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Background

Transmembrane protein 16A (TMEM16A) is associated with mucus secretion and ion transport in asthma. Clarithromycin (CAM) is reported to inhibit IL-13-induced goblet cell metaplasia. However, the effect of CAM on TMEM16A function and expression remains unclear.

Methods

Tracheal epithelial cells from guinea pigs were cultured for ~14 days at an air-liquid interface in medium containing IL-13 (10?ng/ml) in the absence or presence of CAM (20?µg/ml) or a TMEM16A inhibitor, T16Ainh-A01 (10 µg/ml). Electrophysiological studies were performed by Ussing?s short-circuit technique. The cells were used for immunofluorescence staining with antibodies against TMEM16A, MUC5AC, and α-tubulin. The cells were also examined by transmission electron microscopy. TMEM16A protein levels in the cell lysates were determined by ELISA. For the in vivo study, guinea pigs were treated intratracheally with IL-13 in the absence or presence of CAM or T16Ainh-A01.

Results

CAM decreased the MUC5AC-positive cells and reduced TMEM16A expression in them and increased the α-tubulin-positive cells. CAM inhibited TMEM16A protein levels in a dose-dependent manner, and decreased UTP-induced Cl ion transport. In cells treated with IL-13 for 24?h, TMEM16A appeared prior to MUC5AC protein expression, and was inhibited by CAM. In the in vivo study, CAM inhibited IL-13-induced goblet cell metaplasia and TMEM16A expression. The inhibitory effects of CAM were similar to those of T16Ainh-A01.

Conclusions

CAM inhibited IL-13-induced TMEM16A expression, Cl ion transport and goblet cell metaplasia both in vitro and in vivo. CAM may thus improve airway mucociliary differentiation by attenuating TMEM16A expression in IL-13-related asthma.  相似文献   
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The evaluation of a new computer program for analysis and interpretation of pediatric Frank vectorcardiograms is reported. The program includes extensive age- and sex-dependent criteria based on tables of limits for numerous vectorcardiographic parameters. In 728 catheterized patients, the diagnostic performance for type A statements was tested against independent and objective evidence obtained from hemodynamic and angiographic data. The overall diagnostic accuracy ranged from 75 to 89% without difference between children < 2 years of age and those >- 2 years of age. Sensitivities and specificities of the various diagnoses did not differ much between the 2 age groups. In the younger children, the accuracy of a positive diagnosis of left ventricular hypertrophy, right ventricular hypertrophy, and biventricular hypertrophy was 20, 15, and 32% higher, respectively, than in the older children. The accuracy of the diagnosis “normal” was 28% lower in the younger children. These differences were explained by the higher proportion of pathologic findings in the younger children: 93% versus 74% in the older children.Given the strict methods of the evaluation, the diagnostic accuracy of this pediatric program was considered clinically satisfactory. Program performance appears to be dependent not on patient age but on prevalence of abnormalities in the population analyzed. Further improvement can be expected by making the criteria more adaptable to the composition of the population.  相似文献   
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Heart failure (CHF) appearing late after aortic (AV) or mitral valve (MV) replacement (R) may be due to mechanical factors such as prosthetic or native valve dysfunction, or due to myocardial disease. We studied 41 patients who developed CHF late (6 weeks to 11 years) after AVR or MVR with gated blood pool scan (RNV) to analyze the spectrum of ejection fraction (EF) and its clinical correlates. Of the 17 patients who developed CHF after AVR, 10 had RNV EF greater than 0.5 (all of whom had severe valve or prosthetic dysfunction as the primary cause of CHF) and seven had EF less than 0.5 (five with severe myocardial disease and two with prosthetic dysfunction). Of the 24 with CHF after MVR, 13 had RNV EF greater than 0.5. In contrast to post-AVR patients, only 8 of the 13 patients had mechanical causes of CHF (seven prosthetic dysfunction and one constrictive pericarditis). Of the 11 patients after MVR with EF less than 0.5, nine had severe myocardial disease and two had prosthetic dysfunction. Thus (1) reduced EF in patients with CHF-after AVR or MVR suggests myocardial disease as the basis for CHF, and (2) normal EF implies a mechanical cause of CHF after AVR but may be associated with either myocardial or mechanical factors after MVR.  相似文献   
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Hepatocellular carcinoma (HCC) is a highly heterogeneous disease displaying differences in angiogenesis, extracellular matrix proteins, the immune microenvironment and tumor cell populations. Additionally, genetic variations and epigenetic changes of HCC cells could lead to aberrant signaling pathways, induce cancer stem cells and enhance tumor progression. Thus, the heterogeneity in HCC contributes to disease progression and a better understanding of its heterogeneity will greatly aid in the development of strategies for the HCC treatment.  相似文献   
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