• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.403-414
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• 2003

Background : Proteasome inhibitors can promote either cell survival or programmed cell death, depending on both the specific type and proliferative status of the cell. However, it is not well known whether inhibition of proteasome activity is related to apoptosis in lung cancer cells. In addition, the exact mechanisms responsible for apoptosis induced by proteasome inhibition are not well understood. In the present study, we have examined the effect of proteasome inhibition on lung cancer cells and tried to test the mechanisms that may be associated with the apoptosis of these cells. Methods : We examined the effect of proteasome inhibition with MG132 or PS-341 on cell survival in A549 and NCI-H157 lung cancer cells using MTT assay, and analyzed the cleavage of PARP by Western blot analysis to find evidence of apoptosis. Next, we evaluated the activation of caspase 3 by Western blot analysis and the activity of JNK by immunocomplex kinase assay. We also examined the changes in anti-apoptotic pathways like ERK and cIAP1 by Western blot analysis after inhibition of proteasome function. Results : We demonstrated that MG132 reduced cell survival by inducing apoptosis in A549 and NCI-H157 cells. Proteasome inhibition with MG132 or PS-341 was associated with activation of caspase 3 and JNK, reduced expression of activated ERK, and downregulation of cIAP1. Conclusion : Apoptosis induced by proteasome inhibition may be associated with the activation of pro-apoptotic pathways like caspase 3 and JNK and the inactivation of anti-apoptotic pathways in lung cancer cells.

• Journal of agricultural medicine and community health
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• v.12 no.1
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• pp.36-53
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• 1987

It is utmostly important to establish the efficient fitable way of peoples' active participation in primary health care especially in the areas where the public or governmental service input for the basic health care is insufficient like as in rural areas of Korea. In light of above reason, this study focused mainly on the evaluation of roles and activities of village health workers (VHWs) who were selected from grass- root level of village people in order to derive further motivation for active participation. This is believed to be a sort of feedback mechanisms. Actually, the authors collected the activity reports of VHWs who had been devoting themselves in the primary health care services of Jeomdong Area, of Yeoju Gun one of Korea University Community Health Action Programmes and survey record on the VHWs activity from correspondent people. 1 hose data were analyzed through computer programmed package. The activities performed by VHWs were limited to the performance in 1985 for conveniance. The summarized results were as follows; 1) General characteristics of VHWs. Among a total of 28 VHWs in the area, about 39.3g of them have been replaced up to the date since the implementation in 1983, because of moving out, occupational employment and of others. The age of majority (75.0%) lied between the range of 30-50, and educational background of 67.9% belonged to category of primary school graduation, about 50% of them experienced to be or were also entiled "chief of women club" of corresponding villages. 2) Work-load of VHWs. Each VHW was assigned for tasks of health care for average 55 households of 248 persons. They shared approximately 6 days a month for the activity in average and it covered 17 cases of basic health care in a month. A half of the VHWs performed home visits irregularly without solidified schedule. 3) Work performance analysis. Informations collected through VHWs were compared with data from official vital registration at local administration center "Myon Office" in 1985. VHWs collected 100.8 of new born, 116.2 of death, 58.3 of move in and 74.8 of move out in comparison with 100.0 of official registration each. Pregnant women of 79.8% of mothers among the total pregnancy of 94 which were confirmed as normally delivered or aborted cases by all means afterwards had been detected by VHWs as being pregnant and all of them received some of antenatal cares by VHWs. All(100%) of delivered women were detected by VHWs through home visits and they were cared postnatally. Whereas, according to the records of birth registration, the places of delivery were clinic in 33.7%, and mother's home in 66.3%, VHWs reported them to be clinic in 48.9%, midwifery in 20.2%. It was cleared that most of misinformation was caused by uncautious filling of birth registration at notification. Among the total of 717 eligible women under age 44 years, family planning status of 92.6% was reported by VHWs confirming practice of control to be 70.8% of reported fertile women. 4) Attitude of VHW on the roles and functions. Although 92.0% of VHWs expressed VHWs to be worthwhile, only 52.0% of them had dignity and satisfaction in their activity and 44.0% of them had passive attitude of working saying they followed direction regardlessly. Concerning difficulties in performance as a VHW, 60.7% of them pointed out lacking of medical and health related knowledge by themselves. Still, 64.0% of them thought visiting unfamilier house to be awful and 40.0% complained forms of activity to be difficult and hard. It was also revealed that 56.6% confessed lack of interest on community health service itself. Most of VHWs needed more educational training especially on clinical fields such as cares of gynecological diseases, hypertension, diabetes, and other chronic diseaes of the aged. Regular on-the-job basic trainings were said to be needed twice a year.

• Clinical and Experimental Pediatrics
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• v.45 no.9
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• pp.1106-1113
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• 2002

Purpose : Nuclear ($factor-{\kappa}BNF-{\kappa}B$) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of $NF-{\kappa}B$ to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. Methods : To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer($N_2$ 92% and $O_2$ 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors $NF-{\kappa}B$, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the $NF-{\kappa}B$ in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block $NF-{\kappa}B$ translocation into nucleus. Results : The expression of $NF-{\kappa}B$, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the $NF-{\kappa}B$ translocation reduced those expressions of VEGF and IGF-I. Conclusion : These results suggest that $NF-{\kappa}B$ has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1134-1146
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• 1998

Background: The tumor suppressor gene p53 is one of the most frequently altered genes in human tumors, including those of the lung. There is now a compelling evidence that wild-type p53 can negatively influence cell growth by causing G1 arrest or by inducing apoptosis. The possibilities of using p53 for gene therapy are also gathering much interest. Material and Method: Our approach towards understanding p53 function would be to study the biological consequences of overexpression of wild-type p53 in normal and tumor cells by using adenovirus vectors capable of giving high levels of the p53 gene product in cells. We have used this vector containing wild-type p53 to infect tumor cells with different p53 status (null, mutant, or wild-type) to confirm that expression of p53 in null or mutant cell lines becomes possible by Adenovirus-p53 transduction, to examine the effects of high levels of p53 expression on the growth properties of tumor cells, to evaluate the role of apoptosis in p53-mediated biological effects, and to examine the effect of Adenovirus-p53 on the tumorigenicities of the lung cancer cell lines in vitro. Result: The results of our study showed that cells expressing endogenous mutant p53 and those devoid of p53 expression altogether were significantly more sensitive to Adenovirus-p53-mediated cytotoxicity compared to tumor cells expressing endogenous wild-type p53 and that overexpression of wild-type p53 induced programmed cell death. Also we knew that Adenovirus-p53 significantly reduced tumor colony formation of human non-small cell lung cancer cell lines, and decreased the growth of pre-formed colonies in vitro. Conclusion: These results suggest that adenovirus is an efficient vector for mediating transfer and expression of tumor suppressor genes in human non-small cell lung cancer cells and that the tumor cells null for p53 or expressing mutant p53 readily undergo apoptosis by Adenovirus-p53.