Thesis (M.N.)--University of Alberta, 1997. / In partial fulfillment of the requirements for the degree of Master of Nursing. Faculty of Nursing. Also available online.

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "May, 2008." Includes bibliographical references (leaves 117-133). Online version available on the World Wide Web.

The authors present an unusual case of a highly mobile gallbladder which simulated a pancreatic mass on computed tomograms. Radiographic features of this interesting variant are illustrated.

We report a case where colonoscopic ultrasound was used to evaluate the pancreas. In this case the usual method of evaluating the body of the pancreas by upper gastrointestinal ultrasound was unsuccessful because of the presence of a large hiatal hernia. The other abdominal organs evaluated by colonoscopic ultrasound included the ileo-cecal valve, kidney, liver spleen and prostate. To our knowledge this is the first case where ultrasonic colonoscope has been used to evaluate the body of the pancreas.

Basic helix-loop-helix (bHLH) proteins belong to a class of transcription factors that are critical regulators of development, cell growth and differentiation. One particular family member includes the products of the E2A gene, E12 (Pan-2) and E47 (Pan-1), ubiquitous transcription factors localized in the nucleus. E12 and E47 gene products are generated by alternative RNA splicing. E12 and E47 proteins have been implicated as transcriptional regulators of the rat I insulin gene, immunoglobulin light and heavy chain genes and several muscle-specific genes. To delineate the role ofE2A proteins in directing insulin gene transcription, we have characterized an anti-E2A polyclonal antiserum which recognizes both E12 and E47 and used this reagent to study E2A proteins in the pancreas. In these studies, we have demonstrated that the anti-E2A polyclonal antiserum is highly specific for E2A proteins in a variety of different cell lines representing different tissues. Furthermore, using this immunohistochemical tool, we have demonstrated that E2A proteins are posttranslationally modified in beta cells, insulin producing cells in the pancreas. We also provide evidence that a posttranslationally modified form of E2A protein is involved in glucose-induced insulin gene transcription in beta cells. Lastly, we provide evidence that E2A proteins are associated with other bHLH proteins or other non-bHLH proteins in pancreatic beta cells.

<p>  </p> <p>Traditionally, the exocrine and endocrine cellular compartments of the pancreas have been considered distinct functional systems. However, recent studies suggest a more intricate relationship between the exocrine and endocrine, which may impact pancreatic growth and health. Additionally, translational control mechanisms have been linked to organ development. Our lab has shown that the mRNA translation factor eukaryotic initiation factor 5A (eIF5A), when in its post-translationally modified “hypusinated” form, plays a role in pancreas development. The hypusination of eIF5A requires the rate-limiting enzyme deoxyhypusine synthase (<em>Dhps</em>) to post-translationally modify a critical lysine residue which in turn produces the active form of eIF5A that functions in mRNA translation. When we generated animals with a deletion of <em>Dhps</em> in the pancreatic progenitor cells, there was no alteration in islet mass but significant exocrine insufficiency at embryonic (E) day 18.5 concomitant with downregulation of proteins required for exocrine pancreas development and function. Resultantly these animals died by 6 weeks-of-age. These observations prompted the question, is the phenotype caused by the absence of hypusinated eIF5A or the increase of unhypusinated eIF5A? To address this, we generated a mouse model wherein <em>Eif5a</em> is deleted in the pancreas (eIF5A∆PANC) and these mutant animals also display exocrine insufficiency. Interestingly, beta cell mass is increased at E18.5, and the mutant animals maintain euglycemia and survive up to 2 years. Ongoing analyses are interrogating the differences between these animal models with the goal to determine if mRNA translation facilitates cellular communication between the exocrine and endocrine pancreas.</p>

No description available.

Background: Pancreatic disease is a global problem. Severe acute pancreatitis (AP) carries a 30-50% mortality. Current scoring systems fall short in predictive accuracy, sensitivity, specificity and availability. Pancreatic cancer (PC) is a leading cause of cancer-related mortality, most patients die within one year of diagnosis. Late presentation and lack of effective oncological treatment determine a desperate need to focus on early detection of the pancreatic cancer. Current biomarkers fall short in accessibility, sensitivity and specificity and ability to distinguish malignant from benign conditions. Metabolomics aims to decipher molecular signatures that will distinguish disease from controls, ultimately leading to novel targets for diagnosis and treatment. Initial studies are discovery-based, hypothesis-generating and typically aim to establish a snapshot of the metabolism of an individual by metabolite profile. Aims: Establish a prospective phenotypic and demographic database of patients with acute pancreatitis. Determine urinary and serum metabolomic profiles of AP and PC in comparison to controls and establish if metabolomic profiling can distinguish severity of each disease in order to identify potential novel bio-markers. Methods: Urine and serum samples from 73 AP, 32 PC, 62 Healthy Controls, 8 Chronic pancreatitis and 8 Benign jaundice participants were analysed using GC-MS and UPLCMS. Metabolite identification was subject to univariate and multivariate analysis (p<0.05). Results: The differentiation of metabolite profiles was most distinct with AP. There was no differentiation by AP aetiology. AP severity was distinquished by metabolite profile. Profiles of resectable patients were distinct form non-resectable PC. Fatty acids(FA), glycerophoshocholines, eicosanoids, TCA cycle intermediates and melatonin levels were altered in AP. PC was defined by altered concentrations of FAs, eicosanoids, glycerophoshocholines, sphingomyelins, folates and amino acids and peptides (e.g. glutamine). Altered levels of UFAs, neuromedins, Vitamin D3 determined stage of PC. Conclusion: Urinary and serum metabolomic signatures may provide future biomarker panels for grading AP and PC.

This report takes an approach of laying the first steps to create an artificial pancreassystem as treatment for type 1 diabetes. This includes a thoroughly performedanalysis of the most intrusive physical factors, such as hormonal activity, time offset,errors of measurement and metabolism. Such factors raise a need forcompensation. A compensation that will enable the development of the link betweena continuous glugose monitoring(CGM)-device and an insulin infusion pump,a system that can be described as an Artificial Pancreas.Through analysis of measured glucose series, a mathematicalapproximation is presented to solve the time offset of CGM.The approximation gives sufficient results but with room for improvementFrom the analysis of affecting factors, a compensation model isdeveloped. The model is designed as a closed loop which is suitable for timecontinuous systems. The output of the compensation model equation presented here is adirective that would be read by an insulin pump.

Several epidemiological and clinical studies have indicated a possible role of Enterovirus (EV) infection in type 1 diabetes (T1D) development. However, the exact casual mechanism of these viruses in T1D development is not known. The aim of this thesis is to study various EVs that have been shown to differ in their immune phenotype, lytic ability, association with induction of islet autoantibodies, ability to replicate, cause islet disintegration and induce innate antiviral pathways in infected pancreatic cells in vitro. Furthermore, EV presence and pathogenic process in pancreatic tissue and isolated islets of T1D patients was also studied. Studies in this thesis for first time show the detection of EV RNA and protein in recent onset live T1D patients supporting the EV hypothesis in T1D development. Further all EV serotypes studied were able to replicate in islets, causing variable amount of islet disintegration ranging from extensive islet disintegration to not affecting islet morphology at all. However, one of the EV serotype replicated in only two out of seven donors infected, highlighting the importance of individual variation between donors. Further, this serotype impaired the insulin response to glucose stimulation without causing any visible islet disintegration, suggesting that this serotype might impaired the insulin response by inducing a functional block. Infection of human islets with the EV serotypes that are differentially associated with the development of islet autoantibodies showed the islet cell disintegration that is comparable with their degree of islet autoantibody seroconversion. Suggesting that the extent of the epidemic-associated islet autoantibody induction may depend on the ability of the viral serotypes to damage islet cells. Furthermore, one of the EV strains showed unique ability to infect and replicate both in endo and exocrine cells of the pancreas. EV replication in both endo and exocrine cells affected the genes involved in innate and antiviral pathways and induction of certain genes with important antiviral activity significantly varied between different donors. Suggesting that the same EV infection could result in different outcome in different individuals. Finally, we compared the results obtained by lytic and non lytic EV strains in vitro with the findings reported in fulminant and slowly progressing autoimmune T1D and found some similarities. In conclusion the results presented in this thesis further support the role of EV in T1D development and provide more insights regarding viral and host variation.  This will improve our understanding of the possible causative mechanism by EV in T1D development.