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.

Trypanosomiasis in a rural hospital in Tanzania. A retrospective study of its management and the results of treatment.

A retrospective analysis was done of the management and the results of treatment in 158 trypanosomiasis patients seen in a rural hospital in Tanzania during 1985. The distribution of cases in the population and during the year reflected an endemic situation. 109 patients (68.9%) were in the meningoencephalitic (ME) stage and 49 (31.1%) in the hematolymphatic (HL) stage of the disease. In total 19 patients (12.0%) died, 17 with ME and 2 with HL trypanosomiasis. Encephalopathy was seen in 19 (17.9%) of 106 patients treated with melarsoprol, and 10 of them died. In 15 (24.4%) of 64 patients who were discharged as HL trypanosomiasis evidence of CNS-involvement was found during follow-up after 3 and/or 9 months.

Mortality in very preterm and very low birth weight infants according to place of birth and level of care: results of a national collaborative survey of preterm and very low birth weight infants in The Netherlands.

As part of a collaborative project in the Netherlands in 1983, for which data were collected on 1,338 newborn infants (less than 32 weeks' gestation and/or less than 1,500 g birth weight), all infants were assigned to one of three levels of care according to hospital of birth. Considerable centralization was achieved by antenatal and neonatal transport. Although the uncorrected mortality rates were similar, the mortality odds (adjusted for four and 22 potential confounding perinatal factors, respectively) were significantly higher in level 1 and level 2 hospitals compared with level 3 hospitals (tertiary perinatal care centers). By extending the facilities for full perinatal intensive care in level 3 centers and thus providing optimal care for all such infants, the overall mortality rate is expected to decrease further.