Cloning of an isoform of mouse TGF-β type II receptor gene

AbstractA variant of transforming growth factor-β type II receptor (TGF-βRII) cDNA was isolated from a mouse brain cDNA library. The predicted receptor is identical to previously reported mouse TGF-βRII except that the isoform has an insertion sequence of 25 amino acids in the predicted ligand-binding domain. By the use of reverse transcription-polymerase chain reaction (RT-PCR), transcripts for both isoforms were detected in all tissues and developing embryos examined. The isoform transiently expressed in COS cells showed a similar ligand-binding specificity to authentic TGF-βRII. These results suggest that the mouse TGF-βRII gene generates multiple isoforms, possibly by alternative splicing, as reported for activin type IIB receptor; and an isoform which has the extra sequence in the ligand-binding domain is also involved in the TGF-β signal transduction

The dopamine D1 receptor is expressed and induces CREB phosphorylation and MUC5AC expression in human airway epithelium

Background Dopamine receptors comprise two subgroups, Gs protein-coupled “D1-like” receptors (D1, D5) and Gi-coupled “D2-like” receptors (D2, D3, D4). In airways, both dopamine D1 and D2 receptors are expressed on airway smooth muscle and regulate airway smooth muscle force. However, functional expression of the dopamine D1 receptor has never been identified on airway epithelium. Activation of Gs-coupled receptors stimulate adenylyl cyclase leading to cyclic AMP (cAMP) production, which is known to induce mucus overproduction through the cAMP response element binding protein (CREB) in airway epithelial cells. We questioned whether the dopamine D1 receptor is expressed on airway epithelium, and whether it promotes CREB phosphorylation and MUC5AC expression. Methods We evaluated the protein expression of the dopamine D1 receptor on native human airway epithelium and three sources of cultured human airway epithelial cells including primary cultured airway epithelial cells, the bronchial epithelial cell line (16HBE14o-), and the pulmonary mucoepidermoid carcinoma cell line (NCI-H292) using immunohistochemistry and immunoblotting. To characterize the stimulation of cAMP through the dopamine D1 receptor, 16HBE14o- cells and NCI-H292 cells were treated with dopamine or the dopamine D1 receptor agonists (SKF38393 or A68930) before cAMP measurements. The phosphorylation of CREB by A68930 in both 16HBE14o- and NCI-H292 cells was measured by immunoblot. The effect of dopamine or A68930 on the expression of MUC5AC mRNA and protein in NCI-H292 cells was evaluated by real-time PCR and immunofluorescence staining, respectively. Results The dopamine D1 receptor protein was detected in native human airway epithelium and three sources of cultured human airway epithelial cells. Dopamine or the dopamine D1-like receptor agonists stimulated cAMP production in 16HBE14o- cells and NCI-H292 cells, which was reversed by the selective dopamine D1-like receptor antagonists (SCH23390 or SCH39166). A68930 significantly increased phosphorylation of CREB in both 16HBE14o- and NCI-H292 cells, which was attenuated by the inhibitors of PKA (H89) and MEK (U0126). Expression of MUC5AC mRNA and protein were also increased by either dopamine or A68930 in NCI-H292 cells. Conclusions These results suggest that the activation of the dopamine D1 receptor on human airway epithelium could induce mucus overproduction, which could worsen airway obstructive symptoms

Effects of annealing of poly(3-hexylthiophene) film on the performance of double-layered EL devices of ITO/polymer/Alq3/Mg-Ag

Double layer devices with a structure of ITO/pHT/Alq3/Mg-Ag (ITO = indium tin oxide, pHT = regio-regular or random poly(3-hexylthiophene), Alq3 = tris(8-hydroxyquinoline)aluminium) were fabricated. The device with a random pHT film emitted a green-yellow light in all voltage region, while that having a regio-regular pHT film exhibited a color change from green to red by applying the bias voltage higher than 15 V. Annealing the pHT films prepared on ITO at 200 °C for 1 h in nitrogen, prior to vapor-deposition of the Alq3 layer, improved the device performance with lowering the onset bias voltage by 2-3 V. The EL colors and spectra were also affected by annealing. X-ray reflectivity measurements before and after annealing the pHT film on ITO indicated increased density of the pHT layer and structural changes in the pHT/ITO interface by annealing, which seems to be responsible for the improved EL device performanc

Endoscopic therapy using an endoscopic variceal ligation for minute cancer of the esophagogastric junction complicated with esophageal varices: a case report

<p>Abstract</p> <p>Introduction</p> <p>Standard endoscopic mucosal resection or endoscopic submucosal dissection is a procedure for patients with minute cancers, complicated with esophageal varices that puts them at high risk of bleeding.</p> <p>Case presentation</p> <p>We present the case of a 77-year-old Japanese man with alcoholic cirrhosis who underwent a routine endoscopy examination as a screening procedure for esophageal varices and was incidentally diagnosed as having minute cancer of the esophagogastric junction with esophageal varices. Endoscopic ultrasonography findings suggested that the minute cancer was a non-invasive carcinoma (carcinoma <it>in situ</it>) and a 2 mm in diameter blood vessel, feeding the esophageal varices, pierced the lesion. Following the examination, we carried out endoscopic treatment of the minute cancer and esophageal varices. Endoscopic variceal ligation was performed using a pneumo-activated device (Sumitomo Bakelite, Tokyo, Japan). Two years after the treatment, during the follow-up endoscopic examination on the patient, recurrence of carcinoma was not detected endoscopically or histologically.</p> <p>Conclusion</p> <p>Endoscopic therapy using an endoscopic variceal ligation device for minute cancer of the esophagogastric junction, complicated with esophageal varices, may be an acceptable and easily applicable method.</p

Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy.

Background: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs. Methods: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added. Results: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4-124.7] to 67.5 [IQR: 62.1-114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1-114.3] to 70.2 [IQR: 58.3-106.2], and to 74.9 [IQR: 55.6-101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7-288.7] to 297.0 [IQR: 266.2-300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level. Conclusion: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently. © 2016 Tada et al

Factors Predicting Difficult Biliary Cannulation during Endoscopic Retrograde Cholangiopancreatography for Common Bile Duct Stones

Background/Aims Difficult biliary cannulation is an important risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Therefore, this study aimed to identify the factors that predict difficult cannulation for common bile duct stones (CBDS) to reduce the risk for PEP. Methods This multicenter retrospective study included 1,406 consecutive patients with native papillae who underwent ERCP for CBDS. Factors predicting difficult cannulation for CBDS were identified using univariate and multivariate analyses. Results Univariate analysis showed that six factors significantly predicted difficult cannulation: ERCP performed by non-expert endoscopists, low-volume center, absence of acute cholangitis, normal serum bilirubin, intradiverticular papilla, and type of major duodenal papilla. Multivariate analysis identified ERCP performed by non-expert endoscopists (odds ratio [OR], 2.5; p<0.001), low-volume center (OR, 1.6; p<0.001), intradiverticular papilla (OR, 1.3; p=0.007), normal serum bilirubin (OR, 1.3; p=0.038), and absence of acute cholangitis (OR, 1.3; p=0.049) as factors significantly predicting difficult cannulation for CBDS. Conclusions Initial cannulation by an experienced endoscopist, early rescue cannulation, or early takeover by an experienced endoscopist should be considered when performing ERCP for CBDS in the presence of factors predicting difficult cannulation