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Although tuberculosis is a chronic infectious disease that can occur in any section of the body, oral tuberculosis is rare. Here, we report a case of oral tuberculosis in which the patient sought treatment for a painful oral lesion. A histopathologic examination revealed the characteristics of tuberculosis and pulmonary lesions were detected on subsequent examination. The patient was treated with antituberculosis therapy, and his symptoms improved. This case emphasizes the importance of including oral tuberculosis as part of the differential diagnosis for mucosal lesions.

Extrapulmonary organ involvement in human immunodefiaency virus (HIV)-infected patients with pulmonary tuberculosis (TB) is reported to be 26%, however, the clinical predictors of extrapulmonary involvement in pulmonary TB patients has not been reported yet. We tried to determine the clinical predictors of presence of extrapulmonary involvement in patients with pulmonary TB. Cross-sectional study was performed including all adult patients with culture-proven pulmonary TB diagnosed between January 1, 2004 and July 30, 2006, at a tertiary referral hospital in South Korea. The presence of extra-pulmonary TB involvement was diagnosed based on bacteriological, pathological, or clinical evidence. Among 320 patients with a culture-proven pulmonary TB, 40 had extrapulmonary involvement. Patients with bilateral lung involvement were more likely to have extrapulmonary involvement, with an adjusted odds ratio (OR) of 4.21 (95% confidence interval [CI], 1.82-9.72), while patients older than 60 yr (adjusted OR, 0.27; 95% CI, 0.08-0.89), patients with cavitary lesions (adjusted OR, 0.37; 95% CI, 0.16-0.84), and with higher levels of serum albumin (adjusted OR, 0.45; 95% CI, 0.25-0.78) had less frequent involvement. Clinicians should be aware of the possibility of extrapulmonary involvement in TB patients with bilateral lung involvement without cavity formation or lower levels of serum albumin.

Bone scan (BS) and serum alkaline phosphatase (ALP) concentration are used to detect bone metastasis in malignancy, although whole-body fluoro-D-glucose posi- tron emission tomography computed tomography (FDG PET/CT) is being used increasingly. But BS is still used for the detection of metastatic bone lesion. So we compared the usefulness of PET/CT, BS, and serum ALP in detecting bone metas- tases in patients with newly diagnosed lung cancer. The medical record database was queried to identify all patients with a new diagnosis of lung cancer between January 2004 and December 2005, who had a PET/CT, BS, and serum ALP before treatment. We retrospectively reviewed all patients' records and radiological reports. One hundred eighty-two patients met the inclusion criteria. Bone metastases were confirmed in 30 patients. The sensitivity values were 93.3% for PET/CT, 93.3% for BS, 26.7% for serum ALP concentration, and 26.7% for BS complemented with serum ALP concentration. The respective specificity values were 94.1%, 44.1%, 94.1%, and 97.3%. The kappa statistic suggested a poor agreement among the three modalities. FDG PET/CT and BS had similar sensitivity, but PET/CT had better specificity and accuracy than BS. PET/CT is more useful than BS for evalu- ating bone metastasis. However, in the advanced stage, because of its high speci- ficity, BS complemented with serum ALP is a cost-effective modality to avoid hav- ing to use PET/CT.

Human metapneumovirus (hMPV) is a recently recognized human respiratory pathogen, which is known to be associated with upper and lower respiratory tract infections mainly in children, immunocompromised patients, and the elderly. The clinical manifestations of hMPV infections are similar to those of the human respiratory syncytial virus infection, which range from mild upper respiratory tract infection to severe bronchiolitis and pneumonia. Recently, hMPV has come to be thought of as the cause a similar spectrum of disease in adults as that seen in children; however, most of the reports of hMPV infections have focused on infection in children. We report a case of severe hMPV pneumonia requiring mechanical ventilation in an immunocompetent adult in Korea.

Background: Uteroglobin (UG) is a secretary protein that has strong immunomodulatory properties, and which is synthesized in most epithelia including lung tissue. Overexpression of UG is associated with decreased expression of cyclooxygenase (COX)-2 and suppression of cancer cell growth. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan along the kynurenine pathway, and both the reduction in local tryptophan and the production of tryptophan metabolites contribute to the immunosuppressive effects of IDO. Methods: In this study, we investigated the pattern of expression of COX-2 and IDO, and the effect of UG transduction in the expression of COX-2 and IDO in several non-small cell lung cancer cell lines, especially A549. Results: Both COX-2 and IDO were constitutionally expressed in A549 and H460 cells, and was reduced by UG transduction. In A549 cells, the slightly increased expression of COX-2 and IDO with the instillation of interferon-gamma (IFN-γ) was reduced by UG transduction. However, the reduced expression of COX-2 and IDO by UG transduction was not increased with IFN-γ instillation in A549 cells. In both the A549 COX-2 sense and the A549 COX-2 anti-sense small interfering RNA (siRNA)-transfected cells, IDO was expressed; expression was reduced by UG transduction, irrespective of the expression of COX-2. Conclusion: The results suggest that the anti-proliferative function of UG may be associated with the immune tolerance pathway of IDO, which is independent of the COX-2 pathway.

Background Miliary pulmonary nodules are commonly caused by various infections and cancers. We sought to identify the relative frequencies of various aetiologies and the clinical and radiographic predictors of miliary tuberculosis (TB) in patients with miliary pulmonary nodules. Methods We performed a retrospective cohort study of patients who presented with micronodules occupying more than two-thirds of the lung volume, based on computed tomography (CT) of the chest, between November 2001 and April 2007, in a tertiary referral hospital in South Korea. Results We analyzed 76 patients with miliary pulmonary nodules. Their median age was 52 years and 38 (50%) were males; 18 patients (24%) had a previous or current malignancy and five (7%) had a history of TB. The most common diagnoses of miliary nodules were miliary TB (41 patients, 54%) and miliary metastasis of malignancies (20 patients, 26%). Multivariate analysis revealed that age ≤30 years, HIV infection, corticosteroid use, bronchogenic spread of lesions, and ground-glass opacities occupying >25% of total lung volume increased the probability of miliary TB. However, a history of malignancy decreased the probability of miliary TB. Conclusion Miliary TB accounted for approximately half of all causes of miliary pulmonary nodules. Young age, an immune-compromised state, and several clinical and radiographic characteristics increased the probability of miliary TB.

Although it is not rare to find sputum that is positive acid-fast bacilli (AFB) smear but subsequent culture fails to isolate mycobacteria in clinical practice, the incidence and clinical implication of those sputa from new patients has not been clearly elucidated. The aim of this study was to determine the incidence and clinical implication of sputum with positive AFB smear but negative in mycobacterial culture. All sputa that were positive AFB smear requested during diagnostic work up for new patients visiting Seoul National University Hospital from 1 January 2005 through 31 December 2006 were included. Sputa producing a positive AFB smear but negative mycobacterial culture were classified into one of four categories: laboratory failure to isolate mycobacteria, false positive AFB smear, pathogen may show a positive AFB smear other than mycobacteria, and indeterminate results. Out of 447 sputa with a positive AFB smear, 29 (6.5%) failed to culture any organism. Among these 29 sputa, 18 were caused by laboratory failure to isolate mycobacteria, six were false positive smears, and five indeterminate. Although most sputum with a positive AFB smear but negative culture could be classified as a laboratory failure, clinicians should consider the possibility of false positive AFB smear.

Because additive effects of inhaled corticosteroids and long-acting anticholinergics are unclear, we undertook this study to compare the efficacy of tiotropium alone and tiotropium plus budesonide in patients with chronic obstructive pulmonary disease. The study subjects were randomized to receive either tiotropium 18 microg once daily with or without budesonide 200 microg twice daily for 6 weeks. The efficacy variables were changes in trough forced expiratory volume in one second (FEV1), St. George's Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and use of rescue medication. One hundred patients were randomized and 81 completed the study. The mean age was 64.0 yr, and the mean FEV1 was 39.7% predicted. Compared with tiotropium alone (N=40), the tiotropium/budesonide combination (N=41) was related to an improvement in the SGRQ total score (tiotropium -2.8 units and tiotropium/budesonide -5.6 units, p=0.003). 6MWD was improved by 13.5 m in the tiotropium group and by 22.5 m in the tiotropium/budesonide group (p=0.031). Changes in trough FEV1 and the use of rescue medication were similar between two groups. In conclusion, compared with tiotropium alone, the tiotropium/budesonide combination was related to an improved health-related quality of life. These data support that low-dose budesonide may enhance the efficacy of tiotropium.

Background: Pulmonary hypertension is one of the cardiovascular complications of in COPD. However, a diagnosis of pulmonary hypertension requires an invasive test, such as right heart catheterization. NT-proBNP is a cardiac hormone that is elevated when a cardiac volume or pressure overload is present. It was hypothesized that NT-proBNP might play a role in detecting of pulmonary hypertension in COPD patients. Method: The 31 COPD patients, who underwent all of NT-proBNP, echocardiography, and spirometry in Seoul National University Bundang Hospital during the period from November 2003 to July 2005, were retrospectively analyzed. Result: Of the 31 COPD patients, 9 patients had pulmonary hypertension. A significant positive correlation was observed between the NT-proBNP and pulmonary arterial pressure (r=0.589, p=0.002). However, there was no significant correlation observed between the and NT-proBNP and and pulmonary arterial pressure. Conclusion: NT-proBNP might indicate the presence of pulmonary hypertension in COPD patients.

Pulmonary cavities are caused by bacterial pneumonia, fungal diseases, lung cancer, and tuberculosis (TB). However, in Korea, patients with cavitary lung lesions are generally considered to have pulmonary TB, where the incidence of TB is approximately 70/100,000 per year. We report a case of chronic necrotizing pulmonary aspergillosis that was obscured by multidrug-resistant pulmonary TB. (Tuberc Respir Dis 2007; 63: 368-371)

The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/ T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex-matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans.

A primary choriocarcinoma of the lung is extremely rare, and difficult to distinguish from a metastatic choriocarcinoma considering that the lung is also one of the most frequent site s of metastasis. We report a 28-year-old woman patient who was initially misdiagnosed with an ectopic pregnancy and was operated on under the impression of an unidentified malignancy of the lung, which was finally proven to be a chorio carcinoma of the lung. A pelvic examination by a gynecologist, pelvic magnetic resonance imaging and whole body fluorodeoxyglucose positron emission tomography-computed tomography was performed in order to rule out a metastatic choriocarcinoma of the lung. After a curative operation, her serum β-human chorionic gonadotropin (HCG) level, which was highly elevated in the initial evaluation, had decreased dramatically to the normal range. She is currently being followed up regularly without any evidence of recurrence or elevation of her β-HCG level. (Tuberc Respir Dis 2006; 61: 578-584)

Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (< or =65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8+/-113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment.

Mycobacterium kansasii is one of the most common cause of pulmonary diseases due to nontuberculous mycobacteria. We investigated the changing in the number of isolation of M. kansasii and the clinical characteristics of M. kansasii pulmonary disease in Korea. Through searching the database of the Korean Institute of Tuberculosis, we identified the cases of isolated M. kansasii from 1992 to 2002. The number of M. kansasii isolation had increased from once in 1992 to 62 in 2002. Fifteen patients with M. kansasii pulmonary disease were identified during the period January 1997 to December 2002. Twelve patients (80%) were male and fourteen (93%) were from highly industrialized areas. The most common symptom was a cough. Seven patients (47%) had a cavitary lesion and right upper lobe was most commonly involved. Patients responded well to isoniazid and rifampicin based regimens both bacteriologically and radiographically. In conclusion, M. kansasii isolation has increased, especially in highly industrialized areas, as well as other nontuberculous mycobacteria in Korea.

A-67-year-old man was hospitalized due to fever, cough and dyspnea upon exertion, and was treated with intravenous antibiotics. During the hospital course he presented with weakness in his low extremities. The laboratory tests showed an elevated CK level and myoglobinuria. He was diagnosed with rhabdomyolysis with community-acquired pneumonia and treated accordingly. Subsequently, his symptoms and signs of rhabdomyolysis improved.

Background : This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules ( once daily) with a ipratropium metered dose inhaler (2 puffs of q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). Method : After the initial screening assessment and a two-week run-in period, patients received either tiotropium once daily or ipratropium four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second () and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. Result : In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted of 42 (12)% were analyzed. The trough response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. Conclusion : This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.

Background : A pleural effusion is a common medical problem. Despite several diagnostic tests, 15-20% of pleural effusions go undiagnosed. The aim of this study was to evaluate the clinical characteristics and prognosis of a lymphocyte dominant exudative pleural effusion with a low adenosine deaminase (ADA), low carcinoembryonic antigen (CEA), negative cytology and negative acid fast bacilli (AFB) smear. Method : From Jan 2000 to Aug 2001, 43 patients with lymphocyte dominant exudative pleural effusions whose AFB smear and cytologic exam were negative, their pleural fluid ADA level was

Background : The fact that only 10-20% of chronic cigarette smokers develop chronic obstructive pulmonary disease (COPD) reflects the presence of genetic factors associated with the susceptibility to COPD. Recently, it was reported that the surfactant protein A increases the secretion of matrix metalloprotease 9, which degrades extracellular matrices of the lung, through a Toll-like receptor 2 (TLR2). In this context, possible role of TLR2 in the pathogenesis of COPD was postulated, and a functional dinucleotide repeat polymorphism in intron II of TLR2 was evaluated for any association with COPD. Method : Male patients with COPD and male smokers with a normal pulmonary function were enrolled in this study. The number of Guanine-Thymine repeats in intron II of the TLR2 gene were counted. Because the distributions of the repeats were trimodal, the alleles were classified into three subclasses, 12-16 repeats: short (S) alleles; 17-22 repeats: medium length (M) alleles; and 23-27 repeats: long (L) alleles. Result : 125 male patients with COPD and 144 age- and gender-matched blood donors with a normal lung function were enrolled. There were no differences in the distribution of each allele subclass (S, M and L) between the COPD and control group (p=0.75). The frequencies of the genotypes with and without each allele subclass in the COPD and control group were similar. Conclusion : A microsatellite polymorphism in intron II of TLR2 gene was not associated with the development of COPD in Koreans.

연구 배경 : 면역 기능 저하를 초래하여 결핵의 재활성화에 관여할 것으로 생각되는 주기적인 항암화학요법치료 중인 고형암 환자에서 발생한 결핵의 임상적 특징과 치료 반응을 파악하고자 하였다. 대상 및 방법 : 2000년 1월부터 2004년 7월까지 국내 일개 3차 병원에서 항암화학요법 치료 중에 세균학적으로, 병리학적으로 또는 임상적으로 진단된 결핵 환자 중 기존에 알려진 결핵 재활성화의 위험 요인이 없는 22명을 대상으로 후향적 연구를 시행하였다. 결과

Background : When a non small cell lung caner patient at the stage is diagnosed with intrapulmonary nodule(s), the treatment plan and prognosis of the patient largely depend on whether the nodule is benign or malignant. In most cases, however, it is hard to conduct a biopsy on such a nodule, due to its small size. Furthermore, the predictive factors that may imply benignancy or malignancy of the nodules remain unknown. As such, the purpose of our study was to validate the incidence of malignant nodules in such cases, and find if there are any predictive factors. Methods : Chest computed tomography(CT) scans and the medical records of 444 patients, who had undergone non small cell lung cancer surgery, between July, 2001 and September, 2003, at Seoul National University Hospital, were retrospectively reviewed. Among non small cell lung cancer patients, with intrapulmonary nodule(s), only those cases where a CT scan or a biopsy of the nodules had been conducted, and had been followed up at intervals of more than 6 months were included. However, patients who had received chemotherapy or radiation therapy, pre- or post-operatively, or with calcified nodules, were excluded. Results : Our study group consisted of 39 patients, divided into two groups. The first group, 33 patients, had benign nodules, and the second group, 6 patients, had malignant nodules. The two groups were compared with regard to gender, age, cell type, pathologic stage, shape, size, location and number of nodules and presence of calcification around the nodules. There was no statistically significant difference between the two groups. Conclusion : The intrapulmonary nodules in non small cell lung cancer patients at the stage were mostly benign. Therefore, surgical treatment for such patients can be considered. Moreover, without predictive factors, pathological confirmation of the diagnosed nodules should be sought in all patients.

Background : Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines. Methods :T he A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirusuteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography.

Background : The resurgence of tuberculosis and outbreaks of multidrug resistant (MDR) tuberculosis have increased the emphasis for the development of new susceptibility testing of the Mycobacterium tuberculosis for the effective treatment and control of the disease. Conventional drug susceptibility testings, such as those using egg-based or agar-based media have some limits, such as the time required and difficulties in determining critical inhibitory concentrations, but these are still being used in many diagnostic laboratories because of no better lternatives, considering cost and accuracy. To overcome these limits, a rapid and simple method for new susceptibility testing, using live and dead assays, was applied for a bacterial cell viability assay to distinguish dead from live bacterial cells based on two-color fluorescence. Materials and Methods Strains : Forty strains were used in this study, 20 susceptible to all antituberculosis drugs and the other 20 resistant to the four first line antituberculosis drugs isoniazid, rifampicin, streptomycin and ethambutol. Antibiotics : The four antibiotics were dissolved in 7H9 broth to make the following solutions: , , and . Results : Live and dead Mycobacterium tuberculosis cells fluoresced green and red with the acridin (Syto 9) and propidium treatments, respectively. These results are very well accorded with conventional drug susceptibility testing by proportional method on Lowensen-Jensen media (L-J) containing 4 drugs (INH, RMP, EMB and SM), showing a 93.7 % accordance rate in susceptible strains and 95% in resistant strains. Conclusion : The results of the drug susceptibility testing using the live and dead bacterial cell assay showed high accordance rates compared with the conventional proportion method on L-J. This finding suggests that the live and dead bacterial cell assay can be used as an alternative to conventional drug susceptibility testing for M. tuberculosis strains.

and glycogen synthase kinase-3β (GSK-3β) are important modulators of apoptosis. However, their role in PS-341- induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-3β in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-3 β were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-3 β was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-3β enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-3β (DN-GSK-3β ). Inactivation of GSK-3β by pretreatment with lithium chloride or the overexpression of DN-GSK-3β suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-3β in lung cancer cells. (Tuberc Respir Dis 2004; 57:449-460)

Background :I t is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). Methods : HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. Results :A mong the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was

Background :S ynthetic glucocorticoids are widely used in many chronic inflammatory diseases because of their excellent anti-inflammatory activity. Enhancing the transcription of IκB and preventing activated NF-κB from binding to κB sites are thought to be the underlying mechanisms. But these data are largely derived from in vitro studies using cell lines. In this study, after administrating a steroid to volunteers, we evaluated the effect on the NF-κB system. Methods : Prednisolone(0.5mg/kg/d) was orally administered to 5 healthy volunteers for 7 days. Before and after the administration, we sampled their peripheral blood monocytes, and performed western blot analysis both with stimulation, using IL-1β, LPS, TNF, and without stimulation(baseline). We also performed EMSA after stimulation with LPS. Results : After ingestion of the steroid, baseline expressions of IκBα were increased in two of the subjects, while suppressed degradations of IκBα to stimulations were observed in all five. In addition, the binding capacity of NF-κB after the administration was decreased.

Background : Neutrophil-mediated inflammation is usually self-limiting, because neutrophils have a remarkably short life span. Prolonged neutrophil survival, which is caused by decreased spontaneous apoptosis, leads to persistent inflammation in sepsis. Because many inflammatory cytokines, which generate signals that delay apoptosis, are regulated by nuclear factor- κB transcription factor, we hypothesized that nuclear factor-κB might be related to the reduced neutrophil apoptosis observed in sepsis. Methods : Neutrophils of healthy volunteers and sepsis patients were freshly isolated from venous blood. Neutrophil apoptosis was assayed with two approaches : by counting apoptotic cells under a microscope and by flow cytometry using Annexin V. The activity of nuclear factor-κB was assessed by immunofluorescent staining or electrophoretic mobility shift assay. Expression of X-linked inhibitor of apoptosis was measured by western blot assay. Results : We confirmed reduced spontaneous neutrophil apoptosis in patients with sepsis. The number of apoptotic neutrophils in patients with sepsis increased to the level of that in healthy controls after

연구배경 : Proteasome 억제가 세포의 apoptosis에 미치는 영향은 세포 종류에 따라 차이를 보이고 있다. 그러나 아직까지 폐암 세포에서 proteasome 억제가 미치는 효과 및 그 기전에 관해서는 확실하게 규명되어 있지 못한 상태이다. 본 연구에서는 폐암 세포주에서 proteasome 억제에 의한 apoptosis의 유도 유무를 관찰하고, 그 기전을 규명하고자 하였다. 방 법 : 폐암 세포주인 A549와 NCI-H157 세포에 proteasome 억제제인 MG132와 PS-341을 투여하고 세포의 생존율을 MTT 분석으로 평가하였고, apoptosis 유무를 PARP 단백에 대한 Western 분석으로 확인하였다. Proteasome 억제가 caspase 3와 JNK의 활성화에 미치는 효과를 각각 Western 분석과 immunocomplex kinase 분석으로 평가하였다. Proteasome 억제제를 투여하고 항 apoptosis 경로인 ERK와 cIAP1에 미치는 효과를 Western 분석으로 평가하였다. 결 과 : A549와 NCI-H157 세포에 MG132를 투여하였을 때, 세포생존율의 감소가 관찰되었고, 이는 apoptosis의 유도에 의한 것으로 확인되었다. MG132와 PS-341 처치로 caspase 3와 JNK가 활성화되었다. 반면에 활성화된 ERK의 발현과 cIAP1의 발현은 감소하였다. 결 론 : 폐암 세포에서 proteasome 억제에 의한 apoptosis에는 caspase 3, JNK와 같은 apoptosis 유도 경로의 활성화와 함께 항 apoptosis 경로의 억제가 관여할 것으로 생각된다. 【Background : Proteasome inhibitors can promote either cell survival or programmed cell death, depending on both the specific type and proliferative status of the cell. However, it is not well known whether inhibition of proteasome activity is related to apoptosis in lung cancer cells. In addition, the exact mechanisms responsible for apoptosis induced by proteasome inhibition are not well understood. In the present study, we have examined the effect of proteasome inhibition on lung cancer cells and tried to test the mechanisms that may be associated with the apoptosis of these cells. Methods : We examined the effect of proteasome inhibition with MG132 or PS-341 on cell survival in A549 and NCI-H157 lung cancer cells using MTT assay, and analyzed the cleavage of PARP by Western blot analysis to find evidence of apoptosis. Next, we evaluated the activation of caspase 3 by Western blot analysis and the activity of JNK by immunocomplex kinase assay. We also examined the changes in anti-apoptotic pathways like ERK and cIAP1 by Western blot analysis after inhibition of proteasome function. Results : We demonstrated that MG132 reduced cell survival by inducing apoptosis in A549 and NCI-H157 cells. Proteasome inhibition with MG132 or PS-341 was associated with activation of caspase 3 and JNK, reduced expression of activated ERK, and downregulation of cIAP1. Conclusion : Apoptosis induced by proteasome inhibition may be associated with the activation of pro-apoptotic pathways like caspase 3 and JNK and the inactivation of anti-apoptotic pathways in lung cancer cells.】

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the IκB/NF-κB pathway have been shown to vary according to the cell type. However, their effects on the IκB/NF-κB pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the IκB/NF-κB pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the IκB/NF-κB pathway and IκB kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-α, LPS or IL-1β. The IκBα expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using

Background : NF-κB is a characteristic transcriptional factor which has been shown to regulate production of acute inflammatory mediators and to be involved in the pathogenesis of many inflammatory lung diseases. There has been some evidence that PI3K/Akt pathway could activate NF-κB in human cell lines. However, the effect of PI3K/Akt pathway on the activation of NF-κB varied depending on the cell lines used in the experiments. In this study we evaluated the effect of PI3K/Akt pathway on the activation of NF-κB in human respiratory epithelial cell lines. Methods : BEAS-2B, A549 and NCI-H157 cell lines were used in this experiment. To evaluate the activation of Akt activation and IκB degradation, cells were analysed by western blot assay using

Fluoroquinolone is one of the first-line antibiotics recommended for treating community-acquired pneumonia. However, using fluroquinolones for presumptive community-acquired pneumonia can delay the diagnosis and the treatment of pulmonary tuberculosis because of its strong activity against mycobacteria. Here, we report a case of a 54-year-old female taking immunosuppressants after a renal transplant whose diagnosis of pulmonary tuberculosis was delayed as a result of the use of levofloxacin and amikacin under the original impression of community-acquired pneumonia. This case suggests that clinicians should consider the possibility of pulmonary tuberculosis in the case of a partial response of the pneumonia to flouroquinolones and/or aminoglycosides. (Tuberculosis and Respiratory Diseases 2003, 55:395-401)

26세 여자환자가 우측 흉통을 주소로 응급실을 방문하였다. 흉부방사선검사에서 우측 기흉을 진단받고 흉관 삽입술을 시행하였다. 환자는 6년전부터 레이노드 현상이 있었고 양손에 피부경화증이 있었으며 항 DNA 국 소이성화효소 I 항체가 양성으로서 전신성 경화증을 진단받았다. 고해상력 컴퓨터단층촬영에서 양쪽 폐야에 낭종성 병변이 관찰되었고 기흉은 낭종의 파열에 의한 것으로 판단되었다. 전신성 경화증은 폐를 포함한 여러 장기를 침범하는 질환이다. 이 질환에서 기흉과 낭종성 폐병변이 발생하였던 증례들은 1954년 이래로 보고되 어 왔는데 모든 증례에서 기흉은 전신성 경화증을 진단받은 뒤에야 발견된 것이었다. 본 증례는 기흉으로 발 현한 전신성 경화증의 첫 증례라는 점에서 임상적 의의가 있다고 여겨진다. (Tuberculosis and Respiratory

Cigarette smoking is the most important risk factor for obstruction of airflow in chronic obstructive pulmonary disease (COPD). Matrix metalloproteinases (MMPs) or an imbalance between MMPs and their inhibitors, the tissue inhibitors of MMP (TIMPs), is considered to play a role in the pathogenesis of COPD. We investigated whether the MMPs expression or the imbalance between MMPs and TIMP-1 is associated with the amount of cigarette smoking and the FEV1 value, in the lung parenchyma of 26 subjects (6 non-smokers and 20 cigarette smokers). First, we performed zymographic analysis to identify the profile of the MMPs, which revealed gelatinolytic bands mainly equivalent to MMP-9 in the smokers. We then measured, using enzyme immunoassay, the concentrations of MMP-9 and its inhibitor, TIMP-1. Correlation analysis revealed that both the MMP-9 concentrations and the molar ratios of MMP-9 to TIMP-1 (MMP-9/TIMP-1) were correlated with the amount of cigarette smoking. Furthermore, MMP-9 concentrations were inversely correlated with FEV1. In conclusion, this study shows that MMP-9 expression in human lung parenchyma is associated with cigarette smoking and also with the obstruction of airflow, suggesting that MMP-9 may play a role in the pathogenesis of the cigarette smoke-induced obstruction of airflow known as the characteristic of COPD.

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P

연구배경 : 아포프토시스를 억제하는 단백질들은 암의 발생, 진행 및 치료 반응에 있어서 중요한 역할을 한다고 알려져 있다. bcl-2는 지금까지 가장 잘 알려진 항아포프토시스 단백질이고 최근에 survivin이라 하는 IAP군과 HSP 등이 새롭게 밝혀졌고 이들은 많은 암종에서 발견되었다. 이에 저자들은 비소세포폐암을 대상으로 survivin, HSP70, 그리고 bcl-2의 발현에 대해서 면역조직화학적 분석을 시행함으로써 임상적 특성과의 관련성을 알아보고자 하였다. 방 법 : 99예의 비소세포폐암 조직으로 변역조직화학적 염색을 시행하였으며 일차 항체로 anti-survivin rabbit polyclonal antibody, anti-HSP70 mouse monoclonal antibody, anti-Bcl-2 mouse monoclonal antibody를 이용하였다. 각각의 단백질 발현과 여러 임상적, 조직학적 지표들과의 연관성은 Chi-square test를 이용하여 비교하였다. 모든 통계적 분석은 SPSS software를 이용하였다. 결 과 : 99예 중 남녀 비는 78 : 21이었고 평균 연령은 56.1세였으며 조직학적 분류는 편평상피암이 42예로 가장 많았고, 병리학적 병기로는 IB기 가 30예로 가장 많았다. Survivin은 33예 (33.3%)에서 발현되었고 여성에서 발현률이 유의하게 높았고 비흡연자에서 발현률이 높은 경향을 보였으며 흡연자 중 흡연양이 증가할수록 발현률은 유의하게 감소하였다. 또한 재발된 환자군에서 survivin은 유의하게 높은 발현률을 보였다. HSP70은 총 99예 중 84예 (84.8%)에서 발현되어 3 가지 단백질 중 가장 높은 빈도를 보였으나 유의한 관련성을 보이는 임상 지표는 없었다. bcl-2는 18예 (18.2%)에서 발현되었고 bcl-2 발현군에서의 재발률이 유의하게 높았고 흡연양이 많을수록 발현률이 감소하는 경향을 보였으나 다른 임상 지표와는 관련성이 없었다. 각 단백질의 발현군과 비발현군 사이에 중간 생존기간을 비교하였으나 통계적 유의성은 없었다. 결 론 : 본 연구에서 survivin 발현은 비흡연자에서 높은 경향을 보이고 여성과 종양이 재발한 군에서 유의하게 높은 발현률을 보이고 bcl-2 발현군에서 재발률이 유의하게 높은 반면 HSP70의 발현은 임상적, 조직학적 지표들과 관련성이 없었다. 결론적으로 발암과정에 중요한 아포프토시스에 관여하는 survivin, HSP 그리고 bcl-2에 대한 보다 광범위한 연구가 필요할 것으로 생각된다. 【Background : Anti-apoptotic proteins may be involved in tumor development, progression and the response to treatment, Bcl-2 is by far the most studied anti-apoptotic protein. A novel inhibitor of apoptosis, designated survivin, and the heat shock proteins (HSPs) have recently been found in many human cancers. Immunohistochemical methods were used to determine the expression level of survivin, HSP70 and bcl-2 in non-small cell lung cancer (NSCLC) to evaluate their clinical significance. Materials and Methods : Tissue array slides were obtained from 99 surgically resected NSCLCs. Immunohistochemical staining was performed by an immuno-peroxidase technique using an avidin-biotinylated horseradish peroxidase complex. Anti-survivin rabbit polyclonal antibodies, anti-HSP70 mouse monoclonal antibodies and anti-bcl-2 mouse monoclonal antibodies were used as the primary antibodies. Results : Positive staining of survivin was detected in 33.3% of the cases. Survivin positivity is associated with to females and recurrence. A nonstatistically significant trend toward increased survivin expression was observed in non-smokers, and its expression inversely correlated with the number of cigarettes smoked in smokers. HSP70 was detected in 84.8% but this did not correlated with the clinicopathologic characteristics. Bcl-2 was detected in 18.2% and its expression correlated to tumor recurrence. No significant difference in the median survival time was noted in a comparison of all cases with survivin expression and those without. There was no association between HSP70 or bcl-2 expression and survival. Conclusion : Survivin expression was significantly associated with females and tumor recurrence. In addition its expression was inversely associated with the number of cigarettes smoked. However, HSP70 and bcl-2 expression were not associated with the clinical parameters or survival. This suggests that measuring the survivin levels may be useful in identifying patients at high risk for disease recurrence. Therefore, survivin might be a new diagnostic/therapeutic target in cancer.】

Background : The NF- transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF- complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF- complexes into the nucleus where they bind to the elements and regulate the transcription of the target genes. Recent reports also suggest that NF- proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF- expression was reported in many cancer cell lines and tissues. The constitutive activation of NF- was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF- is important for cancer survival. NF- also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF- subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF- in lung cancer has not been reported. Materials and Methods : In this study, the NF- nuclear binding activity in the basal and TNF- stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF- expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF- in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF- These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF- was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF- complexes was markedly higher after stimulation with TNF- In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF- complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF- complex was variant of a p50/p50 homodimer. Conclusion : The NF- activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.

A extrapulmonary small cell carcinoma is a very rare disease, and a primary pleural manifestation is extremely rare. A diagnosis of a small cell carcinoma should be based on the cell morphology, histological pattern, and an immunohistochemical study. We recently experienced a case of small cell carcinoma (SCC) of the pleura in a 59-year-old man who had suffered from right pleuritic chest pain. A histopathological confirmation of SCC was made by a video-associated thoracoscopic lung biopsy. Systemic chemotherapy with etoposide and cisplatin was initiated.