MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression.

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells-all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13-HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13-HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13-HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC.

SnO2 quantum dots decorated on RGO: a superior sensitive, selective and reproducible performance for a H2 and LPG sensor.

We report the H2 and LPG gas sensing behavior of RGO/SnO2 QDs synthesized by a surfactant assisted hydrothermal method. The RGO/SnO2 QD based sensor shows a high response of ∼89.3% to H2 and ∼92.4% to LPG for 500 ppm test gas concentration at operating temperatures of 200 °C and 250 °C, respectively. Further, the RGO/SnO2 QD based sensor shows good selectivity for H2 and LPG in the presence of other interfering gases such as ammonia, chloroform, toluene, benzene, acetone, n-butylacetate, acetic acid and formic acid. We observed that the gas response to H2 is 29.8 times higher than that to acetic acid whereas the gas response to LPG is 17.8 times higher than that to formic acid. Long-term analyses have also been performed to demonstrate the reproducible nature of the RGO/SnO2 QD based sensor over passing time which shows excellent reproducibility.

Granulomatous infiltration with replacement of liver parenchyma: first case report.

A 76-year-old man presented with fever, weight loss and abnormal liver function tests. Imaging demonstrated a diffusely abnormal liver, and a liver biopsy revealed a fibrosing granulomatous process infiltrating and replacing liver parenchyma. There was no clinical, radiological or laboratory evidence of autoimmune liver disease, sarcoidosis, lymphoma or tuberculosis. Treatment with steroids resulted in a remarkable resolution of the clinical symptoms and radiology. This is the first case of granulomatous infiltration of the liver replacing normal hepatic parenchyma.

Chromoendoscopy with methylene blue and associated DNA damage in Barrett's oesophagus.

Chromoendoscopy with methylene blue has been proposed to improve targeting of biopsies to specialised intestinal metaplasia and dysplasia in Barrett's oesophagus. However, methylene blue can induce oxidative damage of DNA when photosensitised by white light. We show that damage to DNA is increased in Barrett's mucosa after chromoendoscopy with methylene blue, an effect apparently dependent on presence of both methylene blue and endoscopic white light. Exposure of Barrett's mucosa to DNA damage during endoscopy warrants caution since it could accelerate carcinogenesis. This risk needs to be carefully balanced against the possible benefit of improved early detection of preneoplastic lesions with methylene blue chromoendoscopy.

Efficacy and optimum dose of omeprazole in a new 1-week triple therapy regimen to eradicate Helicobacter pylori.

OBJECTIVE: To assess the efficacy of a 1-week course of omeprazole, clarithromycin and tinidazole for the eradication of Helicobacter pylori and the optimum dose of omeprazole required. DESIGN: The study was divided into two sequential phases. The first phase was an open, two-centre study. The second phase was a single-blind, single-centre study. METHODS: Patients found to be infected with H. pylori at endoscopy were enrolled in the study. In phase 1, patients were prescribed 20 mg omeprazole, 250 mg clarithromycin and 500 mg tinidazole twice daily for 1 week. In phase 2, all patients were prescribed 250 mg clarithromycin and 500 mg tinidazole twice daily for 1 week. In addition, patients were randomly assigned to receive 20 mg omeprazole twice daily (group A), 20 mg omeprazole daily (group B) or no omeprazole (group C). Eradication was assessed in all patients by 13C-urea breath testing 4 weeks after the completion of therapy. RESULTS: In phase 1, H. pylori eradication was achieved in 132 (88%) of 150 evaluable patients. In phase 2, eradication was achieved in 44 (88%) of 50 individuals in group A, 47 (88.7%) of 53 in group B and 30 (63.8%) of 47 in group C. In the omeprazole groups, 22 patients harboured metronidazole-resistant strains of H. pylori and all were cured by the omeprazole regimen. One patient harboured a strain of H. pylori that was resistant to clarithromycin alone but which was successfully eradicated. Treatment failed in two out of three patients harbouring H. pylori strains resistant to both clarithromycin and tinidazole. CONCLUSION: One week of omeprazole, clarithromycin and tinidazole is effective in eradicating H. pylori. There is no advantage in increasing the dose of omeprazole from once to twice daily. This regimen is effective in patients with 5-nitroimidazole-resistant strains of H. pylori.

Campylobacter jejuni in the stomach.

Campylobacter jejuni is the commonest cause of acute bacterial enteritis in the UK. However, in this case a 74-year-old lady underwent gastroscopy for an upper gastrointestinal haemorrhage and was noted to have a gastric ulcer. Gastric biopsy revealed spiral gram-negative bacteria and culture yielded a moderate growth of C. jejuni. Identification was confirmed by growth characteristics, biochemical tests and PCR amplification of the species-specific flagellin gene--fla A. To prevent misidentification, it is important that laboratories routinely culturing gastric biopsies for Helicobacter pylori should perform a rapid urease test and not rely solely on microscopic morphology.

Non-ulcer dyspepsia: does Helicobacter pylori matter?

Non-ulcer dyspepsia is a heterogenous disorder characterised by chronic or recurrent abdominal or retrosternal discomfort lasting for more than four weeks for which no cause can be determined. Helicobacter pylori has been implicated as a potential cause in a subset of patients but the association has not been proven and H pylori eradication in patients with non-ulcer dyspepsia has had variable results. Large well-controlled studies are needed to clarify the relationship.

Haemodynamic responses following meperidine and promazine induced neuroleptanalgesia in calves.

Induction of neuroleptanalgesia in 6 calves by i/v administration of a combination of meperidine (/ 12 mg/kg body weight) and promazine (/ 3 mg/kg body weight) elicited various haemodynamic responses. The MAP and CVP exhibited significant (p less than 0.01) overall variations with fluctuating fall and rise at different observation periods. A significant (p less than 0.01) rise could be observed in HR which manifested a maximum and an abrupt rise (104.31%) at 5 minutes postinjection. Cardiac output, cardiac index, stroke volume, stroke index and total peripheral resistance exhibited significant (p less than 0.01) overall variations with an initial fall in their values as compared to the respective base values. The cardiac output and cardiac index showed an alternate fall and rise from the preceeding value while the stroke volume, stroke index and total peripheral resistance manifested decreased values throughout the observation period as compared to base value. The values of all parameters measured, except heart rate, stroke volume, stroke index and total peripheral resistance, nearly returned to preinjection level by 120 minutes.