Showing papers by "Diane M. Simeone published in 2002"

Human Pancreatic Acinar Cells Do Not Respond to Cholecystokinin

Abstract: Pancreatic secretion can be influenced by cholecystokinin (CCK) either directly via actions on acinar cells or indirectly via actions on nerves. The presence and functional roles of CCK receptors on human pancreatic acinar cells remains unclear. In the current study human pancreatic acini were isolated and then treated with CCK-8, gastrin and/or carbachol. Functional parameters were measured including intracellular [Ca2+] and amylase secretion. It was observed that human acini did not respond to CCK agonists but did respond to carbachol with robust increases in functional parameters. Adenoviral-mediated gene transfer of CCK1 or CCK2 receptors to the human cells resulted in cell responses to CCK agonists. In order to determine the reason for the lack of responsiveness of the human acini, expression of receptor mRNAs was determined using quantitative RT-PCR and localized by in situ hybridization. mRNA levels for CCK1 receptors were approximately 30 times lower than those of CCK2 receptors, which were approximately 10 times lower than those of m3 Ach receptors as measured by quantitative PCR. Neither CCK1 nor CCK2 receptors were localized in adult human pancreas by in situ hybridization. These results indicate that human pancreatic acinar cells do not respond directly to CCK receptor activation and this is likely due to an insufficient level of receptor expression.

Bacillus anthracis as an agent of bioterrorism: a review emphasizing surgical treatment.

Abstract: The recent terrorist attacks in New York City and Washington D.C. and the subsequent cases of anthrax exposure and infection throughout the United States make the once-theoretical risk of a bioterrorist attack with aerosolized anthrax very real. It is estimated that 100 kg of anthrax spores released upwind of Washington D.C. would result in 130,000 to 3 million deaths; many of these patients would die undiagnosed and untreated. 1 In a covert, large-scale release of anthrax, the initial deaths would result from a delay in recognizing the clinical manifestations of cutaneous, inhalation, or gastrointestinal disease and instituting appropriate treatment. To reduce the death rate, knowledge of the clinical manifestations, disease course, and medical as well as surgical treatment of anthrax infection is imperative. 2 Data regarding the diagnosis and management of anthrax comes from human case reports, mostly from foreign countries in which the disease is endemic, and experimental animal studies. The closest incident to a large-scale bioterrorist attack with aerosolized anthrax was the accidental release of the agent from a military microbiology facility at Sverdlovsk in 1979, from which limited information is available. There were at least 79 cases of anthrax infection, resulting in 68 deaths. 3,4 With such limited data and individual clinical experience, not all recommendations are rigorously evidence-based but rather have been clinically derived, as well as based on established surgical and medical practices. The Centers for Disease Control and Prevention (CDC) has begun a process of physician education to increase familiarity with the clinical manifestations and treatment, but there has been little discussion of the surgical aspects of anthrax infection. Although the primary treatment of anthrax infection is medical, surgical complications can occur, particularly if a large number of individuals are infected. Awareness of these complications and knowledge of their treatment are critical if the deaths and complications are to be limited. Aside from the surgical indications, it is likely that in the case of a large-scale anthrax exposure, all physicians, including surgeons, would play a pivotal role in diagnosing and treating these patients. As such, a review of intentional infection with aerosolized anthrax, emphasizing surgical management, seems timely.

Connecting islet development and developing useful islets

Abstract: The growth of pancreatic endocrine cells occurs early in the developing embryo. The signals that initiate the development are not defined, but several secreted proteins participate directly or indirectly in the differentiation of epithelial cells into hormone-producing cells. A recent study now suggests that vascular endothelial cells produce factors that are crucial for the induction of pancreatic organogenesis and for the formation of insulin-producing cells. The identification of these factors could be key to the efficient generation of insulin-producing cells from embryonic stem cells or other proliferating pancreatic precursor cells.