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Yasuo Masanori

Academic OrganizationAcademic Assembly School of Medicine and Health Sciences Institute of Health ScienceTEL+81-263-37-2393
Education and Research OrganizationSchool of Medicine Department of Health SciencesFAX+81-263-36-3722
Address3-1-1 Asahi, Matsumoto, Nagano, 390-8621, JAPANWeb site



Research Field
Respiratory medicine
Molecular biology
Keywords:Respiratory Medicine , COPD , Interventional pulmonology , Diagnostic Bronchoscopy , Airway Inflammation , Asthma
Current Subject
The role of acrolein in COPD as a systemic inflammation
Keywords:COPD , Systemic inflammation , Acrolein
Usefulness of forced oscillation technique in assessment of therapeutic effect on tracheobronchial central airway obstruction
Keywords:Tracheobronchial obstruction , Forced oscillation technique
Functional and symptomatic difference between central and peripheral airway obstructions
Keywords:Central Airway Obstruction and COPD , Forced Oscillation Technique
Academic Societies
Academic Societies
American Thoracic Society
Academic Background
Graduate School
Shinshu Univ. Postgraduate School , 2005

Shinshu Univ. , 1997

Ph.D , Shinshu Univ. Postgraduate School
2016 , 第一回BQグランプリ最優秀賞
2013 , 第12回信州医学会賞(原著論文部門)
2010 , 北関東信越呼吸器フォーラム優秀賞(平成22年)
Research Career
Research Career
2013- , 信州大学医学部附属病院 講師
2010-2013 , 信州大学医学部附属病院 助教
2005-2008 , 信州大学内科学第一講座 助教
2002-2005 , 信州大学社会人大学院・医員

Other Career
2008-2010 , Virginia Commonwealth University

Overseas Education
2008-2010 , Victoria W. Johnson Center for Obstructive Pulmonary Disease Research, Virginia Commonwealth University


Books, Articles, etc.
Part.2 チャートで読み解くCOPD & 喘息の治療とケア., 46-51
メディカ出版 2021

第5章 体プレチスモグラフ法, 41-46
メディカルレビュー社 2021

COPD(慢性閉塞性肺疾患), クリニカルスタディ 34 5, 41-48

【COPD慢性閉塞性肺疾患(慢性気管支炎、肺気腫)】治療薬:長時間作用性抗コリン薬の位置づけ, クリニシアン 59, 106-111

特集 COPDの薬物療法の新展開 抗炎症薬の将来展望, THE LUNG perspectives 19 2, 58-62
メディカルレビュー社 2011

Prognostic implication of IgG4 and IgG1-positive cell infiltration in the lung in patients with idiopathic interstitial pneumonia
SCIENTIFIC REPORTS,12(1):9303-9303 2022
Author:Komatsu, Masamichi; Yamamoto, Hiroshi; Uehara, Takeshi; Kobayashi, Yukihiro; Hozumi, Hironao; Fujisawa, Tomoyuki; Miyamoto, Atsushi; Kishaba, Tomoo; Kunishima, Fumihito; Okamoto, Masaki; Kitamura, Hideya; Iwasawa, Tae; Matsushita, Shoichiro; Terasaki, Yasuhiro; Kunugi, Shinobu; Ushiki, Atsuhito; Yasuo, Masanori; Suda, Takafumi; Hanaoka, Masayuki
Abstract:Immunoglobulin (Ig) G4-positive cells are rarely observed in the lungs of patients with idiopathic interstitial pneumonias (IIPs). IgG1 may be more pathogenic than IgG4, with IgG4 having both pathogenic and protective roles in IgG4-related disease (IgG4-RD). However, the role of both IgG1 and IgG4 in IIPs remains unclear. We hypothesized that patients with IgG4-positive interstitial pneumonia manifest different clinical characteristics than patients with IgG4-RD. Herein, we identified the correlation of the degree of infiltration of IgG1- and IgG4-positive cells with IIP prognosis, using a Japanese nationwide cloud-based database. We included eighty-eight patients diagnosed with IIPs after multidisciplinary discussion, from April 2009 to March 2014. IgG4-positive cell infiltration was identified in 12/88 patients with IIPs and 8/41 patients with idiopathic pulmonary fibrosis (IPF). Additionally, 31/88 patients with IIPs and 19/41 patients with IPF were diagnosed as having IgG1-positive cell infiltration. IgG4-positive IIPs tended to have a better prognosis. Conversely, overall survival in cases with IgG1-positive IPF was significantly worse. IIPs were prevalent with IgG1- or IgG4-positive cell infiltration. IgG1-positive cell infiltration in IPF significantly correlated with a worse prognosis. Overall, evaluating the degree of IgG1-positive cell infiltration may be prognostically useful in cases of IPF.

Associations Between Morphological Phenotypes of COPD and Clinical Characteristics in Surgically Resected Patients with COPD and Concomitant Lung Cancer
Author:Suzuki, Yusuke; Kitaguchi, Yoshiaki; Ueno, Fumika; Droma, Yunden; Goto, Norihiko; Kinjo, Takumi; Wada, Yosuke; Yasuo, Masanori; Hanaoka, Masayuki
Abstract:PURPOSE: The associations between morphological phenotypes of COPD based on the chest computed tomography (CT) findings and clinical characteristics in surgically resected patients with COPD and concomitant lung cancer are unclear. The purpose of this study was to clarify the differences in clinical characteristics and prognosis among morphological phenotypes based on the chest CT findings in these patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 132 patients with COPD and concomitant lung cancer who had undergone pulmonary resection for primary lung cancer. According to the presence of emphysema and bronchial wall thickness on chest CT, patients were classified into three phenotypes: non-emphysema phenotype, emphysema phenotype, or mixed phenotype. RESULTS: The mixed phenotype was associated with poorer performance status, higher score on the modified British Medical Research Council (mMRC) dyspnea scale, higher residual volume in pulmonary function, and higher proportion of squamous cell carcinoma than the other phenotypes. Univariate and multivariate Cox proportional hazards regression analyses showed that the extent of emphysema on chest CT, presented as a low attenuation area (LAA) score, was an independent determinant that predicted prognosis. In the Kaplan-Meier analysis, the Log rank test showed significant differences in survival between the non-emphysema and mixed phenotypes, and between the emphysema and mixed phenotypes. CONCLUSION: The cross-sectional pre-operative LAA score can predict the prognosis in surgically resected patients with COPD and concomitant lung cancer. The COPD phenotype with both emphysema and bronchial wall thickness on chest CT was associated with poorer performance status, greater extent of dyspnea, greater impairment of pulmonary function, and worse prognosis.

The usefulness of a combination of age, body mass index, and blood urea nitrogen as prognostic factors in predicting oxygen requirements in patients with coronavirus disease 2019
Author:Goto, Norihiko; Wada, Yosuke; Ikuyama, Yuichi; Akahane, Jumpei; Kosaka, Makoto; Ushiki, Atsuhito; Kitaguchi, Yoshiaki; Yasuo, Masanori; Yamamoto, Hiroshi; Matsuo, Akemi; Hachiya, Tsutomu; Ideura, Gen; Yamazaki, Yoshitaka; Hanaoka, Masayuki;
Keywords:Aged; Body mass index; Blood urea nitrogen; COVID-19; Diabetes mellitus; Nomograms;

IL-6 expression helps distinguish Castleman's disease from IgG4-related disease in the lung
BMC PULMONARY MEDICINE,21(1):219-219 2021
Author:Kinugawa, Yasuhiro; Uehara, Takeshi; Iwaya, Mai; Asaka, Shiho; Kobayashi, Shota; Nakajima, Tomoyuki; Komatsu, Masamichi; Yasuo, Masanori; Yamamoto, Hiroshi; Ota, Hiroyoshi
Abstract:BACKGROUND: It is difficult to distinguish between multicentric Castleman's disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung. METHODS: We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected. RESULTS: In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria. IL-6 expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy. IL-6-expressing cells were mainly identified in the stroma. Sites of IL-6 expression were not characteristic and were sparse. IL-6 expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the IL-6 H-score and serum IL-6 level. CONCLUSION: Differences in IL-6 expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.

Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice
RESPIRATORY RESEARCH,22(1):150-150 2021
Author:Morichika, Daisuke; Taniguchi, Akihiko; Oda, Naohiro; Fujii, Utako; Senoo, Satoru; Itano, Junko; Kanehiro, Arihiko; Kitaguchi, Yoshiaki; Yasuo, Masanori; Hanaoka, Masayuki; Satoh, Takashi; Akira, Shizuo; Kiura, Katsuyuki; Maeda, Yoshinobu; Miyahara, Nobuaki
Abstract:BACKGROUND: IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. METHODS: We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33-/- mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. RESULTS: Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33-/- mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33-/- and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33-/- mice than WT mice. IL-33-/- mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. CONCLUSION: These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

Clinical characteristics of non-idiopathic pulmonary fibrosis, progressive fibrosing interstitial lung diseases A single-center retrospective study
MEDICINE,100(13):e25322 2021
Author:Komatsu, Masamichi; Yamamoto, Hiroshi; Kitaguchi, Yoshiaki; Kawakami, Satoshi; Matsushita, Mina; Uehara, Takeshi; Kinjo, Takumi; Wada, Yosuke; Ichiyama, Takashi; Urushihata, Kazuhisa; Ushiki, Atsuhito; Yasuo, Masanori; Hanaoka, Masayuki;
Keywords:idiopathic pulmonary fibrosis; interstitial lung disease; progressive fibrosing interstitial lung disease;

Automated Diseased Lung Volume Percentage Calculation in Quantitative CT Evaluation of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis
Author:Kitaguchi, Yoshiaki; Fujimoto, Keisaku; Droma, Yunden; Yasuo, Masanori; Wada, Yosuke; Ueno, Fumika; Kinjo, Takumi; Kawakami, Satoshi; Fukushima, Kiyoyasu; Hanaoka, Masayuki;
Keywords:quantitative CT; COPD; IPF; CPFE; LungVision;

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease (vol 133, 155123, 2020)
CYTOKINE,133:155171-155171 2020(Sep.)
Author:Komatsu, Masamichi; Yamamoto, Hiroshi; Yasuo, Masanori; Ushiki, Atsuhito; Nakajima, Tomoyuki; Uehara, Takeshi; Kawakami, Satoshi; Hanaoka, Masayuki

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease
CYTOKINE,133:155123-155123 2020(Sep.)
Author:Komatsu, Masamichi; Yamamoto, Hiroshi; Yasuo, Masanori; Ushiki, Atsuhito; Nakajima, Tomoyuki; Uehara, Takeshi; Kawakami, Satoshi; Hanaoka, Masayuki
Abstract:We previously reported higher levels of C-C chemokine ligand (CCL) 1 in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with sarcoidosis than in BALF of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD), indicating that CCL1 might act as a marker of disease activity in sarcoidosis. Notably, less invasive sampling sources are desirable, as BAL cannot always be performed due to its inherent risk. In this study, we sought to decipher the correlation between serum levels of CCL1 and clinical characteristics of sarcoidosis. Serum samples were obtained from 44 patients with clinically confirmed sarcoidosis, 14 patients with IgG4-RD, and 14 healthy controls. The clinical and radiological findings were retrospectively evaluated. Serum levels of CCL1 were measured using a sandwich enzyme-linked immunosorbent assay. Serum levels of other 17 cytokines and chemokines were measured using a MILLIPLEX® MAP KIT and Luminex® magnetic beads. Serum levels of CCL1 were significantly higher in patients with sarcoidosis than in patients with IgG4-RD and healthy controls. Serum CCL1 was positively correlated with the degree of hilar lymph node swelling on chest computed tomography and serum levels of soluble interleukin 2 receptor. Positive correlations were also observed between serum CCL1 and total cell counts, lymphocyte counts in BALF, and serum T helper 1 mediators such as IP-10 and TNF-α in patients with sarcoidosis. Serum CCL1 levels were significantly elevated in sarcoidosis and correlated with clinical parameters of the disease. In addition, serum and BALF levels of CCL1 were positively correlated in a statistically significant manner. Although further research in this field is necessary, CCL1 might have the potential to be a reliable serological marker of disease activity in sarcoidosis.

The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients.
Sci Rep. 2020(Jul.)
Author:Kinjo T, Kitaguchi Y, Droma Y, Yasuo M, Wada Y, Ueno F, Ota M, Hanaoka M.

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease. Cytokine.
Cytokine 2020(May)
Author:Komatsu M, Yamamoto H, Yasuo M, Ushiki A, Nakajima T, Uehara T, Kawakami S, Hanaoka M.

Successful recovery from critical COVID-19 pneumonia with extracorporeal membrane oxygenation: A case report.
Respir Med Case Rep. 2020(May)
Author:Ikuyama Y, Wada Y, Tateishi K, Kitaguchi Y, Yasuo M, Ushiki A, Urushihata K, Yamamoto H, Kamijo H, Mita A, Imamura H, Hanaoka M.

A comparison of the features of fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) between IgG4-related disease with bilateral hilar lymphadenopathy and sarcoidosis
Author:Ozawa, Yoko; Yamamoto, Hiroshi; Yasuo, Masanori; Komatsu, Masamichi; Ushiki, Atsuhito; Hamano, Hideaki; Uehara, Takeshi; Kawakami, Satoshi; Fujita, Akira; Fujinaga, Yasunari; Oguchi, Kazuhiro; Kawa, Shigeyuki; Hanaoka, Masayuki

The Interstitial Lung Disease-Gender-Age-Physiology Index Can Predict the Prognosis in Surgically Resected Patients with Interstitial Lung Disease and Concomitant Lung Cancer
RESPIRATION,99(1):9-18 2020(Jan.)
Author:Ueno, Fumika; Kitaguchi, Yoshiaki; Shiina, Takayuki; Asaka, Shiho; Yasuo, Masanori; Wada, Yosuke; Kinjo, Takumi; Yoshizawa, Akihiko; Hanaoka, Masayuki
Abstract:BACKGROUND: The interstitial lung disease-gender-age-physiology (ILD-GAP) index and staging system have been reported as a clinical prognostic factor for ILD, including all ILD subtypes. OBJECTIVES: The purpose of this study was to clarify the association of various prognostic indices, including the ILD-GAP index, with the prognosis, the incidence of acute exacerbations of ILD (ILD-AE), and the use of long-term oxygen therapy (LTOT) after surgery in surgically resected patients with ILD and concomitant lung cancer, to provide additional information when considering whether it is safe to perform surgery. METHODS: The medical records of patients with ILD and concomitant lung cancer who had undergone surgery at Shinshu University Hospital between August 2001 and September 2016 were retrospectively analyzed. RESULTS: There were significant differences in survival between the ILD-GAP index: 0-1 and ≥4 groups (p = 0.0001) and between the ILD-GAP index: 2-3 and ≥4 groups (p = 0.0236). A higher ILD-GAP index was independently associated with the risk of death (hazard ratio [HR] 1.32030; p = 0.0059). A higher body mass index (BMI) and a higher serum C-reactive protein (CRP) level were independently associated with the incidence of ILD-AE (HR 1.28336; p = 0.0206 and HR 26.3943; p = 0.0165, respectively). A higher severity of ILD on chest high-resolution computed tomography (HRCT) was independently associated with the use of LTOT (HR 2.78670; p = 0.0313). CONCLUSIONS: The ILD-GAP index can predict the prognosis in surgically resected patients with ILD and concomitant lung cancer. The BMI and serum CRP levels were independent determinants that predicted the incidence of ILD-AE. The severity of ILD on chest HRCT was an independent determinant that predicted the use of LTOT.

Myeloperoxidase (MPO) Gene Polymorphisms are not Associated with Japanese Patients with COPD.
Shinshu Medical Journal,68(1):41-48 2020
Author:Ito M, Yasuo M,Droma Y, Kobayashi N, Hanaoka M.

Two Cases of Bronchial Carcinoid
The Journal of the Japan Society for Respiratory Endoscopy,42(6):507-511 2020
Author:Tanaka Shunnosuke; Hachiya Tsutomu; Hirabayashi Taro; Kimoto Masanobu; Hama Mineyuki; Yasuo Masanori

Background. Surgical resection is the preferred treatment for patients presenting with localized bronchial carcinoids. However, no definitive treatment has yet been established for bronchial carcinoids. Case 1. A woman in her 50s was referred to our hospital because of an intraluminal tumor in the right main bronchus on chest computed tomography that was pointed out during a medical checkup. The tumor was resected endoscopically with high-frequency electrosurgical snaring and it was thereafter diagnosed to be a typical carcinoid. No recurrence has so far been seen during a one-year follow-up. Case 2. A man in his 40s was referred to our hospital because of an abnormal shadow on a chest X-ray that was pointed out during a medical checkup. Chest computed tomography showed an intraluminal tumor in the right basal bronchus. Thoracoscopic right lower lobectomy was performed in addition to lymph node dissection (ND2a-1) and the tumor was diagnosed to be an atypical carcinoid. No recurrence has so far been seen during a five-year follow-up. Conclusion. Checking the size, location, tissue type and extension of the tumor is important to select the optimal treatment for bronchial carcinoids.

The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients
SCIENTIFIC REPORTS,10(1):12811 2020
Author:Kinjo, Takumi; Kitaguchi, Yoshiaki; Droma, Yunden; Yasuo, Masanori; Wada, Yosuke; Ueno, Fumika; Ota, Masao; Hanaoka, Masayuki

Differences Between Central Airway Obstruction and Chronic Obstructive Pulmonary Disease Detected with the Forced Oscillation Technique
Author:Yasuo, Masanori; Kitaguchi, Yoshiaki; Tokoro, Yayoi; Kosaka, Makoto; Wada, Yosuke; Kinjo, Takumi; Ushiki, Atsuhito; Yamamoto, Hiroshi; Hanaoka, Masayuki;
Keywords:forced oscillation technique; pulmonary function test; quality of life; central airway obstruction; COPD;

Prognosis of patients with acute exacerbation of combined pulmonary fibrosis and emphysema: a retrospective single-centre study
Author:Ikuyama, Yuichi; Ushiki, Atsuhito; Kosaka, Makoto; Akahane, Jumpei; Mukai, Yuichi; Araki, Taisuke; Kitaguchi, Yoshiaki; Tateishi, Kazunari; Urushihata, Kazuhisa; Yasuo, Masanori; Yamamoto, Hiroshi; Hanaoka, Masayuki;
Keywords:Acute exacerbation; Combined pulmonary fibrosis and emphysema; Idiopathic pulmonary fibrosis; Prognosis; Emphysema;

RESPIROLOGY,24:81-81 2019(Nov.)
Author:Wada, Yosuke; Kitaguchi, Yoshiaki; Yasuo, Masanori; Hanaoka, Masayuki

Comparison of the chemokine profiles in the bronchoalveolar lavage fluid between IgG4-related respiratory disease and sarcoidosis: CC-chemokine ligand 1 might be involved in the pathogenesis of sarcoidosis
CYTOKINE,120:125-129 2019(Aug.)
Author:Yamamoto, Hiroshi; Yasuo, Masanori; Komatsu, Masamichi; Ushiki, Atsuhito; Hamano, Hideaki; Hori, Atsushi; Nakajima, Tomoyuki; Uehara, Takeshi; Fujinaga, Yasunari; Matsui, Shoko; Hanaoka, Masayuki;
Keywords:Bronchoalveolar lavage; Chemokines; IgG4-related respiratory disease; Sarcoidosis; CC-chemokine ligand 1;

Twenty-year Follow-up of the First Bilateral Living-donor Lobar Lung Transplantation in Japan
INTERNAL MEDICINE,58(21):3133-3137 2019
Author:Komatsu, Masamichi; Yamamoto, Hiroshi; Shomura, Toshitaka; Sonehara, Kei; Ichiyama, Takashi; Urushihata, Kazuhisa; Ushiki, Atsuhito; Yasuo, Masanori; Wakamatsu, Toshihide; Sugimoto, Seiichiro; Oto, Takahiro; Date, Hiroshi; Koizumi, Tomonobu; Hanaoka, Masayuki; Kubo, Keishi
Abstract:Patients with end-stage lung disease can undergo living-donor lobar lung transplantation (LDLLT), with survival rates improving every year. We herein report the 20-year follow-up findings of the first patient who underwent LDLLT in Japan. A 24-year-old woman with primary ciliary dyskinesia became ventilator-dependent after severe respiratory failure and right-sided heart failure following repeated respiratory infections. In 1998, she underwent LDLLT and received her sister's right lower lobe and her mother's left lower lobe. Although the patient required 21 hospitalizations and developed unilateral bronchiolitis obliterans syndrome, she is in good physical condition and lives without restriction at 20 years after undergoing LDLLT.

The relationship between acrolein and oxidative stress in COPD: in systemic plasma and in local lung tissue
Author:Yasuo, Masanori; Droma, Yunden; Kitaguchi, Yoshiaki; Ito, Michiko; Imamura, Hitomi; Kawakubo, Masatomo; Hanaoka, Masayuki;
Keywords:acrolein; smoke; antioxidant potential; oxidative stress; plasma; lung tissue;

Diversity of respiratory impedance based on quantitative computed tomography in patients with COPD
International Journal of COPD,13:1841-1849 2018(Jun. 05)
Author:Yosuke Wada; Yoshiaki Kitaguchi; Masanori Yasuo; Fumika Ueno; Satoshi Kawakami; Kiyoyasu Fukushima; Keisaku Fujimoto; Masayuki Hanaoka
Abstract:Introduction: This study was conducted in order to investigate the diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative computed tomography (CT) in patients with COPD. Patients and methods: Medical records of 174 stable COPD patients were retrospectively reviewed to obtain the patients’ clinical data, including the pulmonary function and imaging data. According to the software-based quantification of the degree of emphysema and airway wall thickness, the patients were classified into the “normal by CT” phenotype, the airway-dominant phenotype, the emphysema-dominant phenotype, and the mixed phenotype. The pulmonary function, including the respiratory impedance evaluated by using the forced oscillation technique (FOT) and the reversibility of airway obstruction in response to inhaled short-acting β2-agonists, was then compared among the four phenotypes. Results: The respiratory system resistance at 5 and 20 Hz (R5 and R20) was significantly higher, and the respiratory system reactance at 5 Hz (X5) was significantly more negative in the airway-dominant and mixed phenotypes than in the other phenotypes. The within-breath changes of X5 (ΔX5) were significantly greater in the mixed phenotype than in the “normal by CT” and emphysema-dominant phenotypes. The FOT parameters (R5, R20, and X5) were significantly correlated with indices of the degree of airway wall thickness and significantly but weakly correlated with the reversibility of airway obstruction. There was no significant correlation between the FOT parameters (R5, R20, and X5) and the degree of emphysema. Conclusion: There is a diversity of respiratory physiology, including the respiratory impedance and reversibility of airway obstruction, based on quantitative CT in patients with COPD. The FOT measurements may reflect the degree of airway disease and aid in detecting airway remodeling in patients with COPD.

Bevacizumab-induced tracheoesophageal fistula in a patient suffering from lung cancer with bulky subcarinal lymph node: A case report
Nagoya Journal of Medical Science,80(1):129-134 2018(Feb. 01)
Author:Kenichi Nishie; Masanori Yasuo; Yoshiaki Kitaguchi; Nobumitsu Kobayashi; Kazunari Tateishi; Atsuhito Ushiki; Kazuhisa Urushihata; Hiroshi Yamamoto; Gen Ideura; Masayuki Hanaoka
Abstract:A 66-year-old male with advanced non-small-cell lung cancer (NSCLC) who was previously treated with carboplatin, pemetrexed, and bevacizumab consequently suffered from severe coughing during deglutition. Chest computed tomography (CT) revealed a tracheoesophageal fistula (TEF) between the left main bronchus and esophagus through a subcarinal metastatic lymph node. Given the extreme swelling of the lymph node due to metastatic cancer, it was determined that the walls of the bronchus and esophagus had been injured simultaneously. Delayed and dysfunctional wound healing due to bevacizumab resulted in necrosis of the contact region leading to fistula formation. This case suggests that using bevacizumab for NSCLC in patients with bulky subcarinal lymphadenopathy may increase the risk for TEF.

An unusual case of multicentric castleman’s disease,complicated by pleural effusion.
Shinshu Med J,65(1):51-56 2017(Jan. 01)
Author:Nozawa S; Yasuo M; Yamamoto H; Hama M; Tateishi K; Ushiki A; Hanaoka M

Lack of association of serotonin 2A receptor gene in Japanese patients with obstructive sleep apnea syndrome.
Shinshu Medical Journal.,65(3):153-162 2017
Author:Ikegawa K; Ota M; Kobayashi N; Droma Y; Yaegashi H; Nishizawa M; Yasuo M; Urushihata K; Yamamoto H; Hanaoka M
Abstract:Shinshu Medical Journal.

Bronchial mucoepidermoid carcinoma successfully treated with radiation therapy: A case report.
Oncol Cancer Case Rep,3:2 2017
Author:Nishie K; Yasuo M; Takahashi H; Ozawa Y; Tateishi K; Yamamoto H; Koiwai K; Uehara T; Ideura G; Hanaoka M
Abstract:Oncol Cancer Case Rep

The Preoperative Composite Physiologic Index May Predict Mortality in Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema
RESPIRATION,94(2):198-206 2017
Author:Fumika Ueno; Yoshiaki Kitaguchi; Takayuki Shiina; Shiho Asaka; Kentaro Miura; Masanori Yasuo; Yosuke Wada; Akihiko Yoshizawa; Masayuki Hanaoka
Abstract:Background: It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. Objective: The aim of this study is to identify prognostic determinants in these patients. Methods: The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest highresolution computed tomography (HRCT), and survival. Results: Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil- to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). Conclusion: The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery. (C) 2017 S. Karger AG, Basel

Self-assessment of Allergic Rhinitis and Asthma (SACRA) Questionnaire-based Allergic Rhinitis Treatment Improves Asthma Control in Asthmatic Patients with Allergic Rhinitis
INTERNAL MEDICINE,56(1):31-39 2017
Author:Masanori Yasuo; Yoshiaki Kitaguchi; Yoshimichi Komatsu; Mineyuki Hama; Tomonobu Koizumi; Toshihiko Agatsuma; Takashi Ichiyama; Akane Kato; Hideaki Moteki; Masayuki Hanaoka
Abstract:Objective This study was conducted to investigate whether the add-on treatment of allergic rhinitis (AR) based on the Self-assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire for assessing AR control improves both AR and asthma control in asthmatic patients with AR. Methods This multi-center prospective study was performed in Nagano prefecture, Japan. Two hundred five asthmatic patients and 23 respiratory physicians participated in the study. We administered add-on AR treatments based on the results of the SACRA questionnaire. After the first SACRA questionnaire, 67 asthmatic patients agreed to receive an add-on AR treatment. Three months after the AR treatment, a secondary SACRA questionnaire, asthma control test (ACT), and pulmonary function tests were performed. Results After the add-on AR treatment, the visual analogue scales (VASs) for AR and asthma, as assessed by the SACRA questionnaire and ACT score, were significantly improved in the patients of the AR+ group. With regard to the pulmonary function tests, the percent predicted vital capacity, and percent predicted forced expiratory volume in one second were also significantly improved. Regardless of whether the patients had previously undergone leukotriene receptor antagonists (LTRA) treatment, the VASs for AR and asthma and the ACT score were significantly improved in the AR+ group. However, the vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume (FEV1) were only significantly improved in the AR+ group that had previously undergone LTRA treatment. Conclusion SACRA questionnaire-based add-on AR treatment would be convenient for the detection of AR by respiratory physicians and would offer improved asthma control. This questionnaire can also be used to assess the therapeutic effects.

The histological characteristics and clinical outcomes of lung cancer in patients with combined pulmonary fibrosis and emphysema
CANCER MEDICINE,5(10):2721-2730 2016(Oct.)
Author:Meng Zhang; Akihiko Yoshizawa; Satoshi Kawakami; Shiho Asaka; Hiroshi Yamamoto; Masanori Yasuo; Hiroyuki Agatsuma; Masayuki Toishi; Takayuki Shiina; Kazuo Yoshida; Takayuki Honda; Ken-ichi Ito
Abstract:Combined pulmonary fibrosis and emphysema (CPFE) is an important risk factor for lung cancer (LC), because most patients with CPFE are smokers. However, the histological characteristics of LC in patients with CPFE (LC-CPFE) remain unclear. We conducted this study to explore the clinicopathological characteristics of LC-CPFE. We retrospectively reviewed data from 985 patients who underwent resection for primary LC, and compared the clinicopathological characteristics of patients with LC-CPFE and non-CPFE LC. We identified 72 cases of LC-CPFE, which were significantly associated with squamous cell carcinoma (SqCC) histology (n = 46, P < 0.001) and higher tumor grade (n = 44, P < 0.001), compared to non-CPFE LC. Most LC-CPFE lesions were contiguous with fibrotic areas around the tumor (n = 59, 81.9%), and this association was independent of tumor location. Furthermore, dysplastic epithelium was identified in the fibrotic area for 31 (52.5%) LC-CPFE lesions. Moreover, compared to patients with pulmonary fibrosis alone in the non-CPFE group (n = 31), patients with CPFE were predominantly male (P = 0.008) and smokers (P < 0.001), with LC-CPFE predominantly exhibiting SqCC histology (P = 0.010) and being contiguous with the tumor-associated fibrotic areas (P < 0.001). Multivariate analysis revealed that CPFE was an independent predictor of overall survival (hazard ratio: 1.734; 95% confidence interval: 1.060-2.791; P = 0.028). Our results indicate that LC-CPFE has a distinct histological phenotype, can arise from the dysplastic epithelium in the fibrotic area around the tumor, and is associated with poor survival outcomes.

Usefulness of F-18 FDG PET/CT in a case of relapsing polychondritis.
Shinshu Med J,64(6):349-355 2016(Mar. 01)
Author:Yanagisawa S; Matsushita T; Yasuo M; Machida R; Ishii W; Kadoya M
Abstract:Shinshu Med J

Usefulness of F-18 FDG PET/CT in a case of relapsing polychondritis.
Shinshu Medical Journal,64(6):349-355 2016(Mar. 01)
Author:Yanagisawa S, Matsushita T, Yasuo M, Machida R, Ishii W, Kadoya M

Comparison of pulmonary function in patients with COPD, asthma-COPD overlap syndrome, and asthma with airflow limitation
Author:Yoshiaki Kitaguchi; Masanori Yasuo; Masayuki Hanaoka
Abstract:Background: This study was conducted in order to investigate the differences in the respiratory physiology of patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), and asthma with airflow limitation (asthma FL+). Methods: The medical records for a series of all stable patients with persistent airflow limitation due to COPD, ACOS, or asthma were retrospectively reviewed and divided into the COPD group (n=118), the ACOS group (n=32), and the asthma FL+ group (n=27). All the patients underwent chest high-resolution computed tomography (HRCT) and pulmonary function tests, including respiratory impedance. Results: The low attenuation area score on chest HRCT was significantly higher in the COPD group than in the ACOS group (9.52 +/- 0.76 vs 5.09 +/- 1.16, P < 0.01). The prevalence of bronchial wall thickening on chest HRCT was significantly higher in the asthma FL+ group than in the COPD group (55.6% vs 25.0%, P < 0.01). In pulmonary function, forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate were significantly higher in the asthma FL+ group than in the ACOS group (76.28%+/- 2.54% predicted vs 63.43%+/- 3.22% predicted, P < 0.05 and 74.40%+/- 3.16% predicted vs 61.08%+/- 3.54% predicted, P < 0.05, respectively). Although residual volume was significantly lower in the asthma FL+ group than in the COPD group (112.05%+/- 4.34% predicted vs 137.38%+/- 3.43% predicted, P < 0.01) and the ACOS group (112.05%+/- 4.34% predicted vs148.46%+/- 6.25% predicted, P < 0.01), there were no significant differences in functional residual capacity or total lung capacity. The increase in FEV1 in response to short-acting beta(2)-agonists was significantly greater in the ACOS group than in the COPD group (229 +/- 29 mL vs 72 +/- 10 mL, P < 0.01) and the asthma FL+ group (229 +/- 29 mL vs 153 +/- 21 mL, P < 0.05). Regarding respiratory impedance, resistance at 5 Hz and resistance at 20 Hz, which are oscillatory parameters of respiratory resistance, were significantly higher in the asthma FL+ group than in the COPD group at the whole-breath (4.29 +/- 0.30 cmH(2)O/L/s vs 3.41 +/- 0.14 cmH(2)O/L/s, P < 0.01 and 3.50 +/- 0.24 cmH(2)O/L/s vs 2.68 +/- 0.10 cmH(2)O/L/s, P < 0.01, respectively), expiratory, and inspiratory phases. Conclusion: Although persistent airflow limitation occurs in patients with COPD, ACOS, and asthma FL+, they may have distinct characteristics of the respiratory physiology and different responsiveness to bronchodilators.

RESPIROLOGY,20:22-22 2015(Dec.)
Author:Kato, Akane; Yasuo, Masanori; Hama, Mineyuki; Ichiyama, Takashi; Hanaoka, Masayuki

Hypertrophic Pulmonary Osteoarthropathy in Anaplastic Lymphoma Kinase (ALK)-positive Lung Cancer
INTERNAL MEDICINE,54(16):2045-2049 2015
Author:Masamichi Komatsu; Masanori Yasuo; Nobumitsu Kobayashi; Kazunari Tateishi; Atsuhito Ushiki; Kazuhisa Urushihata; Hiroshi Yamamoto; Masayuki Hanaoka; Hisanori Matoba; Takayuki Honda; Kosuke Ichikawa
Abstract:A 49-year-old man was admitted to a hospital with chest pain and polyarthralgia. Chest radiography showed abnormal findings, and chest computed tomography showed a mass in the right lung. A transbronchial lung biopsy led to a diagnosis of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma. Bone scintigraphy revealed bilateral symmetrical accumulations of (99m)Technetium complexes in the long bones, suggesting co-existing hypertrophic pulmonary osteoarthropathy (HPO). The patient underwent four courses of chemotherapy with cisplatin plus pemetrexed, which led to decreased (99m)Technetium accumulations in the long bones. To the best of our knowledge, this is the first reported case of HPO associated with ALK-positive lung cancer.

Bronchoscopy-Guided Cooled Radiofrequency Ablation as a Novel Intervention Therapy for Peripheral Lung Cancer
RESPIRATION,90(1):47-55 2015
Author:Tomonobu Koizumi; Kenji Tsushima; Tsuyoshi Tanabe; Toshihiko Agatsuma; Toshiki Yokoyama; Michiko Ito; Shintaro Kanda; Takashi Kobayashi; Masanori Yasuo
Abstract:Background: Our previous animal and preliminary human studies indicated that bronchoscopy-guided cooled radio-frequency ablation (RFA) for the lung is a safe and feasible procedure without major complications. Objectives: The present study was performed to evaluate the safety, effectiveness and feasibility of computed tomography (CT)-guided bronchoscopy cooled RFA in patients with medically inoperable non-small-cell lung cancer (NSCLC). Methods: Patients with pathologically diagnosed NSCLC, who had no lymph node involvement or distant metastases (T1-2aN0M0) but were not surgical candidates because of comorbidities (e.g. synchronous multiple nodules, advanced age, cardiovascular disease, poor pulmonary function, etc.) were enrolled in the present study. The diagnosis and location between the nearest bronchus and target tumor were made by CT-guided bronchoscopy before the treatment. A total of 28 bronchoscopy-guided cooled RFA procedures were performed in 20 patients. After treatment, serial CT imaging was performed as follow-up. Results: Eleven lesions showed significant reductions in tumor size and 8 lesions showed stability, resulting in a local control rate of 82.6%. The median progression-free survival was 35 months (95% confidence interval: 22-45 months), and the 5-year overall survival was 61.5% (95% confidence interval: 36-87%). Three patients developed an acute ablation-related reaction (fever, chest pain) and required hospitalization but improved with conservative treatment. There were no other adverse events in the present study. Conclusions: CT-guided bronchoscopy cooled RFA is applicable for only highly selected subjects; however, our trial may be an alternative strategy, especially for disease local control in medically inoperable patients with stage I NSCLC. (C) 2015 S. Karger AG, Basel

The Journal of the Japan Society for Respiratory Endoscopy,37(1):28-32 2015
Author:小松雅宙; 安尾将法; 濵 峰幸; 立石一成; 伊東理子; 牛木淳人; 漆畑一寿; 山本 洋; 花岡正幸
Abstract:The Journal of the Japan Society for Respiratory Endoscopy

RESPIROLOGY,19:217-217 2014(Nov.)
Author:Hama, Mineyuki; Atsuhito, Ushiki; Yasuo, Masanori; Yamamoto, Hiroshi; Hanaoka, Masayuki

Late-onset Rejection of a Unilateral Donor Lung with Vascular C4d Deposition in Bilateral Living-donor Lobar Lung Transplantation: An Autopsy Case Report
INTERNAL MEDICINE,53(15):1645-1650 2014
Author:Hiroshi Yamamoto; Kazuo Yoshida; Tomonobu Koizumi; Yayoi Tokoro; Toshiro Fukushima; Kazunari Tateishi; Atsuhito Ushiki; Toshiki Yokoyama; Masanori Yasuo; Kazuhisa Urushihata; Masayuki Hanaoka; Kunihiko Shingu; Hisashi Shimojo; Hiroyuki Kanno; Akihiko Yoshizawa; Satoshi Kawakami; Aya Miyagawa-Hayashino; Hiroshi Date; Keishi Kubo
Abstract:A 37-year-old woman had undergone bilateral living-donor lobar lung transplantation 11 years previously for idiopathic pulmonary arterial hypertension. Her father donated the right lobe and her brother donated the left lobe. She subsequently developed progressively worsening respiratory dysfunction due to pneumonia. CT showed left dominant pulmonary artery dilatation, bronchial wall thickening and airway stenosis, followed by sudden death. An autopsy showed marked pathologic left dominant rejection of the pulmonary artery, small airway and large airway. Notably, only the left lung showed C4d vascular deposition, thus suggesting that

Does drug-induced emphysema exist?
European Respiratory Journal,42(6):1464-1468 2013(Dec. 01)
Author:Norbert F. Voelkel; Shiro Mizuno; Masanori Yasuo

Fenretinide Causes Emphysema, Which Is Prevented by Sphingosine 1-Phoshate
PLOS ONE,8(1):- 2013(Jan.)
Author:Masanori Yasuo; Shiro Mizuno; Jeremy Allegood; Donatas Kraskauskas; Harm J. Bogaard; Sarah Spiegel; Norbert F. Voelkel
Abstract:Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 mg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive cells were measured. Hypoxia-inducible factor alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1 alpha was also performed. Ceramide, dihydroceramide, S1P, and dihydro-S1P were measured by mass spectrometer. Chronic intraperitoneal injection of fenretinide increased the alveolar airspace surface area and increased the number of caspase-3 positive cells in rat lungs. Fenretinide also suppressed HIF-1 alpha and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1 alpha, VEGF, histone deacetylase 2 (HDAC2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein expression in the lungs. S1P injection also increased phosphorylated sphingosine kinase 1. Dihydroceramide was significantly increased by fenretinide injection and S1P treatment prevented the increase in dihydroceramide levels in rat lungs. These data support the concept that increased de novo ceramide production causes alveolar septal cell apoptosis and causes emphysema via suppressing HIF-1 alpha. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1 alpha protein expression via activation of sphingosine kinase 1; as a consequence, S1P salvages fenretinide induced emphysema in rat lungs.

Increased Interleukin-8 in Epithelial Lining Fluid of Collapsed Lungs During One-Lung Ventilation for Thoracotomy
INFLAMMATION,35(6):1844-1850 2012(Dec.)
Author:Yoshimichi Komatsu; Hiroshi Yamamoto; Kenji Tsushima; Shino Furuya; Sumiko Yoshikawa; Masanori Yasuo; Keishi Kubo; Yoshitaka Yamazaki; Joh Hasegawa; Takashi Eguchi; Ryuichi Kondo; Kazuo Yoshida; Tomonobu Koizumi
Abstract:The present study was designed to evaluate inflammatory changes in collapsed lungs during one-lung ventilation using the assistance of a bronchoscopic microsampling probe. Serial albumin and interleukin (IL)-8 concentrations in epithelial lining fluid (ELF) were measured in seven patients undergoing resection of lung tumors. The samples were taken after induction of anesthesia (baseline), 30 min after one-lung ventilation was started (point 2), just before resuming two-lung ventilation (point 3), and 30 min after two-lung ventilation was restarted (point 4). The albumin and IL-8 concentrations in ELF were significantly increased at point 2 and point 3, respectively, and remained to be high, compared to the baseline. The increase in IL-8 at point 3 was correlated with the interval of one-lung ventilation; however, none developed specific acute lung injury. These findings suggest that inflammatory changes can occur on the epithelium of a collapsed lung even in patients who underwent successful and standard thoracic surgery.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Intrathoracic Lesions: Experience of a Single Academic Medical Center
Shinshu Medical Journal,60(5):249-255 2012(Oct. 01)
Author:Masanori Yasuo; Takashi Kobayashi; Yayoi Tokoro; Toshimichi Horiuchi; Michiko Ito; Kazushi Kojima; Kayoko Ikegawa; Atsuhito Ushiki; Hiroshi Yamamoto; Masayuki Hanaoka; Tomonobu Koizumi; Akihiko Yoshizawa; Takayuki Honda; Keishi Kubo
Abstract:Shinshu Medical Journal

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Intrathoracic Lesions: Experience of a Single Academic Medical Center
Shinshu Medical Journal,60(5):249-255 2012(Oct. 01)
Author:Masanori Yasuo, Takashi Kobayashi, Yayoi Tokoro, Toshimichi Horiuchi, Michiko Ito, Kazushi Kojima, Kayoko Ikegawa, Atsuhito Ushiki, Hiroshi Yamamoto, Masayuki Hanaoka, Tomonobu Koizumi, Akihiko Yoshizawa, Takayuki Honda, Keishi Kubo

A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer
Author:Takashi Kobayashi; Tomonobu Koizumi; Toshihide Agatsuma; Masanori Yasuo; Kenji Tsushima; Keishi Kubo; Seiichiro Eda; Hiroshi Kuraishi; Shigeru Koyama; Tsutomu Hachiya; Nariaki Ohura
Abstract:There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of EGFR, in Japanese patients with EGFR wild-type tumors. Patients with stage III/IV or postoperative recurrence of NSCLC whose tumors have wild-type EGFR were eligible. Erlotinib (150 mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR). Thirty-one patients (23 men and 8 women; median age, 71 years; range, 31-89) were enrolled between January 2008 and June 2011. Twenty-one had adenocarcinoma, nine had squamous cell carcinoma, and one had large cell carcinoma. Ten, nine, eight, and four patients showed performance status 0, 1, 2, and 3, respectively. Erlotinib was administered following the median 3.1 regimens of cytotoxic chemotherapies. One patient achieved complete response, four showed partial response, and eight had stable disease. Thus, response rate was 17.2%, and DCR was 44.8%. Skin rash was the most common side effect (80.6%). Two patients developed interstitial lung disease. Nevertheless, all of these events were reversible, and there were no treatment-related deaths. The median progression-free survival and survival times were 2.1 and 7.7 months, respectively. Erlotinib might be an alternative option for patients resistant to cytotoxic chemotherapy even in those with EGFR wild-type NSCLC.

Copper Deficiency Induced Emphysema Is Associated with Focal Adhesion Kinase Inactivation
PLOS ONE,7(1):- 2012(Jan.)
Author:Shiro Mizuno; Masanori Yasuo; Harm J. Bogaard; Donatas Kraskauskas; Aysar Alhussaini; Jose Gomez-Arroyo; Daniela Farkas; Laszlo Farkas; Norbert F. Voelkel
Abstract:Background: Copper is an important regulator of hypoxia inducible factor 1 alpha (HIF-1 alpha) dependent vascular endothelial growth factor (VEGF) expression, and is also required for the activity of lysyl oxidase (LOX) to effect matrix protein cross-linking. Cell detachment from the extracellular matrix can induce apoptosis (anoikis) via inactivation of focal adhesion kinase (FAK). Methodology: To examine the molecular mechanisms whereby copper depletion causes the destruction of the normal alveolar architecture via anoikis, Male Sprague-Dawley rats were fed a copper deficient diet for 6 weeks while being treated with the copper chelator, tetrathiomolybdate. Other groups of rats were treated with the inhibitor of auto-phosphorylation of FAK, 1,2,4,5-benzenetetraamine tetrahydrochloride (1,2,4,5-BT) or FAK small interfering RNA (siRNA). Principal Findings: Copper depletion caused emphysematous changes, decreased HIF-1 alpha activity, and downregulated VEGF expression in the rat lungs. Cleaved caspase-3, caspase-8 and Bcl-2 interacting mediator of cell death (Bim) expression was increased, and the phosphorylation of FAK was decreased in copper depleted rat lungs. Administration of 1,2,4,5-BT and FAK siRNA caused emphysematous lung destruction associated with increased expression of cleaved capase-3, caspase-8 and Bim. Conclusions: These data indicate that copper-dependent mechanisms contribute to the pathogenesis of emphysema, which may be associated with decreased HIF-1 alpha and FAK activity in the lung.

IgG4-related chronic rhinosinusitis: A new clinical entity of nasal disease
ACTA OTO-LARYNGOLOGICA,131(5):518-526 2011(May)
Author:Hideaki Moteki; Masanori Yasuo; Hideaki Hamano; Takeshi Uehara; Shin-ichi Usami
Abstract:Conclusion: IgG4-related disease involves nasal manifestations with chronic rhinosinusitis (CRS). This type of sinusitis is a new clinical entity of nasal disease associated with a high level of serum IgG4 for which steroid therapy is effective. Objectives. To confirm whether IgG4-related disease has distinctive chronic rhinosinusitis. Methods: We compared serum IgG4 levels as well as nasal computed tomography (CT) and clinicopathological findings before and after glucocorticoid treatment in 31 patients diagnosed as having IgG4-related disease with nasal manifestations. To evaluate immunohistochemical findings of nasal mucosa, we compared them with IgG4-related CRS and common CRS. Results: All patients had levels of high serum IgG4. Ten of the 31 patients had nasal obstruction, nasal discharge, postnasal discharge, hyposmia, and dull headache. They also demonstrated sinus lesions on radiological findings. After glucocorticoid treatment, serum IgG and IgG4 levels were markedly decreased and along with improvement of the symptoms, nasal sinus CT findings also revealed improvement of the sinus opacification. In immunohistochemical examination, the magnitude of IgG4-positive plasma cell infiltration in common CRS was almost the same as in the IgG4-related CRS group. Therefore, in nasal mucosa immunocytochemical positive staining for IgG4 is not specific for definition of IgG4-related disease.

Inhibition of histone deacetylase causes emphysema
Author:Shiro Mizuno; Masanori Yasuo; Herman J. Bogaard; Donatas Kraskauskas; Ramesh Natarajan; Norbert F. Voelkel
Abstract:Mizuno S, Yasuo M, Bogaard HJ, Kraskauskas D, Natarajan R, Voelkel NF. Inhibition of histone deacetylase causes emphysema. Am J Physiol Lung Cell Mol Physiol 300: L402-L413, 2011. First published December 17, 2010; doi:10.1152/ajplung.00207.2010.-In patients with chronic obstructive pulmonary disease (COPD), histone deacetylase (HDAC) expression and activity are reduced in the lung tissue. However, whether HDAC activity controls the maintenance of the lung alveolar septal structures has not been investigated. To explore the consequences of HDAC inhibition and address the question of whether HDAC inhibition causes lung cell apoptosis and emphysema, male Sprague-Dawley rats and human pulmonary microvascular endothelial cells (HPMVEC) were treated with trichostatin A (TSA), a specific inhibitor of HDACs. Chronic TSA treatment increased the alveolar air space area, mean linear intercept, and the number of caspase-3-positive cells in rat lungs. TSA suppressed hypoxia-inducible factor-1 alpha (HIF-1 alpha), VEGF, and lysyl oxidase (LOX) and increased microtubule-associated protein-1 light chain 3 (LC3), p53, and miR34a microRNA expression in both rat lungs and cultured HPMVEC. Gene silencing of HDAC2 using small interfering RNA (siRNA) in cultured HPMVEC resulted in the suppression of HIF-1 alpha, VEGF, and LOX and an increase of p53 expression. These data indicate that HDAC inhibition causes emphysema and that HDAC-dependent mechanisms contribute to the maintenance of the adult lung structure. Our results also suggest that the increase in apoptosis, as a consequence of HDAC inhibition, is associated with decreased VEGF and HIF-1 alpha expression.

IgG4-Related Airway Involvement Which Developed in a Patient Receiving Corticosteroid Therapy for Autoimmune Pancreatitis
INTERNAL MEDICINE,50(24):3023-3026 2011
Author:Hiroshi Yamamoto; Masanori Yasuo; Yayoi Nomura; Toshihiko Agatsuma; Atsuhito Ushiki; Toshiki Yokoyama; Kazuhisa Urushihata; Masayuki Hanaoka; Tomonobu Koizumi; Mai Iwaya; Akihiko Yoshizawa; Satoshi Kawakami; Hideaki Hamano; Shigeyuki Kawa; Keishi Kubo
Abstract:A 66-year-old man was diagnosed with autoimmune pancreatitis in February 2009 and started 40 mg of oral prednisolone followed by a maintenance dose of 5 mg daily. The patient developed a cough in October 2010 and visited our division. He had a high serum concentration of immunoglobulin (Ig) G4 and his chest computed tomography showed airway stenosis without bilateral hilar lymphadenopathy (BHL). The bronchial biopsy specimens revealed lymphoplasmacytic infiltrations with IgG4-positive/IgG-positive plasma cells of more than 50%. Thus, we diagnosed the airway lesion with IgG4-related airway involvement. This is the first report of a patient with IgG4-related airway involvement without BHL.

IgG4-Related Pleural Disease Diagnosed by a Re-Evaluation of Chronic Bilateral Pleuritis in a Patient Who Experienced Occasional Acute Left Bacterial Pleuritis
INTERNAL MEDICINE,50(8):893-897 2011
Author:Hiroshi Yamamoto; Toshiro Suzuki; Masanori Yasuo; Orie Kobayashi; Kenji Tsushima; Michiko Ito; Kazuhisa Urushihata; Yoshitaka Yamazaki; Masayuki Hanaoka; Tomonobu Koizumi; Takeshi Uehara; Satoshi Kawakami; Hideaki Hamano; Shigeyuki Kawa; Keishi Kubo
Abstract:A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.

Successful Salvage Chemotherapy with Gemcitabine and Vinorelbine in a Malignant Pleural Mesothelioma Patient Previously Treated with Pemetrexed
Author:Toshihiko Agatsuma; Tomonobu Koizumi; Masanori Yasuo; Kazuhisa Urushihata; Kenji Tsushima; Hiroshi Yamamoto; Masayuki Hanaoka; Mana Fukushima; Takayuki Honda; Keishi Kubo
Abstract:The role of second-line and salvage chemotherapy in malignant pleural mesothelioma treatment is not yet established. We report a case of relapsed malignant pleural mesothelioma in which the patient failed to respond to pemetrexed-based chemotherapy but was successfully treated with gemcitabine and vinorelbine. The patient underwent a left extrapleural pneumonectomy. Three years later she developed anterior chest wall and retroperitoneal masses. Histological findings revealed metastases from the malignant pleural mesothelioma. Although two cycles of carboplatin plus pemetrexed chemotherapy were administered, she had progressive disease. Then, 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine were administered every 2 weeks. The chemotherapy regimen was tolerated well, and the tumors were remarkably reduced. She was treated with 12 cycles of gemcitabine plus vinorelbine, and 8.5 months of progression-free survival was observed. Gemcitabine plus vinorelbine chemotherapy may be a candidate regimen for salvage chemotherapy against malignant pleural mesotheliomas.

Salvage chemotherapy with amrubicin and platinum for relapsed thymic carcinoma: experience in six cases
MEDICAL ONCOLOGY,27(2):392-396 2010(Jun.)
Author:Tomonobu Koizumi; Toshihiko Agatsuma; Takashi Ichiyama; Toshiki Yokoyama; Atsuhito Ushiki; Yoshimichi Komatsu; Tsuyoshi Tanabe; Takashi Kobayashi; Sumiko Yoshikawa; Masanori Yasuo; Hiroshi Yamamoto; Keishi Kubo; Tsutomu Hachiya
Abstract:It has been reported that cisplatin-based chemotherapy shows beneficial effects in certain patients with advanced thymic carcinoma. However, the usefulness of salvage therapy has not been reported. We focused on a new anthracycline agent, amrubicin, combined with platinum compounds as salvage chemotherapy in patients with thymic carcinoma. Six cases of unresectable and locally advanced thymic carcinoma relapsed from prior cisplatin-containing chemotherapy were treated with amrubicin (30-40 mg/m(2) day 1-3) plus platinum compounds (cisplatin 60 mg/m(2) day 1 or nedaplatin 70 mg/m(2) day 1) chemotherapy as salvage chemotherapy. Two patients showed a partial response. However, Grade 3/4 neutropenia and thrombocytopenia occurred in all and two of the patients, respectively. We conclude that thymic carcinoma is sensitive to platinum-based chemotherapy and that amrubicin appears to have significant activity against thymic carcinoma. The major toxicity is hematological toxicities.

Comparative Study of Three Different Catheters for CT Imaging-Bronchoscopy-Guided Radiofrequency Ablation as a Potential and Novel Interventional Therapy for Lung Cancer
CHEST,137(4):890-897 2010(Apr.)
Author:Tsuyashi Tanabe; Tomonobu Koizumi; Kenji Tsushima; Michiko Ito; Shintaro Kanda; Takashi Kobayashi; Masanori Yasuo; Yoshitaka Yamazaki; Keishi Kubo; Takayuki Honda; Ryouichi Kondo; Kazuo Yoshida
Abstract:Background: We previously reported that bronchoscopy-guided, internally cooled radiofrequency ablation (RFA) in normal sheep lung was a safe, effective, and feasible procedure without major complications. Purpose: The aim of this study was to evaluate the safety, effectiveness, and feasible conditions of bronchoscopy-guided, internally cooled RFA as a clinical application for non-small cell lung cancer (NSCLC). Methods: Ten patients pathologically diagnosed with NSCLC and the clinical stage of T1N0MO were enrolled in the study. Three types of internally cooled electrode catheter tips were prepared using different procedure conditions involving ablation time: an internally cooled electrode with a 5-mm cylindrical active tip at a power output of 20 W, flow rate of 50 mL/min, and an ablation time of 30 s (n = 3), an electrode with an 8-mm active tip with four beads at 20 W, 50 mL/min, and 40 s (n = 3), and an electrode with a 10-mm active tip with five beads at 20 W, 50 mL/min, and 50 s (n = 4). CT image-guided, bronchoscopy-guided, internally cooled RFA was performed, and the patients underwent standard lung resection therapy. The resected lung tissue was examined histopathologically to assess the ablated areas. Results: Ablated areas pathologically evaluated with the 10-mm active tip were significantly larger than those with the 5-mm tip. Thus, the ablated areas were enlarged depending on the tip length and prolonged ablation time. There were no complications during RFA, such as bronchial bleeding or pneumothorax. Conclusions: CT imaging-bronchoscopy-guided, internally cooled RFA in humans is a safe and feasible procedure that could become a potential therapeutic tool for local control in medically inoperable patients with stage I NSCLC. CHEST 2010; 137(4):890-897

Malignant Hepatic Epithelioid Hemangioendothelioma with Rapid Progression and Fatal Outcome
INTERNAL MEDICINE,49(12):1149-1153 2010
Author:Yoshimichi Komatsu; Tomonobu Koizumi; Masanori Yasuo; Kazuhisa Urushihata; Hiroshi Yamamoto; Masayuki Hanaoka; Keishi Kubo; Satoshi Kawakami; Takayuki Honda; Keisaku Fujimoto; Tsutomu Hachiya
Abstract:A 46-year-old woman was admitted to our hospital because of pain in the right upper quadrant and dyspnea. Abdominal and chest computed tomography (CT) scans revealed areas of low attenuation in both hepatic lobes, left pleural effusion, and multiple nodules in both lungs. Laboratory data indicated disseminated intravascular coagulation. She developed rapidly progressive respiratory and hepatic failure despite intensive treatment including mechanical ventilation and died of respiratory failure 3 weeks after admission. Immunohistochemical analysis of liver necropsy and cytology of the left plural effusion stained positive for factor VIII-related antigen and CD31. Based on these observations, a diagnosis of hemangioendothelioma (EHE), a rare vascular tumor, was made. A rapid clinical course and fatal outcome, as in the present case, are rare clinical manifestations in EHE.

Evaluation of Respiratory Impedance in Asthma and COPD by an Impulse Oscillation System
INTERNAL MEDICINE,49(1):23-30 2010
Author:Shintarou Kanda; Keisaku Fujimoto; Yoshimichi Komatsu; Masanori Yasuo; Masayuki Hanaoka; Keishi Kubo
Abstract:Objective The purpose of this study was to clarify the differences in physiological properties of the airways between asthma and COPD using an impulse oscillation system (IOS). Patients and Methods Subjects comprised 95 stable COPD patients, 52 never-smoker asthma patients and 29 healthy never-smokers > 60 years old, all matched for age, in whom respiratory impedance was examined by IOS. Results In both asthma and COPD patients, a significant increase in respiratory resistance (Rrs5) and more negative value of respiratory reactance (Xrs5) at 5 Hz of oscillatory frequency with an increase in resonant frequency (fres) were observed when compared with healthy never-smokers. In asthma, a significant increase in respiratory resistance at 20 Hz (Rrs20) was also observed when compared with healthy never-smokers and COPD. The increases in Rrs5 and relative changes of Xrs5 to more negative were remarkable with increasing severity of COPD. On the other hand, among patients with asthma, these changes in Rrs5 and Xrs5 were also observed in asthmatics with normal FEV(1)/FVC. Interestingly, Xrs5 showed further changes to more negative in expiration of tidal breath in severe COPD, whereas no significant changes in Xrs5 to more negative in expiration was observed in healthy never-smokers and asthmatics with and without normal FEV(1)/FVC. Conclusion IOS may be useful for detecting pathophysiological changes of respiratory system in accordance with severity of COPD and even in asthmatics with normal FEV(1)/FVC. The larger within-breath changes of Xrs5 to more negative in severe COPD may represent easy collapsibility of small airways in expiration of tidal breath. These properties may help to analyze airway mechanics and to identify abnormalities of the airways that cannot be found by spirometry alone.

Clinical utility of bronchoscopy-guided radiofrequency ablation for lung cancer
Author:Koizumi, Tomonobu; Tanabe, Tsuyoshi; Tsushima, Kenji; Yokoyama, Toshiki; Agatsuma, Toshihiko; Suzuki, Toshirou; Kitaguchi, Yoshiaki; Kanda, Shintarou; Itou, Michiko; Yoshikawa, Sumiko; Kobayashi, Takeshi; Yasuo, Masanori; Urushihata, Kazuhisa; Yamamoto, Hiroshi; Hanaoka, Masayuki; Kubo, Keishi

Bronchoscopy-guided radiofrequency ablation as a novel intervention therapy for lung cancer
Author:Tanabe, Tsuyoshi; Koizumi, Tomonobu; Tsushima, Kenji; Agatsuma, Toshihiko; Ushiki, Atsushi; Yokoyama, Toshiki; Suzuki, Toshirou; Itou, Michiko; Kanda, Shintarou; Kobayashi, Takeshi; Yasuo, Masanori; Yamazaki, Yoshitaka; Yoshida, Kazuo; Uehara, Takeshi; Honda, Takayuki; Kubo, Keishi

L-Carbocisteine reduces neutrophil elastase-induced mucin production
Author:Masanori Yasuo; Keisaku Fujimoto; Hitomi Imamura; Atsuhito Ushiki; Shintaro Kanda; Kenji Tsushima; Hiroshi Kubo; Mutsuo Yamaya; Keishi Kubo
Abstract:Human neutrophil elastase (HNE) exists in high concentrations in airway secretions and produces mucus hypersecretion in patients with chronic obstructive pulmonary disease (COPD). L-Carbocisteine improves the quality of life and reduces exacerbation in COPD patients. However the precise mechanism is uncertain. We examined the effects Of L-carbocisteine on HNE-induced mucus hypersecretion and on the production of reactive oxygen species (ROS) which is associated with mucin production induced by HNE. NCI-H292, a human lung mucoepidermoid carcinoma cell line, was treated with or without HNE and L-carbocisteine. MUC5AC mRNA expression and ROS production in the cells, and MUC5AC protein concentration in supernatants were measured. HNE increased MUC5AC mRNA expression and MUC5AC protein concentration in supernatants in the cells. L-Carbocisteine reduces HNE-induced mRNA expression and protein secretion of MUC5AC. L-Carbocisteine also reduced ROS production in the cells induced by HNE. Reduction of HNE-induced mucus secretion by L-carbocisteine in the pulmonary epithelial cells may partly relate to the reduction of ROS. (C) 2009 Elsevier B.V. All rights reserved.

Cisplatin and weekly docetaxel with concurrent thoracic radiotherapy for locally advanced stage III non-small-cell lung cancer
Author:Masaru Nakamura; Tomonobu Koizumi; Munehara Hayasaka; Masanori Yasuo; Kenji Tsushima; Keishi Kubo; Kotaro Gomi; Naoto Shikama
Abstract:Purpose Our objective was to assess the effcacy and toxicity of concurrent chemoradiotherapy with cisplatin + weekly divided-dose docetaxel in patients with stage III non-small-cell lung cancer (NSCLC). Methods A total of 34 patients aged less than 75 years old with locally advanced stage III NSCLC were enrolled. The patients received intravenous infusions of cisplatin (80 mg/m(2); day 1) and docetaxel (20 mg/m2; days 1, 8, 15), followed by a week's drug-free interval. Standard concurrent thoracic radiotherapy was given for 6 weeks (2 Gy per fraction; total dose, 60 Gy). Results Over Grade 3 neutropenia, esophagitis and pulmonary toxicities were observed in 23.5, 17.6 and 11.8% of the cases, respectively. One complete response and 20 partial responses were obtained, with an objective response rate of 61.8%. The median survival time was 26.4 months (95% CI 16.9-not reached) and the 1-and 3-year survival rates were 76.5 and 41.2%, respectively. Conclusion Cisplatin + weekly docetaxel with concurrent radiotherapy is a feasible and effective regimen for locally advanced NSCLC.

Genetic Heterogeneity of EGFR Mutation in Pleomorphic Carcinoma of the Lung: Response to Gefitinib and Clinical Outcome
Author:Atsuhito Ushiki; Tomonobu Koizumi; Nobumitsu Kobayashi; Shintarou Kanda; Masanori Yasuo; Hiroshi Yamamoto; Keishi Kubo; Daiju Aoyagi; Jun Nakayama
Abstract:Somatic epidermal growth factor receptor (EGFR) mutations in exons 19 and 21 have been found in non-small cell lung cancer (NSCLC) and are associated with the therapeutic response to gefitinib in patients with advanced NSCLC. We report a case of pleomorphic carcinoma of the lung with different EGFR mutations. Prior to gefitinib treatment, an exon 19 deletion of EGFR mutation was positive in the specimens obtained from pleural effusion and left cervical lymph node, histologically proven to be adenocarcinoma. However, the response to gefitinib was poor and the patient died of progressive disease 4 months after the initiation of gefitinib therapy. Postmortem examination revealed the major histological component to be of the sarcomatoid or pleomorphic type with scant mixed adenocarcinoma, resulting in a histological diagnosis of pleomorphic carcinoma of the lung. Although the adenocarcinomatous tissue was still positive for exon 19 deletion of EGFR mutation alone, sarcomatous components had both the exons 19 deletion and 20 T790M mutation concomitantly, thought to be a gefitinib resistance mutation. Pulmonary pleomorphic carcinoma is a rare NSCLC composed of biphasic and heterogeneous malignant cell populations. The present case suggested that expression of different EGFR mutations is related to the biphasic histological appearance in pulmonary pleomorphic carcinoma.

Airway hyper-responsiveness in young adults with asthma that remitted either during or before adolescence
RESPIROLOGY,14(2):217-223 2009(Mar.)
Author:Yoshimichi Komatsu; Keisaku Fujimoto; Masanori Yasuo; Kazuhisa Urushihata; Masayuki Hanaoka; Tomonobu Koizumi; Keishi Kubo
Abstract:More than 50% of patients with childhood asthma enter clinical remission by puberty, although 40-50% of these people will probably develop asthma symptoms during early adulthood. The mechanism of relapsing asthma in early adulthood remains unclear. This study determined the characteristics of young adults whose asthma remitted either during or before adolescence. A comparative study was performed on 24 students whose childhood asthma had gone into clinical remission by puberty (remission group), 25 atopic students with no history of asthma (atopy group) and 19 non-atopic students without allergic diseases (control group). Examinations included spirometry, levels of serum-specific IgE-antibodies, airway responsiveness to methacholine, exhaled nitric oxide (eNO) and evidence of airway inflammation in induced sputum. Airway responsiveness (P < 0.01), eosinophil counts in sputum (P < 0.05) and the prevalence of sensitization to Dermatophagoides forinae (P < 0.01) were significantly higher, and FEF(25-75%) and FEF(75%) (P < 0.01) were significantly lower in the remission group than in the atopy and control groups. Furthermore, 50% and 33% of the remission group had airway hyper-responsiveness (AHR) and sputum eosinophilia, respectively. The eNO levels in the remission (P < 0.01) and atopy (P < 0.05) groups were significantly higher than in controls. Remission group members with AHR had a significantly longer period of childhood asthma, a shorter period of remission and greater airway eosinophilic inflammation than those without AHR (P < 0.05). One half of young adults with childhood asthma that remitted either during or before adolescence continued to have evidence of AHR and airway eosinophilic inflammation, and might be at risk of future relapse.

Airway inflammation in employees involved in cultivating Japanese mushrooms (bunashimeji)
RESPIROLOGY,13(4):546-552 2008(Jun.)
Author:Kenji Tsushima; Masanori Yasuo; Tsuyoshi Tanabe; Sumiko Yoshikawa; Yoshitaka Yamazaki; Keishi Kubo
Abstract:Background and objective: Chronic inhalation of spores may cause respiratory symptoms such as productive cough and sputum. The purpose of this study was to determine the clinical pathophysiology of airway inflammation caused by bunashimeji spores and to investigate whether the spores have direct toxic inflammatory effects. Methods: Sensitized employees with respiratory symptoms and a stimulation index (SI) > 200%, and non-sensitized employees with a SI < 200% were enrolled. They underwent sputum induction and chest high-resolution computed tomography (HRCT). The in vitro effect of bunashimeji spore solutions on normal human bronchial epithelial (NHBE) cell cultures was investigated using the air-liquid interface method. Bunashimeji spore solution was added at 10(4) or 10(6) spores per 20 mu L/well. The interleukin (IL)-8 and epithelial neutrophil-activating peptide-78 (ENA-78) concentrations in the medium and IL-8 mRNA expression of NHBE cells were assessed after each stimulation. Results: Sensitized employees were divided into 14 with normal HRCT and 9 with abnormal HRCT. Fifteen of the sensitized group and five of the non-sensitized group had a productive cough and sputum. The neutrophil counts in induced sputum were significantly higher in subjects with abnormal HRCT than in those with normal HRCT. IL-8 and ENA-78 concentrations following stimulation with 10(4) and 10(6) spores were significantly increased compared with PBS only on day 9. IL-8 mRNA expression due to spore stimulation was significantly increased compared with control. IL-8 mRNA expression with 10(6) spore stimulation was significantly increased on days 6 and 12 compared with 10(4) spores. Conclusion: The inhalation of spores directly produces toxic inflammatory effects in the airways, independent of the degree of sensitization.

Characterization of laminin isoforms in human amnion
TISSUE & CELL,40(2):75-81 2008(Apr.)
Author:Seiji Takashima; Masanori Yasuo; Noriko Sanzen; Kiyotoshi Sekiguchi; Motonori Okabe; Toshiko Yoshida; Ayaka Toda; Toshio Nikaido
Abstract:Epithelial cells of the human amnion have been reported to possess similar functions to many types of cells, such as hepatocytes, neurons, and pancreatic P-cells. We reported previously that one of the hepatocyte-like functions of human amniotic epithelial cells was reinforced by the presence of basement membrane components. Laminin is one of the main components of the basement membrane; it critically contributes to cell differentiation. Laminin has several heterotrimer isoforms composed of an alpha, a beta-, and a gamma-chain, and each type of chain has several types of subunit chains: alpha 1-5, alpha 1-3, and gamma 1-3. In this study, we characterized the laminin subunit chains in human amnion. Laminin is produced and secreted from adjacent epithelial cells, and therefore, the gene expression of laminin subunit chains in human amniotic epithelial cells was investigated by RT-PCR. Their localization was examined by immunohistochemical staining of frozen sections. The findings suggested that the basement membrane of the human amnion contains a broad spectrum of laminin isoforms, laminin-2, -4, -5, -6, -7, - 10, -11. These findings will provide clues not only for understanding the physiological roles of the amnion and hAECs, but also for applying this tissue as a source of donor cells for cell transplantation therapy. (C) 2007 Published by Elsevier Ltd.

孤立性肺腫瘤陰影を呈しCA19-9が高値を示した 非結核性抗酸菌症の1例
信州医学雑誌,56(6):365-370 2008
Author:中川 佐和子, 吾妻 俊彦, 横山 俊樹, 牛木 淳人, 田名部 毅, 安尾 将法, 山本 洋, 花岡 正幸, 小泉 知展, 藤本 圭作, 久保 惠嗣, 椎名 隆之, 近藤 竜一, 吉田 和夫, 浅野 功治, 山崎 善隆

Mediastinal Seminoma in a Patient with Multiple Endocrine Neoplasia Type 1
INTERNAL MEDICINE,47(18):1615-1619 2008
Author:Tsuyoshi Tanabe; Masanori Yasuo; Kenji Tsushima; Kazuhisa Urushihata; Hiroshi Yamamoto; Masayuki Hanaoka; Tomonobu Koizumi; Keisaku Fujimoto; Yoshitaka Yamazaki; Yoshiki Hirose; Hideaki Hamano; Akihiro Sakurai; Keishi Kubo
Abstract:A patient with multiple endocrine neoplasia type 1 (MEN1) developed a mediastinal seminoma. The patient was a 46-year-old man who presented with respiratory symptoms. A diagnosis of mediastinal seminoma was pathologically confirmed and a complete remission was achieved by chemotherapy. During his hospital stay, hyperparathyroidism and multiple pancreatic tumors associated with hypergastrinemia were found. A diagnosis of MEN1 was made genetically. Although patients with MEN1 manifest a variety of neoplastic disorders, no cases of concurrent seminoma and MEN1 have previously been reported. In addition, no etiological relationship between seminoma and MEN1 has yet been reported.

A Rare Case of a Tracheal Fibroepithelial Polyp Treated by an Endobronchial Resection
INTERNAL MEDICINE,47(19):1723-1726 2008
Author:Atsuhito Ushiki; Masanori Yasuo; Tsuyoshi Tanabe; Kazuhisa Urushihata; Hiroshi Yamamoto; Masayuki Hanaoka; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo; Yoshitaka Yamazaki; Koji Asano
Abstract:This report describes a very rare case of a tracheal fibroepithelial polyp. A 69-year-old male had been treated in this department because of chronic obstructive pulmonary disease since 2006. In July 2007, chest computed tomography revealed a bronchial tumor located at the distal end of the trachea. A bronchoscopic examination revealed a multilocular polyp. An endobronchial resection was performed to remove the lesion. A tracheobronchial fibroepithelial polyp is very rare. We herein describe and discuss the appropriate therapeutic policy and also review the pertinent literature.

Progressive pulmonary calcification after successful renal transplantation
INTERNAL MEDICINE,47(3):161-164 2008
Author:Masanori Yasuo; Tsuyoshi Tanabe; Yoshimichi Komatsu; Kenji Tsushima; Keishi Kubo; Kyoko Takahashi; Satoshi Kawakami; Takayuki Honda
Abstract:In 2005, a 46-year-old woman consulted our department for an evaluation of a chest radiographic abnormality. She had undergone a successful living renal transplantation in 1999 after being treated by dialysis for four years. A chest computed tomographic scan revealed progressive bilateral fluffy, poorly defined small nodules and the bronchoscopic study revealed a unique linear and nodular lesion pattern. Based on the findings of these modalities, we confirmed the diagnosis of metaplastic pulmonary calcification. This is the first report of these bronchoscopic findings and submucosal calcification in a case of metastatic pulmonary calcification.

Primary tracheal adenoid cystic carcinoma with malignant pleural effusion (vol 47, pg 475, 2008)
INTERNAL MEDICINE,47(5):484-484 2008
Author:Masanori Yasuo; Michiko Ito; Yukihiro Kobayashi; Kenji Tsushima; Masayuki Hanaoka; Tomonobu Koizumi; Keishi Kubo

Primary tracheal adenoid cystic carcinoma with malignant pleural effusion
INTERNAL MEDICINE,47(5):475-475 2008
Author:Yasuo, Masanori; Ito, Michiko; Kobayashi, Yukihiro; Tsushima, Kenji; Hanaoka, Masayuki; Koizumi, Tomonobu; Kubo, Keishi

Pleomorphic Adenoma with an Endobronchial Resection
Author:Mikako Matsubara; Masanori Yasuo; Tsuyoshi Tanabe; Kenji Tsushima; Kazuhisa Urushihata; Hiroshi Yamamoto; Masayuki Hanaoka; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo; Yoshitaka Yamazaki; Takeshi Uehara
Abstract:A case of bronchial pleomorphic adenoma is herein presented. The patient came to the hospital for a detailed examination of a bronchial polyp that was detected by computed tomography. Chest computed tomography revealed a bronchial tumor which was located at the distal end of the left main bronchus. The patient refused surgical resection. An electrosurgical snare was performed two times and the patient received several rounds of argon plasma coagulation with a flexible bronchoscope. The diagnosis of a pleomorphic adenoma was made following examination of the resected specimens. No recurrence has been observed by biopsy at the resected site.

Hypersensitivity pneumonitis caused by Penkillium citrinum, not Enoki spores
Author:Sumiko Yoshikawa; Kenji Tsushima; Masanori Yasuo; Keisaku Fujimoto; Keishi Kubo; Toshiko Kumagai; Yoshitaka Yamazaki
Abstract:Background Flammulina velutipes is called the Enoki mushroom in Japanese and is cultivated indoors. Mushroom workers face occupational exposure to a tremendous number of fungi and organic antigens capable of causing hypersensitivity pneumonitis (HP). One worker employed at an Enoki farm developed HP due to Penicillium citrinum. This study investigated new cases of HP among the workers cultivating Enoki. Methods Serum Krebs von der Lungen-6 (KL-6), surfactant protein (SP)-A and SP-D were measured. Lymphocyte stimulation tests (LST) and double immunodiffusion tests (DIT) were performed to identify P citrinum. Workers showing high levels of KL-6, SP-A, or SP-D and a high LST value or positive DIT were identified and then were further examined by chest computed tomography, bronchoalveolar lavage and transbronchial lung biopsy. The initial patient and new HP patients were defined as the HP group and the other participants were defined as the non-HP group. Results Forty-eight Enoki workers participated in the study. Four of nine workers who met the criteria for further examinations were diagnosed as having HP due to R citrinum. In comparison between non-HP group and HP group, KL-6, SP-D and LST values were significantly higher in HP group. There was a strong correlation between KL-6 and SP-D. DIT had high sensitivity and high specificity. Conclusions KL-6, SP-D, LST, and DIT were useful for detecting HP patients. KL-6 was the most useful predictor of HP in this study. DIT was useful not only as a predictor of HP but also as a detector of the causative antigen. Am. J. Ind. Med. 50:1010-1017, 2007. (c) 2007 Wiley-Liss, Inc.

Inflammatory lesions of the lung, submandibular gland, bile duct and prostate in a patient with IgG4-associated multifocal systemic fibrosclerosis
RESPIROLOGY,12(3):455-457 2007(May)
Author:Ghullam Hamed; Kenji Tsushima; Masanori Yasuo; Keishi Kubo; Seiichi Yamazaki; Shigeyuki Kawa; Hideaki Hamano; Hiroshi Yamamoto
Abstract:Multifocal systemic fibrosclerosis (MSF) is a multisystem disease, which often mimics malignancy. A 70-year-old asymptornatic man with lesions in the lung, prostate, submandibular glands and bile ducts appeared to have malignancy. Biopsy of a lung nodule showed IgG4-positive plasma cell infiltration and the serum IgG4 was elevated. A diagnosis of MSF was made and the patient treated with oral prednisolone at I mg/kg/day. Sclerosing cholangitis, retroperitoneal fibrosis, Riedel's thyroiditis, fibrotic pseudotumor of the orbit and fibrosis of the salivary glands have all been reported to be part of this disease. It is now necessary for MSF to be considered in patients with pulmonary lesions mimicking lung cancer.

Effects of PMX-DHP treatment for patients with directly induced acute respiratory distress syndrome
Author:Kenji Tsushima; Keishi Kubo; Sumiko Yoshikawa; Tomonobu Koizumi; Masanori Yasuo; Shino Furuya; Kazuhiko Hora
Abstract:Endotoxin-removal direct hemoperfusion column containing polymyxin B immobilized fibers (PMX-DHP) is an effective procedure for the treatment of sepsis-induced acute respiratory distress syndrome (ARDS). We investigated retrospectively the effects and appropriate timing of PMX-DHP induction for directly induced ARDS in 38 patients. PMX-DHP was carried out twice for two hours. Blood pressure, heart rate (HR) and PaO2/FIO2 (PF) ratio, leukocytes, platelets, endotoxin, inflammatory cytokines and clusters of differentiated peripheral neutrophils and monocytes were measured before and after PMX-DHP. Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Sequential Organ Failure Assessment (SOFA) scores and lung injury scores (LIS) were determined at the time of starting PMX-DHP. The underlying causes of ARDS were pneumonia in 29 patients and aspiration pneumonia in 9 patients. The patients were divided into Survivors (n = 21) and Nonsurvivors (n = 17). Mortality was 45% at 30 days after PMX-DHP. The APACHE II and SOFA scores and the LIS were not significantly different between the two groups. The time from the onset of ARDS to the start of PMX-DHP was significantly delayed between the two groups. PMX-DHP significantly improved the PIT ratio, HR and systolic blood pressure in the Survivors compared to the Nonsurvivors. The function of active monocytes in the peripheral blood was significantly suppressed after PMX-DHP. Ibis early induction of PMX-DHP is indicated for directly induced ARDS. In the Nonsurvivors, this delay could have led to undesirable responses to oxygenation and circulation after PMX-DHP.

Effects of bronchodilators on dynamic hyperinflation following hyperventilation in patients with COPD
RESPIROLOGY,12(1):93-99 2007(Jan.)
Author:Keisaku Fujimoto; Fumiaki Yoshiike; Masanori Yasuo; Yoshiaki Kitaguchi; Kazuhisa Urushihata; Keishi Kubo; Takayuki Honda
Abstract:Background and objective: The present study was performed to examine the occurrence of dynamic hyperinflation following hyperventilation in COPD patients and former smokers without COPD, and the efficacy of short-acting anticholinergic agents (SAAC) and beta(2)-agonists (SABA) for lung hyperinflation following metronome-paced hyperventilation in COPD. Methods: Fifty-nine patients with COPD, 20 ex-smokers without COPD and 20 healthy subjects who had never smoked were examined for dynamic hyperinflation by metronome-paced hyperventilation with respiratory rate increasing from 20 to 30 and 40 tidal breaths/min. Dynamic hyperinflation was evaluated as the decrease in inspiratory capacity (IC) following hyperventilation, and the effects of SAAC and SABA on dynamic hyperinflation were assessed. Results: COPD patients showed a significant increase in end-expiratory lung volume and a decrease in IC following hyperventilation, and ex-smokers without COPD also showed mild but significant dynamic hyperinflation. Multiple stepwise linear regression analysis revealed that the carbon monoxide transfer coefficient (DLco/V-A) and RV/TLC were significant and independent determinants of dynamic hyperinflation in COPD. Treatment with SAAC and SABA significantly increased IC at each respiratory rate, independently of the increases in FEV1. Furthermore, SABA significantly inhibited the decrease in IC due to hyperventilation. Conclusions: These findings suggest that lung hyperinflation following hyperventilation may be a useful method for detecting dynamic hyperinflation observed not only in patients with COPD but also in ex-smokers without COPD, and both SAAC and SABA are effective in reducing dynamic hyperinflation in COPD.

Second-line chemotherapy of platinum compound plus CPT-11 following ADOC chemotherapy in advanced thymic carcinoma: Analysis of seven cases
ANTICANCER RESEARCH,27(4C):3005-3008 2007
Author:Kanda, Shintaro; Koizumi, Tomonobu; Komatsu, Yoshimichi; Yoshikawa, Sumiko; Okada, Mitsuyo; Hatayama, Orie; Yasuo, Masanori; Tsushima, Kenji; Urushihata, Kazuhisa; Kubo, Keishi; Sasabayashi, Mari; Takamizawa, Akemi

Small-cell lung carcinoma produces salivary-type amylase: A case report with review
INTERNAL MEDICINE,46(12):883-887 2007
Author:Seiichi Yamazaki; Shoichiro Ebisawa; Masanori Yasuo; Kazuhisa Urushihata; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo
Abstract:A 53-year-old woman diagnosed with small-cell lung carcinoma (SCLC) was referred to our hospital because of general malaise and inappetence. Serum amylase levels were drastically elevated at 13,920 IU/ l, with the salivary type dominating. She suffered multiple liver metastases and presented with disseminated intravascular coagulation (DIC). She succumbed to progressive malaise one month after admission. The amylase level was increased to 18,630 IU/ l just before her death. Necropsy of the right supraclavicular lymph node confirmed SCLC with partial necrosis. Immunohistological analysis revealed that the SCLC produced salivary-type amylase. A rare case of salivary-type amylase-producing SCLC with a futile outcome was reported with review of the previous literature.

Adult langerhans cell histiocytosis with independently relapsing lung and liver lesions that was successfully treated with etoposide
INTERNAL MEDICINE,46(15):1231-1235 2007
Author:Satoshi Konno; Nubuyuki Hizawa; Tomoko Betsuyaku; Masanori Yasuo; Hiroshi Yamamoto; Tomonobu Koizumi; Masaharu Nishimura
Abstract:A 35-year-old man initially presented with cough and fever. Computed tomography (CT) revealed diffuse small cysts in the lung, and multiple nodules in the liver. Lung and liver biopsies revealed that pathology was consistent with Langerhans cell histiocytosis. Lung shadows increased despite cessation of smoking, whereas the liver involvement improved. After initiating treatment with prednisolone, the chest CT findings improved. However, the liver nodules started to increase while tapering prednisolone. Intravenous etoposide was started, and the liver nodules decreased markedly. The difference in the clinical course between the lung and liver lesions might have been the result of differences in the clonality of these two organs.

Successful endoscopic dilatation to alleviate airway suffocation in a case with esophageal cancer after stent implantation
INTERNAL MEDICINE,46(20):1745-1748 2007
Author:Masanori Yasuo; Shino Furuya; Shintaro Kanda; Yoshimichi Komatsu; Tsuyoshi Tanabe; Kenji Tsushima; Hiroshi Yamamoto; Tomonobu Koizumi; Keishi Kubo; Shuichi Yokosawa; Yoshitaka Yamazaki; Satoshi Kawakami
Abstract:A case of esophageal cancer who suffered from tracheal stenosis at the tracheostomy after stent implantation is presented. The patient received a covered metallic tracheal stent to seal the esophago-respiratory fistulation. After six months, the tracheal retainer for his tracheostomy was difficult to insert into his trachea due to the growth of the cancer. Argon plasma coagulation (APC) has been successfully employed in the dilatation of tracheal stenosis at the tracheostomy. We herein describe the use of APC as an effective treatment for further palliative therapy of tracheal dilatation in order to treat tracheal stenosis by esophageal cancer after stent implantation.

Unilateral absence of the pulmonary artery incidentally found after an episode of hemoptysis
INTERNAL MEDICINE,46(21):1805-1808 2007
Author:Yoshimichi Komatsu; Masayuki Hanaoka; Michiko Ito; Masanori Yasuo; Kazuhisa Urushihata; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo
Abstract:A 29-year-old woman was admitted to our hospital because of hemoptysis and dyspnea. A chest radiographic study revealed an enlargement of the right lung hilum, and the left pulmonary artery could not be clearly visualized on contrast-enhanced CT scan. Both perfusion scintigraphy and pulmonary angiography confirmed the absence of the left pulmonary artery, and agenesis of the right upper pulmonary artery. Her clinical status has been stable for the previous two years of follow-up, even though she required long-term oxygen therapy. This is a rare case of a young woman with the unilateral absence of the left pulmonary artery incidentally found after an episode of hemoptysis.

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji)
Author:Kenji Tsushima; Shino Furuya; Sumiko Yoshikawa; Masanori Yasuo; Yoshitaka Yamazaki; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo
Abstract:Background Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. Methods Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. Results Complete avoidance resulted in a significant decrease in LST There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. Conclusions Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

Comparison of the clinical efficacy of salmeterol and sustained-release tulobuterol (patch) on inadequately controlled asthma patients on inhaled corticosteroids
JOURNAL OF ASTHMA,43(7):501-507 2006(Sep.)
Author:Keisaku Fujimoto; Yoshimichi Komatsu; Masanori Yasuo; Kazuhisa Urushihata; Keishi Kubo
Abstract:Patients with inadequately controlled asthma on inhaled corticosteroid (400 to 1,600 mu g/day chlorofluorocarbon beclomethasone equivalent) were treated with concomitant salmeterol (n = 18) or sustained- release tulobuterol (patch) (n = 18), or the inhaled corticosteroid dose was doubled (add-on) (n = 13) to compare clinical efficacy. (1) At 8 weeks, morning and evening peak expiratory flow rates were significantly improved in the salmeterol group only (p < 0.01). (2) Symptom and sleeplessness scores improved in the order, salmeterol (symptom score; p < 0.0001), inhaled corticosteroid add-on, and tulobuterol groups. (3) Only the salmeterol group showed significant improvement in the total Asthma Quality of Life Questionnaire score (p < 0.05). (4) No adverse reactions considered related to the study drugs were observed.

Endobronchial argon plasma coagulation for the management of post-intubation tracheal stenosis
RESPIROLOGY,11(5):659-662 2006(Sep.)
Author:Masanori Yasuo; Tsuyoshi Tanabe; Kenji Tsushima; Masaru Nakamura; Shintaro Kanda; Yoshimichi Komatsu; Seiichi Yamazaki; Michiko Ito; Shino Furuya; Sumiko Yoshikawa; Keishi Kubo; Satoshi Kawakami; Yoshitaka Yamazaki
Abstract:Post-intubation tracheal stenosis is usually caused by pressure necrosis at the cuff. Despite the fact that this phenomenon is well known and both large volume and low pressure cuffs have been developed, this lesion nevertheless continues to occur. Although the best results for tracheal reconstruction are obtained by an experienced surgeon, not all patients are able to undergo this operation for either medical or personal reasons. Argon plasma coagulation (APC) using flexible bronchoscopy has been successfully employed in the treatment of post-intubation tracheal stenosis in two of the surgery-refused and inoperable patients. The patients immediately experienced a relief of symptoms after APC. APC was thus performed 3-4 times every 1-2 weeks for each patient. In addition, there were no complications related to this procedure. The number of published clinical reports describing APC in benign airway stenosis are increasing. APC has also been reported to have several advantages over other interventional endobronchial techniques in the management of tracheobronchial stenosis. We report two patients, and to our knowledge this is the first description of APC being used in the treatment of endobronchial dilatation for post-intubation tracheal stenosis.

Clinical differences in the Global Initiative for chronic obstructive lung disease Stage 0
RESPIRATORY MEDICINE,100(8):1360-1367 2006(Aug.)
Author:Kenji Tsushima; Shusuke Sone; Sumiko Yoshikawa; Shino Furuya; Masanori Yasuo; Toshirou Suzuki; Yoshitaka Yamazaki; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo
Abstract:This study was to examine the clinical differences between Stage 0 and normal subjects, using low-dose chest computed tomography (CT) and pulmonary function tests. Enrolled subjects performed as a health check for lung cancer screening including low-dose CT and pulmonary function tests. Subjects were divided into Stage 0, chronic obstructive pulmonary disease according to pulmonary function tests, and normal subjects. The severity of emphysema (visual score) was calculated on three tow-dose CT slices. Low-dose CT and pulmonary function tests were performed in 1359 men and 888 women. The numbers and percentages of men and women smokers were 1076 (79.2%), and 107 (12.0%), respectively. A total of 722 individuals had one or more respiratory symptoms, such as cough (69.8%), sputum (75.8%), or shortness of breathing (0.83%). Of the 722 subjects, 71 (9.8%) individuals satisfied the criteria of chronic respiratory symptoms. Among the normal subjects, smoking caused differences in airflow Limitation as a result of pulmonary function tests. The proportion of smokers and the visual score were significantly higher in Stage 0 than those in the normal subjects. The percentages of the maximal mid-expiratory flow (%MMF) and of the peak expiratory flow rate were significantly tower in Stage 0 than in the normal subjects. %MMF and the proportion of visual score were significantly tower in the smoking Stage 0 than in the nonsmoking Stage 0 subjects. Smoking would indicate early signs of emphysematous change between Stage 0 and normal subjects in comparison of pulmonary function tests and visual score of Low-dose CT (c) 2005 Elsevier Ltd. ALL rights reserved.

Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant thymic carcinoma - Three cases
ANTICANCER RESEARCH,26(6C):4851-4855 2006
Author:Komatsu, Yoshimichi; Koizumi, Tomonobu; Tanabe, Tsuyoshi; Hatayama, Orie; Yasuo, Masanori; Okada, Mitsuyo; Yamamoto, Hiroshi; Kubo, Keishi; Sasabayashi, Mari; Tsunoda, Toshiyuki

Usefulness of preoperative endobronchial ultrasound for airway invasion around the trachea: Esophageal cancer and thyroid cancer
RESPIRATION,73(5):651-657 2006
Author:Toshihide Wakamatsu; Kenji Tsushima; Masanori Yasuo; Yoshitaka Yamazaki; Sumiko Yoshikawa; Naohiko Koide; Minoru Fujimori; Tomonobu Koizumi
Abstract:Background: It is important to confirm preoperative tracheobronchial invasion to enable the selection of the most appropriate treatment. Objective: This study was performed to compare the usefulness of computed tomography (CT), magnetic resonance image (MRI) and bronchoscopy by endobronchial ultrasonography (EBUS) for the assessment of invasion of thyroid or esophageal cancer in cases with suspected tracheobronchial invasion. Methods: In cases with suspected contact between the tumor and tracheobronchial wall, CT, MRI and EBUS indicated deformity of the tracheobronchial wall due to the adjacent mass. The final diagnosis was based on surgical and histological results, and/or clinical follow-up. Results: Fifty-four patients were included in this study. Based on the findings of CT, MRI and EBUS, invasion was suspected in 29, 28 and 25 patients, respectively. Seventeen patients did not undergo surgery based on the results of CT, MRI and bronchoscopy with EBUS. Final diagnosis was intact trachea or bronchial adventitia in 26 patients and invasion in 28 patients. The sensitivity and specificity of CT, MRI and EBUS for invasion were 59 and 56, 75 and 73, and 92 and 83%, respectively. The accuracy of EBUS was significantly greater than that of CT in the present study (p = 0.0011). The accuracy of EBUS was significantly different from that of CT and MRI in the surgically treated patients (p = 0.005 and p = 0.032, respectively). Conclusion: EBUS is the most useful technique for determining the depth and extent of tumor invasion into the airway wall. The combination of MRI and EBUS will contribute to surgical planning in patients with esophageal and thyroid cancer. Copyright (C) 2006 S. Karger AG, Basel.

Angiosarcoma with sacral origin metastasizing to the lung
INTERNAL MEDICINE,45(15):923-926 2006
Author:Masaru Nakamura; Kenji Tsushima; Masanori Yasuo; Yoshitaka Yamazaki; Takayuki Honda; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo
Abstract:A 73-year-old man with fever, lumbago and hemosputum showed ground-glass opacity around multiple lung nodules on chest computed tomography. Examination of the man revealed anemia. Specimens obtained by video-assisted thoracic surgery revealed angiosarcoma, but the primary site of angiosarcoma could not be detected before autopsy. Angiosarcoma is a rare malignant neoplasm with rapid proliferation and they can arise at any region of the body. It can originate in the skin, soft tissue, liver or heart. Their multicentric and local recurrence easily leads us to misdiagnosis, and we have struggled to reach diagnosis and its origin. Angiosarcoma should be included in the different diagnosis of diffuse pulmonary hemorrhage with multiple lung nodules.

Laryngo-tracheo-bronchial amyloidosis presenting severe airway stenosis
INTERNAL MEDICINE,45(17):1121-1022 2006
Author:Seiichi Yamazaki; Shintaro Kanda; Masanori Yasuo; Kazuhisa Urushihata; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo; Shu-ichi Ikeda

IgG4-associated multifocal systemic fibrosis complicating sclerosing sialadenitis, hypophysitis, and retroperitoneal fibrosis, but lacking pancreatic involvement
INTERNAL MEDICINE,45(21):1243-1247 2006
Author:Tsuyoshi Tanabe; Kenji Tsushima; Masanori Yasuo; Kazuhisa Urushihata; Masayuki Hanaoka; Tomonobu Koizumi; Keisaku Fujimoto; Keishi Kubo; Takeshi Uehara; Satoshi Shigematsu; Hideaki Hamano; Shigeyuki Kawa
Abstract:A 71-year-old man was admitted with malaise, mild fever, anorexia, body weight loss, lower back pain, thirst, and polydipsia. He showed bilateral swelling of the submandibular glands. Examinations showed panhypopituitarism and a high serum IgG4 concentration. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed uptake in the pituitary gland, bilateral submandibular gland, bilateral hilar and mediastinal lymph nodes, and a mass consistent with retroperitoneal fibrosis, but not in the pancreas. Biopsy specimens from the submandibular gland and retroperitoneal mass indicated sialadenitis and retroperitoneal fibrosis respectively, and showed severe fibrosis and inflammation with marked lymphoplasmacytic infiltration and IgG4-positive plasma cell infiltration. Hormone replacement therapy with hydrocortisone resulted in marked clinical improvement. Systemic involvement found in this patient possibly corresponded to the new concept of IgG4-associated multifocal systemic fibrosis.

Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells
RESPIRATION,73(3):347-359 2006
Author:Masanori Yasuo; Keisaku Fujimoto; Tsuyoshi Tanabe; Hironobu Yaegashi; Kenji Tsushima; Keiichirou Takasuna; Takeshi Koike; Mutsuo Yamaya; Toshio Nikaido
Abstract:Background: Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. Objectives: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). Methods: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. Results: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor alpha(1) (IL-13R alpha(1)), and an antibody to IL-13R alpha(1) also reduced the number of PAS-positive cells after exposure to IL-13. Conclusions: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic. Copyright (C) 2006 S. Karger AG, Basel.

Successful treatment with corticosteroid in a case of Behcet's syndrome with multiple esophageal ulcerations
INTERNAL MEDICINE,42(8):696-699 2003(Aug.)
Author:M Yasuo; H Miyabayashi; T Okano; H Aoki; K Ichikawa; Y Hirose
Abstract:A 59-year-old woman was diagnosed with incomplete type Behcet's syndrome in 1994. The patient was hospitalized with pharyngitis and fever in August 2000, and was treated using non-steroidal anti-inflammatory drugs (NSAIDs). Symptoms improved and she was discharged. After only 3 weeks, she reported swallowing disturbance due to retrosternal pain. Esophagoscopy revealed multiple shallow oval ulcerations in the middle esophagus. Colonoscopy revealed aphthous lesions in the rectum. Prednisolone (0.5 mg/kg) was initiated for treatment of esophageal involvement. Symptoms gradually improved and subsequent esophagoscopy revealed complete healing of esophageal ulcerations.

Pulmonary embolism due to right ventricular thrombus in a case of Behcet's disease
Author:M Yasuo; S Nagano; Y Yazaki; T Koizumi; H Kitabayashi; H Imamura; J Amano; M Isobe
Abstract:Right ventricular thrombus is a very rare manifestation of cardiovascular Behcet's disease. A 25-year-old man was admitted to hospital due to cough and fever of unknown origin. He experienced repetitive pulmonary embolism due to a right ventricular thrombus, which was surgically removed. A diagnosis of Behcet's disease was made based on his clinical course and the histological findings of the right ventricular wall and the skin lesion. He was quickly relieved of his symptoms after warfarinization and cyclosporine therapy.

第243回日本呼吸器学会関東地方会 2021(Feb. 13)
Presenter:篠崎有矢,生山裕一,矢崎達也,清水智子,和田洋典,北口良晃,立石一成,牛木淳人, 安尾将法,漆畑一寿,山本 洋,花岡正幸.

Potential utility of serum C-C chemokine ligand 1 (CCL1) in Sarcoidosis: A comparison to IgG4-related disease.
ATS2020 2020(May)
Presenter:Masamichi Komatsu, Hiroshi Yamamoto, Kei Sonehara, Ryosuke Machida, Takashi Ichiyama, Atsuhito Ushiki, Masanori Yasuo, Satoshi Kawakami, Masayuki Hanaoka.

The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients
ATS2020 2020(May)
Presenter:Takumi Kinjo, Yoshiaki Kitaguchi, Yunden Droma, Masanori Yasuo, Yosuke Wada, Fumika Ueno, Masao Ota, Masayuki Hanaoka.

内視鏡的インターベンションを要した 食道気管・気管支瘻の3例

2019(Jul. 04)
Presenter:小松 雅宙、安尾 将法、曽根原 圭、小沢 陽子 小坂 充、市山 崇史、山本 洋、花岡 正幸

気管狭窄と 主気管支狭窄における 呼吸インピーダンス、 呼吸機能の比較
2019(Jul. 04)
Presenter:所弥生 安尾将法 北口良晃 和田洋典 小坂充 金城匠 立石一成 漆畑一寿 牛木淳人 山本洋 花岡正幸

Presenter:雲登卓瑪 金城匠 小林信光 太田正穂 安尾将法 花岡正幸

気管狭窄と主気管支狭窄における呼吸 インピーダンス、呼吸機能の比較
Presenter:安尾 将法, 北口 良晃, 和田 洋典, 小坂 充,金城 匠, 立石 一成, 漆畑 一寿, 牛木 淳人, 山本 洋, 花岡 正幸

免疫療法が施行された非小細胞肺癌症例の予後および治療効果予測における 免疫関連有害事象の役割に関する後方視的な検討
Presenter:曽根原圭,立石一成,荒木太亮,小松雅宙,生山裕一,町田良亮,牛木淳人, 安尾将法,山本 洋,花岡正幸.

Presenter:北口良晃,後藤憲彦,金城 匠,上野史香,和田洋典,安尾将法,花岡正幸.

Presenter:赤羽順平,牛木淳人,生山裕一,立石一成,安尾将法,山本 洋,花岡正幸.

Presenter:後藤憲彦,和田洋典,北口良晃,安尾将法,立石一成,漆畑一寿,牛木淳人, 山本 洋,小林信光,小坂 充,松尾明美,蜂谷 勤,山崎善隆,出浦 弦, 森田正重,澤木章二,稲葉敏郎,高濱充貴,花岡正幸

Presenter:野沢修平,漆畑一寿,町田良亮,生山裕一,和田洋典,北口良晃,立石一成, 牛木淳人,安尾将法,山本 洋,花岡正幸

Presenter:北口良晃,中村優志,金城 匠,安尾将法,和田洋典,上野史香,後藤憲彦, 福島喜代康,花岡正幸.

Presenter:小松雅宙,山本 洋,金城 匠,和田洋典,市山崇史,北口良晃,漆畑一寿, 牛木淳人,安尾将法,花岡正幸

SU5416によって誘発された肺高血圧症を伴う肺気腫の若いラットにおける切断された カスパーゼ-3の活性化

信州医学雑誌,61:387-396 2013

信州医学雑誌,60:211-213 2012

臨床と研究,88(12):1545-1550 2011

Research Grants
Cooperative research with industry
2007 - 2008 , ヒト正常気道上皮細胞を用いた慢性気道炎症モデルにおけるカルボシステインの効果検討
2005 - 2006 , ヒト正常気道上皮細胞を用いた慢性気道炎症モデルにおけるカルボシステインの効果検討

Grants‐in‐aid for Scientific Research(Research Representative)
2012 - 2014 , mTOR関連細胞生存シグナルの制御による慢性閉塞性肺疾患発症およびその機序の解明