Project/Area Number |
60440045
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Research Category |
Grant-in-Aid for General Scientific Research (A)
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Allocation Type | Single-year Grants |
Research Field |
Respiratory organ internal medicine
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Research Institution | TOHOKU UNIVERSITY |
Principal Investigator |
TAKISHIMA Tamotsu professor and Chairman, The lst Department of Internal Medicine, Tohoku University School of Medicine., 医学部, 教授 (20004765)
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Co-Investigator(Kenkyū-buntansha) |
INOUE Hiroshi Associate professor, The lst Department of Internal Medicine, Tohoku University, 医学部附属病院, 講師 (40133962)
MUE Suetsugu professor The Colledge of Medical Technology, Tohoku University School of Medici, 医療技術短期大学, 教授 (40004882)
SASAKI Hidetada professor The Geniatric Department of Medicine, Tohoku University School of Medi, 医学部, 教授 (20004731)
井田 士朗 東北大学, 医学部附属病院, 助手 (00142943)
|
Project Period (FY) |
1985 – 1988
|
Project Status |
Completed (Fiscal Year 1988)
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Budget Amount *help |
¥17,900,000 (Direct Cost: ¥17,900,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1986: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1985: ¥10,000,000 (Direct Cost: ¥10,000,000)
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Keywords | TypeC influenza virus / Airway hyperresponsiveness / Late asthmatic response / Eosinophil / Superoxide / SOD / Ozone / 気道粘膜透過性 / 気管支喘息 / 慢制気管支炎 / 粘膜下腺 / 粘方分泌 / VIP / メサコリン / ヒスタミン / α受容体 / タンタルム / ブロンコグラム / 末梢気道 / 中枢気道 / Cー線維経末 / サブスタンスP / β受容体 / オートラジオグラフ / 気道温敏性 / 気道ウイルス感染 / 肥満細胞 / 好中球 / 好酸球 / メチラポン / PAF / 非即時型喘息反応 / 迷走神経 |
Research Abstract |
To elucidate the underlying mechanisms of bronchial hyperreactivity we have employed several sorts of animal models originally developed by us as well as normal subjects and patients with asthma and COPD. A summary of the results and conclusions which the research has attained to the present is as follows; 1) ype C influenza virus infection induced airway hyperresponsiveness in Beagle dogs, especially 1 to 3 weeks after the infection, when an increase in the number of ast cells and concentrations of histamine, TXB2 and PGF2alpha in BALF were observed. Histological study also revealed damage and desquamation of the epithelial cells of the airways, which may suggest dysfunction of the EDRF. 2) Ascaris suum antigen inhalation produced a higher incidence rate of LAR (late asthmatic response) in sensitized guinea pigs with silica as an adjuvant. At the LAR a distinct eosinophilic infiltration was observed in the mucosal tissue. The LAR can be blocked by administration of the selective and com
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petitive leukotriene blocker, ONO-1078. Airway hyperresponsiveness was also observed after the LAR, and was sustained for three to four day, which is possibly attributable to eosinophil infiltration. 3) Superoxide inhalation produced airway contraction and subsequent airway hyperresponsiveness in cats, which was blocked by the administration of SOD, a scavenger of superoxide. In another study SOD also attenuated the increase in airway responsiveness after ozone inhalation. The results indicate that superoxide is an important factor in the production of hyperresponsiveness in the airway. 4) After blocking sympathetic and parasympathetic nerves, inhalation of capsaicin or citric acid produced a dilatation of constricted airways in cats and human subjects, which was blocked by hexamethonium (C6), a ganglion blocker, The results indicate bronchial C-fiber receptors as well irritant receptors are also the receptors for the NAIS, which composes the reflex pathways. In addition, the stimulation of the NAIS also inhibited the immediate allergic reaction, revealing a protection against increase in lung resistance as well as histamine concentration. 5) Through the study of single submucosal glands taken from cat trachea the effects of the autonomic nerves, substance-P, and VIP on contraction and secretion were determined. We also found that a substance is produced by epithelial cells which inhibits the mucous secretion. Less
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