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유철규 ( Chul Gyu Yoo ) 대한내과학회 2009 대한내과학회지 Vol.77 No.4
Chronic obstructive pulmonary disease (COPD) is a slowly progressed disease characterized by chronic irreversible airway obstruction with increased airway resistance and loss of elastic recoil by lung parenchymal destruction. COPD is a leading cause of morbidity and mortality worldwide. COPD is defined as a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Pathological changes characteristic of COPD are found in the proximal airways, peripheral airways, lung parenchyma, and pulmonary vasculature, showing chronic inflammation, and structural changes resulting from repeated injury and repair mostly caused by inhaled cigarette smoke. This pathological changes lead to airway trapping and progressive airway limitation. (Korean J Med 77:383-400, 2009)
내독소에 의한 돼지의 급성 폐손상에서 Cyclooxygenase 대사물의 역할에 관한 연구
유철규 ( Chul Gyu Yoo ),정기호 ( Ki Ho Jeong ),최형석 ( Hyung Seok Choi ),이혁표 ( Hyuk Pyo Lee ),김영환 ( Young Whan Kim ),한성구 ( Sung Koo Han ),심영수 ( Young Soo Shim ),김건열 ( Keun Youl Kim ),한용철 ( Yong Chol Han ) 대한결핵 및 호흡기학회 1992 Tuberculosis and Respiratory Diseases Vol.39 No.1
유철규(Chul Gyu Yoo),이상도(Sang Do Lee),권오정(O Jung Kwon),이춘택(Choon Taek Lee),한성구(Sung Koo Han),심영수(Young Soo Shim),김건열(Keun Youl Kim),한용철(Yong Chol Han) 대한내과학회 1989 대한내과학회지 Vol.37 No.4
N/A The presence of measurable reversibility in airflow obstruction gives us information about the diagnosis, plan of treatment, and prognosis. Many investigators have studied the physiologic responses of normal, bronchitic, and asthmatic subjects to inhaled bronchodilator drugs. Nevertheless, there is stil considerable debate as to which parameter of the pulmonary function test is optimal for assessing bronchodilation, To evaluate the role of airway resistance in the assessment of the reversibility of airway obstruction, the response to inhaled fenoterol was measured in 39 patients with obstructive airway disease. Spirometry and body plethysmography were performed before and 10minutes after inhalation of fenoterol. A clinically significant improvement after bronchodilator inhalation was defined as an improvement of greater than 15% of initial FVC or FEV1.25% of FEF25-75%, 30% of SRaw, or 50% of SGaw. The results were as follows: 1) The largest percent change of the initial value was by SGaw criteria (60.33%), followed by SRaw (33,63%), MEF50 (22,51%), FEF 5-75g (21.62%), FEUI (13,83%), PEFR (13,81%.), FVC (8.60%), and FEVI/FVC criteria (5.70%) in the order of amount of change. 2) The greatest positive response rate was by SRaw or SGaw criteria (61.5%), followed by FEV1 (46.2%), FEF25-75% (41.0%), B11d FVC (15.4%) criteria. 3) There was a significant improvement in SRaw but not in FEV1 on 12 occasion (30.8%), an improvement in FEV1 but not in SRaw on 6 occasions (15.4%), and an improvement in SRaw or FEV1 on 30 occasions (76.9%). From the above findngs, it is concluded that SRaw is a more sensitive indicator for the assessment of reversibility of airflow obstruction than FEU1. The combination of FEVl and SRaw identifies more cases of reversible airflow obstruction.
표면부착에 의한 사람 폐포대식세포의 유전자 발현에 관한 연구
정만표,유철규,한성구,심영수,이종헌,한용철,김영환,Chung, Man Pyo,Yoo, Chul Gyu,Han, Sung Koo,Shim, Young-Soo,Rhee, Chong H.,Han, Yang Chol,Kim, Young Whan 대한결핵및호흡기학회 1996 Tuberculosis and Respiratory Diseases Vol.43 No.6
연구배경: 식세포인 호중구나 단핵세포는 생체 외실험에 사용하기 위한 세포분리법인 플라스틱 표면부착만으로도 세포활성화가 일어나 이후의 실험결과에 영향을 주고 이 과정에 염증반응과 관련된 물질의 유전자 전사 및 부착분자가 연관되어 있는 것으로 알려져 있다. 폐의 주된 면역세포인 폐포대식세포도 대부분 플라스틱 표면부착에 의해 세포를 분리하므로 사람의 폐포대식세포가 표면부착 자체에 의해 활성화되고 여기에 염증관련 유전자 및 부착분자가 관여하는지를 알아보기 위해 연구를 시행하였다. 방법: 적어도 한 쪽 폐가 정상인 사람에서 기관지폐포세척술을 통해 얻은 폐포대식세포를 대상으로 표면부착이 미치는 영향을 얄아보기 위해 부유상태와 부착상태에서 각각 시간에 따른 lL-8, SOD 및 CD11/CD18 mRNA 발현을 Northern blot analysis로 분석하였고 PMA와 fMLP로 추가 자극했을 경우 차이를 보이는지 알아 보았다. 결과: 1) 플라스틱 표면에 부착시킨 폐포대식세포는 염증 또는 면역에 관계되는 IL-8 mRNA 및 SOD mRNA의 발현이 부착시간 정과에 따라 증가하여 부착 8시간후에 최대로 나타났으나 CD18 mRNA 발현은 부착에 의해 증가되지 않았다. 2) 이런 mRNA의 증가는 PMA에 의해서는 부착여부와 관계없이 유도되었지만 fMLP에 의해서는 부착된 세포에서만 유도되었다. 결론: 이상의 결과로 플라스틱 표면부착에 의해 폐포대식세포에서 염증매개성 물질의 유전자발현이 증가되며 이는 표면부착에 의한 세포 활성화와 관계가 있을 것으로 생각된다. Background: Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. Adhesion molecules and gene transcription of the inflammatory mediators are known to be associated in this process. To evaluate whether adhesion molecule and transcriptional activation of the inflammatory substances are also involved in the activation of human alveolar macrophage by the adherence procedure, we designed this experiment. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be nonnal by chest cr and alveolar macrophage was harvested. To measure the expression of Interleukin-8(IL-8) mRNA, manganese superoxide dismutase(SOD) mRNA and CD11/CD18 mRNA in human alveolar macrophage of both adherence state and suspension state, Northern blot analysis was done at 0, 2, 4, 8 and 24hrs after the adherence to plastic surface and during suspension state. Then, phorbol myristate acetate(pMA) and N-formyl-methionyl-leucyl-phenylalanine(fMLP) were added respectively in the same experimental condition. Result : 1) Human alveolar macrophages in the adherent state induced IL-8 mRNA and SOD mRNA expression which was maximal at 8 hours after the adherence to plastic surface. But we could not observe the upregulation of CD18 mRNA by surface adherence. 2) PMA induced these mRNA expression both in the adherent cell and the nonadherem cells, but the induction of mRNA expression by fMLP occurred only in the adherent cells. Conclusion: These results suggest that adherence of huamn alveolar macropahge is an important cell-activating event that may play a critical role in the modulation of lung inflammatory respones.
Retroviral vector를 이용한 종양괴사인자 (TNF-$\alpha$) 유전자 이입 암세포에서 종양괴사인자 수용체의 발현
이혁표,유철규,김영환,심영수,한성구,Lee, Hyuk-Pyo,Yoo, Chul-Gyu,Kim, Young-Whan,Shim, Young-Soo,Han, Sung-Koo 대한결핵및호흡기학회 1997 Tuberculosis and Respiratory Diseases Vol.44 No.6
연구배경 : 종양괴사인자(tumor necrosis factor ; TNF)는 다양한 생물학적 기능을 가지고 있는 바, 그 중 생체 외에서 증명된 뚜렷한 항암 효과로 말미암아 최근 항암 유전자요법의 중요한 대상으로 관심을 모으고 있다. 현재 유전자 이입의 기술적 문제로 생체 외에서 암세포에 유전자 이입을 시행한 후 이를 다시 환자의 생체내로 이식하는 방법이 연구의 주종을 이루고 있다. 그러나 저자들의 과거의 연구를 포함한 여러 연구에서 TNF가 이입된 암세포는 TNF에 대해 내성을 보이는 것으로 증명되었고 이에는 새로이 방어 단백질을 합성하는 것이 관여할 것이라는 시사가 있었다. 이 획득내성의 기전을 밝히는 것이 종양생물학의 이해를 넓히고 보다 효과적인 항암 유전자요법을 개발하기위한 매우 중요한 과제로 생각된다. Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF-resistance in TNF-$\alpha$ cDNA transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate whether the levels of TNF receptor mRNA expression and soluble TNF receptor release from cancer cells are changed after TNF-$\alpha$ cDNA transfection. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, EUSA, MTT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and evaluated the TNF receptor mRNA expression with Northern blot analysis and soluble TNF receptor release with EUSA. Results : The TNF receptor mRNA expressions of parental cells and genetically modified cells were not significantly different. The soluble TNF receptor levels of media from genetically modified cells were lower than those from parental cells. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the TNF receptor and the soluble TNF receptor expression.