• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.275-284
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• 2002

Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.846-855
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• 1999

Background : Secondary pulmonary hypertension is an important final endpoint in patients with chronic hypoxic lung disease, accompanied by deterioration of pulmonary hemodynamics. The clinical diagnosis of pulmonary hypertension and/or cor pulmonale could be difficult, and simple noninvasive evaluation of pulmonary artery pressures has been an relevant clinical challenge for many years. Doppler echocardiography might to be a more reliable method for evaluating pulmonary hemodynamics in such patients in terms of the accuracy, reproducibility and easiness for obtaining an appropriate echocardiographic window than M-mode echocardiography. The aim of this study was to assess echocardiographic parameters associated with pulmonary arterial hypertension, defined by increasing right ventricular systolic pressure(RVSP), calculated from trans-tricuspid gradient in patients with chronic hypoxic lungs. Method : We examined 19 patients with chronic hypoxic lung disease, suspected pulmonary hypertension under the clinical guidelines by two dimensional echocardiography via the left parasternal and subcostal approach in a supine position. Doppler echocardiography measured RVSP from tricuspid regurgitant velocity in continuous wave with 2.5MHz transducer and acceleration time(AT) on right ventricular outflow tract in pulsed wave for the estimation of pulmonary arterial pressure. Results : On echocardiography, moderate to severe degree of pulmonary arterial hypertension was defined as RVSP more than 40mmHg, presenting tricuspid regurgitation. Increased right ventricular endsystolic diameter and shortened AT were noted in the increased RVSP group. Increased RVSP was correlated negatively with the shortening of AT. Other clinical data, including pulmonary functional parameters, arterial blood gas analysis and M mode echocardiographic parameters were not changed significantly with the increased RVSP. Conclusion : These findings suggest that shortened AT on pulsed doppler can be useful when quantifying pulmonary arterial pressure with increased RVSP in patients with chronic lung disease with hypoxemia. Doppler echocardiography in pulmonary hypertension of chronic hypoxic lungs is an useful option, based on noninvasiveness under routine clinical practice.

• Tuberculosis and Respiratory Diseases
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• v.53 no.2
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• pp.127-135
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• 2002

Background : Idiopathic interstitial pneumonia is characterized by chronic inflammation and pulmonary fibrosis. The clara cell 10 kD protein (CC10, also designated CC16) is synthesized by the bronchial epithelium and has been suggested to have a potent anti-inflammatory effect. Therefore, CC-10 might be a candidate for controlling the inflammatory events in patients with idiopathic interstitial pneumonia. The aim of this study was to determine if the degrees of pulmonary fibrosis in idiopathic interstitial pneumonia is associated with CC-10 in the BAL fluid. Materials and Methods : The BAL fluid was collected from 29 patients and 10 controls. Densitometric analysis of the western blot assay for the CC-10 was subsequently performed. The RI (relative intensity) of each band was compared according to the diagnosis, the radiological degrees of pulmonary fibrosis and the relative proportion of inflammatory cells in the BAL fluid. Results : There were no differences in the CC-10 expression levels in the BAL fluid between the patients (RI $77.5{\pm}75.8%$) and the controls ($70.7{\pm}39.8%$) (p>0.05). In addition, the degrees of pulmonary fibrosis and airway inflammation in patients with usual interstitial pneumonia were not associated with CC-10 expression in the BAL fluid (p>0.05). Conclusion : This study suggests that CC-10 expression is not associated with the degrees of pulmonary fibrosis in patients with usual interstitial pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.315-323
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• 2000

Background : An immunochromatographic assay (ICT Diagnostics) which facilitates the diagnosis of tuberculosis(TB) by detecting serum antibodies mainly directed against specific 38KDa of Mycobacterium tuberculosis has come into the market. The test consists of a cardboard folding device containing nitrocellulose strip and absorbent pads. The whole procedure is completed within 15 min and does not require any additional equipment. The test has been reported to be sensitive and specific in diagnosing active TB. Thus the test had been evaluated with sera from TB patients and TB-free subjects. Method : Sera from patients with active pulmonary tuberculosis(40 sputum positives for Mycobacterium tuberculosis, 79 sputum negatives, and 3 extrapulmonary tuberculosis) were obtained from the Double-Cross Chest Clinic of the Korean National Tuberculosis Association (KNTA) in Seoul. The control group consisted of TB-free 68 subjects(21 children under 7 years old and 47 healthy staff members of KNTA). Results : Nine out of 68(13.2%) TB-free controls had positive antibody response. Total 106 of 122(86.9%) radiologically active patients had positive antibodies while 16 (13.1%) showed negative reaction. Antibody was detected in 38 of 40(95.0%) sputum positive patients and 68 of 82(82.9%) sputum negative patients who were under the antituberculosis chemotherapy. The sensitivity and specificity were all 87% and the positive predictive value was 92.2% while the negative predictive value was 78.7%, when the prevalence of TB in the sample was 64.2%. Our results clearly show that the detection of antibodies which mainly react with the 38KDa antigen of M. tuberculosis is not suitable as the first-line method of diagnosis but considered only as an adjunctive test to standard techniques of tuberculosis diagnosis. when considering its high false positivity.

• Tuberculosis and Respiratory Diseases
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• v.48 no.3
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• pp.347-356
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• 2000

Background : Patients with obstructive sleep apnea syndrome are known to have high long-term mortality compared to healthy subjects because of their cardiovascular dysfunction. The observation of hemodynamic changes by obstructive apneas is helpful when attempting to understand the pathophysiological mechanism of the development of cardiovascular dysfunction in those patients. Therefore, we studied the changes in cardiovascular function with an animal model and tried to obtain the basic data for an ideal experimental model (this phrase is unclear), a requirement for a more advanced study. Methods : Sixteen anesthetized dogs with ${\alpha}$-chloralose delete were divided into two groups : 8 dogs of room air breathing group and 8 dogs of oxygen breathing group. We measured $PaO_2$, $PaCO_2$, heart rate, cardiac output, mean femoral artery pressure, and mean pulmonary artery pressure at specified times during the apnea-breathing cycle before endotracheal tube occlusion (baseline), 25 seconds after endotracheal tube occlusion (apneic period), 10 seconds (early phase of postapneic period, EPA) and 25 seconds (late phase of postapneic period, LPA) after spontaneous breathing. Results : In room air breathing group, the heart rate significantly decreased during the apneic period compared to that at baseline (P<0.01) and increased at EPA and LPA compared to that during the apneic period (P<0.01). But, the heart rate showed no significant changes during apneic and postapneic periods in the oxygen breathing group. Cardiac output tended to decrease during apneic period compared to that at baseline, but was statistically significant. Cardiac output significantly decreased at LP A compared to at baseline (P<0.01). Mean femoral artery pressure was significantly decreased at during apneic period compared to that at baseline (P<0.05). Conclusion : Through this experiment, we were partially able to understand the changes of cardiovascular function indirectly, but delete new experimental animal model displaying physiological mechanism close to natural sleep should be established, and the advanced study in the changes of cardiovascular function and their causes should be continued.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.36-43
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• 1999

Background : Tumor growth is the net result of intrinsic proliferation and escape from active cell death. bcl-2 is a member of a new category of oncogenes that is not involved in influencing cell proliferation but is involved in regulating cell death(apoptosis). Based on this information, it seems to be reasonable to expect that there may be clinical prognostic significance of bcl-2 expression in non-small cell lung cancer. But its prognostic significance is not established. Methods: To investigate the role of bcl-2 in lung cancer, we performed immunohistochemical stain of bcl-2 on 57 biopsy specimens from resected primary non-small cell lung cancer. Thereafter, flow cytometric cell cycle analysis was done. And we analyzed the correlation between bcl-2 expression, clinical parameters, S-, $G_1$-phase fraction and survival. Results: bcl-2 were detected in 43.8% of total 57 patients(according to histology, squamous cancer 47%, adenocarcinoma 32%, according to TNM stage, I 28.6%, II 52.3%, III 45.5%. both differences were insignificant). By using the flow cytometric analysis, mean S-phase fraction of bcl-2(+) and (-) group were 14.1($\pm7.8$)%, 24.7($\pm10.5$)% (p<0.005), mean $G_1$-phase fraction of bcl-2(+) and bcl-2(-) group were 75.5($\pm10.8$)%, 65.5($\pm11.4$)%(p<0.05). 2yr, 3yr and 5yr survival and median survival time of bcl-2(+) group were 65%, 54%, 41%, 53 months, and those of bcl-2(-) group were 71%, 52%, 46%, 37 months. (p>0.05, Kaplan-Meier, log rank) Conclusion: bcl-2 was detected in 43.8% of primary non-small cell lung cancer. The S-phase fraction of bcl-2(+) group was less than bcl-2(-) group, and G1-phase fraction of bcl-2(+) group was more than bcl-2(-) group. But, expression of bcl-2 could not be a prognostic factor.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.746-754
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• 1996

Objective: Diffuse interstitial lung disease (DILD) is a group of diverse diseases that share conUTIon clinical, radiologic, and pulomonary function features. Open lung biopsy (OLB) has been regarded as gold standard in differential diagnosis of DILD. However open lung biopsy is a invasive diagnostic tool not free of its own risk or complications. These days, high-resolution computed tomography (HRCf) has become an important diagnostic tool in DILD through its precise image analysis. In many instances, HRCT could provide specific diagnosis or, at least, provide infonnation on the disease activity of DILD. The authors re-evaluate the role of open lung biopsy in this "HRCT era" by investigating the additional diagnostic gain and impacts on the treannent plan in patients who have undergone high-resolution CT. Method : Diagnoses obtained by high-resolution CT and open lung biopsy were compared and changes of treatment plans were evaluated retrospectively in 30 patients who had undergone open lung biopsy for the purpose of diagnosis of diffuse interstitial lung disease from March 1988 to June 1994. Results : High-resolution cr suggeted specific diagnoses in 22 out of 28 patients (78.6%) and the diagnoses were confinned (0 be correct by open lung biopy in 20 of those 22 cases (91%). Open lung biopsy could not give specific diagnosis in 5 out of 30 cases (16.7%). In 5 out of 6 cases (83.3%) in whom high reolution cr was not able to suggest specific diagnosis, open lung biopsy gave specific diagnoses. Treatment plan was altered by the result of open lWlg biopsy in only 2 cases. Conclusion: The aoove fmdings suggest that in "HRCT era", when HRCT could suggest specific diagnosis, the need for open lung biopsy should be re-evaluated.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.378-385
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• 2003

Background : Wheezing is an important clue in the diagnosis of asthma. Previously, a Korean National asthma survey used a written questionnaire, containing the question, "Have you ever experienced a breathing sound-like 'sack-sack' or a flute sound (the Korean description for wheezing) during the last 12 months?" The response to this question showed a large discrepancy between the prevalence of wheezing and physician diagnosed asthma. This might have resulted partly from a misunderstanding of the question, due to an inadequate description for wheezing. This study was aimed at finding how well the layman understands the term "wheezing" when described as a breathing sound-like 'sack-sack', a whistle or a flute. Subjects and method : Sixty subjects, without experience of wheezing(group I), and 45 subjects, with chronic cough alleging wheezing(group II), were recruited from the Hallym University's Sacred Heart Hospital, in Anyang, Korea. Four different breathing sounds; vesicular, wheezing, tracheobronchial and crackle, were played for the subjects, without any experience with wheezing, and they were asked "which sound is most like that you would imagine when asked about a breathing sound-like 'sack-sack', a whistle or a flute?" This was followed by replaying the true wheezing sound, and then a global assessment was requested for the concordance between the real wheezing sound and the imagined wheezing sound. The wheezing sound was played for those subjects alleging wheezing, and they were asked, "have you really experienced that sound". Results : Only 46.7% of group I answered correctly, with 13.3% choosing the vesicular sound, 16.7% the tracheobronchial sound, 5.0% the crackle and 18.3% failed to answer. The concordance between their imagined wheezing and the real sound was $69.3{\pm}22.4%(mean{\pm}S.D.)$. 77.8% of group II recognized the correct sound as the one they had experienced. Conclusions : Language is not sufficient to the layman for describing natural sounds, such as wheezing.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.497-503
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• 2005

Backgrounds : The exacerbations of asthma and chronic obstructive pulmonary disease (COPD) have been suggested to be associated with respiratory tract viral infections (RTVIs). However, the rates of virus detection in previous studies have been quite variable, with lower rates for the exacerbation of COPD. Therefore, the virus detection of patients with exacerbation of asthma and COPD were investigated. Methods : 20 and 24 patients with exacerbation of asthma and COPD, respectively, were enrolled. Nasal and sputum samples were taken, and polymerase chain reaction (PCR) for rhinovirus and coronavirus and virus culture for influenza A, B, RSV and parainfluenza virus performed. Results : The mean $FEV_1/FVC$ in the exacerbation of asthma and COPD patients were 1.9/2.9 L (65.5%) and 1.1/2.6 L (42.3%), respectively. Respiratory virus was detected in 13 (65%) patients with exacerbation of asthma and rhinovirus was detected in 9. Coronavirus, influenza A, RSV and parainfluenza virus were detected in 2, 2, 1 and 1 patients with asthma. Among patients with exacerbation of COPD, a virus was detected in 14 (58.3%) patients, with rhinovirus, coronavirus and influenza A detected in 10, 3 and 4, respectively. Conclusions : This study suggested that RTVIs may have a role in the exacerbation of COPD as well as asthma.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.487-496
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• 2005

Background : 'Major pulmonary thromboembolism' is defined as right ventricular (RV) dysfunction, with or without shock, accompanied by significant morbidity and mortality. In this study, those with major pulmonary thromboembolism were divided into the shock and RV dysfunction only groups, and then investigated the mortality and complications in thrombolysis or anticoagulation, respectively. Methods : In a retrospective study, between January 1995 and December 2004, 60 eligible patients with a major pulmonary thromboembolism, admitted in Asan Medical Center, were included. Results : A total of 57 patients were treated with medical therapy. Thrombolysis was performed in 13 patients (23%) and anticoagulation in 44 (77%). There were no differences in the APACHEII and SOFA scores between the two groups. 6 (46%) and 11 (25%) patients died in the thrombolysis and anticoagulation groups, respectively (p=0.176). In the 19 patients (33%) showing shock, thrombolysis was performed in 9 (47%) and anticoagulation in 10 (53%). 4 (44%) of the 9 patients treated with thrombolytic agents and 3 (30%) of the 10 treated with anticoagulants died (p=0.650). In the 38 patients (67%) showing RV dysfunction only, thrombolysis was performed in 4 (11%) and anticoagulation in 34 (89%). 2 (50%) of the 4 patients treated with thrombolytics and 8 (24%) of the 34 treated with anticoagulants died (p=0.279). Three patients (23%) who underwent thrombolysis had a major bleeding episode, compared with 2 (5%) who were treated with anticoagulants (p=0.072). Conclusion: The results of our study showed that thrombolysis did not lower mortality and tended to increase major bleeding compared with anticoagulation in both the shock and RV dysfunction only groups. Further evaluation of the efficacy and safety of thrombolytic therapy for major thromboembolism appears warranted in Korea.