Pancreatic exocrine secretory processes are challenging to investigate on primary epithelial cells. Pancreatic organoid cultures may help to overcome shortcomings of the current models, however the ion secretory processes in pancreatic organoids-and therefore their physiological relevance or their utility in disease modeling-are not known. To answer these questions, we provide side-by-side comparison of gene expression, morphology, and function of epithelial cells in primary isolated pancreatic ducts and organoids. We used mouse pancreatic ductal fragments for experiments or were grown in Matrigel to obtain organoid cultures. Using PCR analysis we showed that gene expression of ion channels and transporters remarkably overlap in primary ductal cells and organoids. Morphological analysis with scanning electron microscopy revealed that pancreatic organoids form polarized monolayers with brush border on the apical membrane. Whereas the expression and localization of key proteins involved in ductal secretion (cystic fibrosis transmembrane conductance regulator, Na + /H + exchanger 1 and electrogenic Na + /HCO 3 − cotransporter 1) are equivalent to the primary ductal fragments.Measurements of intracellular pH and Cl − levels revealed no significant difference in the activities of the apical Cl − /HCO 3 − exchange, or in the basolateral Na + dependent HCO 3 − uptake. In summary we found that ion transport activities in the mouse pancreatic organoids are remarkably similar to those observed in freshly isolated primary ductal fragments. These results suggest that organoids can be suitable and robust model to study pancreatic ductal epithelial ion transport in health and diseases and facilitate drug development for secretory pancreatic disorders like cystic fibrosis, or chronic pancreatitis.

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Summary A human prostate tumour cell line, LNCaP C4-2, when injected into athymic male nude mice, produced tumours containing:(1) only human cancer cells similar to those injected; (2) only murine stromal cells containing abnormal chromosome constitutions; or (3) both human prostate cancer cells similar to those injected and the transformed murine stromal cells with altered chromosome constitutions.Karyotypic analysis of murine metaphases from all the host-derived tumours showed mostly pseudodiploid chromosome constitutions, with multiple copies (amplification) of mouse chromosome 15 and the absence of a typical Y chromosome. Fluorescence in situ hybridization analysis of these murine cells, using a biotin-labelled total human DNA painting probe, further demonstrated the absence of human DNA and the presence of only mouse metaphase and interphase cells in these transformed stromal cells. These results suggest that cancer cells are capable of inducing neoplastic transformation in stromal cells of the host organ by some, as yet unknown, epigenetic mechanism(s).Keywords: malignant transformation; tumour-stroma interaction; fluorescence in situ hybridization; pseudodiploid karyotype; prostate cancer progression; epigenetic mechanism of carcinogenesis Although the athymic mouse and rat are not natural hosts for the study of the in vivo biology of human neoplasms, they provide excellent models for the growth and maintenance of human tumours in vivo (Fidler, 1986) and for the study of reciprocal cellular interaction between tumour cells and host stroma (Wu et al, 1994). For many tumour biology experiments, the nude mouse routinely serves as a 'biological incubator' for primary and established tumour cells for selecting derivative cell lines with differing metastatic properties and for therapeutic trials monitoring tumour growth and levels of tumour or serum biomarkers (Fidler, 1986(Fidler, , 1990. The focus of the present communication is to document the tumour-stroma interaction that resulted in the induction of host stromal cells to assume non-random genetic alterations.When human tumour cells are injected into nude murine animals, quite frequently human tumour cells grow, but other possibilities also exist (Treit et al, 1980;Goldenberg and Pavia, 1981;Bowen et al, 1983;Hsu and Pathak, 1989;Gupta et al, 1990). In earlier experiments in which we injected human breast cancer cells into the nude mouse, the tumours produced in the host consisted of mouse cells with abnormal metaphases containing double-minute chromosomes (Bowen et al, 1983). Three types of tumour cells were harvested from such an experimental tumour model: (1) The purpose of this study was to investigate whether there were specific cytogenetic abnormalities present in several murine stromal tumours that developed after the injection of human C4-2 tumour cells that metastasized as bony tumour deposits (Thalmann et al, 1994;Wu et al, 1994). We report here cytogenetic findings from the resulting host stromal tumour cell lines from six athymic mice bearing...

Quantitative left ventricular (LV) function was assessed with magnetic resonance imaging in 20 patients by using standard multisection multiphase steady-state free precession (SSFP) imaging and sensitivity encoding (SENSE)-accelerated cine SSFP imaging with identical spatial, contrast, and temporal resolution. The local institutional review board approved the protocol, and all patients gave signed informed consent prior to imaging. The study complied with the Health Insurance Portability and Accountability Act. Results of Bland-Altman analysis showed that both techniques produced similar estimates of LV ejection fraction, LV mass, and blood-to-muscle contrast and demonstrated minimal interobserver variability. The authors showed that it is possible, by combining SENSE with cine SSFP imaging, to reduce acquisition time by 50% without compromising spatial resolution, temporal resolution, or blood-to-muscle contrast-to-noise ratio compared with those achieved by using SSFP imaging without SENSE for quantitative LV function assessment.

The paced IACT has a strong correlation with the echo derived optimal PAV. This method may be used to program PAV intervals without need for echocardiography in patients undergoing BiV pacemaker implantation.