• Tuberculosis and Respiratory Diseases
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• v.67 no.1
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• pp.14-20
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• 2009

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-$\alpha$, MIP-2, IL-1$\beta$ and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-$\alpha$ and IL-1$\beta$ was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-$\alpha$ and IL-1$\beta$. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

• Tuberculosis and Respiratory Diseases
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• v.65 no.3
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• pp.191-197
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• 2008

Background: Due to the irreversible nature of chronic obstructive pulmonary disease (COPD), the treatment aim in patients with COPD is not to cure but to reduce the symptoms, increase lung function, and improve the quality of life. It has been suggested that depression is a common emotional disturbance in patients with COPD who are faced with a major physical impairment and embarrassing symptoms. This study evaluated the prevalence and risk factors of depression in patients with chronic obstructive pulmonary disease. Methods: A total of 59 patients with a registered diagnosis of chronic obstructive pulmonary disease were selected. Depression was assessed using the Centers for Epidemiologic Studies Depression (CES-D) scale. The quality of life was assessed using the Korean version of the St. George's Respiratory Questionnaire. Results: The prevalence of depression was 17.0%. In the correlation model, the interaction of the $FEV_1%$ over predicted value and SGRQ score(symptom, activity, impact, overall score) was statistically significant. The interaction of the $FEV_1%$ over predicted value and depression scale(CES-D) was also statistically significant. There was a positive correlation between the SGRQ scores(symptom, activity, impact, overall score) and the depression scale. Conclusion: The prevalence of depression in patients with chronic obstructive pulmonary disease is relatively high. The pulmonary function and the living standards were found to be significant risk factors for depression.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.35-42
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• 1993

Background: In order to establish the etiology of the pleural effusion, routine analysis of the fluid, bacteriologic studies, cytologic tests and pleural biopsies are currently being employed. However, even with the above mentioned tests, the exact causes cannot be determined in approximately 10-20% of cases. The purpose of our study is to determine the diagnostic value of measuring ADA activity and CEA simultaneously in various pleural fluids which their etiologies have confirmed Methods: We have studied 61 cases of tuberculous pleural effusions, 17 cases of suspected tuberculous pleural effusions, 17 cases of malignant pleural effusions, 22 cases of suspected malignant pleural effusions, and 7 cases of parapneumonic pleural effusions. We have measured the ADA activity and CEA level simultaneously in pleural fluid samples in each cases. Results: 1) The ADA activity in tuberculous pleural effusion was significantly higher than that in malignant effusion. 2) The CEA level in malignant pleural effusion was significantly higher than that in tuberculous effusion. 3) With the cut-off values of the pleural fluid ADA activity more than 40 U/L and the CEA level less than 12 ng/mL, the sensitivity was 86.9%, and the specificity was 100% in the diagnosis of tuberculous effusion. With the cut-off values of the pleural fluid CEA level more than 12 g/mL and the ADA activity less than 40 U/L, the sensitivity was 76.5%, and the specificity was 100% in the diagnosis of malignant effusion. Conclusion: It is suggested that the combined assay of pleural fluid ADA activity and CEA level is very useful in the differential diagnosis of tuberculous and malignant pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.142-148
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• 1995

Background: Despite modern diagnostic, staging, and therapeutic advances, esp. with molecular biologic techniques, the 5-year survival rate of all cases of lung cancer does not exceed 15%. Also, the incidence of lung cancer of both sex in Korea is increasing year by year and the lung cancer is one of the leading causes of cancer death. Therefore, it is strongly needed to develop the new combination of treatment modalities including neoadjuvant chemotherapy and to identify tumor specific characteristics with staging or prognostic markers. Here we present the clinical significance of several biologic tumor markers to use as a prognostic markers in patients with non-small cell lung cancers. Method: The survival has correlated with the expressibility of proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor(EGFR), p53 and/or blood group antigen A(BGAA) using immunohistochemistry in 46 patients with non-small cell lung cancers. Results: 1) The expression rates of PCNA, EGFR, p53 and BGAA were 80.6%, 61.3%, 45.9% and 64.3%, respectively and those were not correlated to cell types or clinical stges. 2) The expression of BGAA was correlated with better survival in median survival and in 2-year survival rate and that of PCNA was correlated with worse survival in median survival and 2-year survival rate. 3) The expression of EGFR or p53 was not valuable to predict prognosis in non-small cell lung cancers. 4) With simultaneous applications of PCNA, EGFR and p53 immunostain, the patients with 2 or more negative expressions showed better prognosis than the patients with 2 or more positive expressions. Conclusion: It is suggested that the expression of blood group antigen may be a positive prognostic factor and that of PCNA may be a negative prognostic factor. Also, the combination of expressions of PCNA, EGFR and p53 may be used as a negative prognostic factor.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.185-194
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• 1999

Background: NF-$\kappa$B is a characteristic transcriptional factor whose functional activity is determined by post-translational modification of protein and subsequent change of subcellular localization. The involvement of the NF-$\kappa$B family of the transcription factors in the control of such vital cellular functions as immune response, acute phase reaction, replication of certain viruses and development and differentiation of cells has been clearly documented in many previous studies. Several recent observations have suggested that the NF-$\kappa$B might also be involved in the carcinogenesis of some hematological and solid tumors. Investigating the possibility that members of the NF-$\kappa$B family participate in the molecular control of malignant cell transformation could provide invaluable information on both molecular pathogenesis and cancer-related gene therapy. Method: To determine the expression patterns and functional roles of NF-$\kappa$B family transcription factors in human lung cancer cell lines NCI-H792, NCI-H709, NCI-H226 and NCI-H157 were analysed by western blot, using their respective antibodies. The nuclear and the cytoplasmic fraction of protein extract of these cell lines were subsequently obtained and NF-$\kappa$B expression in each fraction was again determined by western blot analysis. The type of NF-$\kappa$B complex present in the cells was determined by immunoprecipitation. To detect the binding ability of cell-line nuclear extracts to the KB consensus oligonucleotide, electrophoretic mobility shift assay(EMSA) was performed. Results: In the cultured human lung cancer cell lines tested, transcription factors of the NF-$\kappa$B family, namely the p50 and p65 subunit were expressed and localized in the nuclear fraction of the cellular extract by western blot analysis and immunocytochemistry. Immunoprecipitation assay showed that in the cell, the p50 and p65 subunits made NF-$\kappa$B complex. Finally it was shown by Electrophoretic Mobility Shift Assay(EMSA) that nuclear extracts of lung cancer cell lines are able to bind to NF-$\kappa$B consensus DNA sequences. Conclusion: These data suggest that in human lung cancer cell lines the NF-$\kappa$B p50/p65 complex might be activated. and strengthen the hypothesis that NF-$\kappa$B family transcription factors might be involved in the carcinogenesis of human lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.650-659
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• 1999

Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.195-203
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• 1999

Background: Telomerase enzyme activity is not detected in most normal cells, a phonomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumor, including lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage. Methods: Primary tumor specimens obtained by bronchoscopic biopsies from 33 patients were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplication Protocol(TRAP) assay. Results: Telomerase activity was detected in 23 of the 27 non-small-cell lung cancer and 5 of 6 small-cell lung cancer. A few primary tumors did not appear to have detectable telomerase activity. Positive associations were found between the telomerase-positive rate and tumor stage(p<0.05). Conclusion: High telomerase activity is detected frequently in primary lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.298-305
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• 2005

Background : Obstructive sleep apnea syndrome (OSAS) is believed to have multifactorial causes. The major risk factors for OSAS are obesity, narrowed upper airways, and abnormal cranial-facial structures. A genetic basis for OSAS has been also suggested by reports of families with many members affected. This study analyzed the HLA typing in patients with OSAS to determine the possible role of genetics in OSAS. Methods : Twenty-five Korean patients with OSAS (1 woman and 24 men; age range 30-66 years) were enrolled in this study. A diagnosis of OSAS was made using full-night polysomnography. The control group consisted of 200 healthy Korean people. Serologic typing of the HLA-A and B alleles was performed in all patients using a standard lymphocyte microcytotoxicity test. Analysis of the polymorphic second exons of the HLA-DRB1 gene was performed using a polymerase chain reaction-sequence specific oligonucleotide probe. Results : The allele frequency of HLA-A11 was significantly lower in patients with OSAS compared with the controls (p<0.05). The HLA-B allele frequencies in the patients and controls had a similar distribution. Analysis of the HLADRB1 gene polymorphisms showed an increased frequency of DRB1*09 in the OSA patients compared with the controls (p<0.05). When the analysis was performed after dividing the OSAS patients according to the severity of apnea, the allele frequency of HLA-DRB1*08 was significantly higher in the severe OSA patients (apnea index >45) than in the controls (p<0.05). Conclusion : This study revealed an association between OSAS and the HLA-A11 and DRB1*09 alleles as well as association between the disease severity and the HLA-DRB1*08 allele in Korean patients. These results suggest that genetics plays an important role in both the development and the disease severity of OSAS.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.97-102
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• 1994

Objectives : Since Mountain proposed the new staging system of non-small cell lung cancer in 1986, the indications for operation of NSCLC have been extended. However, operative mortality is from 3 to 6%. Therefore it is important to reduce unnecessary operation and to evaluate unresectability of tumor correctly, preoperatively. The purpose of this study is to find out the causes of unresectability in patients who were initially thought to be resectable preoperatively. Methods : By retrospective analysis, 64 patients out of 291 NSCLC patients who were undergone operation for curative resection in Seoul National University Hospital from Jan. of 1987 to Dec. of 1991, were found to be unresectable at operating room, were selected for this study. Out of 64 patients, 42 were evaluable. The analysis was focused on the change of pre- & post-operative staging and the causes of unresectability of tumors. Results : Among 42 patients with unresectable tumor who could be evaluated, preoperative CT finding showed resectable tumors in 55%(23 patients) and suspicious for unresectable tumors in 45%(19 patients). The causes of unresectability were technically unresectable T3 lesions in 7%(3 patients), T4 lesions in 62%(26 patients), N2 lesions in 17%(7 patients) and N3 lesions in 14%(6 patients). Conclusion : The major causes of unresectability of NSCLC were pulmonary artery invasions. It is suggested that careful evaluation of mediastinal structure, especially great vessels by additional imaging technique other than CT(like MRI) is indicated in selected NSCLC cases.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.397-404
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• 1994

Background: To decide the optimal antibiotics and application of chest tube, examination of pleural fluid is fundamental in the management of empyema. Some criteria for drainage of pleural fluid have been recommended but some controversies have been suggested. Recently, newer radiologic methods including ultrasound and computed tomography scanning, have been applied to the diagnosis and management of pleural effusions. We undertook a retrospective analysis of 30 patients with pleural effusion who had CT scans of the chest in order to apply the criteria of Light et al retrospectively to patients with loculation and to correlate the radiologic appearance of pleural effusions with pleural fluid chemistry. Method: We analyzed the records of 30 out of 147 patients with pleural effusion undergoing chest CT scans. Results: 1) Six of the pleural fluid cultures yielded gram negative organisms and three anaerobic bacterias and one Staphylococcus aureus and one non-hemolytic Streptococci. No organism was cultured in ninteen cases(63.0%). 2) The reasons for taking chest CT scans were to rule out malignancy or parenchymal lung disease(46.7%), poor response to antibiotics(40.0%), hard to aspirate pleural fluid(10.0%) and to decide the site for chest tube insertion(3.3%). 3) There was no significant correlations between ATS stages and loculation but there was a tendency to loculate in stage III. 4) There was a significant inverse relationship between the level of pH and loculation(p<0.05) but there appeared to be no relationship between pleural fluid, LDH, glucose, protein, loculation and pleural thickening. 5) In 12 out of 30, therapeutic measures were changed according to the chest CT scan findings. Conclusion: We were unable to identify any correlations between the plerual fluid chemistry, ATS stages and loculations except pH, and we suggest that tube thoracotomy should be individualized according to the clinical judgement and serial observation. All patients with empyema do not need a chest CT scan but a CT scan can provide determination of loculation, guiding and assessing therapy which should decrease morbidity and hospital stay.