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Background Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. Methods We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. Results ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. Conclusion Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

Background Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC. Methods Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays. Results The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis). Conclusion Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

Background: It is difficult but important to differentiate between bacterial and viral infections, especially for respiratory infections. Hence, there is an ongoing need for sensitive and specific markers of bacterial infections. We investigated novel biomarkers for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infections. Methods: This was a prospective, observational study of patients with community acquired bacterial pneumonia, 2009 H1N1 Influenza A infection, and healthy controls. Serum samples were obtained on the initial visit to the hospital and stored at -80˚C. We evaluated CRP (C-reactive protein), PCT (procalcitonin), LBP (lipopolysaccharide- binding protein) and copeptin. These analytes were all evaluated retrospectively except CRP. Receiver operating characteristic curve (ROC) analyses were performed on the resulting data. Results: Enrolled patients included 27 with community acquired bacterial pneumonia, 20 with 2009 H1N1 Influenza A infection, and 26 who were healthy controls. In an ROC analysis for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection, areas under the curve (AUCs) were 0.799 for CRP (95% Confidence interval [CI], 0.664~0.934), 0.753 for PCT (95% CI, 0.613~0.892) and 0.684 for LBP (95% CI, 0.531~0.837). Copeptin was not different among the three groups. Conclusion: These findings suggest that serum CRP, PCT and LBP can assist physicians in discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection.

Exogenous lipid pneumonia is a rare disease resulting from the aspiration or inhalation of vegetable, animal, or mineral oils. In Korea, the most frequently implicated agent is squalen, which can be obtained from shark liver oil. Lipid pneumonia by aspiration of the vegetable oil is very rare. We experienced a 77-year-old man with a history of ingestion of green perilla oil. His clinical course was favorable; after exposure to the oil was stopped, the patient's symptoms improved.

Background: Airway mucus hypersecretion plays an important role in the pathogenesis of asthma, and is associated with the induction of MUC5AC expression in airway secretion. The MUC5AC gene is highly polymorphic; however, there are few studies about the association between the polymorphisms of the MUC5AC gene and asthma susceptibility or asthma phenotypes. We have investigated the association of MUC5AC promoter polymorphisms with the risk of asthma and asthma phenotypes. Methods: We determined the genotypes of the MUC5AC promoter (-1274G>A) in 78 asthma patients and in 78 age, sex-matched control individuals in the Korean population. Genomic DNAs from blood were analyzed by PCR and RFLP (restriction fragment length polymorphism) determination. We examined , total eosinophil count, serum IgE level, and the presence of atopy (by a skin test) in asthma patients. Results: The mean age of the patients was years and 38.5% were men, and the mean was of predicted in the asthma patients. The -1274G>A polymorphism of the MUC5AC promoter in asthma patients was not significantly different as compared with normal individuals (GG 57.7%, AG 34.6% and AA 7.7% in asthma patients vs. GG 56.4%, AG 38.5% and AA 5.1% in control subject, p = 0.752, Cod). Several clinical parameters in asthma patients such as , total eosinophil count, serum IgE level, and the presence of atopy, were not associated with the -1274G>A polymorphism of the MUC5AC promoter. Conclusion: The -1274G>A single nucleotide polymorphism (SNP) frequency of the MUC5AC promoter was not associated with asthma in a Korean population.

Background: The cognitive function is impaired in patients with hypoxemic chronic obstructive pulmonary disease (COPD). However, there are conflicting results regarding the cognitive function in patients with non-hypoxemic COPD. COPD patients also have sleep disorders. This study examined the cognitive function in non-hypoxemic COPD patients, and nocturnal sleep was assessed in COPD patients with a cognitive dysfunction. Methods: Twenty-eight COPD patients (mean age, 70.7 years) with an oxygen saturation > 90%, and 33 healthy control subjects (mean age, 69.5 years) who had visited for a routine check-up were selected. The neurocognitive tests were performed using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) Neuropsychological Battery. Results: The scores of the word list recall test (p=0.03) and the word list recognition test (p=0.006) in the COPD group were significantly lower than those in the control group. Nine patients showed a significantly impaired cognitive function. Seven of these underwent polysomnography, which revealed apnea-hypopnea indices ≥ five per hour in five patients. The median oxygen desaturation index and median limb movement index were 3.6/h and 38.6/h, respectively. Conclusion: These results suggest that the verbal memory function is impaired in non-hypoxemic COPD patients. Six out of seven COPD patients with an impaired cognitive function had sleep disorders of sleep apnea and/or periodic limb movements during sleep. (Tuberc Respir Dis 2007; 62: 382-388)

연구배경: 광역학 치료는 폐암 치료에 실질적으로 이용 가능하며, 많은 연구들에서 폐암 세포에서 세포사멸을 일으킨다는 것이 이미 알려져 있다. 그러나 이 세포사멸의 기전은 아직 정확히 알려져 있지 않으며, 이에 암세포의 전사에서 초기 변화가 어떻게 일어나는 지를 알아보기 위하여 실험을 수행하였다. 방법: 광과민성 물질인 DH-I-180-3으로 A549 세포에 처리를 하고 광역학 치료를 한 후 관찰하였다. 광역학 치료 후 DEG kit를 이용하여 폐암 세포주에서의 유전자 발현을 보았으며, 유세포 분석기를 이용하여 세포 사멸을 측정하였다. 광역학 치료 후 의미있는 변화를 보인 유전자는 염기서열분석으로 확인하였다. 결과: 유세포분석 결과 폐암세포주는 대부분 세포괴사에 의하여 사멸되었다.광역학 치료 후, 9개의 유전자에서 명확한 변화가 있음을 발견했으며 이 중 8개의 유전자를 밝혀내었다. 3-phosphoglycerate dehydrogenase와 리보솜 단백질 S29의 유전자 발현이 증가되어 있었으며, carbonic anhydrase XII, clusterin, MRP3s1 protein, complement 3, membrane cofactor protein, β-1 integrin의 유전자 발현은 감소되어 있었다. 결론: 본 연구는 광과민성 물질인 DH-I-180-3을 이용한 광역학 치료에서 폐암 세포의 세포사멸의 주된 기전이 세포괴사에 의해 이루어 진 것임을 밝혀냈으며, 이와 관련된 유전자들 대부분이 막단백의 변화를 통해 이루어짐을 알 수 있었다.

Background; Several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. Therefore, we sought to identify the proteomic biomarkers, with wsing proteomic tools, that differed according to the outcome of sepsis patients. Methods; Upon admission to the ICU, blood samples were obtained from the 16 patients with sepsis who were enrolled in this study. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI –TOF MS) was used to identify the markers that could predict the outcome of sepsis. Results; We found six peaks, by using cation and anion chips, that statistically differed between those patients who died and those who survived. Conclusion; The biomarkers we found by using proteomic tools may help predi ct the prognosis and also plan the treatment of sepsis. (Tuberc Respir Dis 2006; 61: 41-45)

Background; The diagnosis of chlamydial infection is based on serology. The current gold standard of diagnosis is MIF(microimmunofluorescence), but this modality is subjective and time-consuming. Protein microarray with using a SPR(surface plasmon resonance) sensor has recently been suggested as a method for detecting infection. For developing a protein chip to diagnose chlamydial infection, EBs(elementary bodies) were immobilized on a gold chip and the interaction between an antibody for Chlamydophila pneumoniae and the EBs(elementary bodies) immobilized on the surface of the gold chip was measured by using an SPR sensor. Methods; For the surface antigen, the EBs of Chlamydophila pneumoniae LKK1 were purified. Charged arrays were prepared by using PDDA(polydiallyldimethylammonium chloride) which has a positive charge. After immobilization of the chlamydial EBs on the PDDA surface, the investigation of the surface was done with using atomic force microscopy. After the antibody for C. pneumoniae was applied on chip, we monitored the SPR wavelength-shift to detect any antigen-antibody interaction with using a self-assembled SPR sensor. Results; The chlamydial EBs on the positively charged PDDA were visible on the surface with using atomic force microscopy. The SPR wavelength increased after interaction of antibody for C. pneumoniae with the EBs immobilized on charged gold surface. The wavelength-shift was correlated with the concentration of antigens. Conclusion; The surface immobilization of EBs on the gold surface with the charged arrays was identified and the antigen-antibody interaction on the gold chip was detected via the SPR sensor. Further investigations are needed to apply this technique to the clinical field.

Pulmonary endometriosis is an uncommon disease, and usually detected by catamenial hemoptysis. Treatment of pulmonary endometriosis may be medical(hormone therapy) or surgical. Since hormone therapy may cause sterility, most of patients who wish to conceive usually choose surgical resection. Although video-assisted thoracic surgery(VATS) has advantage of small scar, reducing postoperative pain and shortening hospital stay, it is not easy to locate the precise lesion and resect whole endometrial tissue not to be remained. 17 years old female with catamenial hemoptysis was treated sucessfully with a partial resection of the lung using VATS, and has been asymptomatic for 7months since the operation.

Background : The Sequential Organ Failure Assessment (SOFA) score can help to assess organ failure over time and is useful to evaluate morbidity. The aim of this study is to evaluate the performance of SOFA score as a descriptor of multiple organ failure in critically ill patients in a local unit hospital, and to compare with APACHE III scoring system. Methods : This study was carried out prospectively. A total of ninety one patients were included who admitted to the medical intensive care unit (ICU) in Chuncheon Sacred Heart Hospital from May 1 through June 30, 2000. We excluded patients with a length of stay in the ICU less than 2 days following scheduled procedure, admissions for ECG monitoring, other department and patients transferred to other hospital. The SOFA score and APACHE III score were calculated on admission and then consecutively every 24 hours until ICU discharge. Results : The ICU mortality rate was 20%. The non-survivors had a higher SOFA score within 24 hours after admission. The number of organ failure was associated with increased mortality. The evaluation of a subgroup of 74 patients who stayed in the ICU for at least 48 hours showed that survivors and non-survivors followed a different course. In this subgroup, the total SOFA score increased in 81% of the non-survivors but in only 21% of the survivors. Conversely, the total SOFA score decreased in 48% of the survivors compared with 6% of the non-survivors. The non-survivors also had a higher APACHE III score within 24 hours and there was a correlation between SOFA score and APACHE III score. Conclusion : The SOFA score is a simple, but effective method to assess organ failure and to predict mortality in critically ill patients. Regular and repeated scoring enables patient's condition and clinical course to be monitored and better understood. The SOFA score well correlates with APACHE III score. (Tuberc Respir Dis 2004; 57:329-335)

Address for correspondence : Seung-Joon Lee, M.D. Department of Internal Medicine Kangwon National University Hospital 17-1 Hyoja-3-dong, Chunchon-si Kangwon-do 200-947, Republic of Korea. Phone : (82) 33-258-2377 Fax : (82) 33-258-2455 E-mail: medfman@knuh.or.kr Received : Nov. 10. 2003. Accepted : Jun. 29. 2004. Background : The statistical analysis is an essential procedure ensuring that the results of researches are based on evidences rather than opinion. The purpose of this study is to evaluate which statistical techniques are used and whether these statistical methods are used appropriately or not in the journal of Tuberculosis and Respiratory Diseases. Materials and Methods : We reviewed 185 articles reported in the journal of Tuberculosis and Respiratory Diseases in 1999. We evaluated the validity of used statistical methods based upon the checklist that was developed on the basis of the guideline for statistical reporting in articles for medical journals by International Committee of Medical Journal Editors. Results : Among 185 articles, original articles and case reports were 110 (59.5%) and 61 (33.0%) respectively. In 112 articles excluding case reports and reviews, statistical techniques were used in 107 articles (95.5%). In 94 articles (83.9%) descriptive and inferential methods were used, while in 13 (11.6%) articles only descriptive methods were used. With the types of inferential statistical techniques, comparison of means was most commonly used (64/94, 68.1%), followed by contingency table (43/94, 45.7%) and correlation or regression (18/94, 19.1%). Among the articles in which descriptive methods were used, 83.2% (89/107) showed inappropriate central tendency and dispersion. In the articles in which inferential methods were used, improper methods were applied in 88.8% (79/89) and the most frequent misuse of statistical methods was inappropriate use of parametric methods (35/89, 39.3%). Only 14 articles (13.1%) were satisfactory in utilization of statistical methodology. Conclusion : Most of the statistical errors found in the journal were misuses of statistical methods related to basic statistics. This study suggests that researchers should be more careful when they describe and apply statistical methods and more extensive statistical refereeing system would be needed. (Tuberc Respir Dis 2004; 57:168-179)

연구배경 : 삼출성 흉수의 원인을 알기위해 일반적으로 흉막천자를 통한 미생물학적, 세포학적 검사와 cope needle을 사용한 흉막생검이 사용되나, 통상적인 방법으로는 약 20%에서 원인 진단에 이르지 못한다고 보고되고 있다. 본 연구는 원인을 알 수 없는 삼출성 흉수환자에서 기존의 맹검적 흉막생검을 대신하여 2mm 흉강경을 시행한 경우의 진단적 정확성 및 합병증의 발생정도를 알아보고자 하였다. 방 법 : 2002년 4월부터 2003년 8월까지 삼출성 흉수의 진단을 위해 강원대학교병원에 입원한 16세 이상의 환자를 대상으로 전향적 연구를 시행하였다. 객담 검사 및 1회 이상의 흉수천자를 통한 미생물 배양검사, 세포진 검사 등을 통해 흉수의 원인을 알 수 없었던 환자를 대상으로, 2mm 흉강경을 이용하여 육안소견 및 병리소견을 확인하였다. 결 과 : 총 15명의 환자가 포함되었으며 중앙연령은 56세(범위 21-77세), 남녀의 비율은 10:5였다. 흉강경 이전에 시행했던 흉수천자에서 11명(73.3%)이 림프구최다, 3명(20.0%)이 호중구최다, 1명(6.7%)이 호산구최다의 소견을 보였다. 흉강경을 통한 조직학적 검사를 통해서 12명(93.3%)의 환자에서 정확한 진단을 얻었으며, 이들의 진단은 결핵성 흉수가 8명(66.7%), 악성흉수가 4명(33.3%)이었고, 세균성농흉이 2명이었다. 흉강경으로 진단되지 않은 1명은 폐흡충증으로 최종 진단되었다. 시술과 관련된 합병증으로서 사망은 없었고, 새로 발생한 발열이 6명(40%), 기흉이 1명(6.7 %) 있었다. 결 론 : 원인을 알 수 없는 삼출성 흉수 환자에서 2mm 흉강경은 매우 정확도가 높고 안전한 검사로서, VATS보다 환자에게 부담을 적게 주면서 진단율을 높일 수 있다. 【Background : To evaluate exudative pleural fluid, thoracentesis for microbiological and cytological examination and pleural biopsy by using a Cope needle are traditionally performed. Even after these studies, about 20% of patients remain undiagnosed. We evaluated the diagnostic accuracy and complications of 2-mm minithoracoscopy instead of blind biopsy in patients with undiagnosed exudative pleural effusion. Method : Fifteen patients with exudative pleural effusion underwent thoracoscopy between April 2002 and August 2003. The indication was undiagnosed pleural effusions after having performed sputum and pleural fluid exami-nations both microbiologically and cytologically. Results : The median age of the patients was 56 years (range 21-77). Pleural effusions were lymphocyte-dominant in 11 patients (73.3%) and neutrophil-dominant in 3 (20.0%). The remaining patient (6.7%) had pleural-fluid eosinophilia. Minithoracoscopic biopsy revealed accurate diagnosis in 14 patients (93.3%), consisting of tuberculous pleurisy in 8 (66.7%), malignant effusions in 4 (33.3%), and parapneumonic effusions in 2 (13.3%). One was diagnosed as having paragonimiasis from thoracoscopic findings and clinical considerations. There was no procedure-associated mortality. There were six cases of new onset fever (40%) and one of pneumothorax (6.7 %). Conclusion : Two-millimeter minithoracoscopy, which is less invasive than conventional thoracoscopy, was an accurate and safe method for undiagnosed exudative pleural effusion.】

A bronchus-associated lymphoid tissue(BALT) lymphoma of the lung is a rare disorder of patients with Sjgren's syndrome. A 49-year-old woman was admitted for an evaluation of exertional dyspnea and general weakness which had persisted for two years. The patient had suffered from dry mouth and dry eyes for five years. The physical examinations showed a coarse breath sound with inspiratory crackles on the whole lung field, particularly on the both basal lungs. The laboratory data disclosed high titers of anti-nuclear antibodies, and anti-SSA (Ro), and anti-SSB (La) antibodies. Chest radiographs demonstrated the presence of bilateral, diffuse, reticulonodular densities in both lungs. Thin-section CT scans showed diffusely distributed mosaic pattern of an inhomogeneous attenuation extending over the entire lung zone. The histological findings from an open-lung biopsy specimen revealed an accumulation of lymphoid cells around the bronchioles and an extension of malignant lymphoma cells from the bronchiolar epithelium toward the alveolar space. Immunohistochemically, the neoplastic cells reacted positively to the CD 20 antigen and were focally positive for the UCHL 1 antigen. The histological diagnosis was consistent with a low grade marginal zone B-cell lymphoma originating in the BALT. Here, we present a case of a histologically proven BALT lymphoma of the lung in a patient with primary Sjgren's Syndrome.

Many disorders and abnormalities are accompanied by cavitary lesoin of the lung and one of the most common causes of cavitary lung disease are primary and metastatic lung neoplasms. but cavitary formation of primary lung cancer is not frequent and cavitary or cystic pulmonary metastases of this is also rare. We report a case of cavitary pulmonry metastases of primary lung cancer proven by bronchoscopic biopsy and chest CT. The patients was 60 year-old heavy smoker who had no known underlying lung diseases 7 years ago and complained chronic cough. The chest CT showed primary lung cancer in right low lobe with multiple cavitary or cystic metastases in both lungs and multiple lymphatic metastases.

Background : Smoking and high-risk occupation have been known to be the risk factors of lung cancer. The carcinogen-metabolizing enzymes in human body such as glutathione S-transferase M1, T1 and N-acetyltransferase 1 have also been regarded as risk factors in many cancers, because the activities of those enzymes play a role in metabolizing the carcinogen. A case-control study was conducted to evaluate the genetic polymorphism of GSTM1, T1 and NAT1 in lung carcinogenesis in Korean men. Methods : The histologically proven lung cancer cases were recruited from Seoul National University Hospital. The patients of more than 40-year-old with the nonmalignant urinary tract diseases were recruited as controls from the same hospitals. The informations of demographical characteristics and smoking were obtained by interview or chart review and the genetic polymorphisms of GSTM1, T1 and NAT1 were determined by PCR-based assay. The statistical analyses were performed by linear logistic regression. Results : The number of case-control was 118 and 150, respectively. The smoking history was significantly higher in the lung cancer patients than the controls. The prevalence of GSTM1 null-type was statistically higher(OR=2.25 ; 95% CI=1.12-4.51) in squamous cell carcinoma than other genotypes, but other histologic types were not The prevalence of GSTT1 null-type were not statistically higher than other genotypes in all histologic types. The fast acetylator of NAT1 was more prevalent than normal(OR=2.13 ; 95% CI=1.04-4.40) in all lung cancer patients. Conclusion : The null-type of GSTM1 and fast acetylator of NAT1 are associated with development of lung cancer in Korean men.

Background: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor from cytoplasm to nucleus by releasing an inhibitory protein subunit, . Activation of is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of . From above facts, we can assume the expression of IL-8 and IL- gene by LPS stimulation may occur through the activation of , which is mediated through the release of by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL- gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL- gene in mononuclear phagocytic cells. Method: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of -induced IL-8 and IL- mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL- mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL- mRNA was performed. Results: In PBMC, dose and time dependent expression of IL-8 and IL- mRNA by exogenous was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL- mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. Conclusion: Oxygen free radical may have some role in the expression of IL-8 and IL- mRNA of PBMC but that radical might not be .