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Molecular Analysis of Fibrosing Processes in the Lungs

Research Project

Project/Area Number 12670552
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTokyo Medical & Dental University

Principal Investigator

YOSHIZAWA Yasuyuki  Tokyo Medical & Dental University, 大学院・医歯学総合研究科, 教授 (20174914)

Co-Investigator(Kenkyū-buntansha) INASE Naohiko  Tokyo Medical & Dental University, 医学部・附属病院, 講師 (60262185)
MIYZKE Shuji  Tokyo Medical & Dental University, 保健管理センター, 助教授 (50239365)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordschronic hypersensitivity pneumonitis / recurrent / insidious / idiopathic pulmonary fibrosis / antigen-induced lymphocyte proliferation / specific antibody / HRCT / honeycomb / genetic background / Interleukin 10 / 免疫グロブリンサブクラス / IL-2RmRNA / 吸入誘発試験 / リンパ球幼弱化試験 / 合成ペプタイド
Research Abstract

Our manuscript claiming that chronic hypersensitivity pneumonitis should be subgrouped into two types, one subgroup of patients develops interstitial pulmonary fibrosis after recurrent acute episodes (recurrent) and the other group of patients has no history of acute episodes that has a slowly progressive chronic respiratory disease (insidious) has been accepted in Am Asthma Allergy Immunology. The recurrent bird fancier's lung (BFL) patients tended to breed dozens of pigeons in a loft, specific antibodies against pigeon dropping extracts were positive in 87%, antigen-induced lymphocyte proliferation was positive in 93%, bronchoalveolar lavage fluids (BALF) showed lymphocytosis, and centrilobular micronodules were observed on chest high resolution computer tomography (HRCT) in 40%. Those findings are similar to those of acute BFL. In contrast, the insidious BFL patients were likely to be exposed to smaller sized birds kept indoors, clubbed fingers were observed in 53%, specific antibod … More ies against pigeon dropping extracts or budgerigar dropping extracts were positive in only 35% showing that the remaining 65% patients were negative. In contrast, antigen-induced lymphocyte proliferation was positive in 94%. BALF showed normal ranges or a slight increase of lymphocytes, HRCT displayed centrilobular micronodules in only 12% and honeycombing in 88%. Histopathological findings on surgically obtained specimens revealed UIP pattern in 8 cases out of 12 cases. All those clinico-pathological features were similar to IPF. The mechanisms involved in the progression of disease process leading to fibrosis after avoidance of direct antigen contacts are under investigation implicating that indirect exposure to birds and/or the persistence of antigen in the lung may be responsible for ensuing pulmonary fibrosis. Currently, the genetic background of the patients who are susceptible to developing pulmonary fibrosis are under investigation. Furthermore, we have explored the mechanisms involved in the initiation of acute HP as compared to protection from disease in asymptomatic counterparts with current exposure. Peripheral blood mononuclear cells from HP patients proliferated in the presence of the antigen and showed enhanced expression of mRNA of proinflammatory cytokines including IL-β and IL-6 as well as IL-2R. In contrast, normal volunteers with current exposure showed elevated levels of mRNA expression of IL-10 and IL-2R suggesting the presence of sensitized cells and protection from pathology as a result of enhanced production of IL-10. These results implicated that IL-10 is inhibitory for the onset of HP and is the key determinant as to whether the disease develops or not. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report

Research Products

(73 results)

All Other

All Publications (73 results)

  • [Publications] Yoshio Ohtani: "Acute Intermittent Porphyria Associated with Transient Elevation of Transaminases during an Acute Attack"Internal Medicine. 39. 45-49 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasunari Miyazaki: "Mucoid Impaction Caused by Monokaryotic Mycelium of Schizophyllum commune in Association with Bronchiectasis"Internal Medicine. 39. 160-162 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Min Kyi: "Acute effects of smoke exposure on the cellular and cytokine profile in isolated perfused lungs"Respiration Physiology. 123. 143-151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 吉澤靖之: "呼吸器疾患の分子病態と臨床"日本内科学会雑誌. 89. 1814-1817 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "Inhalation Provocation Tests in Chronic Bird Fancier's Lung"Chest. 118. 1382-1389 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 今野和典: "隣家の鳩飼育により発症した鳩飼病の1例"日本胸部臨床. 60. 78-83 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 三宅修司: "マウス抗Trichosporon asahiiモノクローナル抗体D-8を用いた抗原接合ELISA法による夏型渦敏性肺炎診断の有用性について"日本呼吸器学会雑誌. 39. 7-11 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuyuki Yoshizawa: "Recent advances in the pathogenesis of hypersensitivity pneumonitis"Recent Res Devel Allergy & Clin Immunol. 2. 105-117 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 坂下博之: "BOOPパターンおよびfibrotic NSIPパターンの画像、病理像を呈した慢性鳥飼病の1例"日本胸部臨床. 61. 1015-1021 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "Fatal outcome in Chronic Bird Fancier's Lung"Am J Med. 112. 588-590 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toshihiko Fukuoka: "The Effect of Seratrodast on Eosinophil Cationic Protein and Symptoms in Asthmatics"Journal of Asthma. 40. 257-264 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasujiro Matsunaga: "TA-19, a Novel Protein Antigen of Trichosporon asahii, in Summer-type Hypersensitivity Pneumonitis"Am J Respir Crit Care Med. 167(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuki Sumi: "Cytokine mRNA expression in isocyanate-induced hypersensitivity pneumonitis"Respiration. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "The Clinical Features of Chronic Bird Fancier's Lung"Ann Allergy, Asthma & Immunol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naohiko Inase: "Feather Duvet Lung"Case Rep Clin Prac Rev. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "Acute Intermittent Porphyria Associated with Transient Elevation of Transminases during an Acute Attack."Internal Medicine. 39. 45-49 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasunari Miyazaki: "Mucoid Impaction Caused by Monokaryotic Mycelium of Schizophyllum commune in Association with Bronchiectasis."Internal Medicine. 39. 160-162 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Min Kyi: "Acute effects of smoke exposure on the cellular and cytokine profile in isolated perfused lungs."Respiration Physiology. 123. 143-151 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "Inhalation Provocation Tests in Chronic Bird Fancier's Lung."Chest. 118. 1382-1389 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuyuki Yoshizawa: "Recent advances in the pathogenesis of hypersensitivity pneumonitis."Recent Res Devel Allergy & Clin Immunol. 2. 105-117 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "Fatal outcome in Chronic Bird Fancier's Lung."Am J Med. 112. 588-590 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toshihiko Fukuoka: "The Effect of Seratrodast on Eosinophil Cationic Protein and Symptoms in Asthmatics."Journal of Asthma. 40. 257-264 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasujiro Matsunaga: "TA-19, a Novel Protein Antiggen of Trichosporon asahii, in Summer-type Hypersensitivity Pneumonitis."Am J Respir Crit Care Med. 167(in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yuki Sumi: "Cytokine mRNA expression in isocyanate-induced hypersensitivity pneumonitis"Respiration. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yoshio Ohtani: "The Clinical Features of Chronic Bird Fancier's Lung."Ann Allergy, Asthma & Immunol. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naohiko Inase: "Feather Duvet Lung."Case Rep Clin Prac Rev. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasuyuki Yoshizawa: "Recent advances in the pathogenesis of hypersensitivity pneumonitis"Recent Res Devel Allergy & Clin Immunol. 2. 105-117 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 今井美和: "Busulfan lung3症例の臨床的検討"第64回間質性肺疾患研究会討議録. 73-79 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 三宅修司: "マウス抗Trichosporon asahiiモノクローナル抗体D-8を用いた抗原接合ELISA法による夏型過敏性肺炎診断の有用性について"日本呼吸器学会誌. 39(1). 7-11 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Naohiko Inase: "Calretinin Promoter for Suicide Gene Expression in Malignant Mesothelioma"Anticancer Research. 21. 1111-1114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Michiko Tanaka: "Neuiron Specific Enlolase Promoter for Suicide Gene Therapy in Small Cell Lung Carcinoma"Anticancer Research. 21. 291-294 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Emiko Morimoto: "Adenovirus-Mediated Suicide Gene Transfer to Small Cell Lung Carcinoma Using a Tumor-specific Promoter"Anticancer Research. 21. 329-332 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Michiko Tanaka: "Isolation of the Human Aquaporin 3 Promoter"J Biochem Mol Biol & Biophys. 5. 177-183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shuji Miyake: "Effect of cyclosporine A on rapidly progressive interstitial pneumonia in dermatomyositis"Sarcoidosis Vasc Diffuse Lung Dis. (accepted).

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshihide Fujie: "Effect of chest wall vibration on dyspnea during exercise in chronic obstructive pulmonary disease"Respir. Physiol.. (accepted).

    • Related Report
      2001 Annual Research Report
  • [Publications] Koichi Horita: Anticancer Research. (accepted).

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉澤靖之: "サイトカインとHP分子呼吸器病"3 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 海野剛: "今日の処方 肺性心"南江堂. 3 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉澤靖之: "喘息・アレルギー疾患の治療と看護"南江堂. 8 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉澤靖之: "内科《アレルギー疾患の治療ガイドライン》"南江堂. 5 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 稲瀬直彦: "医学のあゆみ COPDの画像診断-X線所見-"医歯薬出版. 4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉澤靖之: "THE LUNG perspectives呼吸器疾患における線溶系の役割"2 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉澤靖之: "過敏性肺炎 ガイドライン外来診療2001"日経メディカル開発. 7 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 稲瀬直彦: "呼吸器疾患 最新の治療2001-2003抗炎症・免疫抑制薬(マクロライドも含む)"南江堂. 4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 稲瀬直彦: "最新医学 特発性肺線維症における急性増悪と肺がん合併の病態学的意義と対応"最新医学社. 4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshio Ohtani: "Acute Intermittent Porphyria Associated with Transient Elevation of Transaminases during an Acute Attack"Internal Medicine. 39・1. 45-49 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Naohiko Inase: "Use of Gastrin-Releasing Peptide Promoter for Specific Expression of Thymidine Kinase Gene in Small-Cell Lung Carcinoma Cells"International Journal of Cancer. 85. 716-719 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nobuo Ishiwata: "Relationship Between Apoptosis and Immunohistochemical Staing for Proliferating Cell Nuclear Antiaen and Ki-67 in Non-small Cell Lung Cancer"Anticancer Research. 20. 1445-1450 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Junji Endo: "Deficiency of a STE20/PAK family kinase LOK leads to the acceleration of LFA-1 clustering and cell adhesion of activated lymphocytes"Federation of European Biochemical Societies. 468. 234-238 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasunari Miyazaki: "Mucoid Impaction Caused by Monokaryotic Mycelium of Schizophyllum commune in Association with Bronchiectasis"Internal Medicine. 39・2. 160-162 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoko Sakai: "Purification and characterization of the allergenic components of shimeji mushroom (Tricholoma conglobatum) spore for shimeji workers' hypersensitivity pneumonitis"Journal of Medical and Dental Sciences. 47・1. 67-75 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Susumu Isogai: "Interferon-γ increases IL-12 mRNA expression and attentuates allergic late-onset airway responses in the Brown Norway rat"European Respiratory Journal. 16. 22-29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "呼吸器疾患の分子病態と臨床 アレルギー性肺疾患"日本内科学会雑誌. 89・9. 1814-1817 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Min Kyi: "Acute effects of smoke exposure on the cellular and cytokine profile in isolated perfused lungs"Respiration Physiology. 123. 143-151 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshio Ohtani: "Inhalation Provocation Tests in Chronic Bird Fancier's Lung"Chest. 118. 1382-1389 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuto Jinn: "Primary Extramedullary Plasmacytoma of the Lung with Production of M-protein : a case report"肺癌. 40・7. 783-786 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 澤田めぐみ: "特発性間質性肺炎急性増悪に対するCyclosporin A,副腎皮質ステロイド併用療法の試み"1999年度びまん性肺疾患調査研究. 104-107 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 今野和典: "隣家の鳩飼育により発症した鳩飼病の1例"日本胸部臨床. 60・1. 78-83 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasuyuki Yoshizawa: "Immunological Lung Disease-Recent Advances in the Pathogenesis of Hypersensitivity Pneumonitis"Internal Medicine. 40・2. 164-167 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "総合臨床 放射線肺炎"永井書店. 1 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "総合臨床 好酸球性肺炎"永井書店. 2 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "内科 過敏性肺炎の診断基準・病型分類・重症度"南江堂. 5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "過敏性肺炎"日本医事新報. 4 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 三宅修司: "臨床と研究 PRSP(penicillin resistant strep tococcus pneumoniae)"4 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 稲瀬直彦: "治療薬 ステロイド薬"日本医学出版. 5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "CLINICIAN パルスオキシメーターについて"エーザイ. 2 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "アレルギー疾患の治療ガイドライン 過敏性肺炎"南江堂. 5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 稲瀬直彦: "医学のあゆみ COPDの画像診断 -X線所見-"医歯薬出版. 1 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "アレルギー疾患の治療ガイドライン 過敏性肺炎"南江堂. 5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 澤田めぐみ: "膠原病性肺疾患における自己抗体測定"中外医学社. 2 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 吉澤靖之: "外来でみる呼吸器感染症-治療と管理の実際-"中外医学社. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 澤田めぐみ: "肺線維症とケモカイン"医薬ジャーナル社. 10 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大谷義夫: "画像検査の適応と読影"メジカルビュー社. 12 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-03-31   Modified: 2016-04-21  

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