka Norio, Nakano Chihiro, Oshio Takeshi, Hirouchi Takatomo, Makino Shohei, Egi Moritoki, Omae Yosuke, Nannya Yasuhito, Ueno Takafumi, Katayama Kazuhiko, Ai Masumi, Fukui Yoshinori, Kumanogoh Atsushi, Sato Toshiro, Hasegawa Naoki, Tokunaga Katsushi, Ishii Makoto, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi, Okada Yukinori

    NATURE   609 巻 ( 7928 ) 頁: 754 - +   2022年9月

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    記述言語:英語   出版者・発行元:Nature  

    Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

    DOI: 10.1038/s41586-022-05163-5

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  87. Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host genetics 査読有り

    Otake Shiro, Chubachi Shotaro, Namkoong Ho, Nakagawara Kensuke, Tanaka Hiromu, Lee Ho, Morita Atsuho, Fukushima Takahiro, Watase Mayuko, Kusumoto Tatsuya, Masaki Katsunori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Murakami Koji, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    BMC INFECTIOUS DISEASES   22 巻 ( 1 ) 頁: 735   2022年9月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    Background: The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. Methods: From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. Results: Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, d-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. Conclusions: We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.

    DOI: 10.1186/s12879-022-07701-y

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  88. U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force 査読有り

    Fukushima Takahiro, Chubachi Shotaro, Namkoong Ho, Otake Shiro, Nakagawara Kensuke, Tanaka Hiromu, Lee Ho, Morita Atsuho, Watase Mayuko, Kusumoto Tatsuya, Masaki Katsunori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Murakami Koji, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES   122 巻   頁: 747 - 754   2022年9月

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    記述言語:英語   出版者・発行元:International Journal of Infectious Diseases  

    Objectives: This study aimed to identify the relationship between abnormal serum uric acid levels or a history of hyperuricemia and COVID-19 severity in the Japanese population. Methods: We included 1523 patients enrolled in the Japan COVID-19 Task Force cohort between February 2020 and May 2021. We compared the clinical characteristics, including co-morbidities, laboratory findings, and outcomes, particularly invasive mechanical ventilation (IMV), among patients with and without abnormal uric acid levels or a history of hyperuricemia. Results: Patients with high serum uric acid levels were older and had higher body weight and body mass index than those without. In addition, the multiple logistic regression analysis revealed a significant association between high serum uric acid levels or a history of hyperuricemia and an increased risk of IMV (odds ratio [OR] = 1.77; P = 0.03/OR = 1.56; P = 0.04). Moreover, patients with low uric acid levels on admission were also associated significantly with the requirement of IMV (OR = 5.09; P <0.0001). Conclusion: Abnormal serum uric acid levels or a history of hyperuricemia were significantly associated with COVID-19 severity in the Japanese cohort.

    DOI: 10.1016/j.ijid.2022.07.014

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  89. Mixed Realityを活用した気管支鏡トレーニング支援

    岡地 祥太郎, 桜井 麻奈美, 松井 利憲, 森瀬 昌宏, 伊藤 貴康, 長瀬 文太, 福田 夏帆, 若原 恵子, 石井 誠, 藤原 道隆

    日本VR医学会学術大会プログラム・抄録集   2022 巻 ( 0 ) 頁: 27 - 27   2022年8月

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    記述言語:日本語   出版者・発行元:日本VR医学会  

    DOI: 10.24764/jsmvr.2022.0_27

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  90. Non-invasive early prediction of immune checkpoint inhibitor efficacy in non-small-cell lung cancer patients using on-treatment serum CRP and NLR 査読有り

    Matsuzawa Reiko, Morise Masahiro, Kinoshita Fumie, Tanaka Ichidai, Koyama Junji, Kimura Tomoki, Kondoh Yasuhiro, Tanaka Taro, Shima Koichiro, Hase Tetsunari, Wakahara Keiko, Ishii Makoto, Hashimoto Naozumi

    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY     2022年8月

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    記述言語:英語   出版者・発行元:Journal of Cancer Research and Clinical Oncology  

    Purpose: We determined the clinical relevance of early C-reactive protein (CRP) and neutrophil–lymphocyte ratio (NLR) change in blood as surrogate markers of pro-tumor inflammation (PTI) for predicting clinical outcome of programmed cell death (PD)-1/programmed cell death ligand (PD-L) 1 inhibitor treatment in non-small-cell lung carcinoma (NSCLC). Methods: We retrospectively reviewed NSCLC patients treated with anti-PD-1 or PD-L1 inhibitors. Early CRP change was defined as the ratio of 6 weeks CRP to baseline CRP, and early NLR change was defined as that of the 6 weeks NLR to baseline NLR. PTI index was determined by combinatorial evaluation of early CRP change and early NLR change, PTI index low: both of these were low, intermediate: either of these was low, high; both of these were high. Results: The study included 217 patients. Early CRP change and early NLR change were both associated with PFS and OS. The combinatorial evaluation using these two markers enabled the clear stratification of PFS and OS. The median PFS in patient with PTI index low was 13.9 months, while the median PFS in those with PTI index high was 2.5 months (p < 0.01, log-rank test). The median OS in patients with PTI index low was not reached; the median OS in those with PTI index high was only 15.4 months (p < 0.01, log-rank test). Conclusions: The combinatorial early CRP change and early NLR change as PTI biomarkers have clinical potential in identifying NSCLC patients who can achieve a durable response and long-term survival using PD-1/PD-L1 inhibitors.

    DOI: 10.1007/s00432-022-04300-x

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  91. The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force 査読有り

    Wang Qingbo S., Edahiro Ryuya, Namkoong Ho, Hasegawa Takanori, Shirai Yuya, Sonehara Kyuto, Tanaka Hiromu, Lee Ho, Saiki Ryunosuke, Hyugaji Takayoshi, Shimizu Eigo, Katayama Kotoe, Kanai Masahiro, Naito Tatsuhiko, Sasa Noah, Yamamoto Kenichi, Kato Yasuhiro, Morita Takayoshi, Takahashi Kazuhisa, Harada Norihiro, Naito Toshio, Hiki Makoto, Matsushita Yasushi, Takagi Haruhi, Ichikawa Masako, Nakamura Ai, Harada Sonoko, Sandhu Yuuki, Kabata Hiroki, Masaki Katsunori, Kamata Hirofumi, Ikemura Shinnosuke, Chubachi Shotaro, Okamori Satoshi, Terai Hideki, Morita Atsuho, Asakura Takanori, Sasaki Junichi, Morisaki Hiroshi, Uwamino Yoshifumi, Nanki Kosaku, Uchida Sho, Uno Shunsuke, Nishimura Tomoyasu, Ishiguro Takashri, Isono Taisuke, Shibata Shun, Matsui Yuma, Hosoda Chiaki, Takano Kenji, Nishida Takashi, Kobayashi Yoichi, Takaku Yotaro, Takayanagi Noboru, Ueda Soichiro, Tada Ai, Miyawaki Masayoshi, Yamamoto Masaomi, Yoshida Eriko, Hayashi Reina, Nagasaka Tomoki, Arai Sawako, Kaneko Yutaro, Sasaki Kana, Tagaya Etsuko, Kawana Masatoshi, Arimura Ken, Takahashi Kunihiko, Anzai Tatsuhiko, Ito Satoshi, Endo Akifumi, Uchimura Yuji, Miyazaki Yasunari, Honda Takayuki, Tateishi Tomoya, Tohda Shuji, Ichimura Naoya, Sonobe Kazunari, Sassa Chihiro Tani, Nakajima Jun, Nakano Yasushi, Nakajima Yukiko, Anan Ryusuke, Arai Ryosuke, Kurihara Yuko, Harada Yuko, Nishio Kazumi, Ueda Tetsuya, Azuma Masanori, Saito Ryuichi, Sado Toshikatsu, Miyazaki Yoshimune, Sato Ryuichi, Haruta Yuki, Nagasaki Tadao, Yasui Yoshinori, Hasegawa Yoshinori, Mutoh Yoshikazu, Kimura Tomoki, Sato Tomonori, Takei Reoto, Hagimoto Satoshi, Noguchi Yoichiro, Yamano Yasuhiko, Sasano Hajime, Ota Sho, Nakamori Yasushi, Yoshiya Kazuhisa, Saito Fukuki, Yoshihara Tomoyuki, Wada Daiki, Iwamura Hiromu, Kanayama Syuji, Maruyama Shuhei, Yoshiyama Takashi, Ohta Ken, Kokuto Hiroyuki, Ogata Hideo, Tanaka Yoshiaki, Arakawa Kenichi, Shimoda Masafumi, Osawa Takeshi, Tateno Hiroki, Hase Isano, Yoshida Shuichi, Suzuki Shoji, Kawada Miki, Horinouchi Hirohisa, Saito Fumitake, Mitamura Keiko, Hagihara Masao, Ochi Junichi, Uchida Tomoyuki, Baba Rie, Arai Daisuke, Ogura Takayuki, Takahashi Hidenori, Hagiwara Shigehiro, Nagao Genta, Konishi Shunichiro, Nakachi Ichiro, Murakami Koji, Yamada Mitsuhiro, Sugiura Hisatoshi, Sano Hirohito, Matsumoto Shuichiro, Kimura Nozomu, Ono Yoshinao, Baba Hiroaki, Suzuki Yusuke, Nakayama Sohei, Masuzawa Keita, Namba Shinichi, Shiroyama Takayuki, Noda Yoshimi, Niitsu Takayuki, Adachi Yuichi, Enomoto Takatoshi, Amiya Saori, Hara Reina, Yamaguchi Yuta, Murakami Teruaki, Kuge Tomoki, Matsumoto Kinnosuke, Yamamoto Yuji, Yamamoto Makoto, Yoneda Midori, Tomono Kazunori, Kato Kazuto, Hirata Haruhiko, Takeda Yoshito, Koh Hidefumi, Manabe Tadashi, Funatsu Yohei, Ito Fumimaro, Fukui Takahiro, Shinozuka Keisuke, Kohashi Sumiko, Miyazaki Masatoshi, Shoko Tomohisa, Kojima Mitsuaki, Adachi Tomohiro, Ishikawa Motonao, Takahashi Kenichiro, Inoue Takashi, Hirano Toshiyuki, Kobayashi Keigo, Takaoka Hatsuyo, Watanabe Kazuyoshi, Miyazawa Naoki, Kimura Yasuhiro, Sado Reiko, Sugimoto Hideyasu, Kamiya Akane, Kuwahara Naota, Fujiwara Akiko, Matsunaga Tomohiro, Sato Yoko, Okada Takenori, Hirai Yoshihiro, Kawashima Hidetoshi, Narita Atsuya, Niwa Kazuki, Sekikawa Yoshiyuki, Nishi Koichi, Nishitsuji Masaru, Tani Mayuko, Suzuki Junya, Nakatsumi Hiroki, Ogura Takashi, Kitamura Hideya, Hagiwara Eri, Murohashi Kota, Okabayashi Hiroko, Mochimaru Takao, Nukaga Shigenari, Satomi Ryosuke, Oyamada Yoshitaka, Mori Nobuaki, Baba Tomoya, Fukui Yasutaka, Odate Mitsuru, Mashimo Shuko, Makino Yasushi, Yagi Kazuma, Hashiguchi Mizuha, Kagyo Junko, Shiomi Tetsuya, Fuke Satoshi, Saito Hiroshi, Tsuchida Tomoya, Fujitani Shigeki, Takita Mumon, Morikawa Daiki, Yoshida Toru, Izumo Takehiro, Inomata Minoru, Kuse Naoyuki, Awano Nobuyasu, Tone Mari, Ito Akihiro, Nakamura Yoshihiko, Hoshino Kota, Maruyama Junichi, Ishikura Hiroyasu, Takata Tohru, Odani Toshio, Amishima Masaru, Hattori Takeshi, Shichinohe Yasuo, Kagaya Takashi, Kita Toshiyuki, Ohta Kazuhide, Sakagami Satoru, Koshida Kiyoshi, Hayashi Kentaro, Shimizu Tetsuo, Kozu Yutaka, Hiranuma Hisato, Gon Yasuhiro, Izumi Namiki, Nagata Kaoru, Ueda Ken, Taki Reiko, Hanada Satoko, Kawamura Kodai, Ichikado Kazuya, Nishiyama Kenta, Muranaka Hiroyuki, Nakamura Kazunori, Hashimoto Naozumi, Wakahara Keiko, Koji Sakamoto, Omote Norihito, Ando Akira, Kodama Nobuhiro, Kaneyama Yasunari, Maeda Shunsuke, Kuraki Takashige, Matsumoto Takemasa, Yokote Koutaro, Nakada Taka-Aki, Abe Ryuzo, Oshima Taku, Shimada Tadanaga, Harada Masahiro, Takahashi Takeshi, Ono Hiroshi, Sakurai Toshihiro, Shibusawa Takayuki, Kimizuka Yoshifumi, Kawana Akihiko, Sano Tomoya, Watanabe Chie, Suematsu Ryohei, Sageshima Hisako, Yoshifuji Ayumi, Ito Kazuto, Takahashi Saeko, Ishioka Kota, Nakamura Morio, Masuda Makoto, Wakabayashi Aya, Watanabe Hiroki, Ueda Suguru, Nishikawa Masanori, Chihara Yusuke, Takeuchi Mayumi, Onoi Keisuke, Shinozuka Jun, Sueyoshi Atsushi, Nagasaki Yoji, Okamoto Masaki, Ishihara Sayoko, Shimo Masatoshi, Tokunaga Yoshihisa, Kusaka Yu, Ohba Takehiko, Isogai Susumu, Ogawa Aki, Inoue Takuya, Fukuyama Satoru, Eriguchi Yoshihiro, Yonekawa Akiko, Kan-o Keiko, Matsumoto Koichiro, Kanaoka Kensuke, Ihara Shoichi, Komuta Kiyoshi, Inoue Yoshiaki, Chiba Shigeru, Yamagata Kunihiro, Hiramatsu Yuji, Kai Hirayasu, Asano Koichiro, Oguma Tsuyoshi, Ito Yoko, Hashimoto Satoru, Yamasaki Masaki, Kasamatsu Yu, Komase Yuko, Hida Naoya, Tsuburai Takahiro, Oyama Baku, Takada Minoru, Kanda Hidenori, Kitagawa Yuichiro, Fukuta Tetsuya, Miyake Takahito, Yoshida Shozo, Ogura Shinji, Abe Shinji, Kono Yuta, Togashi Yuki, Takoi Hiroyuki, Kikuchi Ryota, Ogawa Shinichi, Ogata Tomouki, Ishihara Shoichiro, Kanehiro Arihiko, Ozaki Shinji, Fuchimoto Yasuko, Wada Sae, Fujimoto Nobukazu, Nishiyama Kei, Terashima Mariko, Beppu Satoru, Yoshida Kosuke, Narumoto Osamu, Nagai Hideaki, Ooshima Nobuharu, Motegi Mitsuru, Umeda Akira, Miyagawa Kazuya, Shimada Hisato, Endo Mayu, Ohira Yoshiyuki, Watanabe Masafumi, Inoue Sumito, Igarashi Akira, Sato Masamichi, Sagara Hironori, Tanaka Akihiko, Ohta Shin, Kimura Tomoyuki, Shibata Yoko, Tanino Yoshinori, Nikaido Takefumi, Minemura Hiroyuki, Sato Yuki, Yamada Yuichiro, Hashino Takuya, Shinoki Masato, Iwagoe Hajime, Takahashi Hiroshi, Fujii Kazuhiko, Kishi Hiroto, Kanai Masayuki, Imamura Tomonori, Yamashita Tatsuya, Yatomi Masakiyo, Maeno Toshitaka, Hayashi Shinichi, Takahashi Mai, Kuramochi Mizuki, Kamimaki Isamu, Tominaga Yoshiteru, Ishii Tomoo, Utsugi Mitsuyoshi, Ono Akihiro, Tanaka Toru, Kashiwada Takeru, Fujita Kazue, Saito Yoshinobu, Seike Masahiro, Watanabe Hiroko, Matsuse Hiroto, Kodaka Norio, Nakano Chihiro, Oshio Takeshi, Hirouchi Takatomo, Makino Shohei, Egi Moritoki, Omae Yosuke, Nannya Yasuhito, Ueno Takafumi, Takano Tomomi, Katayama Kazuhiko, Ai Masumi, Kumanogoh Atsushi, Sato Toshiro, Hasegawa Naoki, Tokunaga Katsushi, Ishii Makoto, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi, Okada Yukinori

    NATURE COMMUNICATIONS   13 巻 ( 1 ) 頁: 4830   2022年8月

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    記述言語:英語   出版者・発行元:Nature Communications  

    Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

    DOI: 10.1038/s41467-022-32276-2

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  92. Effects of mild obesity on outcomes in Japanese patients with COVID-19: a nationwide consortium to investigate COVID-19 host genetics 査読有り

    Lee Ho, Chubachi Shotaro, Namkoong Ho, Tanaka Hiromu, Otake Shiro, Nakagawara Kensuke, Morita Atsuho, Fukushima Takahiro, Watase Mayuko, Kusumoto Tatsuya, Masaki Katsunori, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Murakami Koji, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    NUTRITION & DIABETES   12 巻 ( 1 ) 頁: 38   2022年8月

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    記述言語:英語   出版者・発行元:Nutrition and Diabetes  

    Background: Obesity is reported to be a risk factor for severe disease in patients with coronavirus disease 2019 (COVID-19). However, there are no specific reports on the risk of severe disease according to body mass index (BMI) in Japan. Thus, this study aimed to investigate the effect of obesity stratified by BMI on the severity of COVID-19 in the general Japanese population. Methods: From February 2020 to May 2021, 1 837 patients aged ≥18 years were enrolled in the Japan COVID-19 Task Force. Patients with known BMI and disease severity were analyzed. Severity was defined as critical if the patient was treated in the intensive care unit, required invasive mechanical ventilation, or died. Results: Class 1 obesity (25.0 ≤ BMI < 30.0 kg/m2), class 2 obesity (30.0 ≤ BMI < 35.0 kg/m2), and class 3 or 4 obesity (BMI ≥ 35 kg/m2) were present in 29%, 8%, and 3% of the cases, respectively. Multiple logistic regression analysis with known risk factors for critical illness indicated that class 2 obesity was an independent risk factor for oxygenation (adjusted odds ratio, 4.75) and critical cases (adjusted odds ratio, 1.81). Class 1 obesity and class 3 or 4 obesity were independent risk factors for oxygen administration (adjusted odds ratios 2.01 and 3.12, respectively), but not for critical cases. However, no differences in the mortality rates were observed between the BMI classes (P = 0.5104). Conclusion: Obesity is a risk factor for respiratory failure in Japanese patients with COVID-19, regardless of the degree of obesity. However, it may not cause severe COVID-19 in a dose–response relationship with BMI. COVID-19 patients with mild obesity may benefit from aggressive intensive care.

    DOI: 10.1038/s41387-022-00217-z

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  93. 特集 新型コロナウイルス感染症(COVID-19)のすべて Ⅱ.病態と診断 発症病態と重症化メカニズム-10のポイント

    小倉 高志, 織田 恒幸, 石井 誠, 石田 正之

    呼吸器ジャーナル   70 巻 ( 3 ) 頁: 351 - 361   2022年8月

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    出版者・発行元:株式会社 医学書院  

    DOI: 10.11477/mf.1437200567

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  94. 非結核性抗酸菌症の臨床1 難治性肺Mycobacterium avium/intracellulare(MAI)症に対するアミカシンリポソーム吸入懸濁液導入例の検討

    森田 篤帆, 南宮 湖, 李 昊, 田中 拓, 楠木 竜也, 小川 卓範, 阿瀬川 周平, 中川原 賢亮, 加治 正憲, 鎌田 浩史, 石井 誠, 福永 興壱, 長谷川 直樹

    結核   97 巻 ( 4 ) 頁: 72 - 72   2022年6月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

  95. Osteoporosis in nontuberculous mycobacterial pulmonary disease: a cross-sectional study 査読有り

    Tanaka Hiromu, Asakura Takanori, Suzuki Shoji, Okamori Satoshi, Kusumoto Tatsuya, Ogawa Takunori, Uno Shunsuke, Morita Atsuho, Lee Ho, Namkoong Ho, Kamata Hirofumi, Sato Yasunori, Uwamino Yoshifumi, Nishimura Tomoyasu, Ishii Makoto, Fukunaga Koichi, Hasegawa Naoki

    BMC PULMONARY MEDICINE   22 巻 ( 1 ) 頁: 202   2022年5月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is common in middle-aged/elderly slender women at risk of osteoporosis, we hypothesized that NTM-PD could be associated with osteoporosis. The study aimed to evaluate the prevalence of osteoporosis in patients with NTM-PD compared with that in the general population and determine the factors associated with osteoporosis in the subjects, including the serum estradiol (E2) and 25-hydroxyvitamin D (25OHD) levels. Methods: We have recruited 228 consecutive adult patients with NTM-PD from a prospective cohort study at the Keio University Hospital, who had no history of osteoporosis or osteoporosis-associated bone fracture but underwent dual-energy X-ray absorptiometry-based bone mineral density (BMD) evaluation from August 2017–September 2019. The E2 and 25OHD levels were measured in 165 patients with available stored serum samples. We performed multivariable logistic regression analyses for osteopenia and osteoporosis. Results: Osteoporosis (T-score ≤ − 2.5) and osteopenia (T-score − 1 to − 2.5) were diagnosed in 35.1% and 36.8% of patients with NTM-PD, respectively. Compared with the general population, the proportion of osteoporosis was significantly higher in 50–59-, 60–69-, and 70–79-year-old women with NTM-PD. Multivariable analysis revealed that older age (adjusted odds ratio [aOR] for 1-year increase = 1.12; 95% confidence interval [CI] = 1.07–1.18), female sex (aOR = 36.3; 95% CI = 7.57–174), lower BMI (aOR for 1 kg/m2 decrease = 1.37; 95% CI = 1.14–1.65), and chronic Pseudomonas aeruginosa (PA) infection (aOR = 6.70; 95% CI = 1.07–41.8) were independently associated with osteoporosis. Additionally, multivariable analysis in 165 patients whose serum E2 and 25OHD levels were measured showed that both low E2 levels (< 10 pg/mL) and lower 25OHD levels were independently associated with osteoporosis. Conclusions: Middle-aged/elderly women with NTM-PD have a higher prevalence of osteoporosis than the general population. BMD screening should be considered in NTM-PD, especially in older females with severe diseases such as chronic PA infection and lower BMI, and low serum E2 and 25OHD levels.

    DOI: 10.1186/s12890-022-01991-3

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  96. COVID-19のいわゆる後遺症に関するシンポジウム わが国における新型コロナウィルス感染症の遷延症状について

    寺井 秀樹, 南宮 湖, 石井 誠, 福永 興壱

    日本呼吸器学会誌   11 巻 ( 増刊 ) 頁: 49 - 49   2022年4月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  97. COVID-19患者における入院後24-48時間後の胸部レントゲン所見増悪の重要性

    楠本 竜也, 中鉢 正太郎, 南宮 湖, 田中 拓, 李 昊, 福島 貴大, 大竹 史朗, 中川原 賢亮, 渡瀬 麻友子, 正木 克宜, 鎌田 浩史, 石井 誠, 長谷川 直樹, 金井 隆典, 福永 興壱

    日本呼吸器学会誌   11 巻 ( 増刊 ) 頁: 310 - 310   2022年4月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  98. COVID-19 特徴的臨床像 日本人COVID-19患者における呼吸器細菌感染合併症例の臨床的特徴の検討

    中川原 賢亮, 鎌田 浩史, 大竹 史朗, 田中 拓, 福島 貴大, 李 昊, 渡瀬 麻友子, 楠本 竜也, 正木 克宜, 南宮 湖, 中鉢 正太郎, 石井 誠, 長谷川 直樹, 金井 隆典, 福永 興壱, コロナ制圧タスクフォース

    日本呼吸器学会誌   11 巻 ( 増刊 ) 頁: 155 - 155   2022年4月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  99. Short-term intermittent cigarette smoke exposure enhances alveolar type 2 cell stemness via fatty acid oxidation

    Irie Hidehiro, Ozaki Mari, Chubachi Shotaro, Hegab Ahmed E., Tsutsumi Akihiro, Kameyama Naofumi, Sakurai Kaori, Nakayama Shingo, Kagawa Shizuko, Wada Sachika, Ishii Makoto, Betsuyaku Tomoko, Fukunaga Koichi

    RESPIRATORY RESEARCH   23 巻 ( 1 ) 頁: 41   2022年3月

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    記述言語:英語   出版者・発行元:Respiratory Research  

    Background: Cigarette smoke (CS) is associated with chronic obstructive pulmonary disease (COPD) and cancer. However, the underlying pathological mechanisms are not well understood. We recently reported that mice exposed to long-term intermittent CS for 3 months developed more severe emphysema and higher incidence of adenocarcinoma than mice exposed to long-term continuous CS for 3 months and long-term continuous CS exposure activated alveolar stem cell proliferation. However, the influence of variations in the CS exposure pattern in alveolar stem cell in unknown. Here, we exposed mice to 3 weeks of continuous or intermittent CS to identify whether different CS exposure patterns would result in differential effects on stem cells and the mechanisms underlying these potential differences. Methods: Female mice expressing GFP in alveolar type 2 (AT2) cells, which are stem cells of the alveolar compartment, were exposed to mainstream CS via nasal inhalation. AT2 cells were collected based on their GFP expression by flow cytometry and co-cultured with fibroblasts in stem cell 3D organoid/colony-forming assays. We compared gene expression profiles of continuous and intermittent CS-exposed AT2 cells using microarray analysis and performed a functional assessment of a differentially expressed gene to confirm its involvement in the process using activator and inhibitor studies. Results: AT2 cells sorted from intermittent CS-exposed mice formed significantly more colonies compared to those from continuous CS-exposed mice, and both CS-exposed groups formed significantly more colonies when compared to air-exposed cells. Comparative microarray analysis revealed the upregulation of genes related to fatty acid oxidation (FAO) pathways in AT2 cells from intermittent CS-exposed mice. Treatment of intermittent CS-exposed mice with etomoxir, an inhibitor of the FAO regulator Cpt1a, for 5 weeks resulted in a significant suppression of the efficiency of AT2 cell colony formation. In vitro treatment of naïve AT2 cells with a FAO activator and inhibitor further confirmed the relationship between FAO and AT2 stem cell function. Conclusions: Alveolar stem cell function was more strongly activated by intermittent CS exposure than by continuous CS exposure. We provide evidence that AT2 stem cells respond to intermittent CS exposure by activating stem cell proliferation via the activation of FAO.

    DOI: 10.1186/s12931-022-01948-4

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  100. 新型コロナウイルス感染症(COVID-19)の重症化を早期に予測する重症化予測システムの確立

    石井 誠, 福永 興壱, 満倉 靖恵

    大和証券ヘルス財団研究業績集   ( 45 ) 頁: 185 - 188   2022年3月

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    記述言語:日本語   出版者・発行元:(公財)大和証券ヘルス財団  

    当院および関連病院14施設で確定診断したCOVID-19患者234例を対象として、次元の異なる生体情報(年齢・性別等の基本情報、症状、採血所見、画像情報など)を網羅的に集積した。また、回復者の症状の推移に関して患者へのアンケートを行った。得られた情報に関してデータクレンジングを行い、COVID-19の重症化例と非重症化例を比較した。多次元特徴解析を行って重症化の予測式を構築し、各患者の総合的な重症化リスクを発症初期の段階で提示することを目指した。その結果、ロジスティック回帰解析において精度89%で重症化と非重症化を予測できる式が得られた。重症化を早期に予測することにより、医療資源の最適化、早期治療介入が行え、死亡率低下につながると考えられた。

  101. Pro108Ser mutation of SARS-CoV-2 3CL(pro) reduces the enzyme activity and ameliorates the clinical severity of COVID-19

    Abe Kodai, Kabe Yasuaki, Uchiyama Susumu, Iwasaki Yuka W., Ishizu Hirotsugu, Uwamino Yoshifumi, Takenouchi Toshiki, Uno Shunsuke, Ishii Makoto, Maruno Takahiro, Noda Masanori, Murata Mitsuru, Hasegawa Naoki, Saya Hideyuki, Kitagawa Yuko, Fukunaga Koichi, Amagai Masayuki, Siomi Haruhiko, Suematsu Makoto, Kosaki Kenjiro

    SCIENTIFIC REPORTS   12 巻 ( 1 ) 頁: 1299   2022年1月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Recently, an international randomized controlled clinical trial showed that patients with SARS-CoV-2 infection treated orally with the 3-chymotrypsin-like protease (3CLpro) inhibitor PF-07321332 within three days of symptom onset showed an 89% lower risk of COVID-19-related hospital admission/ death from any cause as compared with the patients who received placebo. Lending support to this critically important result of the aforementioned trial, we demonstrated in our study that patients infected with a SARS-Cov-2 sub-lineage (B.1.1.284) carrying the Pro108Ser mutation in 3CLpro tended to have a comparatively milder clinical course (i.e., a smaller proportion of patients required oxygen supplementation during the clinical course) than patients infected with the same sub-lineage of virus not carrying the mutation. Characterization of the mutant 3CLpro revealed that the Kcat/Km of the 3CLpro enzyme containing Ser108 was 58% lower than that of Pro108 3CLpro. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) revealed that the reduced activity was associated with structural perturbation surrounding the substrate-binding region of the enzyme, which is positioned behind and distant from the 108th amino acid residue. Our findings of the attenuated clinical course of COVID-19 in patients infected with SARS-CoV-2 strains with reduced 3CLpro enzymatic activity greatly endorses the promising result of the aforementioned clinical trial of the 3CLpro inhibitor.

    DOI: 10.1038/s41598-022-05424-3

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  102. Development of Rheumatoid Arthritis in Cavitary Mycobacterium avium Pulmonary Disease: A Case Report of Successful Treatment with CTLA4-Ig (Abatacept)

    Tanaka Hiromu, Asakura Takanori, Kikuchi Jun, Ishii Makoto, Namkoong Ho, Kaneko Yuko, Fukunaga Koichi, Hasegawa Naoki

    INFECTION AND DRUG RESISTANCE   15 巻   頁: 91 - 97   2022年

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    記述言語:英語   出版者・発行元:Infection and Drug Resistance  

    Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) often develops in patients with rheumatoid arthritis (RA), especially during immunosuppressive treatment, including biological disease-modifying antirheumatic drugs. NTM-PD is associated with airway lesions such as bronchiectasis, which is frequently seen in RA patients. Distinguishing which diseases cause the pulmonary lesion is difficult. However, there are limited reports of the development of RA during the follow-up of NTM-PD and how biological agents should be administered in these conditions, especially with cavitary lesions. Case Presentation: A 62-year-old woman with hemosputum was referred to our hospital, where she was diagnosed with Mycobacterium avium pulmonary disease. She began treatment with several antibiotics, including clarithromycin, ethambutol, rifampicin, and amikacin. In the course of treatment, M. avium became macrolide-resistant. Five years after beginning antibiotic treatment, she felt arthralgia in the fingers and wrists and had a high titer of rheumatoid factor and anticitrullinated peptide antibody, with which we diagnosed RA. Methotrexate, prednisolone, and iguratimod were subsequently admi-nistered, but the activity of RA gradually worsened. Meanwhile, M. avium changed to a macrolide-susceptible strain, her sputum smear results remained almost negative, and the NTM-PD disease was well controlled with antimicrobial therapy, despite her having cavitary lesions. Therefore, we started using CTLA4-Ig (abatacept). RA symptoms were substantially ameliorated. The pulmonary lesions and NTM-PD worsened mildly, but her pulmonary symptoms were stable. Conclusion: Physicians should be mindful of the etiologies of bronchiectasis, including RA, even in patients with a long-term history of treatment for bronchiectasis and NTM-PD. When NTM-PD is well controlled, even with remaining cavitary lesions, abatacept may be an option for patients with RA based on a comprehensive assessment of disease progression using NTM sputum smear/culture, computed tomography findings, and treatment response.

    DOI: 10.2147/IDR.S343763

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  103. Early-Phase Adverse Effects and Management of Liposomal Amikacin Inhalation for Ref ractory Mycobacterium avium Co m p l ex Lung Disease in Real-World Settings 査読有り

    Morita Atsuho, Namkoong Ho, Yagi Kazuma, Asakura Takanori, Hosoya Makoto, Tanaka Hiromu, Lee Ho, Ogawa Takunori, Kusumoto Tatsuya, Azekawa Shuhei, Nakagawara Kensuke, Kamata Hirofumi, Ishii Makoto, Fukunaga Koichi, Ozawa Hiroyuki, Hasegawa Naoki

    INFECTION AND DRUG RESISTANCE   15 巻   頁: 4001 - 4011   2022年

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    記述言語:英語   出版者・発行元:Infection and Drug Resistance  

    Purpose: Amikacin liposome inhalation suspension (ALIS), which efficiently allows amikacin to reach the pulmonary periphery for effect while minimising systemic adverse effects, was recently approved for treating Mycobacterium avium complex (MAC) infections. The international Phase 3 open-label clinical trials showed promising results, contributing to sputum culture conversion, but few studies have examined the efficacy and adverse effects of ALIS using real-world data. We identified the clinical outcome and adverse effects of ALIS in the early phase of treatment, for more effective and safe use in clinical practice. Patients and Methods: The study population consisted of patients with MAC lung disease (MAC-LD), introduced to ALIS therapy after July 2021 at Keio University Hospital due to poor response to multidrug therapy. The sputum smear/culture results, symptoms, adverse effects, and the serum amikacin concentrations of the early phase of ALIS inhalation therapy were examined. Results: A total of 11 patients (9 women; median age 64.6 years) were included in this study. The median disease duration of MAC-LD was 13.7 years, and all patients exhibited a positive culture at the beginning of ALIS inhalation. Three of the six patients (50.0%) who were initially sputum-smear-positive were confirmed to have become sputum-smear-negative within one month, including one culture conversion. ALIS inhalation therapy caused some adverse effects in nine patients (81.8%); however, no serious systemic adverse effects were observed. The most common adverse effect was hoarseness (72.7%), which mostly occurred around 1 week after initiation. The medians of peak serum amikacin concentrations were 1.4 and 2.3 μg/mL for the first and third inhalations, respectively. Trough serum concentrations just before the third inhalation were <1.2 μg/mL in all patients. Conclusion: ALIS therapy might be a treatment option for patients with refractory MAC infection with long disease duration and a poor response to guideline-based therapy.

    DOI: 10.2147/IDR.S373783

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  104. Diagnostic Performance of Computed Tomography Imaging for COVID-19 in a Region with Low Disease Prevalence 査読有り

    Lee Ho, Suzuki Tatsuya, Okada Yohei, Tanaka Hiromu, Okamori Satoshi, Kamata Hirofumi, Ishii Makoto, Jinzaki Masahiro, Fukunaga Koichi

    The Keio Journal of Medicine   71 巻 ( 1 ) 頁: 21 - 30   2022年

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    担当区分:責任著者   記述言語:英語   出版者・発行元:The Keio Journal of Medicine  

    Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019 as an outbreak of pneumonia of unknown origin. Previous studies have suggested the utility of chest computed tomography (CT) in the diagnosis of COVID-19 because of its high sensitivity (93%–97%), relatively simple procedure, and rapid test results. This study, performed in Japan early in the epidemic when COVID-19 prevalence was low, evaluated the diagnostic accuracy of chest CT in a population presenting with lung diseases having CT findings similar to those of COVID-19. We retrospectively included all consecutive patients (≥18 years old) presenting to the outpatient department of Keio University Hospital between March 1 and May 31, 2020, with fever and respiratory symptoms. We evaluated the performance of diagnostic CT for COVID-19 by using polymerase chain reaction (PCR) results as the reference standard. We determined the numbers of false-positive (FP) results and assessed the clinical utility using decision curve analysis. Of the 175 patients, 22 were PCR-positive. CT had a sensitivity of 68% and a specificity of 57%. Patients with FP results on CT diagnosis were mainly diagnosed with diseases mimicking COVID-19, e.g., interstitial lung disease. Decision curve analysis indicated that the clinical utility of CT imaging was limited. The diagnostic performance of CT for COVID-19 was inadequate in an area with low COVID-19 prevalence and a high prevalence of other lung diseases with chest CT findings similar to those of COVID-19. Considering this insufficient diagnostic performance, CT findings should be evaluated in the context of additional medical information to diagnose COVID-19.

    DOI: 10.2302/kjm.2021-0012-oa

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  105. Comprehensive Analysis of Long COVID in a Japanese Nationwide Prospective Cohort Study

    Hideki Terai, Makoto Ishii, Ryo Takemura, Ho Namkoong, Kyoko Shimamoto, Katsunori Masaki, Takae Tanosaki, Shotaro Chubachi, Emiko Matsuyama, Reina Hayashi, Takashi Shimada, Lisa Shigematsu, Fumimaro Ito, Masanori Kaji, Hatsuyo Takaoka, Momoko Kurihara, Kensuke Nakagawara, Saki Tomiyasu, Kotaro Sasahara, Ayaka Saito, Shiro Otake, Shuhei Azegawa, Masahiko Okada, Takahiro Fukushima, Atsuho Morita, Hiromu Tanaka, Keeya Sunata, Masato Asaoka, Miyuki Nishie, Taro Shinozaki, Toshiki Ebisudani, Yuto Akiyama, Akifumi Mitsuishi, Shingo Nakayama, Takunori Ogawa, Kaori Sakurai, Misato Kuwae, Kazuma Yagi, Keiko Ohgino, Jun Miyata, Hiroki Kabata, Shinnosuke Ikemura, Hirofumi Kamata, Hiroyuki Yasuda, Ichiro Kawada, Ryusei Kimura, Masahiro Kondo, Toshiki Iwasaki, Noriyuki Ishida, Gaku Hiruma, Naoki Miyazaki, Yoshiki Ishibashi, Sei Harada, Takanori Fujita, Daisuke Ito, Shogyoku Bun, Hajime Tabuchi, Sho Kanzaki, Eisuke Shimizu, Keitaro Fukuda, Jun Yamagami, Keigo Kobayashi, Toshiyuki Hirano, Takashi Inoue, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Ho Lee, Kai Sugihara, Nao Omori, Koichi Sayama, Kengo Otsuka, Naoki Miyao, Toshio Odani, Takao Mochimaru, Ryosuke Satomi, Yoshitaka Oyamada, Keita Masuzawa, Takanori Asakura, Mayuko Watase, Sohei Nakayama, Yusuke Suzuki, Rie Baba, Satoshi Okamori, Daisuke Arai, Ichiro Nakachi, Naota Kuwahara, Akiko Fujiwara, Takenori Okada, Takashi Ishiguro, Taisuke Isono, Yasushi Makino, Shuko Mashimo, Tatsuya Kaido, Naoto Minematsu, Soichiro Ueda, Kazuhiro Minami, Rie Hagiwara, Tadashi Manabe, Takahiro Fukui, Yohei Funatsu, Hidefumi Koh, Takashi Yoshiyama, Hiroyuki Kokuto, Tatsuya Kusumoto, Ayano Oashi, Masayoshi Miyawaki, Fumitake Saito, Tetsuo Tani, Kota Ishioka, Saeko Takahashi, Morio Nakamura, Norihiro Harada, Hitoshi Sasano, Ai Nakamura, Yu Kusaka, Takehiko Ohba, Yasushi Nakano, Kazumi Nishio, Yukiko Nakajima, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Nobuhiro Kodama, Shunsuke Maeda, Satoshi Sakamoto, Masaki Okamoto, Yoji Nagasaki, Akira Umeda, Kasuya Miyagawa, Naoto Shimada, Kazuto Hagimura, Kengo Nagashima, Toshiro Sato, Yasunori Sato, Naoki Hasegawa, Toru Takebayashi, Jin Nakahara, Masaru Mimura, Kaoru Ogawa, Shigeto Shimmura, Kazuno Negishi, Kazuo Tsubota, Masayuki Amagai, Rei Goto, Yoko Ibuka, Yuko Kitagawa, Takanori Kanai, Koichi Fukunaga

    SSRN Electronic Journal     2022年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.2139/ssrn.4272351

  106. Mapping the human genetic architecture of COVID-19

    Niemi Mari E. K., Karjalainen Juha, Daly Mark, Ganna Andrea, Mehtonen Juha, Cordioli Mattia, Kaunisto Mari, Pigazzini Sara, Donner Kati, Kivinen Katja, Palotie Aarno, Daly Mark J., Liao Rachel G., Kanai Masahiro, Veerapen Kumar, Minica Camelia, Trankiem Amy, Balaconis Mary K., Nguyen Huy, Solomonson Matthew, Francioli Laurent, Wang Qingbo, Green Robert C., Bryant Sam, Finucane Hilary, Martin Alicia R., Zhou Wei, Nkambule Lindokuhle, Karczewski Konrad J., Atkinson Elizabeth G., Tsuo Kristin, Baya Nikolas, Turley Patrick, Gupta Rahul, Walters Raymond K., Palmer Duncan S., Sarma Gopal, Cheng Nathan, Lu Wenhan, Churchhouse Claire, Goldstein Jacqueline I, King Daniel, Seed Cotton, Neale Benjamin M., Satterstrom F. Kyle, Pathak Gita A., Wendt Frank R., Polimanti Renato, Andrews Shea J., Sloofman Laura, Sealfon Stuart C., Fernandez-Cadenas Israel, Schulte Eva C., Protzer Ulrike, Striano Pasquale, Coviello Domenico A., Zara Federico, Salpietro Vincenzo, Iacomino Michele, Scudieri Paolo, Bocciardi Renata, Minetti Carlo, Vari Maria Stella, Madia Francesca, Marouli Eirini, Kanoni Stavroula, Moutsianas Loukas, Karim Mohd Anisul, Ghoussaini Maya, Schwartzentruber Jeremy, Dunham Ian, Savage Jeanne, Posthuma Danielle, Tissink Elleke, Uffelmann Emil, Butler-Laporte Guillaume, Richards J. Brent, Nakanishi Tomoko, Morrison David R., Forgetta Vincenzo, Ghosh Biswarup, Laurent Laetitia, Henry Danielle, Abdullah Tala, Adeleye Olumide, Mamlouk Noor, Kimchi Nofar, Afrasiabi Zaman, Rezk Nardin, Vulesevic Branka, Bouab Meriem, Guzman Charlotte, Petitjean Louis, Tselios Chris, Xue Xiaoqing, Afilalo Jonathan, Adra Darin, Kim Han-Na, Okada Yukinori, Byun Jinyoung, Han Younghun, Uddin Mohammed Jashim, Smith George Davey, Willer Cristen J., Buxbaum Joseph D., Sloofman Laura G., Collins Brett L., Levy Tess, Underwood Slayton J., Britvan Bari, Keller Katherine, Tang Lara, Peruggia Michael, Hiester Liam L., Niblo Kristi, Aksentijevich Alexandra, Labkowsky Alexander, Karp Avromie, Zlatopolsky Menachem, Arora Jatin, Raychaudhuri Soumya, Mercader Josep, Cusick Caroline, Pasaniuc Bogdan, Julienne Hanna, Aschard Hugues, Shi Huwenbo, Yengo Loic, Chwialkowska Karolina, Francescatto Margherita, Davis Lea, Kerchberger V. Eric, Lee Sulggi, Priest James, Vadgama Nirmal, Tanigawa Yosuke, Renieri Alessandra, Sankaran Vijay G., van Heel David, de Salazar Adolfo, van Heel David A., Hunt Karen A., Trivedi Bhavi, Deelen Patrick, Franke Lude, Claringbould Annique, Lopera Esteban, Warmerdam Robert, van Blokland Irene, Lanting Pauline, Mooser Vincent, Li Rui, Belisle Alexandre, Lepage Pierre, Ragoussis Jiannis, Auld Daniel, Lathrop G. Mark, Biesecker Les, Baillie J. Kenneth, Clohisey Sara, Fourman Max Head, Furniss James, Haley Chris, Law Andy, Millar Jonathan, Pairo-Castineira Erola, Parkinson Nicholas, Rawlik Konrad, Russell Clark D., Shih Barbara, Tenesa Albert, Wang Bo, Zechner Marie, Law Andrew, Hendry Ross, Armstrong Ruth, Boz Ceilia, Brown Adam, Cullum Louise, Day Nicky, Duncan Esther, Finernan Paul, Golightly Ailsa, Law Dawn, Law Rachel, Law Sarah, Mal Hanning, Mcmaster Ellie, Meikle Jen, Oosthuyzen Wilna, Paterson Trevor, Stenhouse Andrew, Swets Maaike, Szoor-McElhinney Helen, Taneski Filip, Wackett Tony, Ward Mairi, Weaver Jane, Coyle Judy, Gallagher Bernadette, Lidstone-Scott Rebecca, Hamilton Debbie, Griffiths Fiona, Keating Sean, Walsh Timothy, Bretherick Andrew D., Grimes Graeme, Hayward Caroline, Klaric Lucija, Meynert Alison M., Ponting Chris P., Richmond Anne, Vitart Veronique, Wilson James F., Mari Francesca, Lista Mirjam, Perticaroli Valentina, Fallerini Chiara, Daga Sergio, Baldassarri Margherita, Fava Francesca, Frullanti Elisa, Valentino Floriana, Doddato Gabriella, Giliberti Annarita, Bruttini Mirella, Croci Susanna, Meloni Ilaria, Beligni Giada, Tommasi Andrea, Di Sarno Laura, Palmieri Maria, Carriero Miriam Lucia, Alaverdian Diana, Iuso Nicola, Inchingolo Gabriele, Tita Rossella, Amitrano Sara, Mencarelli Maria Antonietta, Lo Rizzo Caterina, Pinto Anna Maria, Montagnani Francesca, Tumbarello Mario, Furini Simone, Benetti Elisa, Zguro Kristina, Capitani Katia, Zanelli Giacomo, Bianchi Francesco, Bernasconi Anna, Ceri Stefano, Pinoli Pietro, Baillie Stefano Ceri, Canakoglu Arif, Wolford Brooke, Faucon Annika, Dutta Atanu Kumar, Patel Sanjay, Schurmann Claudia, Harry Emi, Birney Ewan, Nasir Jamal, Marttila Minttu, Dueker Nicole, Limou Sophie, Rahmouni Souad, Mbarek Hamdi, Darwish Dima, Ismail Said I., Saad Chadi, Al-Sarraj Yaser, Badji Radja Messai, Al-Muftah Wadha, Al Thani Asma, Uddin Md Mesbah, Albertos Raquel, Ferrer Ricard, Perez-Tur Jordi, Li Ruolin, Medina-Gomez Carolina, Sedaghati-Khayat Bahar, Vallerga Costanza, Boer Cindy, Kennis-Szilagyi Ingrid, Prijatelj Vid, Folkersen Lasse, Moltke Ida, Koelling Nils, Spencer Chris A., Teumer Alexander, Kousathanas Athanasios, Pasko Dorota, Caulfield Mark J., Scott Richard H., Walker Susan, Stuckey Alex, Odhams Christopher A., Rhodes Daniel, Fowler Tom, Rendon Augusto, Chan Georgia, Arumugam Prabhu, Utrilla Alicia, Verdugo Ricardo A., Zarate Ruth, Gomez-Cabrero David, Carnero-Montoro Elena, Alarcon-Riquelme Marta E., Martinez-Bueno Manuel, Cadilla Carmen L., Moreno-Estrada Andres, Garmendia Adriana, Moya Leire, Boua Palwende Romuald, Fave Marie-Julie, Lemacon Audrey, Migeotte Isabelle, Varnai Reka, Szentpeteri Jozsef L., Sipeky Csilla, Colombo Francesca, von Hohenstaufen Kathrin, Lio Pietro, Im Hogune, Han Chulho, Song Han, Lim Jiwoo, Lee Younhe, Kim Sugyeong, Atanasovska Biljana, Ahmad Hajar Fauzan, Jansen Philip, Hottenga Jouke Jan, Bartels Meike, de Geus Eco J. C., Nivard Michel G., Kornilov Sergey A., Sivanadhan Ilangkumaran, Perumal Sarala, Esmaeeli Sahar, Pearson Nathaniel M., Auton Adam, Shelton Janie F., Shastri Anjali J., Filshtein-Sonmez Teresa, Coker Daniella, Symons Antony, Aslibekyan Stella, O'Connell Jared, Ye Chelsea, Weldon Catherine H., Esparza-Gordillo Jorge, Perera Minoli, Yang Guang, Alarcon Cristina, Herrmann Stefanie, Friedman Paula, O'Leary Kevin, Mazurek Sophia, Tuck Matthew, Banagan Jeff, Hamidi Zacharia, O'Brien Travis, Meltzer David, Raffat Noora, de la Horra Carmen, O'Donnell Peter, Nutescu Edith, Moreno Diana, Barbour April, Gallego-Duran Rocio, Ferwerda Bart, van de Beek Diederik, Brouwer Matthijs C., Beudel Martijn, Koning Rutger, Vlaar Alexander P. J., Algera Anne Geke, van Baarle Frank, Bos Lieuwe, Botta Michela, de Bruin Sanne, Bulle Esther, Dongelmans Dave, Elbers Paul, Fleuren Lucas, Girbes Armand, Hagens Laura, Heunks Leo, Horn Janneke, van Mourik Niels, Paulus Frederique, Raasveld Jorinde, Schultz Marcus J., Smit Marry, Teunissen Charlotte, Thoral Patrick, de Vries Heder, Wiersinga W. Joost, van Agtmael Michiel, Bomers Marije, de Brabander Justin, de Bree Godelieve, Chouchane Osoul, Geerlings Suzanne, Goorhuis Bram, Grobusch Martin P., Harris Vanessa, Hermans Sabine M., Hovius Joppe W., Nellen Jeannine, Peters Edgar, van der Poll Tom, Prins Jan M., Reijnders Tom, Schinkel Michiel, Schuurman Alex, Sigaloff Kim, Stijnis Cornelis S., Tsonas Anissa, van der Valk Marc, van Vugt Michele, Zwinderman A. H. Koos, Bax Diane, Cloherty Alex, Geijtenbeek Theo, Hafkamp Florianne, Preckel Bennedikt, Bogaard Harm Jan, Bonta Peter I, Nossent Esther J., Bugiani Marianna, Geerts Bart, Hollmann Markus, Veelo Denise, Hamann Jorg, Hemke Robert, de Jong Menno D., Stilma Willemke, Wouters Dorien, Minnaar Rene P., Kromhout Adrie, van Uffelen Kees W. J., Wolterman Ruud A., Roberts Genevieve, Park Danny, Ball Catherine A., Coignet Marie, McCurdy Shannon, Knight Spencer, Partha Raghavendran, Rhead Brooke, Zhang Miao, Berkowitz Nathan, Gaddis Michael, Noto Keith, Ruiz Luong, Pavlovic Milos, Hong Eurie L., Rand Kristin, Girshick Ahna, Guturu Harendra, Baltzell Asher Haug, Georges Michel, Melo Sofia, Jacques Nicolas, Di Valentin Emmanuel, Giroule Francois, Collignon Alice, Radermecker Coraline, Lebrun Marielle, Peree Helene, Latour Samuel, Barada Olivia, Sanchez Judit, Meunier Margot, Mariavelle Emeline, Anania Sandy, Gazon Helene, Mni Myriam, Wery Marie, Belhaj Yasmine, Guntz Julien, Jadot Laurent, Claassen Sabine, Beguin Yves, Gofflot Stephanie, El Kandoussi Kamilia, Thonon Raphael, Bouysran Youssef, Busson Adeline, Peyrassol Xavier, Wilkin Francoise, Pichon Bruno, Smits Guillaume, Vandernoot Isabelle, Goffard Jean-Christophe, Moutschen Michel, Misset Benoit, Darcis Gilles, Guiot Julien, Azarzar Samira, Dellot Patricia, Bertrand Axelle, Parzibut Gilles, Clarinval Mathilde, Moermans Catherine, Malaise Olivier, Huynen Pascale, Mesdagh Alyssia, Josse Claire, Boujemla Bouchra, Juszczak Danusia, Fadeur Marjorie, Camby Severine, Meuris Christelle, Thys Marie, Jacques Jessica, Henket Monique, Leonard Philippe, Frippiat Frederic, Giot Jean-Baptiste, Sauvage Anne-Sophie, Von Frenckell Christian, Staderoli Alicia, Lambermont Bernard, Louis Edouad, Afilalo Marc, Oliveira Maureen, Brenner Bluma, Brassard Nathalie, Durand Madeleine, Chasse Michael, Kaufmann Daniel E., Schurr Erwin, Davis Lea K., Cox Nancy J., Below Jennifer E., Sealock Julia M., Faucon Annika B., Shuey Megan M., Polikowsky Hannah G., Petty Lauren E., Shaw Douglas M., Chen Hung-Hsin, Zhu Wanying, Ludwig Kerstin U., Schroeder Julia, Rolker Selina, Nothen Markus M., Fazaal Julia, Maj Carlo, Keitel Verena, Jensen Bjorn-Erik Ole, Feldt Torsten, Knopp Lisa, Kurth Ingo, Eggermann Thomas, Marx Nikolaus, Dreher Michael, Pink Isabell, Cornberg Markus, Illig Thomas, Volland Sonja, Lehmann Clara, Schommers Philipp, Augustin Max, Rybniker Jan, Koehler Philipp, Cornely Oliver A., Altmuller Janine, Berger Marc M., Brenner Thorsten, Hinney Anke, Witzke Oliver, Bals Robert, Herr Christian, Ludwig Nicole, Walter Jorn, Fuchsberger Christian, Pattaro Cristian, De Grandi Alessandro, Pramstaller Peter, Emmert David, Melotti Roberto, Foco Luisa, Mascalzoni Deborah, Gogele Martin, Domingues Francisco, Hicks Andrew, Gignoux Christopher R., Wicks Stephen J., Crooks Kristy, Barnes Kathleen C., Daya Michelle, Shortt Jonathan, Rafaels Nicholas, Chavan Sameer, Goldstein David B., Kiryluk Krzysztof, Sengupta Soumitra, Menon Amritha, So Yat S., Chung Wendy, Reilly Muredach P., Khan Atlas, Wang Chen, Gharavi Ali G., Shang Ning, O'Byrne Sheila M., Nandakumar Renu, Povysil Gundula, Bhardwaj Nitin, Ionita-Laza Iuliana, Hod Eldad, Pendrick Danielle, Park Soo-Kyung, Kim Hyung-Lae, Kang Chang Kyung, Park Wan Beom, Lee Hyo-Jung, Song Kyoung-Ho, Ham Sin Young, Jung Jongtak, Kim Eu Suk, Bin Kim Hong, Yoon Kyung Jae, Paik Nam-Jong, Seok Woojin, Yoon Heejun, Joo Eun-Jeong, Chang Yoosoo, Ryu Seungho, Park Jeong Su, Park Kyoung Un, Ellinghaus David, Degenhardt Frauke, Juzenas Simonas, Tran Florian, Rosenstiel Philip, Schreiber Stefan, Franke Andre, Wacker Eike Matthias, Uellendahl-Werth Florian, ElAbd Hesham, Wienbrandt Lars, Ruhlemann Malte Christoph, Wendorff Mareike, Tanck Anja, Gassner Christoph, Hemmrich-Stanisak Georg, Kassens Jan, Basso Maria E. Figuera, Schulzky Martin, Wittig Michael, Braun Nicole, Wesse Tanja, Albrecht Wolfgang, Yi Xiaoli, Nebel Almut, Peschuck Anna, May Sandra, Karina Banasik, Brunak Soren, Caceres Mario, Lerga-Jaso Jon, Lenz Tobias L., Teles Ana, Azuure Clinton, Ozer Onur, Albillos Agustin, Mateos Beatriz, Mesonero Francisco, Tellez Luis, Rodriguez-Gandia Miguel, Bujanda Luis, Banales Jesus M., Romero-Gomez Manuel, Buti Maria, Maya-Miles Douglas, Garcia-Etxebarria Koldo, Izquierdo-Sanchez Laura, Rodrigues Pedro M., Rodriguez-Frias Francisco, Riveiro-Barciela Mar, Julia Antonio, Palom Adriana, Marsal Sara, Heidecker Bettina, Kurth Florian, Sander Leif Erik, Mayer Alena, Braun Alice, Skurk Carsten, Thibeault Charlotte, Helbig Elisa T., Kraft Julia, Lippert Lena J., Suwalski Phillip, Ripke Stephan, Poller Wolfgang, Wang Xiaomin, Karadeniz Zehra, Garcia Federico, Quero Jose Hernandez, Chueca Natalia, Cejudo Trinidad Gonzalez, Hanses Frank, Wilfling Sibylle, Zoller Heinz, Schaefer Benedikt, Holter Jan C., Hov Johannes R., Karlsen Tom H., Folseraas Trine, Holten Aleksander Rygh, Dyrhol-Riise Anne Ma, Tonby Kristian, Lind Andreas, Muller Fredrik, Dudman Susanne, Grimsrud Marit M., Fernandez Javier, Ferrando Carlos, Reverter Enric, Badia Joan Ramon, Hernandez-Tejero Maria, Castro Pedro, de Cid Rafael, Nolla Anna Carreras, Cortes Beatriz, Galvan-Femenia Ivan, Blay Natalia, Farre Xavier, Asselta Rosanna, Duga Stefano, Mantovani Alberto, Protti Alessandro, Aghemo Alessio, Lleo Ana, Voza Antonio, Azzolini Elena, Paraboschi Elvezia Maria, My Ilaria, Cecconi Maurizio, Tentorio Paolo, Badalamenti Salvatore, Bombace Sara, Cappadona Claudio, Rimoldi Valeria, Goerg Siegfried, Hehr Ute, Perez Emma F., Lenning Ole Bernt, Vadla May Sissel, Myhre Ronny, Ortiz Aaron Blandino, de Pablo Raul, Chercoles Adolfo Garrido, Nafria-Jimenez Beatriz, Ruiz Agustin, Hernandez Isabel, de Rojas Itziar, Marquie Marta, Boada Merce, Prati Daniele, Baselli Guido, Valenti Luca, Cherubini Alessandro, Muscatello Antonio, Hu Cinzia, Bianco Cristiana, Galimberti Daniela, Scarpini Elio, Ceriotti Ferruccio, Lamorte Giuseppe, Terranova Leonardo, Ostadreza Mahnoosh, Zanella Alberto, Bandera Alessandra, Gori Andrea, Fracanzani Anna Ludovica, Pesenti Antonio, Paccapelo Cinzia, Martinelli-Boneschi Filippo, Peyvandi Flora, Blasi Francesco, Grasselli Giacomo, Costantino Giorgio, Santoro Luigi, Scudeller Luigia, Carrabba Maria, Baldini Marina, Miozzo Monica, Montano Nicola, Gualtierotti Roberta, Pelusi Serena, Bosari Silvano, Aliberti Stefano, Monzani Valter, Invernizzi Pietro, Gerussi Alessio, Milani Chiara, Ramirez Alfredo, Andrade Victor, Barreira Ana, Kildal Anders Benjamin, Gluck Andreas, Bahmer Thomas, Latiano Anna, Palmieri Orazio, Rando-Segura Ariadna, Roade Luisa, Solier Aurora, Jimenez David, Nieto Rosa, Bellinghausen Carla, Quereda Carmen, Navas Enrique, Spinner Christoph D., Schneider Jochen, Lange Christoph, Heyckendorf Jan, Sancho Cristina, Intxausti Maider, Hoff Dag Arne Lihaug, Afset Jan Egil, Haider Sammra, Pestana David, Toapanta David, Urrechaga Eloisa, Espana Pedro P., Pontali Emanuele, Garbarino Lucia, Mazzocco Michela, Arana Eunate, Ayo Natale Imaz, Sanchez Felix Garcia, Malvestiti Francesco, Pezzoli Gianni, Neb Holger, D'Amato Mauro, Goikoetxea Josune, Muller Karl Erik, Heggelund Lars, Gaede Karoline I, Sumoy Lauro, Kogevinas Manolis, Garcia-Aymerich Judith, Castano-Vinyals Gemma, Dobano Carlota, Moreno Victor, Gutierrez-Stampa Maria A., Vehreschild Maria J. G. T., Khodamoradi Yascha, Castoldi Massimo, Zheng Tenghao, Seilmaier Michael J., Martinez Nilda, Hoffmann Per, Heilmann-Heimbach Stefanie, Bacher Petra, Ciesek Sandra, Landmesser Ulf, Skogen Vegard, Calderon Enrique J., Medrano Francisco J., Delgado Juan, Morilla Ruben, Friaza Vicente, Gudbjartsson Daniel F., Stefansson Kari, Sulem Patrick, Sveinbjornsson Gardar, Melsted Pall, Norddahl Gudmundur, Moore Kristjan Helgi Swerford, Thorsteinsdottir Unnur, Holm Hilma, Bernardo David, Ampuero Javier, Rello Silvia Rojo, Magi Reedik, Milani Lili, Metspalu Andres, Laisk Triin, Lall Kristi, Lepamets Maarja, Esko Tonu, Reimann Ene, Alavere Helene, Metsalu Kristjan, Puusepp Mairo, Naaber Paul, Laane Edward, Pesukova Jaana, Peterson Part, Kisand Kai, Tabri Jekaterina, Allos Raili, Hensen Kati, Starkopf Joel, Ringmets Inge, Tamm Anu, Kallaste Anne, Kristiansson Kati, Koskelainen Sami, Perola Markus, Rivolta Carlo, Quinodoz Mathieu, Kamdar Dhryata, Bochud Pierre-Yves, Bibert Stephanie, Boillat Noemie, Nussle Semira Gonseth, Albrich Werner, Suh Noemie, Neofytos Dionysios, Erard Veronique, Voide Cathy, Bochud P. Y., Rivolta C., Bibert S., Quinodoz M., Kamdar D., Neofytos D., Erard V, Voide C., Friolet R., Vollenweider P., Pagani J. L., Oddo M., zu Bentrup F. Meyer, Conen A., Clerc O., Marchetti O., Guillet A., Guyat-Jacques C., Foucras S., Rime M., Chassot J., Jaquet M., Viollet R. Merlet, Lannepoudenx Y., Portopena L., Desgranges F., Filippidis P., Guery B., Haefliger D., Kampouri E. E., Manuel O., Munting A., Papadimitriou-Olivgeris M., Regina J., Rochat-Stettler L., Suttels V, Tadini E., Tschopp J., Van Singer M., Viala B., Boillat-Blanco N., Brahier T., Hugli O., Meuwly J. Y., Pantet O., Pumarola Tomas, Nussle S. Gonseth, Bochud M., D'Acremont V, Younes S. Estoppey, Albrich W. C., Suh N., Cerny A., O'Mahony L., Frischknecht M., Kleger G-R, Filipovic M., Kahlert C. R., Wozniak H., Negro T. Rochat, Pugin J., Bouras K., Knapp C., Egger T., Perret A., Montillier P., di Bartolomeo C., Barda B., Carreras Anna, Mercader Josep Maria, Guindo-Martinez Marta, Torrents David, Gori Marco, Picchiotti Nicola, Mondelli Mario Umberto, Bruno Raffaele, Ludovisi Serena, Castelli Francesco, Quiros-Roldan Eugenia, Degli Antoni Melania, Vaghi Massimo, Rusconi Stefano, Riva Agostino, Siano Matteo, Gabrieli Arianna, Fabbiani Massimiliano, Rossetti Barbara, Rancan Ilaria, Bargagli Elena, Bergantini Laura, D'Alessandro Miriana, Cameli Paolo, Bennet David, Franchi Federico, Anedda Federico, Marcantonio Simona, Scolletta Sabino, Mazzei Maria Antonietta, Guerrini Susanna, Cantarini Luca, Conticini Edoardo, Frediani Bruno, Tacconi Danilo, Spertilli Chiara, Feri Marco, Donati Alice, Scala Raffaele, Guidelli Luca, Spargi Genni, Corridi Marta, Nencioni Cesira, Croci Leonardo, Bandini Maria, Spagnesi Maurizio, Piacentini Paolo, Desanctis Elena, Cappelli Silvia, Caldarelli Gian Piero, Canaccini Anna, Verzuri Agnese, Anemoli Valentina, Ognibene Agostino, Pancrazi Alessandro, Lorubbio Maria, Monforte Antonella D'Arminio, Merlini Esther, Miraglia Federica Gaia, Girardis Massimo, Busani Stefano, Venturelli Sophie, Antinori Andrea, Emiliozzi Arianna, Vergori Alessandra, Francisci Daniela, Schiaroli Elisabetta, Paciosi Francesco, Scotton Pier Giorgio, Andretta Francesca, Panese Sandro, Scaggiante Renzo, Gatti Francesca, Della Monica Matteo, Piscopo Carmelo, Capasso Mario, Russo Roberta, Andolfo Immacolata, Iolascon Achille, Merla Giuseppe, Fiorentino Giuseppe, Castori Marco, Carella Massimo, Aucella Filippo, Di Biagio Antonio, Bassetti Matteo, Masucci Luca, Guarnaccia Alessandra, Sanguinetti Maurizio, Valente Serafina, De Vivo Oreste, Mandala Marco, Giorli Alessia, Salerni Lorenzo, Zucchi Patrizia, Parravicini Pierpaolo, Giannattasio Ferdinando, Trotta Tullio, Coiro Gabriella, Mussini Cristina, Bosio Giancarlo, Martinelli Enrico, Tavecchia Luisa, Belli Mary Ann, Mancarella Sandro, Crotti Lia, Parati Gianfranco, Rizzi Marco, Maggiolo Franco, Ripamonti Diego, La Rovere Maria Teresa, Sarzi-Braga Simona, Bussotti Maurizio, Ravaglia Sabrina, Sabrina Ravaglia, Artuso Rosangela, Perrella Antonio, Romani Davide, Bergomi Paola, Catena Emanuele, Colombo Riccardo, Dei Simona, Tanfoni Marco, Sanarico Maurizio, Raimondi Francesco, Biscarini Filippo, Stella Alessandra, Bergomi Mattia, Vecchia Marco, Mantovani Stefania, Zanella Isabella, Cossarizza Andrea, Parisi Saverio Giuseppe, Baratti Stefano, Squeo Gabriella Maria, Raggi Pamela, Marciano Carmen, Perna Rita, Menatti Elisabetta, Lena Fabio, Gabbi Chiara, Bachetti Tiziana, Suardi Claudia, Botta Giordano, Di Domenico Paolo, Trembath Richard C., Huang Qin Qin, Martin Hilary C., Mason Dan, Wright John, Finer Sarah, Akhtar Shaheen, Anwar Mohammad, Arciero Elena, Ashraf Samina, Breen Gerome, Chung Raymond, Curtis Charles J., Chowdhury Maharun, Colligan Grainne, Deloukas Panos, Durham Ceri, Griffiths Chris, Hurles Matt, Hussain Shapna, Islam Kamrul, Khan Ahsan, Khan Amara, Lavery Cath, Lee Sang Hyuck, Lerner Robin, MacArthur Daniel, MacLaughlin Bev, Martin Hilary, Miah Shefa, Newman Bill, Safa Nishat, Tahmasebi Farah, Griffiths Christopher J., Smith Albert V, Boughton Andrew P., Li Kevin W., LeFaive Jonathon, Annis Aubrey, Zollner Sebastian, Wang Jiongming, Beck Andrew, Jannes Cinthia E., Krieger Jose E., Pereira Alexandre C., Velho Mariliza, Marques Emanuelle, Lima Isabella Ramos, Tada Mauricio Teruo, Valino Karina, McCarthy Mark, Rosenberger Carrie, Chang Diana, Hammer Christian, Hunkapiller Julie, Mahajan Anubha, Pendergrass Sarah, Sucheston-Campbell Lara, Yaspan Brian, Lee Jong Eun, Lee Hyun Soo, Shin Eunsoon, Jang Hye Yoon, Kim Sunmie, Kym Sungmin, Kim Yeon-Sook, Jeong Hyeongseok, Alegria Ana, Kwon Ki Tae, Kim Shin-Woo, Kim Jin Yong, Jang Young Rock, Kim Hyun Ah, Lee Ji Yeon, Lee Jeong Eun, Lee Shinwon, Choe Kang-Won, Kang Yu Min, Ha Jee Sun, Jung Keum Ji, Parikh Victoria, Wheeler Matthew, Dalton Karen, Christle Jeff, Gorzynski John, de Jong Hannah, Sutton Shirley, Youlton Nathan, Joshi Ruchi, Jimenez-Morales David, Hughes Christopher, Amar David, Hershman Steve, Kirillova Anna, Seo Kinya, Huang Yong, Raja Archana, Zhen Jimmy, Ashley Euan, Bustamante Carlos, Rivas Manuel, Ioannidis Alex, Pinksy Benjamin, Shoura Massa, Hammond Nathan, Watson Nathaniel, Huang ChunHong, Sahoo Malaya, Wang Hannah, Febbo Phillip, Farh Kyle, Schroth Gary P., DeSouza Francis, Deboever Christopher, Szalma Sandor, Rubinacci Simone, Delaneau Olivier, McGuigan Peter J., Wasson Christopher, Finn Stephanie, Green Jackie, Collins Erin, King Bernadette, Moore Luke Stephen Prockter, Vizcaychipi Marcela Paola, de Almeida Martins Laura Gomes, Carungcong Jaime, Hall Kathryn, Mapfunde Isheunesu, Campbell Andy, Smuts Sara, Duffield Joseph, Smith Oliver, Mallon Lewis, Claire Watkins, Nichol Ailstair, Brickell Kathy, Smyth Michelle, Murphy Lorna, Ward Geraldine, Bremmer Pamela, Page Valerie Joan, Carmody Siobhain, Semple Malcolm G., Solomon Tom, Turtle Lance C. W., Hardwick Hayley, Adeniji Kayode, Agranoff Daniel, Eziefula Chi, Agwuh Ken, Ail Dhiraj, Aldera Erin L., Allen Louise, Beranova Eva, Crisp Nikki, Deery Joanne, Hazelton Tracy, Knight Alicia, Price Carly, Tilbey Sorrell, Turki Salah, Turney Sharon, Angus Brian, Ashish Abdul, Atkinson Dougal, Bari Shahedal, Barlow Gavin, Barnass Stella, Barrett Nicholas, Douthwaite Sam, Ostermann Marlies, Shankar-Hari Manu, Bassford Christopher, Basude Sneha, Baxter David, Beadsworth Michael, Welters Ingeborg, Bernatoniene Jolanta, Berridge John, Best Nicola, Bothma Pieter, Tupper-Carey Darell, Chadwick David, Brittain-Long Robin, Bulteel Naomi, Murphy Lee, Wrobel Nicola, McCafferty Sarah, Morrice Kirstie, MacLean Alan, Burden Tom, Burtenshaw Andrew, Caruth Vikki, Chambler Duncan, Chee Nigel, Child Jenny, Chukkambotla Srikanth, Clark Tom, Collini Paul, Evans Cariad, Mills Gary H., Ahmad Norfaizan, Barker Joann, Bauchmuller Kris, Bird Sarah, Cawthron Kay, Harrington Kate, Jackson Yvonne, Kibutu Faith, Lenagh Becky, Masuko Shamiso, Raithatha Ajay, Wiles Matthew, Willson Jayne, Newell Helen, Lye Alison, Nwafor Lorenza, Jarman Claire, Rowland-Jones Sarah, Foote David, Cole Joby, Thompson Roger, Watson James, Hesseldon Lisa, Macharia Irene, Chetam Luke, Smith Jacqui, Ford Amber, Anderson Samantha, Birchall Kathryn, Housley Kay, Walker Sara, Milner Leanne, Hanratty Helena, Trower Helen, Phillips Patrick, Oxspring Simon, Donne Ben, Cosgrove Catherine, Cupitt Jason, Cutino-Moguel Maria-Teresa, Dark Paul, Dawson Chris, Dervisevic Samir, Drummond Andrew, Ustianowski Andrew, DuRand Ingrid, Dushianthan Ahilanadan, Dyer Tristan, Fegan Christopher, Finn Adam, Fullerton Duncan, Matovu Elijah, Garg Sanjeev, Garg Atul, Gkrania-Klotsas Effrossyni, Moore Elinoor, Godden Jo, Goldsmith Arthur, Graham Clive, Hardy Elaine, Hartshorn Stuart, Harvey Daniel, Havalda Peter, Workman Andrew, Hawcutt Daniel B., Hobrok Maria, Hodgson Luke, Hormis Anil, Jacobs Michael, Jain Susan, Jennings Paul, Kaliappan Agilan, Kasipandian Vidya, Kegg Stephen, Kelsey Michael, Kerrison Caroline, Kerslake Ian, Koch Oliver, Baruah Rosie, Morris Sheila, Ferguson Susie, Shepherd Amy, Koduri Gouri, Koshy George, Leiner Tamas, Mortimore Katherine, Laha Shondipon, Laird Steven, Larkin Susan, Lillie Patrick, Limb James, Linnett Vanessa, Little Jeff, Lyttle Mark, MacNaughton Emily, Mankregod Ravish, Masson Huw, McCullough Katherine, McEwen Ruth, Wilson Lawrence, Meda Manjula, Minton Jane, Ward Karl, Mirfenderesky Mariyam, Mohandas Kavya, Mok Quen, Moon James, Capps Nigel, Jose Sanal, Morgan Patrick, Morris Craig, Moses Samuel, Mpenge Mbiye, Mulla Rohinton, Murphy Michael, Nagel Megan, Nagarajan Thapas, Nelson Mark, O'Shea Matthew K., Green Christoper A., Otahal Igor, Pais Mark, Panchatsharam Selva, Papakonstantinou Danai, Bancroft Hollie, Bellamy Mary, Carmody Margaret, Daglish Jacqueline, Moore Faye, Rhodes Joanne, Sangombe Mirriam, Kadiri Salma, Scriven James, Paraiso Hassan, Patel Brij, Pattison Natalie, Pepperell Justin, Phull Mandeep, Pintus Stefania, Pooni Jagtur Singh, Post Frank, Cavazza Anna, Cockrell Maeve, Corcoran Eleanor, Depante Maria, Finney Clare, Jerome Ellen, McPhail Mark, Nayak Monalisa, Noble Harriet, O'Reilly Kevin, Pappa Evita, Saha Rohit, Saha Sian, Smith John, Knighton Abigail, Price David, Prout Rachel, Rae Nikolas, Reschreiter Henrik, Reynolds Tim, Richardson Neil, Roberts Mark, Roberts Devender, Rose Alistair, Rousseau Guy, Ryan Brendan, Saluja Taranprit, Shah Aarti, Shanmuga Prad, Sharma Anil, Shawcross Anna, Sizer Jeremy, Bastion Victoria, Clarke Daphene, David Beena, Kent Harriet, Lorusso Rachel, Lubimbi Gamu, Murdoch Sophie, Penacerrada Melchizedek, Thomas Alastair, Valentine Jennifer, Vochin Ana, Wulandari Retno, Djeugam Brice, Smith Richard, Snelson Catherine, Whitehouse Tony, Spittle Nick, Staines Nikki, Visuvanathan Shico, Stambach Tom, Stewart Richard, Subudhi Pradeep, Szakmany Tamas, Tatham Kate, Thomas Jo, Thompson Chris, Tridente Ascanio, Twagira Mary, Vallotton Nick, Vincent-Smith Lisa, Vuylsteke Alan, Waddy Sam, Wake Rachel, Walden Andrew, Whittaker Paul, Whittington Ashley, Papineni Padmasayee, Wijesinghe Meme, Winchester Stephen, Wiselka Martin, Wolverson Adam, Wooton Daniel G., Yates Bryan, Young Peter, Beale Rupert, Hinds Charles, Gountouna Elvina, Porteous David J., Harrison David, Rowan Kathy, Band Gavin, Klenerman Paul, Knight Julian, Bogaert Debby, Shen Xia, Yang Zhijian, Zhai Ranran, Zheng Chenqing, Bulik Cynthia M., Landen Mikael, Fundin Bengt, Wu Yang, Yang Jian, Norman Lisa, Pius Riinu, Drake Thomas M., Fairfield Cameron J., Knight Stephen R., Mclean Kenneth A., Murphy Derek, Shaw Catherine A., Docherty Annemarie B., Harrison Ewen M., Dalton Jo, Girvan Michelle, Saviciute Egle, Roberts Stephanie, Harrison Janet, Marsh Laura, Connor Marie, Halpin Sophie, Jackson Clare, Gamble Carrol, Donohue Chloe, Leeming Gary, Wham Murray, Scott-Brown James, Alex Beatrice, Bach Benjamin, Begg Colin, Ho Antonia Ying Wai, Horby Peter W., Ling Lowell, Maslove David, McAuley Danny, Montgomery Hugh, Nichol Alistair, Openshaw Peter J. M., Thwaites Ryan S., Moore Shona C., Summers Charlotte, Armstrong Lisa, Bates Hayley, Dooks Emma, Farquhar Fiona, Hairsine Brigid, McParland C., Packham Sophie, Alldis Zoe, Astin-Chamberlain Raine, Bibi Fatima, Biddle Jack, Blow Sarah, Bolton Matthew, Borra Catherine, Bowles Ruth, Burton Maudrian, Choudhury Yasmin, Collier David, Cox Amber, Easthope Amy, Ebano Patrizia, Fotiadis Stavros, Gurasashvili Jana, Halls Rosslyn, Hartridge Pippa, Kallon Delordson, Kassam Jamila, Lancoma-Malcolm Ivone, Matharu Maninderpal, May Peter, Mitchelmore Oliver, Newman Tabitha, Patel Mital, Pheby Jane, Pinzuti Irene, Prime Zoe, Prysyazhna Oleksandra, Shiel Julian, Taylor Melanie, Tierney Carey, Wood Suzanne, Zak Anne, Zongo Olivier, Forsey Miranda, Nicholson Anne, Riches Joanne, Vertue Mark, Grauslyte Lina, Hussain Musarat, Pogreban Tatiana, Rosaroso Lace, Salciute Erika, Franke George, Wong Joanna, George Aparna, Akeroyd Louise, Bano Shereen, Bromley Matt, Gurr Lucy, Lawton Tom, Morgan James, Sellick Kirsten, Warren Deborah, Wilkinson Brian, McGowan Janet, Ledgard Camilla, Stacey Amelia, Pye Kate, Bellwood Ruth, Bentley Michael, Loosley Ronda, McGuinness Heather, Tench Helen, Wolf-Roberts Rebecca, Gibson Sian, Lyle Amanda, McNeela Fiona, Radhakrishnan Jayachandran, Hughes Alistair, Ali Asifa, Brady Megan, Dale Sam, Dance Annalisa, Gledhill Lisa, Greig Jill, Hanson Kathryn, Holdroyd Kelly, Home Marie, Kelly Diane, Kitson Ross, Matapure Lear, Melia Deborah, Mellor Samantha, Nortcliffe Tonicha, Pinnell Jez, Robinson Matthew, Shaw Lisa, Shaw Ryan, Thomis Lesley, Wilson Alison, Wood Tracy, Bayo Lee-Ann, Merwaha Ekta, Ishaq Tahira, Hanley Sarah, Antcliffe David, Banach Dorota, Brett Stephen, Coghlan Phoebe, Fernandez Ziortza, Gordon Anthony, Rojo Roceld, Arias Sonia Sousa, Templeton Maie, Jha Rajeev, Krishnamurthy Vinodh, Lim Lai, Lim Li, Bi Rehana, Scholefield Barney, Ashton Lydia, Williams Alison, Cheyne Claire, Saunderson Anne, Moultrie Sam, Odam M., Allan Angela, Anderson Felicity, Kaye Callum, Liew Jade, Medhora Jasmine, Scott Teresa, Trumper Erin, Botello Adriana, Polgarova Petra, Stroud Katerina, Meaney Eoghan, Jones Megan, Ng Anthony, Agrawal Shruti, Pathan Nazima, White Deborah, Daubney Esther, Elston Kay, Parker Robert, Reddy Amie, Turner-Bone Ian, Wilding Laura, Harding Peter, Jacob Reni, Jones Cathy, Denmade Craig, Croft Maria, White Ian, Griffin Denise, Muchenje Nycola, Mupudzi Mcdonald, Partridge Richard, Conyngham Jo-Anna, Thomas Rachel, Wright Mary, Corral Maria Alvarez, Dawson Joy, Garrioch Sweyn, Tolson Melanie, Aldridge Jonathan, Beavis Sarah, Dale Katie, Gascoyne Rachel, Hawes Joanne, Pritchard Kelly, Stevenson Lesley, Whileman Amanda, Cowley Anne, Highgate Judith, Crawley Rikki, Crew Abigail, Cunningham Mishell, Daniels Allison, Harrison Laura, Hope Susan, Inweregbu Ken, Jones Sian, Lancaster Nicola, Matthews Jamie, Nicholson Alice, Wray Gemma, Benham Leonie, Bradshaw Zena, Brown Joanna, Caswell Melanie, Melling Sarah, Preston Stephen, Slawson Nicola, Stoddard Emma, Warden Scott, Combes Edward, Joefield Teishel, Monnery Sonja, Beech Valerie, Trotman Sallyanne, Hopkins Bridget, Thrasyvoulou Laura, Willis Heather, Anderson Susan, Birch Janine, Collins Emma, Hammerton Kate, O'Leary Ryan, Andrews Eleanor, Abernathy Caroline, Foster Louise, Gratrix Andrew, Martinson Vicky, Parkinson Priyai, Stones Elizabeth, Carbral-Ortega Llucia, Kapoor Ritoo, Loader David, Castle Karen, Brandwood Craig, Smith Lara, Clark Richard, Birchall Katie, Kolakaluri Laurel, Baines Deborah, Sukumaran Anila, Meredith Megan, Morris Lucy, Ryan Lucy, Clark Amy, Sampson Julia, Peters Cecilia, Dent Martin, Langley Margaret, Ashraf Saima, Wei Shuying, Andrew Angela, Chablani Manish, Kirkby Amy, Netherton Kimberley, Bates Michelle, Dasgin Jo, Gill Jaspret, Nilsson Annette, Apetri Elena, Basikolo Cathrine, Blackledge Bethan, Catlow Laura, Charles Bethan, Doonan Reece, Harris Jade, Harvey Alice, Horner Daniel, Knowles Karen, Lee Stephanie, Lomas Diane, Lyons Chloe, Marsden Tracy, McLaughlan Danielle, McMorrow Liam, Pendlebury Jessica, Perez Jane, Poulaka Maria, Proudfoot Nicola, Slaughter Melanie, Slevin Kathryn, Thomas Vicky, Walker Danielle, Michael Angiy, Collis Matthew, Clark Martyn, Coulding Martina, Jude Edward, McCormick Jacqueline, Mercer Oliver, Potla Darsh, Rehman Hafiz, Savill Heather, Turner Victoria, Davey Miriam, Golden David, Seaman Rebecca, Hunt Jodie, Dearden Joy, Dobson Emma, Mulcahy Michelle, Munt Sheila, O'Connor Grainne, Philbin Jennifer, Rishton Chloe, Tully Redmond, Winnard Sarah, Cagova Lenka, Fofano Adama, Garner Lucie, Holcombe Helen, Mepham Sue, Mitchell Alice Michael, Mwaura Lucy, Praman K., Vuylsteke Alain, Zamikula Julie, Bercades Georgia, Brealey David, Hass Ingrid, MacCallum Niall, Martir Gladys, Raith Eamon, Reyes Anna, Smyth Deborah, Taylor Abigail, Hughes Rachel Anne, Thomas Helen, Rees Alun, Duskova Michaela, Phipps Janet, Brooks Suzanne, Edwards Michelle, Alexander Peter, Allen Schvearn, Bradley-Potts Joanne, Brantwood Craig, Egan Jasmine, Felton Timothy, Padden Grace, Ward Luke, Moss Stuart, Glasgow Susannah, Beesley Kate, Board Sarah, Kubisz-Pudelko Agnieszka, Lewis Alison, Perry Jess, Pippard Lucy, Wood Di, Buckley Clare, Brown Alison, Gregory Jane, O'Connell Susan, Smith Tim, Belagodu Zakaula, Fuller Bridget, Gherman Anca, Olufuwa Olumide, Paramsothy Remi, Stuart Carmel, Oakley Naomi, Kamundi Charlotte, Tyl David, Collins Katy, Silva Pedro, Taylor June, King Laura, Coates Charlotte, Crowley Maria, Wakefield Phillipa, Beadle Jane, Johnson Laura, Sargeant Janet, Anderson Madeleine, Jardine Catherine, Williams Dewi, Parris Victoria, Quaid Sheena, Watson Ekaterina, Melville Julie, Naisbitt Jay, Joseph Rosane, Lazo Maria, Walton Olivia, Neal Alan, Hill Michaela, Kannan Thogulava, Wild Laura, Allan Elizabeth, Darlington Kate, Davies Ffyon, Easton Jack, Kumar Sumit, Lean Richard, Menzies Daniel, Pugh Richard, Qiu Xinyi, Davies Llinos, Williams Hannah, Scanlon Jeremy, Davies Gwyneth, Mackay Callum, Lewis Joannne, Rees Stephanie, Coetzee Samantha, Gales Alistair, Raj Meena, Sell Craig, Langton Helen, Watters Malcolm, Novis Catherine, Arbane Gill, Bociek Aneta, Campos Sara, Grau Neus, Jones Tim Owen, Lim Rosario, Marotti Martina, Whitton Christopher, Barron Anthony, Collins Ciara, Kaul Sundeep, Passmore Heather, Prendergast Claire, Reed Anna, Rogers Paula, Shokkar Rajvinder, Woodruff Meriel, Middleton Hayley, Polgar Oliver, Nolan Claire, Thwaites Vicky, Mahay Kanta, Sri-Chandana Chunda, Scherewode Joslan, Stephenson Lorraine, Marsh Sarah, Ayers Amanda, Harrison Wendy, North Julie, Gill Mandy, Paul Paul, Ratnam Valli, Shelton Sarah, Wynter Inez, Baptista David, Crowe Rebecca, Fernandes Rita, Herdman-Grant Rosaleen, Joseph Anna, Loveridge Adam, McKenley India, Morino Eriko, Naranjo Andres, Simms Richard, Sollesta Kathryn, Swain Andrew, Venkatesh Harish, Khera Jacyntha, Fox Jonathan, Barber Russell, Hewitt Claire, Hilldrith Annette, Jackson-Lawrence Karen, Shepardson Sarah, Wills Maryanne, Butler Susan, Tavares Silvia, Cunningham Amy, Hindale Julia, Arif Sarwat, George Linsha, Twiss Sophie, Wright David, Holland Maureen, Keenan Natalie, Lyons Marc, Wassall Helen, Marsh Chris, Mahenthran Mervin, Carter Emma, Kong Thomas, Adanini Oluronke, Bhatia Nikhil, Msiska Maines, Mew Louise, Mwaura Esther, Williams Felicity, Wren Lynn, Sutherland Sara-Beth, Battle Ceri, Brinkworth Elaine, Harford Rachel, Murphy Carl, Newey Luke, Rees Tabitha, Williams Marie, Arnold Sophie, Hardy John, Houlden Henry, Moncur Eleanor, Tariq Ambreen, Tucci Arianna, Convery Karen, Fottrell-Gould Deirdre, Hudig Lisa, Keshet-Price Jocelyn, Randell Georgina, Stammers Katie, Abdelrazik Marwa, Bakthavatsalam Dhanalakshmi, Elhassan Munzir, Ganesan Arunkumar, Haldeos Anne, Moreno-Cuesta Jeronimo, Purohit Dharam, Vincent Rachel, Xavier Kugan, Rohit Kumar, Alasdair Frater, Saleem Malik, David Carter, Jenkins Samuel, Lamond Zoe, Wall Alanna, Reynolds Jessica, Campbell Helen, Thompsom Maria, Dodds Steve, Duffy Stacey, Butcher Deborah, O'Sullivan Susie, Butterworth-Cowin Nicola, Deacon Bethan, Hibbert Meg, Pothecary Carla, Tetla Dariusz, Woodford Christopher, Durga Latha, Kennard-Holden Gareth, De Gordoa Laura Ortiz-Ruiz, Peasgood Emily, Phillips Claire, Skinner Denise, Gaylard Jane, Mullan Dee, Newman Julie, Davies Ellie, Roche Lisa, Sathe Sonia, Brimfield Lutece, Daly Zoe, Pogson David, Rose Steve, Collins Amy, Khaliq Waqas, Gude Estefania Treus, Giles Julian, Booth Simon, Bell Gillian, English Katy, Katary Amro, Wilcox Louise, Campbell Rachael, Clarke Noreen, Whiteside Jonathan, Mascarenhas Mairi, Donaldson Avril, Matheson Joanna, Barrett Fiona, O'Hara Marianne, O'Keefe Laura, Bradley Clare, Collier Dawn, Walker Rachel, Maynard Victoria, Patel Tahera, Smith Matthew, Kazi Aayesha, Hartley Janice, Dykes Joseph, Hijazi Muhammad, Keith Sarah, Khan Meherunnisa, Ryan-Smith Janet, Springle Philippa, Thomas Jacqueline, Truman Nick, Saad Samuel, Coleman Dabheoc, Fine Christopher, Matt Roseanna, Gay Bethan, Dalziel Jack, Ali Syamlan, Goodchild Drew, Harling Rhiannan, Bhatterjee Ravi, Goddard Wendy, Davison Chloe, Duberly Stephen, Hargreaves Jeanette, Bolton Rachel, Verlander Mark, Williams Alexandra, Blackman Helen, Creagh-Brown Ben, Donlon Sinead, Michalak-Glinska Natalia, Mtuwa Sheila, Pristopan Veronika, Salberg Armorel, Smith Eleanor, Stone Sarah, Piercy Charles, Verula Jerik, Burda Dorota, Montaser Rugia, Harden Lesley, Mayangao Irving, Marriott Cheryl, Bradley Paul, Harris Celia, Cooper Joshua, Finch Cheryl, Liderth Sarah, Quinn Alison, Waddington Natalia, Fidler Katy, Tagliavini Emma, Donnelly Kevin, Abel Lynn, Brett Michael, Digby Brian, Gemmell Lisa, Hornsby James, MacGoey Patrick, O'Neil Pauline, Price Richard, Rodden Natalie, Rooney Kevin, Sundaram Radha, Thomson Nicola, Flanagan Rebecca, Hughes Gareth, Latham Scott, McKenna Emma, Anderson Jennifer, Hull Robert, Rhead Kat, Branney Debbie, Frankham Jordan, Pitts Sally, White Nigel, Cristiano Daniele, Dormand Natalie, Farzad Zohreh, Gummadi Mahitha, Liyanage Kamal, Salmi Sara, Sloane Geraldine, Varghese Mathew, Zborowski Anelise C., Patel Brijesh V, Bean Sarah, Burt Karen, Spivey Michael, Eastgate-Jackson Christine, Filipe Helder, Martin Daniel, Maharajh Amitaa, Garcia Sara Mingo, De Neef Mark, Lynch Ceri, Howe Gwenllian Sera, Singh Jayaprakash, Turner Keri, Ellis Hannah, Stroud Natalie, Cherian Shiney, Cutler Sean, Heron Anne Emma, Roynon-Reed Anna, Williams Gemma, Richards Owen, Cheema Yusuf, Bevan Emily, Martin Jane, Trodd Dawn, Watson Geoff, Brown Caroline Wrey, Bunni Lara, Jennings Claire, Latif Monica, Marshall Rebecca, Subramanian Gayathri, Bandla Nageswar, Gellamucho Minnie, Davies Michelle, Thompson Christopher, Donnison Phil, Trim Fiona, Eapen Beena, Ahmed Cecilia, Baines Balvinder, Clamp Sarah, Colley Julie, Haq Risna, Hayes Anne, Hulme Jonathan, Hussain Samia, Joseph Sibet, Kumar Rita, Maqsood Zahira, Purewal Manjit, Chandler Ben, Elliott Kerry, Mallinson Janine, Turnbull Alison, Dent Kathy, Horsley Elizabeth, Akhtar Muhmmad Nauman, Pearson Sandra, Potoczna Dorota, Spencer Sue, Blakemore Hayley, Borislavova Borislava, Faulkner Beverley, Gendall Emma, Goff Elizabeth, Hayes Kati, Thomas Matt, Worner Ruth, Smith Kerry, Stephens Deanna, Delgado Carlos Castro, Dawson Deborah, Ding Lijun, Durrant Georgia, Ezeobu Obiageri, Farnell-Ward Sarah, Harrison Abiola, Kanu Rebecca, Leaver Susannah, Maccacari Elena, Manna Soumendu, Saluzzio Romina Pepermans, Queiroz Joana, Samakomva Tinashe, Sicat Christine, Texeira Joana, Da Gloria Edna Fernandes, Lisboa Ana, Rawlins John, Mathew Jisha, Kinch Ashley, Hurt William James, Shah Nirav, Clark Victoria, Thanasi Maria, Yun Nikki, Patel Kamal, Crickmore Vikki, Debreceni Gabor, Wilkins Joy, Nicol Liz, Burn Iona, Hambrook Geraldine, Manso Katarina, Penn Ruth, Shanmugasundaram Pradeep, Tebbutt Julie, Thornton Danielle, Rostron Anthony, Roy Alistair, Woods Lindsey, Cornell Sarah, Wakinshaw Fiona, Rogerson Kimberley, Jarmain Jordan, Anderson Peter, Archer Katie, Austin Karen, Davis Caroline, Durie Alison, Kelsall Olivia, Thrush Jessica, Vigurs Charlie, Wood Hannah-Louise, Tranter Helen, Harrison Alison, Cowley Nicholas, McAlindon Michael, Digby Stephen, Low Emma, Morgan Aled, Cother Naiara, Rankin Tobias, Clayton Sarah, McCurdy Alex, Allibone Suzanne, Mary-Genetu Roman, Patel Amit, Mac Ainhi, Murphy Anthony, Mahjoob Parisa, Nazari Roonak, Worsley Lucy, Fagan Andrew, Ali Inthakab Ali Mohamed, Beaumont Karen, Blunt Mark, Coton Zoe, Curgenven Hollie, Elsaadany Mohamed, Fernandes Kay, Ally Sameena Mohamed, Rangarajan Harini, Sarathy Varun, Selvanayagam Sivarupan, Vedage Dave, White Matthew, Fernandez-Roman Jaime, Hamilton David O., Johnson Emily, Johnston Brian, Martinez Maria Lopez, Mulla Suleman, Shaw David, Waite Alicia A. C., Waugh Victoria, Welters Ingeborg D., Williams Karen, Bemand Thomas, Black Ethel, Dela Rosa Arnold, Howle Ryan, Jhanji Shaman, Baikady Ravishankar Rao, Tatham Kate Colette, Thomas Benjamin, Halkes Matthew, Mercer Pauline, Thornton Lorraine, West Joe, Baird Tracy, Ruddy Jim, Reece-Anthony Rosie, Birt Mark, Cowton Amanda, Kay Andrea, Kent Melanie, Potts Kathryn, Wilkinson Ami, Naylor Suzanne, Brown Ellen, Clark Michele, Purvis Sarah, Cole Jade, Davies Rhys, Duffin Donna, Hill Helen, Player Ben, Thomas Emma, Williams Angharad, Beith Claire Marie, Black Karen, Clements Suzanne, Morrison Alan, Strachan Dominic, Taylor Margaret, Clarkson Michelle, D'Sylva Stuart, Norman Kathryn, Coventry Tina, Fowler Susan, MacMahon Michael, McGregor Amanda, Brady Ailbhe, Chan Rebekah, McIvor Shane, Prady Helena, Whittle Helen, Mathew Bijoy, Clapham Melanie, Harper Rosemary, Poultney Una, Rice Polly, Mutch Rachel, Baird Yolanda, Butler Aaron, Chadbourn Indra, Folkes Linda, Fox Heather, Gardner Amy, Gomez Raquel, Hobden Gillian, King Kirsten, Margarson Michael, Martindale Tim, Meadows Emma, Raynard Dana, Thirlwall Yvette, Helm David, Margalef Jordi, Greer Sandra, Shuker Karen, Birkinshaw Isobel, Carter Joseph, Howard Kate, Ingham Joanne, Joy Rosie, Pearson Harriet, Roche Samantha, Scott Zoe, Knights Ellen, Price Alicia, Thomas Alice, Thorpe Chris, Abraheem Azmerelda, Bamford Peter, Cawley Kathryn, Dunmore Charlie, Faulkner Maria, Girach Rumanah, Jeffrey Helen, Jones Rhianna, London Emily, Nagra Imrun, Nasir Farah, Sainsbury Hannah, Smedley Clare, Khade Reena, Sundar Ashok, Tsinaslanidis George, Behan Teresa, Burnett Caroline, Hatton Jonathan, Heeney Elaine, Mitra Atideb, Newton Maria, Pollard Rachel, Stead Rachael, Birch Jenny, Bough Laura, Goodsell Josie, Tutton Rebecca, Williams Patricia, Williams Sarah, Winter-Goodwin Barbara, Auld Fiona, Donnachie Joanne, Edmond Ian, Prentice Lynn, Runciman Nikole, Salutous Dario, Symon Lesley, Todd Anne, Turner Patricia, Short Abigail, Sweeney Laura, Murdoch Euan, Senaratne Dhaneesha, Burns Karen, Higham Andrew, Anderson Taya, Hawcutt Dan, O'Malley Laura, Rad Laura, Rogers Naomi, Saunderson Paula, Allison Kathryn Sian, Afolabi Deborah, Whitbread Jennifer, Jones Dawn, Dore Rachael, Lankester Liana, Nikitas Nikitas, Wells Colin, Stowe Bethan, Spencer Kayleigh, Cathcart Susanne, Duffy Katharine, Puxty Alex, Puxty Kathryn, Turner Lynne, Ireland Jane, Semple Gary, Barry Peter, Hilltout Paula, Evitts Jayne, Tyler Amanda, Waldron Joanne, Irvine Val, Shelley Benjamin, Akinkugbe Olugbenga, Bamford Alasdair, Beech Emily, Belfield Holly, Bell Michael, Davies Charlene, Jones Gareth A. L., McHugh Tara, Meghari Hamza, O'Neill Lauran, Peters Mark J., Ray Samiran, Tomas Ana Luisa, Gorman Claire, Gupta Abhinav, Timlick Elizabeth, Brady Rebecca, Bonner Stephen, Hugill Keith, Jones Jessica, Liggett Steven, Bashyal Archana, Davidson Neil, Hutton Paula, McKechnie Stuart, Wilson Jean, Flint Neil, Rekha Patel, Hales Dawn, Cruz Carina, Gopal Shameer, Harris Nichola, Lake Victoria, Metherell Stella, Radford Elizabeth, Clement Ian, Patel Bijal, Gulati A., Hays Carole, Webster K., Hudson Anne, Webster Andrea, Stephenson Elaine, McCormack Louise, Slater Victoria, Nixon Rachel, Hanson Helen, Fearby Maggie, Kelly Sinead, Bridgett Victoria, Robinson Philip, Almaden-Boyle Christine, Austin Pauline, Cabrelli Louise, Cole Stephen, Casey Matt, Chapman Susan, Whyte Clare, Brayne Adam, Fisher Emma, Hunt Jane, Jackson Peter, Kaye Duncan, Love Nicholas, Parkin Juliet, Tuckey Victoria, van Koutrik Lynne, Carter Sasha, Andrew Benedict, Findlay Louise, Adams Katie, Bruce Michelle, Connolly Karen, Duncan Tracy, T-Michael Helen, Lindergard Gabriella, Hey Samuel, Fox Claire, Alfonso Jordan, Durrans Laura Jayne, Guerin Jacinta, Hruska Martin, Eltayeb Ayaa, Lamb Thomas, Hodgkiss Tracey, Cooper Lisa, Rothwell Joanne, Dennis Catherine, McGregor Alastair, Srikaran Sinduya, Sukha Anisha, Davies Kim, O'Brien Linda, Omar Zohra, Perkins Emma, Lewis Tracy, Sutherland Isobel, Brooke Hollie, Buckley Sarah, Suarez Jose Cebrian, Charlesworth Ruth, Hansson Karen, Norris John, Poole Alice, Rose Alastair, Sandhu Rajdeep, Sloan Brendan, Smithson Elizabeth, Thirumaran Muthu, Wagstaff Veronica, Metcalfe Alexandra, Camsooksai Julie, Humphrey Charlotte, Jenkins Sarah, Wadams Beverley, DeAth Yasmin, Adams Colene, Agasou Anita, Bowes Amy, Boyle Pauline, Carnahan Mandy, Carter Anne, Childs Danielle, Hard Kelly, Hussain Yasmin, Leigh Michael, Rikunenko Rachel, Stickley Jo, Tivenan Helen, Wilcox Rebecca, Arden Tracie, Beekes Mandy, Button Heather, Donaldson Denise, Hurford Fran, Javaid Ayesha, Jones James, Martin Terry, Millward Helen, Motherwell Nichola, Summers Julie, Ting Louise, Tonks Louise, Bokhari Maria, Lucas Rachael, McCormick Wendy, Ritzema Jenny, Sanderson Amanda, Wild Helen, Baxter Nicola, Henderson Steven, Kennedy-Hay Sophie, McParland Christopher, Rooney Laura, Sim Malcolm, McCreath Gordan, Brunton Mark, Caterson Jess, Coles Holly, Frise Matthew, Rai Sabi Gurung, Jacques Nicola, Keating Liza, Tilney Emma, Bartley Shauna, Bhuie Parminder, Downes Charlotte, Holding Kathleen, Riches Katie, Hilton Mary, Hayman Mel, Subramanian Deepak, Daniel Priya, Zitter Letizia, Benyon Sarah, Marriott Suzie, Park Linda, Keenan Samantha, Gordon Elizabeth, Quinn Helen, Baines Kizzy, Andrew Gillian, Barclay Lucy, Callaghan Marie, Clark Sarah, Hope Dave, Marshall Lucy, McCulloch Corrienne, Briton Kate, Singleton Jo, Birch Sophie, Simpson Kerry, Craig Jayne, Demetriou Carrie, Eckbad Charlotte, Hierons Sarah, Howie Lucy, Mitchard Sarah, Ramos Lidia, Serrano-Ruiz Alfredo, White Katie, Kelly Fiona, Amin Vishal, Anastasescu Elena, Anumakonda Vikram, Karthik Komala, Kausar Rizwana, Reid Karen, Smith Jacqueline, Imeson-Wood Janet, Bellini Arianna, Bryant Jade, Mayer Anton, Pickard Amy, Roe Nicholas, Sowter Jason, Howlett Alex, Criste Kristine, Cusack Rebecca, Golder Kim, Golding Hannah, Jones Oliver, Leggett Samantha, Male Michelle, Marani Martyna, Prager Kirsty, Williams Toran, Roberts Belinda, Salmon Karen, Gondo Prisca, Hadebe B., Kayani Abdul, Masunda Bridgett, Ahmed Ashar, Morris Anna, Jakkula Srinivas, Long Kate, Whiteley Simon, Wilby Elizabeth, Ogg Bethan, Bewley Jeremy, Garland Zoe, Grimmer Lisa, Gumbrill Bethany, Johnson Rebekah, Sweet Katie, Webster Denise, Efford Georgia, Bennett Sara, Goodwin Emma, Jackson Matthew, Kent Alissa, Tibke Clare, Woodyatt Wiesia, Zaki Ahmed, Daniel Amelia, Finn Joanne, Saha Rajnish, Allan J., Geary T., Houston Gordon, Meikle A., O'Brien P., Bell Dina, Boyle Rosalind, Douglas Katie, Glass Lynn, Lee Emma, Lennon Liz, Rattray Austin, Charnock Rob, McFarland Denise, Cosgrove Denise, Attwood Ben, Parsons Penny, Oblak Metod, Popescu Monica, Thankachen Mini, Altabaibeh Abdelhakim, Alvaro Ana, Gilbert Kayleigh, Ma Louise, Mostoles Loreta, Parmar Chetan, Simpson Kathryn, Jetha Champa, Booker Lauren, Pratley Anezka, Cosier Tracey, Millen Gemma, Schumacher Natasha, Weston Heather, Rand James, Barclay Wendy S., Chand Meera, Cooke Graham S., Sriskandan Shiranee, Dunning Jake, Zambon Maria, Filipe Ana da Silva, Palmarini Massimo, Robertson David L., Scott Janet T., Thomson Emma C., McDonald Sarah E., Fletcher Tom, Hiscox Julian A., Ijaz Samreen, Khoo Saye, Lim Wei Shen, Mentzer Alexander J., Merson Laura, Sigfrid Louise, Carson Gail, Noursadeghi Mahdad, Paxton William A., Pollakis Georgios, Price Nicholas, Rambaut Andrew, Sancho-Shimizu Vanessa, de Silva Thushan, Stuart David, Tedder Richard S., Thompson A. A. Roger, Gupta Rishi K., Palmieri Carlo, Swann Olivia V, Dumas Marc-Emmanuel, Griffin Julian L., Takats Zoltan, Andrikopoulos Petros, Osagie Anthonia, Olanipekun Michael, Liggi Sonia, Chechi Kanta, Lewis Matthew R., Correia Goncalo dos Santos, Sands Caroline J., Takis Panteleimon, Maslen Lynn, Greenhalf William, Shaw Victoria, Cole Sarah, Ahmed Katie A., Armstrong Jane A., Ashworth Milton, Asiimwe Innocent G., Bakshi Siddharth, Barlow Samantha L., Booth Laura, Bullock Katie, Catterall Benjamin W. A., Clark Jordan J., Clarke Emily A., Cooper Louise, Cox Helen, Davis Christopher, Dincarslan Oslem, Dunn Chris, Dyer Philip, Elliott Angela, Evans Anthony, Finch Lorna, Fisher Lewis W. S., Foster Terry, Garcia-Dorival Isabel, Gunning Philip, Hartley Catherine, Jensen Rebecca L., Jones Christopher B., Jones Trevor R., Khandaker Shadia, King Katharine, Kiy Robyn T., Koukorava Chrysa, Lant Suzannah, Latawiec Diane, Lavelle-Langham Lara, Lett Lauren, Livoti Lucia A., Mancini Maria, McDonald Sarah, McEvoy Laurence, Metelmann Soeren, Miah Nahida S., Middleton Joanna, Mitchell Joyce, Murphy Ellen G., Penrice-Randal Rebekah, Pilgrim Jack, Prince Tessa, Reynolds Will, Ridley P. Matthew, Sales Debby, Shaw Victoria E., Shears Rebecca K., Small Benjamin, Subramaniam Krishanthi S., Szemiel Agnieska, Tanianis-Hughes Jolanta, Thomas Jordan, Trochu Erwan, van Tonder Libby, Wilcock Eve, Zhang J. Eunice, Flaherty Lisa, Maziere Nicole, Cass Emily, Carracedo Alejandra Doce, Carlucci Nicola, Holmes Anthony, Massey Hannah, Brennan Benjamin, Lake Annette, Lefteri Daniella, McLauchlan John, Taggart Aislynn, Coutts Audrey, Donnelly Lorna, Fawkes Angie, Gilchrist Tammy, Hafezi Katarzyna, Macgillivray Louise, Schon Katherine, Furlong Anita, Biggs Heather, Rakitko Alexander, Ilinsky Valery, Yermakovich Danat, Popov Iaroslav, Chernitsov Alexander, Kovalenko Elena, Krasnenko Anna, Plotnikov Nikolay, Stetsenko Ivan, Kim Anna, Cirulli Elizabeth T., Barrett Kelly M. Schiabor, Bolze Alexandre, White Simon, Washington Nicole L., Lu James T., Riffle Stephen, Tanudjaja Francisco, Wang Xueqing, Iii Jimmy M. Ramirez, Leonetti Nicole, Sandoval Efren, Neveux Iva, Grzymski Joseph J., Dabe Shaun, Minano Juan Ignacio Esteban, Pazos Manuel de la Mata, Cerrato Luciano, Aguirre Luis A., Lopez-Collazo Eduardo, Lozano-Rodriguez Roberto, Avendano-Ortiz Jose, Arcos Veronica Terron, Montalban-Hernandez Karla Marina, Quiroga Jaime Valentin, Pascual-Iglesias Alejandro, Maroun-Eid Charbel, Martin-Quiros Alejandro, Namkoong Ho, Fukunaga Koichi, Ishii Makoto, Kabata Hiroki, Masaki Katsunori, Kamata Hirofumi, Ikemura Shinnosuke, Chubachi Shotaro, Okamori Satoshi, Terai Hideki, Tanaka Hiromu, Morita Atsuho, Lee Ho, Asakura Takanori, Edahiro Ryuya, Sonehara Kyuto, Shirai Yuya, Suzuki Ken, Kumanogoh Atsushi, Imoto Seiya, Katayama Kazuhiko, Kitagawa Yuko, Sato Toshiro, Hasegawa Naoki, Takeda Yoshito, Hirata Haruhiko, Shiroyama Takayuki, Maeda Yuichi, Nii Takuro, Noda Yoshimi, Niitsu Takayuki, Adachi Yuichi, Enomoto Takatoshi, Amiya Saori, Hara Reina, Kimura Akinori, Ai Masumi, Tokunaga Katsushi, Omae Yosuke, Kanai Takanori, Nanki Kosaku, Mikami Yohei, Miyano Satoru, Takahashi Kunihiko, Anzai Tatsuhiko, Hasegawa Takanori, Ito Satoshi, Ogawa Seishi, Sasaki Junichi, Morisaki Hiroshi, Uwamino Yoshifumi, Tomono Kazunori, Kato Kazuto, Matsuda Fumihiko, Takahashi Meiko, Hizawa Nobuyuki, Miyawaki Satoru, Koike Ryuji, Endo Akifumi, Uchimura Yuji, Miyazaki Yasunari, Honda Takayuki, Tateishi Tomoya, Tohda Shuji, Ichimura Naoya, Sonobe Kazunari, Sassa Chihiro, Nakajima Jun, Nannya Yasuhito, Takahashi Kazuhisa, Harada Norihiro, Takagi Haruhi, Nakamura Ai, Hiki Makoto, Tagaya Etsuko, Arimura Ken, Kawana Masatoshi, Ishiguro Takashi, Takayanagi Noboru, Isono Taisuke, Takaku Yotaro, Takano Kenji, Anan Ryusuke, Nakajima Yukiko, Nakano Yasushi, Nishio Kazumi, Ueda Soichiro, Hayashi Reina, Tateno Hiroki, Hase Isano, Yoshida Shuichi, Suzuki Shoji, Mitamura Keiko, Saito Fumitake, Ueda Tetsuya, Azuma Masanori, Nagasaki Tadao, Hasegawa Yoshinori, Okamoto Masaki, Yasui Yoshinori, Mutoh Yoshikazu, Yoshiyama Takashi, Shoko Tomohisa, Kojima Mitsuaki, Adachi Tomohiro, Ishikawa Motonao, Takahashi Kenichiro, Watanabe Kazuyoshi, Manabe Tadashi, Ito Fumimaro, Fukui Takahiro, Funatsu Yohei, Koh Hidefumi, Hirai Yoshihiro, Kawashima Hidetoshi, Narita Atsuya, Niwa Kazuki, Sekikawa Yoshiyuki, Saito Fukuki, Yoshiya Kazuhisa, Yoshihara Tomoyuki, Suzuki Yusuke, Nakayama Sohei, Masuzawa Keita, Nishi Koichi, Nishitsuji Masaru, Tani Maiko, Inoue Takashi, Hirano Toshiyuki, Kobayashi Keigo, Miyazawa Naoki, Kimura Yasuhiro, Sado Reiko, Ogura Takashi, Kitamura Hideya, Murohashi Kota, Nakachi Ichiro, Baba Rie, Arai Daisuke, Fuke Satoshi, Saito Hiroshi, Kuwahara Naota, Fujiwara Akiko, Okada Takenori, Baba Tomoya, Noda Junya, Mashimo Shuko, Yagi Kazuma, Shiomi Tetsuya, Hashiguchi Mizuha, Odani Toshio, Mochimaru Takao, Oyamada Yoshitaka, Mori Nobuaki, Izumi Namiki, Nagata Kaoru, Taki Reiko, Murakami Koji, Yamada Mitsuhiro, Sugiura Hisatoshi, Hayashi Kentaro, Shimizu Tetsuo, Gon Yasuhiro, Fujitani Shigeki, Yoshida Toru, Tsuchida Tomoya, Kagaya Takashi, Kita Toshiyuki, Sakagami Satoru, Kimizuka Yoshifumi, Kawana Akihiko, Nakamura Yoshihiko, Ishikura Hiroyasu, Takata Tohru, Kikuchi Takahide, Taniyama Daisuke, Nakamura Morio, Kodama Nobuhiro, Kaneyama Yasunari, Maeda Shunsuke, Nagasaki Yoji, Ishihara Sayoko, Ito Akihiro, Chihara Yusuke, Takeuchi Mayumi, Onoi Keisuke, Hashimoto Naozumi, Wakahara Keiko, Ando Akira, Masuda Makoto, Wakabayashi Aya, Watanabe Hiroki, Sageshima Hisako, Nakada Taka-Aki, Abe Ryuzo, Shimada Tadanaga, Kawamura Kodai, Ichikado Kazuya, Nishiyama Kenta, Yamasaki Masaki, Hashimoto Satoru, Kusaka Yu, Ohba Takehiko, Isogai Susumu, Takada Minoru, Kanda Hidenori, Komase Yuko, Sano Fumiaki, Asano Koichiro, Oguma Tsuyoshi, Harada Masahiro, Takahashi Takeshi, Shibusawa Takayuki, Abe Shinji, Kono Yuta, Togashi Yuki, Izumo Takehiro, Inomata Minoru, Awano Nobuyasu, Ogawa Shinichi, Ogata Tomouki, Ishihara Shoichiro, Kanehiro Arihiko, Ozaki Shinji, Fuchimoto Yasuko, Kitagawa Yuichiro, Yoshida Shozo, Ogura Shinji, Nishiyama Kei, Yoshida Kousuke, Beppu Satoru, Fukuyama Satoru, Eriguchi Yoshihiro, Yonekawa Akiko, Inoue Yoshiaki, Yamagata Kunihiro, Chiba Shigeru, Narumoto Osamu, Nagai Hideaki, Ooshima Nobuharu, Motegi Mitsuru, Sagara Hironori, Tanaka Akihiko, Ohta Shin, Shibata Yoko, Tanino Yoshinori, Sato Yuki, Yamada Yuichiro, Hashino Takuya, Shinoki Masato, Iwagoe Hajime, Imamura Tomonori, Umeda Akira, Shimada Hisato, Endo Mayu, Hayashi Shinichi, Takahashi Mai, Nakano Shigefumi, Yatomi Masakiyo, Maeno Toshitaka, Ishii Tomoo, Utsugi Mitsuyoshi, Ono Akihiro, Kanaoka Kensuke, Ihara Shoichi, Komuta Kiyoshi, Boezen Marike, Vonk Judith M., Ori Anil P. S., Obeidat Ma'en, Cordero Ana I. Hernandez, Sin Don D., Bosse Yohan, Joubert Philippe, Hao Ke, Sebra Robert P., Jordan Daniel M., Gettler Kyle, Chaudhary Kumardeep, Salib Irene, Zyndorf Marissa, Schadt Eric E., Cho Judy H., Itan Yuval, Do Ron, Nickle David, Timens Wim, van den Berge Maarten, Feng Yen-Chen Anne, Meigs James B., Weiss Scott T., Karlson Elizabeth W., Woolley Ann E., Smoller Jordan W., Murphy Shawn N., Ascolillo Steven, Thompson Ryan C., Beckmann Noam D., Nadkarni Girish N., Boutros Paul, Charney Alexander W., Hoggart Clive, Choi Sam, O'Reilly Paul, Huckins Laura M., Preuss Michael, Loos Ruth J. F., Belbin Gillian M., Abul-Husn Noura S., Kenny Eimear E., Geschwind Daniel H., Ferreira Manuel A. R., Abecasis Goncalo R., Cantor Michael N., Kosmicki Jack A., Horowitz Julie E., Baras Aris, Yadav Ashish, Leader Joseph B., Gass Matthew C., Justice Anne E., Chittoor Geetha, Josyula Navya Shilpa, Carey Dave J., Mirshahi Tooraj, Verma Anurag, Ritchie Marylyn D., Rader Daniel, Verma Shefali S., Lucas Anastasia, Bradford Yuki, Li Binglan, Brusco Alfredo, Ferrero Giovanni Battista, Butte Manish J., Scala Marcello, Riva Antonella, Rahier Jean-Francois, Giorgio Elisa, Carli Diana, Afifi Nahla, Klovins Janis, Rovite Vita, Rescenko Raimonds, Peculis Raitis, Ustinova Monta, Zeberg Hugo, Frithiof Robert, Hultstrom Michael, Lipcsey Miklos, Johnson Ruth, Freimer Nelson, Ding Yi, Chiu Alec, Chang Timothy S., Wilson Daniel J., Earle Sarah G., Lin Shang-Kuan, Arning Nicolas, Armstrong Jacob, Rudkin Justine K., Crook Derrick W., Wyllie David H., O'Connell Anne Marie, Callier Shawneequa, Soranzo Nicole, Zhao Jing Hua, Danesh John, Di Angelantonio Emanuele, Butterworth Adam S., Sun Yan V, Huffman Jennifer E., O'Donnell Christopher J., Peloso Gina, Cho Kelly, Gaziano J. Michael, Ho Yuk-Lam, Tsao Phil, Mian Michael, Scaggiante Federica, Chang Xiao, Glessner Joseph R., Hakonarson Hakon, Vincenti Antonella, Ferri Claudio, Grassi Davide, Pessina Gloria, Di Pietro Massimo, Luchi Sauro, Barbieri Chiara, Acquilini Donatella, Andreucci Elena, Poscente Monica, Petrocelli Paola, Tiseo Giusy, Falcone Marco, Segala Francesco Vladimiro, Baroni Silvia, Garcia-Fernandez Alba-Estela, Blanco-Grau Albert, Caballero-Garralda Andrea, Cea Cristina, Guerrero Juan M., Angelini Claudio, Kurihara Hayato, Ciccarelli Michele, Bocciolone Monica, Preatoni Paoletta, Omodei Paolo, Muniz-Diaz Eduardo, Sandoval Elena, Aziz Fatima, Ferrusquia-Acosta Jose, Moreira Leticia, Cardamone Giulia, Foti Giuseppe, Matullo Giuseppe, Aneli Serena, Damas Jan Kristian, Risnes Kari, Bettini Laura Rachele, Martin Javier, Acosta-Herrera Marialbert, Erdmann Jeanette, Bergan Jonas, Biondi Andrea, D'Angio Mariella, Solligard Erik, Gustad Lise Tuset, Schaefer Marco, Peter Wolfgang, Valsecchi Maria G., Cazzaniga Marina, Faverio Paola, Bonfanti Paolo, Dopazo Ximo

    NATURE   600 巻 ( 7889 ) 頁: 472 - +   2021年12月

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    出版者・発行元:Nature  

    The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

    DOI: 10.1038/s41586-021-03767-x

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  107. Clinical Characteristics of Patients with Coronavirus Disease (COVID-19): Preliminary Baseline Report of Japan COVID-19 Task Force, a Nationwide Consortium to Investigate Host Genetics of COVID-19

    Tanaka Hiromu, Lee Ho, Morita Atsuho, Namkoong Ho, Chubachi Shotaro, Kabata Hiroki, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Harada Norihiro, Ueda Tetsuya, Ueda Soichiro, Ishiguro Takashi, Arimura Ken, Saito Fukuki, Yoshiyama Takashi, Nakano Yasushi, Mutoh Yoshikazu, Suzuki Yusuke, Murakami Koji, Okada Yukinori, Koike Ryuji, Kitagawa Yuko, Tokunaga Katsushi, Kimura Akinori, Imoto Seiya, Miyano Satoru, Ogawa Seishi, Kanai Takanori, Fukunaga Koichi

    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES   113 巻   頁: 74 - 81   2021年12月

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    記述言語:英語   出版者・発行元:International Journal of Infectious Diseases  

    Background and design:: The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. Results:: The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45–71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. Conclusions:: Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19.

    DOI: 10.1016/j.ijid.2021.09.070

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  108. 集中治療にて救命しえた腎移植後COVID-19の1例

    森田 伸也, 高橋 遼平, 浅岡 雅人, 山元 良, 長田 大雅, 本間 康一郎, 川田 一郎, 吉田 理, 石井 誠, 浅沼 宏, 中川 健, 大家 基嗣

    日本臨床腎移植学会雑誌   9 巻 ( 2 ) 頁: 207 - 210   2021年12月

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    記述言語:英語   出版者・発行元:(一社)日本臨床腎移植学会  

    56歳男性。紫斑病性腎炎による慢性腎不全にてX-19年血液透析導入、同年血液型適合生体腎移植施行。維持免疫抑制剤はシクロスポリン(CyA)、ミコフェノール酸モフェチル(MMF)、プレドニゾロン(PSL)であった。X年に頭重感と微熱を主訴に来院、CTにて肺一部にすりガラス影を認め、鼻咽頭PCRにてSARS-CoV-2陽性となり緊急入院。MMF減量しファビピラビル、セフトリアキソン投与開始した。さらに抗生剤をタゾバクタム/ピペラシリンに、PSLをデキサメタゾンとしMMFを中止した。肺炎増悪したためメチルプレドニゾロン(mPSL)90mg/day投与、抗凝固療法開始しCyA減量した。呼吸状態増悪のため人工呼吸器管理としCyA中止、レムデシビル投与開始、腹臥位療法を施行した。一時血液透析を3回施行。徐々に酸素化は改善しmPSLは漸減とした。細菌性肺炎合併を疑い抗生剤をバンコマイシンとメロペネムとし、肺炎は改善した。下気道PCRにてSARS-CoV-2陰性を2回確認後CyA、MMFを再開し退院となった。(著者抄録)

  109. ADAM10 partially protects mice against influenza pneumonia by suppressing specific myeloid cell population

    Okamori Satoshi, Ishii Makoto, Asakura Takanori, Suzuki Shoji, Namkoong Ho, Kagawa Shizuko, Hegab Ahmed E., Yagi Kazuma, Kamata Hirofumi, Kusumoto Tatsuya, Ogawa Takunori, Takahashi Hayato, Yoda Masaki, Horiuchi Keisuke, Hasegawa Naoki, Fukunaga Koichi

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   321 巻 ( 5 ) 頁: L872 - L884   2021年11月

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    記述言語:英語   出版者・発行元:American Journal of Physiology - Lung Cellular and Molecular Physiology  

    The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contributes to various immune responses; however, the role of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. ADAM10 gene (Adam10)flox/flox/Lyz2-Cre (Adam10DLyz2) and control Adam10flox/flox mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10DLyz2 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines, such as TNF-a, IL-1b, and CCL2, were increased in bronchoalveolar lavage fluid from Adam10DLyz2 mice following infection. CD11b+Ly6G-F4/80+ myeloid cells, which had an inflammatory monocyte/macrophage-like phenotype, were significantly increased in the lungs of Adam10DLyz2 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10DLyz2 mice. Seven days after infection, CD11b+Ly6G-F4/80+ lung cells exhibited significantly higher arginase-1 expression levels in Adam10DLyz2 mice than in control mice, whereas an arginase-1 inhibitor improved the prognosis of Adam10DLyz2 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.

    DOI: 10.1152/ajplung.00619.2020

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  110. Comprehensive and long-term surveys of COVID-19 sequelae in Japan, an ambidirectional multicentre cohort study: study protocol

    Nakagawara Kensuke, Namkoong Ho, Terai Hideki, Masaki Katsunori, Tanosaki Takae, Shimamoto Kyoko, Lee Ho, Tanaka Hiromu, Okamori Satoshi, Kabata Hiroki, Chubachi Shotaro, Ikemura Shinnosuke, Kamata Hirofumi, Yasuda Hiroyuki, Kawada Ichiro, Ishii Makoto, Ishibashi Yoshiki, Harada Sei, Fujita Takanori, Ito Daisuke, Bun Shogyoku, Tabuchi Hajime, Kanzaki Sho, Shimizu Eisuke, Fukuda Keitaro, Yamagami Jun, Kobayashi Keigo, Hirano Toshiyuki, Inoue Takashi, Kagyo Junko, Shiomi Tetsuya, Ohgino Keiko, Sayama Koichi, Otsuka Kengo, Miyao Naoki, Odani Toshio, Oyamada Yoshitaka, Masuzawa Keita, Nakayama Sohei, Suzuki Yusuke, Baba Rie, Nakachi Ichiro, Kuwahara Naota, Ishiguro Takashi, Mashimo Shuko, Minematsu Naoto, Ueda Soichiro, Manabe Tadashi, Funatsu Yohei, Koh Hidefumi, Yoshiyama Takashi, Saito Fumitake, Ishioka Kota, Takahashi Saeko, Nakamura Morio, Goto Ai, Harada Norihiro, Kusaka Yu, Nakano Yasushi, Nishio Kazumi, Tateno Hiroki, Edahiro Ryuya, Takeda Yoshito, Kumanogoh Atsushi, Kodama Nobuhiro, Okamoto Masaki, Umeda Akira, Hagimura Kazuto, Sato Toshiro, Miyazaki Naoki, Takemura Ryo, Sato Yasunori, Takebayashi Toru, Nakahara Jin, Mimura Masaru, Ogawa Kaoru, Shimmura Shigeto, Negishi Kazuno, Tsubota Kazuo, Amagai Masayuki, Goto Rei, Ibuka Yoko, Hasegawa Naoki, Kitagawa Yuko, Kanai Takanori, Fukunaga Koichi

    BMJ OPEN RESPIRATORY RESEARCH   8 巻 ( 1 )   2021年11月

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    記述言語:英語   出版者・発行元:BMJ Open Respiratory Research  

    Introduction The rapid spread of COVID-19 posed a global burden. Substantial number of people died of the disease in the acute phase of infection. In addition, a significant proportion of patients have been reported to suffer from post-acute phase symptoms, sequelae of COVID-19, which may negatively influence the quality of daily living and/or socioeconomic circumstances of the patients. However, no previous study has comprehensively and objectively assessed the quality of life of patients by using existing international scales. Further, evidence of socioeconomic consequences among patients with COVID-19 is scarce. To address the multidimensional issues from sequelae of COVID-19, evidence from comprehensive surveys beyond clinical perspectives is critical that investigates health, and social determinants of disease progression as well as socioeconomic consequences at a large scale. Methods and analysis In this study, we plan to conduct a nationwide and comprehensive survey for the sequelae of COVID-19 in a total of 1000 patients diagnosed at 27 hospitals throughout Japan. This study will evaluate not only the health-related status of patients from clinical perspectives but also the Health-related Quality of Life (HRQoL) scores, socioeconomic status and consequences to discuss the sequelae of the disease and the related risk factors. The primary endpoint is the frequency of long-term complications of COVID-19 infection. The secondary endpoints are risk factors for progression to sequelae of COVID-19 infection. The study will provide robust and important evidence as a resource to tackle the issues from the sequelae of COVID-19 from the multi-dimensional perspectives. Ethics and dissemination This trial was approved by the Keio University School of Medicine Ethics Committee (20200243, UMIN000042299). The results of this study will be reported at a society meeting or published in a peer-reviewed journal.

    DOI: 10.1136/bmjresp-2021-001015

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  111. Book Review 呼吸器疾患最新の治療2021-2022

    石井 誠

    内科   128 巻 ( 4 ) 頁: 828 - 828   2021年10月

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    出版者・発行元:南江堂  

    DOI: 10.15106/j_naika128_828

    CiNii Research

  112. Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis A Multicenter Retrospective Study

    Yagi Kazuma, Ito Akihiro, Fujiwara Keiji, Morino Eriko, Hase Isano, Nakano Yasushi, Asakura Takanori, Furuuchi Koji, Morita Atsuho, Asami Takahiro, Namkoong Ho, Saito Fumitake, Morimoto Kozo, Ishii Makoto, Sato Yasunori, Tateno Hiroki, Nishio Kazumi, Oyamada Yoshitaka, Fukunaga Koichi, Sugiyama Haruhito, Ishida Tadashi, Kurashima Atsuyuki, Hasegawa Naoki

    ANNALS OF THE AMERICAN THORACIC SOCIETY   18 巻 ( 9 ) 頁: 1490 - 1497   2021年9月

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    記述言語:英語   出版者・発行元:Annals of the American Thoracic Society  

    Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the clinical features and prognosis of NTM pleuritis. Methods: This retrospective observational study included patients with NTM pleuritis from January 2001 to June 2018 across eight hospitals in Japan. NTM pleuritis was defined by a positive NTM culture of pleural effusion samples. We matched patients with Mycobacterium avium complex (MAC) lung disease (MAC-LD) without pleuritis by sex and age to obtain comparative data and investigated the association between clinical parameters and the prognosis. Results: We identified 64 patients with NTM pleuritis (median age, 73 yr; 37 female patients). The median follow-up duration was 11 months, and 27 patients died. Patients with MAC pleuritis had a significantly lower survival rate than matched patients with MAC-LD without pleuritis. Multivariate analysis revealed that pleuritis (adjusted hazard ratio, 6.99; 95% confidence interval [CI], 2.58–19.00) and underlying pulmonary diseases (adjusted hazard ratio, 3.01; 95% CI, 1.44–6.28) were independently associated with all-cause mortality in patients with MAC-LD. Conclusions: The prognosis of MAC pleuritis is poorer than that of MAC-LD without pleuritis. Pleuritis is an independent prognostic factor in patients with MAC-LD.

    DOI: 10.1513/AnnalsATS.202008-938OC

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  113. Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease

    Namkoong Ho, Omae Yosuke, Asakura Takanori, Ishii Makoto, Suzuki Shoji, Morimoto Kozo, Kawai Yosuke, Emoto Katsura, Oler Andrew J., Szymanski Eva P., Yoshida Mitsunori, Matsuda Shuichi, Yagi Kazuma, Hase Isano, Nishimura Tomoyasu, Sasaki Yuka, Asami Takahiro, Shiomi Tetsuya, Matsubara Hiroaki, Shimada Hisato, Hamamoto Junko, Jhun Byung Woo, Kim Su-Young, Huh Hee Jae, Won Hong-Hee, Ato Manabu, Kosaki Kenjiro, Betsuyaku Tomoko, Fukunaga Koichi, Kurashima Atsuyuki, Tettelin Herve, Yanai Hideki, Mahasirimongkol Surakameth, Olivier Kenneth N., Hoshino Yoshihiko, Koh Won-Jung, Holland Steven M., Tokunaga Katsushi, Hasegawa Naoki

    EUROPEAN RESPIRATORY JOURNAL   58 巻 ( 2 )   2021年8月

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    記述言語:英語   出版者・発行元:European Respiratory Journal  

    Rationale Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear. Objectives We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen. Methods This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping. Results The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10−13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10−12, OR 0.54) and European (p=5.12×10−03, OR 0.63) ancestry. Conclusions We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.

    DOI: 10.1183/13993003.02269-2019

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  114. Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

    Ho Namkoong, Ryuya Edahiro, Koichi Fukunaga, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Takanori Hasegawa, Masahiro Kanai, Tatsuhiko Naito, Kenichi Yamamoto, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Ryousuke Aoki, Ai Nakamura, Sonoko Harada, Hitoshi Sasano, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Yohei Mikami, Sho Uchida, Shunsuke Uno, Rino Ishihara, Yuta Matsubara, Tomoyasu Nishimura, Takanori Ogawa, Takashi Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Ken Suzuki, Nobuyuki Hizawa, Takayuki Shiroyama, Satoru Miyawaki, Yusuke Kawamura, Akiyoshi Nakayama, Hirotaka Matsuo, Yuichi Maeda, Takuro Nii, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Toshihiro Kishikawa, Shuhei Yamada, Shuhei Kawabata, Noriyuki Kijima, Masatoshi Takagaki, Noa Sasa, Yuya Ueno, Motoyuki Suzuki, Norihiko Takemoto, Hirotaka Eguchi, Takahito Fukusumi, Takao Imai, Munehisa Fukushima, Haruhiko Kishima, Hidenori Inohara, Kazunori Tomono, Kazuto Kato, Meiko Takahashi, Fumihiko Matsuda, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-o, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori K, a, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimo, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Yukinori Okada

        2021年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Cold Spring Harbor Laboratory  

    <jats:p>To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., <jats:italic>LZTFL1</jats:italic>, <jats:italic>FOXP4</jats:italic>, <jats:italic>ABO</jats:italic>, and <jats:italic>IFNAR2</jats:italic>), but also found a variant on 5p35 (rs60200309-A at <jats:italic>DOCK2</jats:italic>) that was significantly associated with severe COVID-19 in younger (&lt;65 years of age) patients with a genome-wide significant p-value of 1.2 × 10<jats:sup>-8</jats:sup> (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.</jats:p>

    DOI: 10.1101/2021.05.17.21256513

  115. Exacerbation of immune thrombocytopenia triggered by COVID-19 in patients with systemic lupus erythematosus

    Kondo Yasushi, Kaneko Yuko, Oshige Tatsuhiro, Fukui Hiroyuki, Saito Shuntaro, Okayama Mikio, Kamata Hirofumi, Ishii Makoto, Hasegawa Naoki, Fukunaga Koichi, Takeuchi Tsutomu

    ANNALS OF THE RHEUMATIC DISEASES   80 巻 ( 5 ) 頁: e77   2021年5月

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    記述言語:英語   出版者・発行元:Annals of the Rheumatic Diseases  

    DOI: 10.1136/annrheumdis-2020-218157

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  116. The real-time reverse transcription-polymerase chain reaction threshold cycle values for severe acute respiratory syndrome coronavirus 2 predict the prognosis of coronavirus disease 2019 pneumonia

    Fukushima Takahiro, Kabata Hiroki, Yamamoto Ryo, Suhara Tomohiro, Uwamino Yoshifumi, Kondo Yasushi, Masaki Katsunori, Kamata Hirofumi, Nagata Hiromasa, Homma Koichiro, Kaneko Yuko, Ishii Makoto, Sasaki Junichi, Morisaki Hiroshi, Hasegawa Naoki, Fukunaga Koichi

    RESPIRATORY INVESTIGATION   59 巻 ( 3 ) 頁: 360 - 363   2021年5月

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    記述言語:英語   出版者・発行元:Respiratory Investigation  

    The clinical course of coronavirus disease 2019 (COVID-19) varies from mild to critical. We retrospectively examined whether clinical and laboratory findings on admission could predict COVID-19 prognosis. Among various factors associated with COVID-19 severity, our results indicated that the real-time reverse transcription-polymerase chain reaction (RT-PCR) threshold cycle (Ct) values for severe acute respiratory syndrome coronavirus 2 were the most useful predictor of COVID-19 prognosis.

    DOI: 10.1016/j.resinv.2020.12.011

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  117. 当院で入院加療した新型コロナウイルス感染症患者の臨床像 第1波と第2波の比較

    藤井 健太郎, 中村 守男, 丸木 孟知, 土屋 悠海, 伊藤 航人, 谷山 大輔, 関根 和彦, 石井 誠, 福永 興壱, 菊池 隆秀

    日本呼吸器学会誌   10 巻 ( 3 ) 頁: 236 - 244   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

    当院の新型コロナウイルス感染症の診療状況について4月前後の第1波と6月以降の第2波で比較検討し、第2波で致死率が低下し重症化が抑制されていた。重症化マーカーである白血球数、CRP、フェリチン、LDH、D-dimerは酸素吸入を要する中等症・重症群で有意な上昇を認め、第2波では一部は有意な低下を呈したが、第1波と同等に高値である群が存在した。第2波では軽症から中等症への悪化は抑制されていないが、中等症から重症への悪化が抑制されており、レムデシビル(remdesivir)やデキサメタゾン(dexamethasone)などの治療の早期介入が寄与している可能性が考えられた。(著者抄録)

  118. Distinct Expression of Coinhibitory Molecules on Alveolar T Cells in Patients With Rheumatoid Arthritis-Associated and Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease

    Nakazawa Maho, Suzuki Katsuya, Takeshita Masaru, Inamo Jun, Kamata Hirofumi, Ishii Makoto, Oyamada Yoshitaka, Oshima Hisaji, Takeuchi Tsutomu

    ARTHRITIS & RHEUMATOLOGY   73 巻 ( 4 ) 頁: 576 - 586   2021年4月

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    記述言語:英語   出版者・発行元:Arthritis and Rheumatology  

    Objective: To identify immunologic factors in the lungs of patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and patients with idiopathic inflammatory myopathy–associated ILD (IIM-ILD) and to examine their pathologic mechanisms. Methods: Eleven patients with RA-ILD, 16 with IIM-ILD, 6 with drug-induced ILD (DI-ILD), and 8 healthy controls were enrolled. Peripheral blood (PB) and bronchoalveolar lavage (BAL) fluid were immunophenotyped by flow cytometry. Alveolar macrophages (AMs) were analyzed by coculture assay with PB naive CD4+ T cells from healthy individuals and RNA sequencing. Results: Several coinhibitory molecules were coexpressed on BAL fluid T cells (CTLA-4, programmed death 1 [PD-1], T cell immunoglobulin and mucin domain–containing protein 3 [TIM-3], and lymphocyte activation gene 3 protein, from most to least), whereas only PD-1 was expressed on PB T cells. CTLA-4+PD-1+CD4+ T cells were characteristic of RA-ILD, whereas CTLA-4+PD-1+TIM-3+CD8+ T cells were characteristic of IIM-ILD. BAL fluid PD-1+CD4+ T cells rarely expressed CXCR5, but their levels correlated with levels of plasmablasts and plasma cells (ρ = 0.57, P = 0.006), indicating that most of them would be considered peripheral helper T cells. In coculture experiments, AMs from patients with RA-ILD and IIM-ILD induced more PD-1 and TIM-3 on T cells (P < 0.05), suggesting that coinhibitory molecule expression on BAL fluid T cells was partly due to AMs. RNA sequencing showed significant down-regulation of PD ligand 1/2 genes in AMs from patients with RA-ILD compared to those with DI-ILD. Conclusion: We have identified differences in coinhibitory molecule expression between patients with RA-ILD and those with IIM-ILD. PD-1 on T cells in RA-ILD and TIM-3 on CD8+ T cells in IIM-ILD might be key factors in the disease process. Evaluation of coinhibitory molecules on BAL fluid T cells could be clinically useful.

    DOI: 10.1002/art.41554

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  119. Incomplete humoral response including neutralizing antibodies in asymptomatic to mild COVID-19 patients in Japan

    Takeshita Masaru, Nishina Naoshi, Moriyama Saya, Takahashi Yoshimasa, Uwamino Yoshifumi, Nagata Mika, Aoki Wataru, Masaki Katsunori, Ishii Makoto, Saya Hideyuki, Kondo Yasushi, Kaneko Yuko, Suzuki Katsuya, Fukunaga Koichi, Takeuchi Tsutomu

    VIROLOGY   555 巻   頁: 35 - 43   2021年3月

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    記述言語:英語   出版者・発行元:Virology  

    The pandemic of COVID-19 is still ongoing, and many studies on serum antibodies have been reported, however, there are few studies about asymptomatic and mild patients. In this study, we enrolled 44 COVID-19 patients with relatively mild disease and 48 pre-pandemic controls. We measured serum antibodies against extracellular domain, S1 domain, and receptor-binding domain of Spike and N protein, examined neutralization titers by authentic virus neutralization assay and newly-developed bead/cell-based Spike-ACE2 inhibition assay, and compared them with clinical features. Most of these antibodies, including neutralizing titers, were mutually correlated, and the production of antibodies were associated with low Ct values of PCR test, disease severity, symptoms especially pneumonia, lymphopenia, and serological test including CRP, LD, D-dimer, and procalcitonin. Notably, 87.5% of asymptomatic and 23.5% of mild patients did not have antibody against SARS-CoV-2. Our results revealed the inadequate acquisition of humoral immunity in patients with asymptomatic and mild COVID-19 patients.

    DOI: 10.1016/j.virol.2020.12.020

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  120. Accuracy and stability of saliva as a sample for reverse transcription PCR detection of SARS-CoV-2

    Uwamino Yoshifumi, Nagata Mika, Aoki Wataru, Fujimori Yuta, Nakagawa Terumichi, Yokota Hiromitsu, Sakai-Tagawa Yuko, Iwatsuki-Horimoto Kiyoko, Shiraki Toshiki, Uchida Sho, Uno Shunsuke, Kabata Hiroki, Ikemura Shinnosuke, Kamata Hirofumi, Ishii Makoto, Fukunaga Koichi, Kawaoka Yoshihiro, Hasegawa Naoki, Murata Mitsuru

    JOURNAL OF CLINICAL PATHOLOGY   74 巻 ( 1 ) 頁: 67 - 68   2021年1月

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    記述言語:英語   出版者・発行元:Journal of Clinical Pathology  

    DOI: 10.1136/jclinpath-2020-206972

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  121. Left Ventricular Thrombus With COVID-19 Complication in a Patient With Dilated Cardiomyopathy

    Imaeda S., Kabata H., Shiraishi Y., Kamata H., Tsuruta H., Yuasa S., Ishii M., Fukuda K., Fukunaga K.

    CJC Open   3 巻 ( 1 ) 頁: 124 - 126   2021年1月

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    記述言語:英語   出版者・発行元:CJC Open  

    Thrombosis, especially venous thromboembolism, is a complication often associated with coronavirus disease 2019 (COVID-19). However, there have been relatively few reports of arterial thrombosis. Here, we describe a case of non-severe COVID-19 in a patient with dilated cardiomyopathy. After admission, symptoms, laboratory data, and imaging findings improved, but D-dimer levels gradually increased. Contrast computed tomography and echocardiography revealed a left ventricular thrombus. Anticoagulant treatment diminished the thrombus, and the patient recovered and was discharged. Although a left ventricular thrombus is a rare COVID-19 complication, performing appropriate diagnostic tests could improve COVID-19 mortality in patients with dilated cardiomyopathy.

    DOI: 10.1016/j.cjco.2020.09.014

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  122. Serum Krebs von den Lungen-6 level in the disease progression and treatment ofMycobacterium aviumcomplex lung disease

    Asakura Takanori, Kimizuka Yoshifumi, Nishimura Tomoyasu, Suzuki Shoji, Namkoong Ho, Masugi Yohei, Sato Yasunori, Ishii Makoto, Hasegawa Naoki

    RESPIROLOGY   26 巻 ( 1 ) 頁: 112 - 119   2021年1月

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    記述言語:英語   出版者・発行元:Respirology  

    Background and objective: The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. Methods: Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). Results: The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. Conclusion: Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.

    DOI: 10.1111/resp.13886

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  123. COVID-19 shares clinical features with anti-melanoma differentiation-associated protein 5 positive dermatomyositis and adult Still's disease

    Kondo Y., Kaneko Y., Takei H., Tamai H., Kabata H., Suhara T., Yamamoto R., Nagata H., Ishii M., Sasaki J., Hasegawa N., Fukunaga K., Takeuchi T.

    CLINICAL AND EXPERIMENTAL RHEUMATOLOGY   39 巻 ( 3 ) 頁: 631 - 638   2021年

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  124. Longitudinal validity and prognostic significance of the St George's Respiratory Questionnaire in Mycobacterium avium complex pulmonary disease

    Ogawa Takunori, Asakura Takanori, Suzuki Shoji, Okamori Satoshi, Kusumoto Tatsuya, Sato Yasunori, Namkoong Ho, Kamata Hirofumi, Ishii Makoto, Fukunaga Koichi, Hasegawa Naoki

    RESPIRATORY MEDICINE   185 巻   頁: 106515   2021年

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    記述言語:英語   出版者・発行元:Respiratory Medicine  

    Background: Although previous cross-sectional studies showed the feasibility and clinical association of the St. George's Respiratory Questionnaire (SGRQ) in Mycobacterium avium complex pulmonary disease (MAC-PD), its longitudinal validity is poorly understood. We aimed to determine the longitudinal validity and prognostic significance of SGRQ. Methods: In this prospective observational study conducted between May 2012 and August 2018, we evaluated 269 enrolled patients with MAC-PD and examined associations between baseline SGRQ total scores and mortality or clinical variables (anchors), including serum C-reactive protein levels and pulmonary function test results. Results: Age- and sex-matched SGRQ scores indicated significantly greater impairment in patients with MAC-PD than in the general population (P < 0.001). On multivariable Cox proportional hazards regression analysis, the SGRQ total score ≥25 was an independent risk factor for mortality (adjusted hazard ratio, 5.90; 95% confidence interval, 1.65–37.7) as well as age, body mass index, and forced vital capacity (FVC). Mixed-effect model results showed a significant association between SGRQ symptom/total scores and forced expiratory volume in 1 s (FEV1), FVC, and diffusing carbon monoxide capacity. Older age, a positive smear, non-nodular/bronchiectatic form, and cavity regions were associated with SGRQ total score deterioration. Patients with a greater decline from baseline FEV1 (% predicted) exhibited significantly worse impairment in the SGRQ total score (mean ± SE, 4.69 ± 10.9 points, P = 0.001). Conclusions: SGRQ showed longitudinal validity in assessing disease severity and was sensitive to changes in patients with MAC-PD, especially changes in %FEV1. The SGRQ total score may be an important prognostic factor.

    DOI: 10.1016/j.rmed.2021.106515

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  125. Thymoma-associated T-cell immunodeficiency after radiotherapy: A case report

    Nakagawara Kensuke, Chubachi Shotaro, Azekawa Shuhei, Otake Shiro, Saito Ayaka, Okada Masahiko, Lee Ko, Masaki Katsunori, Koike Naoyoshi, Kamata Hirofumi, Kawada Ichiro, Suzuki Shigeaki, Ishii Makoto, Fukunaga Koichi

    RESPIRATORY MEDICINE CASE REPORTS   33 巻   頁: 101408   2021年

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    記述言語:英語   出版者・発行元:Respiratory Medicine Case Reports  

    Acquired immunodeficiency in thymoma (Good's syndrome) without hypogammaglobulinemia is a rare condition. Here we describe the case of a 29-year-old Japanese woman with thymoma-associated T cell immunodeficiency after radiation therapy. She was admitted to the hospital with refractory pneumonia, which resulted from as T cell immunodeficiency, as revealed through low peripheral lymphocytes and oral candidiasis triggered through radiotherapy and required long-term antimicrobial therapy. Although radiotherapy is commonly administered for thymoma, our findings suggest that physicians should consider carrying out lymphocyte counts during thymoma treatment.

    DOI: 10.1016/j.rmcr.2021.101408

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  126. Pro108Ser mutant of SARS-CoV-2 3CLpro reduces the enzymatic activity and ameliorates COVID-19 severity in Japan

    medRxiv     2020年11月

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  127. Clinical characteristics of 345 patients with coronavirus disease 2019 in Japan: A multicenter retrospective study

    Ishii Makoto, Terai Hideki, Kabata Hiroki, Masaki Katsunori, Chubachi Shotaro, Tateno Hiroki, Nakamura Morio, Nishio Kazumi, Koh Hidefumi, Watanabe Risa, Ueda Soichiro, Terashima Takeshi, Suzuki Yusuke, Yagi Kazuma, Miyao Naoki, Minematsu Naoto, Inoue Takashi, Nakachi Ichiro, Namkoong Ho, Okamori Satoshi, Ikemura Shinnosuke, Kamata Hirofumi, Yasuda Hiroyuki, Kawada Ichiro, Hasegawa Naoki, Fukunaga Koichi

    JOURNAL OF INFECTION   81 巻 ( 5 ) 頁: E3 - E5   2020年11月

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    記述言語:英語   出版者・発行元:Journal of Infection  

    DOI: 10.1016/j.jinf.2020.08.052

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  128. A case of non-severe COVID-19 complicated by pulmonary embolism

    Akiyama Yuto, Horiuchi Kohei, Kondo Yasushi, Kabata Hiroki, Ishii Makoto, Fukunaga Koichi

    RESPIROLOGY CASE REPORTS   8 巻 ( 7 ) 頁: e00622   2020年10月

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    記述言語:英語   出版者・発行元:Respirology Case Reports  

    Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 is rapidly spreading worldwide. A typical clinical manifestation of COVID-19 is pneumonia, which can progress to acute respiratory distress syndrome and respiratory failure. Recent studies have reported that COVID-19 is often accompanied by coagulopathy, and a significant number of patients with severe or critical COVID-19 develop concomitant thrombosis, including pulmonary embolism (PE). However, there are limited reports of the incidence of PE in non-severe COVID-19 patients. Here, we report a case of non-severe COVID-19 complicated by PE, which indicates that the possibility of PE should consistently be considered, even in non-severe cases of COVID-19 without any risk of thrombosis.

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  129. Acute onset olfactory/taste disorders are associated with a high viral burden in mild or asymptomatic SARS-CoV-2 infections

    Nakagawara Kensuke, Masaki Katsunori, Uwamino Yoshifumi, Kabata Hiroki, Uchida Sho, Uno Shunsuke, Asakura Takanori, Funakoshi Takeru, Kanzaki Sho, Ishii Makoto, Hasegawa Naoki, Fukunaga Koichi

    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES   99 巻   頁: 19 - 22   2020年10月

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    記述言語:英語   出版者・発行元:International Journal of Infectious Diseases  

    This study investigated, using cycle threshold (Ct) qPCR values, the association between symptoms and viral clearance in 57 patients with asymptomatic/mild SARS-CoV-2 infection. Patients with olfactory/taste disorders (OTDs) exhibited lower qPCR Ct values and longer time to negative qPCR than those without OTDs, suggesting an association between OTDs and high viral burden.

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

    Matsuda Shuichi, Asakura Takanori, Morimoto Kozo, Suzuki Shoji, Fujiwara Keiji, Furuuchi Koji, Osawa Takeshi, Namkoong Ho, Ishii Makoto, Kurashima Atsuyuki, Tatsumi Koichiro, Ohta Ken, Hasegawa Naoki, Sasaki Yuka

    RESPIRATORY MEDICINE   171 巻   頁: 106086   2020年9月

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    記述言語:英語   出版者・発行元:Respiratory Medicine  

    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.

    DOI: 10.1016/j.rmed.2020.106086

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  131. Exposure to Cigarette Smoke Enhances the Sternness of Alveolar Type 2 Cells

    Tsutsumi Akihiro, Ozaki Mari, Chubachi Shotaro, Irie Hidehiro, Sato Minako, Kameyama Naofumi, Sasaki Mamoru, Ishii Makoto, Hegab Ahmed E., Betsuyaku Tomoko, Fukunaga Koichi

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY   63 巻 ( 3 ) 頁: 293 - 305   2020年9月

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    記述言語:英語   出版者・発行元:American Journal of Respiratory Cell and Molecular Biology  

    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 GFP1/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.

    DOI: 10.1165/rcmb.2019-0188OC

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  132. Pleuroparenchymal Fibroelastosis様の画像所見を呈した肺非結核性抗酸菌症の検討

    岡森 慧, 朝倉 崇徳, 古内 浩司, 八木 光昭, 松本 武格, 八木 一馬, 長谷 衣佐乃, 鎌田 浩史, 藤原 啓司, 石井 誠, 小川 賢二, 森本 耕三, 藤田 昌樹, 佐々木 結花, 長谷川 直樹

    結核   95 巻 ( 5 ) 頁: 139 - 139   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

  133. Coronavirus disease 2019-associated rapidly progressive organizing pneumonia with fibrotic feature Two case reports

    Okamori Satoshi, Lee Ho, Kondo Yasushi, Akiyama Yuto, Kabata Hiroki, Kaneko Yuko, Ishii Makoto, Hasegawa Naoki, Fukunaga Koichi

    MEDICINE   99 巻 ( 35 ) 頁: e21804   2020年8月

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    記述言語:英語   出版者・発行元:Medicine  

    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.

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  134. ADAM17 protects against elastase-induced emphysema by suppressing CD62L(+) leukocyte infiltration in mice

    Suzuki Shoji, Ishii Makoto, Asakura Takanori, Namkoong Ho, Okamori Satoshi, Yagi Kazuma, Kamata Hirofumi, Kusumoto Tatsuya, Kagawa Shizuko, Hegab Ahmed E., Yoda Masaki, Horiuchi Keisuke, Hasegawa Naoki, Betsuyaku Tomoko

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   318 巻 ( 6 ) 頁: L1172 - L1182   2020年6月

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    記述言語:英語   出版者・発行元:American Journal of Physiology - Lung Cellular and Molecular Physiology  

    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.

    DOI: 10.1152/ajplung.00214.2019

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  135. 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 巻   頁: 232 - 233   2020年6月

  136. Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study (vol 19, 1055, 2019)

    Uwamino Yoshifumi, Nishimura Tomoyasu, Sato Yasunori, Tamizu Eiko, Asakura Takanori, Uno Shunsuke, Mori Masaaki, Fujiwara Hiroshi, Ishii Makoto, Kawabe Hiroshi, Murata Mitsuru, Hasegawa Naoki

    BMC INFECTIOUS DISEASES   20 巻 ( 1 ) 頁: 131   2020年2月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    After publication of the original article [1], we were notified that units of testosterone in main text and abstract and units of DHEA-S in Fig. 1 and Table 4 are incorrect. 1. In the Abstract: 'testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005)' should be replaced with 'testosterone (0.230 ng/mL vs. 0.250 ng/mL, p = 0.005)' 2. In the section 'Serum levels of sex hormones': 'testosterone (0.23 ng/L vs. 0.25 ng/L, p = 0.005)' should be replaced with 'testosterone (0.23 ng/mL vs. 0.25 ng/mL, p = 0.005)' 3. The unit of serum DHEA-S, in Fig. 1 (3rd column): 'μg/mL' should be replaced with 'μg/dL' 4. unit of DHEA-S in Table 4 (4th row): 'μg/mL' should be replaced with 'μg/dL'.

    DOI: 10.1186/s12879-020-4868-4

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  137. Etiology and Health-Related Quality of Life in Non-Cystic Fibrosis Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease: The First Analysis of the Japanese Nontuberculous Mycobacteriosis-Bronchiectasis Registry

    Asakura T., Morimoto K., Ito A., Suzuki S., Morino E., Oshitani Y., Nakagawa T., Yagi K., Kadowaki T., Saito F., Hase I., Furuuchi K., Okamori S., Kusumoto T., Hirabayashi R., Ogawa T., Kamata H., Namkoong H., Takasaki J., Fujita M., Ogawa K., Kitada S., Ishida T., Kurashima A., Ishii M., Miyata H., Ato M., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

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  138. Host Genetic Analysis of Pulmonary NTM Disease and Non-CF Bronchietasis

    Namkoong H., Omae Y., Asakura T., Ishii M., Suzuki S., Morimoto K., Yoshida M., Emoto K., Oler A. J., Szymanski E. P., Matsuda S., Yagi K., Hase I., Nishimura T., Sasaki Y., Asami T., Shiomi T., Matsubara H., Shimada H., Hamamoto J., Jhun B., Kim S., Huh H., Won H., Daniels L., Zariwala M., Dang H., Ato M., Kosaki K., Kurashima A., Tettelin H., Yanai H., Mahasirimongkol S., Knowles M. R., Olivier K. N., Hoshino Y., Koh W., Holland S. M., Tokunaga K., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

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  139. Optimizing the in vitro colony-forming assay for more efficient delineation of the interaction between lung epithelial stem cells and their niche

    Ozaki M., Kagawa S., Ishii M., Hegab A. E.

    JOURNAL OF STEM CELLS & REGENERATIVE MEDICINE   16 巻 ( 2 ) 頁: 50 - 62   2020年

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    記述言語:英語   出版者・発行元:Journal of Stem Cells and Regenerative Medicine  

    The use of in vitro 3D organoid/colony forming assay (CFA); which mimics the in vivo environment have provided insight into the mechanisms by which lung stem cells maintain and repair the lung. In recent years, the use of CFA has markedly expanded. However, variations among laboratories in lung cell isolation methods, media used, type, origin, and processing methods of mesenchymal cells used as feeders for the epithelial colonies, and terms utilized to describe and quantify the growing colonies, have caused difficulty in reproducing results among different labs. In this study, we compared several previously described methods for lung cell isolation and culture media, to identify their influence on retrieved cells and growing colonies. We also characterized the effect of freeze/thaw, and propagation of fibroblasts on their ability to support epithelial colonies. Importantly, we suggested markers to identify fibroblast subtypes that offer the best support to alveolar stem cell proliferation. Then, we used our optimized assay to confirm the in vitro identity of recently described epithelial progenitors. We also tested the effect of hyperoxia on lung stem cells, and examined the expression of the receptors for the SARS-COV-2 virus entry into epithelial cells, on our organoids. In summary, our findings facilitate CFA standardization, help understand how niche cell variations influence growing colonies, and confirm some of the recently described lung stem cells.

    DOI: 10.46582/jsrm.1602009

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  140. Short-Term Intermittent Cigarette Smoking Enhances the Stemness of Alveolar Epithelial Type 2 Cells Through Activation of Fatty Acid Oxidation

    Irie H., Chubachi S., Tsutsumi A., Sakurai K., Ozaki M., Ishii M., Hegab A. E., Fukunaga K.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

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  141. Serum Krebs Von Den Lungen-6 Level in the Prognosis, Disease Progression, and Treatment of Mycobacterium Avium Complex Lung Disease

    Asakura T., Kimizuka Y., Nishimura T., Suzuki S., Masugi Y., Ishii M., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

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  142. Etiology and Health-Related Quality of Life in Non-Cystic Fibrosis Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease: The First Analysis of the Japanese Nontuberculous Mycobacteriosis-Bronchiectasis Registry

    Asakura T, Morimoto K, Ito A, Suzuki S, Morino E, Oshitani Y, Nakagawa T, Yagi K, Kadowaki T, Saito F, Hase I, Furuuchi K, Okamori S, Kusumoto T, Hirabayashi R, Ogawa T, Kamata H, Namkoong H, Takasaki J, Fujita M, Ogawa K, Kitada S, Ishida T, Kurashima A, Ishii M, Miyata H, Ato M, Hasegawa N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

  143. Short-Term Intermittent Cigarette Smoking Enhances the Stemness of Alveolar Epithelial Type 2 Cells Through Activation of Fatty Acid Oxidation

    Irie H, Chubachi S, Tsutsumi A, Sakurai K, Ozaki M, Ishii M, Hegab A. E, Fukunaga K

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

  144. Prevalence and Risk Factors for Osteoporosis in Patients with Pulmonary Nontuberculous Mycobacterial Disease

    Tanaka H, Asakura T, Suzuki S, Okamori S, Kusumoto T, Ogawa T, Morita A, Lee K., So M, Namkoong H, Kamata H, Ishii M, Fukunaga K, Hasegawa N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   201 巻   2020年

  145. Nontuberculous Mycobacterial Lung Disease Complicated by Radiological Pleuroparenchymal Fibroelastosis Pattern

    S Okamori, T Asakura, K Furuuchi, M Yagi, T Matsumoto, K Yagi, I Hase

    C53. GLOBAL EXPERIENCES IN TB AND NTM CARE, A5429-A5429     2020年

  146. Host Genetic Analysis of Pulmonary NTM Disease and Non-CF Bronchietasis

    H Namkoong, Y Omae, T Asakura, M Ishii, S Suzuki, K Morimoto

    C16. NTM DISEASE-NEW DATA AND CHANGING PARADIGMS, A4491-A4491     2020年

  147. Etiology and Health-Related Quality of Life in Non-Cystic Fibrosis Bronchiectasis and Nontuberculous Mycobacterial Pulmonary Disease: The First Analysis of the Japanese …

    T Asakura, K Morimoto, A Ito, S Suzuki, E Morino, Y Oshitani, T Nakagawa

    B106. BREAKTHROUGHS IN NTM DIAGNOSIS AND TREATMENT, A4370-A4370     2020年

  148. Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study

    Uwamino Yoshifumi, Nishimura Tomoyasu, Sato Yasunori, Tamizu Eiko, Asakura Takanori, Uno Shunsuke, Mori Masaaki, Fujiwara Hiroshi, Ishii Makoto, Kawabe Hiroshi, Murata Mitsuru, Hasegawa Naoki

    BMC INFECTIOUS DISEASES   19 巻 ( 1 ) 頁: 1055   2019年12月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    Background: The risk factors for Mycobacterium avium complex lung disease (MAC-LD) are not well known. We hypothesized that low serum estradiol (E2) levels are related to MAC-LD as most patients with MAC-LD are postmenopausal women. Methods: This cross-sectional study compared patients with MAC-LD and healthy controls. Study subjects were postmenopausal women aged 65 years or younger. Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and E2 levels were measured and categorized as high or low based on median levels. We performed multivariate analysis, receiver operating characteristic (ROC) curve analysis, and age-and body mass index (BMI)-matched subgroup analysis to evaluate the association between low serum E2 levels and MAC-LD. Additionally, using blood samples obtained for other clinical studies, the levels of sex steroid hormones were compared between age-and BMI-matched MAC-LD and bronchiectasis female patients without non-tuberculosis mycobacterial infections (non-NTM BE). Results: Forty-two patients with MAC-LD and 91 healthy controls were included. The median E2 (2.20 pg/mL vs. 15.0 pg/mL, p < 0.001), testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005), and DHEA-S (82.5 μg/dL vs. 114.0 μg/dL, p < 0.001) levels were lower in the MAC-LD group than in the control group. Multivariate analysis revealed that low serum E2 (adjusted odds ratio = 34.62, 95% confidence interval = 6.02-199.14) was independently related to MAC-LD, whereas low DHEA-S and testosterone were not. ROC analysis illustrated a strong relationship between low serum E2 levels and MAC-LD (area under the curve = 0.947, 95% confidence interval = 0.899-0.995). Even the age-and BMI-matched subgroup analysis of 17 MAC-LD patients and 17 healthy controls showed lower serum E2 in MAC-LD patients than in healthy controls. Additionally, serum E2 levels of 20 MAC-LD patients were lower than plasma E2 levels of 11 matched non-NTM BE patients (1.79 pg/mL vs. 11.0 pg/mL, p < 0.001). Conclusions: Low serum E2 levels were strongly related to MAC-LD in postmenopausal women.

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  149. Clinical features and prognosis of nontuberculous mycobacterial pleuritis

    Yagi Kazuma, Ito Akihiro, Fujiwara Keiji, Morino Eriko, Hase Isano, Nakano Yasushi, Asakura Takanori, Furuuchi Koji, Suzuki Shoji, Asami Takahiro, Namkoong Ho, Saito Fumitake, Morimoto Kozo, Ishii Makoto, Tateno Hiroki, Nishio Kazumi, Oyamada Yoshitaka, Sugiyama Haruhito, Ishida Tadashi, Kurashima Atsuyuki, Hasegawa Naoki

    EUROPEAN RESPIRATORY JOURNAL   54 巻   2019年9月

  150. Airway M Cells Arise in the Lower Airway Due to RANKL Signaling and Reside in the Bronchiolar Epithelium Associated With iBALT in Murine Models of Respiratory Disease

    Kimura Shunsuke, Mutoh Mami, Hisamoto Meri, Saito Hikaru, Takahashi Shun, Asakura Takanori, Ishii Makoto, Nakamura Yutaka, Iida Junichiro, Hase Koji, Iwanaga Toshihiko

    FRONTIERS IN IMMUNOLOGY   10 巻 ( JUN ) 頁: 1323   2019年6月

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    記述言語:英語   出版者・発行元:Frontiers in Immunology  

    Microfold (M) cells residing in the follicle-associated epithelium of mucosa-associated lymphoid tissues are specialized for sampling luminal antigens to initiate mucosal immune responses. In the past decade, glycoprotein 2 (GP2) and Tnfaip2 were identified as reliable markers for M cells in the Peyer's patches of the intestine. Furthermore, RANKL-RANK signaling, as well as the canonical and non-canonical NFκB pathways downstream, is essential for M-cell differentiation from the intestinal stem cells. However, the molecular characterization and differentiation mechanisms of M cells in the lower respiratory tract, where organized lymphoid tissues exist rarely, remain to be fully elucidated. Therefore, this study aimed to explore M cells in the lower respiratory tract in terms of their specific molecular markers, differentiation mechanism, and functions. Immunofluorescence analysis revealed a small number of M cells expressing GP2, Tnfaip2, and RANK is present in the lower respiratory tract of healthy mice. The intraperitoneal administration of RANKL in mice effectively induced M cells, which have a high capacity to take up luminal substrates, in the lower respiratory epithelium. The airway M cells associated with lymphoid follicles were frequently detected in the pathologically induced bronchus-associated lymphoid tissue (iBALT) in the murine models of autoimmune disease as well as pulmonary emphysema. These findings demonstrate that RANKL is a common inducer of M cells in the airway and digestive tracts and that M cells are associated with the respiratory disease. We also established a two-dimensional culture method for airway M cells from the tracheal epithelium in the presence of RANKL successfully. This model may be useful for functional studies of M cells in the sampling of antigens at airway mucosal surfaces.

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  151. Obesity worsens the outcome of influenza virus infection associated with impaired type I interferon induction in mice

    Namkoong Ho, Ishii Makoto, Fujii Hideki, Asami Takahiro, Yagi Kazuma, Suzuki Shoji, Azekawa Shuhei, Tasaka Sadatomo, Hasegawa Naoki, Betsuyaku Tomoko

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   513 巻 ( 2 ) 頁: 405 - 411   2019年5月

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    記述言語:英語   出版者・発行元:Biochemical and Biophysical Research Communications  

    Increasing evidence indicates that obesity is a risk factor for increased severity of influenza virus infection. However, its precise immunological mechanism is not fully understood. To investigate this, diet-induced obese (DIO)mice were established by feeding C57BL/6 male mice a high-fat diet for 16 weeks. DIO and lean control mice were infected intranasally with 3000 pfu of influenza A virus (IAV)(PR8/H1N1). Interestingly, we found adipose tissue located along the bronchus in naïve DIO mice. In addition, the Nos2 level was significantly higher and Arg1 level was significantly lower in lung macrophages of naïve DIO mice, consistent with an M1-skewed phenotype. The survival rate and body weight of DIO mice infected with IAV were significantly lower than those of lean control mice and associated with higher viral load in the lungs of DIO mice. Histopathological analysis demonstrated higher numbers of inflammatory cells in the lungs of DIO mice after IAV infection. Levels of cytokines, including TNF-α, IL-6, IL-10, and type I IFN (IFN-α and IFN-β), in bronchoalveolar lavage fluid (BALF)were altered after IAV infection; in particular, IFN-α and IFN-β levels were significantly suppressed in the BALF of DIO mice. In vitro, bone marrow-derived macrophages were stimulated with ligands of toll-like receptor (TLR)7/8, a pattern recognition receptor for single-stranded RNA, and levels of TNF-α, IL-6, and IL-10 were similarly altered. In addition, levels of IFN-α and IFN-β were significantly lower in culture supernatants of alveolar macrophages sorted from naïve DIO mice and infected with IAV, compared to those in macrophages sorted from lean control mice. Collectively, these results suggest that macrophages may be the main contributors to poor outcomes of influenza virus infection in obesity.

    DOI: 10.1016/j.bbrc.2019.03.211

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  152. Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease

    Kimizuka Yoshifumi, Hoshino Yoshihiko, Nishimura Tomoyasu, Asami Takahiro, Sakakibara Yumi, Morimoto Kozo, Maeda Shinji, Nakata Noboru, Abe Takayuki, Uno Shunsuke, Namkoong Ho, Fujiwara Hiroshi, Funatsu Yohei, Yagi Kazuma, Fujie Toshihide, Ishii Makoto, Inase Naohiko, Iwata Satoshi, Kurashima Atsuyuki, Betsuyaku Tomoko, Hasegawa Naoki, Sasaki Yuka, Kamata Hirofumi, Suzuki Shoji, Asakura Takanori, Morino Eriko, Nakano Yasushi

    PLOS ONE   14 巻 ( 4 ) 頁: e0216034   2019年4月

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    記述言語:英語   出版者・発行元:PLoS ONE  

    Background There is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease. Methods We conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model. Results Mean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV 1 ), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and % FEV 1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups. Conclusions Mild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.

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  153. Sitafloxacin-Containing Regimen for the Treatment of Refractory Mycobacterium avium Complex Lung Disease

    Asakura Takanori, Suzuki Shoji, Fukano Hanako, Okamori Satoshi, Kusumoto Tatsuya, Uwamino Yoshifumi, Ogawa Takunori, So Matsuo, Uno Shunsuke, Namkoong Ho, Yoshida Mitsunori, Kamata Hirofumi, Ishii Makoto, Nishimura Tomoyasu, Hoshino Yoshihiko, Hasegawa Naoki

    OPEN FORUM INFECTIOUS DISEASES   6 巻 ( 4 ) 頁: ofz108   2019年4月

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    記述言語:英語   出版者・発行元:Open Forum Infectious Diseases  

    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.

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  154. Deficiency of CRTH2, a Prostaglandin D-2 Receptor, Aggravates Bleomycin-induced Pulmonary Inflammation and Fibrosis

    Ueda Soichiro, Fukunaga Koichi, Takihara Takahisa, Shiraishi Yoshiki, Oguma Tsuyoshi, Shiomi Tetsuya, Suzukil Yusuke, Ishii Makoto, Sayama Koichi, Kagawa Shizuko, Hirai Hiroyuki, Nagata Kinya, Nakamura Masataka, Miyasho Taku, Betsuya Tomoko, Asano Koichiro

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY   60 巻 ( 3 ) 頁: 289 - 298   2019年3月

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    記述言語:英語   出版者・発行元:American Journal of Respiratory Cell and Molecular Biology  

    Chemoattractant receptor homologous with T-helper cell type 2 cells (CRTH2), a receptor for prostaglandin D 2 , is preferentially expressed on T-helper cell type 2 lymphocytes, group 2 innate lymphoid cells, eosinophils, and basophils, and elicits the production of type 2 cytokines, including profibrotic IL-13. We hypothesized that lack of CRTH2 might protect against fibrotic lung disease, and we tested this hypothesis using a bleomycin-induced lung inflammation and fibrosis model in CRTH2-deficient (CRTH2 – / – ) or wild-type BALB/c mice. Compared with wild-type mice, CRTH2 – / – mice treated with bleomycin exhibited significantly higher mortality, enhanced accumulation of inflammatory cells 14–21 days after bleomycin injection, reduced pulmonary compliance, and increased levels of collagen and total protein in the lungs. These phenotypes were associated with decreased levels of IFN-g, IL-6, IL-10, and IL-17A in BAL fluid. Adoptive transfer of splenocytes from wild-type, but not CRTH2 – / – , mice 2 days before injection of bleomycin resolved the sustained inflammation as well as the increased collagen and protein accumulation in the lungs of CRTH2 – / – mice. We consider that the disease model is driven by gdT cells that express CRTH2; thus, the adoptive transfer of gdT cells could ameliorate bleomycin-induced alveolar inflammation and fibrosis.

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  155. Efficacy and safety of intermittent maintenance therapy after successful treatment of Mycobacterium avium complex lung disease

    Asakura Takanori, Nakagawa Taku, Suzuki Shoji, Namkoong Ho, Morimoto Kozo, Ishii Makoto, Kurashima Atsuyuki, Betsuyaku Tomoko, Ogawa Kenji, Hasegawa Naoki

    JOURNAL OF INFECTION AND CHEMOTHERAPY   25 巻 ( 3 ) 頁: 218 - 221   2019年3月

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    記述言語:英語   出版者・発行元:Journal of Infection and Chemotherapy  

    Background: The optimal duration of antimicrobial therapy for Mycobacterium avium complex lung disease (MAC-LD) is unknown, and recurrence rates are high after treatment discontinuation. Intermittent therapy is recommended for the initial treatment of non-cavitary nodular/bronchiectatic MAC-LD. We hypothesized that intermittent maintenance therapy (IMT) could effectively prevent recurrence after successful treatment of MAC-LD. Methods: Adult patients diagnosed with MAC-LD who received IMT after successful daily therapy (DT) between January 1, 2006 and December 31, 2016 were identified from clinical databases at three institutions in Japan. Treatment outcomes were evaluated for all patients. Results: Of 38 patients (median age, 66 years; 29 women; nodular/bronchiectatic form, 29 patients) who received IMT after successful treatment, one was excluded due to death from an unknown cause, 1 month after IMT initiation. Finally, treatment outcomes were evaluated for 37 patients. Twenty-eight (76%) patients had sustained negative culture results over a median follow-up duration of 2.7 (interquartile range [IQR], 1.9–6.0) years, while six (16%) required switching to DT because of clinical deterioration over a median follow-up duration of 2.7 (IQR, 1.6–4.1) years. Favorable clinical outcomes were achieved for all patients who exhibited clinical deterioration. All patients tolerated the antimicrobials without discontinuation, and follow-up drug susceptibility testing showed negative results for clarithromycin-resistant MAC in the patients who experienced clinical deterioration. Conclusions: IMT after successful treatment may be a feasible option for patients with MAC-LD. Further studies should determine the population that would benefit from this strategy.

    DOI: 10.1016/j.jiac.2018.07.021

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  156. Development of lung cancer in patients with nontuberculous mycobacterial lung disease

    Kusumoto Tatsuya, Asakura Takanori, Suzuki Shoji, Okamori Satoshi, Namkoong Ho, Fujiwara Hiroshi, Yagi Kazuma, Kamata Hirofumi, Ishii Makoto, Betsuyaku Tomoko, Hasegawa Naoki

    RESPIRATORY INVESTIGATION   57 巻 ( 2 ) 頁: 157 - 164   2019年3月

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    記述言語:英語   出版者・発行元:Respiratory Investigation  

    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.

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  157. インフルエンザ感染におけるADAM10の保護的効果 査読有り

    石井 誠, 岡森 慧, 朝倉 崇徳, 鈴木 翔二, 鎌田 浩史, 南宮 湖, 八木 一馬, 宗 松男, 長谷川 直樹, 堀内 圭輔, 別役 智子, 小川 卓範

    感染症学雑誌   93 巻 ( 臨増 ) 頁: 394 - 394   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

  158. Prognostic values of the Berlin definition criteria, blood lactate level, and fibroproliferative changes on high-resolution computed tomography in ARDS patients

    Kamo Tetsuro, Tasaka Sadatomo, Suzuki Takeshi, Asakura Takanori, Suzuki Shoji, Yagi Kazuma, Namkoong Ho, Ishii Makoto, Morisaki Hiroshi, Betsuyaku Tomoko

    BMC PULMONARY MEDICINE   19 巻 ( 1 ) 頁: 37   2019年2月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: In the Berlin definition, acute respiratory distress syndrome (ARDS) is stratified into three stages according to oxygenation severity at the onset. The relevance between ARDS severity and prognosis varies among published reports and has not been verified, especially in Asian patients. Methods: In this study, we examined the associations between the Berlin definition criteria and prognosis and clinical parameters, including high-resolution computed tomography (HRCT) scores of fibroproliferative changes of the lungs. One hundred fifty-three patients (45 females; mean age, 67 y/o), who met the Berlin definition and received treatment in our intensive care unit between January 2012 and December 2015, were enrolled. Results: The severity of ARDS was mild in 42 patients, moderate in 71, and severe in 40. The underlying diseases included pneumonia in 56 patients and aspiration in 43. Forty-two (27.5%) patients were deceased within 30 days, and the 30-day mortality was 10% in mild ARDS, 23% in moderate, and 55% in severe, which were significantly different (P < 0.05). In the non-survivors, APACHE II, SOFA, and SAPS II scores were higher than in the survivors (P < 0.001). Multivariate analyses revealed that elevated blood lactate level (≥ 2.0 mmol/L) and increased HRCT scores were significantly associated with weaning failure and 30-day mortality of the patients with ARDS. Conclusions: These results suggested that the severity criteria in the Berlin definition might be associated with the prognosis of the patients. Blood lactate levels and HRCT score might be predictive of the outcome of patients with ARDS.

    DOI: 10.1186/s12890-019-0803-0

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  159. Black pleural effusion caused by pancreatic pseudocyst rupture

    Ishigaki Sho, Kuwae Misato, Ishii Makoto, Asakura Takanori, Ueda Soichiro, Betsuyaku Tomoko

    CLINICAL CASE REPORTS   7 巻 ( 2 ) 頁: 385 - 386   2019年2月

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    記述言語:英語   出版者・発行元:Clinical Case Reports  

    The images show the path of pancreatic pleural effusion from the pancreatic pseudocyst in a patient with alcoholic pancreatitis who presented with black pleural effusion, however, without symptoms. Pancreatic pseudocyst rupture rarely causes pleural effusion; however, it should be considered in patients with chronic pancreatitis with black pleural effusion.

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  160. Calorie restriction enhances adult mouse lung stem cells function and reverses several ageing-induced changes

    Hegab Ahmed E., Ozaki Mari, Meligy Fatma Y., Nishino Makoto, Kagawa Shizuko, Ishii Makoto, Betsuyaku Tomoko

    JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE   13 巻 ( 2 ) 頁: 295 - 308   2019年2月

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    記述言語:英語   出版者・発行元:Journal of Tissue Engineering and Regenerative Medicine  

    Ageing is associated with decreased lung function and an increased incidence of lung infections. Several studies have suggested that long-term calorie restriction (CR) promotes health and longevity and results in the reduced risk of several diseases. The effect of CR is thought to be through improving the function of tissue stem cells. Stem cell function is known to decline with ageing. In this study, we examined the effects of ageing on lung epithelial and stem cells and the effect of CR on young and old lungs. We found that ageing results in a decrease in tracheal basal stem cells. CR induced an increase in basal stem cells in both young and old mice. In addition, ageing induced lung inflammation, and CR tended to reduce baseline lung inflammatory cell infiltration in young mice and significantly reduced ageing-induced lung inflammation. Furthermore, ageing reduced the number and function of mitochondria in lung and increased the level of mitochondrial reactive oxygen species. CR increased the number and function of mitochondria both in young and old mice. Moreover, ageing reduced lung stem cell colony-forming efficiency (CFE), and CR increased the CFE in both young and old mice. Finally, CR improved epithelial cell survival in injured lungs of young mice. In conclusion, ageing causes several structural and functional changes/impairments in lung epithelial cells. CR induces several potentially beneficial changes in lung epithelial cells, even when it is initiated at an older age, including reversal of some ageing-induced changes.

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  161. First report of hepatobiliary Mycobacterium avium infection developing obstructive jaundice in a patient with neutralizing anti–interferon-gamma autoantibodies

    Namkoong H., Asakura T., Ishii M., Yoda S., Masaki K., Sakagami T., Iwasaki E., Yamagishi Y., Kanai T., Betsuyaku T., Hasegawa N.

    New Microbes and New Infections   27 巻   頁: 4 - 6   2019年1月

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    記述言語:英語   出版者・発行元:New Microbes and New Infections  

    This study describes a patient who experienced hepatobiliary Mycobacterium avium infection associated with neutralizing anti–interferon gamma (IFN-γ) autoantibodies during treatment for disseminated M. avium disease. Hepatobiliary M. avium infection should be considered in jaundiced patients with neutralizing anti–IFN-γ autoantibodies, including those receiving antimycobacterial therapy for disseminated M. avium disease.

    DOI: 10.1016/j.nmni.2018.10.001

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  162. Direct Reprogramming of Mouse Fibroblasts into Pulmonary Epithelial-Like Cells

    Kusumoto T, Ishii M, Yotsukura M, Hegab A. E, Saito F, Hamamoto J, Asakura T, Kamata H, Namkoong H, Suzuki S, Okamori S, Ogawa T, So M, Asamura H, Ieda M, Betsuyaku T

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

  163. Direct Reprogramming of Mouse Fibroblasts into Pulmonary Epithelial-Like Cells

    Kusumoto T., Ishii M., Yotsukura M., Hegab A. E., Saito F., Hamamoto J., Asakura T., Kamata H., Namkoong H., Suzuki S., Okamori S., Ogawa T., So M., Asamura H., Ieda M., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

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  164. Genome-Wide Association Study in Patients with Pulmonary Mycobacterium Avium Complex Disease

    Namkoong H., Omae Y., Asakura T., Yoshida M., Suzuki S., Morimoto K., Oler A. J., Szymanski E. P., Matsuda S., Yagi K., Ishii M., Hase I., Nishimura T., Sasaki Y., Asami T., Shiomi T., Matsubara H., Shimada H., Ato M., Kosaki K., Betsuyaku T., Kurashima A., Tettelin H., Olivier K. N., Hoshino Y., Holland S. M., Tokunaga K., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

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  165. Longitudinal Validity and Prognostic Significance of the St George's Respiratory Questionnaire in 269 Patients with Pulmonary Mycobacterium Avium Complex Disease

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

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  166. The Role of Histone Methyltransferase EZH2 in a Mouse Model of Bleomycin-Induced Pulmonary Fibrosis

    Okamori S., Ishii M., Suzuki S., Kusumoto T., Ogawa T., So M., Kamata H., Asakura T., Kagawa S., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

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  167. Ablation of ADAM17 protects against cigarette smoke-induced emphysema in mice

    S Suzuki, M Ishii, T Asakura, H Namkoong, S Okamori, K Yagi, H Kamata

    European Respiratory Journal 54 (suppl 63)   9 巻   2019年

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  168. The Role of Histone Methyltransferase EZH2 in a Mouse Model of Bleomycin-Induced Pulmonary Fibrosis

    Okamori S, Ishii M, Suzuki S, Kusumoto T, Ogawa T, So M, Kamata H, Asakura T, Kagawa S, Betsuyaku T

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

  169. Longitudinal Validity and Prognostic Significance of the St George's Respiratory Questionnaire in 269 Patients with Pulmonary Mycobacterium Avium Complex Disease

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

  170. Genome-Wide Association Study in Patients with Pulmonary Mycobacterium Avium Complex Disease

    Namkoong H, Omae Y, Asakura T, Yoshida M, Suzuki S, Morimoto K, Oler A. J, Szymanski E. P, Matsuda S, Yagi K, Ishii M, Hase I, Nishimura T, Sasaki Y, Asami T, Shiomi T, Matsubara H, Shimada H, Ato M, Kosaki K, Betsuyaku T, Kurashima A, Tettelin H, Olivier K. N, Hoshino Y, Holland S. M, Tokunaga K, Hasegawa N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   199 巻   2019年

  171. High fat diet activates adult mouse lung stem cells and accelerates several aging-induced effects

    Hegab Ahmed E., Ozaki Mani, Meligy Fatma Y., Kagawa Shizuko, Ishii Makoto, Betsuyaku Tomoko

    STEM CELL RESEARCH   33 巻   頁: 25 - 35   2018年12月

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    記述言語:英語   出版者・発行元:Stem Cell Research  

    High fat diet (HFD) decreases the lifespan of mice, and is a risk factor for several human diseases. Here, we investigated the effects of a HFD on lung epithelial and stem cells and its interaction with aging. Young and old mice were fed with either a standard diet (SD) or a HFD then their trachea and lung were examined for histological changes, inflammation, and mitochondrial function. Their stem cell function was examined using the in vitro organoid/colony forming efficiency (CFE) assay. Aging reduced the number of tracheal basal and alveolar type-2 (AT2) cells. HFD significantly increased the number of AT2 cells. Aging also caused a significant increase in lung inflammation, and HFD caused a similar increase, in young mice. Aging reduced mitochondrial mass and function, and increased reactive oxygen species. In young mice, HFD caused mitochondrial changes similar to the aging-induced changes. Organoid culture of tracheal and lung epithelial cells collected from both young and old HFD-fed mice showed higher CFE compared to SD-fed mice. Switching the HFD to low calorie/fat diet (LCD) efficiently reversed several of the HFD-induced effects. Thus, HFD induces several histological, inflammatory, and functional changes in the lung, and exacerbates the aging-induced lung inflammation and mitochondrial deterioration. LCD can reverse many of the HFD-induced effects.

    DOI: 10.1016/j.scr.2018.10.006

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

    Asakura Takanori, Yamada Yoshitake, Suzuki Shoji, Namkoong Ho, Okamori Satoshi, Kusumoto Tatsuya, Niijima Yuki, Ozaki Akihiko, Hashimoto Masahiro, Yagi Kazuma, Kamata Hirofumi, Funatsu Yohei, Ishii Makoto, Jinzaki Masahiro, Betsuyaku Tomoko, Hasegawa Naoki

    RESPIRATORY MEDICINE   145 巻   頁: 66 - 72   2018年12月

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    記述言語:英語   出版者・発行元:Respiratory Medicine  

    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.

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  173. Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b(+)Gr-1(+) cell expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine pulmonary emphysema

    Asakura Takanori, Ishii Makoto, Namkoong Ho, Suzuki Shoji, Kagawa Shizuko, Yagi Kazuma, Komiya Takaki, Hashimoto Takafumi, Okamori Satoshi, Kamata Hirofumi, Tasaka Sadatomo, Kihara Akio, Hegab Ahmed E., Hasegawa Naoki, Betsuyaku Tomoko

    MUCOSAL IMMUNOLOGY   11 巻 ( 6 ) 頁: 1606 - 1620   2018年11月

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    記述言語:英語   出版者・発行元: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.

    DOI: 10.1038/s41385-018-0077-5

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  174. ADAM17 protects mice against elastase-induced emphysema via inactivation of CD62L

    Suzuki Shoji, Ishii Makoto, Asakura Takanori, Namkoong Ho, Okamori Satoshi, Yagi Kazuma, Kamata Hirofumi, Kusumoto Tatsuya, Kagawa Shizuko, Hegab Ahmed, Horiuchi Keisuke, Hasegawa Naoki, Betsuyaku Tomoko

    EUROPEAN RESPIRATORY JOURNAL   52 巻   2018年9月

  175. Impact of six-minute walk test on health-related quality of life in pulmonary Mycobacterium avium complex disease

    Yagi Kazuma, Asakura Takanori, Namkoong Ho, Suzuki Shoji, Asami Takahiro, Okamori Satoshi, Kusumoto Tetsuya, Funatsu Yohei, Kamata Hirofumi, Nishimura Tomoyasu, Ishii Makoto, Betsuyaku Tomoko, Hasegawa Naoki

    EUROPEAN RESPIRATORY JOURNAL   52 巻   2018年9月

  176. Perfusion Defect-Concordant Progression of Unilateral Refractory Pulmonary Mycobacterium avium Complex Disease

    Asakura Takanori, Yamada Yoshitake, Ishii Makoto, Ebisudani Toshiki, Ueda Soichiro, Betsuyaku Tomoko, Hasegawa Naoki

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   198 巻 ( 6 ) 頁: 803 - 804   2018年9月

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    記述言語:英語   出版者・発行元:American Journal of Respiratory and Critical Care Medicine  

    DOI: 10.1164/rccm.201801-0173IM

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  177. 特集 呼吸器領域の抗菌薬の使い方 - 最新エビデンスから導く基本と応用 呼吸器領域における抗菌薬の使い方 マクロライド系薬

    石井 誠

    感染と抗菌薬   21 巻 ( 3 ) 頁: 185 - 191   2018年9月

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    出版者・発行元:(株)ヴァンメディカル  

    DOI: 10.34426/j03177.2019012928

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  178. Pulmonary nocardiosis mimicking small cell lung cancer in ectopic ACTH syndrome associated with transformation of olfactory neuroblastoma: a case report

    Kobayashi Keigo, Asakura Takanori, Ishii Makoto, Ueda Soichiro, Irie Hidehiro, Ozawa Hiroyuki, Saitoh Kohei, Kurihara Isao, Itoh Hiroshi, Betsuyaku Tomoko

    BMC PULMONARY MEDICINE   18 巻 ( 1 ) 頁: 142   2018年8月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: Pulmonary nocardiosis frequently develops as an opportunistic infection in cell-mediated immunosuppressive patients, and sometimes requires differentiation from pulmonary malignancy. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a neoplastic disorder which leads to impaired cell-mediated immunity, and is commonly associated with small cell lung cancer (SCLC). Because pulmonary infection and causative malignancy can appear as pulmonary lesions with EAS, differentiation of these diseases remains a critical issue for physicians. Case presentation: A 52-year-old woman with progressive lower limb paralysis and general fatigue was referred to us. She had been diagnosed with olfactory neuroblastoma (ONB) and treated with surgery and radiation therapy 10 years before the referral and had required stereotactic radiosurgery and chemotherapy 4 years later for a relapse of the ONB. On referral, she presented with Cushing's syndrome with elevated cortisol and ACTH levels. Potassium supplement improved her symptoms; however, a month later, she was urgently hospitalized due to acute pleuritic chest pain on inspiration. Chest computed tomography revealed left lower lobular consolidations and a contralateral nodule in the right middle lobe. The clinical history and laboratory work-up suggested that her Cushing's syndrome had most likely arisen from EAS. Additionally, the lungs were suspected as the ACTH source due to high levels of progastrin-releasing peptide and progressive pulmonary consolidation with a contralateral nodule, suggesting SCLC. However, histological examination from bronchoscopy revealed no evidence of malignancy, and Nocardia cyriacigeorgica was isolated from bronchoalveolar lavage fluid. Sulfamethoxazole/trimethoprim improved her pulmonary lesions. Somatostatin receptor scintigraphy revealed strong tracer uptake in the ONB lesions, indicating that the origin of the EAS was the olfactory tumor. However, histological examination of ONB specimens resected 10 years earlier showed no intracytoplasmic immunopositivity for ACTH. Conclusions: We highlight a rare case of pulmonary nocardiosis, which was associated with EAS mimicking SCLC, and was related to ONB transformation. Nocardiosis has to be considered even though anamnestic, clinical, and radiological aspects suggest the presence of metastasis. Additionally, physicians should carefully monitor patients with ONB for the development of Cushing's symptoms because the tumor can transform into an ACTH-producing form, even after long-term follow-up.

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  179. Association between six-minute walk test parameters and the health-related quality of life in patients with pulmonary Mycobacterium avium complex disease

    Yagi Kazuma, Asakura Takanori, Namkoong Ho, Suzuki Shoji, Asami Takahiro, Okamori Satoshi, Kusumoto Tatsuya, Funatsu Yohei, Kamata Hirofumi, Nishimura Tomoyasu, Ishii Makoto, Betsuyaku Tomoko, Hasegawa Naoki

    BMC PULMONARY MEDICINE   18 巻 ( 1 ) 頁: 114   2018年7月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: Pulmonary Mycobacterium avium complex (pMAC) disease is a chronic, slowly progressive disease. The aim of the present study was to determine the association of six-minute walk test (6MWT) parameters with pulmonary function and the health-related quality of life (HRQL) in patients with pMAC disease. Methods: This cross-sectional study included adult patients with pMAC and was conducted at Keio University Hospital. We investigated the relationship of 6MWT parameters with clinical parameters, including pulmonary function, and HRQL, which was assessed using the 36-Item Short Form Health Survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ). Results: In total, 103 consecutive patients with pMAC participated in 6MWT (median age, 64 years; 80 women) and completed SF-36 and SGRQ. The six-minute walk distance (6MWD) showed significant negative and positive correlations with all SGRQ domain scores [ρ = (- 0.54)-(- 0.32)] and the physical component summary (PCS) score (ρ = 0.39) in SF-36, respectively; the opposite was observed for the final Borg scale (FBS) score (all SGRQ scores, ρ = 0.34-0.58; PCS score, ρ = - 0.50). The distance-saturation product showed significant negative and positive correlations with all SGRQ scores [ρ = (- 0.29)-(- 0.55)] and the PCS score (ρ = 0.40), respectively. Multivariate analysis revealed that 6MWD and the FBS score were significant predictors of HRQL. Conclusions: Our findings suggest that 6MWD and the FBS score are useful parameters for evaluating HRQL in patients with pMAC. Further studies should investigate the impact of 6WMT parameters on disease progression, treatment responses, and prognosis.

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  180. Anti-aminoacyl tRNA synthetase antibody-positive clinically amyopathic dermatomyositis

    Ebisudani T., Asakura T., Ueda S., Ishii M., Betsuyaku T.

    QJM-AN INTERNATIONAL JOURNAL OF MEDICINE   111 巻 ( 6 ) 頁: 425 - 426   2018年6月

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    記述言語:英語   出版者・発行元:QJM  

    DOI: 10.1093/qjmed/hcy008

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  181. Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital

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

    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE   22 巻 ( 6 ) 頁: 695 - +   2018年6月

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    記述言語:英語   出版者・発行元:International Journal of Tuberculosis and Lung Disease  

    Background: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. Objectives : To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. Methods : This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged ≥75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. Results : In cross-sectional analyses, elderly patients with pMAC disease had significantly lower rolephysical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. Conclusions : Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

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  182. Mycobacterium triplex pulmonary disease with acquired macrolide resistance in immunocompetent patients

    Matsuda S., Suzuki S., Morimoto K., Aono A., Nishio K., Asakura T., Sasaki Y., Namkoong H., Nishimura T., Ogata H., Hasegawa N., Kurashima A., Ishii M., Tatsumi K., Mitarai S., Goto H.

    CLINICAL MICROBIOLOGY AND INFECTION   24 巻 ( 6 ) 頁: 671 - 672   2018年6月

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    記述言語:英語   出版者・発行元:Clinical Microbiology and Infection  

    DOI: 10.1016/j.cmi.2017.12.018

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  183. Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: A cross-sectional study

    Suzuki Shoji, Asakura Takanori, Namkoong Ho, Okamori Satoshi, Yagi Kazuma, Kamata Hirofumi, Uwamino Yoshifumi, Funatsu Yohei, Nakano Yasushi, Nishimura Tomoyasu, Ishii Makoto, Ebihara Tamotsu, Betsuyaku Tomoko, Hasegawa Naoki

    RESPIRATORY MEDICINE   138 巻   頁: 1 - 6   2018年5月

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    記述言語:英語   出版者・発行元:Respiratory Medicine  

    Rationale: Little is known about the role of Aspergillus precipitating antibody (APAb) in patients with Mycobacterium avium complex lung disease (MAC-LD). Objectives: We investigated the clinical characteristics of patients with MAC-LD positive for APAb. Methods: We conducted a cross-sectional study targeting patients with MAC-LD. APAb was checked in all participants. Clinical variables included laboratory data, pulmonary function, high-resolution computed tomography findings, and health-related quality of life. Results: We analyzed 109 consecutive patients. Their median age was 68 years, and the median duration of MAC-LD was 4.8 years. Twenty (18.3%) patients tested positive for APAb. APAb-positive patients had significantly longer duration of MAC-LD (9.4 vs. 4.0 years, P = 0.017), more severe bronchiectasis evaluated by modified Reiff score (6.5 vs. 4, P = 0.0049), and lower forced expiratory volume in 1 s (%FEV1) (75.1% vs. 86.2%, P = 0.013) than APAb-negative patients. Analysis of covariance adjusted for background factors and underlying pulmonary disease revealed that %FEV1 was also significantly lower in patients with APAb (P = 0.045). Ten patients were newly diagnosed with chronic pulmonary aspergillosis (N = 5) or allergic bronchopulmonary aspergillosis (N = 5). Conclusions: APAb is associated with lower pulmonary function, and observed especially in patients with longer duration of MAC-LD and severe bronchiectasis, even in the absence of cavitary lesions.

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  184. Bilateral upper lobe Pneumocystis pneumonia during aerosolized pentamidine prophylaxis

    Ohara Y., Asakura T., Ueda S., Yamada Y., Ishii M., Betsuyaku T.

    QJM-AN INTERNATIONAL JOURNAL OF MEDICINE   111 巻 ( 5 ) 頁: 337 - 338   2018年5月

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    記述言語:英語   出版者・発行元:QJM  

    DOI: 10.1093/qjmed/hcx233

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  185. Clarithromycin expands CD11b(+)Gr-1(+) cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

    Namkoong Ho, Ishii Makoto, Fujii Hideki, Yagi Kazuma, Asami Takahiro, Asakura Takanori, Suzuki Shoji, Hegab Ahmed E., Kamata Hirofumi, Tasaka Sadatomo, Atarashi Koji, Nakamoto Nobuhiro, Iwata Satoshi, Honda Kenya, Kanai Takanori, Hasegawa Naoki, Koyasu Shigeo, Betsuyaku Tomoko

    PLOS PATHOGENS   14 巻 ( 4 ) 頁: e1006955   2018年4月

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    記述言語:英語   出版者・発行元:PLoS Pathogens  

    Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+cells essential for the immunomodulatory properties of macrolides.

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  186. Anti-inflammatory roles of mesenchymal stromal cells during acute Streptococcus pneumoniae pulmonary infection in mice

    Asami Takahiro, Ishii Makoto, Namkoong Ho, Yagi Kazuma, Tasaka Sadatomo, Asakura Takanori, Suzuki Shoji, Kamo Tetsuro, Okamori Satoshi, Kamata Hirofumi, Zhang Haiyue, Hegab Ahmed E., Hasegawa Naoki, Betsuyaku Tomoko

    CYTOTHERAPY   20 巻 ( 3 ) 頁: 302 - 313   2018年3月

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    記述言語:英語   出版者・発行元:Cytotherapy  

    Background: Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia. Methods: Bone marrow–derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium. For in vivo studies, mice intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs or vehicle, and various parameters were assessed. Results: After stimulation with toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-α and interleukin (IL)–6 levels were significantly decreased, whereas IL-10 was significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection, and this was associated with a decrease in myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, including TNF-α IL-6, GM-CSF and IFN-γ were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. In addition, histopathologic analysis confirmed a decrease in the number of cells recruited to the lungs; however, lung edema, protein leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the BALF were comparable between the groups. Conclusions: These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumoniae.

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  187. Clinical characteristics of pulmonary Mycobacterium lentiflavum disease in adult patients

    Yagi Kazuma, Morimoto Kozo, Ishii Makoto, Namkoong Ho, Okamori Satoshi, Asakura Takanori, Suzuki Shoji, Asami Takahiro, Uwamino Yoshifumi, Funatsu Yohei, Fujiwara Hiroshi, Kamata Hirofumi, Nishimura Tomoyasu, Betsuyaku Tomoko, Kurashima Atsuyuki, Hasegawa Naoki

    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES   67 巻   頁: 65 - 69   2018年2月

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    記述言語:英語   出版者・発行元:International Journal of Infectious Diseases  

    Background Mycobacterium lentiflavum is a slow-growing non-tuberculous Mycobacterium that is often associated with an immunocompromised state and cervical lymphadenitis in young children. However, little is known about the clinical importance of pulmonary infection with M. lentiflavum in adults. Methods The medical records of all adults who met the diagnostic criteria of pulmonary M. lentiflavum disease at Keio University Hospital and Fukujuji Hospital from 2001 to 2015 were reviewed. In addition, the PubMed database was searched to identify further reported cases in non-HIV adults. Results Five cases of pulmonary M. lentiflavum disease were identified in the medical records search and 11 additional cases were identified in the literature review. Eleven of the total 16 cases were female, and 15 of 16 cases showed a nodular/bronchiectatic pattern on chest computed tomography imaging. No cases showed an aggressive clinical course of pulmonary M. lentiflavum disease, although one patient died of an exacerbation of underlying vasculitis and bacterial pneumonia. Conclusions The clinical characteristics of pulmonary M. lentiflavum disease in adult patients were identified. This disease mainly affects females, displays a nodular/bronchiectatic pattern on chest computed tomography imaging, and does not demonstrate an aggressive clinical course. Further larger studies are needed to reveal detailed clinical features.

    DOI: 10.1016/j.ijid.2017.12.001

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  188. Natural history of Mycobacterium fortuitum pulmonary infection presenting with migratory infiltrates: a case report with microbiological analysis

    Okamori Satoshi, Asakura Takanori, Nishimura Tomoyasu, Tamizu Eiko, Ishii Makoto, Yoshida Mitsunori, Fukano Hanako, Hayashi Yuichiro, Fujita Masaki, Hoshino Yoshihiko, Betsuyaku Tomoko, Hasegawa Naoki

    BMC INFECTIOUS DISEASES   18 巻 ( 1 ) 頁: 1   2018年1月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    Background: Presence of Mycobacterium fortuitum in respiratory tracts usually indicates mere colonization or transient infection, whereas true pulmonary infection occurs in patients with gastroesophageal disease. However, little is known about the diagnostic indications for true M. fortuitum pulmonary infection and the natural history of the disease. Case presentation: A 59-year-old man was referred to our hospital for treatment against M. fortuitum pulmonary infection. Fifteen years before the referral, he underwent total gastrectomy, after which he experienced esophageal reflux symptoms. After the referral, the patient was closely monitored without antimicrobial therapy because of mild symptoms and no pathological evidence of M. fortuitum pulmonary infection. During the observation, chest imaging showed migratory infiltrates. Two years after the referral, his lung biopsy specimen revealed foamy macrophages and multinucleated giant cells, indicating lipoid pneumonia. However, he was continually monitored without any treatment because there was no evidence of nontuberculous mycobacterial infection. Four years after the referral, he developed refractory pneumonia despite receiving adequate antibiotic therapy. After confirmation of granulomatous lesions, multiple antimicrobial therapy for M. fortuitum resulted in a remarkable improvement with no exacerbation for over 5 years. Random amplified polymorphic DNA polymerase chain reaction analysis revealed identical M. fortuitum strains in seven isolates from six sputum and one intestinal fluid specimens obtained during the course of the disease. Conclusions: We have described a patient with M. fortuitum pulmonary infection who presented with migratory infiltrates. The pathological evidence and microbiological analysis suggested that M. fortuitum pulmonary infection was associated with lipoid pneumonia and chronic exposure to gastrointestinal fluid. Therefore, physicians should carefully monitor patients with M. fortuitum detected from lower respiratory tract specimens and consider antimicrobial therapy for M. fortuitum infection when the patient does not respond to adequate antibiotic therapy against common pneumonia pathogens.

    DOI: 10.1186/s12879-017-2892-9

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  189. Analysis of Adverse Drug Events in Pulmonary Mycobacterium Avium Complex Disease Using the Japanese Adverse Drug Event Report (JADER) Database

    Namkoong H., Takahashi Y., Ishii M., Asakura T., Suzuki S., Kamata H., Yagi K., Betsuyaku T., Matsumoto K., Kizu J., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

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  190. Quantitative Assessment of Erector Spinae Muscles in Patients with Mycobacterium Avium Complex Lung Disease: Relationship of Disease Severity and Prognosis

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

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  191. The Development of Lung Cancer During Follow-Up of Patients with Mycobacterium Avium Complex Lung Disease

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

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  192. The Protective Role of a Disintegrin and Metalloprotease (ADAM) 10 During Severe Influenza Virus Infection

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

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  193. 1060: THE BERLIN DEFINITION OF ARDS SEVERITY IS ASSOCIATED WITH PROGNOSIS AND HIGH-RESOLUTION CT SCORES

    T Kamo, S Tasaka, T Suzuki, T Asakura, S Suzuki, I Makoto, M Hiroshi

    Critical Care Medicine 46 (1), 514     2018年

  194. The Protective Role of a Disintegrin and Metalloprotease (ADAM) 10 During Severe Influenza Virus Infection

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

  195. The Development of Lung Cancer During Follow-Up of Patients with Mycobacterium Avium Complex Lung Disease

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

  196. Quantitative Assessment of Erector Spinae Muscles in Patients with Mycobacterium Avium Complex Lung Disease: Relationship of Disease Severity and Prognosis

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

  197. Intermittent Cigarette Smoke Promotes Proliferation of Alveolar Epithelial Type 2 Cells More than the Continuous Cigarette Smoke

    Irie H, Chubachi S, Tsutsumi A, Kameyama N, Sakurai K, Ozaki M, Ishii M, Hegab A. E, Betsuyaku T

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

  198. Analysis of Adverse Drug Events in Pulmonary Mycobacterium Avium Complex Disease Using the Japanese Adverse Drug Event Report (JADER) Database

    Namkoong H, Takahashi Y, Ishii M, Asakura T, Suzuki S, Kamata H, Yagi K, Betsuyaku T, Matsumoto K, Kizu J, Hasegawa N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   197 巻   2018年

  199. Impact of chronic Pseudomonas aeruginosa infection on health-related quality of life in Mycobacterium avium complex lung disease

    Kamata Hirofumi, Asakura Takanori, Suzuki Shoji, Namkoong Ho, Yagi Kazuma, Funatsu Yohei, Okamori Satoshi, Uno Shunsuke, Uwamino Yoshifumi, Fujiwara Hiroshi, Nishimura Tomoyasu, Ishii Makoto, Betsuyaku Tomoko, Hasegawa Naoki

    BMC PULMONARY MEDICINE   17 巻 ( 1 ) 頁: 198   2017年12月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: In bronchiectasis patients, chronic Pseudomonas aeruginosa (PA) infection has been associated with worse health-related quality of life (HRQL), but little is known about Mycobacterium avium complex lung disease (MACLD) patients in this context. This study aimed to evaluate HRQL and investigate the impact of chronic PA infection in MACLD patients. Methods: This cross-sectional study was conducted using the Registry of Prospective Cohort Study including MACLD patients. The 36-item Short-Form health survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ) were administered to assess clinical outcomes. Clinical variables included treatment and sputum culture status, pulmonary function tests, cavitary lesions, and modified Reiff scores on high-resolution computed tomography. Results: The study included 244 MACLD patients (median age, 68 years; 196 women), 19 of whom had chronic PA infection. Modified Reiff score was higher in patients with chronic infection than in those without (P=0.028). Regarding SF-36 scores, physical functioning subscale scores were significantly lower in patients with chronic infection (P=0.029). Additionally, SGRQ symptoms, impact, and total scores were significantly higher in patients with chronic infection. During analysis of covariance comparisons, SGRQ symptoms and impact scores were significantly higher for patients with chronic infection (P=0.043 and 0.021, respectively). Conclusions: MACLD patients with chronic PA infection exhibited significantly higher SGRQ scores, indicating impaired HRQL. Chronic PA infection was significantly associated with the severity of bronchiectasis.

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  200. Suspected accelerated disease progression after discontinuation of nintedanib in patients with idiopathic pulmonary fibrosis Two case reports

    Okamori Satoshi, Asakura Takanori, Masuzawa Keita, Yasuda Hiroyuki, Kamata Hirofumi, Ishii Makoto, Betsuyaku Tomoko

    MEDICINE   96 巻 ( 49 ) 頁: e9081   2017年12月

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    記述言語:英語   出版者・発行元:Medicine (United States)  

    Rational: The efficacy of nintedanib, a multitarget receptor tyrosine kinase inhibitor, has been demonstrated in recent randomized controlled trials involving patients with idiopathic pulmonary fibrosis (IPF). However, accelerated disease progression after nintedanib discontinuation has never been reported. Patient concerns: We report 2 cases involving patients with a history of IPF who presented with respiratory deterioration at 3 weeks after the discontinuation of nintedanib therapy for IPF. Neither patient fulfilled the definition of "acute exacerbation of IPF" on unilateral computed tomography. Diagnoses: Accelerated disease progression after the discontinuation of nintedanib therapy for IPF. Interventions: One patient received steroid therapy. The other patient refused to undergo steroid therapy. Outcomes: The first patient showed that the affected lobe exhibited volume loss with traction bronchiectasis after receiving steroid therapy, and succumbed to pneumothorax after 3 months. The other patient was transferred to another hospital because of a decline in his general condition. Lessons: To our knowledge, this report is the first to document accelerated disease progression after the discontinuation of nintedanib therapy for IPF. Although the accurate mechanism remains unclear, the effects of nintedanib against vascular endothelial growth factor and platelet-derived growth factor receptor may play a role. Our findings suggest that physicians should carefully monitor patients with IPF after nintedanib discontinuation.

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  201. Clinical and radiological characteristics of patients with late-onset severe restrictive lung defect after hematopoietic stem cell transplantation

    Namkoong Ho, Ishii Makoto, Mori Takehiko, Sugiura Hiroaki, Tasaka Sadatomo, Sakurai Masatoshi, Koda Yuya, Kato Jun, Hasegawa Naoki, Okamoto Shinichiro, Betsuyaku Tomoko

    BMC PULMONARY MEDICINE   17 巻 ( 1 ) 頁: 123   2017年9月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: Late-onset noninfectious pulmonary complications (LONIPCs), which occur more than 3months after allogeneic hematopoietic stem cell transplantation (HSCT), are major causes of morbidity and mortality after transplantation. Among LONIPCs, we occasionally treat patients with late-onset severe restrictive lung defect after HSCT; however, its clinical features have not been fully elucidated. Methods: A retrospective chart review of a single center on cases of late-onset severe restrictive lung defect after HSCT was performed. Among 453 patients who survived longer than 100days after allogeneic HSCT with evaluable spirometry data, 12 patients (2.6%) developed late-onset severe restrictive lung defect (i.e., vital capacity percent of predicted less than 60%). Results: Median duration from transplantation to diagnosis of late-onset severe restrictive lung defect cases was 44.5months. Major computed tomography (CT) finding was pleuroparenchymal thickening with volume loss, an evidence of fibrosis, predominantly in upper lobes (n=7), which was consistent with pleuroparenchymal fibroelastosis. The remaining patients showed unclassifiable interstitial pneumonia pattern (n=2) and airway-predominant pattern (n=3). The diffusing capacity for carbon oxide tended to decrease, while the residual volume/total lung capacity ratio tended to increase after HSCT. Of 12 patients, 8 patients died and the median month from diagnosis to death was 33.5months. Seven patients died of pulmonary or systemic infection, and one patient died due to relapse of the primary disease. Conclusion: Severe restrictive lung defect could develop in selected cases in the late-phase after HSCT and could be a unique clinical entity with specific radiographical findings.

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  202. The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases

    Yagi Kazuma, Ishii Makoto, Namkoong Ho, Asami Takahiro, Iketani Osamu, Asakura Takanori, Suzuki Shoji, Sugiura Hiroaki, Yamada Yoshitake, Nishimura Tomoyasu, Fujiwara Hiroshi, Funatsu Yohei, Uwamino Yoshifumi, Kamo Tetsuro, Tasaka Sadatomo, Betsuyaku Tomoko, Hasegawa Naoki

    BMC INFECTIOUS DISEASES   17 巻 ( 1 ) 頁: 558   2017年8月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    Background: In multidrug regimens, including an intravenous aminoglycoside (e.g. amikacin [AMK]) is recommended for difficult-to-treat non-tuberculous mycobacterial (NTM) lung diseases. We aimed to evaluate the efficacy, safety, and feasibility of inhaled AMK therapy in patients with difficult-to-treat NTM lung diseases in a retrospective chart review. Methods: The study population consisted of patients with NTM lung diseases who received combination therapy, including inhaled AMK therapy, at Keio University Hospital (Tokyo, Japan), from January 2014 through May 2016. A total of 26 cases, consisting of 23 Mycobacterium avium complex (MAC) and three Mycobacterium abscessus complex (MABC) infections cases, were included in this study. The efficacy, safety, and feasibility of inhaled AMK therapy were retrospectively investigated. The Research Ethics Committee of Keio University Hospital approved this study, and informed consent was obtained from all patients. Results: All 26 patients were culture-positive at enrolment. Twenty-three of the 26 patients (88.5%), including 21/23 MAC patients (91.3%) and 2/3 MABC patients (66.7%), were administered inhaled AMK therapy for >3months. The proportion of patients who had clinical symptoms, including, cough and sputum, declined after inhalation AMK therapy. Ten of the 23 patients (43.5%) who received AMK inhalation, including 8/21 MAC (38.1%) and 2/2 MABC patients (100%), showed sputum conversion, defined as at least three consecutive negative sputum cultures. Seven of the 23 patients, including, 5/21 MAC and 2/2 MABC patients, showed improvements in high-resolution computed tomography imaging of the chest. In addition, the serum AMK trough levels before the second inhalation were <1.2μg/mL in all 26 patients, with no occurrence of severe adverse events, such as renal toxicity. One patient (3.8%) experienced auditory toxicity, in the form of tinnitus. However, this symptom was reversible, after temporary interruption of AMK, the patient was able to safely resume the therapy. Conclusions: Inhaled AMK therapy is an effective and feasible therapy for difficult-to-treat NTM lung disease.

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  203. Long-term Outcome of Pulmonary Resection for Nontuberculous Mycobacterial Pulmonary Disease

    Asakura Takanori, Hayakawa Nobutaka, Hasegawa Naoki, Namkoong Ho, Takeuchi Ken, Suzuki Shoji, Ishii Makoto, Betsuyaku Tomoko, Abe Yoshiaki, Ouchi Motofumi

    CLINICAL INFECTIOUS DISEASES   65 巻 ( 2 ) 頁: 244 - 251   2017年7月

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    記述言語:英語   出版者・発行元:Clinical Infectious Diseases  

    Background. Pulmonary resection along with multiple antimicrobial therapy has produced favorable outcomes at a few centers. However, little is known regarding the risk factors for long-term survival and microbiological recurrence after pulmonary resection for nontuberculous mycobacterial pulmonary disease (NTMPD). We evaluated the long-term outcomes of pulmonary resection, including microbiological recurrence and survival. Methods. This retrospective cohort study included 125 patients (median age, 60 years) with NTMPD treated by pulmonary resection at two referral centers between January 1994 and August 2015. Results. Postoperative complications occurred in 27 patients (22%). The complication rate after pneumonectomy was significantly higher than those after other types of pulmonary resection (odds ratio, 4.1; 95% confidence interval [CI], 1.6-10.3; P =.005). The median follow-up period was 7.1 years. While 19 patients experienced microbiological recurrence, 26 died. Multivariate analysis revealed pneumonectomy (adjusted hazard ratio [aHR], 0.12; 95% CI,.007-.66; P =.0098) and cavitary lesions after surgery (aHR, 6.73; 95% CI, 1.68-22.7; P =.0095) to be predictors of microbiological recurrence and old age (aHR, 1.06; 95% CI, 1.01-1.13; P =.016), low body mass index (BMI; aHR for every 1-kg/m 2 increase, 0.72; 95% CI,.60-.85; P <.0001), pneumonectomy (aHR, 4.38; 95% CI, 1.78-11.3; P =.014), and remnant cavitary lesions (aHR, 3.53; 95% CI, 1.35-9.57; P =.011) to be predictors of poor prognosis. Conclusions. Patients who could benefit from pulmonary resection should be carefully selected considering age, BMI, remnant lesions after surgery, and type of pulmonary resection.

    DOI: 10.1093/cid/cix274

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  204. Impact of cavity and infiltration on pulmonary function and health-related quality of life in pulmonary Mycobacterium avium complex disease: A 3-dimensional computed tomographic analysis

    Asakura Takanori, Yamada Yoshitake, Namkoong Ho, Suzuki Shoji, Niijima Yuki, Kamata Hirofumi, Funatsu Yohei, Yagi Kazuma, Okamori Satoshi, Sugiura Hiroaki, Ishii Makoto, Jinzaki Masahiro, Betsuyaku Tomoko, Hasegawa Naoki

    RESPIRATORY MEDICINE   126 巻   頁: 9 - 16   2017年5月

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    記述言語:英語   出版者・発行元:Respiratory Medicine  

    Background and objectives Pulmonary Mycobacterium avium complex (pMAC) disease manifests as various types of lesions, such as infiltrates, nodules, cavities, and bronchiectasis. However, the important determinants for clinical parameters in lung involvement are poorly understood. The objective of this study was to obtain quantitative parameters by 3-dimensional CT, and investigate the relationship between these parameters and the pulmonary function tests (PFTs) and health-related quality of life. Material and methods Quantitative analysis using CT was performed in 67 pMAC patients. The relationship between new quantitative parameters for evaluating lung involvement using 3-dimensional CT and PFTs or St George's Respiratory Questionnaire (SGRQ) was evaluated. Results The ratio of infiltration to total lung volume showed significant correlation with the PFT results, especially the percent-predicted forced vital capacity (%FVC; ρ = −0.52), residual volume (ρ = −0.51), and total lung capacity (ρ = −0.59). The cavity volume was strongly correlated with the %FVC (ρ = −0.78) in the cavity group, while the ratio of infiltration to total lung volume was strongly correlated with the %FVC (ρ = −0.53) in the non-cavity group. The ratio of infiltration to total lung volume was significantly correlated with all SGRQ parameters (ρ = 0.41–0.52) in the non-cavity group. Conclusions Infiltration was an important parameter for the PFTs and SGRQ in pMAC patients according to the 3-dimensional CT analysis. Moreover, cavity volume was an important parameter of the PFTs in the cavity group. Therefore, infiltration and cavity volume are key features for the management of pMAC disease.

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  205. Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung

    Kuroda Aoi, Hegab Ahmed E., Jingtao Gao, Yamashita Shuji, Hizawa Nobuyuki, Sakamoto Tohru, Yamada Hideyasu, Suzuki Satoshi, Ishii Makoto, Namkoong Ho, Asakura Takanori, Ozaki Mari, Yasuda Hiroyuki, Hamamoto Junko, Kagawa Shizuko, Soejima Kenzo, Betsuyaku Tomoko

    RESPIRATORY RESEARCH   18 巻 ( 1 ) 頁: 69   2017年4月

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    記述言語:英語   出版者・発行元:Respiratory Research  

    Background: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. Methods: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice. Results: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice. Conclusions:ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect.

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  206. Pulmonary Cryptococcosis Developed from a Nodule after Treatment with Infliximab for Arthritis Associated with Ulcerative Colitis

    Asakura Takanori, Arai Daisuke, Ishii Makoto, Takei Hiroshi, Sugiura Hiroaki, Takeuchi Tsutomu, Betsuyaku Tomoko

    ANNALS OF THE AMERICAN THORACIC SOCIETY   14 巻 ( 4 ) 頁: 603 - +   2017年4月

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    記述言語:英語   出版者・発行元:Annals of the American Thoracic Society  

    DOI: 10.1513/AnnalsATS.201612-952LE

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  207. 【呼吸器病学TOPICS 2016-17】 感染症・結核 マクロライド系抗菌薬の新作用の研究の進歩

    石井, 誠

    分子呼吸器病   21 巻 ( 1 ) 頁: 34 - 36   2017年3月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)   出版者・発行元:先端医学社  

    CiNii Books

  208. 【呼吸器病学TOPICS 2016-17】 感染症・結核 マクロライド系抗菌薬の新作用の研究の進歩

    石井, 誠

    分子呼吸器病   21 巻 ( 1 ) 頁: 34 - 36   2017年3月

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    記述言語:日本語   掲載種別:研究論文(その他学術会議資料等)  

  209. 肺細胞学の新展開 直接リプログラミングによる肺上皮細胞の分化誘導法の検討 査読有り

    四倉 正也, 石井 誠, 齋藤 史武, Hegab Ahmed E., 浜本 純子, 南宮 湖, 家田 真樹, 淺村 尚生, 別役 智子

    日本呼吸器学会誌   6 巻 ( 増刊 ) 頁: 128 - 128   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  210. 難治性肺疾患に対する新たな治療法の開発を目指した直接リプログラミングによる肺再生法の確立

    石井, 誠

    大和証券ヘルス財団研究業績集   ( 40 ) 頁: 34 - 36   2017年3月

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    記述言語:日本語  

  211. A Case Of Cutis Laxa With Juvenile Emphysema Arising From Frameshift Mutations In Exon 30 Of The Elastin Gene (eln)

    Namkoong H., Ishii M., Yagi K., Chubachi S., Tsuji A., Kosaki K., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195 巻   2017年

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  212. Protective Role Of A Disintegrin And Metalloprotease 17 (adam17) In Elastase-Induced Emphysema In Mice

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195 巻   2017年

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  213. The Critical Role Of A Disintegrin And Metalloprotease (adam) 10 During Severe Influenza Virus Infection In Vivo And In Vitro

    Okamori S., Ishii M., Asakura T., Suzuki S., Kamata H., Namkoong H., Yagi K., Kagawa S., Kamo T., Asami T., Horiuchi K., Betsuyaku T., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195 巻   2017年

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  214. Sternoclavicular joint osteomyelitis extending to lung abscess complicated by Staphylococcal infective endocarditis

    Masuzawa K., Asakura T., Ishii M., Yasuda H., Sugiura H., Betsuyaku T.

    IDCases   9 巻   頁: 36 - 37   2017年

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    記述言語:英語   出版者・発行元:IDCases  

    DOI: 10.1016/j.idcr.2017.04.005

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  215. S1p Receptor Modulation Expands Cd11b+gr-1+Cells And Inhibits Lymphocyte Infiltration In The Lungs And Ameliorate Murine Pulmonary Emphysema

    Asakura T., Ishii M., Namkoong H., Suzuki S., Kagawa S., Komiya T., Yagi K., Kamata H., Okamori S., Asami T., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195 巻   2017年

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  216. Macrolide-Resistant Mycobacterium avium Complex Lung Disease: Analysis of 102 Consecutive Cases

    Morimoto Kozo, Namkoong Ho, Hasegawa Naoki, Nakagawa Taku, Morino Eriko, Shiraishi Yuji, Ogawa Kenji, Izumi Kiyohiko, Takasaki Jin, Yoshiyama Takashi, Hoshino Yoshihiko, Matsuda Shuichi, Hayashi Yuta, Sasaki Yuka, Ishii Makoto, Kurashima Atsuyuki, Nishimura Tomoyasu, Betsuyaku Tomoko, Goto Hajime

    ANNALS OF THE AMERICAN THORACIC SOCIETY   13 巻 ( 11 ) 頁: 1904 - 1911   2016年11月

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    記述言語:英語   出版者・発行元:Annals of the American Thoracic Society  

    Rationale: The management of macrolide-resistant Mycobacterium aviumcomplex (MR-MAC)pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB). Objectives: This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB. Methods: The medical records of 102 consecutive cases with MR-MACpulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014were reviewed.The data of 311 consecutive caseswith MDR-TB were extracted from the medical data at Fukujuji Hospital. Measurements and Main Results: Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC. Conclusions: Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

    DOI: 10.1513/AnnalsATS.201604-246OC

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  217. Histone Deacetylase Inhibition Protects Mice Against Lethal Postinfluenza Pneumococcal Infection

    Yagi Kazuma, Ishii Makoto, Namkoong Ho, Fujii Hideki, Asami Takahiro, Suzuki Shoji, Asakura Takanori, Mizoguchi Kosuke, Kamo Tetsuro, Tasaka Sadatomo, Iwata Satoshi, Kunkel Steven L., Hasegawa Naoki, Betsuyaku Tomoko

    CRITICAL CARE MEDICINE   44 巻 ( 10 ) 頁: E980 - E987   2016年10月

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    記述言語:英語   出版者・発行元:Critical Care Medicine  

    Objectives: Secondary bacterial pneumonia following influenza virus infection is associated with high mortality, but the mechanism is largely unknown. Epigenetic gene regulation appears to play key roles in innate and adaptive immunity. We hypothesized that histone acetylation, a major epigenetic mechanism associated with transcriptionally active chromatin, might contribute to the poor outcome of postinfluenza pneumonia. Design: Prospective experimental study. Setting: University research laboratory. Subjects: C57BL/6 male mice. Interventions: Mice were infected intranasally with 1.0 × 10 4 colony-forming units of Streptococcus pneumoniae, 7 days after intranasal inoculation with five plaque-forming units of influenza virus A/H1N1/PR8/34. The mice were intraperitoneally injected with the histone deacetylase inhibitor trichostatin A (1 mg/kg) or vehicle once a day from 1 hour after pneumococcal infection throughout the course of the experiment. The primary outcome was survival rate. Measurements and Main Results: Trichostatin A significantly suppressed histone deacetylase activity and significantly improved the survival rate of mice (56.3%) after postinfluenza pneumococcal infection when compared with vehicle-treated mice (20.0%), which was associated with a significant decrease in the total cell count of the bronchoalveolar lavage fluid. The interleukin-1β level in the serum and the number of natural killer cells in the lungs were significantly lower in the trichostatin A-treated group. Conclusions: The histone deacetylase inhibitor trichostatin A protects mice against postinfluenza pneumonia possibly through multiple factors, including decreasing local cell recruitment into the lungs and suppressing systemic inflammation.

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  218. Successful treatment of non-small-cell lung cancer with afatinib and a glucocorticoid following gefitinib- and erlotinib-induced interstitial lung disease: A case report.

    Tani T, Naoki K, Asakura T, Hirano T, Suzuki S, Masuzawa K, Hasegawa H, Kuroda A, Yasuda H, Ishii M, Soejima K, Betsuyaku T

    Molecular and clinical oncology   5 巻 ( 4 ) 頁: 488 - 490   2016年10月

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    記述言語:英語  

    DOI: 10.3892/mco.2016.981

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  219. Clinical efficacy and safety of multidrug therapy including thrice weekly intravenous amikacin administration for Mycobacterium abscessus pulmonary disease in outpatient settings: a case series

    Namkoong Ho, Morimoto Kozo, Nishimura Tomoyasu, Tanaka Hiromu, Sugiura Hiroaki, Yamada Yoshitake, Kurosaki Atsuko, Asakura Takanori, Suzuki Shoji, Fujiwara Hiroshi, Yagi Kazuma, Ishii Makoto, Tasaka Sadatomo, Betsuyaku Tomoko, Hoshino Yoshihiko, Kurashima Atsuyuki, Hasegawa Naoki

    BMC INFECTIOUS DISEASES   16 巻 ( 1 ) 頁: 396   2016年8月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    Background: Mycobacterium abscessus (M. abscessus) pulmonary disease is a refractory chronic infectious disease. Options for treating M. abscessus pulmonary disease are limited, especially in outpatient settings. Among parenteral antibiotics against M. abscessus, intravenous amikacin (AMK) is expected to be an effective outpatient antimicrobial therapy. This study evaluated the clinical efficacy and safety of intravenous AMK therapy in outpatients with M. abscessus pulmonary disease. Methods: This retrospective chart review of cases of M. abscessus pulmonary disease evaluated patient background data, AMK dosage and duration, sputum conversion, clinical symptoms radiological findings, and adverse events. M. massiliense was excluded on the basis of multiplex PCR assay. Results: Thirteen patients (2 men and 11 women) with M. abscessus pulmonary disease were enrolled at 2 hospitals. The median age at the initiation of intravenous AMK treatment was 65 years (range: 50-86 years). Patients received a median AMK dose of 12.5 mg/kg (range: 8.3-16.2 mg/kg) for a median duration of 4 months (range: 3-9 months). The addition of intravenous AMK led to sputum conversion in 10 of 13 patients, and 8 patients continued to have negative sputum status 1 year after treatment. Approximately half of the patients showed improvement on chest high-resolution computed tomography. There were no severe adverse events such as ototoxicity, vestibular toxicity, and renal toxicity. Conclusions: Thrice weekly intravenous AMK administration in outpatient settings is effective and safe for patients with M. abscessus pulmonary disease.

    DOI: 10.1186/s12879-016-1689-6

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  220. Pneumothorax associated with nontuberculous mycobacteria A retrospective study of 69 patients

    Ueyama M., Asakura Takanori, Morimoto Kozo, Namkoong Ho, Matsuda Shuichi, Osawa Takeshi, Ishii Makoto, Hasegawa Naoki, Kurashima Atsuyuki, Goto Hajime

    MEDICINE   95 巻 ( 29 ) 頁: e4246   2016年7月

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    記述言語:英語   出版者・発行元:Medicine (United States)  

    The incidence of nontuberculous mycobacterial pulmonary disease (NTMPD) is increasing worldwide. Secondary spontaneous pneumothorax occurs as a complication of underlying lung disease and is associated with higher morbidity, mortality, and recurrence than primary spontaneous pneumothorax. We here investigated the clinical features and long-term outcomes of pneumothorax associated with NTMPD. We conducted a retrospective study on consecutive adult patients with pneumothorax associated with NTMPD at Fukujuji Hospital and Keio University Hospital from January 1992 to December 2013. We reviewed the medical records of 69 such patients to obtain clinical characteristics, radiological findings, and long-term outcomes, including pneumothorax recurrence and mortality. The median age of the patients was 68 years; 34 patients were women. The median body mass index was 16.8kg/m2. Underlying pulmonary diseases mainly included chronic obstructive pulmonary disease and pulmonary tuberculosis. On computed tomography, nodules and bronchiectasis were observed in 46 (98%) and 45 (96%) patients, respectively. Consolidation, pleural thickening, interlobular septal thickening, and cavities were most common, and observed in 40 (85%), 40 (85%), 37 (79%), and 36 (77%) patients, respectively. Regarding pneumothorax treatment outcomes, complete and incomplete lung expansion were observed in 49 patients (71%) and 15 patients (22%), respectively. The survival rate after pneumothorax was 48% at 5 years. By the end of the follow-up, 33 patients had died, and the median survival was 4.4 years with a median follow-up period of 1.7 years. The rate of absence of recurrence after the first pneumothorax was 59% at 3 years. By the end of the follow-up, 18 patients had experienced pneumothorax recurrence. Furthermore, 12/18 patients (66%) with recurrent pneumothorax died during the study period. Twentythree patients (70%) died because of NTMPD progression. Low body mass index (BMI) was a negative prognostic factor for pneumothorax associated with NTMPD in multivariate analysis (HR 0.79, 95% CI 0.64-0.96; P=0.018) Patients with pneumothorax associated with NTMPD have advanced disease, a high rate of pneumothorax recurrence, and poor prognosis, regardless of the pneumothorax treatment used. Further improvements in early diagnosis of NTMPD and appropriate management in both NTMPD and NTMPD-associated pneumothorax are needed.

    DOI: 10.1097/MD.0000000000004246

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  221. Multiple nodular lesions following Pneumocystis pneumonia in a non-HIV immunocompromised patient.

    Asakura T, Kameyama N, Ishii M, Kawada I, Tasaka S, Soejima K, Betsuyaku T

    Clinical case reports   4 巻 ( 5 ) 頁: 528 - 30   2016年5月

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    記述言語:英語  

    DOI: 10.1002/ccr3.555

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  222. Levels of soluble receptor for advanced glycation end products in bronchoalveolar lavage fluid in patients with various inflammatory lung diseases

    Kamo T., Tasaka S., Tokuda Y., Suzuki S., Asakura T., Yagi K., Namkoong H., Ishii M., Hasegawa N., Betsuyaku T.

    Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine   9 巻   頁: 147 - 154   2016年4月

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    出版者・発行元:Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine  

    Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis.

    DOI: 10.4137/CCRPRPM.S23326

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  223. Pneumococcal Infection Aggravates Elastase-Induced Emphysema via Matrix Metalloproteinase 12 Overexpression

    Takahashi Saeko, Ishii Makoto, Namkoong Ho, Hegab Ahmed E., Asami Takahiro, Yagi Kazuma, Sasaki Mamoru, Haraguchi Mizuha, Sato Minako, Kameyama Naofumi, Asakura Takanori, Suzuki Shoji, Tasaka Sadatomo, Iwata Satoshi, Hasegawa Naoki, Betsuyaku Tomoko

    JOURNAL OF INFECTIOUS DISEASES   213 巻 ( 6 ) 頁: 1018 - 1030   2016年3月

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    記述言語:英語   出版者・発行元:Journal of Infectious Diseases  

    Background. Acute exacerbation of chronic obstructive pulmonary disease (COPD) - typically caused by bacterial or viral infection - is associated with poor prognosis and emphysema progression through unknown mechanisms. We aimed to elucidate the mechanisms responsible for the poor prognosis and emphysema progression associated with COPD exacerbation. Methods. We established a mouse model mimicking acute human COPD exacerbation, wherein mice with elastase-induced emphysema were intranasally infected with Streptococcus pneumoniae. Results. In mice with elastase-induced emphysema, infection with S. pneumoniae resulted in increased mortality, an increased number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and increased matrix metalloproteinase 12 (MMP-12) production in the lungs, as well as enhanced emphysema progression. The increased MMP-12 production was mostly due to alveolar type II cells, alveolar macrophages, and lymphocytes that aggregated around vessels and bronchioles. Dexamethasone treatment suppressed the mortality rate and number of inflammatory cells in BALF but not emphysema progression, possibly owing to the failure of MMP-12 suppression in the lungs, whereas treatment with the MMP inhibitor ONO-4817 dramatically suppressed both mortality rate and emphysema progression. Conclusions. These results suggest that MMP-12 production during COPD exacerbation results in increased mortality and emphysema progression. Our study identifies MMP-12 as a target to prevent further aggravation of COPD.

    DOI: 10.1093/infdis/jiv527

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  224. Disseminated Mycobacterium marinum Infection With a Destructive Nasal Lesion Mimicking Extranodal NK/T Cell Lymphoma A Case Report

    Asakura Takanori, Ishii Makoto, Kikuchi Taku, Kameyama Kaori, Namkoong Ho, Nakata Noboru, Sugita Kayoko, Tasaka Sadatomo, Shimizu Takayuki, Hoshino Yoshihiko, Okamoto Shinichiro, Betsuyaku Tomoko, Hasegawa Naoki

    MEDICINE   95 巻 ( 11 ) 頁: e3131   2016年3月

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    記述言語:英語   出版者・発行元:Medicine (United States)  

    Mycobacterium marinum is a ubiquitous waterborne organism that mainly causes skin infection in immunocompetent patients, and its disseminated infection is rare. Extranodal NK/T cell lymphoma, nasal type (ENKL) usually localizes at the nasal and/or paranasal area, but occasionally disseminates into the skin/soft tissue and gastrointestinal tract. Compromised immunity is a risk factor for developing nontuberculous mycobacterial (NTM) infection and malignant lymphoma, and the 2 diseases may share similar clinical presentation; however, only a few reports have described NTM infection mimicking malignant lymphoma. A 43-year-old Japanese man presented to our hospital complaining of multiple progressive skin nodules and purulent nasal discharge for 3 weeks. He was diagnosed with Crohn disease with refractory enteropathic arthritis and has been treated with anti-tumor necrosis factor alpha agents for 25 years. Fiberoptic nasal examination revealed septal perforation with hemorrhagic mucus and purulent rhinorrhea. Histological examination of the nasal septum revealed the infiltration of atypical medium-to-large-sized cells with erosion. The cells were positive for cytoplasmic CD3, granzyme B, and Epstein-Barr virusencoded small RNA. Histological examination of the skin nodules and auricle also showed infiltration of atypical lymphocytes. The patient was tentatively diagnosed with ENKL, and chemotherapy was considered. However, the skin lesions decreased in size after discontinuation of immunosuppressive agents and minocycline administration. Two weeks later, nasal septum and lavage fluid and left leg skin cultures were positive for M marinum, and minocycline was discontinued. The skin and the nasal lesions improved after 2 months. To the best of our knowledge, this is the first case of disseminated M marinum infection with a destructive nasal lesion mimicking ENKL. The differentiation between M marinum infection and ENKL is clinically important because misdirected treatment leads to a poor prognosis. NTM infections including M marinum should be considered in differential diagnosis of ENKL. Bacterial cultures, pathological analysis, and close monitoring are required for the differentiation of ENKL and disseminated M marinum infection; both are serious diseases and early diagnostic distinction between them and immediate appropriate treatment will improve the patient's prognosis.

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  225. マクロライド剤の宿主免疫系への作用

    石井, 誠

    The Japanese Journal of Antibiotics   69 巻 ( Suppl.A ) 頁: 5 - 7   2016年3月

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    記述言語:日本語  

  226. 医薬品副作用データベース(JADER)を用いた肺Mycobacterium avium complex(MAC)症の化学療法の有害事象解析 査読有り

    南宮 湖, 高橋 佑介, 松元 一明, 石井 誠, 田坂 定智, 別役 智子, 木津 純子, 長谷川 直樹

    日本呼吸器学会誌   5 巻 ( 増刊 ) 頁: 194 - 194   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  227. 肺細胞の分化・機能の新知見 直接リプログラミングによる肺上皮細胞の分化誘導法の検討 査読有り

    四倉 正也, 石井 誠, 齋藤 史武, Hegab Ahmad E., 浜本 純子, 南宮 湖, 家田 真樹, 淺村 尚生, 別役 智子

    日本呼吸器学会誌   5 巻 ( 増刊 ) 頁: 143 - 143   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  228. 特集 呼吸器疾患における慢性炎症を考える 感染免疫と炎症

    石井 誠

    呼吸と循環   64 巻 ( 2 ) 頁: 119 - 124   2016年2月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1404205896

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  229. Blue - black trachea as a result of minocycline-induced hyperpigmentation

    Asakura T., Nukaga S., Namkoong H., Yagi K., Suzuki S., Ishii M., Tasaka S., Betsuyaku T., Hasegawa N.

    American Journal of Respiratory and Critical Care Medicine   193 巻 ( 3 ) 頁: e5 - e6   2016年2月

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    記述言語:英語   出版者・発行元:American Journal of Respiratory and Critical Care Medicine  

    DOI: 10.1164/rccm.201508-1527IM

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  230. Theory and strategy for Pneumococcal vaccines in the elderly

    Namkoong Ho, Ishii Makoto, Funatsu Yohei, Kimizuka Yoshifumi, Yagi Kazuma, Asami Takahiro, Asakura Takanori, Suzuki Shoji, Kamo Testuro, Fujiwara Hiroshi, Tasaka Sadatomo, Betsuyaku Tomoko, Hasegawa Naoki

    HUMAN VACCINES & IMMUNOTHERAPEUTICS   12 巻 ( 2 ) 頁: 336 - 343   2016年2月

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    記述言語:英語   出版者・発行元:Human Vaccines and Immunotherapeutics  

    Pneumonia is the fourth-leading cause of death globally, and Streptococcus pneumoniae is the most important causative pathogen. Because the incidence of pneumococcal diseases is likely to increase with the aging society, we should determine an optimal strategy for pneumococcal vaccination. While consensus indicates that 23-valent pneumococcal polysaccharide vaccine prevents invasive pneumococcal diseases (IPD), its effects on community-acquired pneumonia (CAP) remain controversial. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was released. The latest clinical study (CAPiTA study) showed that PCV13 reduced vaccine-type CAP and IPD. Based on these results, the Advisory Committee on Immunization Practices recommended initial vaccination with PCV13 for the elderly. Scientific evidence regarding immunosenescence is needed to determine a more ideal vaccination strategy for the elderly with impaired innate and adaptive immunity. Continuing research on the cost effectiveness of new vaccine strategies considering constantly changing epidemiology is also warranted.

    DOI: 10.1080/21645515.2015.1075678

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  231. Fournier's gangrene: a surgical emergency

    Namkoong Ho, Ishii Makoto, Koizumi Masayuki, Betsuyaku Tomoko

    INFECTION   44 巻 ( 1 ) 頁: 143 - 144   2016年2月

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    記述言語:英語   出版者・発行元:Infection  

    DOI: 10.1007/s15010-015-0816-4

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  232. Inflammation in infection and immunity

    Ishii M.

    Respiration and Circulation   64 巻 ( 2 ) 頁: 119 - 124   2016年2月

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    出版者・発行元:Respiration and Circulation  

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  233. Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001-2011: A case series and literature review

    Suzuki Shoji, Morino Eriko, Ishii Makoto, Namkoong Ho, Yagi Kazuma, Asakura Takanori, Asami Takahiro, Fujiwara Hiroshi, Uwamino Yoshifumi, Nishimura Tomoyasu, Tasaka Sadatomo, Betsuyaku Tomoko, Takasaki Jin, Iwata Satoshi, Hasegawa Naoki

    JOURNAL OF INFECTION AND CHEMOTHERAPY   22 巻 ( 9-10 ) 頁: 611 - 616   2016年

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    記述言語:英語   出版者・発行元:Journal of Infection and Chemotherapy  

    Background Mycobacterium scrofulaceum is a well-known pathogen associated with cervical lymphadenitis in children. However, pulmonary M. scrofulaceum disease is a rare condition with unknown clinical features. The present study aimed to clarify the clinical features of pulmonary M. scrofulaceum disease described in recent cases and reports. Methods We reviewed the medical records of all adult patients with pulmonary M. scrofulaceum disease at Keio University Hospital and the National Center for Global Health and Medicine Center Hospital between 2001 and 2011. We also conducted a review of the PubMed database to identify additional cases of pulmonary M. scrofulaceum disease in adults. Results Our study identified 8 cases of pulmonary M. scrofulaceum disease at the 2 identified institutions during our study period. Most cases were diagnosed in middle-aged and elderly men with underlying pulmonary diseases such as chronic obstructive pulmonary disease and Mycobacterium avium complex lung disease, as well as those with a history of pulmonary tuberculosis. In contrast, most previously reported cases identified through our literature review had a history of dust inhalation or underlying silicosis. Three of 8 cases at our institutions and 20 of 23 cases from the literature were treated with combination therapies. Conclusions We conclude that in the recent histories of our institutions, pulmonary M. scrofulaceum disease has mainly occurred in patients with chronic pulmonary diseases. We further conclude that combination therapies that include clarithromycin might yield better patient outcomes.

    DOI: 10.1016/j.jiac.2016.06.006

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  234. 3-Deazaneplanocin A-An Inhibitor Of Histone Methyltransferase Ezh2-Exacerbates Elastase-Induced Emphysema In Mice

    Asakura T., Ishii M., Namkoong H., Yagi K., Suzuki S., Tanosaki T., Kagawa S., Kamo T., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193 巻   2016年

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  235. Critical Role Of The Prostaglandin D2 Receptor Crth2 In Acute Lung Injury Caused By Lipopolysaccharide (LPS)-Induced Shock In Mice

    Suzuki S., Ishii M., Asami T., Namkoong H., Yagi K., Asakura T., Kamata H., Tasaka S., Kagawa S., Kamo T., Asano K., Nakamura M., Hirai H., Nagata K., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193 巻   2016年

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  236. Obesity Worsens The Outcome Of Influenza Virus Infection Via Impaired Ifn -Beta Induction And Reduced Expressions Of Antimicrobial Peptides In Mice

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

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193 巻   2016年

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  237. The Berlin Definition Criteria Of Ards Severity Is Associated With Prognosis And Fibroproliferative Changes On High-Resolution CT

    Kamo T., Tasaka S., Suzuki T., Asakura T., Suzuki S., Yagi K., Namkoong H., Ishii M., Morisaki H., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193 巻   2016年

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  238. Pharmacokinetics of intravenous peramivir in the airway epithelial lining fluid of healthy volunteers

    Funatsu Yohei, Tasaka Sadatomo, Asami Takahiro, Namkoong Ho, Fujiwara Hiroshi, Iketani Osamu, Yagi Kazuma, Kimizuka Yoshifumi, Ishii Makoto, Nishimura Tomoyasu, Ogata Haruhiko, Iwata Satoshi, Betsuyaku Tomoko, Hasegawa Naoki

    ANTIVIRAL THERAPY   21 巻 ( 7 ) 頁: 621 - 625   2016年

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    記述言語:英語   出版者・発行元:Antiviral Therapy  

    Background: Some subtypes of influenza virus, such as H5N1 and H7N9, cause severe viral pneumonia, for which the intraluminal concentration of the anti-influenza agent in the airway is critical. However, the pharmacokinetics of peramivir, the only available injectable neuraminidase inhibitor formulation, in the airway epithelial lining fluid (ELF) remains unclear. In this study, we aimed to determine the time course of peramivir in the pharyngeal ELF, bronchial ELF and plasma of healthy volunteers using bronchoscopic microsampling technique. Methods: Six healthy volunteers were studied. After baseline plasma sampling, 0.3 g peramivir was intravenously injected over 0.5 h. ELF was obtained from the upper and lower airways using bronchoscopic microsampling at the end of the infusion (0.5 h) and after 1.0, 1.5, 2.0, 2.5, 3.0, 4.0 and 5.0 h. The concentrations of peramivir in the ELFs and in the plasma were quantified by LC/MS/MS analysis. Results: The mean maximum concentration (Cmax) in pharyngeal ELF, bronchial ELF and plasma was 1.20 ±0.42, 9.60 ±2.30 and 50.52 ±17.51 ng/ml, respectively. The penetration ratio at Cmax in pharyngeal and bronchial ELFs was 2.4 and 19.0, respectively. The ratio of the area under the curve from 0 to infinity in pharyngeal and bronchial ELFs was 4.8 and 39.1 mg•min/l, respectively. Conclusions: The time course of peramivir concentration in the ELFs revealed that concentrations above the 50% inhibitory concentration value of influenza were achieved in the upper and lower airways. Therefore, peramivir could be an important treatment option for influenza viral pneumonia.

    DOI: 10.3851/IMP3096

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  239. P1-55 抗IFNγ中和自己抗体が検出された播種性NTM症の3例

    南宮 湖, 西村 知泰, 中村 朗, 朝倉 崇徳, 鈴木 翔二, 加茂 徹郎, 鎌田 浩史, 石井 誠, 長谷川 直樹, 別役 智子

    日本臨床免疫学会会誌   39 巻 ( 4 ) 頁: 402a - 402a   2016年

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    記述言語:日本語   出版者・発行元:日本臨床免疫学会  

    <p>  【背景】近年,既知の免疫不全を有さず,播種性NTM症を発症した患者の一部から抗IFNγ中和自己抗体の検出が報告されているが,その臨床的特徴は十分に明らかではない.【症例1】70代女性.喀痰・胸水・気管支肺胞洗浄液・肺組織・尿・肝臓・骨髄からMACを認め,播種性MAC症の診断となる.化学療法により病勢の改善を認め,2年間で治療終了とした.その後,微熱・全身倦怠感を認め,精査の結果,骨髄からMACの検出を認めた.【症例2】60代男性.腋窩リンパ節膿瘍を契機に,播種性MAC症の診断となる.化学療法を開始し改善を認めた.経過中に皮膚掻痒・肝機能障害を新規に認め,ERCPを施行した所,胆汁培養からMACの検出を認めた.【症例3】70代男性.頸部リンパ節・腹腔内リンパ節腫脹を認め,悪性リンパ腫疑いで紹介.頚部リンパ節の培養検査でDDH法では同定不能の抗酸菌を認めた.16S rRNAによる解析で<i>M. genavense</i>を同定した.【考察】抗IFNγ中和自己抗体が陽性の播種性NTM症の3例を経験した.長期間に及ぶ化学療法を施行しても,骨髄や肝臓内にNTMを認めた.</p>

    DOI: 10.2177/jsci.39.402a

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  240. The Histone Deacetylase Inhibitor Trichostatin A Protects Mice Against Lethal Post-Influenza Pneumococcal Infection

    Yagi K., Ishii M., Namkoong H., Asami T., Asakura T., Suzuki S., Fujiwara H., Nishimura T., Kamo T., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193 巻   2016年

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  241. The Histone Deacetylase Inhibitor Trichostatin A Protects Mice Against Lethal Post-Influenza Pneumococcal Infection

    Yagi, K, Ishii, M, Namkoong, H, Asami, T, Asakura, T, Suzuki, S, Fujiwara, H, Nishimura, T, Kamo, T, Tasaka, S, Hasegawa, N, Betsuyaku, T

    American Journal of Respiratory and Critical Care Medicine   193 巻   2016年

  242. Health-related quality of life is inversely correlated with C-reactive protein and age in Mycobacterium avium complex lung disease: a cross-sectional analysis of 235 patients

    Asakura Takanori, Funatsu Yohei, Ishii Makoto, Namkoong Ho, Yagi Kazuma, Suzuki Shoji, Asami Takahiro, Kamo Tetsuro, Fujiwara Hiroshi, Uwamino Yoshifumi, Nishimura Tomoyasu, Tasaka Sadatomo, Betsuyaku Tomoko, Hasegawa Naoki

    RESPIRATORY RESEARCH   16 巻 ( 1 ) 頁: 145   2015年12月

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    記述言語:英語   出版者・発行元:Respiratory Research  

    Background: Mycobacterium avium complex (MAC) lung diseases generally cause chronic disease in immunocompetent hosts. Although a few studies have examined health-related quality of life (HRQL) in patients with MAC lung disease, there have been no large studies. This study aimed to evaluate HRQL and its correlation with clinical outcomes in MAC lung disease. Methods: A cross-sectional study was conducted at Keio University Hospital to investigate the factors associated with HRQL in pulmonary nontuberculous mycobacterial diseases. MAC lung diseases were diagnosed according to the 2007 ATS/IDSA guidelines for nontuberculous mycobacterial diseases. The 36-item short form health survey (SF-36) was administered to assess clinical outcomes. Clinical variables included treatment status, latest haematological data, and bacterial smear and culture results. Results: The SF-36 scores for the 235 patients (median age, 69years; 45 men and 190 women) with MAC lung disease, except for the bodily pain and mental health subscale scores, were significantly lower than the Japanese population norms. In the multivariable analyses, current treatment for MAC and a positive sputum smear or culture within the past year were significantly associated with lower SF-36 scores. C-reactive protein (CRP) and age showed stronger inverse correlations with SF-36 scores. Conclusions: HRQL, especially the physical component, was impaired in patients with MAC lung diseases; this appears to be related with current treatment status, positive sputum smear or culture within the previous year, and particularly CRP and age. Further studies including qualitative assessments are needed to investigate the efficacy of CRP as a marker for progression or treatment response in MAC lung disease. Trial registration: Clinical trial registered with UMIN (UMIN000007964 ).

    DOI: 10.1186/s12931-015-0304-5

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  243. 【感染症における新薬開発のジレンマと展望-日本が先駆者となるために-】 感染症治療薬の新しい試み エピジェネティクスの可能性

    石井, 誠

    化学療法の領域   32 巻 ( 1 ) 頁: 107 - 114   2015年12月

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    記述言語:日本語  

    エピジェネティクスとは、DNA配列の変化をともなわない遺伝子発現・情報を調節する機構を言う。発生学や腫瘍学などの分野でのエピジェネティクスの重要性は確立されているが、近年では感染症学でもエピジェネティクスの重要性が報告され、研究が進みつつある。本稿では、筆者らが検討を行ってきた敗血症やインフルエンザウイルス感染症を中心に、エピジェネティクスの関与に関して概説する。呼吸器感染症におけるエピジェネティクスの関与の詳細が明らかになれば、抗菌薬に加え、将来的にはエピジェネティクスをターゲットとした創薬により、エピジェネティクスの調整による治療の可能性が広がると考えられる。(著者抄録)

  244. Pneumococcal Infection Aggravates Elastase-Induced Emphysema via MMP-12 Overexpression

    S. Takahashi, M. Ishii, H. Namkoong, A. E. Hegab, T. Asami, K. Yagi, M. Sasaki, M. Haraguchi, M. Sato, N. Kameyama, T. Asakura, S. Suzuki, S. Tasaka, S. Iwata, N. Hasegawa, T. Betsuyaku

    J Infect Dis     2015年11月

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    記述言語:英語  

    BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD)-typically caused by bacterial or viral infection-is associated with poor prognosis and emphysema progression through unknown mechanisms. We aimed to elucidate the mechanisms responsible for the poor prognosis and emphysema progression associated with COPD exacerbation. METHODS: We established a mouse model mimicking acute human COPD exacerbation, wherein mice with elastase-induced emphysema were intranasally infected with Streptococcus pneumoniae. RESULTS: In mice with elastase-induced emphysema, infection with S. pneumoniae resulted in increased mortality, number of inflammatory cells in bronchoalveolar lavage fluid (BALF), and matrix metalloproteinase (MMP)-12 production in the lungs, as well as enhanced emphysema progression. The increased MMP-12 production was mostly due to alveolar type II cells, alveolar macrophages, and lymphocytes that aggregated around vessels and bronchioles. Dexamethasone treatment suppressed the mortality rate and number of inflammatory cells in BALF but not emphysema progression, possibly due to the failure of MMP-12 suppression in the lungs, whereas treatment with the MMP inhibitor ONO-4817 dramatically suppressed both mortality rate and disease progression. CONCLUSION: These results suggest that MMP-12 production during COPD exacerbation results in increased mortality and emphysema progression. Our study identifies MMP-12 as a target to prevent further aggravation of COPD.

  245. Dry pleurisy complicating solitary pulmonary nodules caused by Mycobacterium avium: A case report

    Asakura T., Ishii M., Haraguchi M., Kamiyama I., Kohno M., Sakamaki H., Emoto K., Hayashi Y., Sugiura H., Kawada I., Soejima K., Namkoong H., Tasaka S., Hasegawa N., Betsuyaku T.

    Journal of Medical Case Reports   9 巻 ( 1 ) 頁: 238   2015年10月

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    記述言語:英語   出版者・発行元:Journal of Medical Case Reports  

    Introduction: Mycobacterium avium complex (MAC) lung disease presenting as a solitary pulmonary nodule (MAC-SPN) is often asymptomatic, is more common in middle to old age, and mimics lung cancer or tuberculoma. We report herein a case of MAC-SPN in an immunocompetent young adult patient, presenting with persistent chest pain and a subacutely progressive nodule with high intense 18F-fluorodeoxyglucose uptake. Histological examination of resected specimens revealed pleurisy, which is a rare finding of MAC-SPN. Case presentation: A 36-year-old Japanese male presented with chest pain and a subacutely progressive pulmonary nodule. Positron emission tomography-computed tomography showed high intense 18F-fluorodeoxyglucose uptake in the nodule. Owing to his continuous chest pain and subacutely progressive nodules, wedge resection was performed using video-assisted thoracoscopic surgery. Histological examination revealed an epithelioid granuloma and pleurisy, and the lung tissue culture was positive for mycobacteria identified as M. avium. Conclusion: This is the first report of MAC-SPN occurring with persistent chest pain, suggesting that MAC should be considered in the differential diagnosis of a solitary pulmonary nodule, even for patients who experience persistent chest pain. As in the present case, surgical resection with video-assisted thoracoscopic surgery is a reasonable approach to the diagnosis and treatment of MAC-SPN with possible malignancy, especially as MAC can be diagnosed using resected lung tissue culture with histological confirmation.

    DOI: 10.1186/s13256-015-0723-4

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  246. Successful resumption of tocilizumab for rheumatoid arthritis after resection of a pulmonary Mycobacterium avium complex lesion: a case report

    Namkoong Ho, Tasaka Sadatomo, Akiyama Mitsuhiro, Yagi Kazuma, Ishii Makoto, Suzuki Katsuya, Kohno Mitsutomo, Hasegawa Naoki, Takeuchi Tsutomu, Betsuyaku Tomoko

    BMC PULMONARY MEDICINE   15 巻 ( 1 ) 頁: 126   2015年10月

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    記述言語:英語   出版者・発行元:BMC Pulmonary Medicine  

    Background: Biological agents inhibiting TNF-aα and other molecules involved in inflammatory cascade have been increasingly used to treat rheumatoid arthritis (RA). However, it remains controversial whether biological agents can be used safely in a patient with an underlying chronic infectious disease. Case presentation: A 63-year-old woman who had been treated with tocilizumab (TCZ), anti-interleukin-6 receptor antibody, for RA presented to our outpatient clinic due to hemoptysis. She was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection, and high-resolution computed tomography (HRCT) showed a single cavitary lesion in the right upper lobe. After diagnosis of pulmonary MAC disease, TCZ was discontinued and combination chemotherapy with clarithromycin, rifampicin, ethambutol and amikacin was started for MAC pulmonary disease. Since the lesion was limited in the right upper lobe as a single cavity formation, she underwent right upper lobectomy. As her RA symptoms were deteriorated around the operation, TCZ was resumed. After resumption of TCZ, her RA symptoms improved and a recurrence of pulmonary MAC infection has not been observed for more than 1 year. Conclusion: This case suggested that TCZ could be safely reintroduced after the resection of a pulmonary MAC lesion. Although the use of biological agents is generally contraindicated in patients with pulmonary MAC disease, especially in those with a fibrocavitary lesion, a multimodality intervention for MAC including both medical and surgical approaches may enable introduction or resumption of biological agents.

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  247. Immune reconstitution inflammatory syndrome due to Mycobacterium avium complex successfully followed up using (18) F-fluorodeoxyglucose positron emission tomography-computed tomography in a patient with human immunodeficiency virus infection: A case report

    Namkoong Ho, Fujiwara Hiroshi, Ishii Makoto, Yagi Kazuma, Haraguchi Mizuha, Matsusaka Masako, Suzuki Shoji, Asakura Takanori, Asami Takahiro, Saito Fumitake, Fukunaga Koichi, Tasaka Sadatomo, Betsuyaku Tomoko, Hasegawa Naoki

    BMC MEDICAL IMAGING   15 巻 ( 1 ) 頁: 24   2015年7月

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    記述言語:英語   出版者・発行元:BMC Medical Imaging  

    Background: In human immunodeficiency virus (HIV)-infected patients, immune reconstitution inflammatory syndrome (IRIS) due to nontuberculous mycobacteria (NTM) infection is one of the most difficult types of IRIS to manage. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) has been suggested as a useful tool for evaluating the inflammatory status of HIV-infected patients. We present the first case of Mycobacterium avium complex (MAC)-associated IRIS (MAC-IRIS) that was successfully followed up using 18 F-FDG PET/CT. Case presentation: A 44-year-old homosexual Japanese man was referred to our hospital with fever and dyspnea. He was diagnosed with Pneumocystis jiroveci pneumonia and found to be HIV positive. After the initiation of combined antiretroviral therapy (cART), the patient's mediastinal and bilateral hilar lymphadenopathy gradually enlarged, and bilateral infiltrates appeared in the upper lung fields. 18 F-FDG PET/CT was performed five months after the initiation of cART and showed intense accumulation of fluorodeoxyglucose (FDG) corresponding to the lesions of infiltration as well as the mediastinal and bilateral hilar lymphadenopathy. A bronchial wash culture and pathology findings led to a diagnosis of MAC-IRIS. Anti-mycobacterial chemotherapy with rifampicin, ethambutol, clarithromycin, and levofloxacin was started. One year after the chemotherapy was initiated, there was a significant reduction in FDG uptake in the area of the lesions except in the mediastinal lymph node. This implied incomplete resolution of the MAC-IRIS-related inflammation. Anti-mycobacterial chemotherapy was continued because of the residual lesion. To date, the patient has not experienced a recurrence of MAC-IRIS, a period of nine months. Conclusion: We present a case of MAC-IRIS in an HIV-infected patient whose disease FDG PET/CT is useful for evaluating the disease activity of NTM-IRIS and assessing the appropriate duration of anti-mycobacterial chemotherapy for NTM-IRIS in HIV-infected patients.

    DOI: 10.1186/s12880-015-0063-2

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  248. Fatal fulminant pneumonia caused by methicillin-sensitive staphylococcus aureus negative for major high-virulence factors following influenza B virus infection

    Masaki K., Ishii M., Anraku M., Namkoong H., Miyakawa R., Nakajima T., Fukunaga K., Naoki K., Tasaka S., Soejima K., Sayama K., Sugita K., Iwata S., Cui L., Hanaki H., Hasegawa N., Betsuyaku T.

    American Journal of Case Reports   16 巻   頁: 454 - 458   2015年7月

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    記述言語:英語   出版者・発行元:American Journal of Case Reports  

    Objective: Rare disease Background: Increasing evidence has indicated that Staphylococcus aureus pneumonia complicated with influenza virus infection is often fatal. In these cases, disease severity is typically determined by susceptibility to antimicrobial agents and the presence of high-virulence factors that are produced by Staphylococcus aureus, such as Panton- Valentine leukocidin (PVL). Case Report: We describe a rare case of fatal community-acquired pneumonia caused by methicillin-sensitive Staphylococcus aureus (MSSA), which did not secrete major high-virulence factors and coexisted with influenza type B infection. The 32-year-old previously healthy male patient presented with dyspnea, high fever, and cough. His roommate had been diagnosed with influenza B virus infection 3 days earlier. Gram-positive clusters of cocci were detected in the patient’s sputum; therefore, he was diagnosed with severe pneumonia and septic shock, and was admitted to the intensive care unit. Despite intensive antibiotic and antiviral treatment, he died of multiple organ failure 5 days after admission. His blood culture from the admission was positive for MSSA, and further analysis revealed that the strain was negative for major high-virulence factors, including PVL and enterotoxins, although influenza B virus RNA was detected by PCR. Conclusions: Physicians should pay special attention to patients with pneumonia following influenza and Staphylococcus aureus infection, as it may be fatal, even if the Staphylococcus aureus strain is PVL-negative and sensitive to antimicrobial agents.

    DOI: 10.12659/AJCR.894022

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  249. Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior

    Hegab Ahmed E., Arai Daisuke, Gao Jingtao, Kuroda Aoi, Yasuda Hiroyuki, Ishii Makoto, Naoki Katsuhiko, Soejima Kenzo, Betsuyaku Tomoko

    STEM CELL RESEARCH   15 巻 ( 1 ) 頁: 109 - 121   2015年7月

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    記述言語:英語   出版者・発行元:Stem Cell Research  

    The niche surrounding stem cells regulate their fate during homeostasis and after injury or infection. The 3D organoid assay has been widely used to study stem cells behavior based on its capacity to evaluate self-renewal, differentiation and the effect of various medium supplements, drugs and co-culture with supportive cells. We established an assay to study both lung and trachea stem cells in vitro. We characterized their proliferation and differentiation spectrum at baseline then evaluated the effect of co-culturing with fibroblasts and endothelial cells and/or treating with several biologically relevant substances as possible contributors to their niche. We found that lung epithelial (but not tracheal basal) stem cells require co-culture with stromal cells to undergo clonal proliferation and differentiation. Fibroblasts were more efficient than endothelial cells in offering this support and the pattern of support varied based on the tissue origin of the stromal cells. Treating distal lung epithelial or basal stem cells with FGF2, FGF9, FGF10, LIF as well as ALK5 and ROCK inhibitors increased their colony formation efficiency and resulted in variable effects on colonies number, size and differentiation spectrum. This model and findings pave the way for better understanding of lung stem cell niche components and factors that can manipulate lung stem cell behavior.

    DOI: 10.1016/j.scr.2015.05.005

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  250. 左主気管支内腔へ突出する腫瘤を認めたMACによる免疫再構築症候群の一例 査読有り

    南宮 湖, 藤原 宏, 八木 一馬, 松坂 雅子, 原口 水葉, 斎藤 史武, 石井 誠, 福永 興壱, 猶木 克彦, 長谷川 直樹, 別役 智子

    気管支学   37 巻 ( Suppl. ) 頁: S292 - S292   2015年5月

  251. The diagnostic usefulness of <sup>18</sup>F-fluorodoxyglucosepositron emission tomography/CT in SAPHO syndrome

    Namkoong H., Ishii M., Tasaka S., Betsuyaku T.

    BMJ Case Reports   2015 巻   2015年3月

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    記述言語:英語   出版者・発行元:BMJ Case Reports  

    DOI: 10.1136/bcr-2015-209394

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  252. 造血幹細胞移植後に晩発性の高度拘束性肺換気障害を呈した特発性肺炎症候群の臨床的特徴

    南宮 湖, 石井 誠, 八木 一馬, 田坂 定智, 長谷川 直樹, 杉浦 弘明, 櫻井 政寿, 甲田 祐也, 加藤 淳, 森 毅彦, 岡本 真一郎, 別役 智子

    分子呼吸器病   19 巻 ( 1 ) 頁: 140 - 144   2015年3月

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    記述言語:日本語   出版者・発行元:(株)先端医学社  

    過去20年間で造血幹細胞移植後に肺機能検査を行った453例のうち晩発性の高度拘束性肺換気障害を呈した特発性肺炎症候群(IPS)症例12例(男女各6例:発症率2.6%)を対象に、臨床的特徴について後ろ向きに検討した。その結果、移植時年齢は30代、40代で各5例、原疾患は急性リンパ性白血病5例、急性骨髄性白血病3例であった。経過観察中の死亡は8例、IPS発症後の生存中央値は33.5ヵ月であり、呼吸器感染症による呼吸不全での死亡や気胸合併の割合が高かった。画像所見では上葉優位の胸膜直下線維化/容積減少7例、気胸6例、気管支拡張・Air Trapping 5例を認め、肺機能は感染や気胸を契機に増悪する傾向を認めた。

  253. 私達の研究 重症呼吸器感染症における免疫機構の解明 新たな治療法確立に向けて

    石井 誠, 南宮 湖, 浅見 貴弘, 八木 一馬, 高橋 左枝子, 田坂 定智, 長谷川 直樹, 別役 智子

    化学療法の領域   31 巻 ( 3 ) 頁: 468 - 477   2015年2月

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    記述言語:日本語   出版者・発行元:(株)医薬ジャーナル社  

    呼吸器感染症や敗血症は重篤な致死的疾患であり、わが国でもこれらの感染症は全死因の上位を占めている。また、慢性閉塞性肺疾患(chronic obstructive lung disease:COPD)も死因の上位を占め、なかでも感染を契機としたCOPD増悪により致死的となることが多い。我々はおもに、これらの重症呼吸器感染症やCOPDにおける免疫制御機構の検討をマウスモデルを用いて行っている。本稿では、特に、(1)Lipopolysaccharide(LPS)ショックにおけるマクロライド系抗菌薬の免疫調整作用、(2)間葉系幹細胞のインフルエンザ感染における免疫調整作用、(3)インフルエンザなどの重症感染症におけるエピジェネティクスの関与、(4)COPD増悪モデルの作成と同モデルを用いた病態の解析の4つの研究に関して紹介したい。(著者抄録)

  254. 非HIV感染者における非結核性抗酸菌菌血症に関する臨床的検討

    上蓑 義典, 藤原 宏, 杉田 香代子, 西村 知泰, 石井 誠, 田坂 定智, 岩田 敏, 長谷川 直樹

    結核   90 巻 ( 2 ) 頁: 291 - 291   2015年2月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

  255. Comparison of the immunogenicity and safety of polysaccharide and protein-conjugated pneumococcal vaccines among the elderly aged 80 years or older in Japan: An open-labeled randomized study

    Namkoong Ho, Funatsu Yohei, Oishi Kazunori, Akeda Yukihiro, Hiraoka Rika, Takeshita Kei, Asami Takahiro, Yagi Kazuma, Kimizuka Yoshifumi, Ishii Makoto, Tasaka Sadatomo, Suzuki Yukio, Iwata Satoshi, Betsuyaku Tomoko, Hasegawa Naoki

    VACCINE   33 巻 ( 2 ) 頁: 327 - 332   2015年1月

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    記述言語:英語   出版者・発行元:Vaccine  

    An open-labeled randomized study was conducted to compare the immunogenicity and safety of polysaccharide (PPV23) or protein-conjugated pneumococcal vaccine (PCV7) among the elderly aged 80 years or older. A total of 105 nursing home residents were enrolled in this study. We analyzed the geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) and the geometric mean titer (GMT) of the opsonization index (OI) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The GMCs of serotype-specific IgG and the GMTs of the OI significantly increased one month after vaccination in both groups for all seven serotypes evaluated. In the PCV7 group, study subjects with serotypes 4, 9V, 18C, and 23F exhibited statistically significant elevations in both serotype-specific IgGs and OIs compared to those of the PPV23 group. Both vaccines were tolerated without any severe adverse events, and no differences in systemic adverse events were observed between the two groups, although adverse reactions such as redness and localized swelling were more common in the PCV7 group. Our data demonstrated that the GMCs of serotype-specific IgG and the GMTs of the OI were higher in the PCV7 group compared to those in the PPV23 group. Our study also confirmed the safety of both the PCV7 and PPV23 vaccines in elderly people aged 80 years or older.

    DOI: 10.1016/j.vaccine.2014.11.023

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  256. Clarithromycin Expands Cd11b+gr-1+cells To Ameliorate Post-Influenza Pneumococcal Pneumonia

    Namkoong H., Ishii M., Fujii H., Yagi K., Asakura T., Suzuki S., Kamo T., Tasaka S., Hasegawa N., Koyasu S., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191 巻   2015年

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  257. Health-Related Quality Of Life In 235 Patients With Mycobacterium Avium Complex Lung Disease In Japan

    Asakura T., Ishii M., Funatsu Y., Yagi K., Namkoong H., Suzuki S., Kamo T., Asami T., Fujiwara H., Uwamino Y., Nishimura T., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191 巻   2015年

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  258. P27-2 左主気管支内腔へ突出する腫瘤を認めたMACによる免疫再構築症候群の一例(炎症性疾患に対する気管支鏡診断,Posterセッション27,第38回日本呼吸器内視鏡学会学術集会)

    南宮 湖, 藤原 宏, 八木 一馬, 松坂 雅子, 原口 水葉, 斎藤 史武, 石井 誠, 福永 興壱, 猶木 克彦, 長谷川 直樹, 別役 智子

    気管支学   37 巻 ( Special ) 頁: S292   2015年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.37.special_s292_2

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  259. The Critical Roles Of Tumor Necrosis Factor a-Converting Enzyme During Influenza Virus And Streptococcus Pneumoniae Infection In Vivo And In Vitro

    Suzuki S., Ishii M., Namkoong H., Yagi K., Asakura T., Tasaka S., Kamo T., Kagawa S., Fujiwara H., Nishimura T., Horiuchi K., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191 巻   2015年

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  260. Role Of Histone Acetylation In Mice Coinfected With Influenza Virus And Streptococcus Pneumoniae

    Yagi K., Ishii M., Namkoong H., Asami T., Asakura T., Suzuki S., Fujiwara H., Nishimura T., Kamo T., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191 巻   2015年

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  261. The reasons for triple therapy in stable COPD patients in Japanese clinical practice

    Miyazaki Masaki, Nakamura Hidetoshi, Takahashi Saeko, Chubachi Shotaro, Sasaki Mamoru, Haraguchi Mizuha, Terai Hideki, Ishii Makoto, Fukunaga Koichi, Tasaka Sadatomo, Soejima Kenzo, Asano Koichiro, Betsuyaku Tomoko

    INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE   10 巻   頁: 1053 - 1059   2015年

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    記述言語:英語   出版者・発行元:International Journal of COPD  

    Background: Triple combination therapy involving long-acting muscarinic antagonists long-acting β2 agonists, and inhaled corticosteroids has recently become an option for maintenance treatment of COPD. Some add-on clinical trials have reported the benefits of these combinations. However, the process to step up to triple therapy varies for individual cases. Methods: Keio University and affiliated hospitals conducted an observational COPD cohort study, recruiting patients diagnosed as having COPD by pulmonary physicians and those referred for investigation of possible COPD. Their prescription history and clinical course were retrospectively analyzed based on the physicians’ medical records and patient questionnaires. This study was registered with UMIN (UMIN000003470, April 10, 2010). Results: A total of 95 of the 445 COPD patients (21%) were treated with inhaled corticosteroids/long-acting β2 agonists/long-acting muscarinic antagonists as maintenance therapy, including 12 in COPD Grade I, 31 in Grade II, 38 in Grade III, and 14 in Grade IV, based on the Global Initiative for Chronic Obstructive Lung Disease spirometric grading. For more than half of the patients on triple therapy, the treatment had been intensified due to unsatisfactory improvement of symptoms, and 32% were treated with triple therapy due to comorbid asthma. In contrast, there were COPD patients whose therapy was maintained after starting with triple therapy because of their serious conditions or concurrent exacerbation at diagnosis (8%). Conclusion: Triple therapy was often prescribed in the real-life management of COPD, even in patients whose airflow limitation was not severe. To better control symptoms was the major reason for choosing triple therapy, regardless of the severity of COPD, in Japan.

    DOI: 10.2147/COPD.S79864

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  262. Pulmonary nocardiosis caused by Nocardia cyriacigeorgica in patients with Mycobacterium avium complex lung disease: two case reports

    Yagi Kazuma, Ishii Makoto, Namkoong Ho, Asami Takahiro, Fujiwara Hiroshi, Nishimura Tomoyasu, Saito Fumitake, Kimizuka Yoshifumi, Asakura Takanori, Suzuki Shoji, Kamo Tetsuro, Tasaka Sadatomo, Gonoi Tohru, Kamei Katsuhiko, Betsuyaku Tomoko, Hasegawa Naoki

    BMC INFECTIOUS DISEASES   14 巻 ( 1 ) 頁: 684   2014年12月

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    記述言語:英語   出版者・発行元:BMC Infectious Diseases  

    Pulmonary nocardiosis frequently occurs in immunocompromised hosts and in some immunocompetent hosts with chronic lung disease; however, few reports have described pulmonary nocardiosis with nontuberculous mycobacterial lung infection. Here we report for the first time two cases of pulmonary nocardiosis caused by Nocardia cyriacigeorgica associated with Mycobacterium avium complex (MAC) lung disease caused by M. avium. Case presentation: Case 1 is that of a 72-year-old Japanese man with untreated MAC lung disease, who was diagnosed with rheumatoid arthritis and initiated on methotrexate. After 3 years of methotrexate therapy, the patient remained smear-negative and culture-positive for MAC, but also became smear-positive for Nocardia species. He received trimethoprim/sulfamethoxazole, and his symptoms and lung infiltrates improved. Case 2 is that of an immunocompetent 53-year-old Japanese woman with MAC lung disease, who was treated with a combined therapy of clarithromycin, rifampicin, ethambutol, and levofloxacin. MAC sputum culture was negative after 1 year of combined treatment, which was maintained for 2 years. After four treatment-free years, Nocardia species were occasionally isolated from her sputum, although MAC was rarely isolated from sputum cultures over the same period. In both cases, the Nocardia species were identified as the recently defined N. cyriacigeorgica by 16S ribosomal RNA gene sequencing. Conclusion: We report two cases of pulmonary nocardiosis caused by N. cyriacigeorgica associated with MAC lung disease caused by M. avium and suggest that N. cyriacigeorgica may be a major infective agent associated with MAC lung disease.

    DOI: 10.1186/s12879-014-0684-z

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  263. Serum (1 -> 3) beta-D-glucan assay for discrimination between Pneumocystis jirovecii pneumonia and colonization

    Tasaka Sadatomo, Kobayashi Seiki, Yagi Kazuma, Asami Takahiro, Namkoong Ho, Yamasawa Wakako, Ishii Makoto, Hasegawa Naoki, Betsuyaku Tomoko

    JOURNAL OF INFECTION AND CHEMOTHERAPY   20 巻 ( 11 ) 頁: 678 - 681   2014年11月

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    記述言語:英語   出版者・発行元:Journal of Infection and Chemotherapy  

    Polymerase chain reaction (PCR) technique is being increasingly used for the microbiological diagnosis of Pneumocystis pneumonia (PCP). As PCR is highly sensitive, it can be positive even in a patient with Pneumocystis colonization. In this study, we evaluated whether the β-d-glucan assay could be used to differentiate between PCP and Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. We retrospectively evaluated data from 166 consecutive patients who underwent bronchoalveolar lavage for the diagnosis of PCP. Serum levels of β-d-glucan in the negative, colonization, probable PCP, and definite PCP groups were 20.2 ± 6.3, 48.8 ± 15.9, 89.9 ± 20.2, 224.9 ± 25.9 pg/mL, respectively. The β-d-glucan levels in the definite PCP group were significantly higher than those in the other 3 groups (p < 0.001). Serum β-d-glucan levels in patients with either definite or probable PCP (173.1 ± 18.8 pg/mL) were significantly greater than those in patients with colonization who had positive PCR results but improved without anti-PCP treatment (p < 0.002). The cut-off level for discrimination was estimated to be 33.5 pg/mL, with which the positive predictive value was 0.925. These results indicate that β-d-glucan is a useful marker to differentiate between PCP and Pneumocystis colonization. A positive β-D-glucan assay result might be a good indication to begin anti-PCP treatment.

    DOI: 10.1016/j.jiac.2014.07.001

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  264. CLARITHROMYCIN EXPANDS CD11B+GR-1+CELLS TO PROTECT AGAINST LPS-INDUCED LETHAL SHOCK

    Namkoong H., Ishii M., Fujii H., Asami T., Yagi K., Fujiwara H., Saitoh F., Tasaka S., Hasegawa N., Koyasu S., Betsuyaku T.

    SHOCK   41 巻   頁: 18 - 18   2014年6月

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  265. ALI/ARDSにおける遺伝子研究

    石井, 誠

    呼吸器内科   25 巻 ( 3 ) 頁: 263 - 269   2014年3月

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    記述言語:日本語   出版者・発行元:科学評論社  

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  266. クラリスロマイシンはCD11b(+)Gr-1(+)細胞を誘導し、LPS腹腔内投与ショックモデルの予後を改善させる

    南宮 湖, 石井 誠, 藤猪 英樹, 浅見 貴弘, 八木 一馬, 斉藤 史武, 田坂 定智, 小安 重夫, 長谷川 直樹, 別役 智子

    Shock: 日本Shock学会雑誌   28 巻 ( 2 ) 頁: 1 - 6   2014年2月

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    記述言語:日本語   出版者・発行元:(一社)日本Shock学会  

    クラリスロマイシン(CAM)はCD11b(+)Gr-1(+)細胞を誘導し、LPS腹腔内投与ショックモデルの予後を改善させるか検討した。CAM投与により肺・脾臓にそれぞれ、CD11b(+)Gr-1(+)細胞が有意に増加した。in vitroにおいて、CAMによって誘導されるCD11b(+)Gr-1(+)細胞は免疫抑制性に作用することが示された。CAMはCD11b(+)Gr-1(+)細胞を介して、LPS腹腔内投与ショックモデルの予後を改善させることが示された。CAMにより誘導されるCD11b(+)Gr-1(+)cellsからのIL-10産生が、LPS腹腔内投与ショックモデルに対する保護的効果に必須であることが示された。CAMは抗炎症作用を有するCD11b(+)Gr-1(+)cellsを誘導し、LPS腹腔内投与ショックモデルの予後を改善させることが示唆された。

  267. Clinical And Bacteriological Evaluations During Observation Of Mycobacterium Avium Complex Lung Disease Without Treatment

    Kimizuka Y., Ishii M., Hoshino Y., Asami T., Nishimura T., Maeda S., Tasaka S., Namkoong H., Fujiwara H., Funatsu Y., Yagi K., Abe T., Iwata S., Betsuyaku T., Hasegawa N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   189 巻   2014年

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  268. Critical Roles Of Enhancer Of Zeste Homolog 2(ezh2) During Influenza A Virus Infection

    Yagi K., Ishii M., Namkoong H., Asami T., Fujiwara H., Nishimura T., Saito F., Tasaka S., Kunke S. I, Hasegawa N., Betsuyakul T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   189 巻   2014年

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  269. P1-8-2 経気管支肺生検で診断した血管内リンパ腫と考えられた2例(びまん性疾患/BAL 2,一般演題(ポスター),第37回日本呼吸器内視鏡学会学術集会)

    浅見 貴弘, 石井 誠, 宮脇 正芳, 田中 希宇人, 猶木 克彦, 田坂 定智, 副島 研造, 別役 智子

    気管支学   36 巻 ( Special ) 頁: S245   2014年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.36.special_s245_2

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  270. Pharmacokinetics of arbekacin in bronchial epithelial lining fluid of healthy volunteers

    Funatsu Yohei, Hasegawa Naoki, Fujiwara Hiroshi, Namkoong Ho, Asami Takahiro, Tasaka Sadatomo, Kimizuka Yoshifumi, Kamata Hirofumi, Ishii Makoto, Iketani Osamu, Ogata Haruhiko, Iwata Satoshi, Betsuyaku Tomoko

    JOURNAL OF INFECTION AND CHEMOTHERAPY   20 巻 ( 9-10 ) 頁: 607 - 611   2014年

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    記述言語:英語   出版者・発行元:Journal of Infection and Chemotherapy  

    Arbekacin is a unique aminoglycoside antibiotic with anti-methicillin-resistant Staphylococcus aureus activity. The efficacy of aminoglycosides is related to their serum maximum concentration. Local concentration of antibiotics in pulmonary epithelial lining fluid, rather than its serum concentration, can help determine its clinical efficacy more precisely for treatment of respiratory infectious disease. The objective of this study was to sequentially measure arbekacin concentration in epithelial lining fluid after infusion of a single clinically available dose.

    DOI: 10.1016/j.jiac.2014.05.007

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  271. The efficacy, safety, and pharmacokinetics of biapenem administered thrice daily for the treatment of pneumonia in the elderly

    Namkoong Ho, Kameyama Youjyu, Yasuda Hiroyuki, Nakayama Sohei, Kaneko Hiroshi, Kawashima Chieko, Terajima Tomoko, Maezawa Kayoko, Hayashi Takeshi, Sandoh Mitsuru, Ishii Makoto, Tasaka Sadatomo, Kanayama Akiko, Kobayashi Intetsu, Betsuyaku Tomoko, Kizu Junko, Iwata Satoshi, Sato Yoshitake, Hasegawa Naoki

    JOURNAL OF INFECTION AND CHEMOTHERAPY   20 巻 ( 5-6 ) 頁: 356 - 360   2014年

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    記述言語:英語   出版者・発行元:Journal of Infection and Chemotherapy  

    Biapenem has been widely used to treat bacterial pneumonia; however, there is little information concerning its efficacy and safety in elderly patients. Based on pharmacokinetic-pharmacodynamic theory, administration of biapenem thrice rather than twice daily would be expected to be more effective because of longer time above the minimum inhibitory concentration. In this study, we aimed to evaluate the efficacy, safety, and pharmacokinetics of biapenem (300 mg) administered thrice daily in pneumonic patients aged 65 years or older. Biapenem was effective in 22 of 25 patients, as assessed by the improvement in clinical symptoms and/or the eradication of the causative organisms, and caused no serious adverse events. The pharmacokinetic profile was established based on simulations using a modeling program. Among 17 patients whose causative organisms were detected, time above the minimum inhibitory concentration was estimated to be 100% in 16 patients, all of whom showed clinical improvement. The results of this study confirmed the efficacy and safety of 300 mg of biapenem administered thrice daily for the treatment of pneumonia in elderly patients. © 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jiac.2013.12.010

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  272. A case of skeletal tuberculosis and psoas abscess: disease activity evaluated using F-18-fluorodeoxyglucose positron emission tomography-computed tomography

    Kimizuka Yoshifumi, Ishii Makoto, Murakami Koji, Ishioka Kota, Yagi Kazuma, Ishii Ken, Watanabe Kota, Soejima Kenzo, Betsuyaku Tomoko, Hasegawa Naoki

    BMC MEDICAL IMAGING   13 巻 ( 1 ) 頁: 37   2013年11月

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    記述言語:英語   出版者・発行元:BMC Medical Imaging  

    Background: Psoas abscess complicating tuberculous spondylitis is a rare morbidity in extrapulmonary tuberculosis. There are no established guidelines for evaluating the clinical response of psoas abscess. Although several studies have shown that positron emission tomography-computed tomography with 18 F-fluorodeoxyglucose can play a potential role in diagnosing multifocal tuberculosis and monitoring the clinical response of pulmonary tuberculosis, to our knowledge, this is the first report demonstrating that positron emission tomography-computed tomography is useful for evaluating local inflammation and disease activity of a tuberculous psoas abscess. Case presentation: We report a case of multifocal bone and lymph node tuberculosis with concomitant lumbar psoas abscess in a 77-year-old man, along with a literature review. An initial positron emission tomography-computed tomography scan showed intense 18 F-fluorodeoxyglucose accumulation in the sternum, ribs, vertebrae, and lymph nodes. The patient was successfully treated with antitubercular agents and computed tomography-guided drainage therapy. A follow-up positron emission tomography-computed tomography after abscess drainage and 9 months of antitubercular drug treatment revealed that the majority of lesions improved; however, protracted inflammation surrounding the psoas abscess was still observed. These results indicate that disease activity of psoas abscess can remain, even after successful drainage and antitubercular medication regime of appropriate duration.Conclusion: We have successfully followed up the extent of skeletal tuberculosis complicated with psoas abscess by positron emission tomography-computed tomography. In this patient, positron emission tomography-computed tomography is useful for evaluating the disease activity of tuberculous psoas abscess and for assessing the appropriate duration of antitubercular drug therapy in psoas abscess. © 2013 Kimizuka et al.; licensee BioMed Central Ltd.

    DOI: 10.1186/1471-2342-13-37

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  273. Penetration and pharmacokinetics of peramivir in upper and lower airway epithelia and plasma

    Funatsu Yohei, Hasegawa Naoki, Namkoong Ho, Asami Takahiro, Fujiwara Hiroshi, Kimizuka Yoshifumi, Tasaka Sadatomo, Ishii Makoto, Saito Fumitake, Yagi Kazuma, Iwata Satoshi, Betsuyaku Tomoko

    EUROPEAN RESPIRATORY JOURNAL   42 巻   2013年9月

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  274. Retrospective observation of mycobacterium avium complex lung disease followed without treatment

    Kimizuka Yoshifumi, Asami Takahiro, Ishii Makoto, Tasaka Sadatomo, Namkoong Ho, Fujiwara Hiroshi, Funatsu Yohei, Abe Takayuki, Iwata Satoshi, Sato Yuji, Betsuyaku Tomoko, Hasegawa Naoki

    EUROPEAN RESPIRATORY JOURNAL   42 巻   2013年9月

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  275. Clarithromycin expands CD11b+Gr-1+cells to protect against LPS-induced lethal shock and polymicrobial sepsis

    Namkoong H., Ishii M., Fujii H., Asami T., Yagi K., Fujiwara H., Saitoh F., Tasaka S., Hasegawa N., Koyasu S., Betsuyaku T.

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   42 巻   頁: S44 - S45   2013年6月

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  276. Clinical and radiological features of Mycobacterium avium complex lung disease observed without chemotherapy

    Kimizuka Y., Asami T., Ishii M., Tasaka S., Namkoong H., Fujiwara H., Funatsu Y., Abe T., Iwata S., Sato Y., Betsuyaku T., Hasegawa N.

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   42 巻   頁: S136 - S136   2013年6月

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  277. Pharmacokinetics of peramivir in upper and lower airway epithelia and plasma

    Funatsu Y., Hasegawa N., Namkoong H., Asami T., Fujiwara H., Kimizuka Y., Tasaka S., Ishii M., Saito F., Yagi K., Betsuyaku T., Iwata S.

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   42 巻   頁: S48 - S49   2013年6月

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  278. Prostaglandin D2 receptor CRTH2 is a critical regulator of neutrophilmigration and resistance to polymicrobial sepsis

    Ishii M., Asano K., Namkoong H., Tasaka S., Miyata J., Kagawa S., Nakamura M., Hirai H., Nagata K., Hasegawa N., Kunkel S., Betsuyaku T.

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   42 巻   頁: S43 - S43   2013年6月

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  279. クラリスロマイシンはCD11b+Gr-1+細胞を誘導し、LPS腹腔内投与ショックモデルの予後を改善させる 査読有り

    南宮 湖, 石井 誠, 田坂 定智, 長谷川 直樹, 別役 智子

    Shock: 日本Shock学会雑誌   28 巻 ( 1 ) 頁: 49 - 49   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本Shock学会  

  280. 【呼吸器病学TOPICS 2012-13】 細胞・分子生物学 呼吸器感染症とエピジェネティクス

    石井, 誠

    分子呼吸器病   17 巻 ( 1 ) 頁: 11 - 15   2013年3月

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    記述言語:日本語   出版者・発行元:先端医学社  

    CiNii Books

  281. Differential Mechanisms of the Effect of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Bleomycin-Induced Lung Fibrosis.

    Miyamoto, K, Tasaka, S, Nakano, S, Shinoda, H, Kamata, H, Yamasawa, W, Ishii, M, Hasegawa, N, Betsuyaku, T

    Open Journal of Respiratory Diseases   3 巻   頁: 31 - 38   2013年

  282. 16.PET-CTを契機に経気管支肺生検にて確定診断に至った血管内リンパ腫の1例(第145回 日本呼吸器内視鏡学会関東支部会)

    浅見 貴弘, 石井 誠, 宮崎 雅樹, 甲田 祐也, 宮脇 正芳, 猶木 克彦, 田坂 定智, 副島 研造, 加藤 淳, 森 毅彦, 三上 修治, 別役 智子

    気管支学   35 巻 ( 4 ) 頁: 464   2013年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.35.4_464_1

    CiNii Research

  283. Clarithromycin Expands Cd11b+gr-1+Cells To Protect Against LPS-Induced Lethal Shock And Polymicrobial Sepsis

    Namkoong H., Ishii M., Fujii H., Asami T., Yagi K., Funatsu Y., Fujiwara H., Saitoh F., Tasaka S., Hasegawa N., Koyasu S., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187 巻   2013年

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  284. 17. IgG4関連疾患に胸膜炎を合併した1例(第144回日本呼吸器内視鏡学会関東支部会)

    平良 朱理, 重信 敬夫, 鈴木 繁紀, 木下 智成, 福富 寿典, 山本 純, 八木 一馬, 石井 誠, 副島 研造, 羽藤 泰, 神山 育男, 後藤 太一郎, 大塚 崇, 日比 紀文, 別役 智子, 河野 智子, 三上 修治

    気管支学   35 巻 ( 3 ) 頁: 352   2013年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.35.3_352_1

    CiNii Research

  285. Diet-Induced Obesity Modulates The Macrophage Response To Influenza Virus Infection

    Nakagawa T., Ishii M., Namkoong H., Fujii H., Asami T., Yagi K., Saito F., Funatsu Y., Fujiwara H., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187 巻   2013年

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  286. In Vitro Effect Of 14-Hydroxy Clarithromycin, A Major Metabolite Of Clarithromycin, On Cytokine Expressions In Murine Macrophages And Dendritic Cells During Influenza A Virus Infection

    Matsui Y., Ishii M., Namkoong H., Fujii H., Asami T., Yagi K., Saito F., Funatsu Y., Fujiwara H., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187 巻   2013年

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  287. Mesenchymal Stem Cell-Conditioned Medium Modulates Murine Macrophage Cytokine Expression Induced By Tlr7/8 Ligand Stimulation And Influenza A Virus Infection

    Asami T., Ishii M., Fujii H., Namkoong H., Yagi K., Funatsu Y., Kimizuka Y., Fujiwara H., Tasaka S., Hasegawa N., Betsuyaku T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187 巻   2013年

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  288. P1-3-6 経気管支肺生検後に肺化膿症を認めたサルコイドーシスの1例(合併症・安全対策-2,一般演題ポスター,第36回日本呼吸器内視鏡学会学術集会)

    八木 一馬, 猶木 克彦, 石田 洋子, 浅見 貴弘, 田中 希宇人, 舩津 洋平, 鈴木 雄介, 石井 誠, 福永 興壱, 田坂 定智, 副島 研造, 別役 智子

    気管支学   35 巻 ( Special ) 頁: S196   2013年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.35.special_s196_3

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  289. P1-2-4 上気道及び下気道におけるペラミビルの薬物動態(合併症・安全対策-1,一般演題ポスター,第36回日本呼吸器内視鏡学会学術集会)

    舩津 洋平, 長谷川 直樹, 南宮 湖, 浅見 貴弘, 藤原 宏, 君塚 善文, 田坂 定智, 石井 誠, 斉藤 史武, 八木 一馬, 別役 智子, 岩田 敏

    気管支学   35 巻 ( Special ) 頁: S194   2013年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.35.special_s194_1

    CiNii Research

  290. Modulation of Murine Macrophage TLR7/8-Mediated Cytokine Expression by Mesenchymal Stem Cell-Conditioned Medium

    Asami Takahiro, Ishii Makoto, Fujii Hideki, Namkoong Ho, Tasaka Sadatomo, Matsushita Kenichi, Ishii Ken, Yagi Kazuma, Fujiwara Hiroshi, Funatsu Yohei, Hasegawa Naoki, Betsuyaku Tomoko

    MEDIATORS OF INFLAMMATION   2013 巻   頁: 264260   2013年

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    記述言語:英語   出版者・発行元:Mediators of Inflammation  

    Increasing evidence suggests that mesenchymal stem cells (MSCs) play anti-inflammatory roles during innate immune responses. However, little is known about the effect of MSCs or their secretions on the ligand response of Toll-like receptor (TLR) 7 and TLR8, receptors that recognize viral single-stranded RNA (ssRNA). Macrophages play a critical role in the innate immune response to ssRNA virus infection; therefore, we investigated the effect of MSC-conditioned medium on cytokine expression in macrophages following stimulation with TLR7/8 ligands. After stimulation with TLR7/8 ligand, bone marrow-derived macrophages cultured with MSCs or in MSC-conditioned medium expressed lower levels of tumor necrosis factor (TNF) α and interleukin (IL) 6 and higher levels of IL-10 compared to macrophages cultured without MSCs or in control medium, respectively. The modulations of cytokine expression were associated with prostaglandin E(PGE secreted by the MSCs. PGEenhanced extracellular signal-related kinase (ERK) signaling and suppressed nuclear factor-B (NF-B) signaling. Enhanced ERK signaling contributed to enhanced IL-10 production, and suppression of NF-B signaling contributed to the low production of TNF-α. Collectively, these results indicate that MSCs and MSC-conditioned medium modulate the cytokine expression profile in macrophages following TLR7/8-mediated stimulation, which suggests that MSCs play an immunomodulatory role during ssRNA virus infection. © 2013 Takahiro Asami et al.

    DOI: 10.1155/2013/264260

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  291. The Efficacy Of Amikacin In Combination With Standard Regimen To Patients With Nontuberculous Mycobacterial Infection

    Tanaka H., Funatsu Y., Namkoong H., Yagi K., Asami T., Fujiwara H., Kimizuka Y., Nishimura T., Ishii M., Tasaka S., Hasegawa N., Betsuyaku T., Iwata S.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187 巻   2013年

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  292. Tuberous sclerosis diagnosed by incidental computed tomography findings of multifocal micronodular pneumocyte hyperplasia: A case report

    Ishii M., Asano K., Kamiishi N., Hayashi Y., Arai D., Haraguchi M., Sugiura H., Naoki K., Tasaka S., Soejima K., Sayama K., Betsuyaku T.

    Journal of Medical Case Reports   6 巻   頁: 352   2012年10月

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    記述言語:英語   出版者・発行元:Journal of Medical Case Reports  

    Introduction. The majority of multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis complex is diagnosed with the classical clinical triad of seizures, mental retardation, and skin lesions. We report a rare case of tuberous sclerosis complex with no classical clinical findings, which was diagnosed through incidental computed tomography findings of multiple nodular lesions of multifocal micronodular pneumocyte hyperplasia. Case presentation. A chest computed tomography scan of a 51-year-old Japanese woman showed multiple nodular ground-glass opacities that were not seen on chest X-ray. Video-assisted thoracoscopic surgery was performed. A histological examination demonstrated type II pneumocyte hyperplasia with thickened fibrotic alveolar septa, which was consistent with multifocal micronodular pneumocyte hyperplasia. Brain magnetic resonance imaging displayed multiple cortical tubers, and abdominal computed tomography showed bilateral renal angiomyolipoma. Our patient was finally diagnosed as having tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia, although she had no episodes of epilepsy, no skin lesions, and no family history. Conclusions: Multifocal micronodular pneumocyte hyperplasia with latent tuberous sclerosis complex should be considered in the differential diagnosis of multiple ground-glass opacities. © 2012 Ishii et al.; licensee BioMed Central Ltd.

    DOI: 10.1186/1752-1947-6-352

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  293. Cytokine profiles of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema

    Tasaka Sadatomo, Mizoguchi Kosuke, Funatsu Yohei, Namkoong Ho, Yamasawa Wakako, Ishii Makoto, Hasegawa Naoki, Betsuyaku Tomoko

    EUROPEAN RESPIRATORY JOURNAL   40 巻   2012年9月

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  294. Cytokine profile of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema

    Tasaka Sadatomo, Mizoguchi Kosuke, Funatsu Yohei, Namkoong Ho, Yamasawa Wakako, Ishii Makoto, Hasegawa Naoki, Betsuyaku Tomoko

    RESPIROLOGY   17 巻 ( 5 ) 頁: 814 - 820   2012年7月

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    記述言語:英語   出版者・発行元:Respirology  

    Background and objective: Combined pulmonary fibrosis and emphysema (CPFE) is characterized by upper lobe emphysema together with lower lobe fibrosis. The aim of this study was to examine whether cytokine levels in the alveolar space are associated with emphysematous changes superimposed on pulmonary fibrosis. Methods: Consecutive patients (n = 102), diagnosed with pulmonary fibrosis were retrospectively evaluated. Cytokine levels and differential cell counts in bronchoalveolar lavage (BAL) fluid, pulmonary function, computed tomography (CT) scores and levels of serum markers were compared between patients with or without emphysema. Results: Among the 102 patients (14 females, mean age 68 years), 38 (37%) had evidence of upper lobe emphysema on computed tomography (CT). Levels of epithelial neutrophil activating peptide 78 (ENA-78/CXCL5) and interleukin (IL)-8/CXCL8 in BAL fluid were significantly higher in patients with emphysema. Vital capacity (VC, % predicted) was greater, and ratio of forced expiratory volume in 1 s/forced vital capacity and diffusing capacity of carbon monoxide (DLCO)/alveolar volume (VA) were lower in patients with emphysema. CXCL8 and CXCL5 levels were associated with percentage or absolute numbers of neutrophils in BAL fluid. In addition, CXCL8 levels were inversely correlated with VC and DLCO/VA, and positively correlated with composite physiological index (CPI) and the extent of areas of low attenuation on CT. Conclusions: Increased CXC chemokine levels in the airspaces may be associated with emphysematous lung changes in patients with pulmonary fibrosis. The levels of various inflammatory mediators in bronchoalveolar lavage fluid were measured in patients with combined pulmonary fibrosis and emphysema. In patients with pulmonary fibrosis, elevated concentrations of CXC chemokines (CXCL5 and CXCL8) were associated with the development of emphysematous changes, neutrophil accumulation in the alveolar space, and impaired diffusing capacity. © 2012 Asian Pacific Society of Respirology.

    DOI: 10.1111/j.1440-1843.2012.02182.x

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  295. CRTH2 Is A Critical Regulator of Neutrophil Migration and Resistance to Polymicrobial Sepsis

    Ishii Makoto, Asano Koichiro, Namkoong Ho, Tasaka Sadatomo, Mizoguchi Kosuke, Asami Takahiro, Kamata Hirofumi, Kimizuka Yoshifumi, Fujiwara Hiroshi, Funatsu Yohei, Kagawa Shizuko, Miyata Jun, Ishii Ken, Nakamura Masataka, Hirai Hiroyuki, Nagata Kinya, Kunkel Steven L., Hasegawa Naoki, Betsuyaku Tomoko

    JOURNAL OF IMMUNOLOGY   188 巻 ( 11 ) 頁: 5655 - 5664   2012年6月

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    記述言語:英語   出版者・発行元:Journal of Immunology  

    Although arachidonic acid cascade has been shown to be involved in sepsis, little is known about the role of PGD2 and its newly found receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), on the septic response. Severe sepsis is associated with the failure of neutrophil migration. To investigate whether CRTH2 influences neutrophil recruitment and the lethality during sepsis, sepsis was induced by cecal ligation and puncture (CLP) surgery in mice. CRTH2 knockout (CRTH2 -/-) mice were highly resistant to CLP-induced sepsis, which was associated with lower bacterial load and lower production of TNF-α, IL-6, and CCL3. IL-10, an anti-inflammatory cytokine, was higher in CRTH2 -/- mice, blunting CLP-induced lethality in CRTH2 -/- mice. Neutrophil accumulation in the peritoneum was more pronounced after CLP in CRTH22/2 mice, which was associated with higher CXCR2 levels in circulating neutrophils. Furthermore, sepsis caused a decrease in the level of acetylation of histone H3, an activation mark, at the CXCR2 promoter in wild-type neutrophils, suggesting that CXCR2 expression levels are epigenetically regulated. Finally, both pharmacological depletion of neutrophils and inhibition of CXCR2 abrogated the survival benefit in CRTH2 -/- mice. These results demonstrate that genetic ablation of CRTH2 improved impaired neutrophil migration and survival during severe sepsis, which was mechanistically associated with epigenetic-mediated CXCR2 expression. Thus, CRTH2 is a potential therapeutic target for polymicrobial sepsis. Copyright©2012 by The American Association of Immunologists, Inc.

    DOI: 10.4049/jimmunol.1102330

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  296. レジオネラ肺炎におけるIL-17の役割

    君塚, 善文, 木村, 聡一郎, 石井, 誠, 舘田, 一博

    呼吸器内科   21 巻 ( 4 ) 頁: 354 - 358   2012年4月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

  297. Roles of Interleukin-17 in an Experimental Legionella pneumophila Pneumonia Model

    Kimizuka Yoshifumi, Kimura Soichiro, Saga Tomoo, Ishii Makoto, Hasegawa Naoki, Betsuyaku Tomoko, Iwakura Yoichiro, Tateda Kazuhiro, Yamaguchi Keizo

    INFECTION AND IMMUNITY   80 巻 ( 3 ) 頁: 1121 - 1127   2012年3月

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    出版者・発行元:Infection and Immunity  

    Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host responses and plays critical roles in immunological control of a variety of infectious diseases. Although Legionella pneumophila, an intracellular bacterium found widely in the environment, often causes a serious and life-threatening pneumonia in humans, the contribution of IL-17 to immune function during Legionella pneumonia is unknown. In the present study, we used an experimental Legionella pneumonia infection to clarify the role of IL-17 in the resulting immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL-17A/ F), peaking on day 1 and declining thereafter. Upregulated production of tumor necrosis factor alpha (TNF-α), IL-6, and IL-1β, but not monocyte chemotactic protein 1 (MCP-1), was observed in Legionella-infected bone marrow-derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL-17F. A significant decrease in the production of proinflammatory cytokines IL-6 and TNF-α was observed in IL-17A/F-deficient mice (BALB/c background) infected with L. pneumophila. Moreover, we found impaired neutrophil migration and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice. IL-17A/F-deficient mice also eliminated L. pneumophila more slowly and were less likely to survive a lethal challenge. These results demonstrate that IL-17A/F plays a critical role in L. pneumophila pneumonia, probably through induction of proinflammatory cytokines and accumulation of neutrophils at the infection site. © 2012, American Society for Microbiology.

    DOI: 10.1128/IAI.05544-11

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  298. インフルエンザウィルス感染症におけるエピジェネティック制御

    石井, 誠, 溝口, 孝輔

    大和証券ヘルス財団研究業績集   ( 35 ) 頁: 53 - 57   2012年3月

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    記述言語:日本語  

    インフルエンザウイルス肺炎惹起マウスを用いて、ヒストン脱アセチル化酵素(HDAC)阻害薬であるトリコスタチンA(TSA)投与の及ぼす効果について検討した。その結果、1)TSA連日投与群はコントロール群に比べ、インフルエンザウイルス感染後の体重減少が有意に抑制され、TSAの保護的効果が示唆された。2)感染3日後と6日後の肺内のサイトカインmRNA発現は両群間で有意差を認められなかった。3)マウスマクロファージのインフルエンザウイルス感染やTLR7/8リガンド刺激において、TSA投与はサイトカイン発現の抑制効果を示した。特にHDAC1やHDAC6のmRNAはTSA投与により上昇しており、TSAの作用はHDAC1やHDAC6が関与する可能性が示唆された。

  299. 造血幹細胞移植後に晩発性の高度拘束性換気障害を呈した特発性肺炎症候群の臨床的特徴 査読有り

    南宮 湖, 石井 誠, 田坂 定智, 杉浦 弘明, 加藤 淳, 森 毅彦, 長谷川 直樹, 岡本 真一郎, 別役 智子

    日本呼吸器学会誌   1 巻 ( 増刊 ) 頁: 337 - 337   2012年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  300. PROSTAGLANDIN D2 RECEPTOR CRTH2 IS A CRITICAL REGULATOR IN A MICE MODEL OF POLYMICROBIAL SEPSIS

    Ishii M., Asano K., Namkoong H., Kagawa S., Nakamura M., Hirai H., Nagata K., Tasaka S., Hasegawa N.

    SHOCK   35 巻   頁: 7 - 7   2011年6月

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  301. Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice

    Kamata Hirofumi, Tasaka Sadatomo, Inoue Ken-ichiro, Miyamoto Keisuke, Nakano Yasushi, Shinoda Hiromi, Kimizuka Yoshifumi, Fujiwara Hiroshi, Ishii Makoto, Hasegawa Naoki, Takamiya Rina, Fujishima Seitaro, Takano Hirohisa, Ishizaka Akitoshi

    EXPERIMENTAL BIOLOGY AND MEDICINE   236 巻 ( 3 ) 頁: 315 - 324   2011年3月

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    記述言語:英語   出版者・発行元:Experimental Biology and Medicine  

    With the recent increasing use of nanoparticles, there is concern that they may become an environmental risk factor as airborne particles. However, the impact of these particles on susceptible subjects with predisposing lung disease have not been sufficiently elucidated. In the present study, we investigated the effects of nanoparticles on pulmonary inflammatory and fibrotic changes induced by intratracheal bleomycin (BLM) challenge in mice. Mice were intratracheally administered either vehicle, 14-nm carbon black nanoparticles (CBNPs), BLM or BLM plus CBNP. First, we assessed lung collagen content, lung compliance and fibrotic changes in histopathology on day 21 after instillation. Then, to elucidate how CBNP contributes to the development of BLM-induced fibrosis, we collected bronchoalveolar lavage (BAL) fluid on days 2, 7, 14 and 21 and determined the total and differential cell counts and concentrations of two proinflammatory cytokines (keratinocyte chemoattractant [KC] and interleukin [IL]-6) and two fibrogenic mediators (CC chemokine ligand 2 [CCL2] and transforming growth factor-β 1 [TGF-β 1]). Expression of nitrotyrosine, an indicator of oxidant injury, was also evaluated on days 7 and 21. CBNP, when combined with BLM, significantly enhanced BLM-induced increase in lung collagen content, decrease in lung compliance, and fibrotic changes in histopathology. CBNP significantly augmented BLM-induced increase in the numbers of inflammatory cells in BAL fluid on days 2 and 7 and levels of KC and IL-6 on day 2. In addition, CBNP administered in combination with BLM significantly elevated the levels of CCL2 on days 2, 7 and 14, and TGF-β 1 on day 14 in BAL fluid as compared with BLM alone. Nitrotyrosine expression was also increased by BLM plus CBNP compared with BLM alone. In contrast, CBNP did not exert any significant effect on these parameters by itself. These results indicate that CBNP can exaggerate BLM-induced inflammatory and fibrotic changes in the lung, suggesting the potential impact of nanoparticles on lung inflammation and fibrosis. Copyright © 2011 by the Society for Experimental Biology and Medicine.

    DOI: 10.1258/ebm.2011.010180

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  302. 感染症とエピジェネティクス

    石井, 誠

    呼吸器内科   19 巻 ( 1 ) 頁: 71 - 76   2011年1月

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    記述言語:日本語   出版者・発行元:科学評論社  

  303. P19-4 薬剤性肺障害における末梢血リンパ球幼弱化反応および気管支肺胞洗浄液所見の比較検討(びまん性/BAL,ポスター19,第34回日本呼吸器内視鏡学会学術集会)

    君塚 善文, 田坂 定智, 山澤 稚子, 石井 誠, 鎌田 浩史, 藤原 宏, 舩津 洋平, 南宮 湖, 長谷川 直樹, 村田 満, 浅野 浩一郎

    気管支学   33 巻 ( Special ) 頁: S270   2011年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.33.special_s270_1

    CiNii Research

  304. 特集呼吸器病原体-病原因特集呼吸器病原体-病原因子-生体反応感染症におけるエピジェネティクス

    石井 誠

    呼吸器内科   19 巻   頁: 71 - 76   2011年

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  305. 感染症におけるエピジェネティクス

    石井 誠

    呼吸器内科   19 巻   頁: 71 - 76   2011年

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  306. 【最新ARDSのすべて】 (第4章)ARDSの基礎疾患 ARDSの疾患感受性遺伝子とエピジェネティック制御 あらたな治療法開発に向けて

    石井, 誠, 山口, 佳寿博

    医学のあゆみ   別冊 巻 ( 最新ARDSのすべて ) 頁: 231 - 236   2010年9月

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    記述言語:日本語  

    ヒトゲノムの全塩基配列解読の完了が2003年に宣言され、現在ではその意味を解読するという機能解析に焦点が当てられ、genome-wide association study(GWAS)などゲノムワイドでの関連解析も行われるようになった。ARDSにおいてもその病態を遺伝子レベルで再検討することが積極的に行われつつある。ARDSはさまざまな環境因子と遺伝的因子が関与して病態を形成する多因子疾患と考えられ、ある複数個の遺伝子変異の存在によりARDSの易発症性あるいは易重症化が規定される可能性が指摘されている。これらの遺伝子はARDS疾患特異的感受性遺伝子と定義される。さらにDNA配列の変化を伴わない遺伝子発現制御としてヒストン修飾等のエピジェネティックな遺伝子制御機構の存在の可能性も示唆されており、これらの解析がさらに進めば、ARDSの病態が遺伝子レベルで詳細に解明され、その関与分子を標的とした新規治療薬の開発、さらには各患者の遺伝子変異の相違に応じた個別化医療も近い将来可能となり、ARDSに対する治療法の質が大幅に変化するものと期待される。(著者抄録)

  307. Cytokine profiles of bronchoalveolar lavage fluid in patients with pneumocystis pneumonia

    Tasaka Sadatomo, Kobayashi Seiki, Kamata Hirofumi, Kimizuka Yoshifumi, Fujiwara Hiroshi, Funatsu Yohei, Mizoguchi Kosuke, Ishii Makoto, Takeuchi Tsutomu, Hasegawa Naoki

    MICROBIOLOGY AND IMMUNOLOGY   54 巻 ( 7 ) 頁: 425 - 433   2010年7月

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    記述言語:英語   出版者・発行元:Microbiology and Immunology  

    The clinical features of PCP differ according to the factors responsible for the predisposing immunosuppression. Although the diagnosis of PCP often requires BAL, the profiles of the inflammatory mediators in the BAL fluid are not thoroughly documented. The aim of the current study was to characterize the profiles of inflammatory mediators in BAL fluid during PCP in patients with underlying autoimmune diseases, malignancies, or AIDS. The medical records of 14 patients with autoimmune diseases, 10 with malignancies, and 8 with AIDS, all of whom had been diagnosed with PCP by microscopic examination of BAL fluid, were reviewed. The concentrations of TNF-α, MCP-1, HMGB1, IL-8, IL-6, IL-10, and IFN-γ in the BAL fluid that had been obtained for the diagnosis of PCP were measured. The concentrations of MCP-1, IL-8, and IL-6 differed according to the underlying disease, tending to be higher in patients with autoimmune diseases and lower in those with AIDS. The concentrations of HMGB1, IL-8, and IL-6 were positively correlated with the proportion of neutrophils in BAL fluid and inversely with the oxygenation index. Although the serum concentrations of CRP and LDH were positively correlated with those of IL-8 and MCP-1, none of the mediators in BAL fluid was correlated with the serum β-D-glucan concentration. The production of inflammatory mediators in the lung differed between the patient groups with different underlying disorders. The modest upregulation of IL-8 and IL-6 might be associated with the milder clinical manifestations of PCP in AIDS patients. © 2010 The Societies and Blackwell Publishing Asia Pty Ltd.

    DOI: 10.1111/j.1348-0421.2010.00229.x

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  308. The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth

    Cavassani K.A., Carson IV W.F., Moreira A.P., Wen H., Schaller M.A., Ishii M., Lindell D.M., Dou Y., Lukacs N.W., Keshamouni V.G., Hogaboam C.M., Kunkel S.L.

    Blood   115 巻 ( 22 ) 頁: 4403 - 4411   2010年6月

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    出版者・発行元:Blood  

    One of the more insidious outcomes of patients who survive severe sepsis is profound immunosuppression. In this study, we addressed the hypothesis that post septic immune defects were due, in part, to the presence and/or expansion of regulatory T cells (Tregs). After recovery from severe sepsis, mice exhibited significantly higher numbers of Tregs, which exerted greater in vitro suppressive activity compared with controls. The expansion of Tregs was not limited to CD25+ cells, because Foxp3 expression was also detected in CD25- cells from post septic mice. This latter group exhibited a significant increase of chromatin remodeling at the Foxp3 promoter, because a marked increase in acetylation at H3K9 was associated with an increase in Foxp3 transcription. Post septic splenic dendritic cells promoted Treg conversion in vitro. Using a solid tumor model to explore the function of Tregs in an in vivo setting, we found post septic mice showed an increase in tumor growth compared with sham-treated mice with a syngeneic tumor model. This observation could mechanistically be related to the ability of post septic Tregs to impair the antitumor response mediated by CD8+ T cells. Together, these data show that the post septic immune system obstructs tumor immunosurveillance, in part, by augmented Treg expansion and function. © 2010 by The American Society of Hematology.

    DOI: 10.1182/blood-2009-09-241083

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  309. Impaired CD4<sup>+</sup> T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis

    Carson IV W., Cavassani K., Ito T., Schaller M., Ishii M., Dou Y., Kunkel S.

    European Journal of Immunology   40 巻 ( 4 ) 頁: 998 - 1010   2010年4月

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    出版者・発行元:European Journal of Immunology  

    Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4+ T-cell responses remains unclear. In the present study, CD4 + T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro. CD4 +CD62L+ T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4 +CD62L+ T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the TH1 or TH2 lineage. Repressive histone methylation marks were also evident at promoter regions for the TH1 cytokine IFN-γ and the T H2 transcription factor GATA-3 in naïve CD4+ T cells from CLP mice. These results provide evidence that CD4+ T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

    DOI: 10.1002/eji.200939739

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  310. P14-2 気管支鏡にて初めて診断に至った肺非結核性抗酸菌症の臨床的検討(抗酸菌感染症,ポスター14,第33回日本呼吸器内視鏡学会学術集会)

    藤原 宏, 長谷川 直樹, 舩津 洋平, 溝口 孝輔, 君塚 善文, 鎌田 浩史, 石井 誠, 田坂 定智, 浅野 浩一郎, 石坂 彰敏

    気管支学   32 巻 ( Special ) 頁: S217   2010年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.32.special_s217_2

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  311. 最新ARDSの全てーARDSの疾患感受性遺伝子とエピジェネティック制御-あらたな治療法開発に向けて

    石井 誠

    医学のあゆみ別冊ARDSのすべて     頁: 231 - 236   2010年

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  312. Epigenetic regulation of the alternatively activated macrophage phenotype

    Ishii M., Wen H., Corsa C.A.S., Liu T., Coelho A.L., Allen R.M., Carson IV W.F., Cavassani K.A., Li X., Lukacs N.W., Hogaboam C.M., Dou Y., Kunkel S.L.

    Blood   114 巻 ( 15 ) 頁: 3244 - 3254   2009年

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    出版者・発行元:Blood  

    Alternatively activated (M2) macrophages play critical roles in diverse chronic diseases, including parasite infections, cancer, and allergic responses. However, little is known about the acquisition and maintenance of their phenotype. We report that M2-macrophage marker genes are epigenetically regulated by reciprocal changes in histone H3 lysine-4 (H3K4) and histone H3 lysine-27 (H3K27) methylation; and the latter methylation marks are removed by the H3K27 demethylase Jumonji domain containing 3 (Jmjd3). We found that continuous interleukin-4 (IL-4) treatment leads to decreased H3K27 methylation, at the promoter of M2 marker genes, and a concomitant increase in Jmjd3 expression. Furthermore, we demonstrate that IL-4-dependent Jmjd3 expression is mediated by STAT6, a major transcription factor of IL-4-mediated signaling. After IL-4 stimulation, activated STAT6 is increased and binds to consensus sites at the Jmjd3 promoter. Increased Jmjd3 contributes to the decrease of H3K27 dimethylation and trimethylation (H3K27me2/3) marks as well as the transcriptional activation of specific M2 marker genes. The decrease in H3K27me2/3 and increase in Jmjd3 recruitment were confirmed by in vivo studies using a Schistosoma mansoni egg-challenged mouse model, a wellstudied system known to support an M2 phenotype. Collectively, these data indicate that chromatin remodeling is mechanistically important in the acquisition of the M2-macrophage phenotype. © 2009 by The American Society of Hematology.

    DOI: 10.1182/blood-2009-04-217620

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  313. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events

    Cavassani K.A., Ishii M., Wen H., Schaller M.A., Lincoln P.M., Lukacs N.W., Hogaboam C.M., Kunkel S.L.

    Journal of Experimental Medicine   205 巻 ( 11 ) 頁: 2609 - 2621   2008年10月

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    出版者・発行元:Journal of Experimental Medicine  

    Ligands from dying cells are a source of Toll-like receptor (TLR) activating agents. Although TLR3 is known to respond to RNA from necrotic cells, the relative importance of this response in vivo during acute inflammatory processes has not been fully explored. We observed the involvement of TLR3 activation during experimental polymicrobial septic peritonitis and ischemic gut injury in the absence of an exogenous viral stimulus. In TLR3-deficient mice, increased chemokine/cytokine levels and neutrophil recruitment characterized the initial inflammatory responses in both injury models. However, the levels of inflammatory chemo- kines and tumor necrosis factor α; quickly returned to baseline in tlr3 -/- mice, and these mice were protected from the lethal effects of sustained inflammation. Macrophages from tlr3 -/- mice responded normally to other TLR ligands but did not respond to RNA from necrotic neutrophils. Importantly, an immunoneutralizing antibody directed against TLR3 attenuated the generation of inflammatory chemokines evoked by byproducts from necrotic neutrophils cultured with wild-type macrophages. In vivo, anti-TLR3 antibody attenuated the tissue injury associated with gut ischemia and significantly decreased sepsis-induced mortality. Collectively, these data show that TLR3 is a regulator of the amplification of immune response and serves an endogenous sensor of necrosis, independent of viral activation.

    DOI: 10.1084/jem.20081370

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  314. CC chemokine receptor 4 modulates Toll-like receptor 9-mediated innate immunity and signaling

    Ishii M., Hogaboam C.M., Joshi A., Ito T., Fong D.J., Kunkel S.L.

    European Journal of Immunology   38 巻 ( 8 ) 頁: 2290 - 2302   2008年8月

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    出版者・発行元:European Journal of Immunology  

    The present study addressed the modulatory role of CC chemokine receptor 4 (CCR4) in Toll-like receptor (TLR) 9-mediated innate immunity and explored the underlying molecular mechanisms. Our results demonstrated that CCR4-deficient mice were resistant to both septic peritonitis induced by cecal ligation and puncture (CLP) and CpG DNA/ D-galactosamine-induced shock. In bone marrow-derived macrophages (BMMΦ) from CLP-treated CCR4-deficient mice, TLR9-mediated pathways of MAPK/AP-1, PI3K/Akt, and IκB kinase (IKK)/NF-κB were impaired compared to wild-type (WT) cells. While TLR9 expression was not altered, the intensity of internalized CpG DNA was increased in CCR4-deficient macrophages when compared to WT macrophages. Pharmacological inhibitor studies revealed that impaired activation of JNK, PI3K/Akt, and/or IKK/NF-κB could be responsible for decreased proinflammatory cytokine expression in CCR4-deficient macrophages. Interestingly, the CCR4-deficient BMMΦ exhibited an alternatively activated (M2) phenotype and the impaired TLR9-mediated signal transduction responses in CCR4-deficient cells were similar to the signaling responses observed in WT BMMΦ skewed to an alternatively activated phenotype. These results indicate that macrophages deficient in CCR4 impart a regulatory influence on TLR9-mediated innate immunity. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

    DOI: 10.1002/eji.200838360

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  315. Various adhesion molecules impair microvascular leukocyte kinetics in ventilator-induced lung injury

    Miyao N, Suzuki Y, Takeshita K, Kudo H, Ishii M, Hiraoka R, Nishio K, Tamatani T, Sakamoto S, Suematsu M, Tsumura H, Ishizaka A, Yamaguchi K

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   290 巻 ( 6 ) 頁: L1059 - L1068   2006年6月

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    出版者・発行元:American Journal of Physiology - Lung Cellular and Molecular Physiology  

    Although the endothelial expression of various adhesion molecules substantially differs between pulmonary microvessels, their importance for neutrophil and lymphocyte sequestration in ventilator-induced lung injury (VILI) has not been systematically analyzed. We investigated the kinetics of polymorphonuclear cells (PMN) and mononuclear cells (MN) in the acinar microcirculation of the isolated rat lung with VILI by real-time confocal laser fluorescence microscopy, with or without inhibition of ICAM-1, VCAM-1, or P-selectin by monoclonal antibodies (MAb). Adhesion molecules in each microvessel were estimated by intravital fluorescence microscopy or immunohistochemical staining. In high tidal volume-ventilated lungs, 1) ICAM-1, VCAM-1, and P-selectin were differently upregulated in venules, arterioles, and capillaries; 2) venular PMN rolling was improved by inhibition of ICAM-1, VCAM-1, or P-selectin, whereas arteriolar PMN rolling was improved by ICAM-1 or VCAM-1 inhibition; 3) capillary PMN entrapment was ameliorated only by anti-ICAM-1 MAb; and 4) MN rolling in venules and arterioles and MN entrapment in capillaries were improved by ICAM-1 and VCAM-1 inhibition. In conclusion, the contribution of endothelial adhesion molecules to abnormal leukocyte behavior in VILI-injured microcirculation is microvessel and leukocyte specific. ICAM-1- and VCAM-1-dependent, but P-selectin-independent, arteriolar PMN rolling, which is expected to reflect the initial stage of tissue injury, should be taken as a phenomenon unique to ventilator-associated lung injury. Copyright © 2006 the American Physiological Society.

    DOI: 10.1152/ajplung.00365.2005

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  316. 肺循環障害と肺疾患 高二酸化炭素性アシドーシスはエンドトキシンによるNF-κB活性化を抑制する

    竹下, 啓, 鈴木, 幸男, 西尾, 和三, 工藤, 裕康, 宮尾, 直樹, 石井, 誠, 佐藤, 長人, 猶木, 克彦, 青木, 琢也, 平岡, 理佳, 石坂, 彰敏, 山口, 佳寿博

    臨床呼吸生理   37 巻 ( 1 ) 頁: 29 - 32   2005年5月

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    記述言語:日本語  

    ヒト肺動脈血管内皮細胞(HPAEC)を用いてhypercapnic acidosisがNF-κB,ICAM-1ならびにIL-8発現に与える影響について検討した.その結果,hypercapnic acidosisがLPS刺激によるHPAECのNF-κB-DNA結合活性,ICAM-1およびIL-8の発現,LDHを指標とした内皮細胞傷害,好中球の接着を抑制することが明らかとなった

  317. 【ARDSの診療 どう治療するか】 GUIDANCE ARDSの疾患概念と疫学

    石井, 誠, 石坂, 彰敏

    臨床医   31 巻 ( 4 ) 頁: 416 - 418   2005年4月

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    記述言語:日本語  

  318. ARDSの新しい治療戦略

    石井, 誠, 田坂, 定智, 石坂, 彰敏

    臨床麻酔   29 巻 ( 1 ) 頁: 7 - 13   2005年1月

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    記述言語:日本語  

  319. Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs

    Ishii M, Suzuki Y, Takeshita K, Miyao N, Kudo H, Hiraoka R, Nishio K, Sato N, Naoki K, Aoki T, Yamaguchi K

    JOURNAL OF IMMUNOLOGY   172 巻 ( 4 ) 頁: 2569 - 2577   2004年2月

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    記述言語:英語   出版者・発行元:Journal of Immunology  

    Although c-Jun NH2-terminal kinase (JNK) has been implicated in the pathogenesis of transplantation-induced ischemia/reperfusion (I/R) injury in various organs, its significance in lung transplantation has not been conclusively elucidated. We therefore attempted to measure the transitional changes in JNK and AP-1 activities in I/R-injured lungs. Subsequently, we assessed the effects of JNK inhibition by the three agents including SP600125 on the degree of lung injury assessed by means of various biological markers in bronchoalveolar lavage fluid and histological examination including detection of apoptosis. In addition, we evaluated the changes in p38, extracellular signal-regulated kinase, and NF-κB-DNA binding activity. I/R injury was established in the isolated rat lung preserved in modified Euro-Collins solution at 4°C for 4 h followed by reperfusion at 37°C for 3 h. We found that AP-1 was transiently activated during ischemia but showed sustained activation during reperfusion, leading to significant lung injury and apoptosis. The change in AP-1 was generally in parallel with that of JNK, which was activated in epithelial cells (bronchial and alveolar), alveolar macrophages, and smooth muscle cells (bronchial and vascular) on immunohistochemical examination. The change in NF-κB qualitatively differed from that of AP-1. Protein leakage, release of lactate dehydrogenase and TNF-α into bronchoalveolar lavage fluid, and lung injury were improved, and apoptosis was suppressed by JNK inhibition. In conclusion, JNK plays a pivotal role in mediating lung injury caused by I/R. Therefore, inhibition of JNK activity has potential as an effective therapeutic strategy for preventing I/R injury during lung transplantation.

    DOI: 10.4049/jimmunol.172.4.2569

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  320. X COPDに合併しやすい疾患,鑑別が必要な疾患 「一次性肺嚢胞とCOPDの類似点,相違点を教えてください。」

    石井, 誠

    COPD診療ガイダンス     頁: 180 - 181   2004年

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    記述言語:日本語   出版者・発行元:メディカルビュー社  

  321. XII.患者さんの質問にどう答えるべきか 「海外に在住する場合どのようなことに注意したらよいですか。」

    石井, 誠

    COPD診療ガイダンス     頁: 273 - 274   2004年

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    記述言語:日本語   出版者・発行元:メディカルビュー社  

  322. X COPDに合併しやすい疾患,鑑別が必要な疾患 「閉塞性細気管支炎(BO)とCOPDの類似点,相違点を教えてください。」

    石井, 誠

    COPD診療ガイダンス     頁: 178 - 179   2004年

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    記述言語:日本語   出版者・発行元:メディカルビュー社  

  323. Hypercapnic acidosis attenuates endotoxin-induced nuclear factor-kappa B activation

    Takeshita K, Suzuki Y, Nishio K, Takeuchi O, Toda K, Kudo H, Miyao N, Ishii M, Sato N, Naoki K, Aoki T, Suzuki K, Hiraoka R, Yamaguchi K

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY   29 巻 ( 1 ) 頁: 124 - 132   2003年7月

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    記述言語:英語   出版者・発行元:American Journal of Respiratory Cell and Molecular Biology  

    Although permissive hypercapnia improves the prognosis of patients with acute respiratory distress syndrome, it has not been conclusively determined whether hypercapnic acidosis (HA) is harmful or beneficial to sustained inflammation of the lung. The present study was designed to explore the molecular mechanism of HA in modifying lipopolysaccharide (LPS)-associated signals in pulmonary endothelial cells. LPS elicited degradation of inhibitory protein κB (IκB)-α, but not IκB-β, resulting in activation of nuclear factor (NF)-κB in human pulmonary artery endothelial cells. Exposure to HA significantly attenuated LPS-induced NF-κB activation through suppressing IκB-α degradation. Isocapnic acidosis and buffered hypercapnia showed qualitatively similar but quantitatively smaller effects. HA did not attenuate the LPS-enhanced activation of activator protein-1. Following the reduced NF-κB activation, HA suppressed the mRNA and protein levels of intercellular adhesion molecule-1 and interleukin-8, resulting in a decrease in both lactate dehydrogenase release into the medium and neutrophil adherence to LPS-activated human pulmonary artery endothelial cells. In contrast, HA did not inhibit LPS-enhanced neutrophil expression of integrin, Mac-1. Based on these findings, we concluded that hypercapnic acidosis would have anti-inflammatory effects essentially through a mechanism inhibiting NF-κB activation, leading to downregulation of intercellular adhesion molecule-1 and interleukin-8, which in turn inhibits neutrophil adherence to pulmonary endothelial cells.

    DOI: 10.1165/rcmb.2002-0126OC

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  324. 胸腔鏡下肺生検後に急性増悪した剥離性間質性肺炎の1例

    余語 由里香, 小山田 吉孝, 石井 誠, 伯野 春彦, 藤田 愛子, 山内 徳子, 澤藤 誠, 小林 紘一, 向井 万起男, 山口 佳寿博

    日本呼吸器学会雑誌 = The journal of the Japanese Respiratory Society   41 巻 ( 6 ) 頁: 386 - 391   2003年6月

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    記述言語:日本語  

    CiNii Research

  325. [A case of acute exacerbation of desquamative interstitial pneumonia after video-assisted thoracoscopic surgery (VATS)].

    Yogo Y, Oyamada Y, Ishii M, Hakuno H, Fujita A, Yamauchi T, Sawafuji M, Kobayashi K, Mukai M, Yamaguchi K

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society   41 巻 ( 6 ) 頁: 386 - 91   2003年6月

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    記述言語:日本語  

    PubMed

  326. A case of acute exacerbation of desquamative interstitial pneumonia after video-assisted thoracoscopic surgery (VATS)

    Yogo Y., Oyamada Y., Ishii M., Hakuno H., Fujita A., Yamauchi T., Sawafuji M., Kobayashi K., Mukai M., Yamaguchi K.

    Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society   41 巻 ( 6 ) 頁: 386 - 391   2003年6月

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    出版者・発行元:Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society  

    A 70-year-old man in whom nodular and reticular shadows had been noted on chest radiography since 1992 was admitted to our hospital with complaints of persistent cough and dyspnea on exertion in August, 2000. The definitive diagnosis of lung abnormalities was not confirmed by TBLB. He was re-admitted to our hospital to undergo a lung biopsy by video-assisted thoracoscopic surgery. Although desquamative interstitial pneumonia was diagnosed, respiratory failure developed rapidly after surgery. He responded well to high-dose steroid administration followed by maintenance therapy with a moderate dose of steroid, resulting in a considerable importance of the clinical condition associated with a significant decrease in the ground-glass opacities and infiltrative shadows. Although we could find no literature reporting acute exacerbation of DIP, our case demonstrates that DIP may also be acutely exacerbated when a severe insult is superimposed.

    Scopus

  327. 気管支拡張症

    石井, 誠

    呼吸器内科処方ノート 中外医学社     頁: 203 - 212   2003年

     詳細を見る

    出版者・発行元:南江堂  

  328. 縦隔腫瘍

    石井, 誠

    呼吸器内科処方ノート 中外医学社     頁: 300 - 314   2003年

  329. 慢性呼吸不全

    石井, 誠

    呼吸器内科処方ノート 中外医学社     頁: 368 - 378   2003年

  330. NOS and COX isoforms and abnormal microvessel responses to CO2 and H+ in hyperoxia-injured lungs

    Naoki K, Kudo H, Suzuki K, Takeshita K, Miyao N, Ishii M, Sato N, Suzuki Y, Tsumura H, Yamaguchi K

    EUROPEAN RESPIRATORY JOURNAL   20 巻 ( 1 ) 頁: 43 - 51   2002年7月

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    記述言語:英語   出版者・発行元:European Respiratory Journal  

    The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX). Real-time confocal luminescence microscopy was used to measure changes in the diameter of acinar arterioles, venules and capillaries in response to stimulation with hypercapnic and isocapnic acidosis in isolated rat lungs injured by 90% oxygen exposure for 48 h. Observations were made with and without inhibition of constitutive (endothelial constitutive NOS (ecNOS) and COX-1) and inducible isoforms (iNOS and COX-2) of NOS and COX. Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX-related pathway was judged from perfusate concentrations of 6-ketoprostaglandin F1α. ecNOS and COX-1, but not iNOS and COX-2, were upregulated in hyperoxia-injured lungs. The nitric oxide produced by ecNOS attenuated COX-1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. Although a high hydrogen ion concentration was unnecessary for excitation of COX-1, venule constriction in response to H+ was enhanced by COX-1 inhibition. Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs.

    DOI: 10.1183/09031936.02.00263502

    Web of Science

    Scopus

    PubMed

  331. Effects of hypercapnia and hypocapnia on [Ca2+](i) mobilization in human pulmonary artery endothelial cells

    Nishio K, Suzuki Y, Takeshita K, Aoki T, Kudo H, Sato N, Naoki K, Miyao N, Ishii M, Yamaguchi K

    JOURNAL OF APPLIED PHYSIOLOGY   90 巻 ( 6 ) 頁: 2094 - 2100   2001年6月

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    出版者・発行元:Journal of Applied Physiology  

    The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 ± 24 to 157 ± 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 ± 56 to 50 ± 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.

    DOI: 10.1152/jappl.2001.90.6.2094

    Web of Science

    Scopus

  332. 横断性脊髄炎を呈した原発性シェーグレン症候群の1例

    金子善博, 諏訪昭, 中島亜矢子, 石井誠, 青木正紀, 堤野みち, 山田隆, 後藤眞, 上原隆夫, 田中耕太郎, 稲田進一

    リウマチ   38 巻 ( 4 ) 頁: 600-604   1998年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

▼全件表示

MISC 121

  1. いまなぜ感冒や肺炎に注目すべきか

    小林 治, 國島 広之, 石井 誠, 関 雅文, 阿部 修一  

    日本化学療法学会雑誌69 巻 ( 5 ) 頁: 361 - 366   2021年9月

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    記述言語:日本語   出版者・発行元:(公社)日本化学療法学会  

    感冒やインフルエンザはしばしば肺炎球菌性肺炎を合併することが知られているが、COVID-19における合併例は多くない。インフルエンザもCOVID-19もそれぞれ呼吸器ウイルス感染症であるので、その病像は宿主免疫反応に依存している。したがって、臨床的には病初期における正確な病原診断によって緻密な治療計画を策定することで、患者の予後改善に寄与する可能性がある。今後は感冒、インフルエンザ、COVID-19を含めた呼吸器ウイルス感染症と細菌性肺炎とを一連の病態と考えた研究と開発の必要性を発信したい。(著者抄録)

  2. 急性呼吸窮迫症候群に対する新規治療法確立に向けた直接リプログラミングによる肺再生の試み

    石井 誠  

    Shock: 日本Shock学会雑誌35 巻 ( 1 ) 頁: 16 - 16   2021年5月

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    記述言語:日本語   出版者・発行元:(一社)日本Shock学会  

  3. 【感染症とステロイド 感染リスクと感染症への効果を理解して使いこなす】感染症に対するステロイド治療の考え方と使い方 市中肺炎・ARDS

    岡森 慧, 石井 誠  

    薬局72 巻 ( 5 ) 頁: 2301 - 2304   2021年4月

     詳細を見る

    記述言語:日本語   出版者・発行元:(株)南山堂  

    <Key Points>◎軽症の市中肺炎患者に対するステロイド投与は推奨されない。◎重症の市中肺炎患者に対してステロイド投与を検討してよいが、至適投与方法は不明である。◎早期の急性呼吸窮迫症候群(ARDS)患者に対してステロイド投与(メチルプレドニゾロン1mg/kg/日相当)を検討してよい。◎いずれにおいてもエビデンスの確実性は低いためルーチン投与は推奨されず、個々の症例で慎重に判断する必要がある。(著者抄録)

  4. 【ARDS再考】幹細胞治療 iPS細胞に頼らない再生医療

    石井 誠  

    ICUとCCU45 巻 ( 3 ) 頁: 191 - 198   2021年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:医学図書出版(株)  

    急性呼吸促迫症候群(ARDS)は、種々の原因により肺血管内皮の透過性亢進を来し、進行性の低酸素血症、呼吸不全からしばしば人工呼吸管理を要する。近年ARDSに対する人工呼吸管理や体液管理などの集学的治療の発展は認めているが、なおARDSに対する確立した薬物療法はなく、その死亡率も高い。また2019年12月に原因不明の肺炎として報告され2020年にパンデミックとなった新型コロナウイルス感染症は、しばしばARDSを来す。その点でもARDSに対する新規治療法の確立は急務である。ARDSにおける幹細胞を用いた治療のなかで、とくに間葉系幹細胞による治療は、ARDSに対する動物実験や臨床試験が数多く遂行されており、有望な治療法といえる。また筆者らが近年行っている、iPS細胞などの幹細胞を経ずに線維芽細胞から直接目的とする肺上皮系細胞を誘導する直接リプログラミング法も有望と考えている。本稿では、iPS細胞によらない幹細胞治療とその将来展望に関して概説したい。(著者抄録)

  5. 再発性胸腺腫に対し放射線照射後に難治性肺炎を発症した1例

    中川原 賢亮, 阿瀬川 周平, 大竹 史朗, 齋藤 彩夏, 岡田 真彦, 李 昊, 中鉢 正太郎, 鎌田 浩史, 川田 一郎, 石井 誠, 福永 興壱  

    日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会合同学会プログラム・抄録集179回・243回 巻   頁: 15 - 15   2021年2月

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    記述言語:日本語   出版者・発行元:日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

  6. Gene Xpertを用いた空気予防策解除の妥当性評価

    上蓑 義典, 宇野 俊介, 鎌田 浩史, 西村 知泰, 石井 誠, 長谷川 直樹  

    結核95 巻 ( 5 ) 頁: 122 - 122   2020年9月

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    記述言語:日本語   出版者・発行元:(一社)日本結核・非結核性抗酸菌症学会  

  7. Pembrolizumabによる致死的な薬剤性細気管支炎を来した扁平上皮肺癌の1例

    小川 卓範, 宮田 純, 亀山 直史, 鍛治場 寛, 石井 誠, 井上 卓, 福永 興壱  

    日本呼吸器学会誌9 巻 ( 増刊 ) 頁: 179 - 179   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  8. インフルエンザ診療Up to date インフルエンザの病態と重症化機序

    石井 誠  

    日本呼吸器学会誌9 巻 ( 増刊 ) 頁: 20 - 20   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  9. ブレオマイシン誘導性肺線維症マウスモデルにおけるEZH2の役割

    岡森 慧, 石井 誠, 鎌田 浩史, 鈴木 翔二, 楠本 竜也, 小川 卓範, 宗 松男, 田中 拓, 森田 篤帆, 李 昊, 福永 興壱  

    日本呼吸器学会誌9 巻 ( 増刊 ) 頁: 248 - 248   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  10. 日本における気管支拡張症の原因および健康関連QOLの実態調査

    石井 誠  

    日本呼吸器学会誌9 巻 ( 増刊 ) 頁: 74 - 74   2020年8月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  11. 間歇喫煙曝露による2型肺胞上皮細胞の自己増殖能亢進の機序の解明

    入江 秀大, 中鉢 正太郎, 尾崎 真理, 堤 昭宏, 石井 誠, Hegab Ahmed E, 福永 興壱  

    日本呼吸器学会誌9 巻 ( 増刊 ) 頁: 189 - 189   2020年8月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  12. 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94 巻 ( 臨増 ) 頁: 167 - 167   2020年3月

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

  13. 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75 巻 ( 1 ) 頁: 7 - 7   2020年1月

     詳細を見る

    記述言語:日本語   出版者・発行元:日本細菌学会  

  14. 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41 巻 ( Suppl. ) 頁: S157 - S157   2019年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

  15. 呼吸器領域における新しい恒常性メカニズムの提唱 直接リプログラミングで誘導した肺上皮様細胞の分析

    楠本 竜也, 石井 誠, 四倉 正也, Hegab Ahmed E., 齋藤 史武, 浜本 純子, 朝倉 崇徳, 鎌田 浩史, 南宮 湖, 鈴木 翔二, 岡森 慧, 小川 卓範, 宗 松男, 淺村 尚生, 家田 真樹, 別役 智子  

    日本呼吸器学会誌8 巻 ( 増刊 ) 頁: 159 - 159   2019年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  16. 炎症性肺疾患病態解明に向けた基礎研究からのアプローチ

    石井 誠  

    日本呼吸器学会誌8 巻 ( 増刊 ) 頁: 98 - 98   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  17. 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8 巻 ( 増刊 ) 頁: 42 - 42   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  18. 呼吸器感染症の検査 インフルエンザウイルス感染におけるADAM10の保護的役割の機序の検討

    岡森 慧, 石井 誠, 朝倉 崇徳, 鈴木 翔二, 楠本 竜也, 小川 卓範, 宗 松男, 鎌田 浩史, 南宮 湖, 八木 一馬, Hegab Ahmed E., 堀内 圭輔, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌8 巻 ( 増刊 ) 頁: 160 - 160   2019年3月

     詳細を見る

    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  19. 肺Mycobacterium avium complex(MAC)症におけるSt George's Respiratory Questionnaire(SGRQ)の縦断的使用妥当性の検討

    小川 卓範, 朝倉 崇徳, 鈴木 翔二, 岡森 慧, 楠本 竜也, 宗 松男, 南宮 湖, 八木 一馬, 鎌田 浩史, 石井 誠, 長谷川 直樹  

    結核94 巻 ( 3 ) 頁: 247 - 247   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  20. 非結核性抗酸菌症 肺Mycobacterium avium complex症におけるSt George's Respiratory Questionnaireの縦断的使用妥当性の検討

    小川 卓範, 朝倉 崇徳, 鈴木 翔二, 岡森 慧, 楠本 竜也, 宗 松男, 南宮 湖, 八木 一馬, 鎌田 浩史, 石井 誠, 長谷川 直樹  

    日本呼吸器学会誌8 巻 ( 増刊 ) 頁: 158 - 158   2019年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  21. インフルエンザ後の呼吸器感染症の病態

    石井 誠, 南宮 湖  

    呼吸器内科35 巻 ( 1 ) 頁: 88 - 96   2019年1月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

  22. インフルエンザウイルス感染におけるADAM10の保護的役割の機序の検討

    岡森慧, 石井誠, 朝倉崇徳, 鈴木翔二, 楠本竜也, 小川卓範, 宗松男, 鎌田浩史, 南宮湖, 八木一馬, HEGAB Ahmed E., 堀内圭輔, 長谷川直樹, 別役智子  

    日本呼吸器学会誌(Web)8 巻   2019年

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  23. 直接リプログラミングで誘導した肺上皮様細胞の分析

    楠本竜也, 石井誠, 四倉正也, HEGAB Ahmed E., 齋藤史武, 浜本純子, 朝倉崇徳, 鎌田浩史, 南宮湖, 鈴木翔二, 岡森慧, 小川卓範, 宗松男, 淺村尚生, 家田真樹, 別役智子  

    日本呼吸器学会誌(Web)8 巻   2019年

     詳細を見る

  24. 肺Mycobacterium avium complex症におけるSt George’s Respiratory Questionnaireの縦断的使用妥当性の検討

    小川卓範, 朝倉崇徳, 鈴木翔二, 岡森慧, 楠本竜也, 宗松男, 南宮湖, 八木一馬, 鎌田浩史, 石井誠, 長谷川直樹  

    日本呼吸器学会誌(Web)8 巻   2019年

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  25. 【呼吸器領域の抗菌薬の使い方-最新エビデンスから導く基本と応用】 呼吸器領域における抗菌薬の使い方 マクロライド系薬

    石井 誠  

    感染と抗菌薬21 巻 ( 3 ) 頁: 185 - 191   2018年9月

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    記述言語:日本語   出版者・発行元:(株)ヴァンメディカル  

    マクロライド系抗菌薬は、マイコプラズマなどの非定型肺炎に第一選択の薬剤である。その抗菌作用に加え、菌への修飾作用や宿主側への免疫調整作用が知られ、実臨床でもびまん性汎細気管支炎(DPB)を含む好中球性炎症性気道疾患に対するマクロライド少量長期療法が標準治療として行われている。本稿では、マクロライドの抗菌薬としての作用と、さらに抗菌薬以外の免疫調整作用に関して、特に筆者がマウスモデルを用いた検討で得た、マクロライドで誘導される免疫調整性細胞集団の新しい知見も含め紹介したい。(著者抄録)

  26. 慢性膵炎の経過観察中に発症し、発症経路を確認し得た膵性胸水の1例

    桑江 美聡, 上田 壮一郎, 胡谷 俊樹, 長谷川 華子, 朝倉 崇徳, 石井 誠, 別役 智子  

    日本結核病学会関東支部学会・日本呼吸器学会関東地方会合同学会プログラム・抄録集174回・231回 巻   頁: 13 - 13   2018年9月

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    記述言語:日本語   出版者・発行元:日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

  27. 【呼吸器内科診療マニュアル】呼吸器疾患の主な治療薬・治療手技 主な治療手技 酸素療法

    石井 誠  

    呼吸器内科34 巻 ( Suppl.1 ) 頁: 270 - 274   2018年7月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

  28. 感冒から肺炎にいたる疾病のメカニズム・治療・予防 感冒・インフルエンザから肺炎にいたる病態の解析

    石井 誠  

    日本化学療法学会雑誌66 巻 ( 3 ) 頁: 400 - 400   2018年5月

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    記述言語:日本語   出版者・発行元:(公社)日本化学療法学会  

  29. 感冒から肺炎に至る疾患のメカニズム・治療・予防 感冒・インフルエンザから肺炎に至る病態の解析

    石井 誠  

    感染症学雑誌92 巻 ( 3 ) 頁: 410 - 410   2018年5月

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

  30. Xpert MTB/RIFにより迅速によりリファンピシン耐性が判明した肺結核の1例

    青木 渉, 上蓑 義典, 竹原 朋宏, 猪瀬 里夏, 永田 美香, 上遠野 保裕, 宇野 俊介, 藤原 宏, 鎌田 浩史, 上田 壮一郎, 石井 誠, 長谷川 直樹, 村田 満  

    日本化学療法学会雑誌66 巻 ( Suppl.A ) 頁: 258 - 258   2018年4月

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    記述言語:日本語   出版者・発行元:(公社)日本化学療法学会  

  31. 肺Mycobacterium avium complex症に対する治療成功後の間欠的維持療法の効果と安全性に関する検討 多施設後ろ向き観察研究

    朝倉 崇徳, 中川 拓, 南宮 湖, 鈴木 翔二, 森本 耕三, 石井 誠, 倉島 篤行, 小川 賢二, 長谷川 直樹  

    結核93 巻 ( 4 ) 頁: 368 - 368   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  32. 肺Mycobacterium avium complex症のフォローアップ中の肺癌合併患者の検討

    楠本 竜也, 朝倉 崇徳, 鈴木 翔二, 岡森 慧, 南宮 湖, 藤原 宏, 八木 一馬, 鎌田 浩史, 石井 誠, 長谷川 直樹  

    結核93 巻 ( 4 ) 頁: 282 - 282   2018年4月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  33. ADAM10のインフルエンザウイルス感染における保護的役割の検討

    岡森 慧, 石井 誠, 朝倉 崇徳, 鈴木 翔二, 楠本 竜也, 鎌田 浩史, 南宮 湖, 八木 一馬, Hegab Ahmed E., 堀内 圭輔, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌7 巻 ( 増刊 ) 頁: 139 - 139   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  34. 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  

    日本呼吸器学会誌7 巻 ( 増刊 ) 頁: 299 - 299   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  35. クラリスロマイシンにより誘導されるCD11b+Gr-1+細胞の誘導機序に関する検討

    石井 誠  

    The Japanese Journal of Antibiotics71 巻 ( Suppl.A ) 頁: 16 - 16   2018年3月

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    記述言語:日本語   出版者・発行元:(公財)日本感染症医薬品協会  

  36. 直接リプログラミングによる肺上皮細胞の分化誘導法の検討

    楠本 竜也, 石井 誠, 四倉 正也, Hegab Ahmed E., 齋藤 史武, 浜本 純子, 朝倉 崇徳, 鎌田 浩史, 南宮 湖, 岡森 慧, 淺村 尚生, 家田 真樹, 別役 智子  

    日本呼吸器学会誌7 巻 ( 増刊 ) 頁: 153 - 153   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  37. 肺切除術を施行した肺非結核性抗酸菌(NTM)症の長期予後の検討

    朝倉 崇徳, 早川 信崇, 長谷川 直樹, 南宮 湖, 竹内 健, 鈴木 翔二, 石井 誠, 別役 智子, 阿部 能明, 大内 基史  

    日本呼吸器学会誌7 巻 ( 増刊 ) 頁: 185 - 185   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  38. リファンピシン内服に伴いプレドニゾロン倍量投与を要した尋常性天疱瘡の1例

    増田 容子, 入來 景悟, 栗原 佑一, 舩越 建, 山上 淳, 天谷 雅行, 石井 誠, 井波 真矢子, 五十嵐 敦之  

    日本皮膚科学会雑誌128 巻 ( 3 ) 頁: 445 - 445   2018年3月

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    記述言語:日本語   出版者・発行元:(公社)日本皮膚科学会  

  39. 間歇的な喫煙曝露は肺胞II型上皮幹細胞の自己増殖能を高める

    入江 秀大, 中鉢 正太郎, 堤 昭宏, 亀山 直史, 櫻井 香, 石井 誠, 尾崎 真理, Hegab Ahmed E, 別役 智子  

    日本呼吸器学会誌7 巻 ( 増刊 ) 頁: 220 - 220   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  40. 肺気腫発症のメカニズムにおける肺上皮幹細胞の検討

    堤 昭宏, Hegab Ahmed E, 石井 誠, 尾崎 真理, 櫻井 香, 入江 秀大, 亀山 直史, 中鉢 正太郎, 別役 智子  

    日本呼吸器学会誌7 巻 ( 増刊 ) 頁: 293 - 293   2018年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  41. ARDSにおける幹細胞治療

    石井 誠  

    呼吸器内科33 巻 ( 1 ) 頁: 77 - 83   2018年1月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

  42. The efficacy, safety and feasibility of inhaled amikacin for the treatment of refractory non-tuberculous mycobacterial lung diseases

    Kazuma Yagi, Makoto Ishii, Ho Namkoong, Takahiro Asami, Osamu Iketani, Takanori Asakura, Shoji Suzuki, Satoshi Okamori, Hiroaki Sugiura, Yoshitake Yamada, Tomoyasu Nishimura, Hirofumi Kamata, Hiroshi Fujiwara, Yohei Funatsu, Yoshifumi Uwamino, Tomoko Betsuyaku, Naoki Hasegawa  

    EUROPEAN RESPIRATORY JOURNAL50 巻   2017年9月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:EUROPEAN RESPIRATORY SOC JOURNALS LTD  

    DOI: 10.1183/1393003.congress-2017.PA4073

    Web of Science

  43. ヒストンメチル基転移酵素Ezh2はインフルエンザウイルス感染後肺炎球菌2次感染マウスに保護的に作用する

    八木一馬, 八木一馬, 石井誠, 鎌田浩史, 平原潔, 南宮湖, 浅見貴弘, 朝倉崇徳, 鈴木翔二, 岡森慧, 加茂徹郎, 中山俊憲, 長谷川直樹, 別役智子  

    日本呼吸器学会誌(Web)6 巻   頁: 133   2017年3月

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    記述言語:日本語  

    J-GLOBAL

  44. 肺炎球菌による慢性閉塞性肺疾患の増悪マウスモデルにおいてS1P受容体修飾薬(ONO‐4641)は気腫進行を抑制する

    朝倉崇徳, 石井誠, 南宮湖, 鈴木翔二, 八木一馬, 岡森慧, 鎌田浩史, 岩田敏, 長谷川直樹  

    日本化学療法学会雑誌65 巻 ( Supplement-A ) 頁: 338   2017年3月

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    記述言語:日本語  

    J-GLOBAL

  45. ADAM17が肺気腫発症に与える影響の検討

    鈴木 翔二, 石井 誠, 朝倉 崇徳, 南宮 湖, 八木 一馬, 加茂 徹郎, 岡森 慧, 鎌田 浩史, 堀内 圭輔, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌6 巻 ( 増刊 ) 頁: 161 - 161   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  46. 気胸を合併した非結核性抗酸菌症の検討 2施設後ろ向きコホート研究69例

    上山 雅子, 朝倉 崇徳, 森本 耕三, 南宮 湖, 松田 周一, 大澤 武司, 石井 誠, 長谷川 直樹, 倉島 篤行, 後藤 元  

    日本呼吸器学会誌6 巻 ( 増刊 ) 頁: 296 - 296   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  47. 肺感染症 動物モデル インフルエンザウイルス感染におけるADAM10の役割に関する検討

    岡森 慧, 石井 誠, 朝倉 崇徳, 鈴木 翔二, 鎌田 浩史, 南宮 湖, 八木 一馬, 加茂 徹郎, 堀内 圭輔, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌6 巻 ( 増刊 ) 頁: 133 - 133   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  48. 高齢者肺Mycobacterium avium complex症における健康関連QOLの検討

    石井 公美子, 朝倉 崇徳, 石井 誠, 南宮 湖, 鈴木 翔二, 岡森 慧, 鎌田 浩史, 八木 一馬, 舩津 洋平, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌6 巻 ( 増刊 ) 頁: 260 - 260   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  49. 肺炎球菌による慢性閉塞性肺疾患の増悪マウスモデルにおいてS1P受容体修飾薬(ONO-4641)は気腫進行を抑制する

    朝倉 崇徳, 石井 誠, 南宮 湖, 鈴木 翔二, 八木 一馬, 岡森 慧, 鎌田 浩史, 岩田 敏, 長谷川 直樹  

    感染症学雑誌91 巻 ( 臨増 ) 頁: 338 - 338   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本感染症学会  

  50. 肺感染症 動物モデル ヒストンメチル基転移酵素Ezh2はインフルエンザウイルス感染後肺炎球菌2次感染マウスに保護的に作用する

    八木 一馬, 石井 誠, 鎌田 浩史, 平原 潔, 南宮 湖, 浅見 貴弘, 朝倉 崇徳, 鈴木 翔二, 岡森 慧, 加茂 徹郎, 中山 俊憲, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌6 巻 ( 増刊 ) 頁: 133 - 133   2017年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  51. M.abscessus complexの臨床微生物学的分析

    森本 耕三, 中川 拓, 森野 英里子, 浅見 貴弘, 長谷 衣佐乃, 松田 周一, 林 悠太, 辻本 佳恵, 藤原 宏, 佐々木 結花, 小川 賢二, 高崎 仁, 南宮 湖, 倉島 篤行, 星野 仁彦, 石井 誠, 後藤 元, 朝倉 崇徳, 青野 昭男, 長谷川 直樹, 御手洗 聡  

    結核92 巻 ( 2 ) 頁: 277 - 277   2017年2月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  52. 胃癌術後の患者に発症し、繰り返す誤嚥性肺炎と鑑別を要した肺Mycobacterium fortuitum症の1例

    岡森 慧, 朝倉 崇徳, 鎌田 浩史, 鈴木 翔二, 南宮 湖, 八木 一馬, 石井 誠, 西村 知泰, 長谷川 直樹, 別役 智子, 林 雄一郎  

    結核92 巻 ( 2 ) 頁: 245 - 245   2017年2月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  53. 過敏性肺炎様の陰影を伴い増悪した肺Mycobacterium avium complex症の一例

    八木 一馬, 南宮 湖, 朝倉 崇徳, 鈴木 翔二, 岡森 慧, 上蓑 義典, 浅見 貴弘, 舩津 洋平, 藤原 宏, 鎌田 浩史, 西村 知泰, 石井 誠, 長谷川 直樹  

    結核92 巻 ( 2 ) 頁: 306 - 306   2017年2月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  54. ミノサイクリン長期投与により気管軟骨に黒色変化を認めた一例

    額賀 重成, 朝倉 崇徳, 南宮 湖, 八木 一馬, 鈴木 翔二, 石井 誠, 田坂 定智, 別役 智子, 長谷川 直樹  

    気管支学38 巻 ( Suppl. ) 頁: S269 - S269   2016年5月

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    記述言語:日本語   出版者・発行元:(NPO)日本呼吸器内視鏡学会  

  55. 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, 八木 一馬, 南宮 湖, 浅見 貴弘, 鎌田 浩史, 上蓑 義典, 藤原 宏, 西村 知泰, 石井 誠, 田坂 定智, 長谷川 直樹  

    結核91 巻 ( 3 ) 頁: 332 - 332   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  56. インフルエンザウイルス感染後肺炎球菌2次感染マウスにおけるHDAC阻害薬 TSAの保護的効果

    八木 一馬, 石井 誠, 南宮 湖, 朝倉 崇徳, 鈴木 翔二, 藤原 宏, 西村 知泰, 加茂 徹郎, 田坂 定智, 岩田 敏, 長谷川 直樹, 別役 智子  

    日本呼吸器学会誌5 巻 ( 増刊 ) 頁: 304 - 304   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  57. ベルリン定義によるARDS重症度と患者予後、CTスコアとの関連性

    加茂 徹郎, 田坂 定智, 鈴木 武志, 朝倉 崇徳, 鈴木 翔二, 八木 一馬, 南宮 湖, 石井 誠, 森崎 浩, 別役 智子  

    日本呼吸器学会誌5 巻 ( 増刊 ) 頁: 335 - 335   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本呼吸器学会  

  58. 節外性鼻型NK/T細胞リンパ腫と鑑別を要した播種性Mycobacterium marinum症の1例

    朝倉 崇徳, 石井 誠, 南宮 湖, 八木 一馬, 鈴木 翔二, 鎌田 浩史, 鹿住 祐子, 中田 登, 上蓑 義典, 藤原 宏, 西村 知泰, 田坂 定智, 星野 仁彦, 長谷川 直樹, 菊池 拓, 清水 隆之, 岡本 真一郎, 亀山 香織  

    結核91 巻 ( 3 ) 頁: 411 - 411   2016年3月

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    記述言語:日本語   出版者・発行元:(一社)日本結核病学会  

  59. 肺Mycobacterium avium complex症で肺野浸潤影・粒状影の体積は最も肺機能と相関する CT画像解析ソフトを用いた検討

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