• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1353-1365
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• 1997

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 the role of MnSOD, an antioxidant enzyme, in the acquired resistance to TNF of TNF-$\alpha$ cDN A transfected cancer cells. 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, ELISA, MIT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and the changes of MnSOD mRNA expressions with Northern blot analysis. Results : The MnSOD mRNA expressions of parental cells and genetically modified cells of WEHI164 and ME180 cells(both are naturally TNF sensitive) were not significantly different The MnSOD mRNA expressions of genetically modified cells of NCI-H2058 and A549(both are naturally TNF resistant) were higher than those of the parental cells, while those of parental cells with exogenous TNF were also elevated. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the MnSOD expression, but the difference in natural TNF sensitivity of each cell may be associated with the level of the MnSOD expression.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1234-1244
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• 1997

Background : Nowadays drug resistant tuberculosis is making problems in the treatment of pulmonary tuberculosis and its number is increasing. Several reasons for this are considered including irregular medication, poor drug compliance and wrong regimens. But there are treatment failure cases in spite of regular medication with short-term standard regimens. We reviewed clinical data of 50 patients to find out possible causes of this. Method : Subject of this study was 50 patients who failed in the primary treatment of pulmonary tuberculosis in spite of regular medication with short-term standard regimens. All of them were under treatment with secondary regimens in National Masan Tuberculosis Hospital on Oct 1996. The patient's records were analyzed retrospectively and direct interviews with patients were done. Results : There were relatively more patients in the age of 20th. Male overwhelmed in number. There were smoking in 22 patients and drinking in 24 patients during medication. 17(34%) patients had family history of tuberculosis. Public health center was the most common site for the initial diagnosis among medical institutes. 42 patients had subjective symptoms for pulmonary tuberculosis. 38 patients got sufficient explanation from medical institute about tuberculosis and medication courses. 24 patients had bilateral lesions on chest X-ray film and 43 patients had cavitary lesions. 29 patients had past history for pulmonary tuberculosis with regular medication. The results of drug sensitivity test showed resistance in 41 patients of whom we could get the results. Conclusion : Main cause of treatment failure of pulmonary tuberculosis in spite of regular medication with short-term standard regimens was drug resistance. Several factors were considered to be related to high prevalence of drug resistance, including age of 20th, male, family history for tuberculosis, bilateral lesions or remaining cavitary lesion on chest X-ray film.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1263-1270
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• 1997

Background : Differentiation of malignity and benignity is crucial for management of solitary pulmonary nodule(SPN). Clinical parameters such as patient's age, nodule size, smoking history, doubling time, typical calcification in X-ray and CT findings have been reported as helpful in this purpose. However, in most cases, these parameters are not conclusive. Glucose metabolism is increased in cancer tissues including lung cancer tissues. After uptake of 2-[F-18]-fluoro-2-deoxy-D-glucose(FDG), the glucose analogue, by cancer cell, FDG is trapped in the cell without further metabolism after phosphorylation. Thus, hypermetabolic focus in FDG-positron emission tomography (PET) imaging suggest malignancy. We evaluated the diagnostic efficacy of FDG-PET imaging in distinguishing malignant and benign SPN. Methods : We evaluated 28 patients with SPN from Jan. 1995 to Jan. 1997. CT scan of chest and whole-body FDG-PET imaging were performed in all patients. Histologic diagnosis was confirmed by transthoracic fine needle aspiration and biopsy, bronchoscopic biopsy and open thoracotomy. Results : Of the 28 SPN's, 22 nodules were malignant and 6 nodules were benign. FDG-PET imaging diagnosed all malignant nodules correctly as positive, and diagnosed 4 of 6 benign nodules correctly as negative. One tuberculous granuloma and one aspergilloma showed hypennetabolic focus and were diagnosed falsely positve with FDG-PET imaging. In the diagnosis of SPN with FDG-PET, sensitivity and specificity were 100% and 66.7%, positive predictive value and negative predictive value were 92% and 100%. Conclusion : FDG-PET imaging is highly useful noninvasive diagnostic tool in distinguishing between malignant SPN and benign SPN.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1256-1262
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• 1997

Background : Leukocyte-endothelial adhesion molecules have been implicated in the pathogenesis of inflammatory disease. ICAM-1, VCAM-1 and E-selectin are cell surface adhesion molecule on vascular endothelial cells. They are up-regulated by inflammatory cytokines and regulate the adhesion and migration of leukocytes across the endothelium. Tuberculosis, a granulomatous disorder is an infection caused by Mycobacterium tuberculosis. The clinical manifestations of tuberculosis are dependent on the cellular immune response to tubercule bacilli. Circulating adhesion molecules are probably formed by cleavage and release into the circulation of the extracellular domain of the membrane bound form. The elevated levels of circulating adhesion molecules have been reported in numerous disease state. To evaluate their role as markers of disease activity in tuberculosis, we measured a sE-selectin, sVCAM-1 and sICAM-1 levels in the serum with severities of mild, moderate and far advanced pulmonary tuberculosis. Methods : The control and test groups were divided as follows. Group I : control(n=5), Group II : patients with mild pulmonary tuberculosis(n=12), Group III : pateints with moderate pulmonary tuberculosis(n=20), Group IV : patients with far advanced pulmonary tuberculosis(n=19). Serum sICAM-1, sVCAM-1 and sE-selectin were measured by ELISA kit Results : Serum soluble adhesion molecules are elevated in patients with pulmonary tuberculosis, Circulating ICAM-1 levels were significantly elevated in patients with moderate and far advanced pulmonary tuberculosis when compared with control group. When compared with control group, serum sVCAM-1 levels showed significant elevation in patients with mild, moderate and far advanced pulmonary tuberculosis. Serum sE-selectin levels were significantly elevated in patients with far advanced pulmonary tuberculosis when compared with control group. Conclusion : These results suggest that sICAM-1, sVCAM-1, and sE-selectin may be invloved in the pathogenesis of tuberculosis. And, particularly, sICAM-1 and sVCAM-1 may be useful markers of the disease activity.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1285-1295
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• 1997

Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.351-359
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• 1998

Background: The effects of exercise on pulmonary function are complex and have been the subject of many investigations. But, there has been disputes about the effect of exercise on spirometric parameters and there is no study about the effect of exercise on IOS(Impulse Oscillometry)parameters. IOS, a new method of pulmonary function test, is based on the relationship between the pressure and flow oscillation which is produced by applying sinusoidal pressure oscillation to the respiratory system via the mouth. Method: Fifty-nine young adults without respiratory symptoms were divided into three groups according to degree of exercise(hard exercise group: mean exercise time is over three hours per week at least for the last one month, light exercise group : between thirty minutes to three hours, nonexercise group : less than thirty minutes) and undertaken pulmonary function test(simple spirometry and IOS). Results: The effects of exercise on spirometric parameters; percentage of predictive value of forced vital capacity(FVC % pred) was higher in hard exercise group than nonexercise group(hard exercise group: $102.4{\pm}14.8$, nonexercise group: $93.7{\pm}9.9$, p=0.017), but there was no significant difference in percentage of predicted value of forced expiratory volume in one second(FEV 1 % pred) and percentage of predicted value of forced expiratory flow 50% (FEF 50% pred) between groups. The effects of exercise on IOS parameters: Reactance at 5Hz(X5) was significantly lower in hard exercise group than nonexercise group(hard exercise group: $-0.166{\pm}0.123hPa/1/s$, nonexercise group: $-0.093{\pm}0.036hPa/1/s$, p=0.006) but there was no significant difference in central resistance(Rc), peripheral resistance(Rp), resonance frequency(RF) and resistance at 5Hz, 20Hz between groups. Conclusion: Hard exercise increased FVC % pred on spirometric parameters and decreased reactance at 5Hz(X5) on IOS parameters.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.397-403
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• 1998

Background: Little information is available concerning the value of bronchoscopy in patients with a lymphocytic exudative pleural effusion in which percutaneous pleural biopsy have been regarded as cornerstone in investigating the etiology. Recently, a few reports suggest that bronchoscopy may be more effective diagnostic method in patients with unexplained pleural effusion accompanied by hemoptysis or other roentgenographic abnormalities, such as mass, infiltrate, atelectasis. Method: Mter initial examinations of sputum and pleural fluid through thoracentesis in 112 patients(male 75 cases, female 37 cases, mean age 53.2 years) who were admitted for evaluation of the cause of pleural effusion, we performed bronchoscopy and closed pleural biology in most patients with undiagnosed lymphocytic exudate and compared the diagnostic yield of both invasive methods according to hemoptysis or other roentgenographic abnormalities, and investigated the sole diagnostic contribution of bronchoscopy. Results: Tuberculosis(57 cases, 51%) was the most common cause of pleural effusion. Percutaneous pleural biopsy showed more diagnostic yield than bronchoscopy regardless of presence or absence of other clinical or radiologic abnormalities. In 25 cases with unknown etiology after pleural biopsy, additional diagnostic yield by bronchoscopy was 36 % (4/11) in patients with associated features and only 7 % (1/14) with lone effusion, and, as the sole mean for diagnsosis in all patients with pleural effusion, was only 4.5%(5/12). Conclusion : In a region of high prevalence of tuberculosis as a cause of pleural effusion, percutaneous pleural biospy is more effective method when invasive method is required for confirmative diagnosis of unexplained lymphocytic exudative pleural effusion, and bronchoscopy is unlikely to aid in the diagnosis of lone pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.404-415
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• 1998

Background: Sleep apnea syndrome, which occurs in 1~4 % of the adult population, frequently has different cardiovascular complications such as hypertension, ischemic heart disease, cardiac arrythmia as well as sleep-wake disorder such as excessive daytime hypersomnolence or insomnia. Mortality and vascular morbidity are reported to be significantly higher in sleep apnea syndrome patients than in normal population. According to the recent studies, autonomic dysfunction as well as hypoxemia, hypercapneic acidosis, and increased respiratory effort, may playa role in the high prevalence of cardiovascular complications in patients with sleep apnea syndrome. However the cause and mechanism of autonomic neuropathy in patients with sleep apnea syndrome are not well understood. We studied the existence of autonomic neuropathy in patients with sleep apnea syndrome and factors which influence the pathogenesis of autonomic neuropathy. Method: We used the cardiovascular autonomic neuropathy(CAN) test as a method for evaluation of autonomic neuropathy. The subjects of this study were 20 patients who diagnosed sleep apnea syndrome by polysomnography and 15 persons who were normal by polysomnography. Results: Body mass index and resting systolic blood pressure were higher in sleep apnea group than control group. Apnea index(Al), respiratory disturbance index(RDI) and snoring time percentage were significantly higher in sleep apnea group compared with control group. But there were no significant differences in saturation of oxygen and sleep efficiency in two groups. In the cardiac autonomic neuropathy test, the valsalva ratio was significantly low in sleep apnea group compared with control group but other tests had no differences between two groups. The CAN scores and corrected QT(QTc) interval were calculated significantly higher in sleep apnea group, but there were no significant correlations between CAN scores and QTc interval. There were no significant data of polysomnography to correlate to the CAN score. It meant that the autonomic neuropathy in patients with sleep apnea was affected by other multiple factors. Conclusion: The cardiovascular autonomic neuropathy test was a useful method for the evaluation of autonomic neuropathy in patients with sleep apnea syndrome and abnormalities of cardiovascular autonomic neuropathy were observed in patients with sleep apnea syndrome. However, we failed to define the factors that influence the pathogenesis of autonomic neuropathy of sleep apnea syndrome. This study warrants futher investigations in order to define the pathogenesis of autonomic neuropathy in patients with sleep apnea syndrome.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.271-279
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• 1998

Background: Diagnosis by direct microscopy and/or by culture of the Mycobacterium tuberculosis from body fluids or biopsy specimens is "Gold standard". However, the sensitivity of direct microscopy after Ziehl-Neelsen staining is relatively low and culture of mycobacteria is time consuming. Detection of mycobacterial DNA in clinical samples by the polymerase chain reaction is highly sensitive but laborious and expensive. Therefore, rapid, sensitive and readily applicable new tests need to be developed. So we had evaluated the clinical significance of serologic detection of antibody to 38 kDa antigen, which is known as the most specific to the M. tuberculosis complex, and culture filtrate antigen by ELISA in sputum AFB smear negative patients. Method: In this study, culture tests for acid fast bacilli with sputa or bronchial washing fluids of 183 consecutive patients who were negative of sputum AFB smear were performed. Simultaneously serum antibodies to 38 kDa antigen and unheated culture filtrate of M. tuberculosis were detected by an ELISA method. Results: The optical densities of ELISA test with 38 kDa and culture filtrate antigen were significantly higher in active pulmonary tuberculosis cases than in non tuberculous pulmonary diseases (p<0.05), but in patients with active pulmonary tuberculosis, those of the sputum culture positive patients for M. tuberculosis were not significantly different from those of the sputum culture negative cases(p>0.05). In the smear-negative active pulmonary tuberculosis patients, the sensitivity of the ELISA using 38 kDa antigen and culture filtrate was 20.0% and 31.4%. respectively. The specificity was 95.3% and 93.9%. respectively. Conclusion : In active pulmonary tuberculosis but smear negative, the serologic detection of antibody to 38 kDa antigen and culture filtrate by ELISA cannot substitute traditional diagnostic tests and does not have clinically significant role to differenciate the patient with active pulmonary tuberculosis from other with non-tuberculous pulmonary diseases.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.311-321
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• 1998

Background: Mucoepidermoid carcinoma of the lung arises from submucosal gland of tracheobronchial tree. Histologically, the tumor is composed of mucin-secreting cells, squamous cells, and intermediated cells, which show no particular differentiating characteristics, in varying proportions. The tumor is divided into low grade and high grade depending on the proportion of cells, and the degree of the mitotic activity, cellular necrosis and nuclear pleomorphism. While favorable prognosis of low grade tumor, high grade tumor, which is very difficult to differentiate from adenosquamous carcinoma, has an aggressive clinical course. The tumor is rare, comprising 0.1 to 0.2% of primary lung cancers and 1 to 5% of bronchial adenomas. Method: A retrospective clinical study was done on 17 cases of mucoepidermoid carcinoma. The study investigated the clinical features, radiologic findings, bronchoscopic findings, histology and clinical courses. Results: Age ranged between second to seventh decade with a mean age of 42 years. Twelve out of 17 cases were male. Five out of 17 cases were smokers with a mean 11 pack-years. Common symptoms included dyspnea, cough, hemoptysis, and wheezing. Two out of 17 cases was asymptomatic. Atelectasis or mass was common radiologic finding. Plain chest radiography was normal in one patient whom the tumor was located in upper trachea. Bonchoscopy revealed exophytic mass in 12 cases and nodular infiltrations in 4 cases. One case having solitary pulmonary nodule in the right lower lung was normal on bronchoscopy. Histologically, ten out of 17 cases were low grade, and seven out of 17 cases were high grade. Among 10 patients with low grade tumor,9 patients were performed operation and have been alive without recurrence during a mean follow-up of 30 months. Two out of 7 patients with high grade tumor were performed pneumonectomy and have been alive during a follow-up of 3 and 8 months, respectively. Conclusion: Most of mucoepidermoid carcinoma is located at central airway and is presented symptoms by mucosal irirtation. Although atelectasis or mass is common radiologic finding. chest X -ray can be normal. The histologic grading and the extent of tumor are two most important factors for prognosis.