1993 Fiscal Year Final Research Report Summary
Studies on The Expression of Genes during Lung Development and Differentiation
| Project/Area Number |
02404040
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Hokkaido University |
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Principal Investigator |
YAMAGUCHI Etsuro Hokkaido University Hospital, Lecturer, 医学部・附属病院, 講師 (10201831)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Yoshikazu Hokkaido University, School of Medicine, Professor, 医学部, 教授 (10001877)
AKITA Hirotoshi Hokkaido University Hospital, Instructor, 医学部・附属病院, 助手 (70222528)
MUNAKATA Mitsuru Hokkaido University, School of Medicine, Lecturer, 医学部, 講師 (00209991)
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| Project Period (FY) |
1990 – 1993
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| Keywords | p53 Oncogene / PCR-SSCP / Lung Cancer / Idiopathic Interstitial Pneumonia / Collagen Vascular Disease / Silica / TNFalpha / GM-CSF |
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| Research Abstract |
We analyzed abnormalities of p53 gene of prifmary lung cancer tissues, using a immunohistochemical method and PCR-SSCP.Abnormal p53 genes were observed in a high frequency for squamous cell carcinoma and small cell carcinoma, and in a low frequency for adenocarcinoma. The frequency of the abnormalities was higher in smokers than in nonsmokers, suggesting p53 is the target gene in the development of lung cancer in smokers. The abnormalities were significantly associated with the poor prognosis in cure resection cases.
Collagen vascular diseases (CVD) have been thought to be involved in the etiology of idiopathic interstitial pneumonia (IIP). Silica particles were directly instilled into the trachea of 1pr/1pr mice which develop CVD spontaneously and +/+ mice as the control strain. Fibrosis was unexpectedly weaker in 1pr/1pr than +/+. We next examined fibrogenic effects of bleomycin and silica in ozone-sensitive C57/B16J mice and ozone-insensitive C3H/HeJ mice. Though fibrosis in the acute phase was strong in C57/B16J when bleomycin was injected, it was similar when silica was instilled, suggesting the fibrotic process induced by bleomycin is different from that induced by silica.
TNF alpha is a potent granulomatogenic cytokine released from monocyte-macrophage lineage cells. We studied the ability of LPS-stimulated alveolar macrophages to release TNFalpha, and found significantly increased production in sarcoid patients compared with healthy subjects. We also detected GM-CSF mRNA expressed by bronchoalveolar lavage cells in sarcoid patients by the sensitive RT-PCR method. Its expression was significantly associated with a protracted clinical course and the presence of extra-pulmonary lesions. These results further strengthened the important roles of the cytokine network in the formation and maintenance of sarcoid granulomas.
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