The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Joachim Mössner - One of the best experts on this subject based on the ideXlab platform.
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Update lecture: benign diseases of the Exocrine Pancreas.
Digestive diseases (Basel Switzerland), 2011Co-Authors: Joachim MössnerAbstract:A brief overview on the physiology and regulation of digestive enzyme secretion by the Exocrine Pancreas is presented. Knowledge about the physiology of the Exocrine Pancreas should help for a better understanding of the pathophysiology of both acute and chronic pancreatitis. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes, which leads to intracellular activation of trypsinogen, is still regarded as a key step in pathophysiology. The role of activation by cathepsins and the role of autoactivation of trypsinogen are still under debate. Studies on genetic alterations in various forms of human chronic pancreatitis can be interpreted that an imbalance between protease inhibitors and active proteases plays a key role. Toxic Ca(2+) signals by excessive liberation from the endoplasmic reticulum may play another role. The mortality of necrotizing pancreatitis is still high. Early mortality is caused by a systemic inflammatory response syndrome with or without concomitant infection of necrosis; late mortality by multi-organ failure syndrome due to sepsis. Therapy of necroses should be performed as late as possible. A step-up approach using CT-guided and/or transgastric endoscopic necrosectomy seems to be superior to a primary surgical approach. A brief overview of the German S3 guidelines, not yet published, regarding diagnosis and treatment of chronic pancreatitis is presented.
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Update Lecture: Benign Diseases of the Exocrine Pancreas
Digestive Diseases, 2011Co-Authors: Joachim MössnerAbstract:A brief overview on the physiology and regulation of digestive enzyme secretion by the Exocrine Pancreas is presented. Knowledge about the physiology of the Exocrine Pancreas should help for a better
Matthias Hebrok - One of the best experts on this subject based on the ideXlab platform.
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Bmi1 Is Required for Regeneration of the Exocrine Pancreas in Mice
Gastroenterology, 2012Co-Authors: Akihisa Fukuda, John P. Morris, Matthias HebrokAbstract:Background & Aims Bmi1 is a member of the Polycomb protein family and represses transcription by modifying chromatin organization at specific promoters. Bmi1 is implicated in the control of stem cell self-renewal and has been shown to regulate cell proliferation, tissue homeostasis, and differentiation. Bmi1 is present in a subpopulation of self-renewing pancreatic acinar cells and is expressed in response to pancreatic damage. We investigated the role of Bmi1 in regeneration of Exocrine Pancreas. Methods Acute pancreatitis was induced in Bmi1 −/− mice with cerulein; pancreatic cell regeneration, differentiation, and apoptosis were assessed. Cultured Bmi1 −/− and wild-type primary acini were analyzed in vitro to determine acinar-specific consequences of Bmi1 deletion. To investigate cell autonomous versus non–cell autonomous roles for Bmi1 in vivo, pancreatitis was induced in Bmi1 −/− mice reconstituted with a wild-type hematopoietic system. Results Bmi1 expression was up-regulated in the Exocrine Pancreas during regeneration after cerulein-induced pancreatitis. Exocrine regeneration was impaired following administration of cerulein to Bmi1 −/− mice. Pancreata of Bmi1 −/− mice were hypoplastic, and the Exocrine Pancreas was replaced with ductal metaplasia that had increased apoptosis and decreased cell proliferation compared with that of wild-type mice. Expression of Cdkn2a and p53-dependent apoptotic genes was markedly up-regulated in Bmi1 −/− Pancreas compared with wild-type mice after injury. Furthermore, after transplantation of bone marrow from wild-type to Bmi1 −/− mice, the chimeric mice had intermediate levels of pancreatic hypoplasia and significant but incomplete rescue of impaired Exocrine regeneration after cerulein injury. Conclusions Bmi1 contributes to regeneration of the Exocrine Pancreas after cerulein-induced injury through cell autonomous mechanisms, in part by regulating Cdkn2a expression, and non–cell autonomous mechanisms.
Douglas R. Cavener - One of the best experts on this subject based on the ideXlab platform.
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PERK eIF2 alpha kinase is required to regulate the viability of the Exocrine Pancreas in mice
BMC cell biology, 2007Co-Authors: Kaori Iida, Barbara C. Mcgrath, Ami Frank, Douglas R. CavenerAbstract:Deficiency of the PERK eIF2α kinase in humans and mice results in postnatal Exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues. To determine if the Exocrine pancreatic atrophy is due to a cell-autonomous defect, the Perk gene was specifically ablated in acinar cells of the Exocrine Pancreas in mice. We show that expression of PERK in the acinar cells is required to maintain their viability but is not required for normal protein synthesis and secretion. Exocrine pancreatic atrophy in PERK-deficient mice was previously attributed to uncontrolled ER-stress followed by apoptotic cell death based on studies in cultured fibroblasts. However, we have found no evidence for perturbations in the endoplasmic reticulum or ER-stress and show that acinar cells succumb to a non-apoptotic form of cell death, oncosis, which is associated with a pronounced inflammatory response and induction of the pancreatitis stress response genes. We also show that mice carrying a knockout mutation of PERK's downstream target, ATF4, exhibit pancreatic deficiency caused by developmental defects and that mice ablated for ATF4's transcriptional target CHOP have a normal Exocrine Pancreas. We conclude that PERK modulates secretory capacity of the Exocrine Pancreas by regulating cell viability of acinar cells.
Akihisa Fukuda - One of the best experts on this subject based on the ideXlab platform.
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Bmi1 Is Required for Regeneration of the Exocrine Pancreas in Mice
Gastroenterology, 2012Co-Authors: Akihisa Fukuda, John P. Morris, Matthias HebrokAbstract:Background & Aims Bmi1 is a member of the Polycomb protein family and represses transcription by modifying chromatin organization at specific promoters. Bmi1 is implicated in the control of stem cell self-renewal and has been shown to regulate cell proliferation, tissue homeostasis, and differentiation. Bmi1 is present in a subpopulation of self-renewing pancreatic acinar cells and is expressed in response to pancreatic damage. We investigated the role of Bmi1 in regeneration of Exocrine Pancreas. Methods Acute pancreatitis was induced in Bmi1 −/− mice with cerulein; pancreatic cell regeneration, differentiation, and apoptosis were assessed. Cultured Bmi1 −/− and wild-type primary acini were analyzed in vitro to determine acinar-specific consequences of Bmi1 deletion. To investigate cell autonomous versus non–cell autonomous roles for Bmi1 in vivo, pancreatitis was induced in Bmi1 −/− mice reconstituted with a wild-type hematopoietic system. Results Bmi1 expression was up-regulated in the Exocrine Pancreas during regeneration after cerulein-induced pancreatitis. Exocrine regeneration was impaired following administration of cerulein to Bmi1 −/− mice. Pancreata of Bmi1 −/− mice were hypoplastic, and the Exocrine Pancreas was replaced with ductal metaplasia that had increased apoptosis and decreased cell proliferation compared with that of wild-type mice. Expression of Cdkn2a and p53-dependent apoptotic genes was markedly up-regulated in Bmi1 −/− Pancreas compared with wild-type mice after injury. Furthermore, after transplantation of bone marrow from wild-type to Bmi1 −/− mice, the chimeric mice had intermediate levels of pancreatic hypoplasia and significant but incomplete rescue of impaired Exocrine regeneration after cerulein injury. Conclusions Bmi1 contributes to regeneration of the Exocrine Pancreas after cerulein-induced injury through cell autonomous mechanisms, in part by regulating Cdkn2a expression, and non–cell autonomous mechanisms.
Kaori Iida - One of the best experts on this subject based on the ideXlab platform.
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PERK eIF2 alpha kinase is required to regulate the viability of the Exocrine Pancreas in mice
BMC cell biology, 2007Co-Authors: Kaori Iida, Barbara C. Mcgrath, Ami Frank, Douglas R. CavenerAbstract:Deficiency of the PERK eIF2α kinase in humans and mice results in postnatal Exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues. To determine if the Exocrine pancreatic atrophy is due to a cell-autonomous defect, the Perk gene was specifically ablated in acinar cells of the Exocrine Pancreas in mice. We show that expression of PERK in the acinar cells is required to maintain their viability but is not required for normal protein synthesis and secretion. Exocrine pancreatic atrophy in PERK-deficient mice was previously attributed to uncontrolled ER-stress followed by apoptotic cell death based on studies in cultured fibroblasts. However, we have found no evidence for perturbations in the endoplasmic reticulum or ER-stress and show that acinar cells succumb to a non-apoptotic form of cell death, oncosis, which is associated with a pronounced inflammatory response and induction of the pancreatitis stress response genes. We also show that mice carrying a knockout mutation of PERK's downstream target, ATF4, exhibit pancreatic deficiency caused by developmental defects and that mice ablated for ATF4's transcriptional target CHOP have a normal Exocrine Pancreas. We conclude that PERK modulates secretory capacity of the Exocrine Pancreas by regulating cell viability of acinar cells.