• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.315-324
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• 2001

Background : IL-8 is a potent chemotactic cytokine that plays an important role in the host defense mechanism against M. tuberculosis by recruiting inflammatory cells to the site of the infection. Lung epithelial cells, as well as alveolar macrophages are known to produce IL-8 in response to M. tuberculosis. IL-8 gene expression is mainly regulated on the level of transcription by NF-${\kappa}B$. This study investigated whether or not A549 cells produce IL-8 in NF-${\kappa}B$ dependent mechanism in response to macrophages phagocytosing M. tuberculosis. Methods : Peripheral blood monocytes that were obtained from healthy donors were cultured for 24 h with M. tuberculosis and a conditioned medium(CoMTB) was obtained. As a negative control, the conditioned medium without M. tuberculosis (CoMCont) was used. A549 cells were stimulated with M. tuberculosis, CoMCont and CoMTB and the IL-8 concentration in the culture media was measured by ELISA. The CoMTB induced IL-8 mRNA expression in the A549 cells was evaluated using RT-PCR, and CoMTB induced $I{\kappa}B{\alpha}$ degradation was measured using western blot analysis. CoMTB induced nuclear translocation and DNA binding of NF-${\kappa}B$ was also examined using an electrophoretic mobility shift assay(EMSA), and the CoMTB induced NF-${\kappa}B$ dependent IL-8 transcriptional activity was measured using a luciferase reporter gene assay. Results : CoMTB induced IL-8 production by A549 cells($46.8{\pm}4.8\;ng/ml$) was higher than with direct stimulation with M. tuberculosis ($6.8{\pm}2.9\;ng/ml$). CoMTB induced IL-8 mRNA expression increased after 2 h of stimulation and was sustained for 24 h. $I{\kappa}B{\alpha}$ was degraded after 10 min of CoMTB stimulation and reappeared by 60 min. CoMTB stimulated the nuclear translocation and DNA binding of NF-${\kappa}B$. The CoMTB induced NF-${\kappa}B$ dependent IL-8 transcriptional activity($13.6{\pm}4.3$ times control) was higher than either CoMCont($2.0{\pm}0.6$ times control) or M. tuberculosis ($1.4{\pm}0.6$ times control). Conclusion : A conditioned medium of peripheral blood monocytes phagocytosing M. tuberculosis stimulates NF-${\kappa}B$ dependent IL-8 production by the lung epithelial cells.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.234-241
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• 2004

Background : There has been a gradual increase in the number of newly diagnosed cases of Mycobacterium avium complex (MAC) pulmonary disease. However, the optimal therapeutic regimen for the disease has not yet established and there is no report about the treatment outcome of MAC pulmonary disease in Korea. This study examined the effect of clarithromycin-based regimen in patients with pulmonary MAC disease without a HIV infection. Materials and Methods : Fifty-six patients with pulmonary MAC disease were diagnosed according to the American Thoracic Society criteria from January 2000 to December 2003 at this hospital. Of these patients, 15 were treated with clarithromycin, rifampin, and ethambutol for more than 6 months, together with streptomycin initially (first 6 months) in 8 patients. Results : Six months after the treatment, the sputum cultures converted from positive to negative in 8 patients (53%) and the radiological findings improved in 10 (67%). At 12 months 4 patients (44%) achieved sputum negative conversion and 6 patients out of 9 patients (67%) who were treated for more than 12 months showed radiological improvement. Overall, the sputum findings converted to negative in nine patients (60%) who underwent medical treatment. A pulmonary resection was successfully performed in one patient. Only one patient discontinued the treatment due to side effects such as gastrointestinal intolerance and optic neuritis. Conclusion : A combined regimen containing clarithromycin is relatively safe and tolerable even in the elderly outpatients. However, the results of this combined chemotherapy were unsatisfactory and new companion drugs for MAC pulmonary disease are needed. A resection may be considered for localized disease.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.226-233
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• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.452-458
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• 2005

Background : In Korea, polymerase chain reaction (PCR) test for M. tuberculosis has been used for the diagnosis of acid-fast bacilli (AFB) smear-negative tuberculosis in order to increase diagnostic sensitivity. However, there have been no data dealing with the clinical utility of PCR in AFB smear-positive patients to differentiate between M. tuberculosis and nontuberculous mycobacteria. Method : We retrospectively analyzed the PCR test results which have been performed in patients who had AFB smear-positive sputum but had ambiguous clinical manifestations of active tuberculosis. PCR test was done using $AMPLICOR^{\hat{a}}$ M. tuberculosis kit. The sensitivity, specificity, and positive and negative predictive values of the PCR test were calculated based on culture and final clinical diagnosis result. Results : Fifty-six consecutive patients (62 PCR tests) were included in the study. Active tuberculosis was diagnosed in 23 patients (41.0%), while 9 patients had NTM infection (16.0%). The sensitivity, specificity, positive- and negative-predictive value of PCR test were 88.8%, 86.8%, 76.1% and 94.3%, respectively, according to the culture result. In comparison, they were 91.3%, 100%, 100%, 94.3%, respectively, according to the final clinical diagnosis. All 15 patients with NTM isolates, including 6 patients who had other lung diseases but expectorated NTM isolate, were negative for PCR test. Conclusion : Even though tuberculosis is still prevalent in Korea, PCR test is useful to differentiate between M. tuberculosis and NTM in patients with AFB-smear positive sputum but with ambiguous clinical manifestations of active tuberculosis.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.279-285
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• 2005

Background : Ambient particles during Asian dust events are usually less than $10{\mu}m$ in size, and known to be associated with the adverse effects on the general population. There is little evidence linking Asian dust to adverse effects on the airways. In 2002, the authors found that particulate matter during Asian dust events had an effect on the symptoms and pulmonary function of patients with bronchial asthma. An aggravating factor might be that of a viral infection, but this remains unclear. Conversely, it has been speculated that African dust may carry the virus responsible for foot and mouth disease. Asian dust events are also likely to be responsible for transporting viruses, some of which are pathogenic, and common in many environments. Therefore, in this study, air samples were screened for the presence of viruses. Methods : Air samples were collected 20 times each during Asian dust events and under non-dust conditions, for at least 6 hours per sample, using a high volume air sampler (Sibata Model HV500F), with an airflow rate of 500L/min, between April and August 2003, and between April and August 2004. The samples were then screened for the presence of targeted viruses (Influenza A, B, Hog cholera virus, and Aphthovirus) using a polymerase chain reaction method. Results : One Asian dust event occurred between April and August 2003, and 3 between April and August 2004, with a 24 hour average PM10 level of $148.0{\mu}g/m^3$. The 24 hour average PM10 level was $57{\mu}g/m^3$. There was a significant difference in the PM10 concentration between dusty and clear days. No viruses (Influenza virus, Aphthovirus, and Hog cholera virus) were identified in the air samples obtained during the dusty days. Conclusions : Although no virus was detected in this study, further studies will be needed to identify suspected viruses carried during Asian dust events, employing more appropriate virus detection conditions.

• Tuberculosis and Respiratory Diseases
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• v.41 no.1
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• pp.11-19
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• 1994

Background: Mycobacterium tuberculosis is a facultative intracellular pathogen which persists and multiplies within macrophage. Competent cell mediated immunity by cooperation of both T lymphocyte and macrophage of the host is required to kill the Mycobacterium tuberculosis. But a precise understanding of the pathogenesis of tuberculosis infection in pulmonary alveolar macrophage has not been achived. Research on the macrophage's basic microbicidal mechanism has elucidated the importance of oxygen-dependent or oxygen-independent components. Oxygen dependent processing begins with the reduction of oxygen by NADPH oxidase and generation of superoxide. In this study, the oxidative metabolic status of blood monocyte and pulmonary alveolar macrophage in patients with active pulmonary tuberculosis was accessed and compared with that of healthy control subjects to know whether there was a basic difference in superoxide generation by mononuclear cells between two groups. Methods: Pulmonary alveolar macrophage was purified after performing BAL(bronchoalveolar lavage) through the bronchi of infected lesion by plastic adhesion method. Blood monocyte was purified by Ficoll-Hypaque method. Superoxide generation by blood monocyte and pulmonary alveolar macrophage was measured by ferricytochrome-C reduction method after either stimulated with PMA(phorbol myristate acerate) or non-stimulated states. We also measured the effect of pulmonary tuberculosis patient's serum on superoxide generation by monocyte. Results: 1) Generation of superoxide by alveolar macrophage obtained from patients with pulmonary tuberculosis was little higher than those of controls, and PMA enhanced the generation of 2) Generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis was little higher than those of control(p>0.05), and PMA more enhanced the generation of superoxide in patientswith pulmonary tuberculosis than those in controls(p<0.02). 3) Patient's serum enhanced the generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis and controls, but not in the case of PMA stimulated blood monocyte. Conclusion: The present study suggest that the phenomenon of M.tuberculosis escape the microbicidal action of macrophage was not result of suppressed superoxide generation by blood monocyte and pulmonary alveolar macrophage, rather there might be a factor to stimulate the generation of superoxide by blood monocyte in pulmonary tuberculosis patient serum, but the comparision with effect of control's serum on superoxide generation needs further elucidation.

• Tuberculosis and Respiratory Diseases
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• v.66 no.1
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• pp.37-41
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• 2009

Hot tub lung has been described as a pulmonary illness associated with exposure to nontuberculous mycobacteria,mainly hot bathtub water contaminated with Mycobacterium avium complex (MAC) and hence the name. Although not entirely clear, its etiology has been thought to involve either an infection or a hypersensitivity pneumonitis secondary to MAC. Herein, we describe 2 female patients (60 and 53 years old) admitted to our hospital with hot tub lung, and both of whom worked in a public bath. Both women were initially admitted following several months of exertional dyspnea and cough. The patients had been working as body-scrubbers in a public bath for several years. Their chest CT scans showed bilateral diffuse ground-glass opacities with multifocal air-trappings and poorly defined centrilobular nodules in both lungs. Pathological findings from lung specimens revealed small non-necrotizing granuloma in the lung parenchyme with relatively normal-looking adjacent alveoli. Discontinuation of working in the public bath led to an improvement in symptoms and radiographic abnormalities, without antimycobacterial therapy.

• Tuberculosis and Respiratory Diseases
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• v.62 no.6
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• pp.492-498
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• 2007

Background: Several lines of evidence suggest that a host's genetic factors influence the outcome of exposure to Mycobacterium tuberculosis. The aim of this study was to determine whether polymorphism in NRAMP1 (natural resistance associated macrophage protein 1) gene is associated with the susceptibility or resistance to tuberculosis infection for patients with drug-sensitive pulmonary tuberculosis (DS-TB) and multi-drug resistant pulmonary tuberculosis (MDR-TB). Methods: Eight genetic polymorphisms of the NRAMP1 gene were investigated in patients suffering with DS-TB (n=100) or MDR-TB (n=102), and in healthy normal controls (NC, n=96). The genetic polymorphisms of NRAMP1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of D543N A/G heterogygotes was significantly higher in the DS-TB subjects than the NCs (OR=2.10, 95% CI: 1.00 to 4.41, p=0.049). The frequency of 823C/T T/C heterozygotes was significantly higher in the DS-TB subjects (OR=2.79, 95% CI: 1.11 to 7.04, p=0.029) and the MDR-TB subject (OR=3.30, 95% CI 1.33 to 8.18, p=0.010) than in the NCs. However, the frequency of these genotypes was not different between the DS-TB and MDR-TB subjects. Conclusion: A significant association was found between NRAMP1 823 C/T polymorphism and pulmonary tuberculosis. This result suggests that NRAMP1 polymorphism may be involved in the development of pulmonary tuberculosis in Koreans.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.966-971
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• 2003

Purpose : It is now well established that infection and inflammation play an important role in the pathogenesis of ischemic brain damage. The loss of neutrophils from systemic circulation is an associated finding in injury mediated by granulocyte. Periventricular leukomalacia(PVL) caused by ischemia is the principal form of brain injury in premature infants. This study was conducted to evaluate whether the low neutrophil count is associated with periventricular leukomalacia(PVL) in premature infants. Methods : Retrospective review of medical records was undertaken. Subjects were premature infants with a birth weight of less than 1,500 gm, admitted to the Neonatal Intensive Care Unit of Kyungpook University Hospital. A complete blood count of peripheral blood was done within the 1st hour of life. Neutropenia was defined as absolute neutrophil count < $1,500/mm^3$, PVL as increased periventricular echodensities followed by cyst formation on ultrasonography or corresponding signs on brain MRI. Results : Thirteen infants out of a total population of 37 revealed neutropenia. Respiratory distress syndrome and requirement for respiratory support were not different between infants with neutropenia( neutropenia group) and infants without neutropenia(control group). Intraventricular hemorrhage (IVH) and grade 3 and 4 IVH were more frequent in neutropenia group(P<0.05). There was no statistically significant increase of PVL in neutropenia group. The neutrophil count was $18,760.0{\pm}10,266.1/mm^3$, $7,272.0{\pm}7,435.0/mm^3$ infants with PVL and $11,131.7{\pm}3,386.5/mm^3$, $2,407.5{\pm}1,933.1/mm^3$ in infants without PVL, respectively. The frequency of mechanical ventilation and artificial surfactant therapy was higher in infants with PVL compared with infants without PVL, but statistical analysis was not performed due to small number of subjects. Conclusion : A low number of neutrophils in the systemic circulation was not associated with an increased risk of PVL in premature infants.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.67-74
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• 2005

Purpose : The incidence of mortality associated with respiratory difficulties is decreasing nowadays contributed to the development of neonatology. However, complications associated with mechanical ventilator are increasing. This study is to determine clinical manifestations, diagnositc availability of the endotracheal tip culture in patients with Ventilator-Associated Pneumonia(VAP) in neonatal intensive care unit(NICU). Methods : A retrospective analysis of 50 neonates who were admitted to the NICU of Kangnam Sacred Heart Hospital and had given mechanical ventilator from 1 January 2000 to 30 June 2003. VAP group defined as neonates who had pneumonia with mechanical ventilation longer than 48 hours. They were classified into VAP group(n=13) and control group (n=37) and the prevalence, microorganisms cultured from the endotracheal tube tip and risk factors were investigated. Results : The prevalence of VAP was 26.0%(n=13) and the most dominant microorganism cultured in our NICU was methicillin-resistant coagulase negative staphylococcus(MR-CNS) in 4 cases. Other microorganisms were Pseudomonas, Enterobacter, methicillin-resistant Staphylococcus aureus(MRSA) and Klebsiella. Gestational age, birth weight, Apgar score, respiratory distress syndrome, retinopathy of prematurity, bronchopulmonary dysplasia, sepsis, renal failure, pulmonary hemorrhage, pneumothorax were not different significantly between two groups except intraventricular hemorrhage(P<0.001) and patent ductus arteriosus(P<0.05). Duration of hospital stay and mortality rate were also not different significantly. Conclusion : VAP occurred at a significant rate among mechanically ventilated NICU patients. Despite of limitation of encotracheal tip culture, the most common microorganism was MR-CNS. We should be aware of occurrence of VAP in NICU neonate who were with mechanical ventilator and should treat with great care.