• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.530-535
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• 2005

Background and Aims : Cigarette smoking induces an inflammatory response in the airways, which may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Interleukin-6 (IL-6) is one of the cytokines that plays an important role in inducing bronchial inflammation. The aim of this study was to determine if the level of the pro-inflammatory cytokine, Interleukin-6, is increased when the bronchial epithelial cells are exposed to a cigarette smoke extract (CSE) and an extract from stop smoking-aiding cigarettes, and examined the safety of these commercially available stop smoking-aiding cigarettes. Method : Bronchial epithelial cells were exposed to CSE from cigarette and stop smoking-aiding cigarettes for 24 hours. ELISA was used to measure the IL-6 levels in the supernatant from each condition. The IL-6 mRNA levels were measured by Taqman Real time RT-PCR. N-acetyl-L-cysteine(NAC) was added to each condition to determine if NAC can inhibit the release of IL-6 from the bronchial epithelial cells when they are exposed to CSE from cigarette and stop smoking-aiding cigarettes. Result : When bronchial epithelial cells were exposed to a CSE from cigarettes and stop smoking-aiding cigarettes, each type of CSE stimulated IL-6 production from the bronchial epithelial cells. The IL-6 mRNA level in the Bronchial epithelial cells was also elevated and NAC was found to inhibit the release of IL-6 from bronchial epithelial cells when they were exposed to the CSE from cigarettes and stop smoking-aiding cigarettes. Conclusion : Commercially available stop smoking-aiding cigarette can induce bronchial inflammation and can be harmful to smokers. Therefore, the safety of these cigarettes for smoking cessation should be evaluated.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.195-201
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• 2011

Background: Osteopontin (Opn) is recognized as an important adhesive bone matrix protein and a key cytokine involved in immune cell recruitment and tissue repair and remolding. However, serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease (COPD). Thus, the aim of this study was to evaluate and compare the serum levels of osteopontin in patients experiencing COPD exacerbations and in patients with stable COPD. Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of osteopontin were measured by the ELISA method. Results: Serum levels of osteopontin were higher in patients with acute exacerbation than with stable COPD and in healthy control subjects ($62.4{\pm}51.9ng/mL$, $36.9{\pm}11.1ng/mL$, $30{\pm}11ng/mL$, test for trend p=0.003). In the patients with COPD exacerbation, the osteopontin levels when the patient was discharged from the hospital tended to decrease compared to those at admission ($45{\pm}52.1ng/mL$, $62.4{\pm}51.9ng/mL$, p=0.160). Osteopontin levels significantly increased according to patient factors, including never-smoker, ex-smoker and current smoker ($23{\pm}5.7ng/mL$, $35.5{\pm}17.6ng/mL$, $58.6{\pm}47.8ng/mL$, test for trend p=0.006). Also, osteopontin levels showed a significantly negative correlation with forced expiratory volume in one second ($FEV_1$%) predicted in healthy controls and stable COPD patients (r=-0.389; p=0.013). C-reactive protein (CRP) was positively correlated with osteopontin levels in patients with COPD exacerbation (r=0.775; p=0.002). Conclusion: The serum levels of osteopontin increased in patients with COPD exacerbation and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of acute exacerbation of COPD.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.19-26
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• 2007

Background: Toxocariasis is a common cause of eosinophilia and eosinophilic lung disease in Korea. We analyzed the characteristics of eosinophilic lung disease in toxocariasis. Method: One hundred and forty one patients with eosinophilia caused by a toxocara larval infection were evaluated from September 1, 2001 through March 30, 2006. The plain chest x-ray, chest CT(computed tomography), and bronchoalveolar larvage(BAL) were examined. A diagnosis of toxocariasis was made by ELISA using that secretory-excretory antigen from the T. canis larvae. Results: Toxocarial eosinophilic lung diseases was diagnosed in 32 out of 141 patients. Ground glass attenuation was the main feature on the CT scans in 23 out of 141 patients (71.9%). Thirteen patients (40.6%) had a random in zonal distribution on CT. Pleural effusion was observed in 9 patients (28.1%). Twenty eight patients (87.5%) complained of respiratory symptoms. Eleven patients (34.4%) had gastrointestinal symptoms and 12 patients (37.5%) had liver infiltration. Conclusions: The most common findings of the chest CT in patients with toxocariasis was a randomly distributed ground grass attenuation. A toxocara infection should be considered in a differential diagnosis of patients who exhibit pulmonary infiltration with eosinophilia in Korea.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1214-1222
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• 1998

Background : The intrapleural hypofibrinolysis is caused by mainly excessive concentration of pleural plasminogen activator inhibitor-1 antigen(PAI-1 Ag), which binds tissue type plasminogen activator. In pleural inflammation induced by sclerosing agents for pleurodesis, levels of pleural PAI-1 antigen increase in relation to decreasing D-dimer levels. It has been known that the pleural mesothelial cells have the capability of secreting PAI-1 Ag in response to inflammation in vivo. Therefore, we estimated whether pleural inflammation changes the balance between fibrinolytic and coagulative properties in exudative pleural effusions. Method : The thirty cases was included in our study. We determined the pleural levels of glucose, lactic dehydrogenase(LDH), pH and the counts of white blood cell(WBC), polymorpho leukocyte(PMN), lymphocyte as the parameters of pleural inflammation and cellular components of pleural fluid. The plasma level of fibrinogen in fluid and the neutrophil count in blood were determined. The levels of D-dimer, PAI-1 Ag and thrombinantithrombin III complex(TAT) were determined by ELISA(Behring, Marburg, Germany). Result : The causes of pleural effusion were as following : tuberculous in 14 cases, malignant in 10 cases and parapneumonic in 6 cases. The levels of pleural D-dimer, PAI-1 Ag and TAT was significantly higher than that of plasma(p<0..001). The severity of pleural inflammation did not correlated with pleural D-dimer, PAI-1 Ag, TAT and their plasma levels. But the level of pleural TAT correlated with pleural WBC and lymphocyte count. Conclusion : We found that the severity of pleural inflammations did not correlated with pleural D-dimer, PAI-1 Ag, TAT and the possibility of local production of PAI-1 antigen is present.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1167-1177
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• 1998

Background : Pulmonary tuberculosis is one of the diseases characterized granuloma formation which was controlled by cellular immune reactions. In the process of granulomatous changes, activated alveolar macrophages and T lymphocytes secrete many cytokines including interleukin-1 (IL-1), tumor necrosis factor-alpha(TNF-$\alpha$), interferon-gamma(IFN-$\gamma$) which mediate inflammatory reactions. Intercelluar adhesion molecule-1(ICAM-1) also known to major role player in inflammatory processes, and increased cellular expressions when endothelial cell was stimulated by IL-1, TNF and IFN. Method : To evaluate relationships among cellular immune reactions and clinical stages, pulmonary tuberculosis patients were classified into three groups according to their clinical stages including minimal, moderate and far advanced tuberculosis. TNF-$\alpha$ IFN-$\gamma$, sICAM-1 (soluble form of ICAM-1) were measured at the time of diagnosis and after 6-months anti-tuberculosis medications by radioimmuno assay or enzyme linked immunosolvent assay. Result : TNF-$\alpha$, IFN-$\gamma$, sICAM-1 were significantly increased in moderate and far advanced pulmonary tuberculosis patients but no meaningful changes in minimal staged patients. 6-months anti-tuberculosis medications reduced serum sICAM-1 levels significantly, related to clinical improvement but no significant changes were found in the serum levels of TNF-$\alpha$ and IFN-$\gamma$. In the point of correlations. positive ones revealed between TNF-$\alpha$ and sICAM-1, also between IFN-$\gamma$ and sICAM-1 but no correlation between TNF-$\alpha$ and IFN-$\gamma$. Conclusion : Measurement of serum sICAM-1 could be useful parameter to evaluate the severity of pulmonary tuberculosis and to monitor disease activities during anti-tuberculosis medications.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.90-98
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• 1998

Background : The CD4+ T-helper cells comprise functionally distinct subsets of Th1 and Th2 cells that are distinguished on the basis of differential cytokines production Th1 cells secrete interferon-$\gamma$, lymphotoxin, interleukin-2. Th2 cells produce interleukin-4, interleukin-5, interleukin-10. A previous study shown that Th2 cells and their cytokines increased in patients with atopic asthma. We compared cytokines(IL-4, IFN-$\gamma$) activity and subpopulation of T-lymphocytes in peripheral blood from atopic asthmatics versus non-asthmatics. Method: Fifteen patients with atopic asthma(nine men, six women), twelve patients with chronic bronchitis(six men, six women), five healthy persons(three men, two women) were studied. Activity of IL-4, IFN-$\gamma$ and T-cell subpopulation in peripheral blood were estimated. Results: Patients had a median age of 55yr. The mean activity of IL-4 of asthmatics was significantly increased(control $0.75{\pm}1.1pmol/L$, atopic asthmatics $3.50{\pm}0.75pmol/L$, chronic bronchitis $2.01{\pm}1.2pmol/L$), but IFN-$\gamma$ was not significantly increased. In the T lymphocyte sunsets the percent of CD62L+ T-lymphoeytes of asthmatics was not significantly increased (control $16.7{\pm}16.4%$, atopic asthmatics $24.8{\pm}23.6%$, chronic bronchitis $17.0{\pm}16.9%$). Conclusion: In this study elevated production of IL-4 was observed in atopic asthmatics. CD62L+T-lymphoeytes was not increased in atopic asthma.

• KSBB Journal
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• v.13 no.2
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• pp.181-186
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• 1998

In order to obtain high-level production of recombinant human thrombopoietin (rhTPO) in insect cell line, HTI-TN-5B1-4 (TN5), conditions for optimal rhTPO expression such as multiplicity of infection (MOI), the cell density at infection, harvesting time and type of culture method as well as growth media were determined. When TN5 cells were cultured as anchorage-dependent state in 60-mm dish, cell density $2\times^6$ cells,MOI of 10 and Garvesting the culture media at 72 hr post-infection wrere the cinditions for highest rh TPO production. High production of rhTPO was also achieved by using EXPRESS FIVE serum free media rather than SF900II serum free media-1. Anchorage-dependent TN5 cells were adapted as a suspension culture when they were grown in the presence of heparin. TN5 cells were successfully cultured at 0.2 L scale in suspension culture without having aggregation. When TN5 cells were cultured as suspension state, cell density of $0.6\times10^6$ cells/mL, MOI of 1 and harvesting the culture media at 72 hr post-infection, gave the highest yield of rhTPO.

• Tuberculosis and Respiratory Diseases
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• v.50 no.1
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• pp.76-83
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• 2001

Background : Coal workers' pneumoconiosis is a fibrotic lung disease resulting from chronic inhalation of coal dust. The precise mechanism of lung fibrosis in coal workers' pneumoconiosis is uncertain. However, a relationship between the stimulation of fibroblast proliferation and collagen production by mediators released from in flammatory and resident lung cells is thought to be a major factor. The transforming growth factor-$\beta$(TGF-$\beta$), a multifunctional cytokine and growth factor, plays a key role in the scarring and fibrotic processes due to its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. To determine the involvement of TGF-$\beta$ in the development of lung fibrosis in coal workers' pneumoconiosis, the TGF-${\beta}_1$ level in plasma was measured in patients with coal workers' pneumoconiosis. Methods : Plasma was collected from 40 patients with coal workers' pneumoconiosis (20 with simple coal workers' pneumoconiosis and 20 with complicated coal workers' pneumoconiosis) and from 10 normal controls. The ELISA method was used to measure the plasma TGF-${\beta}_1$ concentration. Results : Compared to the control group ($0.63{\pm}01.8$ ng/mL), there was no significant difference in the plasma TGF-${\beta}_1$ level in patients with simple coal workers' pneumoconiosis ($0.64{\pm}0.17$ ng/mL) (p>0.05). However, in patients with complicated coal workers' pneumoconiosis the plasma TGF-${\beta}_1$ level ($0.79{\pm}0.18$ ng/mL) was significantly higher than in patients with simple coal workers' pneumoconiosis and the control group (p<0.05). Conclusion : The data suggests that TGF-${\beta}_1$ has some influence in the development of lung fibrosis in coal workers' pneumoconiosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.1047-1057
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• 1998

Background : Sarcoidosis is a systemic granulomatous disorder of unknown origin and characterized by accumulation of T cells and macrophages. Various cytokines may play crucial roles in the activation of T cells and macrophages, and thereby in the formation of granulomas. However, little is known about the balance between proinflammatory cytokines and antiinflammatory cytokines in the development of sarcoid granulomas and disease activities. In the present study, we measured IL-6, IL-8 and IL-10 in the bronchoalveolar lavage fluid(BALF) from patients with pulmonary sarcoidosis to find out whether there is an imbalance between proinflammatory cytokines and antiinflammatory cytokines in the lung. Methods: Fourteen subjects with the diagnosis of sarcoidosis and six healthy volunteers were included. BALF was concentrated ten-fold by pressure ultrafiltration and each cytokine levels were measured by EUSA method. Active sarcoidosis was defined by major organ involvement or clinically progressive diseases. Results: The mean IL-6 levels in the BALF of the active sarcoidosis group were significantly increased than in controls or inactive sarcoidosis group(p<0.05). Meanwhile, the IL-8 levels were increased and IL-10 levels were decreased in the active sarcoidosis group than in controls or inactive sarcoidosis group without significance(p>0.05). In active pulmonary sarcoidosis patients, the IL-6 levels in BALF correlated with the BALF CD4/CD8 ratio(r=0.768, p<0.05) and IL-8 levels(r=0.564, p<0.05). Conclusions : The data presented showed that pro-inflammatory cytokine IL-6 is important in the pathogenesis of sarcoidosis and decreased tendency of anti-inflammatory cytokine IL-10 might also be involved in the development of granulomatous inflammation in sarcoidosis.

• Journal of Chest Surgery
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• v.37 no.5
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• pp.391-400
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• 2004

Xenotransplantation in discordant species results in immediate and irreversible hyperacute rejection due to natural antibodies, IgM. With this, antibody depletion is one option to reduce hyperacute rejection, we investigated the effect of PCPP (postcentrifugal plasmapheresis) on the depletion of natural antibodies and the effect of antibody titer on xenograft survival. Material and Method: Outbred swines (n=4) weighing 10∼20 kg were used as donors and mongrel dogs (n=4) weighing 25∼30 kg were used as recipients. Recipient canines underwent plasmapheresis (COBE TPE Laboratories, Lakewood. CO, USA). Pre-transplantation PCPP was peformed on day －2 and day 0. There were three groups (Group 0: no PCPP, Group 1: 1 pla sma-volume (PV) at day －2 and 2 PV at day 0, Group 2: 2 PV at day －2 and 2 PV at day 0). A swine heart was heterotopically transplanted into a recipient's abdominal infrarenal aorta and inferior vena cava. Mean percent depletion of total IgM and IgG in plasma of the recipients was calculated. Serum albumin, electrolyte, complement activity and coagulation factors were measured. Histopathologic examination of heart specimens was performed. Result: Mean percent depletion of IgM and IgG were 95.7$\pm$1.2%, 80.5$\pm$2.4% in the group 2 at the end of PCPP. The percent depletion of serum albumin concentration was decreased from 2.8 to 1.4 g/㎗ in the group 1 and 3.0 to 1.5 g/㎗ in the group 2. Complement hemolytic activity was decreased in group 1 and 2, but returned to normal level within 24 hours. Complement hemolytic activity was reduced to 10% of pre-PCPP level in group 2. Serum fibrinogen decreased to 20% or less and was recovered within 24 hours in group 2. Antithrombin III decreased but less than fibrinogen. PT and aPTT were sometimes but not always prolonged during plasmapheresis. After plasmapheresis, PT and aPTT were prolonged beyond the measurable level. D-dimer was not found during PCPP, but appeared and maintained from 10 minutes after trasplantation. Graft Survival time was 5 min in group 0, and it was 90$\pm$0 min in the group 2. Histopathologic changes were more typically characterized by edema, hemorrhages, thrombosis in all groups at the end of experiment. Conclusion: PCPP effectively removed immuoglobulins and reduced the titer of natural antibodies, as a result, significantly prololonged swine heart xenograft survival.