Study of the elucidation of the vole of Hck in pathophysiolegy of COPD
| Project/Area Number |
17590801
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
YAMAGATA Toshiyuki Wakayama Medical University, School of Medicine, Assistant Professor (80285410)
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| Co-Investigator(Kenkyū-buntansha) |
ICHINOSE Masakazu Wakayama Medical University, School of Medicine, Professor (80223105)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Chronic obstructive pulmonary disease / Airway inflammation / Neutrophils / Integrin / Chemokine receptor / Hck |
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| Research Abstract |
Neutrophils are thought to play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). There are various molecules involved in migration and activation of neutrophils in airways. However, the intracellular signal transduction pathways, which cause infiltration and activation of neutrophils in airways, are still unclear. The aim of the present study was to investigate the various molecules expression including integrin, chemokine receptor (CXCR) and hematopoietic cell kinase (Hck) in peripheral blood neutrophils and to clarify their possible role in the pathophysiology of COPD.
The surface expression of integrin (CD-11b / CD-18), CXC receptor 1 and 2 (CXCR1, CXCR2) of circulating neutrophils from COPD patients and healthy subjects (HS) was measured by flow cytometry analysis. The protein level of Hck and phosphorylated-Hck (p-Hck) were measured by Western blotting.
Both CD-11b and CXCR1 expression were significantly higher in COPD patients than in HS. The expression of CD-11b and CXCR1 showed a significant negative correlation with the severity of airflow limitation. The Hck protein level was also significantly higher in COPD patients compared with HS. This increase in Hck protein also negatively correlated with the severity of airflow limitation. In addition, significant correlation was seen between the protein level of Hck and the surface expression of CD-11b or CXCR1. In contrast, the p-Hck protein levels showed no difference between COPD patients and HS.
The over expression of CD-11b and CXCR1 on circulating neutrophils may be associated with the development of airflow limitation in COPD. In addition, the expression of Hck protein in peripheral blood neutrophils might also play an important role in the development of COPD. These results suggest that integrin, CXCR or Hck might be novel biomarkers for COPD monitoring and the modulation of these molecules expression might be a promising therapeutic target in COPD.
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Report
(4 results)
Research Products
(152 results)
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[Journal Article] Comparison of bronchodilatory properties of transdermal and inhaled long-acting beta2-agonists2008
Author(s)
Yamagata T, Hirano T, Sugiura H, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M
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Journal Title
Pulm Pharm Ther 21
Pages: 160-165
Description
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[Journal Article] Improvement of pulmonary function and dyspnea by tiotropium in COPD patients using a transdermal β_2-agonist2007
Author(s)
Akamatsu K, Yamagata T, Takahashi T, Miura K, Maeda S, Yamagata Y, Ichikawa T, Yanagisawa S, Ueshima K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinosea, M
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Journal Title
Pulm Pharm Ther 20
Pages: 701-707
Description
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[Journal Article] Overexpression of CD-11b and CXCR1 on circulating neutrophils : its possible role in COPD2007
Author(s)
Yamagata T, Sugiura H, Yokoyama T, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata Y, Matsunaga K, Minakata Y, Ichinose M
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[Journal Article] The Infl uence of Free 3-Nitrotyrosine and Saliva on the Quantitative Analysis of Protein-Bound 3-Nitrotyrosine in Sputum2007
Author(s)
Ueshima K, Minakata Y, Sugiura H, Yanagisawa S, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Yamagata T, Ichinose M
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Journal Title
Analytical Chemistry Insights 1
Pages: 1-7
Description
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[Journal Article] Airway cytokine expression measured by means protein array in exhaled breath condensate : Correlation with physiologic properties in asthmatic patients2006
Author(s)
Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima T, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichnose, M
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Journal Title
J Allergy Clin Immunol 118
Pages: 84-90
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[Journal Article] Inhibition of reactive nitrogen species production in COPD airways : comparison of inhaled corticosteroid and oral theophylline2006
Author(s)
Hirano T, Yamagata T, Gohda M, Yamagata Y, Ichikawa T, Yanagisawa S, Ueshima K, Akamatsu K, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M
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[Presentation] Mini-symposium 5 Asthma management-Management of elderly asthma2007
Author(s)
Matsunaga K, Yanagisawa S, Ichikawa T, Akamatsu K, Koarai A, Hirano T, Sugiura H, Yamagata T, Minakata Y, Ichinose, M
Organizer
57th Annual Meeting of Japanese Society of Allergology
Place of Presentation
Yokohama
Year and Date
2007-11-01
Description
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[Presentation] Steroid responsiveness of inflammatory molecules in exhaled breath condensate : correlation with physiological properties in asthmatic patients2007
Author(s)
Matsunaga K, Ichikawa T, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Sugiura H, Yamagata T, Minakata Y, Ichinose, M
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ATS 2007 International Conference
Place of Presentation
San Francisco, USA
Year and Date
2007-05-20
Description
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[Presentation] Mini-symposium COPD 2-Relationship between Hck expression in peripheral neutrophils in COPD patients and pulmonary function2007
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Yanagisawa S, Yamagata T, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Sugiura H, Matsunaga K, Minakata Y, Ichinose, M
Organizer
47th Annual Meeting of The Japanese Respiratory Society
Place of Presentation
Tokyo
Year and Date
2007-05-12
Description
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[Presentation] Mini-symposium Influence of saliva on exhaled breath condensate analysis2007
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Ichikawa T, Matsunaga K, Minakata Y, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Sugiura H, Nakanishi M, Yamagata T, Ichinose, M
Organizer
47th Annual Meeting of The Japanese Respiratory Society
Place of Presentation
Tokyo
Year and Date
2007-05-11
Description
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[Presentation] English Mini-Symposium Bronchial Asthma 1. Steroid responsiveness of inflammatory molecules in exhaled breath condensate : correlation with physiological properties in asthmatic patients2007
Author(s)
Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Sugiura H, Yamagata T, Minakata Y, Ichinose, M
Organizer
47th Annual Meeting of The Japanese Respiratory Society
Place of Presentation
Tokyo
Year and Date
2007-05-10
Description
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[Presentation] Influence of saliva on exhaled breath condensate analysis2007
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Ichikawa T, Matsunaga K, Minakata Y, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Sugiura H, Yamagata T, Ichinose, M
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3rd Meeting of Respiratory Biomarkers
Place of Presentation
Tokyo
Year and Date
2007-03-03
Description
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[Presentation] Analysis of beta2-integrin and chemokine receptor expression in peripheral neutrophils in COPD patients2006
Author(s)
Yamagata T, Yanagisawa S, Yokoyama T, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
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15th PneumoForum
Place of Presentation
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Year and Date
2006-12-02
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[Presentation] Cytokine expression in exhaled breath condensate measured by protein array : correlation with physiological properties in asthmatic patients2006
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Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
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11th Congress of the Asian Pacific Society of Respirology
Place of Presentation
Kyoto
Year and Date
2006-11-21
Description
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[Presentation] Importance of assistance by caregivers in inhaled corticosteroid therapy for elderly patients with asthma2006
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11th Congress of the Asian Pacific Society of Respirology
Place of Presentation
Kyoto
Year and Date
2006-11-21
Description
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[Presentation] Elevated albumin concentration in epithelial lining fluid of COPD airways2006
Author(s)
Minakata Y, Nakanishi M, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Matsunaga K, Yamagata T, Ichinose, M
Organizer
11th Congress of the Asian Pacific Society of Respirology
Place of Presentation
Kyoto
Year and Date
2006-11-20
Description
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[Presentation] The influence of saliva on the quantitative analysis of protein-bound 3-nitrotyrosine in sputum2006
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Ueshima K, Yanagisawa S, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Yamagata T, Minakata Y, Ichinose, M
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11th Congress of the Asian Pacific Society of Respirology
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Kyoto
Year and Date
2006-11-20
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[Presentation] Upregulation of peripheral blood neutrophil function in COPD2006
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Yamagata T, Yokoyama T, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
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11th Congress of the Asian Pacific Society of Respirology
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Year and Date
2006-11-20
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[Presentation] Usefulness of aggressive lung function testing in outpatients of general practice2006
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Akamatsu K, Yamagata T, Tanaka H, Ueda H, Ichikawa T, Yanagisawa S, Ueshima K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
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11th Congress of the Asian Pacific Society of Respirology
Place of Presentation
Kyoto
Year and Date
2006-11-20
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[Presentation] Additive effects of tiotropium on lung function and dyspnea in COPD patients treated with transdermal β_2-agonist2006
Author(s)
Akamatsu K, Yamagata T, Takahashi T, Miura K, Maeda S, Yamagata Y, Ichikawa T, Yanagisawa S, Ueshima K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
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11th Congress of the Asian Pacific Society of Respirology
Place of Presentation
Kyoto
Year and Date
2006-11-20
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[Presentation] Reliability of analysis of exhaled breath condensate : influence of saliva contamination2006
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Ichikawa T, Matsunaga K, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
Organizer
11th Congress of the Asian Pacific Society of Respirology
Place of Presentation
Kyoto
Year and Date
2006-11-20
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[Presentation] Mini-symposium 3 Airway inflammation 1-Influence of saliva on exhaled breath condensate analysis2006
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Ichikawa T, Matsunaga K, Minakata Y, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Ichinose, M
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56th Annual Meeting of Japanese Society of Allergology
Place of Presentation
Tokyo
Year and Date
2006-11-02
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[Presentation] Mini-symposium 3 Airway inflammation 1-Relationship between cytokines expression in exhaled breath condensate and pulmonary function in asthma and COPD2006
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Nakanishi M, Matsunaga K, Ichikawa T, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Yamagata T, Minakata Y, Ichinose, M
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56th Annual Meeting of Japanese Society of Allergology
Place of Presentation
Tokyo
Year and Date
2006-11-02
Description
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[Presentation] The upregulation of CD-11b expression on circulating neutrophils by CXCL8 and the involvement of CXCR1 in COPD2006
Author(s)
Yamagata T, Yokoyama T, Yanagisawa S, Yamagata Y, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
Organizer
European Respiratory Society 16th Annual Congress
Place of Presentation
Munich, Germany
Year and Date
2006-09-05
Description
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[Presentation] Airway cytokine expression measured by protein array in exhaled breath condensate : correlation with physiological properties in asthmatic patients2006
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Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
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European Respiratory Society 16th Annual Congress
Place of Presentation
Munich, Germany
Year and Date
2006-09-04
Description
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[Presentation] Analysis of inflammatory mediators in exhaled breath condensate in asthma patients2006
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Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
Organizer
73rd Meeting of Obstructive Lung Diseases
Place of Presentation
Tokyo
Year and Date
2006-07-15
Description
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[Presentation] Mini-symposium Asthmal-Relationship between cytokines expression in exhaled breath condensate and pulmonary function in asthma2006
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Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
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18th Spring Meeting of Japanese Society of Allergology
Place of Presentation
Tokyo
Year and Date
2006-05-30
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[Presentation] The Enhanced Adherent Function of Peripheral Blood Neutrophils in COPD Is Associated with the Increaed Expression of CXCR12006
Author(s)
amagata T, Yokoyama T, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
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ATS 2006 International Conference
Place of Presentation
San Diego, USA
Year and Date
2006-05-23
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[Presentation] Cytokine Expression in Asthmatic Airways : A Possible Role in Airway Obstruction and Hyperresponsiveness2006
Author(s)
Matsuhaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
Organizer
ATS 2006 International Conference
Place of Presentation
San Diego, USA
Year and Date
2006-05-22
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[Presentation] Analysis of integrin and chemokine receptor expression in peripheral neutrophils in COPD patients2006
Author(s)
Yanagisawa S, Yamagata T, Yokoyama T, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose, M
Organizer
2nd Meeting of Respiratory Biomarkers
Place of Presentation
Tokyo
Year and Date
2006-03-18
Description
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[Presentation] Usefulness of aggressive lung function testing in outpatients of general practice2006
Author(s)
Akamatsu K, Tanaka H, Ueda H, Yanagisawa S, Ichikawa T, Ueshima K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Yamagata T, Ichinose, M
Organizer
72th Meeting of Obstructive Lung Diseases
Place of Presentation
Tokyo
Year and Date
2006-01-21
Description
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[Presentation] Inhibition of reactive nitrogen species production in COPD nirways : comparison between steroid and theophylline2005
Author(s)
Hirano T, Nakanishi M, Gohda M, Yamagata T, Fukui K, Ueshima K, Akamatsu K, Yamagata Y, Matsunaga K, Minakata Y, Ichinose, M
Organizer
European Respiratory Society 15th Annual Congress
Place of Presentation
Copenhagen, Denmark
Year and Date
2005-09-19
Description
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[Presentation] Plasma leakage is elevated in COPD airways2005
Author(s)
Minakata Y, Nakanishi M, Ueshima K, Akamatsu K, Hirano T, Matsunaga K, Yamagata T, Ichinose, M
Organizer
European Respiratory Society 15th Annual Congress
Place of Presentation
Copenhagen, Denmark
Year and Date
2005-09-19
Description
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[Presentation] Useful monitoring parameters for airway hyperresponsiveness2005
Author(s)
Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
Organizer
14th Airway club in Sendai
Place of Presentation
Sendai
Year and Date
2005-09-10
Description
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[Presentation] Microvascular hyperpermeability in COPD airways2005
Author(s)
Minakata Y, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Yamagata T, Ichinose, M
Organizer
14th Airway club in Sendaic
Place of Presentation
Sendai
Year and Date
2005-09-10
Description
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[Presentation] Effectiveness of assistance by caregivers for inhaled corticosteroid therapy in elderly patients with asthma2005
Author(s)
Matsunaga K, Ichikawa T, Yanagisawa S, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose, M
Organizer
21st Meeting of Aerosols in Medicine Inhaled
Place of Presentation
Tokyo
Year and Date
2005-07-09
Description
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[Presentation] Theophylline reduces nitrosative stress in COPD airways2005
Author(s)
Hirano T, Goda M, Fukui K, Yamagata T, Ueshima K, Nakanishi M, Yamagata Y, Matsunaga K, Minakata Y, Ichinose, M
Organizer
ATS 2005 International Conference
Place of Presentation
San Diego, USA
Year and Date
2005-05-22
Description
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