• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1114-1124
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• 1997

Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.142-150
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• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.337-345
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• 2007

Backgrounds: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting ${\beta}_2-agonists$ (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control. Methods: One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including $FEV_1%$ predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians. Results: The mean ACQ score decreased significantly on montelukast ($11.5{\pm}5.4$ at baseline vs. $6.7{\pm}5.0$), with a significant improvement in all individual symptom scores (p<0.01). The $FEV_1%$ predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (${\kappa}=0.85$). Conclusion: These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.776-784
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• 1997

Background : Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC). however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, and survival of concurrent chemotherapy with etoposide and cisplatin(EP) and radiation therapy for unresectable stage III NSCLC. Method : Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide and cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. Results : Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient. The median survival was 12.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia($\geq$ grade 3, 46%). Thrombocytopenia over grade 3 was found in 11%. Radiation pneumonitis occurred in 13 patients(46%). Conclusion : Concurrent chemotherapy(EP) plus radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.836-843
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• 1997

Background : The prevalence of Gastro-esophageal reflux(GER) in patients with asthma is estimated to be 50~60% and treatment of GER has been shown to improve asthma symptoms in Western. But GER has been known to be less common in Eastern and GER prevalence rates in asthmatics are not available in Korea. Method : We compared the prevalence rate of GER in 42 patients with asthma to that in 20 healthy normal controls and examed the efficacy of new prokinetic drug, cisapride(40mg/day, 8weeks) in patients with GER and asthma. For acid GER to be considered pathological, 24 hour esophageal pH monitoring should reveal values exceeding upper limit of 95 percentile for at least one of 6 parameter of DeMesseter's table. Result : The results showed GER was more common in patients with asthma(11/42, 26.2%) than normal controls(3/20, 15%) and asthmatics group showed a significant longer supine time pH<4(%) and total time pH<4(%), and more reflux episodes as compared with normal control group. After 4 asthmatics with GER were treated with cisapride, their asthma symtom scores, FEV1 and composite scores of pH monitoring were improved. Conclusion : GER is more common in asthmatics than in normal controls in Korea and prepulsid reduces asthma symptoms in patients with GER and asthma.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.203-209
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• 2000

Background: Exercise is a very common precipitant of asthma. Bronche-constriction associated with exercise can occur in 75~90% of individuals with asthma The estimated prevalence(30~85%) of gastroesophageal reflux(GER) in patients with asthma is significantly higher than in general population. We performed pH monitoring during the exercise in order to evaluate whether exercise induced asthma(EIA) could be related to GER and acid reflux-induced esophagobronchial reflex-mediated bronchospasm might be a factor for EIA. Method: Following an overnight fast, 18 patients with a suspected EIA(6 men, 12 women) were studied. Monitoring of intraesophageal pH, ECG and spirometry was done for 1 hour before treadmill exercise. After baseline monitoring, subjects underwent symptom-limited treadmill exercise with Bruce protocol and continuous monitoring for 60 min after exercise. Spirometry was done at baseline prior to exercise, and repeated every 10 min after full exercise for 60 min. Results: Exercise-induced bronchoconstriction was noted in 15 patients, who performed MBPT and 12 patients confirmed for bronchial asthma and 3 patients were diagnosed exercise-induced astham. Five of 15 EIA patients demonstrated a pathologic degree of GER. Conclusion: We suggest that GER may be one of pathophysiologic factors of EIA and evoke further concentration on the GER in the EIA patients.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.547-557
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• 1996

Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.366-373
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• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.485-494
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• 2004

Background : To assess the effects of mDOT implementation on sputum smear conversion for AFB (Acid fast bacilli) positive pulmonary tuberculosis patients, modified Directly Observed Treatment (mDOT) was started on October $8^{th}$ 2001 at a health center in Seoul. mDOT was defined through weekly interviewing and supervising of a patient by a supervisor (doctor, nurse, or lay health worker). The sputum smear conversion of a mDOT group was compared with that of a self-medication (self) group. Methods : This study included 52 AFB positive pulmonary tuberculosis patients registered at a health center in Seoul between October $8^{th}$ 2001 and April $23^{rd}$ 2002. 24 and 28 patients were enrolled in the mDOT and self medication groups, respectively. Paired (1:1) individual matching, by gender, extent of disease, relapse and age-matching variables, was performed between the two groups, resulting in 20 paired matches. This prospective study was planned as an unblinded, non-randomized quasiexperimental pilot project. Outcomes were identified from results of sputum smear examinations for AFB in both groups at 2 weeks, and 1 and 2 months. The paired matching data were analyzed using the SAS program version 8.1 by McNemar test. Results : At the end of 2 weeks of treatment, the sputum smear conversion of the mDOT group was somewhat higher than that of the self medication group (78.57 vs. 50%, p-value=0.289), and after 1 month of treatment no statistically significant difference was shown between the two groups (83.33 vs. 50, p-value=0.125). At the end of 2 months of treatment (initial intensive phase), the sputum smear conversions of the mDOT and self groups were 95 and 75%, respectively (p-value=0.219). Conclusions : The implementation of mDOT did not result in clinically significant increases in the sputum smear conversion at 2 weeks, and 1 and 2 months compared with that of the self medication group. However, the increases experienced might contribute to diminishing the infectious period of AFB positive patients, and this approach may act as a guide for a specific group of patients. In this study, mDOT was performed for one hundred percent of the intensive treatment phase. It can also be an effective treatment for pulmonary tuberculosis patients, and may be useful for some high risk tuberculosis patients.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.574-582
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• 1998

Background: Bronchofiberscopy is a procedure with a chance of airway irritation and it may cause pathophysiologic changes of respiratory system. So we tried to evaluate the influence of bronchofibercopy on $O_2$ saturation, ABGA and PIT by patient's basal status and procedure type. Method: $O_2$ saturation was measured every 1 minute from the left index finger tip with percutaneous oximetry. ABGA was done before and right after the bronchofiberscopy and PIT was done before and within 10 minutes after the bronchofiberscopy. Results: The mean time for bronchofiberscopy procedure was 14.5mim and $SaO_2$ maximally fall to 89.0 below 8% of the baseline after mean time of 8.4min, which was recovered at the end of the procedure. $SaO_2$ change amount was 8.4 % on Non-$O_2$ supply group, which was lower compared to 6.4 % of the $O_2$-supply group without statistically significance. Biopsy Group and BAL group showed more $SaO_2$ fall than washing only group. The level of $PaO_2$ and FEV1 of the patient didn't influence significantly on $SaO_2$ fall during the procedure. ABGA taken before and after the bronchofiberscopy showed mild fall of $PaO_2$ and mild rise of $PaCO_2$. Whereas PFT showed decrease of FEV1(P<0.05) and increase of RV without changes in airway resistance and pulmonary diffusion capacity. Comparing before and after the bronchofiberscopy, the washing group showed no significant changes on PIT, while the biopsy group and the BAL group showed increase of RV & decrease of $FEV_1$ after the bronchofiberscopy. BAL group showed more changing tendency rather than biopsy group although not statistically significant. Conclusion: Bronchofiberscopy is considered as a relatively safe procedure, but it would be better to be done with $O_2$ supply especially in the patient with low $PaO_2$ and in the case of biopsy and BAL.