A Case of Capecitabine-Induced Sarcoidosis / 결핵및호흡기질환

Sarcoidosis is an inflammatory disease involving multiple-organs with an unknown cause. The new onset of sarcoidosis associated with therapeutic agents has been observed in 3 clinical settings; tumor necrosis factor antagonists in autoimmune rheumatologic diseases, interferon alpha with or without ribavirin in patients with chronic hepatitis C or melanoma, and antineoplastic agent-associated sarcoidosis in patients with hematologic malignancies. Here, we report a female patient who developed sarcoidosis after capecitabine treatment as an adjuvant chemotherapy for sigmoid colon cancer. To our knowledge, this is the first report of a capecitabine-induced sarcoidosis.

First Isolation of Segniliparus rugosus from a Patient with Radiologic Features Similar to Non-Tuberculous Mycobacteriosis / 결핵및호흡기질환

In 2005, a group of mycolic acid-containing bacteria was characterized as belonging to a novel genus, Segniliparus with species Segniliparus rugosus and S. rotundus. We report a case of the S. rugosus isolated from a 54-year-old woman with radiologic features mimicking that of non-tuberculous mycobacteriosis (NTM). When the patient first visited our hospital, an acid-fast bacteria (AFB) smear tested positive and Mycobacterium tuberculosis polymerase chain reaction (TB PCR) was negative in the bronchoalveolar lavage sample. After 2 months, the growing colonies were reported as NTM, but could not be identified because they had died. One year after the initial visit, induced sputum samples showed the same results, positive AFB smear and negative TB PCR. At this point, the growing colonies were identified as S. rugosus. Therefore, we should consider Segniliparus genus as a differential diagnosis for AFB in respiratory specimens in addition to the genus Mycobacterium.

Gastric Metastasis of Primary Lung Adenocarcinoma Mistaken for Primary Gastric Cancer / 결핵및호흡기질환

The stomach is a rare site for metastasis, with autopsy incidence rates of 0.2% to 1.7%. This low rate makes diagnosis of metastatic gastric cancer challenging for clinicians. The authors report a case of a 64-year-old man diagnosed with gastric metastasis of primary lung adenocarcinoma that was initially mistaken for primary gastric cancer, as well as a review of the medical literature.

Clinical Characteristics and Prognosis of Lymphocyte Dominant Exudative Pleural Effusion with Low ADA, Low CEA, Negative Cytology and Negative AFB Smear / 결핵및호흡기질환

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 < 40 IU/L, and their CEA level was < 10 ng/mL were enrolled in this study. A retrospective analysis of the patients' medical records was carried out. RESULT: Among 31 of the 43 cases (72%), probable underlying diseases causing the pleural effusion were identified: 21cases of malignant diseases, 4 cases of liver cirrhosis, 2 cases of pulmonary tuberculosis, 1 case of end stage renal disease, 1 case of a chylothorax, 1 case of a post?CABG (coronary artery bypass graft) state, 1 case of a pulmonary embolism. No clinically suspected etiology was identified in the remaining 12 cases (28%). Of these 12 pleural effusions, 7 cases spontaneously resolved, 2 effusions resolved with antibiotics, and the other 2 cases were persistent. CONCLUSION: Lymphocyte dominant exudative pleural effusions with a low ADA, low CEA, negative cytological exam, and negative AFB smear, but without a definite cause might have a benign course and clinicians can observe them with attention.

Lack of the Association between Microsatellite Polymorphism in Toll-like Receptor 2 Gene and Development of COPD / 결핵및호흡기질환

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.

Effect of FK506 and Cyclosporin A on I(kappa)B(alpha) Degradation and IKK Pathway in Bronchial Epithelial Cells, Monocytes, Lymphocytes and Alveolar Macrophages / 결핵

BACKGROUND: Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the IkappaB/NF-kappaB pathway have been shown to vary according to the cell type. However, their effects on the IkappaB/NF-kappaB pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the IkappaB/NF-kappaB pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the IkappaB/NF-kappaB pathway and IkappaB 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-alpha, LPS or IL-1beta. The I(kappa)B(alpha) expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-I(kappa)B(alpha) as the substrate. RESULTS: Neither CsA nor FK506 affected the level of I(kappa)B(alpha) expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNFalpha-induced I(kappa)B(alpha) degradation in bronchial epithelial cells. In contrast, the TNFalpha-induced I(kappa)B(alpha) degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced I(kappa)B(alpha) degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on I(kappa)B(alpha) degradation was not related to IKK. CONCLUSIONS: CsA and FK506 suppressed the I(kappa)B(alpha) degradation in bronchial epithelial cells, mono. cytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

A Case of Pulmonary Tuberculosis with Delayed Diagnosis Due to the Temporary Clinical Improvement After Use of Levofloxacin and Amikacin Under the Impression of Community Acquired Pneumonia / 결핵

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.

Effect of Steroid Administration Ex Vivo on the IkappaB/NF-kappaB Pathway in Human Peripheral Blood Monocytes / 결핵

BACKGROUND: Synthetic glucocorticoids are widely used in many chronic inflammatory diseases because of their excellent anti-inflammatory activity. Enhancing the transcription of IkappaB and preventing activated NF-kappaB from binding to kappaB 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-kappaB 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-1beta, LPS, TNF, and without stimulation(baseline). We also performed EMSA after stimulation with LPS. RESULTS: After ingestion of the steroid, baseline expressions of I(kappa)B(alpha) were increased in two of the subjects, while suppressed degradations of I(kappa)B(alpha) to stimulations were observed in all five. In addition, the binding capacity of NF-kappaB after the administration was decreased. CONCLUSION: Steroid plays such roles as enhancing the transcription of I(kappa)B(alpha), suppressing the DNA binding capacity of NF-kappaB, and suppressing the degradation of I(kappa)B(alpha).

Role of PI3K/Akt Pathway in the Activation of IkappaB/NF-kappaB Pathway in Lung Epithelial Cells / 결핵

BACKGROUND: NF-kappaB 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-kappaB in human cell lines. However, the effect of PI3K/Akt pathway on the activation of NF-kappaB 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-kappaB 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 IkappaB degradation, cells were analysed by western blot assay using phospho-specific Akt Ab and IkappaB Ab. To block PI3K/Akt pathway, cells were pretreated with wortmannin or LY294002 and transfected with dominant negative Akt (DN-Akt). For IKK activity, immune complex kinase assay was performed. To evaluate the DNA binding affinity and transcriptional activity of NF-kappaB, electrophoretic mobility shift assay (EMSA) and luciferase assay were performed, respectively. RESULTS: In BEAS-2B, A549 and NCI-H157 cell lines, Akt was activated by TNF-alpha and insulin. Activation of Akt by insulin did not induce I(kappa)B(alpha) degradation. Blocking of PI3K/Akt pathway via wortmannin/LY294002 or DN-Akt did not inhibit TNF-alpha- induced I(kappa)B(alpha) degradation or IKK activation. Inhibition of PI3K/Akt did not affect TNF-alpha-induced NF-kappaB activation. Overexpression of DN-Akt did not block TNF-alpha-induced transcriptional activation of NF-kappaB, but wortmannin enhanced TNF-alpha-induced in NF-kappaB transcriptional activity. CONCLUSION: PI3K/Akt was not involved in TNF-alpha-induced I(kappa)B(alpha) degradation or transcriptional activity of NF-kappaB in human respiratory epithelial cell lines.