Updated on 2024/03/29

写真a

 
TAKADA Toshinori
 
Organization
University Medical and Dental Hospital Uonuma Institute of Community Medicine Specially Appointed Professor
Title
Specially Appointed Professor
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Degree

  • 医学博士「医学」 ( 1993.3   新潟大学 )

Research Interests

  • 希少肺疾患

  • 呼吸器内科

  • びまん性肺疾患

Research Areas

  • Life Science / Respiratory medicine  / びまん性肺疾患

Research History (researchmap)

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control   Associate Professor

    2011.4 - 2013.10

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  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control   Lecturer

    2004.4 - 2011.3

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  • Niigata University   Graduate School of Medical and Dental Sciences   Assistant

    2003.6 - 2004.3

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Research History

  • Niigata University   University Medical and Dental Hospital UONUMA CHIIKI IRYO KYOIKU CENTER JUNBISHITU   Specially Appointed Professor

    2013.11

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control   Associate Professor

    2011.4 - 2013.10

  • Niigata University   Faculty of Medicine School of Medicine   Associate Professor

    2011.4 - 2013.10

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control   Lecturer

    2004.4 - 2011.3

  • Niigata University   Graduate School of Medical and Dental Sciences   Research Assistant

    2003.6 - 2004.3

Education

  • Niigata University   Graduate School of Medicine

    1989.4 - 1993.3

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  • Niigata University   Faculty of Medicine   School of Medicine

    1979.4 - 1985.3

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Professional Memberships

  • 日本サルコイドーシス/肉芽腫性疾患学会

    2019.4

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  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

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  • THE JAPANESE RESPIRATORY SOCIETY

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  • The American Thoracic Society

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Papers

  • Dynamics of iron metabolism in patients with bloodstream infections: a time-course clinical study

    Hiroshi Moro, Yuuki Bamba, Kei Nagano, Mariko Hakamata, Hideyuki Ogata, Satoshi Shibata, Hiromi Cho, Nobumasa Aoki, Mizuho Sato, Yasuyoshi Ohshima, Satoshi Watanabe, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    Scientific Reports   13 ( 1 )   2023.11

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    Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    The close relationship between infectious diseases and iron metabolism is well known, but a more detailed understanding based on current knowledge may provide new insights into the diagnosis and treatment of infectious diseases, considering the growing threat of antibiotic-resistant bacteria. This study investigated adult patients with bloodstream infections, temporal changes, and relationships between blood levels of iron and related markers, including hepcidin and lipocalin-2 (LCN2). We included 144 samples from 48 patients (mean age 72 years, 50% male), with 30 diagnosed with sepsis. During the acute phase of infection, blood levels of hepcidin and LCN2 increased rapidly, whereas iron levels decreased, with values in 95.8% of cases below the normal range (40–188 μg/dL). Later, hepcidin and LCN2 decreased significantly during the recovery phase, and the decreased iron concentrations were restored. In the case of persistent inflammation, iron remained decreased. Acute LCN2 levels were significantly higher in patients with sepsis (p < 0.01). Hypoferremia induced by increased hepcidin would reduce iron in the environment of extracellular pathogens, and the increased LCN2 would inhibit siderophores, resulting in the prevention of the pathogen’s iron acquisition in each manner during the acute phase of bloodstream infection.

    DOI: 10.1038/s41598-023-46383-7

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    Other Link: https://www.nature.com/articles/s41598-023-46383-7

  • Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation. Reviewed International journal

    Miku Oda, Kentaro Yamaura, Haruyuki Ishii, Nobutaka Kitamura, Ryushi Tazawa, Mitsuhiro Abe, Koichiro Tatsumi, Ryosuke Eda, Shotaro Kondoh, Konosuke Morimoto, Takeshi Tanaka, Etsuro Yamaguchi, Ayumu Takahashi, Shinyu Izumi, Haruhito Sugiyama, Atsushi Nakagawa, Keisuke Tomii, Masaru Suzuki, Satoshi Konno, Shinya Ohkouchi, Naoki Tode, Tomohiro Handa, Toyohiro Hirai, Yoshikazu Inoue, Toru Arai, Katsuaki Asakawa, Takahiro Tanaka, Toshinori Takada, Hirofumi Nonaka, Koh Nakata

    Respiration; international review of thoracic diseases   1 - 9   2022.12

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    BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

    DOI: 10.1159/000528038

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  • A Japanese-American female with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis. Reviewed International journal

    Toshinori Takada, Katsuaki Asakawa, Roberto Barrios

    Clinical rheumatology   40 ( 3 )   1159 - 1165   2021.3

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    Patients with clinically amyopathic dermatomyositis (CADM) have a risk of developing rapidly progressive interstitial lung disease (ILD). CADM-ILD is associated with the anti-MDA-5 antibody. In the USA, however, patients with CADM have these antibodies less frequently than those in Japan. In addition, those with this disorder are less often complicated with rapidly progressive ILD than those in Japan. We present a case of a 42-year-old Japanese-American female with a 3-month history of a rash on her hands and face with joint pain. Based on the negative results from lupus tests, her primary care provider and a rheumatologist treated her with steroids, hydroxychloroquine, and methotrexate. During treatment, the patient started noticing shortness of breath because of pneumonia, which was revealed by a CT scan. The woman was finally diagnosed with acute respiratory failure due to CADM with ILD. She underwent a double lung transplant as well as treatment with multiple immunosuppressive agents and repeated plasma exchange but died 15 days after transplantation. Her clinical course is similar to that of Japanese patients with CADM-ILD. Outside Japan, primary care providers, rheumatologists, and dermatologists, as well as pulmonary physicians, may be less familiar with this disorder than those in Japan. Since CADM-ILD progresses very quickly and could be fatal, these doctors should be aware of this disease to treat such patients as soon as possible, particularly when seeing a patient of Japanese descent.

    DOI: 10.1007/s10067-020-05292-0

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  • Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis. Reviewed International journal

    Saori Sakaue, Etsuro Yamaguchi, Yoshikazu Inoue, Meiko Takahashi, Jun Hirata, Ken Suzuki, Satoru Ito, Toru Arai, Masaki Hirose, Yoshinori Tanino, Takefumi Nikaido, Toshio Ichiwata, Shinya Ohkouchi, Taizou Hirano, Toshinori Takada, Satoru Miyawaki, Shogo Dofuku, Yuichi Maeda, Takuro Nii, Toshihiro Kishikawa, Kotaro Ogawa, Tatsuo Masuda, Kenichi Yamamoto, Kyuto Sonehara, Ryushi Tazawa, Konosuke Morimoto, Masahiro Takaki, Satoshi Konno, Masaru Suzuki, Keisuke Tomii, Atsushi Nakagawa, Tomohiro Handa, Kiminobu Tanizawa, Haruyuki Ishii, Manabu Ishida, Toshiyuki Kato, Naoya Takeda, Koshi Yokomura, Takashi Matsui, Masaki Watanabe, Hiromasa Inoue, Kazuyoshi Imaizumi, Yasuhiro Goto, Hiroshi Kida, Tomoyuki Fujisawa, Takafumi Suda, Takashi Yamada, Yasuomi Satake, Hidenori Ibata, Nobuyuki Hizawa, Hideki Mochizuki, Atsushi Kumanogoh, Fumihiko Matsuda, Koh Nakata, Tomomitsu Hirota, Mayumi Tamari, Yukinori Okada

    Nature communications   12 ( 1 )   1032 - 1032   2021.2

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    Pulmonary alveolar proteinosis (PAP) is a devastating lung disease caused by abnormal surfactant homeostasis, with a prevalence of 6-7 cases per million population worldwide. While mutations causing hereditary PAP have been reported, the genetic basis contributing to autoimmune PAP (aPAP) has not been thoroughly investigated. Here, we conducted a genome-wide association study of aPAP in 198 patients and 395 control participants of Japanese ancestry. The common genetic variant, rs138024423 at 6p21, in the major-histocompatibility-complex (MHC) region was significantly associated with disease risk (Odds ratio [OR] = 5.2; P = 2.4 × 10-12). HLA fine-mapping revealed that the common HLA class II allele, HLA-DRB1*08:03, strongly drove this signal (OR = 4.8; P = 4.8 × 10-12), followed by an additional independent risk allele at HLA-DPβ1 amino acid position 8 (OR = 0.28; P = 3.4 × 10-7). HLA-DRB1*08:03 was also associated with an increased level of anti-GM-CSF antibody, a key driver of the disease (β = 0.32; P = 0.035). Our study demonstrated a heritable component of aPAP, suggesting an underlying genetic predisposition toward an abnormal antibody production.

    DOI: 10.1038/s41467-021-21011-y

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  • Tuberculous Spondylitis in a Woman without Pulmonary Lesions. Reviewed

    Shinichi Morita, Toshinori Takada, Kazumasa Ohashi, Shuji Terai

    Internal medicine (Tokyo, Japan)   60 ( 13 )   2157 - 2158   2021.2

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    DOI: 10.2169/internalmedicine.5054-20

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  • Efficacy of the new β-D-glucan measurement kit for diagnosing invasive fungal infections, as compared with that of four conventional kits. Reviewed International journal

    Yuuki Bamba, Kei Nagano, Hiroshi Moro, Hideyuki Ogata, Mariko Hakamata, Satoshi Shibata, Takeshi Koizumi, Nobumasa Aoki, Yasuyoshi Ohshima, Satoshi Watanabe, Takeshi Nakamura, Sugako Kobayashi, Yoshiki Hoshiyama, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    PloS one   16 ( 8 )   e0255172   2021

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    BACKGROUND: Each of the currently available (1→3)-β-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits. METHODS: The plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the β-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared. RESULTS: Of the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results. CONCLUSIONS: The newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.

    DOI: 10.1371/journal.pone.0255172

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  • 肺胞蛋白症をめぐって 肺胞蛋白症に対するGM-CSF吸入の多施設共同医師主導治験(PAGE試験)

    田澤 立之, 上田 隆宏, 安部 光洋, 巽 浩一郎, 江田 良輔, 近藤 正太郎, 森本 浩之輔, 田中 健之, 山口 悦郎, 高橋 歩, 小田 未来, 石井 晴之, 泉 信有, 杉山 温人, 中川 淳, 富井 啓介, 鈴木 雅, 今野 哲, 大河内 眞也, 東出 直樹, 半田 知宏, 平井 豊博, 井上 義一, 新井 徹, 朝川 勝明, 坂上 拓郎, 橋本 淳史, 田中 崇裕, 高田 俊範, 三上 礼子, 北村 信隆, 中田 光, PAGE試験スタディグループ

    日本呼吸器学会誌   9 ( 増刊 )   142 - 142   2020.8

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  • 肺胞蛋白症をめぐって 自己免疫性肺胞蛋白症におけるCT値測定による定量的評価の解析

    小田 未来, 石井 晴之, 北村 信隆, 鈴木 雅, 大河内 眞也, 高田 俊範, 巽 浩一郎, 泉 信有, 三上 礼子, 山口 悦郎, 井上 義一, 新井 徹, 半田 知宏, 富井 啓介, 江田 良輔, 森本 浩之輔, 田中 健之, 赤坂 圭一, 坂上 拓郎, 田中 崇裕, 田澤 立之, 中田 光, 肺胞蛋白症GMCSF吸入製剤多施設共同二重盲検比較試験(PAGE)PAGE研究班

    日本呼吸器学会誌   9 ( 増刊 )   142 - 142   2020.8

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  • Comparison of cytokine profiles between anti-ARS antibody-positive interstitial lung diseases and those with anti-MDA-5 antibodies. Reviewed International journal

    Katsuaki Asakawa, Kazutaka Yoshizawa, Ami Aoki, Yosuke Kimura, Takahiro Tanaka, Kazumasa Ohashi, Masachika Hayashi, Toshiaki Kikuchi, Shinji Sato, Toshinori Takada

    Clinical rheumatology   39 ( 7 )   2171 - 2178   2020.7

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    INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is a significant cause of mortality among patients with dermatomyositis (DM) or polymyositis (PM). There are two subtypes of PM and DM often complicated with ILD: those with anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies and those with anti-MDA-5-associated amyopathic DM (ADM). Our aim is to clarify the inflammatory and immunological differences between the disorders. METHODS: We retrospectively collected consecutive patients with anti-ARS-ILD and those with anti-MDA-5 antibody-positive ADM-ILD. The serum concentration of 38 cytokines was measured using a cytokine panel. The relative risks for anti-MDA-5 antibody-positive ADM-ILD were examined with univariate and multivariate logistic regression models. Spearman's rank correlation coefficient was calculated between cytokine levels and clinical parameters in the disease. Levels of cytokines were compared between anti-ARS-ILD and anti-MDA-5-positive ADM-ILD patients (alive or dead) using Dunnett's test. RESULTS: Twenty-three patients with anti-ARS-ILD and the same number of patients with anti-MDA-5-positive ADM-ILD were enrolled. The anti-MDA-5 group had poor survival (p = 0.025). Univariate logistic regression models showed that eotaxin, IL-10, IP-10, and MCP-1 were associated with the diagnosis of anti-MDA-5-positive ADM-ILD. Multivariate logistic regression models revealed that IP-10 was the most significantly associated (p = 0.001). Relationship analyses showed that IL-10 had significant positive correlations with CK (r = 0.5267, p = 0.009) and ferritin (r = 0.4528, p = 0.045). A comparison of the cytokine levels found that IP-10 was elevated in both patients who were alive and patients who had died with ADM-ILD compared with the levels in those with ARS-ILD (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Anti-MDA-5-positive ADM-ILD had poorer survival than anti-ARS-ILD. IP-10 seems to be most deeply involved in the pathophysiology of anti-MDA-5-associated ADM-ILD.Key Points• To clarify differences in the inflammatory and immunological features of anti-MDA-5-positive ADM-ILD and anti-ARS-ILD, we performed an observational study to measure serum cytokine concentrations before treatment using a multiplex immunoassay system.• Multivariate logistic regression models revealed that IP-10 was associated with the most significant relative risk for ADM-ILD with anti-MDA-5 antibodies.• Levels of IP-10 were elevated considerably in anti-MDA-5-positive survivors and nonsurvivors compared with the levels in anti-ARS patients.• These results suggest that IP-10 is the most deeply involved in the pathophysiology of anti-MDA-5-positive ADM-ILD.

    DOI: 10.1007/s10067-020-04984-x

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  • Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer. Reviewed

    Nobumasa Ohara, Michi Kobayashi, Yohei Ikeda, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Kazuyoshi Yagi, Takeshi Suda, Toshinori Takada, Go Hasegawa, Yo Sato, Kenichiro Hirano, Shin-Ichi Kosugi

    Internal medicine (Tokyo, Japan)   59 ( 4 )   551 - 556   2020.2

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    A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.

    DOI: 10.2169/internalmedicine.3208-19

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  • Quantitative analysis of computed tomography of the lungs in patients with lymphangioleiomyomatosis treated with sirolimus. Reviewed International journal

    Yuki Ko, Katsuaki Asakawa, Kazunori Tobino, Tsuyoshi Oguma, Toyohiro Hirai, Toshinori Takada, Kazuhisa Takahashi, Kuniaki Seyama

    Heliyon   6 ( 2 )   e03345   2020.2

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    Objectives: We aimed to study sirolimus-related lung parenchymal changes by quantitative analysis of computed tomography (CT) of the lungs in patients with lymphangioleiomyomatosis (LAM). Methods: We studied 20 participants from the Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety study, who had undergone both thin-section CT scans and pulmonary function tests at baseline, 12, and 24 months. Quantitative CT parameters such as CT-derived total lung capacity, percentage of low attenuation area (LAA%), lung density histogram, fractal property of low attenuation area, and airway dimensions were analyzed, and correlations were conducted between the longitudinal change in each quantitative CT measurement and changes in pulmonary function were examined. Among 20 participants, pre-trial (n = 8) and post-trial (n = 16) CT data were also analyzed to deduce pathophysiologic implications of the serial changes in CT parameters during trial periods. Results: FEV1 significantly increased from baseline to 24 months (slope 3.71 ± 1.50 ml/month) whereas FVC didn't during sirolimus therapy. Strikingly, LAA%, and skewness and kurtosis of density histogram significantly increased from baseline to 24 months, while mean and mode CT values significantly decreased from baseline to 24 months. Statistically significant positive correlations were found between ΔFEV1 and Δskewness (r = 0.465, p = 0.045). Taking the changes in lung density during pre-trial period into consideration, sirolimus decreases the area of -800 to -750 Housefield unit (HU) density and inhibits the decrease of -950 to -800 HU area during treatment, then producing the increased LAA% during the trial and post-trial periods. Given few sirolimus-related changes in airway dimensions, possible changes in lung mechanics may have contributed to increased FEV1. Conclusion: Our study suggests that the lung density histogram parameters, kurtosis, and skewness, may be useful as indicators of the efficacy of sirolimus.

    DOI: 10.1016/j.heliyon.2020.e03345

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  • Validation of a new serum granulocyte-macrophage colony-stimulating factor autoantibody testing kit. Reviewed International journal

    Koh Nakata, Tatsuki Sugi, Keiko Kuroda, Kazutaka Yoshizawa, Toshinori Takada, Ryushi Tazawa, Takahiro Ueda, Ami Aoki, Mitsuhiro Abe, Koichiro Tatsumi, Ryosuke Eda, Shotaro Kondoh, Konosuke Morimoto, Takeshi Tanaka, Etsuro Yamaguchi, Ayumu Takahashi, Miku Oda, Haruyuki Ishii, Shinyu Izumi, Haruhito Sugiyama, Atsushi Nakagawa, Keisuke Tomii, Masaru Suzuki, Satoshi Konno, Shinya Ohkouchi, Taizou Hirano, Tomohiro Handa, Toyohiro Hirai, Yoshikazu Inoue, Toru Arai, Katsuaki Asakawa, Takuro Sakagami, Takahiro Tanaka, Ayako Mikami, Nobutaka Kitamura

    ERJ open research   6 ( 1 )   2020.1

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    Very recently, a modest but significant efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy for the treatment of mild to moderate autoimmune pulmonary alveolar proteinosis (aPAP) has been reported. As the ability to measure the level of GM-CSF autoantibody (GMAb) in the serum is required to decide the indication for this therapy, we developed a high-performance GMAb testing kit for clinical use. As the kit succeeded in reducing nonspecific IgG binding to the ELISA plate, the predictive performance shown in the training study to discriminate aPAP patients from healthy subjects was perfect, providing a cut-off value of 1.65 U·mL-1 in 78 patients with aPAP and 90 healthy subjects in an operator-blinded manner using logistic regression analysis. As in the validation study, serum samples from another 213 patients with aPAP were also blinded and evaluated in an operator-blinded manner against external 207 samples from patients with other types of PAP and patients exhibiting various ground-glass opacities on chest high-resolution computed tomography that require discrimination from PAP. The logistic regression analysis of these validation data sets revealed values of 97.6% and 100% for specificity and sensitivity, respectively. Thus, this new GMAb testing kit is reliable for the diagnosis of aPAP and differential diagnosis of other lung diseases.

    DOI: 10.1183/23120541.00259-2019

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  • Inhaled GM-CSF for Pulmonary Alveolar Proteinosis. Reviewed International journal

    Ryushi Tazawa, Takahiro Ueda, Mitsuhiro Abe, Koichiro Tatsumi, Ryosuke Eda, Shotaro Kondoh, Konosuke Morimoto, Takeshi Tanaka, Etsuro Yamaguchi, Ayumu Takahashi, Miku Oda, Haruyuki Ishii, Shinyu Izumi, Haruhito Sugiyama, Atsushi Nakagawa, Keisuke Tomii, Masaru Suzuki, Satoshi Konno, Shinya Ohkouchi, Naoki Tode, Tomohiro Handa, Toyohiro Hirai, Yoshikazu Inoue, Toru Arai, Katsuaki Asakawa, Takuro Sakagami, Atsushi Hashimoto, Takahiro Tanaka, Toshinori Takada, Ayako Mikami, Nobutaka Kitamura, Koh Nakata

    The New England journal of medicine   381 ( 10 )   923 - 932   2019.9

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    BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 μg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).

    DOI: 10.1056/NEJMoa1816216

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  • Multiplex cytokine analysis in Mycobacterium avium complex lung disease: relationship between CXCL10 and poor prognostic factors. Reviewed International journal

    Yuuki Bamba, Hiroshi Moro, Nobumasa Aoki, Takeshi Koizumi, Yasuyoshi Ohshima, Satoshi Watanabe, Takuro Sakagami, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    BMC infectious diseases   19 ( 1 )   263 - 263   2019.3

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    BACKGROUND: Mycobacterium avium complex lung disease (MAC-LD) can deteriorate rapidly to become fatal. Reported poor prognostic factors include radiographic findings, undernutrition, anemia and high inflammation test values. However, the association of these prognostic factors with the pathophysiology of the disease remains unknown. We aimed to clarify the pathophysiology of MAC-LD and develop a new biomarker that reflects the immune response to the disease. METHODS: We performed the cytokine panel analyses of serum from patients with MAC-LD and compared each cytokine level with clinically negative prognostic factors (radiographic disease type, body mass index, albumin, C-reactive protein and hemoglobin) and high-resolution CT scores. RESULTS: We analyzed 27 patients with MAC-LD, 6 with the fibrocavitary form and 21 with the nodular bronchiectatic form on high-resolution CT. Serum CXC motif ligand 10 (CXCL10) concentration was significantly elevated in patients with the fibrocavitary form (p = 0.008). CXCL10 levels correlated with body mass index (r = - 0.60, p = 0.0008), serum albumin concentration (r = - 0.45, p = 0.016) and high-resolution CT scores (r = 0.61, p = 0.0006). Among 14 patients initially untreated, antibiotic therapy was initiated for five during the study period. CXCL10 concentration was significantly higher in these patients (p = 0.046), and receiver operating characteristic analysis for CXCL10 concentration on treatment initiation produced an area under the curve of 0.844, with a sensitivity of 100%, specificity of 66.7%, and cut-off value of 366.5 pg/mL. CONCLUSION: We revealed cytokine profiles in patients with MAC-LD. Serum CXCL10 levels probably reflect the severity of MAC-LD. Our findings suggest that CXCL10 concentration may be a promising biomarker for managing treatment for patients with MAC disease of the lung.

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  • Isolated adrenocorticotropic hormone deficiency and thyroiditis associated with nivolumab therapy in a patient with advanced lung adenocarcinoma: a case report and review of the literature. Reviewed

    Ohara N, Kobayashi M, Ohashi K, Ito R, Ikeda Y, Kawaguchi G, Yoneoka Y, Hasegawa G, Takada T

    Journal of medical case reports   13 ( 1 )   88   2019.3

  • 抗MDA-5抗体陽性皮膚筋炎にともなう間質性肺炎におけるIL-15の役割

    高田 俊範, 青木 亜美, 大橋 和政, 木村 陽介, 林 正周, 菊地 利明

    日本呼吸器学会誌   8 ( 増刊 )   227 - 227   2019.3

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  • 肺胞蛋白症の20年史 自己免疫性肺胞蛋白症に対するGM-CSF吸入療法

    田澤 立之, 鈴木 雅, 大河内 眞也, 朝川 勝明, 巽 浩一郎, 石井 晴之, 泉 信有, 山口 悦郎, 井上 義一, 半田 知宏, 富井 啓介, 江田 良輔, 森本 浩之輔, 三上 礼子, 田中 崇裕, 北村 信隆, 高田 俊範, 上田 隆宏, 中垣 和英, 中田 光

    日本呼吸器学会誌   8 ( 増刊 )   23 - 23   2019.3

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  • Incidence of autoimmune pulmonary alveolar proteinosis estimated using Poisson distribution. Reviewed International journal

    Nobutaka Kitamura, Shinya Ohkouchi, Ryushi Tazawa, Haruyuki Ishii, Toshinori Takada, Takuro Sakagami, Takahiro Tanaka, Koh Nakata

    ERJ open research   5 ( 1 )   2019.2

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    The incidence and prevalence of autoimmune pulmonary alveolar proteinosis in Japan were previously estimated to be 0.49 and 6.2 per million, respectively. Thereafter, an increase in serological diagnosis forced a re-estimation of the incidence based on more contemporaneous data using more robust methods. Sera of 702 patients were positive for granulocyte-macrophage colony-stimulating factor autoantibody during the 2006-2016 period (group A). Of these patients, 43 were actively surveyed in Niigata prefecture (group B) for estimation of the incidence. To estimate the survival period, 103 patients (group C) were investigated retrospectively for the 1999-2017 period using restricted mean survival time. In group A, the number of patients diagnosed in each prefecture was closely correlated with the corresponding population, indicating no regional integration of onset. In group B, a total of 43 patients were diagnosed, the annual number followed a Poisson distribution and the incidence was thus estimated to be 1.65 per million. In group C, the retrospective cohort study revealed the mean survival period to be 16.1 years. Taken together, the prevalence was estimated to be 26.6 per million, indicating that the previous data for incidence and prevalence was an underestimation.

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  • Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody. Reviewed International journal

    Toshinori Takada, Kazumasa Ohashi, Masachika Hayashi, Katsuaki Asakawa, Takuro Sakagami, Toshiaki Kikuchi, Shinji Sato

    Respiratory medicine   141   7 - 13   2018.8

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    BACKGROUND: Anti-MDA-5 antibody is closely associated with interstitial lung disease (ILD) in amyopathic dermatomyositis (ADM). Patients with ADM with anti-MDA-5 antibody sometimes develop fatal ILD in spite of intensive immunosuppressive therapy. However, an initial decrease after treatment in anti-MDA-5 antibody titers may not be predictive of subsequent better survival of the disease. METHODS: To clarify immunoregulatory features of deadly ILD in ADM with the anti-MDA-5 antibody, we retrospectively examined clinical records of consecutive patients with anti-MDA-5 antibody positive ADM-ILD with preserved serum since 2000. Serum cytokine/growth factor (GF) protein concentration was measured using a cytokine panel analysis. We compared concentrations of each cytokine/GF between survivors and non-survivors and further examined changes in cytokines/GF levels during treatment in some patients. RESULTS: Twenty-six patients were enrolled in the study. Nine out of 26 patients did not respond to intensive immunosuppressive therapy and died due to respiratory failure. We compared cytokine/GF concentrations and found that serum IL-15 before treatment was significantly elevated in non-survivors than in survivors (p < 0.05). 11 out of 17 responders and 6 of 9 dead patients had preserved serum taken more than one time. We then calculated rates of change per day (slopes) in each cytokine/GF concentration. Comparison of slopes of cytokine/GF protein over the treatment duration showed that the slopes in non-survivors were significantly increased in IL-10 and IL-15 (p < 0.01). CONCLUSIONS: IL-15, as well as IL-10, may play a key role in the progression of the patients with ADM-ILD with anti-MDA-5 antibody positive.

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  • Glutamic Acid Decarboxylase Autoantibody-negative Slowly Progressive Type 1 Diabetes Mellitus: A Case Report and Literature Review. Reviewed

    Kobayashi M, Ohara N, Ikeda Y, Nagano O, Takada T, Kodama M, Sone H

    Internal medicine (Tokyo, Japan)   57 ( 24 )   3581 - 3587   2018.8

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    A 59-year-old non-obese Japanese woman developed diabetes mellitus with a negative glutamic acid decarboxylase autoantibody (GADA) test result. Her hyperglycemia was initially well controlled by oral hypoglycemic agents; however, despite continued treatment the hyperglycemia gradually worsened. As she had endogenous insulin deficiency and tested positive for insulin autoantibody (IAA), insulin therapy was initiated. Few studies have investigated GADA-negative patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA-positive SPT1D patient progressed from the clinical onset of diabetes mellitus to starting insulin therapy relatively quickly (1.5 years), similarly to other previously reported non-obese patients with GADA-positive SPT1D.

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  • Legionella Pneumonia Complicated with Acquired Fanconi Syndrome: A Case Report. Reviewed

    Koda R, Itoh R, Tsuchida M, Ohashi K, Iino N, Takada T, Narita I

    Internal medicine (Tokyo, Japan)   57 ( 20 )   2975 - 2980   2018.6

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  • Bevacizumab-induced Aortic Arterial Thrombosis. Reviewed

    Suzuki K, Yanagimura T, Ohashi K, Kagamu H, Takada T

    Internal medicine (Tokyo, Japan)   2018.5

  • Mycophenolate mofetil as a therapeutic agent for interstitial lung diseases in systemic sclerosis. Reviewed International journal

    Takahiro Ueda, Takuro Sakagami, Toshiaki Kikuchi, Toshinori Takada

    Respiratory investigation   56 ( 1 )   14 - 20   2018.1

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    Systemic sclerosis (SSc) is an intractable disease that causes fibrosis in all organs. Approximately 40% of patients with SSc have some degree of interstitial lung disease (ILD). One third of patients with SSc and ILD, approximately 15% of all patients, have pulmonary lesions, which slowly progress to respiratory failure resistant to corticosteroid and other treatments. A randomized controlled trial conducted in the United States indicated that one year of treatment with oral cyclophosphamide in patients with SSc-ILD had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and health-related quality of life. However, all the effects, except for a sustained impact on dyspnea, disappeared approximately one year after stopping oral administration of cyclophosphamide. A randomized controlled trial using cyclophosphamide and mycophenolate mofetil (MMF) was then held in the United States for 142 patients with SSc-ILD. Treatment of SSc-ILD with MMF for two years or cyclophosphamide for one year both resulted in significant improvements in lung function over the 2-year course of the study. Leukopenia and thrombocytopenia occurred less often in patients administered MMF than in those administered cyclophosphamide. MMF is currently not approved for the treatment of SSc-ILD in Japan. Both MMF and cyclophosphamide were effective against ILD associated with SSc and, in particular, MMF was useful in terms of tolerability. When MMF is approved, it should be positioned as one of the first treatment options for SSc-ILD, which will further enhance the treatment of this disease in Japan.

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  • Isolated adrenocorticotropin deficiency due to nivolumab-induced hypophysitis in a patient with advanced lung adenocarcinoma: A case report and literature review Reviewed

    Nobumasa Ohara, Kazumasa Ohashi, Toshiya Fujisaki, Chiyumi Oda, Yohei Ikeda, Yuichiro Yoneoka, Takehisa Hashimoto, Go Hasegawa, Kazuo Suzuki, Toshinori Takada

    Internal Medicine   57 ( 4 )   527 - 535   2018

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    A 63-year-old Japanese woman with advanced lung adenocarcinoma developed isolated adrenocorticotropin deficiency caused by immune checkpoint inhibitor (ICI)-related hypophysitis following 8 months of nivolumab therapy. Prompt corticosteroid replacement therapy effectively relieved her secondary adrenal insufficiency symptoms and allowed her to pursue nivolumab therapy, which had been effective for the control of lung adenocarcinoma. Human leukocyte antigen (HLA) typing revealed the presence of the DRB1*04:05-DQA1*03:03-DQB1*04:01 haplotype, which is associated with susceptibility to autoimmune polyglandular syndrome with pituitary disorder in the Japanese population. This case suggests that genetic factors, such as HLA, contribute to the development of endocrinopathies induced by ICIs.

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  • Increased presepsin levels are associated with the severity of fungal bloodstream infections. Reviewed International journal

    Yuuki Bamba, Hiroshi Moro, Nobumasa Aoki, Takeshi Koizumi, Yasuyoshi Ohshima, Satoshi Watanabe, Takuro Sakagami, Toshiyuki Koya, Toshinori Takada, Toshiaki Kikuchi

    PloS one   13 ( 10 )   e0206089   2018

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    BACKGROUND: Presepsin is a widely recognized biomarker for sepsis. However, little is known about the usefulness of presepsin in invasive fungal infection. The aim of this study was to determine the plasma levels of presepsin in fungal bloodstream infections and to investigate whether it reflects the disease severity, similar to its utility in bacterial infections. METHODS: We prospectively measured presepsin in plasma samples from participants with fungemia from April 2016 to December 2017. The associations of C-reactive protein, procalcitonin, and presepsin concentrations with the severity of fungemia were statistically analyzed. In vitro assay was performed by incubating Escherichia coli, Candida albicans, and lipopolysaccharide to whole blood cells collected from healthy subjects; after 3 h, the presepsin concentration was measured in the supernatant and was compared among the bacteria, fungi, and LPS groups. RESULTS: Presepsin was increased in 11 patients with fungal bloodstream infections. Serial measurement of presepsin levels demonstrated a prompt decrease in 7 patients in whom treatment was effective, but no decrease or further increase in the patients with poor improvement. Additionally, presepsin concentrations were significantly correlated with the Sequential Organ Failure Assessment score (r = 0.89, p < 0.001). In vitro assay with co-incubation of C. albicans and human whole blood cells indicated that the viable cells of C. albicans caused an increase in presepsin, as seen with E. coli. CONCLUSIONS: Plasma presepsin levels increased in patients with fungal bloodstream infection, with positive association with the disease severity. Presepsin could be a useful biomarker of sepsis secondary to fungal infections.

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  • Risk factors for stomatitis in patients with lymphangioleiomyomatosis during treatment with sirolimus: A multicenter investigator-initiated prospective study Reviewed

    Nobutaka Kitamura, Kuniaki Seyama, Yoshikazu Inoue, Katsura Nagai, Masaru Suzuki, Hiroshi Moriyama, Toshinori Takada, Ryushi Tazawa, Toyohiro Hirai, Michiaki Mishima, Mie Hayashida, Masaki Hirose, Toru Arai, Chikatoshi Sugimoto, Noboru Hattori, Kentaro Watanabe, Tsutomu Tamada, Kohei Akazawa, Takahiro Tanaka, Koh Nakata

    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY   26 ( 10 )   1182 - 1189   2017.10

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    PurposeLymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial.
    MethodsSubjects received sirolimus for 2years at doses adjusted to maintain a trough blood level of 5 to 15ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses.
    ResultsThe most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (&lt;14.5g/dL) showed significantly higher incidence than those with high Hb (14.5g/dL, P&lt;.01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study.
    ConclusionsBaseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.

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  • A semiquantitative computed tomographic grading system for evaluating therapeutic response in pulmonary alveolar proteinosis Reviewed

    Sayoko Tokura, Masanori Akira, Tomohisa Okuma, Ryushi Tazawa, Toru Arai, Chikatoshi Sugimoto, Akiko Matsumuro, Masaki Hirose, Toshinori Takada, Koh Nakata, Haruyuki Ishii, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshiko Tsuchihashi, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Takahito Nei, Konosuke Morimoto, Yasuyuki Nasuhara, Masahito Ebina, Toshio Ichiwata, Koichiro Tatsumi, Etsuro Yamaguchi, Yoshikazu Inoue

    Annals of the American Thoracic Society   14 ( 9 )   1403 - 1411   2017.9

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    Rationale: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used. Objectives: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP. Methods: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte-macrophage colony-stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results. Results: CT grade score and CT extent score had significant correlationwith diffusing capacity of the lung for carbon monoxide percent predicted (%DLCO), PaO2, VC percent predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The change in CT grade score between pre- and post-treatment examinations (ΔCT grade) correlated better with difference of PaO2 between pre- and post-treatment examinations (ΔPaO2) than DCT extent (difference of CT extent score between pre- and post-treatment examinations). In univariate analysis, ΔCT grade, ΔCT extent, ΔKL-6, Δ%DLCO, Δ%VC, and change in surfactant protein D correlated significantly with ΔPaO2. Inmultivariate analysis, ΔCT grade and ΔKL-6 correlated more closely with ΔPaO2.

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  • A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis. Reviewed

    Tokura S, Akira M, Okuma T, Tazawa R, Arai T, Sugimoto C, Matsumuro A, Hirose M, Takada T, Nakata K, Ishii H, Kasahara Y, Hojo M, Ohkouchi S, Tsuchihashi Y, Yokoba M, Eda R, Nakayama H, Nei T, Morimoto K, Nasuhara Y, Ebina M, Ichiwata T, Tatsumi K, Yamaguchi E, Inoue Y

    Annals of the American Thoracic Society   14 ( 9 )   1403 - 1411   2017.9

  • A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis Reviewed

    Sayoko Tokura, Masanori Akira, Tomohisa Okuma, Ryushi Tazawa, Toru Arai, Chikatoshi Sugimoto, Akiko Matsumuro, Masaki Hirose, Toshinori Takada, Koh Nakata, Haruyuki Ishii, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshiko Tsuchihashi, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Takahito Nei, Konosuke Morimoto, Yasuyuki Nasuhara, Masahito Ebina, Toshio Ichiwata, Koichiro Tatsumi, Etsuro Yamaguchi, Yoshikazu Inoue

    ANNALS OF THE AMERICAN THORACIC SOCIETY   14 ( 9 )   1403 - 1411   2017.9

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    Rationale: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used.
    Objectives: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP.
    Methods: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte-macrophage colony-stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results.
    Results: CT grade score and CT extent score had significant correlationwith diffusing capacity of the lung for carbon monoxide percent predicted (% DLCO), Pa-O2, VC percent predicted (% VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The change in CT grade score between pre-and post-treatment examinations (Delta CT grade) correlated better with difference of Pa-O2 between pre-and post-treatment examinations (Delta Pa-O2) than Delta CT extent (difference of CT extent score between pre-and post-treatment examinations). In univariate analysis, Delta CT grade, Delta CT extent, Delta KL-6, Delta%DLCO, Delta%VC, and change in surfactant protein D correlated significantly with Delta Pa-O2. Inmultivariate analysis, Delta CT grade and DKL-6 correlated more closely with Delta Pa-O2.
    Conclusions: Although a number of CT variables were collected, the currently proposed grading system that correlates well with Pa-O2 should be viewed as a retrospective scoring system that needs future validation with another PAP cohort.

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  • Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: A case report Reviewed

    Nobumasa Ohara, Yuichiro Yoneoka, Yasuhiro Seki, Katsuhiko Akiyama, Masataka Arita, Kazumasa Ohashi, Kazuo Suzuki, Toshinori Takada

    Journal of Medical Case Reports   11 ( 1 )   235   2017.8

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    Background: Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. Case presentation: An 83-year-old Japanese man developed acute anterior hypopituitarism
    he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Conclusions: Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

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  • Sequential granulocyte-macrophage colony-stimulating factor inhalation after whole-lung lavage for pulmonary alveolar proteinosis: A report of five intractable cases Reviewed

    Shinya Ohkouchi, Keiichi Akasaka, Toshio Ichiwata, Shu Hisata, Hideya Iijima, Toshinori Takada, Hiroki Tsukada, Hideaki Nakayama, Jun-Ichi Machiya, Toshiya Irokawa, Hiromasa Ogawa, Yoko Shibata, Masakazu Ichinose, Masahito Ebina, Toshihiro Nukiwa, Hajime Kurosawa, Koh Nakata, Ryushi Tazawa

    Annals of the American Thoracic Society   14 ( 8 )   1298 - 1304   2017.8

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    Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The antibodies inhibit the maturation and phagocytosis of alveolar macrophages. Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years. GM-CSF inhalation therapy is a new procedure for treating aPAP and can induce remission with less invasiveness, although it is generally less effective in severe cases. We evaluated five cases with remarkable improvement by using sequential GM-CSF inhalation therapy after WLL
    however, the treatment failed when this therapy preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the efficiency of WLL in patients with severe aPAP.

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  • Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after Whole-Lung Lavage for Pulmonary Alveolar Proteinosis. A Report of Five Intractable Cases. Reviewed

    Ohkouchi S, Akasaka K, Ichiwata T, Hisata S, Iijima H, Takada T, Tsukada H, Nakayama H, Machiya JI, Irokawa T, Ogawa H, Shibata Y, Ichinose M, Ebina M, Nukiwa T, Kurosawa H, Nakata K, Tazawa R

    Annals of the American Thoracic Society   14 ( 8 )   1298 - 1304   2017.8

  • Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after Whole-Lung Lavage for Pulmonary Alveolar Proteinosis A Report of Five Intractable Cases Reviewed

    Shinya Ohkouchi, Keiichi Akasaka, Toshio Ichiwata, Shu Hisata, Hideya Iijima, Toshinori Takada, Hiroki Tsukada, Hideaki Nakayama, Jun-ichi Machiya, Toshiya Irokawa, Hiromasa Ogawa, Yoko Shibata, Masakazu Ichinose, Masahito Ebina, Toshihiro Nukiwa, Hajime Kurosawa, Koh Nakata, Ryushi Tazawa

    ANNALS OF THE AMERICAN THORACIC SOCIETY   14 ( 8 )   1298 - 1304   2017.8

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    Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The antibodies inhibit the maturation and phagocytosis of alveolar macrophages. Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years. GM-CSF inhalation therapy is a new procedure for treating aPAP and can induce remission with less invasiveness, although it is generally less effective in severe cases. We evaluated five cases with remarkable improvement by using sequential GM-CSF inhalation therapy after WLL; however, the treatment failed when this therapy preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the efficiency of WLL in patients with severe aPAP.

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  • Cytokine profiles of amyopathic dermatomyositis with interstitial lung diseases treated with mycophenolate. Reviewed International journal

    Masachika Hayashi, Ami Aoki, Katsuaki Asakawa, Takuro Sakagami, Toshiaki Kikuchi, Toshinori Takada

    Respirology case reports   5 ( 4 )   e00235   2017.7

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    A 59-year-old Japanese man diagnosed with interstitial lung disease associated with amyopathic dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA-5) antibodies was treated with intravenous methyl prednisolone (PSL) 1000 mg, oral PSL 1 mg/kg, and oral cyclosporin 200 mg daily. His respiratory condition worsened after treatment with two times of intravenous cyclophosphamide and another steroid pulse therapy as well as PSL and cyclosporin. Addition of mycophenolate mofetil (MMF), 1.5 g daily improved PaO2/FiO2 (PF) ratio of the patient from 294 to 360 at 4 weeks and 416 at 15 weeks after addition of MMF. We measured cytokine concentration in preserved serum taken at 11 and 7 weeks before addition of MMF and at 4, 11, and 15 weeks after MMF administration. Of the 28 cytokines evaluated, the concentrations of fibroblast growth factors-2 (FGF-2), chemokine (C-X3-C motif) ligand 1 (CX3CL1), interleukin (IL)-1ra, IL-17A, inducible protein 10 (IP-10), and monocyte chemotactic protein-1 (MCP-1) decreased after addition of MMF. These results suggest that MMF may be beneficial to patients with interstitial lung disease by modification of the cytokine/growth factor protein expression.

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  • 次世代シークエンサーによる自己免疫性肺胞蛋白症のGM-CSF自己抗体軽鎖配列の解析

    橋本 淳史, 竹内 志穂, 中垣 和英, 伊藤 祐子, 高田 俊範, 赤坂 圭一, 田澤 立之, 根井 貴仁, 田中 崇裕, 中田 光

    分子呼吸器病   21 ( 1 )   98 - 102   2017.3

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    自己免疫性肺胞蛋白症患者の血液から比重遠心法を用いて末梢血単核細胞(PBMC)を分離した。分離したB細胞とビオチン化GM-CSFを反応させ、結合した細胞をGM-CSF反応性B細胞(自己抗体BCR陽性細胞)と考え、抗ビオチン抗体ビーズを用いて磁気分離した。33検体(患者24、健常者3)の解析をおこない、全体のリード数が16万リード、合計クラスターは2万4千クラスターであった。抗体が実際に産生されていると考えられるproductive sequenceの割合は全体の76%を占めた。アイソタイプの違いについて検討し、ほぼ全ての検体においてκ鎖の場合、Vκ1およびVκ3、Lambda鎖の場合、Vλ1、Vλ2、Vλ3のシークエンスが占める割合が高かった。患者検体CDR1の配列において平均連結法を用いてAlignmentおよび樹形図解析をおこなった。GM-CSFに反応するBCR陽性B細胞とGM-CSFに反応しないBCRをもつB細胞のシークエンスの間では、お互いの配列にまったく類似性がなく、自己抗体の軽鎖配列がそれ以外の軽鎖配列と分子レベルで異なることを確認した。

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  • CT画像解析を用いた、リンパ脈管筋腫症(LAM)におけるシロリムスの効果の検討

    神 幸希, 朝川 勝明, 高田 俊範, 飛野 和則, 瀬山 邦明, 平井 豊博, 高橋 和久

    日本呼吸器学会誌   6 ( 増刊 )   116 - 116   2017.3

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  • Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile Reviewed

    Masayuki Ito, Kazuyuki Nakagome, Hiromitsu Ohta, Keiichi Akasaka, Yoshitaka Uchida, Atsushi Hashimoto, Ayako Shiono, Toshinori Takada, Makoto Nagata, Jun Tohyama, Koichi Hagiwara, Minoru Kanazawa, Koh Nakata, Ryushi Tazawa

    BMC PULMONARY MEDICINE   17 ( 1 )   40   2017.2

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    Background: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP.
    Case presentation: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage. She tested negative for GM-CSF autoantibodies, with no underlying disease. Her serum GM-CSF level was elevated (91.3 pg/mL), indicating GM-CSF signaling impairment and genetic defects in the GM-CSF receptor. GM-CSF-stimulated phosphorylation in signal transducer and activator of transcription 5 (STAT5) was not observed, and GM-CSF-Ra expression was defective in her blood cells. Genetic screening revealed a homozygous, single-base C &gt; T mutation at nt 508-a nonsense mutation that yields a stop codon (Q170X)-in exon 7 of CSF2RA. High-resolution analysis of single nucleotide polymorphism array confirmed a 22.8-Mb loss of heterozygosity region in Xp22.33p22.11, encompassing the CSF2RA gene. She was successfully treated with whole lung lavage (WLL), which reduced the serum levels of interleukin (IL)-2, IL-5, and IL-17, although IL-3 and M-CSF levels remained high.
    Conclusions: This is the first known report of elderly-onset hPAP associated with a CSF2RA mutation, which caused defective GM-CSF-Ra expression and impaired signaling. The analyses of serum cytokine levels during WLL suggested that GM-CSF signaling might be compensated by other signaling pathways, leading to elderly-onset PAP.

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  • Mycophenolate mofetil for the patients with interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibodies Reviewed

    Masachika Hayashi, Toshiaki Kikuchi, Toshinori Takada

    CLINICAL RHEUMATOLOGY   36 ( 1 )   239 - 240   2017.1

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  • 閉塞性睡眠時無呼吸を合併し、神経痛性筋萎縮症に続発したと思われた両側横隔神経麻痺の1例

    穂苅 諭, 大嶋 康義, 鈴木 涼子, 梶原 大季, 高田 俊範, 鈴木 栄一

    日本胸部臨床   75 ( 12 )   1420 - 1426   2016.12

  • PMX-DHP療法が奏効した食道癌術後ARDSの1例

    大橋 和政, 鈴木 和夫, 高田 俊範, 渡辺 博文, 甲田 亮, 飯野 則昭, 柳村 尚寛

    新潟急性血液浄化研究会抄録集   3回   4 - 4   2016.12

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  • Efficacy and safety of long-term sirolimus therapy for asian patients with lymphangioleiomyomatosis Reviewed

    Toshinori Takada, Ayako Mikami, Nobutaka Kitamura, Kuniaki Seyama, Yoshikazu Inoue, Katsura Nagai, Masaru Suzuki, Hiroshi Moriyama, Keiichi Akasaka, Ryushi Tazawa, Toyohiro Hirai, Michiaki Mishima, Mie Hayashida, Masaki Hirose, Chikatoshi Sugimoto, Toru Arai, Noboru Hattori, Kentaro Watanabe, Tsutomu Tamada, Hirohisa Yoshizawa, Kohei Akazawa, Takahiro Tanaka, Keita Yagi, Lisa R. Young, Francis X. McCormack, Koh Nakata

    Annals of the American Thoracic Society   13 ( 11 )   1912 - 1922   2016.11

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    Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period
    however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression. Objectives: To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM. Methods: We conducted a single-arm, open-label, investigatorinitiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml. Measurements and Main Results: Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in 30 patients (48%)
    microcytosis in 10 patients
    loss of body weight in 33 patients
    and increase in blood pressure that required treatment in 5 patients. FEV1, FVC, and quality-of-life parameters were stable in the overall study cohort during the study period, but baseline to 2-year improvements in lung function occurred in the subset of patients with a prior history of chylothorax. Conclusions: Although long-term sirolimus treatment of Asian patients with LAM was associated with a large number of adverse events, including three episodes of pneumonitis, most patients completed the 2-year course of medication with good drug compliance and stable quality of life and lung function.

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  • Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis Reviewed

    Takada, Toshinori, Mikami, Ayako, Kitamura, Nobutaka, Seyama, Kuniaki, Inoue, Yoshikazu, Nagai, Katsura, Suzuki, Masaru, Moriyama, Hiroshi, Akasaka, Keiichi, Tazawa, Ryushi, Hirai, Toyohiro, Mishima, Michiaki, Hayashida, Mie, Hirose, Masaki, Sugimoto, Chikatoshi, Arai, Toru, Hattori, Noboru, Watanabe, Kentaro, Tamada, Tsutomu, Yoshizawa, Hirohisa, Akazawa, Kohei, Tanaka, Takahiro, Yagi, Keita, Young, Lisa R, McCormack, Francis X, Nakata, Koh

    ANNALS OF THE AMERICAN THORACIC SOCIETY   13 ( 11 )   1912 - 1922   2016.11

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    Rationale: Sirolimus has been shown in a randomized, controlled clinical trial to stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated for a 12-month time period; however the pretreatment decline in lung function after the drug was discontinued indicated that continued exposure is required to suppress disease progression. Objectives: To elucidate the durability and tolerability of long-term sirolimus treatment in Asian patients with LAM. Methods: We conducted a single-arm, open-label, investigator-initiated safety and efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5-15 ng/ml. Measurements and Main Results: Fifty-two subjects (82.5%) completed the trial with mean drug compliance of more than 80% overall during the study. The number of adverse events was greatest during the initial 6 months of therapy, but they continued to occur with declining frequency throughout the 2-year study period. Of the 1,549 adverse events, 27 were classified as serious, including reversible sirolimus pneumonitis in 3 patients. New hypercholesterolemia occurred in

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  • Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis. Reviewed

    Takada T, Mikami A, Kitamura N, Seyama K, Inoue Y, Nagai K, Suzuki M, Moriyama H, Akasaka K, Tazawa R, Hirai T, Mishima M, Hayashida M, Hirose M, Sugimoto C, Arai T, Hattori N, Watanabe K, Tamada T, Yoshizawa H, Akazawa K, Tanaka T, Yagi K, Young LR, McCormack FX, Nakata K

    Annals of the American Thoracic Society   13 ( 11 )   1912 - 1922   2016.11

  • Establishment of the consecutive registration system for pulmonary alveolar proteinosis in Japan: Updated incidence, prevalence and surveillance for intractable cases Reviewed

    Yoshikazu Inoue, Koh Nakata, Etsuro Yamaguchi, Toru Arai, Chikatoshi Sugimoto, Yasuhiro Setoguchi, Toshio Ichiwata, Masahito Ebina, Kazutoshi Cho, Ryushi Tazawa, Haruyuki Ishii, Takahiro Kasai, Masanori Akira, Kanji Uchida, Hiroshi Kida, Sakae Homma, Koichiro Tatsumi, Arata Azuma, Koichi Hagiwara, Keisuke Tomii, Masanori Kitaichi, Masaru Suzuki, Kohnosuke Morimoto, Toshinori Takada, Hideaki Nakayama, Shinya Ohkouchi, Takahiro Tanaka, Masaki Hirose, Akiko Matsumuro

    EUROPEAN RESPIRATORY JOURNAL   48   2016.9

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  • Serum cytokine profiles of patients with interstitial lung disease associated with anti-CADM-140/MDA5 antibody positive amyopathic dermatomyositis Reviewed

    Toshinori Takada, Ami Aoki, Katsuaki Asakawa, Takuro Sakagami, Hiroshi Moriyama, Ichiei Narita, Shinji Sato

    RESPIRATORY MEDICINE   109 ( 9 )   1174 - 1180   2015.9

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    Background: Patients with amyopathic dermatomyositis (ADM) sometimes develop rapidly progressive interstitial lung disease (ILD) predominantly in Asia. Although anti-CADM-140/MDA5 antibody titer could correlate with disease activity and predict the course of ILD associated with ADM, it is not clear how this antibody is involved in the pathogenesis of ILD in ADM.
    Methods: We retrospectively collected clinical records and preserved serum before treatment of consecutive patients with ADM-ILD treated in the Niigata University Medical and Dental Hospital since 2000. We measured anti-CADM-140/MDA5 antibody titer and compared it between survivors and non-survivors. Serum cytokine/growth factor protein concentration was measured using a multiplex immunoassay system. The associations between anti-CADM-140/MDA5 antibody titer and each cytokine/growth factor protein concentration were evaluated.
    Results: Thirteen patients were enrolled into the study. Among them, four patients did not respond to intensive immunosuppressive therapy and died. The mean anti-CADM-140/MDA5 antibody titer was significantly higher in patients who did not responded to therapy than in those who survived (p &lt; 0.05). Relationship analyses between the antibody titer and each cytokine/GF protein concentration revealed that Spearman's rank correlation coefficients were more than 0.4 in thirteen cytokine/GF proteins. In particular, the strongest correlation was found between anti-CADM-140/MDA5 antibody titer and CX3CL1 (r = 0.8897).
    Conclusions: These results confirmed that anti-CADM-140/MDA5 antibody levels could predict outcomes of ADM-ILD. Relationship analyses suggested that CX3CL1 might be involved in the pathogenesis of anti-CADM-140/MDA5 antibody positive ADM-ILD. (C) 2015 Elsevier Ltd. All rights reserved.

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  • Possible Involvement of Lung Cells Harboring an Abnormal Karyotype in the Pathogenesis of Pulmonary Alveolar Proteinosis Associated with Myelodysplastic Syndrome. Reviewed

    Moriyama M, Yano T, Furukawa T, Takada T, Ushiki T, Masuko M, Takizawa J, Sone H, Tazawa R, Saijo Y, Ishii H, Nakata K

    Annals of the American Thoracic Society   12 ( 8 )   1251 - 1253   2015.8

  • Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study Reviewed

    Keiichi Akasaka, Takahiro Tanaka, Nobutaka Kitamura, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Toshio Ichiwata, Etsuro Yamaguchi, Masaki Hirose, Toru Arai, Kentaro Nakano, Takahito Nei, Haruyuki Ishii, Tomohiro Handa, Yoshikazu Inoue, Koh Nakata

    BMC PULMONARY MEDICINE   15   88   2015.8

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    Background: Although no report has demonstrated the efficacy of corticosteroid therapy for autoimmune pulmonary alveolar proteinosis (aPAP), we sometimes encounter patients who have received this therapy for various reasons. However, as corticosteroids can suppress alveolar macrophage function, corticosteroid therapy might worsen disease severity and increase the risk of infections.
    Methods: For this retrospective cohort study, we sent a screening form to 165 institutions asking for information on aPAP patients treated with corticosteroids. Of the resulting 45 patients screened, 31 were enrolled in this study. We collected demographic data and information about corticosteroid treatment period, dose, disease severity score (DSS) over the treatment period, and complications.
    Results: DSS deteriorated during corticosteroid therapy in 23 cases (74.1 %) and the estimated overall cumulative worsening rate was 80.8 % for the total observation period. The worsening rate was significantly higher in patients treated with high-dose prednisolone (&gt; 18.9 mg/day, n = 16) than treated with low-dose prednisolone (&lt;= 18.9 mg/day, n = 15) divided by median daily dose (p &lt; 0.02). Of patients with worsening, one died of disseminated aspergillosis and another of respiratory failure. Infections newly emerged in 6 cases during corticosteroid therapy (p &lt; 0.05). Median serum granulocyte/macrophage colony-stimulating factor (GM-CSF) autoantibody levels were similar to previously reported data in a large cohort study.
    Conclusion: The results demonstrate that corticosteroid therapy may worsen DSS of aPAP, increasing the risk for infections.

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  • Superiority of respiratory failure risk index in prediction of postoperative pulmonary complications after digestive surgery in Japanese patients Reviewed

    Satoshi Hokari, Yasuyoshi Ohshima, Hideaki Nakayama, Ryoko Suzuki, Tomosue Kajiwara, Toshiyuki Koya, Hiroshi Kagamu, Toshinori Takada, Eiichi Suzuki, Ichiei Narita

    Respiratory Investigation   53 ( 3 )   104 - 110   2015.5

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    Background: Several multifactorial risk indexes have been proposed by Western countries for identifying patients at a high risk of developing postoperative pulmonary complications (PPC). However, there is no consensus on how to evaluate the risk of PPC and what multifactorial risk index should be adapted for Japanese patients. This study aimed at clarifying the utility of risk indexes to predict PPC following digestive surgeries in Japanese patients. Methods: We retrospectively analyzed 892 patients who underwent digestive surgeries under general anesthesia in Niigata University Medical and Dental Hospital between January 2009 and March 2011. PPC was defined as postoperative respiratory failure and postoperative pneumonia. We calculated three risk indexes (respiratory failure risk index (RFRI), postoperative pneumonia risk index, and PPC risk score), and compared them between the PPC group and the non-PPC group. A receiver operating characteristic (ROC) curve analysis was employed to compare the usefulness of each index. Results: PPC developed in 55 patients (6.2%). All risk indexes were significantly higher in the PPC group than the non-PPC group. The category classification of the risk scores demonstrated a significant tendency to increase the incidence rate of PPC. In the ROC analysis, the area under the curve for RFRI was 0.762 (95% CI 0.697-0.826), which was the highest value observed among these indexes. Conclusions: Multifactorial risk indexes are useful tools for identifying Japanese patients at a high risk of developing PPC following digestive surgeries. Of the risk indexes evaluated in this study, RFRI is potentially the most accurate in predicting PPC.

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  • ミコフェノール酸モフェチルを含む3剤併用療法を行った皮膚筋炎合併間質性肺疾患の1例

    島 賢治郎, 坂上 拓郎, 市川 紘将, 穂苅 諭, 朝川 勝明, 小屋 俊之, 各務 博, 高田 俊範, 成田 一衛

    日本呼吸器学会誌   4 ( 1 )   76 - 80   2015.1

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    Other Link: http://search.jamas.or.jp/link/ui/2015129304

  • A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis Reviewed

    Keiichi Akasaka, Takahiro Tanaka, Takashi Maruyama, Nobutaka Kitamura, Atsushi Hashimoto, Yuko Ito, Hiroyoshi Watanabe, Tomoshige Wakayama, Takero Arai, Masachika Hayashi, Hiroshi Moriyama, Kanji Uchida, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Etsuro Yamaguchi, Toshio Ichiwata, Masaki Hirose, Toru Arai, Yoshikazu Inoue, Hirosuke Kobayashi, Koh Nakata

    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY   308 ( 2 )   L105 - L117   2015.1

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    Whole-lung lavage (WLL) remains the standard therapy for pulmonary alveolar proteinosis (PAP), a process in which accumulated surfactants are washed out of the lung with 0.5-2.0 l of saline aliquots for 10 -30 wash cycles. The method has been established empirically. In contrast, the kinetics of protein transfer into the lavage fluid has not been fully evaluated either theoretically or practically. Seventeen lungs from patients with autoimmune PAP underwent WLL. We made accurate timetables for each stage of WLL, namely, instilling, retaining, draining, and preparing. Subsequently, we measured the volumes of both instilled saline and drained lavage fluid, as well as the concentrations of proteins in the drained lavage fluid. We also proposed a mathematical model of protein transfer into the lavage fluid in which time is a single variable as the protein moves in response to the simple diffusion. The measured concentrations of IgG, transferrin, albumin, and beta(2)-microglobulin closely matched the corresponding theoretical values calculated through differential equations. Coefficients for transfer of beta(2)-microglobulin from the blood to the lavage fluid were two orders of magnitude higher than those of IgG, transferrin, and albumin. Simulations using the mathematical model showed that the cumulative amount of eliminated protein was not affected by the duration of each cycle but dependent mostly on the total time of lavage and partially on the volume instilled. Although physicians have paid little attention to the transfer of substances from the lung to lavage fluid, WLL seems to be a procedure that follows a diffusion-based mathematical model.

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  • Fever of Unknown Origin: Do Well-known Diseases Remain Undiagnosed? Reviewed

    Takaaki Ishiyama, Toshinori Takada

    INTERNAL MEDICINE   54 ( 16 )   1959 - 1960   2015

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  • Duration of Benefit in Patients With Autoimmune Pulmonary Alveolar Proteinosis After Inhaled Granulocyte-Macrophage Colony-Stimulating Factor Therapy Reviewed

    Ryushi Tazawa, Yoshikazu Inoue, Toru Arai, Toshinori Takada, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshiko Tsuchihashi, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Haruyuki Ishii, Takahito Nei, Konosuke Morimoto, Yasuyuki Nasuhara, Masahito Ebina, Masanori Akira, Toshio Ichiwata, Koichiro Tatsumi, Etsuro Yamaguchi, Koh Nakata

    CHEST   145 ( 4 )   729 - 737   2014.4

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    Background: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized.
    Methods: To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy.
    Results: During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, % VC) were higher among those who required additional treatment (P &lt;.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high % VC group (% VC &gt;= 80.5) and the low % VC group was seen by a Kaplan-Meier analysis and a log-rank test (P &lt;.0005).
    Conclusions: These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline % VC might be a prognostic factor for disease recurrence.

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  • Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan. Reviewed International journal

    Haruyuki Ishii, John F Seymour, Ryushi Tazawa, Yoshikazu Inoue, Naoyuki Uchida, Aya Nishida, Yoshihito Kogure, Takeshi Saraya, Keisuke Tomii, Toshinori Takada, Yuko Itoh, Masayuki Hojo, Toshio Ichiwata, Hajime Goto, Koh Nakata

    BMC pulmonary medicine   14   37 - 37   2014.3

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    BACKGROUND: Secondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS. METHODS: Thirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups. RESULTS: In contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis. CONCLUSION: Development of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.

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  • Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer Reviewed

    Toshinori Takada, Hiroshi Moriyama, Eiichi Suzuki

    Respiratory Investigation   52 ( 1 )   5 - 13   2014.1

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    Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. © 2013 The Japanese Respiratory Society.

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  • Clinical features of three cases with pulmonary alveolar proteinosis secondary to myelodysplastic syndrome developed during the course of Behçet's disease Reviewed

    Tomohiro Handa, Takeshi Nakatsue, Motoo Baba, Toshinori Takada, Koh Nakata, Haruyuki Ishii

    Respiratory Investigation   52 ( 1 )   75 - 79   2014.1

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    We have previously reported that myelodysplastic syndrome (MDS) is the most common underlying disease in cases of secondary pulmonary alveolar proteinosis (PAP). Here, we present 3 MDS cases in which PAP developed during the course of Behçet's disease (BD). All patients carried trisomy 8 in the bone marrow. Chest HRCT scans showed variable distribution of ground glass opacities, but none of the scans showed so called "crazy paving appearance". Two patients with intestinal BD who underwent potent immunosuppressive therapy died of sepsis. These findings demonstrate that PAP secondary to MDS may be occasionally associated with BD. © 2013 The Japanese Respiratory Society.

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  • An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease Reviewed

    Junichi Tanaka, Hiroshi Moriyama, Masaki Terada, Toshinori Takada, Eiichi Suzuki, Ichiei Narita, Yoshinori Kawabata, Tetsuo Yamaguchi, Akira Hebisawa, Fumikazu Sakai, Hiroaki Arakawa

    BMJ OPEN   4 ( 3 )   e004407   2014

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    Background
    Hard metal lung disease has various pathological patterns including giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP). Although the UIP pattern is considered the prominent feature in advanced disease, it is unknown whether GIP finally progresses to the UIP pattern.
    Objectives
    To clarify clinical, pathological and elemental differences between the GIP and UIP patterns in hard metal lung disease.
    Methods
    A cross-sectional study of patients from 17 institutes participating in the 10th annual meeting of the Tokyo Research Group for Diffuse Parenchymal Lung Diseases, 2009. Nineteen patients (seven female) diagnosed with hard metal lung disease by the presence of tungsten in lung specimens were studied.
    Results
    Fourteen cases were pathologically diagnosed as GIP or centrilobular inflammation/fibrosing. The other five cases were the UIP pattern or upper lobe fibrosis. Elemental analyses of lung specimens of GIP showed tungsten throughout the centrilobular fibrotic areas. In the UIP pattern, tungsten was detected in the periarteriolar area with subpleural fibrosis, but no association with centrilobular fibrosis or inflammatory cell infiltration. The GIP group was younger (43.1 vs 58.6 years), with shorter exposure duration (73 vs 285 months; p &lt; 0.01), lower serum KL-6 (398 vs 710 U/mL) and higher lymphocyte percentage in bronchoalveolar lavage fluid (31.5% vs 3.22%; p &lt; 0.05) than the fibrosis group.
    Conclusions
    The UIP pattern or upper lobe fibrosis is remarkably different from GIP in distribution of hard metal elements, associated interstitial inflammation and fibrosis, and clinical features. In hard metal lung disease, the UIP pattern or upper lobe fibrosis may not be an advanced form of GIP.

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  • Effects of Direct Hemoperfusion with Polymyxin B-immobilized Fiber on Rapidly Progressive Interstitial Lung Diseases Reviewed

    Toshinori Takada, Katsuaki Asakawa, Takuro Sakagami, Hiroshi Moriyama, Junichiro Kazama, Eiichi Suzuki, Ichiei Narita

    INTERNAL MEDICINE   53 ( 17 )   1921 - 1926   2014

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    Objective Direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX-DHP) has been used for the treatment of septic shock. It was recently suggested that PMX-DHP may also be effective in acute exacerbations of idiopathic pulmonary fibrosis (IPF). However, all previous reports are case series without controls. The aim of the study was to determine the effects of PMX-DHP on the prognosis of the patients with rapidly progressive interstitial lung diseases (ILDs) in a case-control setting.
    Methods We herein retrospectively examined the clinical records of consecutive patients with acute exacerbation of IPF or rapidly progressive ILDs treated in our institute. We excluded those who had been treated with steroid pulse therapy for lung diseases, including those who had been taking more than 15 mg of oral prednisolone daily, or had undergone an operation within one month before the onset of acute respiratory failure. We compared the results of the laboratory tests and survivals between patients treated with and without PMX-DHP.
    Results Twenty-six patients were enrolled in the study. Among them, 13 patients were treated with PMX-DHP in addition to immunosuppressive therapy, including steroid pulse therapy. The mean survival time of patients treated with PMX-DHP tended to be longer than patients not treated with PXM-DHP (p = 0.067). Six patients who underwent PMX-DHP on the first day of steroid pulse therapy had significantly longer survival times than those who were treated with standard medication alone (p &lt; 0.01).
    Conclusion These results suggest that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs.

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  • Preventive effect of irbesartan on bleomycin-induced lung injury in mice. Reviewed International journal

    Junichi Tanaka, Shunji Tajima, Katsuaki Asakawa, Takuro Sakagami, Hiroshi Moriyama, Toshinori Takada, Eiichi Suzuki, Ichiei Narita

    Respiratory investigation   51 ( 2 )   76 - 83   2013.6

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    BACKGROUND: Idiopathic pulmonary fibrosis is a specific form of chronic fibrosing interstitial pneumonia that is limited to the lung. Angiotensin receptor blockers (ARBs) and peroxisome proliferator-activated receptor (PPAR) γ ligands have anti-inflammatory and anti-fibrotic effects. We investigated the effects of irbesartan-an ARB with PPAR γ activity-on the development of bleomycin-induced pulmonary fibrosis in mice. METHODS: Lung injury was induced in imprinting control region (ICR) mice by intratracheal instillation of 2mg/kg of bleomycin. The treatment group orally received 20mg/kg of irbesartan for 5 consecutive days before instillation. The mice were sacrificed and were evaluated 14 days after bleomycin instillation. RESULTS: Irbesartan reduced the fluid content and hydroxyproline level in the lung and improved the pathological findings as indicated by the Ashcroft score. Total cell counts, the numbers of macrophages, neutrophils, and lymphocytes, and the levels of transforming growth factor (TGF) β1 and monocyte chemotactic protein (MCP) 1 in the bronchoalveolar lavage fluid (BALF) were decreased. Treatment with a PPARγ antagonist GW9662 reversed some of the effects of irbesartan. CONCLUSIONS: The results of this study indicated that irbesartan attenuated the development of bleomycin-induced pulmonary fibrosis in mice by decreasing TGF-β1 and MCP-1 via blocking of ATI, by binding to CCR2b, and by PPARγ-mediated inhibition of inflammation.

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  • Treatment of interstitial lung disease associated with polymyositis-dermatomyositis: An update Reviewed

    Toshinori Takada, Ichiei Narita, Eiichi Suzuki

    Current Respiratory Medicine Reviews   9 ( 2 )   130 - 136   2013

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    Polymyositis and dermatomyositis (PM-DM) are forms of idiopathic inflammatory myositis. Interstitial lung disease (ILD) in PM-DM is recognized as a serious complication and a major cause of death in this disease. In particular, patients with clinically amyopathic dermatomyositis (ADM) sometimes develop rapidly progressive ILD that remains unresponsive to intensive immunosuppresive therapy. A novel autoantibody associated with PM-DM was identified and termed anti-CADM-140/MDA5 antibody. Anti-CADM-140/MDA5 antibody titer correlates with disease activity and predicts the course of ILD associated with ADM. Glucocorticoids are considered the first-line drug treatment for PM-DM patients with ILD, however they are often not sufficient to obtain improvement of ILD as a single agent. Furthermore, the addition of immunosuppressive drugs becomes necessary as steroid sparing agents to avoid the severe side-effects often seen with high-dose steroid treatment. Cyclophosphamide, cyclosporin, and tacrolimus were reported to be effective in treatment of refractory ILD in PM-DM. Although other immunosuppressive agents
    mycophenolate mofetil, intravenous immunoglobulin, and anti-TNF agents have appeared as promising agents for refractory PM-DM, the efficacy on ILD in PM-DM is still unknown. Even if treatment is initiated early in the course of the disease, some patients still develop irreversible fatal lung fibrosis under aggressive immunosuppressive therapy. Recently, cases with rapidly progressive ILD associated with clinically ADM were successfully treated with direct hemoperfusion with polymyxin B-immobilized fiber column. © 2013 Bentham Science Publishers.

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  • O36-1 新潟県の咳喘息,7年間の経年変化(O36 咳嗽,口演,第63回日本アレルギー学会秋季学術大会)

    藤森 勝也, 各務 博, 高田 俊範, 成田 一衛, 長谷川 隆志, 鈴木 栄一

    アレルギー   62 ( 9 )   1368 - 1368   2013

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  • 1.難治性気胸を合併した特発性肺線維症に, EWSを用いた気管支充填術を行った1例(第56回 日本呼吸器内視鏡学会北陸支部会)

    月岡 啓輔, 森山 寛史, 青木 信将, 岡島 正明, 小屋 俊之, 中山 秀章, 各務 博, 高田 俊範, 成田 一衛, 星野 芳史, 佐藤 征二郎, 小池 輝元, 橋本 毅久, 土田 正則, 鈴木 栄一, 大橋 和政, 小林 義昭

    気管支学   35 ( 4 )   460 - 460   2013

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    DOI: 10.18907/jjsre.35.4_460_1

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  • Occupational and environmental impact on the clinical course of autoimmune pulmonary alveolar proteinosis Reviewed

    Yoshikazu Inoue, Koh Nakata, Toru Arai, Etsuro Yamaguchi, Toshio Ichiwata, Masahito Ebina, Ryushi Tazawa, Haruyuki Ishii, Yasuhiro Setoguchi, Masanori Kitaichi, Masanori Akira, Koichiro Tatsumi, Yasuyuki Nasuhara, Kazutoshi Cho, Yoshiko Tsuchihashi, Kanji Uchida, Toshinori Takada, Hideaki Nakayama, Keisuke Tomii, Chikatoshi Sugimoto, Yasuo Kohashi, Shinya Ohkouchi, Yasunori Kasahara, Kohnosuke Morimoto, Naoko Sakamoto

    EUROPEAN RESPIRATORY JOURNAL   40   2012.9

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  • 先端巨大症患者における肺胞低換気と睡眠呼吸障害

    穂苅 諭, 大嶋 康義, 中山 秀章, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本睡眠学会定期学術集会プログラム・抄録集   37回   261 - 261   2012.6

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  • Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis Reviewed

    K. Ohashi, A. Sato, T. Takada, T. Arai, Y. Kasahara, M. Hojo, T. Nei, H. Nakayama, N. Motoi, S. Urano, R. Eda, M. Yokoba, Y. Tsuchihashi, Y. Nasuhara, H. Ishii, M. Ebina, E. Yamaguchi, Y. Inoue, K. Nakata, R. Tazawa

    European Respiratory Journal   39 ( 3 )   777 - 780   2012.3

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    DOI: 10.1183/09031936.00076711

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  • 消化管手術後の呼吸器合併症リスク評価の検討 多因子リスクスコアの比較

    穂苅 諭, 大嶋 康義, 中山 秀章, 高田 俊範, 成田 一衛, 鈴木 栄一

    日本呼吸器学会誌   1 ( 増刊 )   283 - 283   2012.3

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  • Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis Reviewed

    Kazumasa Ohashi, Atsuyasu Sato, Toshinori Takada, Toru Arai, Takahito Nei, Yasunori Kasahara, Natsuki Motoi, Masayuki Hojo, Shinya Urano, Haruyuki Ishii, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Yasuyuki Nasuhara, Yoshiko Tsuchihashi, Chinatsu Kaneko, Hiroko Kanazawa, Masahito Ebina, Etsuro Yamaguchi, Jacqueline Kirchner, Yoshikazu Inoue, Koh Nakata, Ryushi Tazawa

    RESPIRATORY MEDICINE   106 ( 2 )   284 - 293   2012.2

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    Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. It is plausible that inhaled GM-CSF improves the dysfunction of alveolar macrophages and promotes the clearance of the surfactant. However, effect of the therapy on components in bronchoalveolar lavage fluid (BALF) remains unclear.
    Objectives: To figure out changes in surfactant clearance during GM-CSF inhalation therapy. Methods: We performed retrospective analyses of BALF obtained under a standardized protocol from the same bronchus in each of 19 aPAP patients before and after GM-CSF inhalation therapy (ISRCTN18931678, JMA-IIA00013; total dose 10.5-21 mg, duration 12-24 weeks). For evaluation, the participants were divided into two groups, high responders with improvement in alveolar-arterial oxygen difference &gt;= 13 mmHg (n = 10) and low responders with that &lt; 13 mmHg (n = 9).
    Results: Counts of both total cells and alveolar macrophages in BALF did not increase during the therapy. However, total protein and surfactant protein-A (SP-A) were significantly decreased in high responders, but not in low responders, suggesting that clearance of surfactant materials is correlated with the efficacy of the therapy. Among 94 biomarkers screened in bronchoalveolar lavage fluid, we found that the concentration of interleukin-17 and cancer antigen-125 were significantly increased after GM-CSF inhalation treatment.
    Conclusions: GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleukin-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis. (C) 2011 Elsevier Ltd. All rights reserved.

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  • 閉塞性睡眠時無呼吸は尿中アルブミン排泄を増加させる

    穂苅 諭, 中山 秀章, 大嶋 康義, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本内科学会雑誌   101 ( Suppl. )   254 - 254   2012.2

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  • 4. MALTリンパ腫による転移性気管腫瘍の1例(第54回 日本呼吸器内視鏡学会北陸支部会)

    三浦 理, 森山 寛史, 星野 芳史, 小屋 俊之, 中山 秀章, 各務 博, 高田 俊範, 成田 一衛, 吉永 清宏, 小堺 貴司, 瀧澤 淳, 鈴木 栄一, 味岡 洋一

    気管支学   34 ( 4 )   407 - 407   2012

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  • 【超硬合金肺とその周辺】超硬合金肺の臨床像 Reviewed

    田中 淳一, 高田 俊範, 森山 寛史

    日本胸部臨床   70 ( 12 )   1219 - 1229   2011.12

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    超硬合金肺は、超硬合金の吸入により発生するまれな職業性肺疾患である。症例が少なく臨床像が明らかではないため、全国より19例の超硬合金肺症例を集め、詳細な検討を行った。平均年齢は46.4歳、性別では男性が12名とやや多く、非喫煙者が16名と多く、平均曝露期間は10.1年であった。定型的な病理学像(巨細胞性間質性肺炎、小葉中心性炎症線維化)を呈する例は、19例中14例に認められた。定型例は、非定型例と比べ若年で、曝露期間が短く、KL-6が有意に低いことが明らかになった。(著者抄録)

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  • 呼吸機能低下患者における術後呼吸器合併症リスク評価の検討

    穂苅 諭, 中山 秀章, 梶原 大季, 鈴木 涼子, 大嶋 康義, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本呼吸ケア・リハビリテーション学会誌   21 ( 1 )   30 - 34   2011.6

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    DOI: 10.15032/jsrcr.21.1_30

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    Other Link: http://search.jamas.or.jp/link/ui/2011352296

  • [Effects of anticoagulant therapy for rapidly progressive interstitial pneumonias]. Reviewed

    Watanabe K, Tajima S, Tanaka J, Moriyama H, Nakayama H, Terada M, Takada T, Suzuki E, Narita I

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society   49 ( 6 )   407 - 412   2011.6

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  • 急速に進行する間質性肺炎に対する抗凝固療法併用の有効性についての検討 Reviewed

    渡辺 憲弥, 田島 俊児, 田中 淳一, 森山 寛史, 中山 秀章, 寺田 正樹, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本呼吸器学会雑誌   49 ( 6 )   407 - 412   2011.6

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    急速に進行する間質性肺炎に対する抗凝固療法併用の有効性を後ろ向きに検討した。1999年4月から2010年1月までに当科に入院した特発性または続発性の間質性肺炎で、2ヵ月以内に呼吸不全が進行する症例を急速に進行する間質性肺炎と定義した。対象は20例で、基礎疾患はnon-IPF6例、IPF3例、Amyopathic DM(ADM)6例、DM2例、RA2例、MCTD1例であった。治療に抗凝固療法を併用した群をA群(n=11)、非併用群をB群(n=9)として比較検討した。Kaplan-Meier法で、A群に有意な生存期間の延長が認められた(p=0.0389)。急速に進行する間質性肺炎では、抗凝固療法の併用により予後が改善し得る可能性が示唆された。(著者抄録)

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  • 呼吸の不安定性は多系統萎縮症患者の睡眠時無呼吸に関与するか?

    穂苅 諭, 鈴木 涼子, 中山 秀章, 高田 俊範, 成田 一衛, 鈴木 栄一, 下畑 享良, 小澤 鉄太郎, 西澤 正豊

    日本呼吸器学会雑誌   49 ( 増刊 )   217 - 217   2011.3

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  • Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan. International journal

    H Ishii, R Tazawa, C Kaneko, T Saraya, Y Inoue, E Hamano, Y Kogure, K Tomii, M Terada, T Takada, M Hojo, A Nishida, T Ichiwata, B C Trapnell, H Goto, K Nakata

    The European respiratory journal   37 ( 2 )   465 - 8   2011.2

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  • 超硬合金肺の臨床病理学的検討 Reviewed

    田中 淳一, 森山 寛史, 田島 俊児, 寺田 正樹, 高田 俊範, 鈴木 栄一, 成田 一衛, 河端 美則, 山口 哲生, 小倉 高志

    日本内科学会雑誌   100 ( Suppl. )   230 - 230   2011.2

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  • O46-3 喘息治療効果不十分症例に対するブデソニド/ホルモテロール配合剤(BUD/FM)4吸入12週投与後の有効性の検討(O46 気管支喘息におけるフォルモテロール/ブデソニド配合剤療法,口演,第61回日本アレルギー学会秋季学術大会)

    小林 義昭, 大橋 和政, 岩田 文英, 長谷川 隆志, 鈴木 榮一, 高田 俊範, 成田 一衛

    アレルギー   60 ( 9 )   1431 - 1431   2011

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  • O13-5 新潟県の咳喘息の検討 : 2006,2008,2010年の経年変化(O13 咳喘息慢性咳嗽,口演,第61回日本アレルギー学会秋季学術大会)

    藤森 勝也, 各務 博, 高田 俊範, 成田 一衛, 長谷川 隆志, 鈴木 栄一

    アレルギー   60 ( 9 )   1380 - 1380   2011

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  • P2-13-1 月経喘息におけるAsthma control testについて : コントロール良好群および不良群の検討(P2-13 成人喘息9,ポスターセッション,第23回日本アレルギー学会春季臨床大会)

    鈴木 和夫, 小屋 俊之, 高田 俊範, 成田 一衛, 荒川 正昭, 長谷川 隆志, 鈴木 栄一

    アレルギー   60 ( 3 )   492 - 492   2011

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  • Inhaled Granulocyte/Macrophage-Colony Stimulating Factor as Therapy for Pulmonary Alveolar Proteinosis Reviewed

    Ryushi Tazawa, Bruce C. Trapnell, Yoshikazu Inoue, Toru Arai, Toshinori Takada, Yasuyuki Nasuhara, Nobuyuki Hizawa, Yasunori Kasahara, Koichiro Tatsumi, Masayuki Hojo, Haruyuki Ishii, Masanori Yokoba, Naohiko Tanaka, Etsuro Yamaguchi, Ryosttke Eda, Yoshiko Tsuchihashi, Konosuke Morimoto, Masanori Akira, Masaki Terada, Junji Otsuka, Masahito Ebina, Chinatsu Kaneko, Toshihiro Nukiwa, Jeffery P. Krischer, Kohei Akazawa, Koh Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   181 ( 12 )   1345 - 1354   2010.6

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    Rationale: Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied.
    Objectives: To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP.
    Methods: We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O2) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 mu g Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 mu g Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk).
    Measurements and Main Results: Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P &lt; 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year.
    Conclusions: Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP.

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  • 低肺機能患者における周術期呼吸リハビリテーションの検討 Reviewed

    穂苅 諭, 梶原 大季, 中山 秀章, 高田 俊範, 鈴木 栄一

    日本呼吸器学会雑誌   48 ( 増刊 )   217 - 217   2010.3

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  • 当科における急速進行性間質性肺炎の治療についての検討 Reviewed

    渡辺 憲弥, 田島 俊児, 田中 淳一, 森山 寛史, 山本 尚, 中山 秀章, 寺田 正樹, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本呼吸器学会雑誌   48 ( 増刊 )   189 - 189   2010.3

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  • 臨床諸問題 超硬合金肺(Hard metal lung disease;HMLD)の臨床病理学的検討 Reviewed

    田中 淳一, 森山 寛史, 高田 俊範, 寺田 正樹, 鈴木 栄一, 成田 一衛, 河端 美則, 蛇澤 晶, 酒井 文和, 荒川 浩明, 山口 哲生, 井上 義一, 小倉 高志

    日本呼吸器学会雑誌   48 ( 増刊 )   116 - 116   2010.3

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  • A prostacyclin agonist with thromboxane inhibitory activity for airway allergic inflammation in mice Reviewed

    M. Hayashi, T. Koya, H. Kawakami, T. Sakagami, T. Hasegawa, H. Kagamu, T. Takada, Y. Sakai, E. Suzuki, E. W. Gelfand, F. Gejyo

    CLINICAL AND EXPERIMENTAL ALLERGY   40 ( 2 )   317 - 326   2010.2

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    P&gt;Background
    ONO-1301 is a novel drug that acts as a prostacyclin agonist with thromboxane A(2) (TxA(2)) synthase inhibitory activity. We investigated the effect of ONO-1301 on development of airway allergic inflammation.
    Methods
    Mice sensitized and challenged to ovalbumin (OVA) received ONO-1301, OKY-046 (TxA(2) synthase inhibitor), beraprost, a prostacyclin receptor (IP) agonist, ONO-1301 plus CAY10449 (selective IP antagonist) or vehicle during the challenge period. Twenty-four hours after the OVA challenge, airway hyperresponsiveness (AHR) to methacholine was assessed and bronchoalveolar lavage was performed. Lung specimens were excised for goblet cell staining and analysis of lung dendritic cells (DCs). Bone marrow-derived dendritic cells (BMDCs) were generated, in the presence or absence of drugs, for analysis of DC function.
    Results
    Mice that received ONO-1301 showed significantly lower AHR, airway eosinophilia, T-helper type 2 cytokine levels, mucus production and lung DCs numbers than vehicle-treated mice. These effects of ONO-1301 were mostly reversed by CAY10449. BMDCs treated with ONO-1301 alone showed lower DC functions, such as expression of costimulatory factors or stimulation to spleen T cells.
    Conclusions
    These data suggest that ONO-1301 may suppress AHR and airway allergic inflammation through modulation of DCs, mainly mediated through the IP receptor. This agent may be effective as an anti-inflammatory drug in the treatment of asthma.
    Cite this as: M. Hayashi, T. Koya, H. Kawakami, T. Sakagami, T. Hasegawa, H. Kagamu, T. Takada, Y. Sakai, E. Suzuki, E. W. Gelfand and F. Gejyo, Clinical & Experimental Allergy, 2010 (40) 317- 326.

    DOI: 10.1111/j.1365-2222.2009.03418.x

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  • 咽頭・気管に再発した肺MALTリンパ腫の1例 Reviewed

    田中 淳一, 田島 俊児, 梶原 大季, 茂呂 寛, 成田 淳一, 田邊 嘉也, 各務 博, 中山 秀章, 寺田 正樹, 高田 俊範, 成田 一衛, 瀧澤 淳, 長谷川 隆志, 鈴木 栄一, 中村 直哉, 手塚 貴文, 今井 洋介

    気管支学   32 ( 1 )   84 - 84   2010.1

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  • MW17-5 新潟県多施設アンケート調査からの月経喘息とAsthma control testについての検討(MW17 喘息管理・コントロール状態の評価,ミニワークショップ,第60回日本アレルギー学会秋季学術大会)

    鈴木 和夫, 小屋 俊之, 高田 俊範, 成田 一衛, 荒川 正昭, 長谷川 隆志, 鈴木 栄一

    アレルギー   59 ( 9 )   1366 - 1366   2010

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    DOI: 10.15036/arerugi.59.1366_3

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  • Comparative Study of High-Resolution CT Findings Between Autoimmune and Secondary Pulmonary Alveolar Proteinosis Reviewed

    Haruyuki Ishii, Bruce C. Trapnell, Ryushi Tazawa, Yoshikazu Inoue, Masanori Akira, Yoshihito Kogure, Keisuke Tomii, Toshinori Takada, Masayuki Hojo, Toshio Ichiwata, Hajime Goto, Koh Nakata

    CHEST   136 ( 5 )   1348 - 1355   2009.11

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    Background: Acquired pulmonary alveolar proteinosis (PAP) has been reclassified into autoimmune or secondary PAP according to the occurrence of serum granulocyte macrophage colony-stimulating factor autoantibody. Most patients undergo high-resolution CT (HRCT) scanning in order for physicians to make a differential diagnosis of diffuse lung diseases, but no information is available to distinguish the HRCT scan features of secondary PAP from those of autoimmune PAP. The objective of this study was to characterize the HRCT scan features of autoimmune and secondary PAP.
    Methods: HRCT scans of 42 patients (21 patients each in the autoimmune PAP and secondary PAP groups) were centrally collected and evaluated in a blinded manner.
    Results: Ground-glass opacities (GGO) were a major finding in both the autoimmune PAP and secondary PAP groups. In the secondary PAP group, GGOs typically showed a diffuse pattern (62%), whereas GGOs showed a patchy geographic pattern in the autoimmune PAP group (71%; p &lt; 0.005). The so-called "crazy-paving" appearance and subpleural sparing were frequently seen in the autoimmune PAP group (both 71%), whereas they were less frequently seen in the secondary PAP group (14% and 33%, respectively). The involved area of GGO was even in craniocaudal distribution for the secondary PAP group, whereas it was predominant in the lower lung field compared with the upper lung field in the autoimmune PAP group (p &lt; 0.05).
    Conclusions: Typical HRCT scan findings for autoimmune PAP patients were GGO with a patchy geographic pattern, subpleural sparing, crazy-paving appearance, and predominance in the lower lung field. These findings were rather infrequent for secondary PAP patients. (CHEST 2009; 136:1348-135-5)

    DOI: 10.1378/chest.09-0097

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  • Effects of IS-741, a Synthetic Anti-Inflammatory Agent, on Bleomycin-Induced Lung Injury in Mice Reviewed

    Yuichi Shimaoka, Shunji Tajima, Fumio Fujimori, Cristiane Yamabayashi, Hiroshi Moriyama, Masaki Terada, Toshinori Takada, Eiichi Suzuki, Masashi Bando, Yukihiko Sugiyama, Ichiei Narita

    LUNG   187 ( 5 )   331 - 339   2009.10

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    Bleomycin (BLM)-induced lung injury consists of excessive inflammatory cell infiltration and fibrosis. IS-741 has been reported to be an anti-inflammatory drug through an inhibitory action on cell adhesion. In this study we investigated whether IS-741 could inhibit the progression of pulmonary fibrosis through inflammatory cell infiltration. Lung injury was induced in female C57BL/6 mice by intratracheal instillation of BLM. IS-741 was administered daily intraperitoneally. The hydroxyproline content and fluid content in the lung on Day 28 were significantly lower in the IS-741-treated mice. The histological degree of lung injury or fibrosis was reduced in IS-741-treated mice. Administration of IS-741 caused significant reduction in the absolute number of total cells, monocyte chemoattractant protein (MCP)-1, and cysteinyl leukotriene (cysLTs) levels in bronchoalveolar lavage fluid on Day 7. Furthermore, the hydroxyproline content was significantly lower in IS-741-treated mice even though IS-741 was started on Day 14 after BLM instillation. Treatment with IS-741 had an inhibitory effect on BLM-induced lung injury and fibrosis via the repression of MCP-1 or cysLTs in this murine experimental model.

    DOI: 10.1007/s00408-009-9162-6

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  • Dermatomyositis with hemorrhagic myositis Reviewed

    Masashi Yamagishi, Shunji Tajima, Aki Suetake, Hidenori Kawakami, Takeo Watanabe, Hideyuki Kuriyama, Toshinori Takada, Eiichi Suzuki, Fumitake Gejyo

    RHEUMATOLOGY INTERNATIONAL   29 ( 11 )   1363 - 1366   2009.9

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    A 64-year-old Japanese female, diagnosed as dermatomyositis with acute interstitial pneumonia, complained of acute abdominal pain. Computed tomography of the abdomen showed hematoma in the right retroperitoneum and left rectus-sheath. Angiogram showed multiple small aneurysms on left iliolumbar artery and a horizontal linear flush, suggesting active bleeding foci in the muscles. Although arterial embolization therapy was effective for hemostatic treatment, she died of thrombotic thrombocytopenic purpura and multiple organ failure without respiratory insufficiency. Other causes of microaneurysm, such as systemic vasculitides or infectious diseases, were excluded. We considered that this is the first case report of dermatomyositis with hemorrhagic myositis associated with small aneurysms.

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  • 急速な肺内転移を来たし呼吸不全にて死亡した進行非小細胞肺癌の1例 Reviewed

    田中 淳一, 田島 俊児, 伊藤 竜, 島岡 雄一, 栗山 英之, 各務 博, 寺田 正樹, 高田 俊範, 下条 文武, 鈴木 栄一, 吉澤 弘久, 成田 一衛

    日本呼吸器学会雑誌   47 ( 7 )   652 - 657   2009.7

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    症例は63歳男性。腰痛、皮膚そう痒感を主訴に、当院皮膚科に精査目的に入院した。入院時の胸部X線写真で左中下肺野に広範な浸潤影を認め、当科で精査を行った。気管支鏡検査を施行し、左B4の洗浄液より細気管支肺胞上皮癌と診断した。骨転移があり、cT4N2M1 stage IVでPS3と不良であったため、除痛目的に放射線照射を行った。その後、呼吸困難、発熱、右中下肺野に浸潤影が出現し、院内感染を考え、抗菌剤を投与したところ一旦は軽快した。12月28日に外泊したが、31日には、呼吸不全のため帰院した。すりガラス陰影が右肺野に広範に出現し、抗菌剤、ステロイドなどを投与したが、以後急速に進行した呼吸不全のため1月5日に永眠した。右側肺の生検針を用いた死後組織採取では、細気管支肺胞上皮癌が同定された。既存の肺胞壁を非破壊性に被覆するように非連続性に、増殖進展している像があり、臨床経過とあわせて対側肺への経気道転移が疑われた。以上、本例は急速な経過で肺内転移を来たし、呼吸不全にて死亡した進行非小細胞肺癌と考える。(著者抄録)

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  • [A case of non-small cell lung carcinoma dying of acute respiratory failure due to aerogenous metastasis]. Reviewed

    Junichi Tanaka, Shunji Tajima, Ryo Ito, Yuichi Shimaoka, Hideyuki Kuriyama, Hiroshi Kagamu, Masaki Terada, Toshinori Takada, Fumitake Gejyo, Eiichi Suzuki, Hirohisa Yoshizawa, Ichiei Narita

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society   47 ( 7 )   652 - 7   2009.7

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    A 63-year-old man was admitted to our hospital, because of exacerbation of backache and erythema. At the time of admission the chest X-ray film showed infiltrative shadows in the left middle and lower lung fields. Our investigation revealed primary mucinous type bronchioloalveolar carcinoma in the left lung (cT4N2M1 Stage IV). Radiotherapy (C7-Th2, L3-L5. Total 30 Gy/10 fr) was administered to relieve his pain. After radiotherapy, he developed respiratory failure, fever, and infiltrative shadow in his chest X-ray. Antibiotic therapy improved his symptoms, laboratory findings and radiological abnormal findings. We suspected complication with nosocomial infection. However the ground-glass appearance appeared in the right lung a few days later. Although antibiotics and steroids were administered, he died of respiratory failure in 6 days. Necropsy findings revealed bronchioloalveolar carcinoma in the right lung suggesting aerogenous metastasis. Considering these facts together, we diagnosed non-small cell lung carcinoma dying of acute respiratory failure due to aerogenous metastasis.

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  • マウスLipopolysaccharide(LPS)誘起性急性肺損傷モデルにおけるPioglitazoneによる抑制効果の検討 Reviewed

    田中 淳一, 田島 俊児, 富士盛 文夫, 島岡 雄一, 森山 寛史, 寺田 正樹, 高田 俊範, 鈴木 栄一, 下条 文武

    日本呼吸器学会雑誌   47 ( 増刊 )   127 - 127   2009.5

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  • Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium avium complex Reviewed

    Toshiyuki Koya, Chikako Tsubata, Hiroshi Kagamu, Ken-ichi Koyama, Masachika Hayashi, Katsuhiro Kuwabara, Takui Itoh, Yoshinari Tanabe, Toshinori Takada, Fumitake Gejyo

    JOURNAL OF INFECTION AND CHEMOTHERAPY   15 ( 2 )   118 - 122   2009.4

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    We report the case of a 44-year-old woman with disseminated Mycobacterium avium complex (MAC) infection involving multiple bone lesions despite a normal healthy status until 6 months previously. Because she was suspected to have acquired immunodeficiency, we tested interferon (IFN)-gamma production by peripheral blood mononuclear cells (PBMC) after phytohemagglutinin (PHA) or anti-CD3 stimulation, and found that these cells produced no, or undetectable, levels of IFN-gamma in the presence of the patient's plasma, but produced nearly normal levels of IFN-gamma in the presence of healthy donor plasma. Since the IgG fraction of the patient's plasma was capable of blocking in vitro responses to IFN-gamma, the cause of disseminated MAC infection in this case appeared to be anti-IFN-gamma autoantibodies. To reduce the titer of anti-IFN-gamma autoantibodies, the patient received intravenous immunoglobulin (IVIG). However, titer of autoantibodies changed little compared to that before IVIG administration. According to our literature search, this is only the second case of disseminated MAC infection associated with anti-IFN-gamma autoantibodies in Japan.

    DOI: 10.1007/s10156-008-0662-8

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  • Inflammatory Cells in Lung Disease Associated with Rheumatoid Arthritis Reviewed

    Yoshiya Nagasawa, Toshinori Takada, Takashi Shimizu, Jun-ichi Narita, Hiroshi Moriyama, Masaki Terada, Eiichi Suzuki, Fumitake Gejyo

    INTERNAL MEDICINE   48 ( 14 )   1209 - 1217   2009

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    Objective Rheumatoid arthritis (RA) is associated with numerous pulmonary manifestations. However, the inflammatory mechanism remains undetermined. We studied the features of inflammatory cells in bronchoalveolar lavage (BAL) fluid and biopsy lung tissue from patients with RA-associated lung disease.
    Methods BAL findings were statistically compared between diseases. We divided RA patients into two groups, airway lesion group (AW) and interstitial lesion group (INT) according to predominant HRCT findings and compared the BAL findings. We immunohistochemically stained lung tissue for CD4, CD8, CD20, and CD163 and counted the immunopositive cells in five different regions.
    Patients Twenty patients fulfilling the Japanese criteria for RA, 13 patients with systemic sclerosis (SSc), and 21 patients with polymyositis and dermatomyositis (PM-DM) with pulmonary disease detected by high-resolution CT (HRCT) were enrolled in this study.
    Results As for BAL in RA, we found a lower lymphocyte frequency with higher CD4/8 ratio compared with PM-DM and a higher neutrophil percentage than both PM-DM and SSc. Nine and eleven patients with RA were classified into AW and INT groups, respectively. BAL findings did not differ between the two groups. Immunohistochemically, most CD4(+) and CD20(+) lymphocytes were accumulated in lymphoid follicles and in the alveolar wall and T-lymphocytes; in particular CD8(+) lymphocytes were predominant in lung interstitium.
    Conclusion These results suggest that 1) neutrophils may play an important role, 2) the inflammatory mechanism may be similar between airway lesion and interstitial pneumonia, and 3) CD8(+) lymphocytes may be major inflammatory cells in lung interstitium in RA-associated interstitial lung disease.

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  • 132 当院通院中の気管支喘息患者の肥満度と重症度・Asthma control testについての検討(気管支喘息-疫学・統計3,一般演題,第21回日本アレルギー学会春季臨床大会)

    鈴木 和夫, 大久保 猛司, 小屋 俊之, 高田 俊範, 長谷川 隆志, 鈴木 栄一

    アレルギー   58 ( 3 )   421 - 421   2009

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    DOI: 10.15036/arerugi.58.421_4

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  • 1.心臓大血管転位術後の肺動脈気管支動脈瘻より喀血を呈した1例(第47回日本呼吸器内視鏡学会北陸支部会)

    山岸 格史, 茂呂 寛, 田邊 嘉也, 中山 秀章, 寺田 正樹, 高田 俊範, 下条 文武, 田中 洋史, 吉澤 弘久, 渡邉 マヤ, 白石 修一, 高橋 昌, 渡辺 弘, 林 純一

    気管支学   31 ( 1 )   43 - 43   2009

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    Language:Japanese   Publisher:特定非営利活動法人 日本呼吸器内視鏡学会  

    DOI: 10.18907/jjsre.31.1_43_1

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  • Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice Reviewed

    S. Tajima, M. Bando, Y. Ishii, T. Hosono, H. Yamasawa, S. Ohno, T. Takada, E. Suzuki, F. Gejyo, Y. Sugiyama

    European Respiratory Journal   32 ( 5 )   1337 - 1343   2008.11

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    Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg·kg-1 of BLM. Edaravone (300 mg·kg-1) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E2 concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E2 production in the present experimental murine system. Copyright©ERS Journals Ltd 2008.

    DOI: 10.1183/09031936.00164407

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  • [Case of central neurosarcoidosis with panhypopituitalism]. Reviewed

    Shimaoka Y, Tajima S, Koshio N, Fujimori F, Tsubata C, Koya T, Moriyama H, Terada M, Takada T, Gejyo F, Hasegawa T, Suzuki E

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society   46 ( 10 )   814 - 819   2008.10

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    A 63-year-old man was admitted because of dizziness, polydipsia, polyuria, and diminished libido. His brain MRI showed swelling of the pituitary gland. Because of panhypopituitarism suggested by hormonal examination, hydrocortisone, desmopressin and levothyroxine sodium were started as hormone replacement therapy. He was given a clinical diagnosis of central neurosarcoidosis with panhypopituitarism because of the presence of an abnormal lung shadow, positive gallium scintigram in bilateral hilar lymph nodes, negative tuberculin skin test, lymphocytosis and a high CD4/8 ratio in bronchoalveolar lavage fluid. After prednisolone therapy, his lung shadow and pituitary swelling reduced significantly. Anti-diuretic hormones and anterior pituitary hormones tended to increase, and his urine volume also decreased. This case suggested that endocrinological abnormalities in central neurosarcoidosis might be improved by prednisolone therapy even if the initiation of treatment is delayed.

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  • Preventive effects of edaravone, a free radical scavenger, onlipopolysaccharide-induced lung injury in mice Reviewed

    Shunji Tajima, Manabu Soda, Masashi Bando, Munehiro Enomoto, Hideaki Yamasawa, Shoji Ohno, Toshinori Takada, Eiichi Suzuki, Fumitake Gejyo, Yukihiko Sugiyama

    RESPIROLOGY   13 ( 5 )   646 - 653   2008.7

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    Background and objective: Reactive oxygen species (ROS) play an important role in the pathogenesis of acute lung injury (ALI) and pulmonary fibrosis. It was hypothesized that edaravone, a free radical scavenger, would be able to attenuate LPS-induced lung injury in mice by decreasing oxidative stress.
    Methods: For the in vivo experiments, lung injury was induced in female BALB/c mice by the intranasal instillation of LPS. Edaravone was given by intraperitoneal administration 1 h before the LPS challenge. For the in vitro experiments, MH-S cells (murine alveolar macrophage cell line) were exposed to edaravone, followed by stimulation with LPS.
    Results: In the LPS-induced ALI mouse model, the administration of edaravone attenuated cellular infiltration into and the concentrations of albumin, IL-6, tumour necrosis factor-alpha, keratinocyte-derived chemokine and macrophage inflammatory protein-2 in BAL fluid. In addition, the in vitro studies showed that the elevated IL-6 secretion from MH-S cells in response to LPS was significantly attenuated by co-incubation with edaravone.
    Conclusions: In an experimental murine model, a free radical scavenger may prevent ALI via repression of pro-inflammatory cytokine production by lung macrophages.

    DOI: 10.1111/j.1440-1843.2008.01322.x

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  • Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan Reviewed

    Yoshikazu Inoue, Bruce C. Trapnell, Ryushi Tazawa, Toru Arai, Toshinori Takada, Nobuyuki HIizawa, Yasunori Kasahara, Koichiro Tatsumi, Masaaki Hojo, Toshio Ichiwata, Naohiko Tanaka, Etsuro Yamaguchi, Ryosuke Eda, Kazunori Oishi, Yoshiko Tsuchihashi, Chinatsu Kaneko, Toshihiro Nukiwa, Mitsunori Sakatani, Jeffrey P. Krischer, Koh Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   177 ( 7 )   752 - 762   2008.4

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    Rationale Acquired pulmonary alveolar proteinosis (PAP) is a syndrome characterized by pulmonary surfactant accumulation occurring in association with granulocyte/macrophage colony-stimulating factor autoantibodies (autoimmune PAP) or as a consequence of another disease (secondary PAP). Because PAP is rare, prior reports were based on limited patient numbers or a synthesis of historical data.
    Objectives: To describe the epidemiologic, clinical, physiologic, and laboratory features of autoimmune PAP in a large, contemporaneous cohort of patients with PAP.
    Methods: Over 6 years, 248 patients with PAP were enrolled in a Japanese national registry, including 223 with autoimmune PAP.
    Measurements and Main Results: Autoimmune PAP represented 89.9% of cases and had a minimum incidence and prevalence of 0.49 and 6.2 per million, respectively. The male to female ratio was 2.1: 1, and the median age at diagnosis was 51 years. A history of smoking occurred in 56%, and dust exposure occurred in 23%; instances of familial onset did not occur. Dyspnea was the most common presenting symptom, occurring in 54.3%. Importantly, 31.8% of patients were asymptomatic and were identified by health screening. Intercurrent illnesses, including infections, were infrequent. A disease severity score reflecting the presence of symptoms and degree of hypoxemia correlated well with carbon monoxide diffusing capacity and serum biomarkers, less well with pulmonary function, and not with granulocyte/macrophage colony-stimulating factor autoantibody levels or duration of disease.
    Conclusions: Autoimmune PAP had an incidence and prevalence higher than previously reported and was not strongly linked to smoking, occupational exposure, or other illnesses. The disease severity score and biomarkers provide novel and potentially useful outcome measures in PAP.

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  • Differences in lymphocyte profile between BAL fluid and human lung tissue from patients with interstitial lung disease Reviewed

    F. Fujimori, I. Shimizu, T. Takada, J. Narita, E. Suzuki, F. Gejyo

    BRITISH JOURNAL OF BIOMEDICAL SCIENCE   65 ( 2 )   63 - 67   2008

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    Bronchoalveolar lavage (BAL) is a technique that samples the inflammatory cells from distal airways and alveoli; however, it is unclear whether or not cellular profiles in the BAL fluid reflect the cellular components of the lung parenchyma in interstitial lung disease (ILD). The aim of this study is to compare immunophenotypes of lymphocytes between BAL fluid and human lung tissue from patients with ILD. Fourteen consecutive patients with ILD who underwent BAL and surgical lung biopsy were enrolled. The diagnosis of ILD was confirmed by the presence of clinical symptoms and impaired respiratory function and on high-resolution computed tomography (CT) of the chest. Mononuclear cells in BAL were immunophenotyped for the expression of CD3, CD4, CD8, CD19, CD45, and CD103 by flow cytometry. Lung tissue obtained by surgical biopsy was digested with collagenase and then centrifuged to extract parenchymal cells. Isolated cells were also immunophenotyped for the same CD expression. Frequencies of positive cells were compared statistically between BAL and different lobes. Seven out of 14 patients were diagnosed clinically as suffering idiopathic interstitial pneumonia. Frequency of CD19(+) cells from BAL was significantly lower than that from the upper/middle lobes (P &lt; 0.05). Frequency of CD103(+) cells from BAL was significantly higher than that from the upper/middle lobes and the lower lobe (P=0.01 and P &lt; 0.05, respectively). Comparison between different lobes demonstrated that the frequency of CD4(+) cells from the upper/middle lobes was significantly lower than that from the lower lobe (P &lt; 0.05). The results suggest that lymphocyte immunophenotype profiles from BAL may not reflect those in the inflammatory tissue of ILD.

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  • 276 エノキ栽培業者の夫婦に同時期に発症した過敏性肺炎(職業アレルギー2,第58回日本アレルギー学会秋季学術大会)

    鈴木 和夫, 大久保 猛司, 笠井 昭男, 吉田 和清, 小屋 俊之, 高田 俊範, 長谷川 隆志, 鈴木 栄一

    アレルギー   57 ( 9 )   1515 - 1515   2008

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    DOI: 10.15036/arerugi.57.1515_4

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  • 1. 縦隔リンパ節腫張を伴った好酸球性肺炎の1例(第45回日本呼吸器内視鏡学会北陸支部会)

    富士盛 文夫, 島岡 雄一, 田島 俊児, 小屋 俊之, 森山 寛史, 田中 純太, 寺田 正樹, 高田 俊範, 下条 文武, 長谷川 隆志, 鈴木 栄一, 竹重 麻里子, 篠原 博彦, 土田 正則, 櫻田 潤子, 梅津 哉

    気管支学   30 ( 1 )   49 - 49   2008

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  • Preventive effect of hochu-ekki-to, a Japanese herbal medicine, on bleomycin-induced lung injury in mice Reviewed

    Shunji Tajima, Masashi Bando, Hideaki Yamasawa, Shoji Ohno, Hiroshi Moriyama, Masaki Terada, Toshinori Takada, Eiichi Suzuki, Fumitake Gejyo, Yukihiko Sugiyama

    RESPIROLOGY   12 ( 6 )   814 - 822   2007.11

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    Objective: Pulmonary fibrosis is thought to be closely associated with the T-helper type-2 (Th2) immune response. Recent studies have shown that hochu-ekki-to (TJ-41), a Japanese herbal medicine, may correct the Th1/Th2 imbalance skewed to Th2. The present study was designed to investigate the preventive effect of TJ-41 on the development of bleomycin (BLM)-induced lung injury in mice.
    Methods: Female C57BL/6 mice were divided into a group given ordinary feed and another group given the same feed plus TJ-41 mixed in at a dose of 1 g/kg/day. Both groups were maintained on this diet for 8 weeks before and 5 weeks after administration of 2 mg/kg BLM intratracheally.
    Results: Mortality after BLM-induced lung injury was significantly lower in the TJ-41-treated mice. The hydroxyproline content and fluid content in the lung on day 35 was significantly lower in the TJ-41-treated mice. Histologically, TJ-41 reduced the number of infiltrating cells, thus ameliorating the destruction of the lung architecture, and attenuated the lung fibrosis score. Furthermore, TJ-41 inhibited the expression of the interleukin-5/interferon-gamma mRNA ratio in the lung on day 7.
    Conclusion: Treatment with TJ-41 partially prevented experimental lung fibrosis through the correction of the Th1/Th2 imbalance skewed to Th2.

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  • Two-dimensional analysis of elements and mononuclear cells in hard metal lung disease Reviewed

    Hiroshi Moriyama, Masayoshi Kobayashi, Toshinori Takada, Takashi Shimizu, Masaki Terada, Jun-ichi Narita, Michio Maruyama, Kouichi Watanabe, Eiichi Suzuki, Fumitake Gejyo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   176 ( 1 )   70 - 77   2007.7

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    Rationale: Hard metal lung disease is caused by exposure to hard metal, a synthetic compound that combines tungsten carbide with cobalt as well as a number of other metals. Interstitial lung disease caused by hard metal is uniquely characterized by giant cell interstitial pneumonia. The pathogenesis of hard metal lung disease is unclear.
    Objectives: To elucidate the distribution of inhaled hard metal and reactive inflammatory cells in biopsy lung tissue from patients with hard metal lung disease.
    Methods: Seventeen patients with interstitial lung disease in which tungsten was detected and five control subjects were studied. Detection and mapping of elements were performed with an electron probe microanalyzer equipped with a wavelength dispersive spectrometer. We immunohistochemically stained mononuclear cells in tissue samples available from five patients, with anti-human CD4, CD8, CD20, CD68, and CD163 antibodies, and compared the distribution of positive cells with hard metal elements.
    Measurements and Main Results: Thirteen of 17 patients were pathologically diagnosed as having giant cell interstitial pneumonia. Tungsten and cobalt were accumulated in the centrilobular fibrotic lesions, but were never found in the control lungs. CD8(+) lymphocytes and CD163(+) monocyte-macrophages were distributed predominantly in centrilobular fibrotic lesions around the hard metal elements. CD163(+) colocalized with tungsten. Small numbers of CD8(+) and CD163(+) cells were also immunohistochemically shown in peribronchiolar areas and alveolar walls.
    Conclusions: Macrophages may phagocytose inhaled tungsten via CID163 and play an important role in forming the fibrotic lesion of hard metal lung disease with cytotoxic T lymphocytes.

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  • ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine stimuli may modulate lung injury and fibrosis Reviewed

    Shunji Tajima, Masashi Bando, Shoji Ohno, Yukihiko Sugiyama, Katsuhisa Oshikawa, Shin-ichi Tominaga, Kouichi Itoh, Toshinori Takada, Eiichi Suzuki, Fumitake Gejyo

    EXPERIMENTAL LUNG RESEARCH   33 ( 2 )   81 - 97   2007.3

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    The authors have investigated gene expression of ST2 in the lung tissue of a bleomycin (BLM)-induced lung fibrosis model in vivo and in a human lung fibroblast cell line, WI38, and a human type II alveolar epithelial cell line, A549, reacting to proinflammatory and type 2 helper T cell (Th2)-type cytokine stimuli in vitro. The lung mRNA expression of interleukin (IL)-4, IL-5, IL-1 beta, and tumor necrosis factor (TNT)-alpha increased significantly at day 7 after instillation of BLM, whereas interferon (IFN)-gamma mRNA expression did not increase. ST2 and transforming growth factor (TGF)-beta 1 mRNA expression of the lung increased significantly between days 7 and 21, and increased to maximal levels at day 14 post-BLM challenge. ST2 mRNA expression statistically correlated with TGF-beta 1 mPLNA expression. In addition, the combination of IL-1 beta, TAT-alpha, and IL-4 had an additive effect on ST2 mRNA expression from A549 cells and WI38 cells. These findings suggest that soluble ST2 gene may increase, possibly reflecting the development of the inflammatory process and the Th2-type immune response in the fibrotic lung tissue, and may modulate a process of pulmonary fibrosis.

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  • Isolation and immunophenotyping of mononuclear cells from human lung tissue Reviewed

    Takashi Shimizu, Fumio Fujimori, Yuichi Shimaoka, Jun-ichi Narita, Toshinori Takada, Shunji Tajima, Hiroshi Moriyama, Masaki Terada, Eiichi Suzuki, Fumitake Gejyo

    INTERNAL MEDICINE   46 ( 4 )   163 - 169   2007

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    Objective To quantitatively isolate and immunologically phenotype mononuclear cells contained in human lung tissue.
    Methods Normal appearing lung tissue as far distal to the resected lesion as possible was obtained from lung cancer patients. Lung tissue was thoroughly washed and cut into small pieces and digested with collagenase. Peripheral blood mononuclear cells (PBMNC) were prepared from controls using Ficoll gradient. Isolated cells and PBMNC were analyzed by flow cytometry. We immunohistochemically stained snap-frozen lung tissue with anti-CD3, CD4, CD8, CD20, and CD161 antibodies.
    Participants Nineteen patients with lung cancer who underwent lobectomy were enrolled. Twelve healthy volunteers also participated as controls for flow cytometric analysis of PBMNC.
    Results In forward scatter vs side scatter, 92.1 +/- 7.8% of isolated cells in the lymphoid population expressed leukocyte common antigen, CD45. The frequency of CD45-positive cells in the lymphoid population from lung tissue was as high as that from PBMNC (p = 0.118). CD45-positive cells were successfully further extended by anti-CD3, CD4, CD8, CD19, and CD161 antibodies. Monocyte-macrophages bearing CD68 were also detected. CD68-positive alveolar macrophages dissapeared from alveolar spaces after thorough washing by immunohistochemical staining. Mononuclear cells in the interstitium were positively stained by anti-CD3, CD4, CD8, CD20, and CD161 monoclonal antibodies.
    Conclusions We could isolate interstitial cells and analyze cell surface markers via flow cytometry from fresh lung specimens by collagenase digestion without further purification. Immunohistochemistry confirmed the presence of the cells detected by flow cytometry in the lung interstitium.

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  • P118 成人百日咳患者の検討(慢性咳嗽・他3, 第19回日本アレルギー学会春季臨床大会)

    鈴木 和夫, 佐藤 文則, 笠井 昭男, 吉田 和清, 田邊 嘉也, 高田 俊範, 下条 文武, 長谷川 隆志, 鈴木 栄一

    アレルギー   56 ( 3 )   358 - 358   2007

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  • Preventive effect of Hochu-ekki-to on lipopolysaccharide-induced acute lung injury in BALB/c mice Reviewed

    Shunji Tajima, Masashi Bando, Hideaki Yamasawa, Shoji Ohno, Hiroshi Moriyama, Toshinori Takada, Eiichi Suzuki, Fumitake Gejyo, Yukihiko Sugiyama

    LUNG   184 ( 6 )   318 - 323   2006.12

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    This study was designed to investigate the effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in female BALB/c mice by the intranasal administration of 0.1 mg/kg LPS. The mice were divided into a group receiving normal feed and another group receiving feed mixed with TJ-41 at a dose of 1 g/kg/day for 8 weeks before LPS challenge. In the bronchoalveolar lavage fluid, the preadministration of TJ-41 caused significant reduction in the absolute number of total cells, neutrophils, and macrophages. The preadministration of TJ-41 significantly inhibited increases in the serum level of keratinocyte chemoattractant (KC), which is a murine chemotaxin for neutrophils that corresponds to human interleukin-8, with respect to its concentration at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the TJ-41-treated mice than in the control mice. These findings indicated that the preadministration of TJ-41 could show an inhibitory effect on ALI in this experimental murine system associated with the suppression of chemokine production.

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  • [A case of refractory Wegener's granulomatosis successfully treated with high-dose methotrexate]. Reviewed

    Shimizu T, Shimizu N, Takada T, Gejyo F, Hasegawa T, Suzuki E

    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society   44 ( 11 )   853 - 857   2006.11

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  • Alveolar hemorrhage in a patient with sarcoidosis [1] Reviewed

    Shunji Tajima, Mitsugu Hironaka, Shoko Nakazawa, Masashi Bando, Shoji Ohno, Hitoaki Okazaki, Ken Saito, Toshinori Takada, Eiichi Suzuchi, Fumitake Grejyo, Yukihiko Sugiyama

    Sarcoidosis Vasculitis and Diffuse Lung Diseases   23 ( 3 )   236 - 237   2006.10

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  • Analysis of the effect of surgical lung biopsy on serum KL-6 levels in patients with interstitial pneumonia: Surgical lung biopsy does not elevate serum KL-6 levels Reviewed

    Jun-ichi Narita, Takashi Hasegawa, Masanori Tsuchida, Masaki Terada, Toshinori Takada, Takehisa Hashimoto, Tadashi Aoki, Hiroki Tsukada, Ichiei Narita, Jun-ichi Hayashi, Fumitake Gejyo, Eiichi Suzuki

    INTERNAL MEDICINE   45 ( 9 )   615 - 619   2006

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    Objective It is well known that the serum level of KL-6 can be an indicator of disease activity in patients with interstitial pneumonia (IP). However, surgical lung biopsy is often required for the diagnosis of IP, although this can result in IP exacerbation.
    Methods The effect of surgical lung biopsy on the serum level of KL-6 in patients with IP was analyzed. Thirty-two cases of IP were examined in this study. There were no cases showing exacerbation of IP.
    Results The serum level of KL-6 demonstrated 1067 +/- 550 U/ml (mean +/- SD) before lung biopsy, 991 +/- 471 U/ml a day, 824 +/- 377 U/ml 4 days and 826 +/- 384 U/ml 7 days after lung biopsy. The serum KL-6 levels on the 1st, 4th, 7th day after the lung biopsy were significantly lower than that before the lung biopsy (P &lt; 0.05, P &lt; 0.01 and P &lt; 0.01, respectively). The percent decrease of the serum KL-6 levels on the 4th day (the lowest level) was dependent on the urine volume, and the analysis of the urinary levels of KL-6 showed a transient increase in urinary KL-6 excretion, suggesting that the decrease in serum KL-6 levels associated with surgical lung biopsy may be caused by this increase in urinary KL-6 excretion.
    Conclusion Surgical lung biopsy of patients with IP has little effect on the increase in serum KL-6 levels. An elevation of serum KL-6 after surgical lung biopsy may indicate exacerbation of IP.

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  • Serotonin-2A and 2C receptor gene polymorphisms in Japanese patients with obstructive sleep apnea Reviewed

    K Sakai, T Takada, H Nakayama, Y Kubota, M Nakamata, M Satoh, E Suzuki, K Akazawa, F Gejyo

    INTERNAL MEDICINE   44 ( 9 )   928 - 933   2005.9

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    Objective The serotonin (5-HT) 2A and 2C receptor subtype plays an important role in the maintenance of upper airway stability and normal breathing in obesity. Polymorphisms in the 5-HT 2A receptor gene (HTR2A) and 5-HT 2C receptor gene (HTR2C) are associated with various diseases. The aim of this study was to investigate whether or not the HTR2A/C genotypes are associated with obstructive sleep apnea (OSA).
    Methods The PCR-restriction fragment length polymorphism method was used to determine genotypes of the HTR2A/C gene. The genotype distributions and allele frequencies were statistically analyzed. Subjects We studied 177 consecutive male patients with excessive daytime somnolence and an apnea plus hypopnea number [apnea-hypopnea index (AHI)] of greater than five per hour of sleep established by full polysomnography. One hundred Japanese men in whom OSA was clinically excluded were randomly selected as a control group.
    Results Genotypes and allele frequencies of 102T/C polymorphism of the HTR2A and 796G/C polymorphism of the HTR2C did not differ between controls and patients with OSA. HTR2C polymorphism was considered inappropriate for association studies because of low frequency of the mutant allele. Multiple regression analysis showed that age and body mass index (BMI) were significantly associated with OSA, but HTR2A polymorphisms were not. HTR2A polymorphisms had no significant relationship with AHI or BMI, although further study with more samples will be needed for powerful statistical analyses.
    Conclusions These results indicate that age and BMI, not these polymorphisms, are associated with OSA in this population.

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  • Facial axis angle as a risk factor for obstructive sleep apnea Reviewed

    Y Kubota, H Nakayama, T Takada, N Matsuyama, K Sakai, H Yoshizawa, M Nakamata, M Satoh, K Akazawa, E Suzuki, F Gejyo

    INTERNAL MEDICINE   44 ( 8 )   805 - 810   2005.8

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    Objective Many Japanese patients with obstructive sleep apnea (OSA) are less obese than Caucasian OSA patients despite their similar severity of OSA, suggesting that their etiology of OSA may differ. The purpose of this study was to identify bony factors associated with OSA in the Japanese population.
    Methods The clinical records of study subjects were retrospectively reviewed, and cephalometric measurements based on Sella-Nasion references and the Ricketts method were statistically compared.
    Patients Two hundred and six consecutive Japanese men complaining of habitual snoring and daytime sleepiness were enrolled in the study. All subsequently underwent an overnight polysomnographic examination.
    Results Multiple regression analysis showed that the body mass index (p &lt; 0.0001) and facial axis angle (p=0.007) were the dominant overall determinants for the apnea hypopnea index. The sella to nasion to subspinale angle (SNA) and sella to nasion to supramentale angle (SNB) were lower in the non-obese, severe group than for non-obese, mild and moderate patients with OSA (p=0.0047 and 0.0016, respectively).
    Conclusion The risk factors for OSA in Japanese men may be obesity and the dolico facial pattern seen by the Ricketts method. In addition, a smaller SNA and SNB seem to be associated with the severity of OSA in nonobese patients.

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  • Tracheo-bronchitis associated with Crohn's disease improved on inhaled corticotherapy Reviewed

    S Kinebuchi, K Oohashi, T Takada, H Moriyama, H Yoshizawa, O Kobayashi, E Suzuki, F Gejyo

    INTERNAL MEDICINE   43 ( 9 )   829 - 834   2004.9

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    We report a case of tracheo-bronchitis in Crohn's disease. A 23-year-old Japanese woman who had been diagnosed with Crohn's disease three years previously was hospitalized. She had been suffering from dry cough for one month. Computed tomography of the chest revealed marked thickening of the tracheal wall. Bronchoscopy showed erythematous and edematous mucosa with diffuse whitish granular lesions in the trachea and bronchi. The bronchial biopsy specimens showed non-specific inflammatory infiltrates consisting of lymphocytes and plasma cells, and hyperplasia of bronchial glands. Inhaled corticotherapy, fluticasone propionate 800 mug/day, was effective for both the inflammatory mucosa and thickened tracheal wall.

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  • Peroxisome proliferator-activated receptor γ C161T polymorphisms and survival of Japanese patients with immunoglobulin A nephropathy Reviewed

    J. Song, Minoru Sakatsume, I. Narita, S. Goto, K. Omori, T. Takada, N. Saito, M. Ueno, F. Gejyo

    Clinical Genetics   64 ( 5 )   398 - 403   2003.11

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    Peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in lipid metabolism, insulin sensitivity, atherogenesis, and immune regulation. A genetic polymorphism (C161T) at exon 6 of PPARγ gene (PPARG) was reported to be associated with the onset of coronary artery disease. However, there has been no report of an association with renal disease. Genomic DNAs were isolated from 225 Japanese patients with histologically confirmed immunoglobulin A nephropathy (IgAN). The PPARG C161T genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. The association of the polymorphism with renal prognosis in IgAN patients was analyzed using the Kaplan-Meier method and Cox proportional hazard regression model. The PPARG polymorphism was not associated with the renal survival rate. However, when patients were stratified into those either with or without hypertension at the time of diagnosis, the renal survival of the CT/TT genotypes was significantly better in those without hypertension than those with the CC genotype. We report that the PPARG C161T polymorphism is associated with the survival of IgAN patients without hypertension. The T allele of the polymorphism might have a protective effect on the progression of IgAN.

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  • Bronchoalveolar lavage fluid cells in mixed connective tissue disease Reviewed

    K Enomoto, T Takada, D Suzuki, T Ishida, H Moriyama, H Ooi, T Hasegawa, H Tsukada, M Nakano, F Gejyo

    RESPIROLOGY   8 ( 2 )   149 - 156   2003.6

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    Objective: Patients with mixed connective tissue disease (MCTD) exhibit clinical features of systemic lupus erythernatosus (SLE), systemic sclerosis (SSc), and polymyositis and dermatomyositis (PM-DM). The objective of this study was to clarify differences in BAL findings and immunophenotypes of BAL fluid (BALF) cells of patients with interstitial lung disease associated with these diseases.
    Methodology: We were unable to recruit a sufficient number of SLE patients with lung disease. We compared immunophenotypes of lymphocytes and alveolar macrophages (AM) in BALF of 20 MCTD patients with those of 21 SSc and 27 PM-DM patients and tested the relationships between immunophenotypes and pulmonary function in MCTD.
    Results: MCTD patients had a significantly higher CD4/CD8 ratio with more CD4 positive lymphocytes than PM-DM patients (P = 0.025). In AM phenotypes, MCTD patients had a significantly lower percentage of CD71 positive AM compared with SSc patients (P = 0.023). DLCO was negatively related to absolute numbers of CD8 positive lymphocytes (R = -0.517, P = 0.033).
    Conclusions: CD4 positive lymphocytes in BALF were increased in MCTD compared to PM-DM patients, while CD71 positive AM were decreased in MCTD compared to SSc patients. CD8 positive lymphocytes correlated negatively with DLCO measurements in MCTD patients.

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  • Vascular endothelial growth factor gene polymorphisms in Japanese patients with sarcoidosis Reviewed

    K Morohashi, T Takada, K Omori, E Suzuki, F Gejyo

    CHEST   123 ( 5 )   1520 - 1526   2003.5

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    Objectives: Vascular endothelial growth factor (VEGF) promotes angiogenesis, mediates vascular permeability, and activates and recruits monocytes. VEGF is produced in activated alveolar macrophages, in epithelioid cells, and in multinuclear giant cells of pulmonary sarcoid granulomas. Recent reports have shown that a polymorphism at - 627 of the VEGF gene is related to VEGF protein production, and a polymorphism at + 813 is associated with VEGF plasma levels. We investigated the roles of such polymorphisms in the development and extent of sarcoidosis.
    Methods: We examined polymorphisms of the VEGF gene in 103 Japanese patients with sarcoidosis and 146 healthy Japanese control subjects. The position - 627 polymorphism was determined using the TaqMan (TaqMan Laboratory, University of Pittsburgh Cancer Institute; Pittsburgh, PA) polymerase chain reaction (PCR) method. For genotyping of the position + 813 polymorphism, the PCR restriction fragment length polymorphism method was performed.
    Results: As for + 813 genotypes, the less-common genotypes CT and TT were found more often in control subjects than in patients (odds ratio, 0.490; 95% confidence interval, 0.276 to 0.868). A significant increase in the frequency of the T allele (p = 0.005, Pc = 0.020 after Bonferroni correction) was observed in control subjects. As for - 627 genotypes, the mean value of the FEV1/FVC percentage in GG type was lower than that in CC or CG type, however, the other clinical findings did not suggest airway diseases in the GG type.
    Conclusions: We suggest that in VEGF gene polymorphisms the T allele at + 813 may decrease susceptibility to sarcoidosis.

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  • 2.吸入ステロイド薬のみで改善したクローン病に伴う気管気管支炎の1例(第36回日本呼吸器内視鏡学会北陸支部会)

    大橋 和政, 杵渕 進一, 西堀 武明, 高田 俊範, 長谷川 隆志, 塚田 弘樹, 吉澤 弘久, 下条 文武, 鈴木 栄一, 本間 照, 小林 理

    気管支学   25 ( 6 )   480 - 480   2003

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  • MCP-1 and MIP-1A gene polymorphisms in Japanese patients with sarcoidosis Reviewed

    T Takada, E Suzuki, K Morohashi, K Omori, F Gejyo

    INTERNAL MEDICINE   41 ( 10 )   813 - 818   2002.10

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    Objectives Monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-lalpha exhibit chemotactic activity toward macrophages/monocytes and induce the production of inflammatory cytokines affecting granuloma formation. Recently, a single nucleotide polymorphism (SNP) in the MCP-1 distal regulatory region and a dinucleotide repeat in the MIP-1A gene promoter region were identified. We investigated the relationships between the polymorphisms and susceptibility to sarcoidosis, clinical manifestations, and BALF findings of sarcoidosis.
    Methods The polymorphisms of the MCP-1 and MIP-1A genes in 118 patients with sarcoidosis and 145 healthy control subjects were examined. The MCP-1 polymorphism was genotyped by a PCR-restriction fragment length polymorphism method and the MIP-1A genotype was determined using PCR.
    Results No significant difference in the genotype distribution or in the allele frequency between the patients and control subjects was observed. We found no relationship between the polymorphisms and the serum ACE level, organ involvement, roentgenographic stages, or deterioration in chest radiographs during the follow-up. A significant difference in the absolute counts of AMs in BALF of 51 patients among the genotypes of the MCP-1 gene was found (p=0.048). The AM counts in BALF of the G/A and G/G genotypes were significantly increased compared with that of the A/A genotype (p&lt;0.05).
    Conclusion The polymorphisms of the MCP-1 and MIP-1A genes do not play a substantial role in genetic predisposition for sarcoidosis or in clinical manifestations of sarcoidosis in this Japanese population. The MCP-1 SNP might be related to the recruitment of monocytes/macrophages to the alveolar spaces in sarcoidosis.

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  • Association of the MCP-1 gene polymorphism A-2518G with carpal-tunnel syndrome in hemodialysis patients Reviewed

    K Omori, JJ Kazama, J Song, S Goto, T Takada, N Saito, M Sakatsume, K Narita, F Gejyo

    AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS   9 ( 3 )   175 - 182   2002.9

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    Carpal-tunnel syndrome (CTS) in long-term hemodialysis patients is caused by the deposition of amyloid as well as by the local inflammatory process. The recruitment of monocytes/macrophages in the tenosynovium, promoted by chemokines such as monocyte chemoattractant protein-1alpha (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), is thought to play an important role in CTS development. The genetic polymorphism of these chemokines has been identified and their clinical function has been partly revealed We attempted to analyze the relationship between these polymorphisms and their susceptibility to CTS. The subjects of this study were 366 patients who underwent hemodialysis. Ninety-five patients received surgery for CTS. No significant difference was observed in the genotype distributions of MCP-1 or MIP-1alpha between patients who received CTS surgery and those that did not. However, with the use of a logistic regression model, the MCP-1 GG genotype was identified as a risk factor for the development of CTS, in addition to the duration and the age of initiation of dialysis, as confirmed by a Cox proportional hazards model. In conclusion, homozygosity for G at -2518 in the MCP-1 gene might be a candidate for the genetic marker of CTS development in Japanese hemodialysis patients.

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  • Association of single nucleotide polymorphisms in the IL-18 gene with sarcoidosis in a Japanese population Reviewed

    T Takada, E Suzuki, K Morohashi, F Gejyo

    TISSUE ANTIGENS   60 ( 1 )   36 - 42   2002.7

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    Interleukin-18 (IL-18) and interleukin-12 (IL-12) synergistically stimulate interferon-gamma (IFN-gamma) production from Th1 cells. The levels of serum IL-18 and IFN-gamma and bronchoalveolar lavage fluid IL-18 were elevated in patients with sarcoidosis. The polymorphisms of the IL-18 gene may play a possible role in expression regulation of the gene. We investigated the roles of the polymorphisms in the development of sarcoidosis. We examined two single nucleotide polymorphisms of the IL-18 gene in 119 patients with sarcoidosis and 130 healthy control subjects. Our results showed that the frequency of sarcoidosis patients with the CA genotype at position -607 was significantly higher than that with the AA genotype (OR=2.200) and a significantly higher proportion of patients had the C allele at -607 compared with that of the controls (OR=2.123). No significant differences were seen in the distribution of the genotypes or phenotype frequencies at position 137. There was no specific organ involvement associated with a certain genotype or phenotype. In IL-18 gene polymorphisms, the C allele at position -607 might be a genetic risk factor for sarcoidosis in this Japanese population.

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  • Pulmonary involvement in mixed connective tissue disease: Comparison with other collagen vascular diseases using high resolution CT Reviewed

    Y Saito, M Terada, T Takada, T Ishida, H Moriyama, H Ooi, T Hasegawa, H Tsukada, E Suzuki, F Gejyo, Y Kihara

    JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY   26 ( 3 )   349 - 357   2002.5

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    Purpose: The purpose of this work was to compare the CT findings of lung involvement in patients with mixed connective tissue disease (MCTD) with those in patients with other CTDs: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis and dermatomyositis (PM-DM).
    Method: CT scans of 35 patients with interstitial lung disease and associated MCTD were evaluated retrospectively. The CT assessment included determination of the findings and evaluation of whether the findings in MCTD were different from those in other CTDs.
    Results: The frequency of ground-glass opacity in MCTD was significantly lower than in CTDs (p &lt; 0.05). The frequency of honeycombing in MCTD was lower than in SSc (p &lt; 0.05) and higher than in PM-DM (p &lt; 0.005). Regarding the predominant CT patterns, the frequency of septal thickening in MCTD was significantly higher than in CTDs (p &lt; 0.05).
    Conclusion: CT findings in MCTD were a combination of those in other CTDs.

    DOI: 10.1097/01.RCT.0000015525.51830.61

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  • Pulmonary diffusion capacity in patients with systemic lupus erythematosus Reviewed

    M Nakano, H Hasegawa, T Takada, S Ito, Y Muramatsu, M Satoh, E Suzuki, F Gejyo

    RESPIROLOGY   7 ( 1 )   45 - 49   2002.3

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    Objective: The aim of this study was to clarify the characteristics of pulmonary function tests (PFT), especially carbon monoxide diffusion capacity (DLCO), and their correlation with clinical features and immunological findings in patients with systemic lupus erythematosus (SLE).
    Methodology: Vital capacity (VC) and DLCO were analysed retrospectively in 110 sequential Japanese SLE patients with active disease between 1985 and 1999. In 38 patients, serial measurements of PFT were also assessed during high-dose corticosteroid therapy.
    Results: DLCO was reduced in 52 patients (47%) and a restrictive impairment of PFT was observed in nine patients (8%). The prevalence of pulmonary fibrosis was 13%. Reduced DLCO was frequently observed, even in patients with neither pulmonary fibrosis nor a restrictive pattern. No correlation between immunological data and reduced DLCO was found, except for the presence of anti-RNP Patients with Raynaud's phenomenon showed a higher prevalence of DLco impairment than those without this phenomenon. Although immunological parameters improved significantly after the corticosteroid therapy, no significant change in the level of DLco was observed.
    Conclusions: Impairment of DLCO was frequently observed in patients with SLE who had no clinical respiratory abnormalities. DLCO impairments were correlated with Raynaud's phenomenon clinically, and the presence of anti-RNP immunologically. No significant correlation was found between impairment of DLCO and disease activity of SLE.

    DOI: 10.1046/j.1440-1843.2002.00361.x

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  • Polymorphism in RANTES chemokine promoter affects extent of sarcoidosis in a Japanese population Reviewed

    T Takada, E Suzuki, T Ishida, H Moriyama, H Ooi, T Hasegawa, H Tsukuda, F Gejyo

    TISSUE ANTIGENS   58 ( 5 )   293 - 298   2001.11

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    RANTES, a member of C-C chemokine, is known to be produced at sites of granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO(+) T cells and eosinophils. Polymorphism of the RANTES promoter has recently been shown to be related to allergic and infectious diseases; atopic dermatitis, asthma, and polymyalgia rheumatica. Considering that this might affect sarcoidosis, we studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no difference in the genotype distribution between healthy control subjects and sarcoidosis patients was identified, the difference in the frequencies of the patients with three or more organ involvement was significant (P&lt;0.01) with the frequency of those in AA genotype being elevated (P&lt;0.05). BAL findings in 48 out of 114 patients who underwent bronchoscopy were reviewed. The patients CD4/8 ratio of lymphocytes in bronchoalveolar lavage fluid in the pat with AA genotype was significantly increased (P&lt;0.05). From the results, we suggest that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.

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  • 220 胸部CTと気管支肺胞洗浄所見からみた多発性筋炎と皮膚筋炎との比較

    森山 寛史, 石田 卓上, 寺田 正樹, 大井 秀美, 高田 俊範, 長谷川 隆志, 塚田 弘樹, 鈴木 栄一, 下条 文武

    アレルギー   50 ( 2 )   299 - 299   2001

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    DOI: 10.15036/arerugi.50.299_4

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  • 4 膠原病肺の臨床-画像所見とBAL所見を中心に(12 膠原病肺の病態と治療)

    寺田 正樹, 鈴木 栄一, 石田 卓士, 森山 寛史, 大井 秀美, 長谷川 隆志, 塚田 弘樹, 高田 俊範, 下条 文武, 斎藤 泰晴

    アレルギー   49 ( 9 )   835 - 835   2000

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    DOI: 10.15036/arerugi.49.835_1

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  • Clinical features of polymyositis/dermatomyositis with steroid-resistant interstitial lung disease Reviewed

    Toshinori Takada, Eiichi Suzuki, Masaaki Nakano, Hiroshi Kagamu, Hiroki Tsukada, Takashi Hasegawa, Makoto Satoh, Michihiko Haraguchi, Tatsuo Ebe, Masaaki Arakawa

    Internal Medicine   37 ( 8 )   669 - 673   1998

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    Polymyositis and dermatomyositis (PM/DM) without creatine kinase (CK) elevation shows a poor prognosis. PM/DM is complicated with interstitial lung disease (ILD), some of which progress rapidly. To clarify the clinical features of PM/DM from the viewpoint of ILD progression, the clinical data of 25 PM/DM patients with ILD were reviewed. They were classified as responders or non-responders. The patients whose ILD responded to steroid therapy and elicited good clinical courses were termed as responders. On the other hand, the patients who had rapidly progressive ILD resistent steroid therapy were considered as non-responders. The patients diagnosed to have DM were likely to be steroid-resistant. The non-responder group revealed significantly high aspartate aminotransferase (AST), low CK, low white blood cell (WBC), and low absolute lymphocyte counts in their peripheral blood. High CK/AST may be a favorable predictor of the disease. The percentages of lymphocytes in bronchoalveolar lavage fluid were increased in both groups. However, the percentages of two responders with low CK/AST were lower than those of three non-responders. A steroid-resistant ILD group with PM/DM may be clinically different from a steroid-responsive ILD group.

    DOI: 10.2169/internalmedicine.37.669

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  • A case of sarcoidosis with nasopharyngeal tumor, hepatosplenomegaly, multiple patchy lung shadow and mediastinal lymph node swelling

    NIHON SARUKOIDOSHISU / NIKUGESHUSHIKKAN (The Japanese journal of sarcoidosis and other granulomatous disorders )   16   145 - 146   1997

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    DOI: 10.14830/jssog1987.16.145

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  • Recovery from descending necrotizing mediastinitis and multiple organic failure after seven months of mechanical ventilation Reviewed

    K. Ohno, T. Takada, M. Terada, M. Satoh, E. Suzuki, K. Wada, T. Hirono, M. Arakawa

    Japanese Journal of Thoracic Diseases   34 ( 9 )   1021 - 1029   1996

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    A 61-year-old man with a history of hypertension and diabetes mellitus had a tooth extracted. Nine days later, he was admitted to the hospital with complaints of high fever, dyspnea, and anterior chest pain. Physical examination revealed a drowsy man for a fever of 38.2°C, blood pressure of 66/44 mmHg, and marked redness and swelling from he neck to anterior part of the chest. Laboratory examination indicated severe infection and multiple organ, consisting of cardiac, respiratory, renal, and hepatic failure, with disseminated intravascular coagulation. Chest X-ray and CT-scan films showed abscesses extending from the neck to the mediastinum, and bilateral pleural effusion. Immediately, he was treated with cathecholamines, furosemide, mechanical ventilation with a high concentration of oxygen, continuous drainage, repeated skin incisions, and broad-spectrum antibiotics. In addition, steroid pulse therapy was administered for persistent respiratory failure. On the 28th hospital day, a fistula developed between the trachea and the mediastinum, and an intratracheal tube had to be inserted through the fistula. On the 212th hospital day, after intravenous hyperalimentation, continuous intravenous insulin infusion, and administration of broad-spectrum antibodies, catecholamines, and furosemide, the patient was weaned from mechanical ventilation. A restrictive ventilatory defect due to ankylosis and atrophy of underused muscles was noted after weaning, but the PaO2 was high with a low dose of oxygen (1 to 2.1/min), and 21 months later, the blood gases were normal while the patient was breathing room air. As of January, 1996, he was undergoing rehabilitation to promote his recovery from ankylosis, muscle atrophy, and speech dysfunction.

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  • A case of interstitial lung disease in primary Sjögren's syndrome associated with pulmonary sarcoidosis

    NIHON SARUKOIDOSHISU / NIKUGESHUSHIKKAN (The Japanese journal of sarcoidosis and other granulomatous disorders )   15   90 - 91   1996

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    DOI: 10.14830/jssog1987.15.90

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  • 29 多発筋炎/皮膚筋炎と強皮症に伴う間質性肺炎における気管支肺胞洗浄液中のリンパ球とマクロファージ表面マーカーの解析(BAL 2)

    田口 洋子, 丹呉 益夫, 榎本 克巳, 小浦方 啓代, 桑原 克弘, 高田 俊範, 鈴木 栄一, 荒川 正昭

    気管支学   18 ( 3 )   270 - 270   1996

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    DOI: 10.18907/jjsre.18.3_270_1

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  • 28 当科における混合性結合織病に伴う間質性肺病変の気管支肺胞洗浄液所見の検討(BAL 2)

    榎本 克巳, 丹呉 益夫, 田口 洋子, 小浦方 啓代, 高田 俊範, 鈴木 栄一, 荒川 正昭

    気管支学   18 ( 3 )   269 - 269   1996

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    DOI: 10.18907/jjsre.18.3_269_4

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  • 32 特発性間質性肺炎と間質性肺炎を伴う強皮症の肺胞洗浄液所見の比較検討(BAL 3)

    小浦方 啓代, 丹呉 益夫, 榎本 克巳, 田口 洋子, 高田 俊範, 鈴木 栄一, 荒川 正昭

    気管支学   18 ( 3 )   270 - 270   1996

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    DOI: 10.18907/jjsre.18.3_270_4

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  • 97 Competitive RT-PCR 法を用いた, サルコイドーシス患者 BALF 中マクロファージでの PDGF(A)(B)・TGF-βmRNA 発現の解析(BAL (IV))

    桑原 克弘, 田口 洋子, 小浦方 啓代, 高田 俊範, 塚田 弘樹, 丸山 倫夫, 佐藤 誠, 鈴木 栄一, 荒川 正昭

    気管支学   17 ( 3 )   271 - 271   1995

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    DOI: 10.18907/jjsre.17.3_271_1

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  • A Case of Pneumonitis due to Rikkunshi-to.

    Maruyama Yoshie, Maruyama Michio, Takada Toshinori, Haraguchi Michihiko, Uno Katsuji

    The Japanese journal of thoracic diseases   32 ( 1 )   84 - 89   1994

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    We report a case of pneumonitis due to Rikkunshi-to. A 79-year-old woman was admitted to our hospital because of interstitial pneumonia. She complained of dry cough and dyspnea on exertion. Fine crepitations were heard on physical examination. The chest X-ray film revealed diffuse reticulonodular shadows in both lung fields. Under the suspicion of drug-induced pneumonitis, all drugs were stopped and she was given prednisolone. Consequently her complaints, laboratory data and chest X-ray findings markedly improved.<br>Microscopic examination of transbronchial lung biopsy specimens showed interstitial pneumonia. The results of lymphocyte stimulation test and lymphocyte migration inhibition test were positive for Rikkunshi-to.<br>Based on these findings, we diagnosed this case as pneumonitis due to Rikkunshi-to. To our knowledge, there has been no previous case of pulmonary hypersensitivity due to Rikkunshi-to reported in the world.

    DOI: 10.11389/jjrs1963.32.84

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  • A Clinical Guide to Occupational and Environmental Lung Diseases

    TAKADA Toshinori, MORIYAMA Hiroshi( Role: Joint author ,  217-230)

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  • 自己免疫性肺胞蛋白症に対するGM‐CSF吸入療法

    田澤立之, 鈴木雅, 大河内眞也, 朝川勝明, 巽浩一郎, 石井晴之, 泉信有, 山口悦郎, 井上義一, 半田知宏, 富井啓介, 江田良輔, 森本浩之輔, 三上礼子, 田中崇裕, 北村信隆, 北村信隆, 高田俊範, 上田隆宏, 上田隆宏, 中垣和英, 中田光

    日本呼吸器学会誌(Web)   8   23   2019.3

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  • 抗MDA-5抗体陽性皮膚筋炎にともなう間質性肺炎におけるIL-15の役割

    高田 俊範, 青木 亜美, 大橋 和政, 木村 陽介, 林 正周, 菊地 利明

    日本呼吸器学会誌   8 ( 増刊 )   227 - 227   2019.3

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  • 肺胞蛋白症の20年史 自己免疫性肺胞蛋白症の最新疫学

    北村 信隆, 大河内 眞也, 田澤 立之, 石井 晴之, 高田 俊範, 坂上 拓郎, 田中 崇裕, 中田 光

    日本呼吸器学会誌   8 ( 増刊 )   22 - 22   2019.3

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  • 肺胞蛋白症の20年史 自己免疫性肺胞蛋白症に対するGM-CSF吸入療法

    田澤 立之, 鈴木 雅, 大河内 眞也, 朝川 勝明, 巽 浩一郎, 石井 晴之, 泉 信有, 山口 悦郎, 井上 義一, 半田 知宏, 富井 啓介, 江田 良輔, 森本 浩之輔, 三上 礼子, 田中 崇裕, 北村 信隆, 高田 俊範, 上田 隆宏, 中垣 和英, 中田 光

    日本呼吸器学会誌   8 ( 増刊 )   23 - 23   2019.3

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  • 電子線マイクロアナライザーによる肺組織の元素分析のオンライン受付システムの確立

    森山 寛史, 小林 正義, 朝川 勝明, 坂上 拓郎, 小屋 俊之, 桑原 克弘, 大平 徹郎, 高田 俊範, 菊地 利明

    日本呼吸器学会誌   7 ( 増刊 )   145 - 145   2018.3

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  • 筋症状に乏しい抗MDA-5抗体陽性皮膚筋炎にともなう間質性肺疾患に対するミコフェノール酸モフェチル治療

    高田 俊範, 吉澤 和孝, 林 正周, 朝川 勝明, 坂上 拓郎, 菊地 利明

    日本呼吸器学会誌   7 ( 増刊 )   310 - 310   2018.3

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  • 電子線マイクロアナライザーによる肺組織の元素分析のオンライン受付システムの確立

    森山 寛史, 小林 正義, 朝川 勝明, 坂上 拓郎, 小屋 俊之, 桑原 克弘, 大平 徹郎, 高田 俊範, 菊地 利明

    日本呼吸器学会誌   7 ( 増刊 )   145 - 145   2018.3

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  • 自己免疫性肺胞蛋白症の有病率を推定する

    吉澤和孝, 北村信隆, 坂上拓郎, 田中崇裕, 伊藤裕子, 朝川勝明, 高田俊範, 小屋俊之, 菊地利明, 田澤立之, 中田光

    日本肺サーファクタント・界面医学会学術研究会プログラム・抄録集   53rd   214‐215   2017.9

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  • 超硬合金肺 (特集 仕事と病気)

    森山 寛史, 高田 俊範

    成人病と生活習慣病 : 日本成人病(生活習慣病)学会準機関誌   47 ( 8 )   963 - 967   2017.8

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    Other Link: http://search.jamas.or.jp/link/ui/2017399171

  • 間質性肺疾患における血清抗BPIFBI抗体の検討

    吉澤 和孝, 青木 亜美, 坂上 拓郎, 朝川 勝明, 小屋 俊之, 高田 俊範, 菊地 利明

    日本呼吸器学会誌   6 ( 増刊 )   215 - 215   2017.3

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  • 肺抗酸菌症 病態解析 肺MAC症におけるサイトカインの網羅的解析

    番場 祐基, 茂呂 寛, 青木 信将, 朝川 勝明, 林 正周, 大嶋 康義, 渡部 聡, 坂上 拓郎, 阿部 徹哉, 小屋 俊之, 高田 俊範, 菊地 利明

    日本呼吸器学会誌   6 ( 増刊 )   121 - 121   2017.3

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  • 本邦のリンパ脈管筋腫症に対するシロリムス長期治療の効果 Reviewed

    高田俊範, 田中崇裕, 北村信隆, 田澤立之, 中田光

    日本呼吸器学会誌   6(suppl)   134 - 134   2017

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  • 呼吸不全に関する調査研究 アジア人リンパ脈管筋腫症患者における長期シロリムス投与の効果と安全性

    林田美江, 高田俊範, 三上礼子, 北村信隆, 瀬山邦明, 井上義一, 長井桂, 鈴木雅, 森山寛史, 赤坂圭一, 田澤立之, 平井豊博, 三嶋理晃, 林田美江, 広瀬雅樹, 杉本親寿, 新井徹, 服部登, 渡辺憲太朗, 玉田勉, 吉澤弘久, 赤澤宏平, 田中崇裕, 八木圭太, Young Lisa R, Mccormack Francis X, 中田光

    呼吸不全に関する調査研究 平成28年度 総括研究報告書(Web)   14‐15 (WEB ONLY)   2017

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  • 肺MAC症におけるサイトカインの網羅的解析

    番場祐基, 茂呂寛, 青木信将, 朝川勝明, 林正周, 大嶋康義, 渡部聡, 坂上拓郎, 阿部徹哉, 小屋俊之, 高田俊範, 菊地利明

    日本呼吸器学会誌(Web)   6   2017

  • Risk Factors For Stomatitis In Patients With Lymphangioleiomyomatosis During Treatment With Sirolimus: A Multicenter Investigator-Initiated Prospective Study

    K. Nakata, K. Seyama, Y. Inoue, T. Takada, M. Suzuki, T. Tamada, T. Arai, T. Hirai, T. Handa, C. Sugimoto, N. Kitamura, R. Tazawa

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195   2017

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  • Anti-Bpifb1 Autoantibodies Were Identified In Three Cases With Idiopathic Interstitial Lung Disease

    K. Yoshizawa, T. Sakagami, A. Aoki, K. Asakawa, T. Koya, T. Takada, T. Kikuchi

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195   2017

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  • Establishment Of A Web-Based Inquiry System For Elemental Analysis Of Lung Tissue Of Occupational Lung Diseases

    H. Moriyama, M. Kobayashi, A. Aoki, K. Asakawa, T. Sakagami, T. Koya, T. Ohdaira, T. Takada, T. Kikuchi

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   195   2017

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  • 抗CADM-140/MDA5抗体陽性皮膚筋炎に伴う間質性肺疾患患者の血清サイトカインプロファイル

    高田 俊範, 青木 亜美, 朝川 勝明, 坂上 拓郎, 森山 寛史, 菊地 利明

    日本呼吸器学会誌   5 ( 増刊 )   349 - 349   2016.3

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  • Elderly-Onset Hereditary Pulmonary Alveolar ProteINOSis And Csf2ra Mutation

    R. Tazawa, M. Ito, K. Nakagome, K. Akasaka, H. Ohta, Y. Uchida, A. Shiono, T. Takada, M. Nagata, J. Tohyama, K. Hagiwara, M. Kanazawa, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193   2016

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  • Light Chain Genotype Analysis Of Gm-Csf Autoantibody In Autoimmune Pulmonary Alveolar ProteINOSis By Next Generation Sequencing

    A. Hashimoto, T. Tanaka, A. Hayakawa, Y. Itoh, T. Nei, K. Shiiya, M. Higuchi, K. Nakagaki, T. Takada, K. Akasaka, R. Tazawa, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193   2016

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  • Early Intervention With Sirolimus Benefits Mild Lymphangioleiomyomatosis-Related Lung Disease

    T. Takada, K. Seyama, Y. Inoue, K. Nagai, M. Suzuki, H. Moriyama, K. Akasaka, R. Tazawa, T. Hirai, M. Mishima, M. Hayashida, M. Hirose, C. Sugimoto, T. Arai, N. Hattori, K. Watanabe, A. Mikami, T. Tamada, H. Yoshizawa, K. Akazawa, T. Tanaka, N. Kitamura, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193   2016

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  • Serum Cytokine Profiles Of Anti-Cadm-140/mda5 Positive Patients With Amyopathic Dermatomyositis And Rapidly Progressive Interstitial Lung Disease

    T. Takada, A. Aoki, K. Asakawa, T. Sakagami, H. Moriyama, T. Kikuchi, S. Sato

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   193   2016

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  • Possible involvement of lung cells harboring an abnormal karyotype in the pathogenesis of pulmonary alveolar proteinosis associated with myelodysplastic syndrome

    Masato Moriyama, Toshio Yano, Tatsuo Furukawa, Toshinori Takada, Takashi Ushiki, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Ryushi Tazawa, Yasuo Saijo, Haruyuki Ishii, Koh Nakata

    Annals of the American Thoracic Society   12 ( 8 )   1251 - 1253   2015.8

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    DOI: 10.1513/AnnalsATS.201503-175LE

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  • 当院における間質性肺炎合併肺癌例の後方視的検討

    石川 大輔, 坂上 拓郎, 朝川 勝明, 岡島 正明, 三浦 理, 渡部 聡, 小屋 俊之, 森山 寛史, 田中 純太, 各務 博, 高田 俊範, 成田 一衛, 土田 正則

    日本呼吸器学会誌   4 ( 増刊 )   201 - 201   2015.3

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  • 2型呼吸不全への抗ミトコンドリア抗体に関連した筋炎の影響

    大嶋 康義, 鈴木 涼子, 穂苅 諭, 小屋 俊之, 各務 博, 高田 俊範, 鈴木 榮一, 成田 一衛

    日本呼吸器学会誌   4 ( 増刊 )   311 - 311   2015.3

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  • 睡眠呼吸障害の病態生理と治療 閉塞性睡眠時無呼吸に対するCPAP療法はアルブミン尿を改善する

    穂苅 諭, 大嶋 康義, 鈴木 涼子, 小屋 俊之, 各務 博, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本呼吸器学会誌   4 ( 増刊 )   144 - 144   2015.3

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  • 本邦の膠原病に伴う間質性肺疾患に対するミコフェノール酸モフェチルの安全性と有効性

    高田 俊範, 青木 亜美, 朝川 勝明, 坂上 拓郎, 森山 寛史, 成田 一衛

    日本呼吸器学会誌   4 ( 増刊 )   257 - 257   2015.3

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  • 肺胞蛋白症,遺伝性間質性肺疾患に関する研究:重症難治化要因とその克服 ステロイドは自己免疫性肺胞蛋白症を悪化させるのか?

    赤坂圭一, 田中崇裕, 椎谷恵子, 橋本淳史, 石井晴之, 大河内眞也, 田澤立之, 北村信隆, 高田俊範, 中田光

    肺胞蛋白症、遺伝性間質性肺疾患に関する研究:重症難治化要因とその克服 平成26年度 委託業務成果報告書   86‐87   2015

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  • Elemental Analysis Of Autoimmune Pulmonary Alveolar ProteINOSis

    H. Moriyama, M. Kobayashi, A. Aoki, K. Asakawa, T. Sakagami, T. Koya, H. Kagamu, T. Takada, I. Narita, Y. Inoue, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191   2015

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  • Outcome Of Corticosteroids Therapy In Autoimmune Pulmonary Alveolar ProteINOSis

    K. Akasaka, T. Tanaka, K. Shiiya, A. Hashimoto, H. Ishii, S. Ohkouchi, R. Tazawa, N. Kitamura, T. Takada, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191   2015

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  • Serum Cytokine Profiles Of Anti-Cadm-140/mda5 Positive Patients With Amyopathic Dermatomyositis And Rapidly Progressive Interstitial Lung Disease

    T. Takada, A. Aoki, K. Asakawa, T. Sakagami, H. Moriyama, E. Suzuki, I. Narita, S. Sato

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   191   2015

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  • シロリムスによる副作用としての口内炎の予防と治療について Invited

    北村信隆, 森山寛史, 高田俊範, 芳澤享子, 中田光

    呼吸と循環   63 ( 12 )   1167 - 1175   2015

  • Imaging of Hard Metal Lung Disease

    73 ( 12 )   1430 - 1441   2014.12

  • 12 原発性胆汁性肝硬変の経過中に筋炎・II型呼吸不全・不整脈を呈した1例(一般演題, 第54回下越内科集談会)

    128 ( 6 )   281 - 281   2014.6

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  • 抗CADM-140/MDA5自己抗体は間質性肺炎を伴う皮膚筋炎の予後予測因子となる

    高田 俊範, 朝川 勝明, 坂上 拓郎, 森山 寛史, 鈴木 栄一, 成田 一衛

    日本呼吸器学会誌   3 ( 増刊 )   284 - 284   2014.3

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  • 重症自己免疫性肺胞蛋白症患者における全肺洗浄・GM‐CSF吸入療法併用の有用性

    大河内眞也, 田澤立之, 赤坂圭一, 高田俊範, 中山秀章, 一和多俊男, 中田光, 一ノ瀬正和

    日本内科学会雑誌   103 ( Suppl. )   167 - 167   2014.2

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  • 抗Interferon-γ中和自己抗体陽性の播種性非結核性抗酸菌症 新たな疾患概念

    島 賢治郎, 坂上 拓郎, 青木 信将, 茂呂 寛, 田邊 嘉也, 各務 博, 長谷川 隆志, 高田 俊範, 成田 一衛

    日本内科学会雑誌   103 ( Suppl. )   229 - 229   2014.2

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  • Effects Of Mycophenolate Mofetil In Connective Tissue Disease-Associated Interstitial Lung Disease

    T. Takada, K. Asakawa, T. Sakagami, H. Moriyama, I. Narita

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   189   2014

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  • ANTI-CADM-140/MDA5 AUTOANTIBODY TITER PREDICTS DISEASE OUTCOME IN PATIENTS WITH DERMATOMYOSITIS AND RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE

    Toshinori Takada, Katsuaki Asakawa, Takuro Sakagami, Hiroshi Moriyama, Eiichi Suzuki, Ichiei Narita

    RESPIROLOGY   18   42 - 42   2013.11

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  • 6 細気管支肺胞上皮癌を合併した顕微鏡的多発血管炎の1例(一般演題, 第53回下越内科集談会)

    古寺 一樹, 木村 陽介, 月岡 啓輔, 中枝 武司, 和田 庸子, 小屋 俊之, 高田 俊範, 成田 一衛, 鈴木 栄一

    新潟医学会雑誌   127 ( 7 )   387 - 387   2013.7

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    Other Link: http://search.jamas.or.jp/link/ui/2014076250

  • OSAS患者におけるCPAP内部データとPSGデータの検討

    大嶋 康義, 穂苅 諭, 中山 秀章, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本睡眠学会定期学術集会プログラム・抄録集   38回   209 - 209   2013.6

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  • 後発喘息治療薬使用中の患者についての検討

    鈴木 和夫, 梶原 大季, 坂上 拓郎, 小屋 俊之, 各務 博, 高田 俊範, 成田 一衛, 長谷川 隆志, 鈴木 栄一

    アレルギー   62 ( 3-4 )   404 - 404   2013.4

  • 肺胞蛋白症のGM‐CSF吸入治療の予後と肺活量

    田澤立之, 新井徹, 笠原靖紀, 放生雅章, 大河内眞也, 江田良輔, 横場正典, 土橋佳子, 中山秀章, 石井晴之, 森本浩之輔, 南須原康行, 高田俊範, 海老名雅仁, 山口悦郎, 井上義一, 中田光

    日本呼吸器学会誌   2 ( 増刊 )   223 - 223   2013.3

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  • 膠原病関連間質性肺炎に対するミコフェノール酸モフェチルの当院での使用経験

    朝川 勝明, 市川 紘将, 穂苅 諭, 坂上 拓郎, 小屋 俊之, 高田 俊範, 成田 一衛, 鈴木 栄一

    日本呼吸器学会誌   2 ( 増刊 )   194 - 194   2013.3

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  • OSAS患者におけるCPAP内部データの正確性の検討

    大嶋 康義, 穂苅 諭, 中山 秀章, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本呼吸器学会誌   2 ( 増刊 )   227 - 227   2013.3

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  • 急速進行性間質性肺疾患に対するPMX-DHPの治療効果

    高田 俊範, 朝川 勝明, 坂上 拓郎, 森山 寛史, 風間 順一郎, 鈴木 栄一, 成田 一衛

    日本内科学会雑誌   102 ( Suppl. )   182 - 182   2013.2

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  • Treatment and Prognosis of Interstitial Lung Diseases Associated with Polymyositis - dermatomyositis

    Takada Toshinori

    127 ( 2 )   61 - 69   2013.2

  • リンパ脈管筋腫症に対するシロリムスの安全性確立のための医師主導治験―ベースラインデータ及びシロリムス血中濃度の横断的統計解析―

    田中崇裕, 池野碧, 北村信隆, 赤澤宏平, 高田俊範, 森山博史, 中田光, 吉澤弘久

    リンパ脈管筋腫症に対するシロリムスの安全性確立のための医師主導治験 平成24年度総括・分担研究報告書   84 - 87   2013

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  • Effects Of Direct Hemoperfusion With Polymyxin B-Immobilized Fiber For Rapidly Progressive Interstitial Lung Diseases

    T. Takada, K. Asakawa, T. Sakagami, H. Moriyama, J. Kazama, E. Suzuki, I. Narita

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187   2013

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  • Vital Capacity And Recurrence After Granulocyte-Macrophage Colony Stimulating Factor (gm-Csf) Inhalation Therapy For Pulmonary Alveolar ProteINOSis

    R. Tazawa, T. Arai, Y. Kasahara, M. Hojo, S. Ohkouchi, R. Eda, M. Yokoba, Y. Tsuchihashi, T. Nei, H. Nakayama, H. Ishii, K. Morimoto, Y. Nasuhara, T. Takada, M. Ebina, E. Yamaguchi, Y. Inoue, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   187   2013

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  • ブナシメジによる過敏性肺炎例の検討

    鈴木 和夫, 坂上 拓郎, 小屋 俊之, 各務 博, 高田 俊範, 成田 一衛, 長谷川 隆志, 鈴木 栄一

    アレルギー   61 ( 9-10 )   1494 - 1494   2012.10

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    DOI: 10.15036/arerugi.61.1494_3

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  • Pulmonary alveolar proteinosis

    22 ( 2 )   90 - 96   2012.8

  • 多発肺腫瘍塞栓症として紹介された一例

    遠藤 悠, 小泉 健, 三浦 理, 市川 紘将, 坂上 拓郎, 中山 秀章, 田邊 嘉也, 高田 俊範, 鈴木 栄一, 成田 一衛, 斉藤 泰晴

    日本呼吸器学会誌   1 ( 増刊 )   353 - 353   2012.3

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  • 健康成人に発症した粟粒結核の1例

    佐藤 昂, 三船 大樹, 田中 淳一, 鈴木 涼子, 坂上 拓郎, 田島 俊児, 中山 秀章, 高田 俊範, 成田 一衛, 鈴木 栄一, 田中 洋史

    結核   87 ( 2 )   93 - 93   2012.2

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  • 良き呼吸器科指導医としての理想像の検討 研修医の専門領域選択因子のアンケート結果

    田中 淳一, 坂上 拓郎, 各務 博, 高田 俊範, 成田 一衛, 鈴木 栄一

    日本呼吸器学会誌   1 ( 2 )   107 - 113   2012.2

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    臨床研修医が専門分野を選択する際、指導医の影響が大きいと報告されている。昨今、呼吸器科医師不足が指摘され、呼吸器科を志望する医師を増やすことは急務である。研修医が進路を選択する際に、何を重視するのかを明らかにし、またその過程における指導医の影響を評価する目的で、臨床研修医、若手呼吸器科医師にアンケート調査を行った。その結果、選択時に重視する点は、やりがい、医学的な興味に続き、良き指導医の存在であった。一方で、研修医1年次と2年次で、また研修医と若手呼吸器科医師で、選択時に重視する点、理想の指導医像に差異が認められた。本調査を通して、多くの臨床研修医が呼吸器科を選択するためには、呼吸器科のやりがいを伝え、興味を喚起する努力をし、研修医の経験・志向に応じ指導の仕方を変化させ、そのうえで若手呼吸器科医が目指す全人的診療を行う「良医」をロールモデルとして認識させることが必要であることが示唆された。(著者抄録)

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  • 当院における人工呼吸器管理中の患者に対するリハビリスタッフと呼吸器内科医の連携について

    大脇教光, 大滝直子, 遠藤直人, 穂苅諭, 大嶋康義, 中山秀章, 高田俊範, 成田一衛

    日本呼吸ケア・リハビリテーション学会誌   22   2012

  • HUMAN MOLECULAR GENETICS

    2011.11

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  • 2009-2010年における喘息患者へのインフルエンザ・ワクチンの効果 新潟県多施設アンケート調査から

    鈴木 和夫, 坂上 拓郎, 小屋 俊之, 高田 俊範, 成田 一衛, 荒川 正昭, 長谷川 隆志, 鈴木 栄一, 新潟県喘息治療研究会

    アレルギー   60 ( 9-10 )   1456 - 1456   2011.10

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  • 1 抗CADM-140抗体陽性を呈した間質性肺炎合併皮膚炎の1例(一般演題,第51回下越内科集談会)

    鈴木 達郎, 朝川 勝明, 古川 俊貴, 小屋 俊之, 中山 秀章, 各務 博, 高田 俊範, 成田 一衛, 長谷川 隆志, 鈴木 栄一

    新潟医学会雑誌   125 ( 5 )   291 - 291   2011.5

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  • 間質性肺炎のメカニズム ブレオマイシン(BLM)肺線維症モデルにおけるイルベサルタンの有効性の検討

    田中 淳一, 田島 俊児, 朝川 勝明, 森山 寛史, 各務 博, 高田 俊範, 鈴木 栄一, 成田 一衛

    日本呼吸器学会雑誌   49 ( 増刊 )   129 - 129   2011.3

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  • 急速に進行する間質性肺炎を合併したclinicaly amyopathic dermatomyositis(C-ADM)の臨床的検討 抗CADM-140抗体と予後について

    田島 俊児, 渡辺 憲弥, 田中 淳一, 朝川 勝明, 森山 寛史, 各務 博, 高田 俊範, 鈴木 栄一, 佐藤 慎二, 桑名 正隆, 成田 一衛

    日本呼吸器学会雑誌   49 ( 増刊 )   309 - 309   2011.3

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  • Pathogenesis and treatment of Goodpasture syndrome

    55 ( 11 )   1312 - 1317   2011

  • Effect Of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Inhalation On Bronchoalveolar Lavage Fluid And Serum In Pulmonary Alveolar ProteINOSis

    R. Tazawa, K. Ohashi, A. Sato, T. Arai, Y. Kasahara, M. Hojo, M. Yokoba, Y. Tsuchihashi, H. Ishii, Y. Nasuhara, M. Ebina, T. Takada, E. Yamaguchi, Y. Inoue, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   183   2011

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  • A Case of Recurrent Acute Eosinophilic Pneumonia due to Resumption of Cigarette Somoking

    Mifune Daiki, Watanabe Satoshi, Kondou Rie, Moriyama Hiroshi, Kagamu Hiroshi, Takada Toshinori, Narita Ichiei, Hasegawa Takashi, Suzuki Eiichi, Tetsuka Takafumi

    124 ( 7 )   407 - 412   2010.7

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  • 14 著しい低ナトリウム血症を呈した陳旧性肺結核症の1例(一般演題,第50回下越内科集談会)

    田中 雅人, 照喜名 重朋, 小嶋 智子, 才田 優, 梶原 大季, 大森 健太郎, 飯野 則昭, 寺田 正樹, 高田 俊範, 成田 一衛, 阿部 英里

    新潟医学会雑誌   124 ( 6 )   353 - 354   2010.6

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  • Characterization Of Bronchoalveolar Lavage Fluid During Granulocyte-macrophage Colony-stimulating Factor Inhalation In Patients With Autoimmune Pulmonary Alveolar Proteinosis

    R. Tazawa, K. Ohashi, A. Sato, Y. Inoue, M. Akira, M. Terada, H. Nakayama, T. Takada, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   181   2010

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  • 肺胞蛋白症に対するGM-CSF吸入治療の効果予測因子の検討

    田澤立之, 浦野真也, 金子千夏, 元井奈都紀, 根井貴仁, 中山秀章, 寺田正樹, 高田俊範, 井上義一, 貫和敏博, 中田光

    日本呼吸器学会雑誌   48 ( 増刊 )   193 - 193   2010

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  • メトトレキサートとタクロリムス使用中にニューモシスチス肺炎を合併した関節リウマチの1例

    津畑 千佳子, 田邊 嘉也, 田中 淳一, 朝川 勝明, 平原 潔, 手塚 貴文, 坂上 拓郎, 小屋 俊之, 寺田 正樹, 高田 俊範, 成田 一衛, 村上 修一, 黒田 毅, 長谷川 隆志, 鈴木 栄一

    新潟医学会雑誌   123 ( 11 )   585 - 589   2009.11

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    症例は70歳、女性。2005年に関節リウマチを発症し、プレドニゾロン、メトトレキサートによる治療を受けたが症状コントロール困難であった。2006年10月からタクロリムスを追加され、関節症状の改善を認めた。2007年2月末から咳嗽、喀痰、呼吸困難感、全身倦怠感が出現し、画像上両側肺野にground glass opacityを認めたため、メトトレキサート肺臓炎、ニューモシスチス肺炎を疑い、メトトレキサートとタクロリムスを中止し、メチルプレドニゾロン・パルス療法とTrimethoprim-sulfamethoxazole投与を行った。気管支肺胞洗浄液からニューモシスチスの嚢子が検出されニューモシスチス肺炎と診断した。関節リウマチに対してメトトレキサート、タクロリムスを使用する症例が近年増加しており、日和見感染のリスクが高まると考えられる。さらにメトトレキサートによる肺臓炎とニューモシスチス肺炎の鑑別も重要である。(著者抄録)

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  • 2 呼吸不全で発見された筋萎縮性側索硬化症の1例(一般演題,第49回下越内科集談会)

    吉岡 大雄, 鈴木 栄一, 山岸 格史, 田島 俊児, 小屋 俊之, 田中 洋史, 中山 秀章, 高田 俊範, 下条 文武, 下畑 享良

    新潟医学会雑誌   123 ( 7 )   373 - 373   2009.7

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  • A Candidate Marker Protein in the Bronchoalveolar Lavage Fluid Predictive for Future Emphysema in the Current Smokers.

    N. Motoi, M. Hayashi, A. Yamagata, K. Oofusa, T. Takada, T. Betsuyaku, M. Nishimura, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   179   2009

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  • GM-CSF Inhalation Promotes the Clearance of GM-CSF Autoantibody in the Lung of Autoimmune Pulmonary Alveolar Proteinosis.

    K. Nakata, K. Ohashi, R. Tazawa, Y. Inoue, B. C. Trapnell, M. Terada, H. Nakayama, T. Takada

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   179   2009

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  • Aerosolized GM-CSF Therapy of Pulmonary Alveolar Proteinosis (PAP).

    R. Tazawa, Y. Inoue, T. Takada, T. Arai, Y. Nasuhara, N. Hizawa, Y. Kasahara, K. Tatsumi, M. Hojo, M. Yokoba, N. Tanaka, E. Yamaguchi, R. Eda, Y. Tsuchihashi, K. Oishi, M. Terada, C. Kaneko, T. Nukiwa, J. P. Krischer, B. C. Trapnell, K. Nakata

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   179   2009

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  • 気管支喘息 化学伝達物質 ONO-1301(PGI2アゴニスト+TX合成酵素阻害)のマウス喘息モデルにおける好酸球性炎症の抑制効果

    林 正周, 小屋 俊之, 坂上 拓郎, 高田 俊範, 長谷川 隆志, 酒井 芳紀, 鈴木 栄一, 下条 文武

    アレルギー   57 ( 9-10 )   1392 - 1392   2008.10

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    DOI: 10.15036/arerugi.57.1392_2

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  • 汎下垂体機能低下症をきたした中枢神経サルコイドーシスの1例

    島岡 雄一, 田島 俊児, 古塩 奈央, 富士盛 文夫, 津畑 千佳子, 小屋 俊之, 森山 寛史, 寺田 正樹, 高田 俊範, 下条 文武, 長谷川 隆志, 鈴木 栄一

    日本呼吸器学会雑誌   46 ( 10 )   814 - 819   2008.10

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    症例は63歳の男性。めまい、多飲多尿、性欲減退などの症状で受診した。頭部MRIで下垂体の腫大があり、内分泌学的に汎下垂体機能低下を認めた。ホルモン補充療法としてヒドロコルチゾン、デスモプレシン、レボチロキシンナトリウムが開始された。胸部X線とCTで肺野の多発濃度上昇、ガリウムシンチでの肺門部への取り込み、ツ反陰性、気管支肺胞洗浄液中のリンパ球増加とCD4/8比の上昇を認めた。経気管支肺生検で組織診断は得られなかったが、臨床的に汎下垂体機能低下症を合併した中枢神経サルコイドーシスと診断した。プレドニゾロン60mg内服を開始したところ、下垂体および肺野病変の明らかな縮小が認められた。尿量は一時増加するもその後減少し、抗利尿ホルモンや下垂体前葉ホルモンの上昇傾向を認めた。本症例は症状出現から治療まで約5ヵ月経過していたが、ステロイド治療によって内分泌学的所見の改善傾向を認めた示唆に富む症例と考えられた。(著者抄録)

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  • 5 GM-CSF吸入無効例に対して, 体外循環併用全肺洗浄を行った重症肺胞蛋白症の1例(一般演題,第48回下越内科集談会)

    佐藤 大介, 鈴木 栄一, 林 正周, 中山 秀章, 寺田 正樹, 高田 俊範, 下条 文武, 中田 光, 名村 理, 今井 英一, 西塔 毅

    新潟医学会雑誌   122 ( 7 )   406 - 406   2008.7

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  • Is giant cell interstitial pneumonitis synonymous with hard metal lung disease? From the authors

    Toshinori Takada, Hiroshi Moriyama, Fumitake Gejyo

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   176 ( 8 )   834 - 835   2007.10

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  • ONO-1301(PGI2アゴニスト+TX合成酵素阻害)のマウス喘息モデルにおける好酸球性炎症の抑制効果

    林 正周, 小屋 俊之, 坂上 拓郎, 高田 俊範, 長谷川 隆志, 酒井 芳紀, 鈴木 栄一, 下条 文武

    アレルギー   56 ( 8-9 )   1098 - 1098   2007.9

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    DOI: 10.15036/arerugi.56.1098_1

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  • 1 高カルシウム血症と高度腎障害で発症したサルコイドーシスの1例(第47回下越内科集談会)

    新谷 茂樹, 小林 大介, 保坂 聖子, 飯野 則昭, 成田 淳一, 寺田 正樹, 高田 俊範, 下条 文武, 鈴木 栄一, 吉澤 弘久

    新潟医学会雑誌   121 ( 9 )   535 - 536   2007.9

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  • Interstitial lung disease associated with polymyositis-dermatomyositis

    Toshinori Takada, Jun-Ichi Narita, Eiichi Suzuki, Fumitake Gejyo

    Current Respiratory Medicine Reviews   3 ( 3 )   221 - 228   2007.8

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    Polymyositis and dermatomyositis (PM-DM) are forms of idiopathic inflammatory myositis. Interstitial lung disease (ILD) in PM-DM is recognized as a serious complication and a major cause of death in this disease. According to the results of immunophenotyping of lymphocytes in bronchoalveolar lavage fluid, cytotoxic T lymphocytes may be major pulmonary inflammatory cells of ILD in PM-DM. Glucocorticoids are considered the first-line drug treatment for PM-DM patients with ILD, however they are often not sufficient to obtain improvement of ILD as a single agent. Furthermore, the addition of immunosuppressive drugs becomes necessary as steroid sparing agents to avoid the severe side-effects often seen with high-dose steroid treatment. Cyclophosphamide, cyclosporin, and tacrolimus were reported to be effective in treatment of refractory ILD in PM-DM. Although other immunosuppressive agents
    mycophenolate mofetil, intravenous immunoglobulin, and anti-TNF agents have appeared as promising agents for refractory PM-DM, the efficacy on ILD in PM-DM is still unknown. Even if treatment is initiated early in the course of the disease, some patients still develop irreversible fatal lung fibrosis under aggressive immunosuppressive therapy. The fastest way to find the most effective treatment may be to investigate the pathogenesis of the disease in detail before initiation of immunosuppressive therapy including glucocorticoids. © 2007 Bentham Science Publishers Ltd.

    DOI: 10.2174/157339807781387508

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  • 多発性筋炎-皮膚筋炎に伴う間質性肺炎症例の検討 生存例と死亡例について

    成田 淳一, 高田 俊範, 坂上 拓郎, 田島 俊児, 小屋 俊之, 森山 寛史, 寺田 正樹, 長谷川 隆志, 下条 文武, 鈴木 栄一

    日本呼吸器学会雑誌   45 ( 増刊 )   190 - 190   2007.4

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  • 成人気管支喘息における呼吸機能低下とPaf-acethylhydrolase機能的遺伝子多型の検討

    坂上 拓郎, 関川 宗, 長谷川 隆志, 高田 俊範, 鈴木 栄一, 井ノ上 逸朗, 下条 文武

    日本呼吸器学会雑誌   45 ( 増刊 )   296 - 296   2007.4

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  • 肺胞蛋白質はどこまで明らかとなったか?

    中田光, 井上義一, 高田俊範, 寺田正樹, 新井徹, 坂谷光則, 田澤立之, 貫和敏博

    日本呼吸器学会雑誌   45 ( 増刊 )   82 - 82   2007

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  • 【喀痰学のup-to-date】 肺胞蛋白症の臨床 (THE LUNG-perspectives)

    中田光, 井上義一, 高田俊範, 寺田正樹, 新井徹, 坂谷光則, 田澤立之, 貫和敏博

    THE LUNG-perspectives   15 ( 1 )   59 - 63   2007

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  • 肺障害・線維化に関わる肺細胞とその産生分子 わが国の特発性肺胞蛋白症の病勢、予後、GM-CSF吸入療法のUp-to-date (分子呼吸器病)

    中田光, 井上義一, 高田俊範, 寺田正樹, 新井徹, 坂谷光則, 田澤立之, 貫和敏博, 桧澤伸之, 山口悦郎, 江田良輔, 土橋佳子, 田中直彦, 笠原靖紀

    分子呼吸器病   11 ( 1 )   72 - 74   2007

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  • Factors Influencing Cardiopulmonary Exercise Testing in Obstructive Sleep Apnea Syndrome Patients

    Yamabayashi Cristiane, Nakayama Hideaki, Matsuyama Naho, Watanabe Takeo, Sakai Kunihiko, Ohdaira Tetsuro, Takada Toshinori, Akazawa Kohei, Kobayashi Kuriko, Gejyo Fumitake

    Acta medica et biologica   54 ( 4 )   125 - 131   2006.12

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    The exercise capacity of obstructive sleep apnea syndrome (OSAS) patients has been demonstrated to be impaired, but the factors responsible are still unclear. In addition, ventilatory efficiency during exercise has never been studied in OSAS. Hypertension (HT), commonly found in OSAS patients, could be a contributing factor to exercise capacity. The aim of the study is: 1) to determine possible factors that could influence the exercise in OSAS patients, and 2) to compare the exercise capacity and ventilatory efficiency of patients with and without HT. Twenty-two male OSAS patients were submitted to cardiopulmonary exercise testing. Multiple linear regression analyses were used to find possible factors that could influence the exercise capacity and ventilatory efficiency of OSAS patients. Patients were divided into two groups according to the presence of HT, and cardiopulmonary exercise testing (CPET) results were compared between them. No factors emerged as predictors of oxygen consumption at peak exercise (FOipeak). The slope of increase of ventilation relative to carbon dioxide production (FE/FCOi-slope) was associated with body mass index (BMI) negatively and with apneahypopnea index (AHI) positively (p = 0.019 and p =0.047, respectively). There were no differences in either FOipeak or anaerobic threshold (AT) between OSAS with and without HT, but the FE/FCOi-slope was higher in the HT group (p = 0.008). Our results suggest that the severity of sleep apnea can influence the ventilatory efficiency of OSAS patients along with BMI and HT.

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  • Reduced Fibrinolytic Activity in Bronchoalveolar Lavage Fluids is not Related to Alveolar Macrophages in the Fibrosis of Interstitial Pneumonia : An Analysis of Bronchoalveolar Lavage Fluids

    YAMAGUCHI Seigo, HASEGAWA Takashi, KOYA Toshiyuki, SAITO Yasuharu, NARITA Jun-ichi, TERADA Masaki, MORIYAMA Hiroshi, TSUKADA Hiroki, TAKADA Toshinori, GEJYO Fumitake, SUZUKI Eiichi

    Acta medica et biologica   53 ( 3 )   79 - 86   2005.9

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    Reduced fibrinolytic activity in the alveolar space of patients with interstitial pneumonia (IP) is considered the key factor in the development of pulmonary fibrosis. However, the origin of this fibrinolytic activity and its relationship to the fibrosis in IP is still unclear. Levels of the urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen were measured in bronchoalveolar lavage fluids (BALF) obtained from patients with IP, and the data were compared between the two groups (fibrosing group and non-fibrosing group) based mainly on honeycomb formation revealed by pulmonary high-resolution computed tomography (HRCT) and partially on lung histology. In addition, the cell surface plasmin generation of various alveolar macrophages (AM) and its correlation with the u-PA/PAI-1 levels in each of the two groups were studied. The u-PA level was significantly lower in BALF from IP patients than from sarcoidosis patients with no interstitial shadows on HRCT used as the contols. Although u-PA and PAI-1 levels did not differ between the fibrosing and the non-fibrosing group, the macrophage count and the percentage of macrophages in BALF were significantly greater in the fibrosing group. The major regulatory cytokines, interleukin 1-β and transforming growth factor-β, however, did not affect cell surface plasmin generation by AM, indicating that the AM-related fibrinolytic activity was constant. These results indicate that the decreased fibrinolytic activity in BALF is not related to AM although it is associated with the fibrosis of IP. We speculate that other cells such as alveolar epithelial cells contribute to the fibrosis although further clinical studies will be required.

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  • 11 5年間経過を追った,骨髄移植後の特発性肺炎症候群(IPS;idiopathic pneumonia syndrome)の1例(第45回下越内科集談会)

    江部 佑輔, 成田 淳一, 森山 寛史, 寺田 正樹, 高田 俊範, 長谷川 隆志, 塚田 弘樹, 吉澤 弘久, 下条 文武, 古川 達夫, 鈴木 栄一

    新潟医学会雑誌   119 ( 4 )   274 - 274   2005.4

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  • 間質性肺炎を伴う多発性筋炎/皮膚筋炎(PM/DM)患者における末梢血リンパ球表面αEβ7インテグリン(CD103)の解析

    成田 淳一, 高田 俊範, 清水 崇, 小屋 俊之, 森山 寛史, 寺田 正樹, 長谷川 隆志, 吉澤 弘久, 下条 文武, 鈴木 榮一

    日本呼吸器学会雑誌   42 ( 増刊 )   115 - 115   2004.3

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  • Pulmonary Hyalinizing Granuloma with Massive Infiltration of Lymphocytes

    FUJISHIMA Naoto, TAKADA Toshinori, MORIYAMA Hiroshi, SAITO Yasuharu, SUZUKI Eiichi, YOSHIYA Katsuo, KOURAKATA Hiroyo, HONMA Tomoko, GEJYO Fumitake, YAMATO Yasushi

    39 ( 12 )   924 - 929   2001.12

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  • A Case of Pulmonary Inflammatory Pseudotumor with Hypergammaglobulinemia, Elevated ANA, and Uveitis

    KAIZU Chikako, TAKADA Toshinori, MORIYAMA Hiroshi, TERADA Masaki, SUZUKI Eiichi, GEJYO Fumitake, KUWABARA Katsuhiro, SAITO Yasuharu

    39 ( 8 )   603 - 608   2001.8

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  • A Case of Isolated Sarcoidosis of the Cerebral Falx

    HARA Katsuhito, TANAKA Hiroshi, MORIYAMA Hiroshi, OHDAIRA Tetsurou, TAKADA Toshinori, SUZUKI Eiichi, ARAKAWA Masaaki, GEJYO Fumitakeu

    38 ( 7 )   566 - 570   2000.7

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  • 1)MTXによる肝不全を来したRA・amyloidosisの一例(I. 一般演題, 第66回膠原病研究会)

    西浦 智子, 首村 守俊, 若杉 三奈子, 黒田 毅, 高田 俊範, 伊藤 聡, 中野 正明, 荒川 正昭, 桃井 明仁, 馬場 靖幸, 朝倉 均

    新潟医学会雑誌   114 ( 1 )   30 - 31   2000.1

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    Language:Japanese   Publisher:新潟医学会  

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    Other Link: http://search.jamas.or.jp/link/ui/2000168657

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Awards

  • Francis G. Byrnes Platform Presentation Award

    2016.9   Rare Lung Diseases Research Conference and LAMposium  

    TAKADA Toshinori

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  • 「岡本敏記念肺線維症研究基金」助成金

    2009.9  

    高田 俊範

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  • 新潟県医師会平成20年度学術奨励賞

    2008.9  

    高田 俊範

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  • 新潟県医師会平成13年度学術研究助成金

    2001.9  

    高田 俊範

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Research Projects

  • 血球吸着モデルを用いたLAM患者におけるシロリムス最適薬用量決定法の提案

    Grant number:20K08537

    2020.4 - 2023.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    田中 崇裕, 中田 光, 北村 信隆, 高田 俊範

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    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    今年度は昨年度に引き続き本課題の第2段階目のステップであるin vitro におけるシロリムスの赤血球への結合試験について得られた実測値からシロリムスの薬物動態モデルについて薬物動態解析ソフト(Phoenix WinNonlin)を用いて2-コンパートメントモデルの構築を進めた。
    現在までの検討ではMLSTS医師主導治験で測定されたシロリムス服薬量を2mg(治験における規定量)に固定した場合の基本となる血球吸着モデルを構築しているため、ここで作成された血球吸着モデルが服薬量1mg、3mgに増減された場合ついても拡張可能であるかについて検討を進めている。
    また、本課題の第3段階目のステップである血球吸着モデルのバリデーションテストについて進めていくために他疾患及び小児における薬物動態データ、トラフ値データが必要となることからシロリムスの新作用の発見と応用に関して、基礎研究と臨床研究の両面の情報交換の場となっているジャスミン研究会に参加している。研究会の活動の一環として会員が実施した薬物動態に関する各臨床試験・臨床研究の症例データリポジトリの構築を行い、データの相互利用を行う体制を築くことを目指している。当該活動の進捗状況としては各試験の症例データを用いるデータベースを構築する臨床研究を立ち上げることについて研究会の合意を得た。今後の方針としてはUMIN-ICDRを利用したデータベースの運用を計画しておりデータベースの利用規約や利用範囲については現在調整中である。

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  • Usefulness of CXCL10 as a biomarker for pulmonary MAC disease

    Grant number:20K08536

    2020.4 - 2023.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  • 免疫組織化学と元素分析による肺組織解析~職業性肺疾患の正しい病態理解のために~

    2017.4 - 2020.3

    Awarding organization:日本学術振興会

    森山 寛史

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    Grant type:Competitive

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  • 急速進行性間質性肺疾患に対するポリミキシンB吸着カラム療法の作用機序の解明

    2017.4 - 2020.3

    Awarding organization:日本学術振興会

    大橋 和政

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    Grant type:Competitive

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  • 敗血症急性期において鉄調節因子ヘプシジンが果たす役割~新規治療法の開発に向けて

    2017.4 - 2020.3

    Awarding organization:日本学術振興会

    茂呂 寛

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    Grant type:Competitive

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  • サイトカインパネル解析を用いた急速進行性性間質性肺疾患の難治化機序の解明

    2016.4 - 2019.3

    Awarding organization:日本学術振興会

    高田 俊範

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    Authorship:Principal investigator  Grant type:Competitive

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  • サイトカインパネル解析を用いた自己免疫性肺胞蛋白症の病態変化機序の解明

    2016.4 - 2019.3

    Awarding organization:日本学術振興会

    赤坂 圭一

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    Grant type:Competitive

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  • リンパ脈管筋腫症に対するラパマイシン長期内服の効果と安全性評価のためのコホート調査

    2015.5 - 2018.3

    Awarding organization:日本医療研究開発機構

    高田 俊範

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    Authorship:Principal investigator  Grant type:Competitive

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  • 自己免疫性肺胞蛋白症に対する酵母由来組換えGM-CSF吸入の多施設共同医師主導治験

    2015.4 - 2018.3

    Awarding organization:日本医療研究開発機構

    中田 光

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    Grant type:Competitive

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  • オンラインによる元素分析受付システムの確立

    2014.4 - 2017.3

    Awarding organization:日本学術振興会

    森山 寛史

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    Grant type:Competitive

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  • 肺MAC症の重症化・致死化と鉄代謝異常との関連~新規治療法の開発に向けて

    2014.4 - 2017.3

    Awarding organization:日本学術振興会

    茂呂 寛

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    Grant type:Competitive

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  • 皮膚筋炎に伴う難治性急速進行性間質性肺炎における抗CADM-140抗体の役割

    2013.4 - 2016.3

    Awarding organization:日本学術振興会

    高田 俊範

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    Authorship:Principal investigator  Grant type:Competitive

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  • リンパ脈管筋腫症に対するシロリムスの安全性確立のための医師主導治験

    2012 - 2014

    Awarding organization:厚生労働省

    中田 光

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    Grant type:Competitive

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  • シロリムスによるリンパ脈管筋腫症の第Ⅲ相国際共同臨床試験 MILES trial

    2008 - 2009

    Awarding organization:厚生労働省

    中田 光

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    Grant type:Competitive

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  • 特発性間質性肺炎は本当に原因不明の間質性肺炎か?~定量的元素分析を用いた解析~

    2007.4 - 2009.3

    Awarding organization:日本学術振興会

    高田 俊範

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    Authorship:Principal investigator  Grant type:Competitive

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  • 新潟県内の疫学的研究に基づいた月経喘息の臨床および生化学・遺伝学的研究

    2007 - 2008

    Awarding organization:日本学術振興会

    長谷川 隆志

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    Grant type:Competitive

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  • 間質性肺炎の急性増悪における凝固線溶系の関与

    2006 - 2008

    Awarding organization:日本学術振興会

    寺田 正樹

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    Grant type:Competitive

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  • 波長分散型X線マイクロアナライザーと免疫組織化学を用いた間質性肺炎の病理学的検討

    2004 - 2006

    Awarding organization:日本学術振興会

    鈴木 栄一

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    Grant type:Competitive

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