Extensive Bilateral Lemierre Syndrome due to Methicillin-Resistant Staphylococcus epidermidis in a Patient with Lung Adenocarcinoma / 결핵및호흡기질환

Lemierre syndrome (LS) is a septic thrombophlebitis of the internal jugular vein (IJV) following an oropharyngeal infection. LS is commonly caused by normal anaerobic flora and treated with appropriate antibiotics and anticoagulation therapy. Although the incidence of disease is very rare, 15% cases of LS are fatal even in the antibiotic era because of disseminated septic thromboemboli. We reported a case of extensive bilateral LS due to methicillin-resistant Staphylococcus epidermidis in a 63-year-old female with lung adenocarcinoma. Initial examination revealed a retropharyngeal abscess; hence, intravenous ceftriaxone and steroid were initiated empirically. However, pulmonary thromboembolism developed and methicillin-resistant S. epidermidis was identified in the bacterial culture. Despite intensive antibiotic and anticoagulation therapies, extensive septic thrombophlebitis involving the bilateral IJV and superior vena cava developed. Adjunctive catheter-directed thrombolysis and superior vena cava stenting were performed and the patient received antibiotic therapy for an additional 4 weeks, resulting in complete recovery.

Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-beta-induced alveolar epithelial to mesenchymal transition

Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in most adult tissues except the lung. In this study, we evaluated the interaction of ligand advanced glycation end products (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs. Our results indicate that AGE inhibited the TGF-beta-dependent alveolar EMT by increasing Smad7 expression, and that the effect was abolished by RAGE siRNA treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the development of pulmonary fibrosis by inhibiting TGF-beta-dependent signaling in AECs.

Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro. In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.

IP-10 Decreases TNF-alpha Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis / 결핵및호흡기질환

BACKGROUND: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. METHODS: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-alpha with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. RESULTS: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-alpha induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. CONCLUSION: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

A Case of Erdheim-Chester Disease Who Has Policythemia Vera / 결핵및호흡기질환

Erdheim-Chester disease (ECD) is a rare disease that is characterized by multi-organ involvement of foamy histiocytes. It causes systemic inflammation, and also demonstrates various clinical manifestations and has a poor prognosis. We encountered a case of ECD in a patient that had been treated for underlying polycythemia vera. As far as we know, this is the first reported case worldwide where ECD developed in association with polycythemia vera. A 59-year-old man visited our hospital due to pleuric pain at the right side of the chest. Pleural tissue that was obtained following a thoracoscopic biopsy showed non-Langerhan's cell histiocytosis, suggesting the presence of ECD. The histiocytes stained positively for CD68, but were negative for S-100 and CD1a. The patient also complained of pain at both hips and the right shoulder area. An X-ray and magnetic resonance image demonstrated that the lesion showed sclerosis and osteolysis in both the proximal femur and right humerus. Treatment was started with predinisolone, and subsequently cyclophosphamide was added. ECD is a very rare multi-systemic disease, and its cause and therapeutic options have not yet been defined. ECD has a poor prognosis. Therefore, we believe that additional case studies are needed prior to the determination of a novel therapy for ECD.

Mutational Analysis of JAK1 Exons 10 and 13 in Non-small Cell Lung Cancers

PURPOSE : JAK kinases play important roles not only in normal cellular processes, but they are also important in tumor development. A recent study identified two somatic mutations of JAK1 in leukemia cells that were detected in exon 10 (p.T478S) and exon 13 (p.V623A). The aim of this study was to see whether the JAK1 mutations in these exons occur in non-small cell lung cancers (NSCLC). MATERIALS AND METHODS : We analyzed the exons 10 and 13 of JAK1 for detecting somatic mutations in NSCLC by performing polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) assay. RESULTS : The SSCP analysis revealed no evidence of somatic mutation in the DNA sequences of JAK1 exon 10 and exon 13 in the 47 NSCLCs. CONCLUSION : The data presented here indicate that the JAK1 exons 10 and 13 may not be somatically mutated in human NSCLCs, and this suggests that the JAK1 mutation in exons 10 and 13 may not play an important role in the tumorigenesis of NSCLCs

Neutrophil Elastase Causes MUC5AC Mucin Synthesis Via EGF Receptor, ERK and NF-kB Pathways in A549 Cells

BACKGROUND: Neutrophil elastase (NE) was found to increase the respiratory mucin gene, MUC5AC, although the molecular mechanisms of this process remain unknown. We attempted to determine the signal transduction pathway through which NE induces MUC5AC gene expression in bronchial epithelial cells. METHODS: A fragment of 1.3 Kb MUC5AC promoter which had been cloned into the pGL3-Basic luciferase vector was transfected to the A549 cells. By measuring the luciferase activity, we were able to evaluate the MUC5AC promoter activity in A549 cells. The involvement of mitogen-activated protein kinases (MAPK) was confirmed by Western blotting. To confirm the involvement of nuclear factor kappaB (NF-kB), we used site-directed mutagenesis and electrophoretic mobility shift assay (EMSA) autoradiogram. The MUC5AC mRNA expression was confirmed by RT-PCR. RESULTS: NE increased the transcriptional activity of the MUC5AC promoter in A549 cells. The increased transcriptional activity of the MUC5AC promoter by NE was found to be associated with increased NF-kB activity. Site-directed mutagenesis showed that the transfection of the mutated NF-kB binding sites from the PGL3-MUC5AC-3752 promoter luciferase reporter plasmid decreased the luciferase activity after NE stimulation. Among the MAPKs, only extracellular signal-regulated kinases (ERK) were involved in this NE-induced MUC5AC mucin expression. RT-PCR also showed that NE increased MUC5AC mRNA. An EMSA autoradiogram revealed that NE induced NF-kB: DNA binding. CONCLUSIONS: These results indicate that human NE induces MUC5AC mucin through the epidermal growth factor receptor (EGF-R), ERK, and NF-kB pathways in A549 cells.

Mechanism of Decrease in Lung Injury by Low Dose of Endotoxin During Hyperoxia in the Rats / 결핵

No abstract available.

Clinical Analysis of Pulmonary Hamartoma: 29 Cases / 결핵

BACKGROUND: Pulmonary hamartomas are the most common form of benign tumors, occurring in approximately 0.2% of routine autopsies. However, only a few reports on the clinical characteristics of pulmonary hamartoma in Korea have been published. METHODS: The charts, X-rays and pathological specimens of 29 pulmonary hamartoma patients who were diagnosed by a pathological examination from 1990 to 1999 at the Catholic Medical Center were retrospectively reviewed. RESULTS: The peak incidence of the tumor occurred in the sixth decade of life (37.5%). Seventeen patients (58.6%) were asymptomatic and 12 patients (41.4%) had symptoms. Chest discomfort was the most common symptom (31.0%). A total of 25 tumors (86.2%) were parenchymal, and 4 (13.8%) were endobronchial. Twenty cases were in the right lung and 9 cases were in the left lung (approximately 1:2.2). The RLL was the most commonly involved lobe (31.0%). Calcification was noted in 5 cases (19.2%) on a plain X-ray and in 5 cases (29.4%) on chest CT. Accompanied neoplasms were observed in 2 cases. Twenty-four hamartomas (82.8%) were diagnosed by a surgical resection and 4 cases (13.8%) were diagnosed by a fine needle aspiration biopsy. Twenty-six hamartomas (89.7%) were managed by a surgical resection. The follow up ranged from 4 to 55 months (mean, 19.6 months) and no recurrent pulmonary hamartomas were noted. CONCLUSION: Pulmonary hamartoma is more common in females and more commonly involved in the right lung. Calcification was noted only in 19.2% on a plain chest X-ray and 29.4% on a chest CT. No recurrent hamartomas had developed during the follow up period.