The Prevalence Rate of Tuberculin Skin Test Positive by Contacts Group to Predict the Development of Active Tuberculosis After School Outbreaks.

BACKGROUND: The tuberculin skin test (TST) is the standard tool to diagnose latent tuberculosis infection (LTBI) in mass screening. The aim of this study is to find an optimal cut-off point of the TST+ rate within tuberculosis (TB) contacts to predict the active TB development among adolescents in school TB outbreaks. METHODS: The Korean National Health Insurance Review and Assessment database was used to identify active TB development in relation to the initial TST (cut-off, 10 mm). The 7,475 contacts in 89 schools were divided into two groups: Incident TB group (43 schools) and no incident TB group (46 schools). LTBI treatment was initiated in 607 of the 1,761 TST+ contacts. The association with active TB progression was examined at different cut-off points of the TST+ rate. RESULTS: The mean duration of follow-up was 3.9±0.9 years. Thirty-three contacts developed active TB during the 4,504 person-years among the TST+ contacts without LTBI treatment (n=1,154). The average TST+ rate for the incident TB group (n=43) and no incident TB group (n=46) were 31.0% and 15.5%, respectively. The TST+ rate per group was related with TB progression (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.001-1.050; p=0.037). Based on the TST+ rate per group, active TB was best predicted at TST+ ≥ 16% (OR, 3.11; 95% CI, 1.29-7.51; area under curve, 0.64). CONCLUSION: Sixteen percent of the TST+ rate per group within the same grade students can be suggested as an optimal cut-off to predict active TB development in middle and high schools TB outbreaks.

Relationships of coagulation factor XIII activity with cell-type and stage of non-small cell lung cancer.

PURPOSE: Factor XIII (FXIII), a thrombin-activated plasma transglutaminase zymogen, is involved in cancer development and progression through a triggered coagulation pathway. The aim of this study was to examine whether FXIII activity levels differed in non-small cell lung cancer (NSCLC) patients according to histological types and TNM stage when compared with healthy subjects. MATERIALS AND METHODS: Twenty-eight NSCLC patients and 28 normal controls who had been individually age-, gender-, body mass index-, smoking status-, and smoking amount-matched were enrolled: 13 adenocarcinomas, 11 squamous cell carcinomas, and four undifferentiated NSCLCs; four stage I, two stage II, 12 stage III, and 10 stage IV NSCLCs. FXIII activity was measured using fluorescence- based protein arrays. RESULTS: The median FXIII activity level of the NSCLC group [24.2 Loewy U/mL, interquartile range (IQR) 14.9-40.4 Loewy U/mL] was significantly higher than that of the healthy group (17.5 Loewy U/mL, IQR 12.6-26.4 Loewy U/mL) (p=0.01). There were no differences in FXIII activity between adenocarcinoma (median 18.6 Loewy U/mL) and squamous cell carcinoma (median 28.7 Loewy U/mL). NSCLC stage significantly influenced FXIII activity (p=0.02). The FXIII activity of patients with stage III NSCLC (median 27.3 Loewy U/mL, IQR 19.3-40.5 Loewy U/mL) was significantly higher than those of patients with stage I or II (median 14.0 Loewy U/mL, IQR 13.1-23.1 Loewy U/mL, p=0.04). FXIII activity was negatively correlated with aPTT in NSCLC patients (r=-0.38, p=0.04). CONCLUSION: Patients with advanced-stage NSCLC exhibited higher coagulation FXIII activity than healthy controls and early-stage NSCLC patients.

The start of chemotherapy until the end of radiotherapy in patients with limited-stage small cell lung cancer.

BACKGROUND/AIMS: Chemotherapy combined with radiation therapy is the standard treatment for limited stage small cell lung cancer (LS-SCLC). Although numerous studies indicate that the overall duration of chemoradiotherapy is the most relevant predictor of outcome, the optimal chemotherapy and radiation schedule for LS-SCLC remains controversial. Therefore we analyzed the time from the start of any treatment until the end of radiotherapy (SER) in patients with LS-SCLC. METHODS: We retrospectively analyzed 29 patients diagnosed histologically with LS-SCLC and divided them into two groups: a short SER group (< 60 days) and a long SER (> 60 days) group. Patients were treated with irinotecan-based chemotherapy and thoracic radiotherapy. RESULTS: Sixteen patients were in the short SER group and 13 patients were in the long SER group. Short SER significantly prolonged survival rate (p = 0.03) compared with that of long SER. However, no significant differences in side effects were observed. CONCLUSIONS: Short SER should be considered to improve the outcome of concurrent chemoradiotherapy for LS-SCLC.

A case of paraneoplastic limbic encephalitis associated with small cell lung cancer.

Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, affective and behavioral disturbances and seizures. Among many different neoplasms known to cause PLE, small cell lung cancer (SCLC) is the most frequently reported. The pathogenesis is not fully understood but is believed to be autoimmune-related. We experienced a patient with typical clinical features of PLE. A 67-year-old man presented with seizure and disorientation. Brain magnetic resonance imaging demonstrated high signal intensity in the bilateral amygdala and hippocampus in flair and T2-weighted images suggestive of limbic encephalitis. Cerebrospinal fluid tapping revealed no evidence of malignant cells or infection. Positron emission tomography/computed tomography showed a lung mass with pleural effusion and a consequent biopsy confirmed the diagnosis of PLE associated with SCLC. The patient was subsequently treated with chemotherapy and neurologic symptoms gradually improved.

Routine pulmonary function test can estimate the extent of tuberculous destroyed lung.

Tuberculous destroyed lung (TDL) is diagnosed by a clear past history of tuberculosis with findings of parenchymal destruction verified by chest X-ray. Despite the resultant deterioration of lung function and quality of lives seen in TDL patients, the exact mechanism or characteristics of pulmonary function worsening have not been clearly studied. We investigated the feature of respiratory impairment of TDL patients, and studied whether extent of destroyed lung measured with chest CT has any correlation with routine lung function. To evaluate the degree of destruction, the Goddard classification scoring system was modified into a novel scoring system (destroyed lung score, (DLS)) with a score from 0 to 4. Twenty-five subjects were enrolled. TDL predominantly manifested as an obstructive pattern (64%, 16/25). Median value of DLS of the entire lung was 2.6 (1.7-3.9). Absolute values of FEV1 and FVC were both negatively associated with DLS (r = -0.78, P = 0.001, and r = -0.61, P = 0.021). Percentage of predicted value of FEV1 and FVC were also negatively associated with DLS (r = -0.62, P = 0.019, and r = -0.76, P = 0.002). Our study shows that lung function of TDL patients were notably correlated with the extent of destroyed lung measured with chest CT scan.

The expression of HSPs, anti-oxidants, and cytokines in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome.

OBJECTIVES: We studied several acute inflammatory materials (AIM) such as various inflammatory cytokines, oxidative stress, and heat shock proteins in ARDS patients by simultaneously measuring from bronchoalveolar lavage fluid (BALF) and plasma. DESIGN AND METHODS: AIM were measured by using plasma and BALF sampling obtained from ARDS group (n=12) and non-ARDS group (n=12). RESULTS: In the BALF, only HSP 47 was significantly increased in ARDS group than non-ARDS group. In plasma, GRP 94, HSP 90, HSP 60, HSP 47, GPx-3, and IL-8 were increased significantly in ARDS group. In short, most of the AIM in BALF or plasma were not significantly different in ARDS group as compared with non-ARDS group. Ninety-day mortality was significantly related to HSP90, HSP 60 and GPx-3 in plasma but not in BALF. CONCLUSION: Alteration of AIM levels in both BALF or plasma of ARDS group was not remarkable compared with the non-ARDS group. Our result suggests the need to reconsider ARDS pathophysiology and therapeutic strategy.

Asthma-like symptoms are increased in the metabolic syndrome.

BACKGROUND: The prevalence of obesity and asthma has been increasing during the last several decades. Obesity has been reported to be associated with asthma. Obesity, especially abdominal obesity, is the main component of the metabolic syndrome. OBJECTIVES: We thus hypothesized that metabolic syndrome is an important contributing factor for the development of asthma-like symptoms. METHODS: The Korean Health and Genome Study started in 2001 as an ongoing population-based study of Korean adults 40 to 69 years of age. The prevalence of asthma-like symptoms in the previous 12 months was obtained by a questionnaire, and spirometric testing was conducted. RESULTS: Among the 10,038 participants, the data from 9,942 individuals (4,716 men and 5,226 women) was available. Asthma-like symptoms (wheeze [p = 0.0006], resting dyspnea [p = 0.0062], and post-exercise dyspnea [p < 0.0001]) were increased in the subjects of the metabolic syndrome group. Subjects with asthma-like symptoms had a decreased lung function compared to subjects without asthma-like symptoms. Among the components of the metabolic syndrome, abdominal obesity and hypertension were the risk factors for asthma-like symptoms. CONCLUSIONS: Metabolic syndrome is associated with asthma-like symptoms. Among the components of metabolic syndrome, abdominal obesity and hypertension are the risk factors for asthma-like symptoms.

The immune tolerance of cancer is mediated by IDO that is inhibited by COX-2 inhibitors through regulatory T cells.

Prostaglandin (PGE2), synthesized by cyclooxygenase-2 (COX-2), is associated with cellular immune tolerance during the process of cancer development. Induction of tolerance requires a specific environment in which dendritic cells and regulatory T cells (Tregs) play an essential role. It was recently shown that maturation of dendritic cells in the presence of indoleamine 2, 3-dioxygenase (IDO) results in activation of Tregs, and inhibition of COX-2 activity regulated IDO expression within the tumor microenvironment. Thus, we hypothesized that the tumor immune tolerance would be inhibited by COX-2 inhibitor and this inhibition would be mediated by IDO-dependent Tregs inhibition. The PGE2 in Lewis lung cancer cells (3LL) and serum of mice were measured for the evaluation of COX-2 inhibitors' local and systemic effects. The production of PGE2 in 3LL cells and serum of 3LL tumor-bearing mice were decreased by COX-2 inhibition. However, there were no significant differences in serum PGE2 levels among normal control and celecoxib-treated nontumor-bearing mice. The accumulation of Tregs was reduced in the celecoxib-treated 3LL tumor-bearing mice. In addition, the expressions of COX-2, IDO, and Foxp3 were reduced in the mice treated with a COX-2 inhibitor, and this was found to correlate with a reduction in the size of tumor mass and metastasis. These results suggest that the antitumor effects of COX-2 inhibitors seemed to be correlated with the inhibition of IDO and Tregs. Therefore, COX-2 inhibitors might provide a therapeutic strategy for Tregs-induced tumor immune tolerance.

Proteomic analysis in lung tissue of smokers and COPD patients.

RATIONALE: Although cigarette smoking is the most important risk factor for COPD, COPD develops in only a minority of smokers, suggesting a significant genetic role. To solve the underlying pathophysiologic mechanism, it is critical to understand genes and their final product, ie, proteins. We investigated the exclusive proteins from the lung tissues obtained from COPD patients using proteomics. METHODS: Nontumorous lung tissue specimens were obtained from patients who underwent surgery for lung cancer. We included 22 subjects: nonsmokers (n = 8), smokers without COPD (healthy smokers, n = 7), and smokers with COPD (n = 7). Proteins were separated from their spots with two-dimensional polyacrylamide gel electrophoresis and examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). To validate the proteins from the above procedures, Western blotting and immunohistochemistry were conducted. RESULTS: Twelve protein spots from COPD group significantly increased or decreased compared with the other two groups were chosen for MALDI-TOF-MS analysis. Eight proteins were up-regulated in the COPD group as compared with the nonsmokers. Meanwhile, five proteins from the COPD group were up-regulated and five were down-regulated when compared with healthy smokers. Of these, matrix metalloproteinase (MMP)-13 and thioredoxin-like 2 were significantly increased in the COPD patients by Western blot and immunohistochemistry. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes; however, thioredoxin-like 2 was primarily seen in the bronchial epithelium. CONCLUSIONS: MMP-13 and thioredoxin-like 2 in lungs increased in patients with COPD. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes. In contrast, thioredoxin-like 2 was primarily seen in the bronchial epithelium.

Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury.

INTRODUCTION: Poly (ADP-ribose) polymerase (PARP) participates in inflammation by cellular necrosis and the nuclear factor-kappa-B (NF-kappaB)-dependent transcription. The purpose of this study was to examine the roles of PARP in ventilator-induced lung injury (VILI) in normal mice lung. METHODS: Male C57BL/6 mice were divided into four groups: sham tracheostomized (sham), lung-protective ventilation (LPV), VILI, and VILI with PARP inhibitor PJ34 pretreatment (PJ34+VILI) groups. Mechanical ventilation (MV) settings were peak inspiratory pressure (PIP) 15 cm H2O + positive end-expiratory pressure (PEEP) 3 cm H2O + 90 breaths per minute for the LPV group and PIP 40 cm H2O + PEEP 0 cm H2O + 90 breaths per minute for the VILI and PJ34+VILI groups. After 2 hours of MV, acute lung injury (ALI) score, wet-to-dry (W/D) weight ratio, PARP activity, and dynamic compliance (CD) were recorded. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myeloperoxidase (MPO) activity, and nitrite/nitrate (NOX) in the bronchoalveolar lavage fluid and NF-kappaB DNA-binding activity in tissue homogenates were measured. RESULTS: The VILI group showed higher ALI score, W/D weight ratio, MPO activity, NOX, and concentrations of TNF-alpha and IL-6 along with lower CD than the sham and LPV groups (P < 0.05). In the PJ34+VILI group, PJ34 pretreatment improved all histopathologic ALI, inflammatory profiles, and pulmonary dynamics (P < 0.05). NF-kappaB activity was increased in the VILI group as compared with the sham and LPV groups (P < 0.05) and was decreased in the PJ34+VILI group as compared with the VILI group (P = 0.009). Changes in all parameters were closely correlated with the PARP activity (P < 0.05). CONCLUSION: Overactivation of PARP plays an important role in the inflammatory and transcriptional pathogenesis of VILI, and PARP inhibition has potentially beneficial effects on the prevention and treatment of VILI.

Aspiration pneumonia due to polyethylene glycol-electrolyte solution (Golytely) treated by bronchoalveolar lavage.

Polyethylene glycol (PEG)-electrolyte solution (Golytely), is most commonly used for bowel preparation before colonoscopy, as well as for barium enema and colon surgery. In this case, a 70-year-old man developed ARDS following the administration of Golytely by mouth before a scheduled colonoscopy. Aspiration of PEG-electrolyte solution was suspected, and the patient was successfully treated by BAL. Therefore, early bronchoscopy and BAL should be considered as initial treatment for PEG aspiration, because removal of PEG is most important for managing the disease.

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation.

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefinitib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

Proteomic analysis of peripheral T-lymphocytes in patients with asthma.

BACKGROUND: Asthma is chronic airway inflammation that occurs together with reversible airway obstruction. T-lymphocytes play an important role in the pathogenesis of asthma. Proteomic technology has rapidly developed in the postgenomic era, and it is now widely accepted as a complementary technology to genetic profiling. We investigated the changes of proteins in T-lymphocytes of asthma patients by using standard proteome technology: two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and a database search. METHODS: The proteins of CD3+ T-lymphocytes were isolated from whole blood of six steroid-naive asthmatic patients and of six healthy volunteers. 2D-PAGE was performed and the silver-stained protein spots were comparatively analyzed between the asthma and control groups using an image analyzer. Some differentially expressed spots were identified by MALDI-TOF-MS and database search. The messenger RNA expressions of some identified proteins were examined by real-time polymerase chain reaction (RT-PCR). RESULTS: Thirteen protein spots in the T-lymphocytes of the asthmatic patients were increased and 12 spots were decreased compared to those of the normal subjects. Among the identified proteins, the increased expression of the messenger RNA of phosphodiesterase 4C and thioredoxin-2 and the decreased expression of the messenger RNA of glutathione S-transferase M3 were confirmed by RT-PCR in the asthmatic patients. CONCLUSIONS: Proteomic examination of the peripheral T-lymphocytes revealed some differentially expressed proteins in the asthmatic patients. The possibility of using the differentially expressed proteins as important biomarkers and therapeutic targets in asthma patients warrants further studies.

Phase II study of irinotecan plus cisplatin with concurrent radiotherapy for the patients with limited-disease small-cell lung cancer.

BACKGROUND: A recently conducted randomized, phase III study that compared irinotecan plus cisplatin (IP) with etoposide plus cisplatin for the patients with extensive disease SCLC revealed a superior median survival rate and a superior 2-year survival rate for the IP combination therapy. Yet there have been few such reports on the patients suffering with limited disease SCLC (LD-SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of administering IP with concurrent radiotherapy for the patients with LD-SCLC. PATIENTS AND METHODS: Twenty chemotherapy-naïve patients with LD-SCLC were enrolled in our study. The patients were treated with 40 mg/m(2) irinotecan on days 1, 8 and 15 and with 60 mg/m(2) cisplatin on day 1 every 4 weeks until a maximum of six cycles was delivered. Once-daily radiotherapy included the administration of 50.4 Gy in 28 fractions. After completion of the radiation therapy, the dose of irinotecan was increased to 60 mg/m(2). RESULTS: The response rate was 85% (CR: 6; partial response, PR: 11). The median survival was 20.0 months (95% CI: 15.6-24.4 months) with 1-year and 2-year overall survival rates of 85 and 35%, respectively. The median progression free survival (PFS) was 12 months (95% CI: 6.2-18.1 months) with a 1-year PFS of 36%. The major hematologic toxicities of this regimen were neutropenia (60%), leukopenia (55%), anemia (20%) and thrombocytopenia (10%). The non-hematologic toxicities were nausea/vomiting (55%), diarrhea (35%) and dysphagia (15%). CONCLUSIONS: Our data show that IP with concurrent radiotherapy is an effective and tolerable regimen for the treatment of LD-SCLC and these findings warrant further investigation.

Successful removal of a slowly growing mediastinal cavernous haemangioma after vascular embolization.

Mediastinal haemangioma is a rare disease. We report a 23-year-old male patient with a posterior mediastinal cavernous haemangioma. The CXR revealed a progressively enlarging mediastinal mass which on chest CT and angiography appeared to be a well-enhanced hypervascular tumour. Angiographic gel foam embolization of the feeding vessels was undertaken prior to the surgical removal of the mass. The mass lesion following surgical removal was shown to be a cavernous haemangioma on histological examination.

Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury.

Neutrophils are considered to play a central role in ventilator-induced lung injury (VILI). However, the pulmonary consequences of neutrophil accumulation have not been fully elucidated. Matrix metalloproteinase-9 (MMP-9) had been postulated to participate in neutrophil transmigration. The purpose of this study was to investigate the role of MMP-9 in the neutrophilic inflammation of VILI. Male Sprague-Dawley rats were divided into three groups: 1) low tidal volume (LVT), 7 ml/kg of tidal volume (VT); 2) high tidal volume (HVT), 30 ml/kg of VT; and 3) HVT with MMP inhibitor (HVT+MMPI). As a MMPI, CMT-3 was administered daily from 3 days before mechanical ventilation. Degree of VILI was assessed by wet-to-dry weight ratio and acute lung injury (ALI) scores. Neutrophilic inflammation was determined from the neutrophil count in the lung tissue and myeloperoxidase (MPO) activity in the bronchoalveolar lavage fluid (BALF). MMP-9 expression and activity were examined by immunohistochemical staining and gelatinase zymography, respectively. The wet-to-dry weight ratio, ALI score, neutrophil infiltration, and MPO activity were increased significantly in the HVT group. However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity. These changes correlated significantly with MMP-9 immunoreactivity and MMP-9 activity. Most outcomes were significantly worse in the HVT+MMPI group compared with the LVT group. In conclusion, VILI mediated by neutrophilic inflammation is closely related to MMP-9 expression and activity. The inhibition of MMP-9 protects against the development of VILI through the downregulation of neutrophil-mediated inflammation.

PPAR-gamma agonist increase gefitinib's antitumor activity through PTEN expression.

Gefitinib exhibits antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10-20% of patients exhibit clinical response to this drug. The molecular mechanisms underlying gefitinib sensitivity remain unknown. Peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays roles in the regulation of cellular differentiation and growth. This regulation was mediated by increasing Phosphatase and tensin homologue deleted on chromosome Ten (PTEN) levels. PTEN plays a role in the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival. This study investigated the effects of PPAR-gamma agonist (rosiglitazone) on the expression of PTEN, as well as EGFR tyrosine kinase inhibitor (gefitinib)'s antitumor activity in A549 cells. The treatment of A549 cells with rosiglitazone reduced the growth of A549 cells in a dose-dependent manner, and facilitated the anti-proliferative effects of gefitinib. PPAR-gamma and PTEN expression were found to have increased in the gefitinib- and rosiglitazone-treated cells. This suggests that PPAR-gamma agonist (rosiglitazone) potentiated gefitinib's anti-proliferative effects by increased of PTEN expression, and suggest that PPAR-gamma ligands may serve as potential therapeutic agents for NSCLC.

Peroxisome proliferator-activated receptor-gamma inhibits cigarette smoke solution-induced mucin production in human airway epithelial (NCI-H292) cells.

The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to cigarette smoke is reported to induce goblet cell hyperplasia and mucus production. Mucin synthesis in airways has been reported to be regulated by the EGFR system. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the ligand-activated nuclear receptor superfamily. PPAR-gamma is implicated in anti-inflammatory responses, but mechanisms underlying these varied roles remain ill-defined. Recently, reports have shown that upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of the mechanisms through which PPAR-gamma agonists exert their anti-inflammatory actions. However, no data are available on the role of PPAR-gamma in smoke-induced mucin production. In this study, we investigated the effect of PPAR-gamma agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells. Exposure to cigarette smoke causes a significant decrease in PTEN expression and increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in MUC5AC mucin production in NCI-H292 cells. PPAR-gamma agonists or specific inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke-induced mucin production, with the upregulation of PTEN signaling and downregulation of Akt expression. This study demonstrates that PPAR-gamma agonist functions as a regulator of epithelial cell inflammation that may result in reduction of mucin-producing cells in airway epithelium.

The inhibitory effects of rebamipide on cigarette smoke-induced airway mucin production.

Cigarette smoke may be the main cause of chronic bronchitis. Exposure of cigarette smoke induces the recruitment of inflammatory cells in the airway epithelium, and release of the tumor necrosis factor alpha (TNFalpha) from airways. Previous reports have shown that cigarette smoke induces goblet cell metaplasia by activating an epidermal growth factor receptor (EGFR) cascade, and that this results in mucin production. Rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, OPC-12759) directly inhibits the production of superoxide (O2-) and inhibits proinflammatory cytokines (such as TNFalpha and IL-8). In the present study, we aimed to analyze the inhibitory effects of rebamipide on TNFalpha and EGFR activation after cigarette smoke treatment in vitro and in vivo. NCl-H292 cells and Sprague-Dawley rats were used for in vitro and in vivo studies. In vitro studies, cigarette smoke solution was found to increase TNFalpha secretion, and EGFR-specific tyrosine phosphorylation, and to elevate MUC5AC production. These effects were inhibited dose-dependently by pretreatment with rebamipide (MUC5AC protein levels were inhibited from 44% to 17%, P<0.05). In vivo studies, cigarette smoke was found to cause inflammatory cell recruitment and to increase the secretion of TNFalpha in bronchoalveolar lavage (BAL) fluids (from 198+/-78 to 2270+/-158 pg/ml, P<0.01). Moreover, the pretreatment of rats with rebamipide inhibited goblet cell metaplasia and TNFalpha secretion, dose-dependently (from 2270+/-158 to 1377+/-112 pg/ml, P<0.05). In conclusion, the exposure of airway epithelium to cigarette smoke-induced TNFalpha production, neutrophil recruitment, activated EGFR, and caused MUC5AC mucin synthesis. Moreover, rebamipide was found to prevent this cigarette smoke-induced TNFalpha release, and mucin production.

A case of extramedullary plasmacytoma arising from the posterior mediastinum.

Plasmacytomas are a localized proliferation of plasma cells in the bone marrow, and are less frequently seen in extraosseous organs or tissues. Extramedullary plasmacytoma is a rare malignant neoplasm, and is especially uncommon when it arises from the mediastinum. Here, we report on a case of posterior mediastinal extramedullary plasmacytoma in a 64-year-old man. He was admitted with an asymptomatic right apical mediastinal mass, which was provisionally diagnosed as a neurogenic mass. However, a subsequent investigation revealed that this tumor was a rare case of IgG kappa type extramedullary plasmacytoma arising from the posterior mediastinum. The patient was treated with local radiation to the mediastinum and is doing well without further evidence of disease.