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Sample records for exocrine pancreas innocent

  1. CARCINOMA OF THE EXOCRINE PANCREAS IN MEDAKA

    EPA Science Inventory

    Eight cases of acinar cell carcinoma of the exocrine pancreas were diagnosed in Japanese medaka (Oryzias latipes) from a pool of approximately 10,000 specimens used in a variety of carcinogenesis bioassays. hree cases occurred in specimens from control groups and one case in a sp...

  2. Regeneration and repair of the exocrine pancreas.

    PubMed

    Murtaugh, L Charles; Keefe, Matthew D

    2015-01-01

    Pancreatitis is caused by inflammatory injury to the exocrine pancreas, from which both humans and animal models appear to recover via regeneration of digestive enzyme-producing acinar cells. This regenerative process involves transient phases of inflammation, metaplasia, and redifferentiation, driven by cell-cell interactions between acinar cells, leukocytes, and resident fibroblasts. The NFκB signaling pathway is a critical determinant of pancreatic inflammation and metaplasia, whereas a number of developmental signals and transcription factors are devoted to promoting acinar redifferentiation after injury. Imbalances between these proinflammatory and prodifferentiation pathways contribute to chronic pancreatitis, characterized by persistent inflammation, fibrosis, and acinar dedifferentiation. Loss of acinar cell differentiation also drives pancreatic cancer initiation, providing a mechanistic link between pancreatitis and cancer risk. Unraveling the molecular bases of exocrine regeneration may identify new therapeutic targets for treatment and prevention of both of these deadly diseases. PMID:25386992

  3. Regeneration and Repair of the Exocrine Pancreas

    PubMed Central

    Murtaugh, L. Charles; Keefe, Matthew

    2015-01-01

    Pancreatitis is caused by inflammatory injury to the exocrine pancreas, from which both humans and animal models appear to recover via regeneration of digestive enzyme-producing acinar cells. This regenerative process involves transient phases of inflammation, metaplasia and redifferentiation, driven by cell-cell interactions between acinar cells, leukocytes and resident fibroblasts. The NFκB signaling pathway is a critical determinant of pancreatic inflammation and metaplasia, whereas a number of developmental signals and transcription factors are devoted to promoting acinar redifferentiation after injury. Imbalances between these pro-inflammatory and pro-differentiation pathways contribute to chronic pancreatitis, characterized by persistent inflammation, fibrosis and acinar dedifferentiation. Loss of acinar cell differentiation also drives pancreatic cancer initiation, providing a mechanistic link between pancreatitis and cancer risk. Unraveling the molecular bases of exocrine regeneration may identify new therapeutic targets for treatment and prevention of both of these deadly diseases. PMID:25386992

  4. ULTRASTRUCTURE OF NORMAL AND NEOPLASTIC EXOCRINE PANCREAS IN THE MUMMICHOG, FUNDULUS HETEROLCLITUS

    EPA Science Inventory

    The ultrastructure of normal exocrine pancreas and exocrine pancreatic neoplasms in Fundulus heteroclitus from a creosote-contaminated environment in the Elizabeth River, Virginia, is described. he normal exocrine pancreas in this species was an anastomosing tubular rather than a...

  5. Exocrine Pancreas in Cats With Diabetes Mellitus.

    PubMed

    Zini, E; Ferro, S; Lunardi, F; Zanetti, R; Heller, R S; Coppola, L M; Guscetti, F; Osto, M; Lutz, T A; Cavicchioli, L; Reusch, C E

    2016-01-01

    Pancreatitis has been described in cats with diabetes mellitus, although the number of studies currently available is very limited. In addition, ketoacidosis has been hypothesized to be associated with pancreatitis in diabetic cats. The aims of the present study were to investigate whether diabetic cats have pancreatitis and to determine if pancreatitis is more frequent with ketoacidosis. Samples of pancreas were collected postmortem from 37 diabetic cats, including 15 with ketoacidosis, and 20 control cats matched for age, sex, breed, and body weight. Sections were stained with hematoxylin and eosin, double-labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/PCNA, and glucagon/Ki67, and single-labeled for Iba1. A previously proposed semiquantitative score was used to characterize pancreatitis, along with counts of inflammatory cells. Scores of pancreatitis and the number of neutrophils, macrophages, and lymphocytes in the exocrine pancreas did not differ between diabetic and control cats or between diabetic cats with and without ketoacidosis. Of note, PCNA-positive acinar cells were increased (P = .002) in diabetic cats, particularly near islets (P < .001). Ki67-positive acinar cells were increased only near islets (P = .038). Ketoacidosis was not linked to proliferation. The results suggest that histopathologic evidence of pancreatitis may not be more frequent in diabetic cats and that ketoacidosis may not be associated with it at the time of death. Augmented PCNA-positive acinar cells might indicate increased proliferation due to chronic pancreatitis. The reason behind the prevalent proliferation of acinar cells surrounding pancreatic islets deserves further investigation. PMID:26319779

  6. Exocrine drainage in vascularized pancreas transplantation in the new millennium

    PubMed Central

    El-Hennawy, Hany; Stratta, Robert J; Smith, Fowler

    2016-01-01

    The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder (systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin (systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion (portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to re-create the natural physiology of the pancreas with first-pass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine the literature on exocrine drainage in the new millennium (the purported

  7. Abnormalities of the Exocrine Pancreas in Type 1 Diabetes.

    PubMed

    Campbell-Thompson, Martha; Rodriguez-Calvo, Teresa; Battaglia, Manuela

    2015-10-01

    Type 1 diabetes (T1D) is considered a pancreatic beta cell-specific disease that results in absolute insulin deficiency. Nevertheless, clinical studies from 1940 onwards showed that patients with T1D had an abnormal exocrine pancreas due to the presence of subclinical exocrine insufficiency and acinar atrophy. Exocrine abnormalities are an important, and mostly neglected, characteristic associated with T1D. It is however still unclear whether the exocrine dysfunction in T1D is a primary damage caused by the same pathogenic event that led to beta cell destruction or secondary to beta cell loss. In this review, we collect evidence supporting the hypothesis that T1D is a combined endocrine-exocrine disease in which the loss of functional beta cell mass is most clinically apparent. PMID:26318606

  8. Cystic Neoplasms of the Exocrine Pancreas

    PubMed Central

    Ribaux, C.; Schnyder, P.

    1990-01-01

    Cystic neoplasms of the pancreas are rare and their diagnosis and treatment can be difficult. This report details 7 patients who had histologically proven serous cystadenoma4, mucinous cystadenoma2 and cystadeno carcinoma1. Computed tomography and sonography allowed excellent preoperative assessment but to attempt a distinction between the histological variants may be hazardous. Two tumours were only autopsy findings and 5 patients underwent laparotomy. It is confirmed that potentially malignant mucinous cystadenomas and cytadenocarcinomas should be resected whenever possible; serous cystadenomas are always benign and should therefore be resected only when the diagnosis is doubtful or if they cause symptoms. PMID:2278913

  9. Making β(-like)-cells from exocrine pancreas.

    PubMed

    Staels, W; De Groef, S; Bussche, L; Leuckx, G; Van de Casteele, M; De Leu, N; Baeyens, L; Heremans, Y; Heimberg, H

    2016-09-01

    Creating an abundant source of β(-like)-cells has been a major goal in diabetes research for many decades. The concept of cell plasticity has inspired many strategies towards regenerative medicine, but its successes have been limited until very recently. Today, most cell types in the pancreas are considered candidates for the generation of β(-like)-cells through transdifferentiation. While β(-like)-cells that are in vitro differentiated from human embryonic stem cells are already being grafted in patients, β(-like)-cells generated by transdifferentiation are not yet ready for clinical application. These cells would however offer several advantages over the current β(-like)-cells generated by directed differentiation, especially concerning safety issues. In addition, perfect control of the transdifferentiation efficiency would through targeted drug delivery support a non-invasive cell therapy for diabetes. Lastly, focusing on the exocrine pancreas as prime candidate makes sense in view of their abundance and high plasticity. Keeping these hopeful perspectives in mind, it is worth to continue focused research on the mechanisms that control transdifferentiation from pancreas exocrine to β-cells. PMID:27615144

  10. Purinergic receptors in the endocrine and exocrine pancreas

    PubMed Central

    2007-01-01

    The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In β cells, stimulation of P2Y1 receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y1 receptors, there is also evidence for other P2 and adenosine receptors in β cells (P2Y2, P2Y4, P2Y6, P2X subtypes and A1 receptors) and in glucagon-secreting α cells (P2X7, A2 receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y2, P2Y4, P2Y11, P2X4 and P2X7 receptors could regulate secretion, primarily by affecting Cl− and K+ channels and intracellular Ca2+ signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases. PMID:18368520

  11. Postnatal development of the exocrine pancreas in suckling goat kids.

    PubMed

    Lopez, V; Martínez-Victoria, E; Yago, M D; Lupiani, M J; Mañas, M

    1997-04-01

    A total of 25 preruminant Granadina breed goats were used. They were bottle-fed goat milk ad libitum from postnatal day 3 to 28. Until the age of 3 d, kids were fed colostrum. Body weight, pancreas weight, total protein concentration, enzyme activities in pancreatic tissue and hormone concentrations (cortisol, gastrin, T3 and T4) were determined at 3, 7, 14, 21 and 28 d of age. Our results show that the rates of pancreatic synthesis and secretion of chymotrypsin are well developed at birth in the kid, and may compensate for possible deficiencies in gastric and/or enterocytes intracellular proteolysis. In week 4, there was a marked increase in amylase activity, change that can be attributed to the beginning of the transitional period known as weaning. The significant increase in circulating concentration of cortisol during week 4 suggests the involvement of corticosteroid as a mediator of pancreatic development at weaning. Changes in blood levels of this hormone are believed to be important in the expression of amylase in the neonatal period. However, T3-T4 blood levels remained unchanged from d 3 to 28, suggesting that, in the kid, these hormones appear to have no clear influence upon the postnatal development of the exocrine pancreas. PMID:9255407

  12. AN EMBRYONIC CHICK PANCREAS ORGAN CULTURE MODEL: CHARACTERIZATION AND NEURAL CONTROL OF EXOCRINE RELEASE

    EPA Science Inventory

    An embryonic chick (Gallus domesticus) whole-organ pancreas culture system was developed for use as an in vitro model to study cholinergic regulation of exocrine pancreatic function. The culture system was examined for characteristic exocrine function and viability by measuring e...

  13. Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter

    SciTech Connect

    Wan Haiyan; Korzh, Svitlana; Li Zhen; Mudumana, Sudha Puttur; Korzh, Vladimir; Jiang Yunjin; Lin Shuo; Gong Zhiyuan . E-mail: dbsgzy@nus.edu.sg

    2006-05-15

    In contrast to what we know on development of endocrine pancreas, the formation of exocrine pancreas remains poorly understood. To create an animal model that allows observation of exocrine cell differentiation, proliferation, and morphogenesis in living animals, we used the zebrafish elastaseA (elaA) regulatory sequence to develop transgenic zebrafish that display highly specific exocrine pancreas expression of GFP in both larvae and adult. By following GFP expression, we found that the pancreas in early development was a relatively compact organ and later extended posterior along the intestine. By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is required for exocrine morphogenesis but not for cell differentiation. We also applied the morpholino knockdown and toxin-mediated cell ablation approaches to this transgenic line. We showed that the development of exocrine pancreas is Islet-1 dependent. Injection of the diphtheria toxin A (DTA) construct under the elastaseA promoter resulted in selective ablation of exocrine cells while the endocrine cells and other endodermal derivatives (liver and intestine) were not affected. Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development.

  14. Aroclor 1254 causes atrophy of exocrine pancreas in mice and the mechanism involved.

    PubMed

    Lin, Moudan; Wu, Tian; Sun, Lingbin; Lin, Jackie Jin; Zuo, Zhenghong; Wang, Chonggang

    2016-06-01

    Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been linked to pancreatic disease. However, their role in affecting the exocrine function of pancreas and the underlying mechanism remains elusive. In the present study, male C57 mice were treated with Aroclor 1254, a commercially available PCBs mixture, at a dosage of 0.5, 5, 50, or 500 μg kg(-1) every 3 days by oral gavage. Decrease in pancreas/soma index and acinar atrophy were observed in the mice after exposure for 50 days. Aroclor 1254 exposure significantly decreased the PCNA-positive cells in the pancreatic acini in a dose-dependent manner. In addition, western blot analysis showed that PCNA expression was decreased in pancreas in the presence of Aroclor 1254, which suggests that Aroclor 1254 suppresses cell proliferation. TUNEL-positive apoptotic cells as well as the expression of Bcl2, BclXL, BAX, and Bad of exocrine pancreas did not show significant changes in the treated mice, indicating that Aroclor 1254 has no effect on apoptosis. We also found that phosphorylation of ERK1/2, P90RSK1 and Bad was increased in the treated groups; this compensatory activation of phosphorylation in ERK1/2-P90RSK1-Bad signaling cascade could protect cell from apoptosis to maintain the cell numbers and function of exocrine pancreas. Moreover, we found that the expression of Kras and TNFα was increased in the pancreas, indicating that Aroclor 1254 exposure could result in increased risk of inflammation and carcinoma. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 671-678, 2016. PMID:25409620

  15. Light and Electron Microscopic Studies on Prenatal Differentiation of Exocrine Pancreas in Buffalo

    PubMed Central

    Gupta, Divya; Uppal, Varinder; Bansal, Neelam; Gupta, Anuradha

    2016-01-01

    The study was conducted on pancreas of 24 buffalo fetuses collected from abattoir and Veterinary clinics, GADVASU, Ludhiana. The buffalo fetuses were divided into three groups after measuring their CVRL, namely, group I (CVRL between 0 and 20 cm), group II (CVRL above 20 cm and up to 40 cm), and group III (CVRL above 40 cm) and their approximate age was calculated. The tissues were processed for light and ultrastructural studies. In group I, at 1.2 cm CVRL (34 days), the pancreas comprised tubules and solid nest of undifferentiated epithelial cells. At 7.5 cm CVRL (63 days) acinar cells with zymogen granules were observed. These acinar cells varied in shape from columnar to pyramidal. At 12.8 cm CVRL (86 days), parenchyma began to organize into lobes and lobules. The centroacinar cells were observed at 12.8 cm CVRL (86 days). In group II, at 28.3 cm CVRL (137 days), there was extensive branching of tubules that resulted in highly branched ductal tree connecting exocrine secretary units to the duct system. The interlobular and intralobular ducts were well observed at this age yet the intercalated ducts were not completely developed. In group III, exocrine pancreas showed a massive growth at 48 cm CVRL (182 days) with distinct pancreatic lobes and lobules. At 54 cm CVRL (195 days), well developed pancreatic architecture was seen with the presence of extensive development of exocrine part organized in lobes and lobules with interlobular and intralobular ducts whereas the intercalated ducts were observed in 80 cm CVRL (254 days). PMID:26981314

  16. Organogenesis of exocrine pancreas in sharpsnout sea bream (Diplodus puntazzo) larvae: characterization of trypsin expression.

    PubMed

    Kamaci, H Okan; Suzer, Cüneyt; Coban, Deniz; Saka, Sahin; Firat, Kürşat

    2010-12-01

    The ontogeny and differentiation stages of digestive systems related with trypsin expression in larvae of sharpsnout sea bream, Diplodus puntazzo, were investigated from hatching to 40 DAH (days after hatching), and total lengths and weights of larvae were determined. Histologic and enzymatic techniques were used to explain the functional development of the pancreas including trypsin activity. The pancreas was identified as a compact structure located in the region slightly posterior to the liver. At 3 DAH, first anus and then mouth opened. Incipient pancreas secretion polyhedral cells could be first observed as zymogen granules. During larval metamorphosis, the pancreas became diffuse, spreading throughout the mesentery in proximity to the stomach, the anterior intestine and the pyloric caeca. The specific activity of trypsin (42.54±6.8 mU/mg protein(-1)) was found as early as after hatching at larvae size of 2.87±0.34 mm at 0 DAH. Activity further increased until 10 DAH, especially after exogenous feeding. The highest trypsin activity was detected at 25 DAH as 119.26±11.6 mU/mg protein(-1). It is concluded that exocrine pancreas organogenesis is the main critical step in the development of digestive system that results in zymogen granules accumulation and increased trypsin activity. PMID:20077135

  17. Early indicators of exocrine pancreas carcinogenesis produced by non-genotoxic agents.

    PubMed

    Woutersen, R A; van Garderen-Hoetmer, A; Lamers, C B; Scherer, E

    1991-06-01

    In the past 40 years the incidence of pancreatic cancer in many Western countries had increased. Since no single factor responsible for the development of pancreatic cancer has been identified, it is believed that non-genotoxic factors may play an important role in the pathogenesis of this highly fatal form of cancer. Focal abnormalities of acinar cells, referred to as atypical acinar cell foci or nodules, occur spontaneously in rats and some other species. Their incidence increases with age from zero at birth to about 75% in 2-year-old rats. These spontaneous lesions have a phenotype that cannot be distinguished from the putative, atypical preneoplastic, acinar cell foci induced in rat pancreas by the carcinogen azaserine. Unsaturated fat (corn oil) has been found to increase the incidence of atypical acinar cell nodules and adenomas in the pancreas of non-carcinogen-treated rats without influencing the weight of the pancreas. Furthermore, unsaturated fat has a specific promoting effect on the growth potential of atypical acinar cell foci and nodules induced in rat pancreas by azaserine, resulting in an increase in the number and size of these lesions. Rats fed raw soya flour or trypsin inhibitors develop an enlarged pancreas as a result of hypertrophy and hyperplasia. They also develop acidophilic atypical acinar cell foci and nodules, adenomas and adenocarcinomas after being fed full-fat raw soya flour for 2 years. It may be concluded from the observations in rat pancreas that non-genotoxic compounds or conditions that enhance pancreatic growth may be classified as non-genotoxic pancreatic tumour promoters. The observations with corn oil, however, indicate that there may be non-genotoxic compounds that specifically enhance growth of spontaneous initiated atypical acinar cell foci without causing hyperplasia of the pancreas. The possible mechanisms whereby unsaturated fat and trypsin inhibitors exert their effects on exocrine pancreatic carcinogenesis are

  18. Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate

    PubMed Central

    Gomez, Danielle L.; O’Driscoll, Marci; Sheets, Timothy P.; Hruban, Ralph H.; Oberholzer, Jose; McGarrigle, James J.; Shamblott, Michael J.

    2015-01-01

    Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation during pancreatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets. NGN3 protein can be detected in the adult rodent pancreas only following certain types of injury, when it is transiently expressed by exocrine cells undergoing reprogramming to an endocrine cell fate. Here, NGN3 protein can be detected in 2% of acinar and duct cells in living biopsies of histologically normal adult human pancreata and 10% in cadaveric biopsies of organ donor pancreata. The percentage and total number of NGN3+ cells increase during culture without evidence of proliferation or selective cell death. Isolation of highly purified and viable NGN3+ cell populations can be achieved based on coexpression of the cell surface glycoprotein CD133. Transcriptome and targeted expression analyses of isolated CD133+ / NGN3+ cells indicate that they are distinct from surrounding exocrine tissue with respect to expression phenotype and Notch signaling activity, but retain high level mRNA expression of genes indicative of acinar and duct cell function. NGN3+ cells have an mRNA expression profile that resembles that of mouse early endocrine progenitor cells. During in vitro differentiation, NGN3+ cells express genes in a pattern characteristic of endocrine development and result in cells that resemble beta cells on the basis of coexpression of insulin C-peptide, chromogranin A and pancreatic and duodenal homeobox 1. NGN3 expression in the adult human exocrine pancreas marks a dedifferentiating cell population with the capacity to take on an endocrine cell fate. These cells represent a potential source for the treatment of diabetes either through ex vivo manipulation, or in vivo by targeting mechanisms controlling their population size and endocrine cell fate commitment. PMID:26288179

  19. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.

    PubMed

    Pierre, Joseph F; Neuman, Joshua C; Brill, Allison L; Brar, Harpreet K; Thompson, Mary F; Cadena, Mark T; Connors, Kelsey M; Busch, Rebecca A; Heneghan, Aaron F; Cham, Candace M; Jones, Elaina K; Kibbe, Carly R; Davis, Dawn B; Groblewski, Guy E; Kudsk, Kenneth A; Kimple, Michelle E

    2015-09-15

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  20. Generation of Functional Beta-Like Cells from Human Exocrine Pancreas

    PubMed Central

    Lima, Maria J.; Muir, Kenneth R.; Docherty, Hilary M.; McGowan, Neil W. A.; Forbes, Shareen; Heremans, Yves; Heimberg, Harry; Casey, John; Docherty, Kevin

    2016-01-01

    Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15–30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants. PMID:27243814

  1. Possible site of calcium regulation in rat exocrine pancreas cells: an X-ray microanalytical study

    SciTech Connect

    Roos, N.

    1988-03-01

    We analysed four subcellular compartments in rat exocrine pancreas cells, zymogen granules, cytoplasm surrounding the zymogen granules, mitochondria and cytoplasm in the basal part of the cells for sodium, magnesium, phosphorus, sulfur, chlorine, potassium and calcium content, using ultrathin frozen-dried cryosections. The highest concentrations of calcium were measured in the zymogen granules and the surrounding apical part of the cell containing Golgi apparatus, smooth endoplasmic reticulum and condensing vacuoles. Calcium concentrations in the basal part of the cells (mostly rough endoplasmic reticulum) were 60% lower than in the apical part of the cells. The lowest calcium concentrations were measured in mitochondria. The results suggest that other subcellular compartments than the rough endoplasmic reticulum and mitochondria might be involved in the intracellular Ca2+ regulation.

  2. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas

    PubMed Central

    Won, Minho; Ro, Hyunju; Dawid, Igor B.

    2015-01-01

    The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice morpholino resulted in specific inhibition of the differentiation of ventral bud derived exocrine cell types, with little effect on endocrine cell types. A frame shifting null mutation in lnx2a did not mimic this phenotype, but a mutation that removed the exon 2 splice donor site did. We found that Lnx2b functions in a redundant manner with its paralog Lnx2a. Inhibition of lnx2a exon 2/3 splicing causes exon 2 skipping and leads to the production of an N-truncated protein that acts as an interfering molecule. Thus, the phenotype characterized by inhibition of exocrine cell differentiation requires inactivation of both Lnx2a and Lnx2b. Human LNX1 is known to destabilize Numb, and we show that inhibition of Numb expression rescues the Lnx2a/b-deficient phenotype. Further, Lnx2a/b inhibition leads to a reduction in the number of Notch active cells in the pancreas. We suggest that Lnx2a/b function to fine tune the regulation of Notch through Numb in the differentiation of cell types in the early zebrafish pancreas. Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use. PMID:26392552

  3. Mesenchymal Stem Cells Derived from Human Exocrine Pancreas Spontaneously Express Pancreas Progenitor-Cell Markers in a Cell-Passage-Dependent Manner

    PubMed Central

    Lee, Song; Lee, Chanmi; Oh, Jooyun

    2016-01-01

    Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies. Pancreatic tissue was digested by collagenase and an enriched exocrine-cell fraction was obtained by density-gradient separation. Crude exocrine cells were methodically cultured in suspension and then in adherent culture. We expanded the human pancreatic exocrine-derived MSCs (hpMSCs) by cell passaging in culture and confirmed by flow cytometry that >90% expressed human classic surface markers of MSCs. Interestingly, these cells expressed pancreatic transcription factors, such as Pdx1, Ngn3, and MafA, similar to pancreatic progenitor cells. These results indicated that hpMSCs can be used for the differentiation of pancreatic endocrine cells and may be used in type 1 diabetes treatment.

  4. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe Deer

    PubMed Central

    2012-01-01

    Background Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Results Forty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric) or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva) which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals. Conclusions Bovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins) compared with Roe deer

  5. Importance of endogenous prostaglandins for the toxicity of cyclosporin A to rat endocrine and exocrine pancreas?

    PubMed Central

    Rünzi, M; Peskar, B M; von Schönfeld, J; Müller, M K

    1992-01-01

    Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered. PMID:1280611

  6. Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs.

    PubMed

    Lozinska, Liudmyla; Weström, Björn; Prykhodko, Olena; Lindqvist, Andreas; Wierup, Nils; Ahrén, Bo; Szwiec, Katarzyna; Pierzynowski, Stefan G

    2016-01-01

    The effect of exocrine pancreatic function on the glucose-mediated insulin response and glucose utilization were studied in an exocrine pancreas-insufficient (EPI) pig model. Five 10-week-old EPI pigs after pancreatic duct ligation and 6 age-matched, non-operated control pigs were used in the study. Blood glucose, plasma insulin and C-peptide concentrations were monitored during meal (MGTT), oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. Upon post-mortem examination, the pancreatic remnants of the EPI pigs showed acinar fibrotic atrophy but normal islets and β-cell morphology. The EPI pigs displayed increased fasting glucose concentrations compared with control animals (6.4 ± 0.4 versus 4.8 ± 0.1 mmol l(-1) , P < 0.0001) but unchanged insulin concentrations (2.4 ± 0.6 versus 2.1 ± 0.2 pmol l(-1) ). During the OGTT and IVGTT, the EPI pigs showed slower, impaired glucose utilization, with the disruption of a well-timed insulin response. Plasma C-peptide concentrations confirmed the delayed insulin response during the IVGTT in EPI pigs. Oral pancreatic enzyme supplementation (PES) of EPI pigs improved glucose clearance during IVGTT [AUC(glucose) 1295 ± 70 mmol l(-1) × (120 min) in EPI versus 1044 ± 32 mmol l(-1) × (120 min) in EPI + PES, P < 0.0001] without reinforcing the release of insulin [AUC(C-peptide) 14.4 ± 3.8 nmol l(-1) × (120 min) in EPI versus 6.4 ± 1.3 nmol l(-1) × (120 min) in EPI + PES, P < 0.002]. The results suggest the existence of an acino-insular axis regulatory communication. The presence of pancreatic enzymes in the gut facilitates glucose utilization in an insulin-independent manner, indicating the existence of a gut-derived pancreatic enzyme-dependent mechanism involved in peripheral glucose utilization. PMID:26663041

  7. Distribution of neuropeptides in endocrine and exocrine pancreas of long-legged buzzard (Buteo rufinus): an immunohistochemical study.

    PubMed

    Bayrakdar, Ali; Yaman, Mine; Atalar, Omer; Gencer Tarakci, Berrin; Ceribasi, Songul

    2011-01-17

    This study aimed to determine the existence and distribution of certain neuropeptides in endocrine and exocrine pancreas of the long-legged buzzard by using immunohistochemical methods. SOM-14-, NPY- and CGRP-IR endocrine cells were determined in both central and peripheral regions in A-islets within the pancreas, while SP-IR endocrine cells were found only in the central region, and CCK-8- and galanin-IR endocrine cells were only detected in peripheral region. On the other hand, in B-islets; SP-, NPY- and CGRP-IRendocrine cells were determined in both central and peripheral regions, while SOM-14- CCK-8- and galanin-IRendocrine cells were found only in the peripheral region. In addition; SOM-14-, NPY-, CGRP-, CCK-8- and galanin-IR cells were also observed in exocrine pancreas. This distribution pattern in the pancreas of the long-legged buzzard demonstrates that neuropeptides perform their probable affects through endocrine and/or paracrine mechanisms. In conclusion, the existence and distribution of neuropeptides in the pancreas of long-legged buzzard have been introduced in this study for the first time and this bird species has also been found to differ from other types of avian species. PMID:20959123

  8. Development of the islets, exocrine pancreas, and related ducts in the Nile tilapia, Oreochromis niloticus (Pisces: Cichlidae).

    PubMed

    Morrison, Carol M; Pohajdak, Bill; Tam, Janet; Wright, James R

    2004-09-01

    Pancreatic development and the relationship of the islets with the pancreatic, hepatic, and bile ducts were studied in the Nile tilapia, Oreochromis niloticus, from hatching to the onset of maturity at 7 months. The number of islets formed during development was counted, using either serial sections or dithizone staining of isolated islets. There was a general increase in islet number with both age and size. Tilapia housed in individual tanks grew more quickly and had more islets than siblings of the same age left in crowded conditions. The pancreas is a compact organ in early development, and at 1 day posthatch (dph) a single principal islet, positive for all hormones tested (insulin, SST-14, SST-28, glucagon, and PYY), is partially surrounded by exocrine pancreas. However, the exocrine pancreas becomes more disseminated in older fish, following blood vessels along the mesenteries and entering the liver to form a hepatopancreas. The epithelium of the pancreatic duct system from the intercalated ducts to the main duct entering the duodenum was positive for glucagon and SST-14 in 8 and 16 dph tilapia. Individual insulin-immunopositive cells were found in one specimen. At this early stage in development, therefore, the pancreatic duct epithelial cells appear to be pluripotent and may give rise to the small islets found near the pancreatic ducts in 16-37 dph tilapia. Glucagon, SST-14, and some PPY-positive enteroendocrine cells were present in the intestine of the 8 dph larva and in the first part of the intestine of the 16 dph juvenile. Glucagon and SST-14-positive inclusions were found in the apical cytoplasm of the mid-gut epithelium of the 16 dph tilapia. These hormones may have been absorbed from the gut lumen, since they are produced in both the pancreatic ducts and the enteroendocrine cells. At least three hepatic ducts join the cystic duct to form the bile duct, which runs alongside the pancreatic duct to the duodenum. PMID:15281064

  9. Secretion and fluid transport mechanisms in the mammary gland: comparisons with the exocrine pancreas and the salivary gland.

    PubMed

    McManaman, James L; Reyland, Mary E; Thrower, Edwin C

    2006-10-01

    Milk is a complex fluid composed of proteins, sugars, lipids and minerals, in addition to a wide variety of bioactive molecules including vitamins, trace elements and growth factors. The composition of these components reflects the integrated activities of distinct synthetic, secretion and transport processes found in mammary epithelial cells, and mirrors the differing nutritional and developmental requirements of mammalian neonates. Five general pathways have been described for secretion of milk components. With the exception of lipids, which are secreted a unique pathway, milk components are thought to be secreted by adaptations of pathways found in other secretory organs. However little is known about the molecular and cellular mechanisms that constitute these pathways or the physiological mechanisms by which they are regulated. Comparisons of current secretion and transport models in the mammary gland, exocrine pancreas and salivary gland indicate that significant differences exist between the mammary gland and other exocrine organs in how proteins and lipids are packaged and secreted, and how fluid is transported. PMID:17136613

  10. Clear cell carcinoma of exocrine pancreas: a rare tumor with an unusual presentation.

    PubMed

    Ray, Biswajit; New, Norman E; Wedgwood, Kevin R

    2005-03-01

    Metastatic clear cell carcinomas are relatively common from primary tumors arising in the kidney, female genital tract, adrenal cortex, and lung, but they rarely occur from primary tumors of the pancreas. We report a case of metastatic pancreatic tumor with marked clear cell changes in a 46-year-old white man presenting with a pseudocyst of the pancreas. At laparotomy, there was a hard area in the head of the pancreas and another hard nodule was present in the omentum. The histologic and immunohistochemical test of the excised omental nodule exhibited features consistent with clear cell carcinoma from pancreatic primary. To our knowledge, this is the first report of a metastatic clear cell pancreatic tumor with such an unusual presentation. PMID:15714142

  11. Identification of a vesicle-associated membrane protein (VAMP)-like membrane protein in zymogen granules of the rat exocrine pancreas.

    PubMed

    Braun, J E; Fritz, B A; Wong, S M; Lowe, A W

    1994-02-18

    Zymogen granules of the exocrine pancreas are the secretory organelles responsible for the regulated secretion of digestive enzymes. Several proteins are associated with or are integral components of the lipid bilayer that forms the zymogen granule membrane. These proteins likely represent important components in the regulated secretion of digestive enzymes. VAMPs (vesicle-associated membrane proteins)/synaptobrevins are a family of 18-kDa integral membrane proteins originally characterized in synaptic vesicles. Polyclonal antisera raised against either a VAMP/glutathione S-transferase (GST) fusion protein or rat brain synaptic vesicles, detected an 18-kDa immunoreactive protein in zymogen granule membranes that co-migrates electrophorectically with rat brain synaptic vesicle VAMP. Rat brain synaptic vesicle VAMP was detected by both antisera. Botulinum-B toxin treatment of zymogen granule membranes did not result in cleavage of zymogen granule membrane VAMP, indicating that exocrine pancreatic VAMP is either VAMP1 or a novel VAMP-isoform. Immunofluorescent studies demonstrated that exocrine pancreatic VAMP localized with GP2, a zymogen granule membrane protein, to the apical region of pancreatic acinar cells. No significant labeling was observed in basolateral regions of pancreatic acinar cells. These results establish the presence of a VAMP protein in the zymogen granule of the rat pancreas and suggest that VAMPs have a role in exocrine secretion. PMID:8106518

  12. [Function and morphology of intraperitoneal segmental pancreas allotransplants with cyclosporin monotherapy in the dog--a comparison of 4 drainage procedures of exocrine secretions].

    PubMed

    Rosenberger, J; Hesse, U J; Holland, M; Arnold, G; Hübinger, A

    1988-01-01

    Dogs which had received cyclosporine A for immunosuppression were investigated to elucidate functionality and morphological alterations in pancreas allografts, with enteral, vesical, peritoneal or occluded exocrine drainage. None of the animals with enteral drainage survived the first four postoperative weeks, with lethal infections being responsible for allograft failure. Full functionality three months from transplantation was recorded from three of seven transplants with ductal occlusion and unobstructed drainage into the abdominal cavity. Ductal occlusion was repeatedly accompanied by pancreatitis and pseudo-cysts. Fibrotisation of the organ and loss of endocrine islets of pancreas were recordable from these cases just as from grafts with unobstructed drainage into the abdominal cavity. Drainage of exocrine secretion into the bladder yielded good success in one of seven animals and was morphologically and functionally characterised primarily by occlusive metaplastic ossification along the transition to the anastomosis. PMID:2464880

  13. In vivo spectroscopic photoacoustic tomography imaging of a far red fluorescent protein expressed in the exocrine pancreas of adult zebrafish

    NASA Astrophysics Data System (ADS)

    Liu, Mengyang; Schmitner, Nicole; Sandrian, Michelle G.; Zabihian, Behrooz; Hermann, Boris; Salvenmoser, Willi; Meyer, Dirk; Drexler, Wolfgang

    2014-03-01

    Fluorescent proteins brought a revolution in life sciences and biological research in that they make a powerful tool for researchers to study not only the structural and morphological information, but also dynamic and functional information in living cells and organisms. While green fluorescent proteins (GFP) have become a common labeling tool, red-shifted or even near infrared fluorescent proteins are becoming the research focus due to the fact that longer excitation wavelengths are more suitable for deep tissue imaging. In this study, E2-Crimson, a far red fluorescent protein whose excitation wavelength is 611 nm, was genetically expressed in the exocrine pancreas of adult zebrafish. Using spectroscopic all optical detection photoacoustic tomography, we mapped the distribution of E2-Crimson in 3D after imaging the transgenic zebrafish in vivo using two different wavelengths. With complementary morphological information provided by imaging the same fish using a spectral domain optical coherence tomography system, the E2-Crimson distribution acquired from spectroscopic photoacoustic tomography was confirmed in 2D by epifluorescence microscopy and in 3D by histology. To the authors' knowledge, this is the first time a far red fluorescent protein is imaged in vivo by spectroscopic photoacoustic tomography. Due to the regeneration feature of zebrafish pancreas, this work preludes the longitudinal studies of animal models of diseases such as pancreatitis by spectroscopic photoacoustic tomography. Since the effective penetration depth of photoacoustic tomography is beyond the transport mean free path length, other E2-Crimson labeled inner organs will also be able to be studied dynamically using spectroscopic photoacoustic tomography.

  14. Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation.

    PubMed

    De Groef, Sofie; Leuckx, Gunter; Van Gassen, Naomi; Staels, Willem; Cai, Ying; Yuchi, Yixing; Coppens, Violette; De Leu, Nico; Heremans, Yves; Baeyens, Luc; Van de Casteele, Mark; Heimberg, Harry

    2015-01-01

    Expansion of pancreatic beta cells in vivo or ex vivo, or generation of beta cells by differentiation from an embryonic or adult stem cell, can provide new expandable sources of beta cells to alleviate the donor scarcity in human islet transplantation as therapy for diabetes. Although recent advances have been made towards this aim, mechanisms that regulate beta cell expansion and differentiation from a stem/progenitor cell remain to be characterized. Here, we describe a protocol for an injury model in the adult mouse pancreas that can function as a tool to study mechanisms of tissue remodeling and beta cell proliferation and differentiation. Partial duct ligation (PDL) is an experimentally induced injury of the rodent pancreas involving surgical ligation of the main pancreatic duct resulting in an obstruction of drainage of exocrine products out of the tail region of the pancreas. The inflicted damage induces acinar atrophy, immune cell infiltration and severe tissue remodeling. We have previously reported the activation of Neurogenin (Ngn) 3 expressing endogenous progenitor-like cells and an increase in beta cell proliferation after PDL. Therefore, PDL provides a basis to study signals involved in beta cell dynamics and the properties of an endocrine progenitor in adult pancreas. Since, it still remains largely unclear, which factors and pathways contribute to beta cell neogenesis and proliferation in PDL, a standardized protocol for PDL will allow for comparison across laboratories. PMID:26273954

  15. Splenic vein thrombosis is associated with an increase in pancreas-specific complications and reduced survival in patients undergoing distal pancreatectomy for pancreatic exocrine cancer.

    PubMed

    Dedania, Nishi; Agrawal, Nidhi; Winter, Jordan M; Koniaris, Leonidas G; Rosato, Ernest L; Sauter, Patricia K; Leiby, Ben; Pequignot, Edward; Yeo, Charles J; Lavu, Harish

    2013-08-01

    Distal pancreatectomy and splenectomy (DPS) is the procedure of choice for the surgical treatment of pancreatic exocrine cancer localized to the body and tail of the pancreas. Splenic vein thrombosis (SVT) can occur in patients with malignant pancreatic exocrine tumors secondary to direct tumor invasion or compression of the splenic vein by mass effect. This study examines the effect of preoperative SVT on postoperative outcomes. In this retrospective cohort study, we queried our pancreatic surgery database to identify patients who underwent DPS from October 2005 to June 2011. These cases were evaluated for evidence of preoperative SVT on clinical records and cross-sectional imaging (CT,MRI, endoscopic US). Outcomes for patients with and without SVT were compared. From an overall cohort of 285 consecutive patients who underwent DPS during the study period, data were evaluated for 70 subjects who underwent surgery for pancreatic exocrine cancer (27 with SVT, 43 without SVT). The preoperative demographics and co-morbidities were similar between the groups, except the average age was higher for those without SVT (p<0.05). The median estimated blood loss was significantly higher in the SVT group (675 versus 250 ml, p=<0.001).While the overall morbidity rates were similar between the two groups (48 % SVT versus 56% no SVT, p=NS), the group with SVT had a significantly higher rate of pancreas-specific complications, including pancreatic fistula (33 versus 7 %,p<0.01) and delayed gastric emptying (15 versus 0%, p<0.02). Hospital readmission rates were similar between the groups(30 versus 28 %, p=NS). Patients without SVT had a trend toward longer median survival (40 versus 20.8 months),although the difference was not statistically significant (p=0.1). DPS for pancreatic ductal adenocarcinoma can be performed safely in patients with SVT, but with higher intraoperative blood loss, increased pancreas-specific complications, and a trend towards lower long-term survival rates

  16. Overview of Exocrine Pancreatic Pathobiology

    PubMed Central

    Pandiri, Arun R

    2014-01-01

    Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis. PMID:24190915

  17. Pancreas.

    PubMed

    Kandaswamy, R; Skeans, M A; Gustafson, S K; Carrico, R J; Prentice, M A; Israni, A K; Snyder, J J; Kasiske, B L

    2016-01-01

    Even though pancreas transplant numbers have steadily declined over the past decade, new listings increased in 2014 compared with the previous year, notably for pancreas transplant alone (PTA) and simultaneous pancreas-kidney transplant. The number of new PTAs also increased over the past two years. Whether this is a sustainable trend remains to be seen. Significant events in 2014 included implementation of a new pancreas allocation system and development of a proposed uniform definition of pancreas graft failure. Meanwhile, overall pancreas transplant rates and outcomes continued to improve. Substantial decline in pancreas after kidney transplants remains a serious concern. SRTR has not published pancreas graft failure data in the program-specific reports for the past two years. While this will not change in the near future, the acceptance of a uniform definition of graft failure is a crucial first step toward resuming graft failure reporting. Continued improvements and innovation, both surgical and immunological, will be critical to keep pancreas transplant as a viable option for treatment of insulin-dependent diabetes. As alternative therapies for diabetes such as islet transplant and artificial pancreas are evolving, improved outcomes with minimizations of complications are more important than ever. PMID:26755263

  18. Evidence that the (/sup 3/H)estradiol-binding protein in pancreas is localized in exocrine cells

    SciTech Connect

    Grossman, A.; Richardson, S.B.; Altszuler, N.; Lane, B.

    1985-06-01

    Extracts of rat pancreas contain significant amounts of an (/sup 3/H)estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining (/sup 3/H)estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of (/sup 3/H)estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for (/sup 3/H)estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of (/sup 3/H)estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in (/sup 3/H)estradiol-binding activity.

  19. The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: a quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis.

    PubMed

    Vrang, Niels; Jelsing, Jacob; Simonsen, Lotte; Jensen, Andres Eskjær; Thorup, Inger; Søeborg, Henrik; Knudsen, Lotte Bjerre

    2012-07-15

    A possible association between glucagon-like peptide-1 (GLP-1) analogs and incidences of pancreatitis has been suggested based on clinical studies. In male and female diabetic Zucker diabetic fatty (ZDF) rats, we investigated the effects of continuous administration of liraglutide and exenatide on biochemical [lipase, pancreatic amylase (P-amylase)] and histopathological markers of pancreatitis. Male and female ZDF rats were dosed for 13 wk with liraglutide (0.4 or 1.0 mg·kg(-1)·day(-1) sc once daily) or exenatide (0.25 mg·kg(-1)·day(-1) sc, Alzet osmotic minipumps). P-amylase and lipase plasma activity were measured, and an extended histopathological and stereological (specific cell mass and proliferation rate) evaluation of the exocrine and the endocrine pancreas was performed. Expectedly, liraglutide and exenatide lowered blood glucose and Hb A(1c) in male and female ZDF rats, whereas β-cell mass and proliferation rate were increased with greatly improved blood glucose control. Whereas neither analog affected lipase activity, small increases in P-amylase activity were observed in animals treated with liraglutide and exenatide. However, concurrent or permanent increases in lipase and P-amylase activity were never observed. Triglycerides were lowered by both GLP-1 analogs. The qualitative histopathological findings did not reveal adverse effects of liraglutide. The findings were mainly minimal in severity and focal in distribution. Similarly, the quantitative stereological analyses revealed no effects of liraglutide or exenatide on overall pancreas weight or exocrine and duct cell mass or proliferation. The present study demonstrates that, in overtly diabetic male and female ZDF rats, prolonged exposure to GLP-1 receptor agonists does not affect biochemical or histopathological markers of pancreatitis, and whereas both exenatide and liraglutide increase β-cell mass, they have no effect on the exocrine pancreas. However, clinical outcome studies and studies

  20. [Exocrine pancreatic insufficiency in dogs].

    PubMed

    van Noort, R

    1990-07-01

    Pancreatic exocrine insufficiency is the most common cause of maldigestion in dogs. This is usually caused by irreversible atrophy of the pancreas which subsequently requires life-long substitution therapy. The pathophysiology, symptoms and diagnosis are briefly reviewed in the present paper. The Trypsin-like-immunoreactivity test is recommended for establishing the diagnosis. Finally, treatment and possible causes of the failure of therapy are discussed. PMID:2196714

  1. Protein tyrosine phosphatase κ and SHP-1 are involved in the regulation of cell-cell contacts at adherens junctions in the exocrine pancreas

    PubMed Central

    Schnekenburger, J; Mayerle, J; Krüger, B; Buchwalow, I; Weiss, F U; Albrecht, E; Samoilova, V E; Domschke, W; Lerch, M M

    2005-01-01

    Background: We have previously shown that cell contacts between pancreatic acinar cells dissociate early in pancreatitis and that this is a prerequisite for the development of pancreatic oedema. Here we studied the underlying mechanism. Methods: Employing experimental caerulein induced pancreatitis in vivo and isolated pancreatic acini ex vivo, in conjunction with protein chemistry, morphology, and electron microscopy, we determined whether cell contact regulation in the pancreas requires or involves: (1) changes in cadherin-catenin protein expression, (2) tyrosine phosphorylation of adhesion proteins, or (3) alterations in the actin cytoskeleton. Results: During initial cell-cell contact dissociation at adherens junctions, expression of adhesion proteins remained stable. At time points of dissociated adherens junctions, the cadherin-catenin complex was found to be tyrosine phosphorylated and internalised. The receptor type protein tyrosine phosphatase (PTP)κ was constitutively associated with the cadherin-catenin complex at intact cell contacts whereas following the dissociation of adherens junctions, the internalised components of the cadherin-catenin complex were tyrosine phosphorylated and associated with the cytosolic PTP SHP-1. In isolated acini, inhibition of endogenous protein tyrosine phosphatases alone was sufficient to induce dissociation of adherens junctions analogous to that found with supramaximal caerulein stimulation. Dissociation of actin microfilaments had no effect on adherens junction integrity. Conclusions: These data identify tyrosine phosphorylation as the key regulator for cell contacts at adherens junctions and suggest a definitive role for the protein tyrosine phosphatases PTPκ and SHP-1 in the regulation, maintenance, and restitution of cell adhesions in a complex epithelial organ such as the pancreas. PMID:15987791

  2. Pancreatic exocrine response to parenteral nutrition.

    PubMed

    Bivins, B A; Bell, R M; Rapp, R P; Toedebusch, W H

    1984-01-01

    Animal experimental data concerning pancreatic exocrine secretory response to parenteral nutrition is contradictory. We have studied the pancreatic exocrine output in a patient with a pure pancreatic fistula. In this patient, parenteral nutrition with hypertonic glucose, amino acids and fat emulsion was not associated with increases in fistula volume or protein output. Enteral protein and fat in this patient caused rapid increases in both fistula volume and protein output. This study supports the use of parenteral nutrition as a means of maintaining the pancreas at rest. PMID:6321813

  3. Deconstructing Pancreas Developmental Biology

    PubMed Central

    Benitez, Cecil M.; Goodyer, William R.

    2012-01-01

    The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development. PMID:22587935

  4. Reprogramming of human pancreatic exocrine cells to β-like cells

    PubMed Central

    Lemper, M; Leuckx, G; Heremans, Y; German, M S; Heimberg, H; Bouwens, L; Baeyens, L

    2015-01-01

    Rodent acinar cells exhibit a remarkable plasticity as they can transdifferentiate to duct-, hepatocyte- and islet β-like cells. We evaluated whether exocrine cells from adult human pancreas can similarly respond to proendocrine stimuli. Exocrine cells from adult human pancreas were transduced directly with lentiviruses expressing activated MAPK (mitogen-activated protein kinase) and STAT3 (signal transducer and activator of transcription 3) and cultured as monolayers or as 3D structures. Expression of STAT3 and MAPK in human exocrine cells activated expression of the proendocrine factor neurogenin 3 in 50% to 80% of transduced exocrine cells. However, the number of insulin-positive cells increased only in the exocrine cells grown initially in suspension before 3D culture. Lineage tracing identified human acinar cells as the source of Ngn3- and insulin-expressing cells. Long-term engraftment into immunocompromised mice increased the efficiency of reprogramming to insulin-positive cells. Our data demonstrate that exocrine cells from human pancreas can be reprogrammed to transplantable insulin-producing cells that acquire functionality. Given the large number of exocrine cells in a donor pancreas, this approach presents a novel strategy to expand cell therapy in type 1 diabetes. PMID:25476775

  5. Tale of an Innocent

    ERIC Educational Resources Information Center

    Singer, Nicky

    2006-01-01

    The British novelist Nicky Singer talks about becoming a writer, the role of editors and about who decides what can--and what cannot--be published on either side of the Atlantic. Her three novels explore territory which can make publishers nervous: "Feather Boy" (initiation rites and domestic violence), "Doll" (self-harm) and "The Innocent's…

  6. Why Confessions Trump Innocence

    ERIC Educational Resources Information Center

    Kassin, Saul M.

    2012-01-01

    As illustrated by the story of Amanda Knox and many others wrongfully convicted, false confessions often trump factual innocence. Focusing on consequences, recent research suggests that confessions are powerfully persuasive as a matter of logic and common sense; that many false confessions contain richly detailed narratives and accurate crime…

  7. [The pancreas and alcohol].

    PubMed

    Singer, M V

    1985-07-20

    The action of acute and chronic administration of ethanol on pancreatic exocrine secretion in humans and several animal species is reviewed. If the data concerning the secretory action of ethanol on the pancreas are to the property assessed, several experimental variables have to be considered. Acute intravenous administration of ethanol inhibits basal and hormonally stimulated pancreatic secretion of bicarbonate and protein in nonalcoholic humans and most species of animals tested. Oral or intraduodenal ethanol causes moderate stimulation of pancreatic bicarbonate and enzyme secretion. Since anticholinergic agents and truncal vagotomy diminish the ethanol-induced inhibition of pancreatic secretion in the intact animal, it is possible that the action of ethanol on the pancreas is at least partly mediated by inhibitory cholinergic mechanisms. The action of ethanol on the pancreas may also be mediated by release of gastrointestinal hormones. Intravenous and oral administration of ethanol releases gastrin in dogs but not in humans. Pancreatic polypeptide is unlikely to be the hormonal mediator of the ethanol-induced inhibition of exocrine pancreatic secretion in humans and dogs, since ethanol does not release pancreatic polypeptide. The main secretory changes induced by chronic alcoholism in humans and dogs are increased basal secretion of pancreatic enzymes and decreased basal bicarbonate output, and these secretory changes may favour the occurrence of protein precipitates which are believed to be the first lesion of chronic pancreatitis in man. A decrease in the concentration of "pancreatic stone protein" in pancreatic juice may favour the development of protein precipitates in chronic alcoholic patients. PMID:3901251

  8. Imaging of Pancreas Transplantation and Its Complications.

    PubMed

    O'Malley, Ryan B; Moshiri, Mariam; Osman, Sherif; Menias, Christine O; Katz, Douglas S

    2016-03-01

    Whole pancreas transplantation is an effective treatment for obtaining euglycemic status in patients with insulin-dependent diabetes mellitus, and is usually performed concurrent with renal transplantation in the affected patient. This article discusses complex surgical anatomical details of pancreas transplantation including surgical options for endocrine and exocrine drainage pathways. It then describes several possible complications related to surgical factors in the immediate post operative period followed by other complications related to systemic issues, vasculature, and the pancreatic parenchyma. PMID:26896223

  9. Pancreas Transplantation

    MedlinePlus

    The pancreas is a gland behind your stomach and in front of your spine. It produces the juices that ... hormones that help control blood sugar levels. A pancreas transplant is surgery to place a healthy pancreas ...

  10. Pancreas transplant

    MedlinePlus

    ... pancreas from a donor into a person with diabetes. Pancreas transplants give the person a chance to ... used as fuel. In people with type 1 diabetes , the pancreas does not make enough, or sometimes ...

  11. Pancreas transplant

    MedlinePlus

    ... liver cells, where it can be used as fuel. In people with type 1 diabetes , the pancreas ... and kidney for the rest of your life. Alternative Names Transplant - pancreas; Transplantation - pancreas Images Endocrine glands ...

  12. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin {beta}E subunit

    SciTech Connect

    Hashimoto, Osamu . E-mail: ohashim@vmas.kitasato-u.ac.jp; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-03-10

    Activins, TGF-{beta} superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin {beta} subunit genes, {beta}C and {beta}E, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin {beta}E subunit. There were pronounced differences in the pancreata of the transgenic animals as compared with their wild-type counterparts. Pancreatic weight, expressed relative to total body weight, was significantly reduced. Histologically, adipose replacement of acini in the exocrine pancreas was observed. There was a significant decrease in the number of PCNA-positive cells in the acinar cells, indicating reduced proliferation in the exocrine pancreas of the transgenic mice. However, quantitative pancreatic morphometry showed that the total number and mass of the islets of the transgenic mice were comparable with those of the nontransgenic control mice. Our findings suggest a role for activin E in regulating the proliferation of pancreatic exocrine cells.

  13. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders.

    PubMed

    Keller, Jutta; Aghdassi, Ali Alexander; Lerch, Markus M; Mayerle, Julia V; Layer, Peter

    2009-01-01

    The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders. PMID:19505669

  14. Annular pancreas

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001142.htm Annular pancreas To use the sharing features on this page, please enable JavaScript. An annular pancreas is a ring of pancreatic tissue that encircles ...

  15. Pancreas Transplantation

    MedlinePlus

    ... Text Size: A A A Listen En Español Pancreas Transplantation Some patients with type 1 diabetes have ... weigh the potential benefits and risks. Benefits of Pancreas Transplants You may be able to maintain a ...

  16. Polycystic Pancreas.

    PubMed

    Sonavane, Amey D; Amarapurkar, Deepak N; Amarapurkar, Anjali D

    2016-04-01

    Polycystic disease of the pancreas is a very rare entity with very few cases reported in the literature. We report a symptomatic case of polycystic pancreas associated with pheochromocytoma that was treated surgically. PMID:27144204

  17. Polycystic Pancreas

    PubMed Central

    Amarapurkar, Deepak N.; Amarapurkar, Anjali D.

    2016-01-01

    Polycystic disease of the pancreas is a very rare entity with very few cases reported in the literature. We report a symptomatic case of polycystic pancreas associated with pheochromocytoma that was treated surgically. PMID:27144204

  18. What Is the Pancreas?

    MedlinePlus

    ... Pancreas Function of the Pancreas What is the pancreas? The pancreas is a long flattened gland located ... controller of blood sugar levels. Where is the pancreas? The pancreas is located deep in the abdomen. ...

  19. Effects of Ca2+ on phosphoinositide breakdown in exocrine pancreas.

    PubMed Central

    Taylor, C W; Merritt, J E; Putney, J W; Rubin, R P

    1986-01-01

    Recent studies have established that inositol 1,4,5-trisphosphate [I(1,4,5)P3] provides the link between receptor-regulated polyphosphoinositide hydrolysis and mobilization of intracellular Ca2+. Here, we report the effects of Ca2+ on inositol trisphosphate (IP3) formation from phosphatidylinositol bisphosphate (PIP2) catalysed by phospholipase C in intact and electrically permeabilized rat pancreatic acinar cells. In permeabilized cells, the Ca2+-mobilizing agonist caerulein stimulated [3H]IP3 formation when the free [Ca2+] was buffered at 140 nM, the cytosolic free [Ca2+] of unstimulated pancreatic acinar cells. When the free [Ca2+] was reduced to less than 10 nM, caerulein did not stimulate [3H]IP3 formation. Ca2+ in the physiological range stimulated [3H]IP3 formation and reduced the amount of [3H]PIP2 in permeabilized cells. The effects of Ca2+ and the receptor agonist caerulein were additive, but we have not established whether this reflects independent effects on the same or different enzymes. The effect of Ca2+ on [3H]IP3 formation by permeabilized cells was unaffected by inhibitors of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism; nor were the effects of Ca2+ mimicked by addition of arachidonic acid. These results suggest that the effects of Ca2+ on phospholipase C activity are not a secondary consequence of Ca2+ activation of phospholipase A2. Changes in free [Ca2+] (less than 10 nM-1.2 mM) did not affect the metabolism of exogenous [3H]I(1,4,5)P3 by permeabilized cells. In permeabilized cells, breakdown of exogenous [3H]IP3 to [3H]IP2 (inositol bisphosphate), and formation of [3H]IP3 in response to receptor agonists were equally inhibited by 2,3-bisphosphoglyceric acid. This suggests that the [3H]IP2 formed in response to receptor agonists is entirely derived from [3H]IP3. In intact cells, [3H]IP3 formation was stimulated when ionomycin was used to increase the cytosolic free [Ca2+]. However, a maximal concentration of caerulein elicited ten times as much IP3 formation as did the highest physiologically relevant [Ca2+]. We conclude that the major effect of receptor agonists on IP3 formation does not require an elevation of cytosolic free [Ca2+], although the increase in free [Ca2+] that normally follows IP3 formation may itself have a small stimulatory effect on phospholipase C. PMID:3026361

  20. [Effectiveness of panzytrat--modern physiological enzyme preparation in complex therapy of pancreatic exocrine secretory insufficiency in cholelithiasis].

    PubMed

    Petukhov, V A; Mironov, A V; Semenov, Zh S; Ustinov, F S

    2009-01-01

    In the article the analysis of the survey with 102 patients with gallstone disease involved, 68 of whom underwent cholecystectomy and 34 were treated conservatively, is made. The content of fecal elastase 1 in stool was estimated for diagnostics of exocrine enzyme insufficiency of pancreas by immune-enzyme analysis. It was stated that 90% of patients possess secondary exocrine insufficiency of pancreas in case of gallstone disease. It is the result of complex metabolic liver abnormalities, portal and mesenterial haemodynamics, dysbiosis of large intestine which are the components of a syndrom of maldigestion and appear during gallstone disease progressing long time before hospitalization. Cholecystectomy doesn't eliminate enzyme insufficiency of pancreas. The effectiveness of using new physiological enzymatic drug Panzytrat in a complex therapy of a syndrom of maldigestion in case of gallstone disease is shown. PMID:19551960

  1. Pancreas divisum

    MedlinePlus

    ... to form the pancreas. Each part has a tube, called a duct. When the parts join together, a final duct, called the pancreatic duct, is formed. Fluid and digestive juices (enzymes) produced by the pancreas normally flow through this duct. If the ducts do not ...

  2. Cellular expression of Noc2, a Rab effector protein, in endocrine and exocrine tissues in the mouse.

    PubMed

    Teramae, Hiroki; Fujimoto, Wakako; Seino, Susumu; Iwanaga, Toshihiko

    2007-01-01

    Noc2 is a Rab effector which participates in regulated exocytosis. It is expressed abundantly in endocrine cells but at low levels in exocrine tissues. Noc2-deficient mice, however, exhibit marked accumulation of secretory granules in exocrine cells rather than endocrine cells. In the present study, we investigated localization of Noc2 immunohistochemically in various endocrine and exocrine tissues in normal mice. Western blotting detected a Noc2-immunoreactive band of 38 kDa in isolated pancreatic islets, the adrenal gland, pituitary gland, and thyroid gland. Immunostaining for Noc2 labeled endocrine cells in the adrenal medulla and adenohypophysis, pancreatic islet cells, thyroid parafollicular cells, and gut endocrine cells, supporting the notion that Noc2 is a Rab effector protein shared by amine/peptide-secreting endocrine cells. Besides endocrine tissues, granular ducts in salivary glands contained Noc2. Although immunostaining failed to detect Noc2 in acinar cells of all exocrine glands examined, reverse transcriptase-polymerase chain reaction analysis detected the mRNA expression in exocrine pancreas. Ultrastructurally, Noc2 immunoreactivity was associated with the limiting membrane of granules in both pancreatic endocrine and salivary duct exocrine cells. The cellular and subcellular localizations of Noc2 should yield key information on its functional significance as well as account for the phenotype in Noc2-deficient mice. PMID:16835753

  3. The epistemic innocence of psychedelic states.

    PubMed

    Letheby, Chris

    2016-01-01

    One recent development in epistemology, the philosophical study of knowledge, is the notion of 'epistemic innocence' introduced by Bortolotti and colleagues. This concept expresses the idea that certain suboptimal cognitive processes may nonetheless have epistemic (knowledge-related) benefits. The idea that delusion or confabulation may have psychological benefits is familiar enough. What is novel and interesting is the idea that such conditions may also yield significant and otherwise unavailable epistemic benefits. I apply the notion of epistemic innocence to research on the transformative potential of psychedelic drugs. The popular epithet 'hallucinogen' exemplifies a view of these substances as fundamentally epistemically detrimental. I argue that the picture is more complicated and that some psychedelic states can be epistemically innocent. This conclusion is highly relevant to policy debates about psychedelic therapy. Moreover, analysing the case of psychedelics can shed further light on the concept of epistemic innocence itself. PMID:26675408

  4. Change of Both Endocrine and Exocrine Insufficiencies After Acute Pancreatitis in Non-Diabetic Patients

    PubMed Central

    Ho, Te-Wei; Wu, Jin-Ming; Kuo, Ting-Chun; Yang, Ching-Yao; Lai, Hong-Shiee; Hsieh, Su-Hua; Lai, Feipei; Tien, Yu-Wen

    2015-01-01

    Abstract Acute pancreatitis (AP) is the most common pancreatic disease and consists of an acute inflammation of the pancreas. AP can contribute to endocrine and exocrine insufficiencies in survivors as a result of the key role of the pancreas in both glucose metabolism and nutritional digestion. The aim of this population-based study was to determine the endocrine or exocrine insufficiencies in patients after initial AP with biliary or alcohol-associated causes. We conducted a nationwide cohort study using data from Taiwan's National Health Insurance Research Database collected between 2001 and 2010. A total of 12,284 patients with AP were identified. Alcohol-associated AP (odds ratio, 1.894; 95% CI, 1.520–2.268; P < 0.001) and ≥2 admissions for AP (odds ratio, 1.937; 95% CI, 1.483–2.391; P < 0.001) were significantly associated with newly diagnosed diabetes mellitus after AP. Further, only alcohol-associated AP (odds ratio, 1.215; 95% CI, 1.133–1.297; P < 0.001) was significantly associated with pancreatic exocrine insufficiency after AP. Additionally, alcohol-associated AP (odds ratio, 1.804; 95% CI, 1.345–2.263; P < 0.001) and ≥2 readmissions for AP (odds ratio, 3.190; 95% CI, 2.317–4.063; P < 0.001) were significantly associated with both exocrine and endocrine insufficiencies after AP. Our data showed that alcohol-associated AP, rather than a biliary cause, contributed to a higher extent to exocrine or endocrine insufficiencies. Furthermore, recurrent AP also led to endocrine insufficiency. PMID:26166112

  5. Hippo Signaling Regulates Pancreas Development through Inactivation of Yap

    PubMed Central

    Day, Caroline E.; Boerner, Brian P.; Johnson, Randy L.; Sarvetnick, Nora E.

    2012-01-01

    The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition, and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo kinase cascade is a critical regulator of organ growth. To investigate the role of Hippo signaling in pancreas biology, we deleted Hippo pathway components in the developing mouse pancreas. Unexpectedly, the pancreas from Hippo-deficient offspring was reduced in size, with defects evident throughout the organ. Increases in the dephosphorylated nuclear form of Yap are apparent throughout the exocrine compartment and correlate with increases in levels of cell proliferation. However, the mutant exocrine tissue displays extensive disorganization leading to pancreatitis-like autodigestion. Interestingly, our results suggest that Hippo signaling does not directly regulate the pancreas endocrine compartment as Yap expression is lost following endocrine specification through a Hippo-independent mechanism. Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ. PMID:23071096

  6. Artifical Pancreas

    NASA Astrophysics Data System (ADS)

    Fei, Jiangfeng

    2013-03-01

    In 2006, JDRF launched the Artificial Pancreas Project (APP) to accelerate the development of a commercially-viable artificial pancreas system to closely mimic the biological function of the pancreas individuals with insulin-dependent diabetes, particularly type 1 diabetes. By automating detection of blood sugar levels and delivery of insulin in response to those levels, an artificial pancreas has the potential to transform the lives of people with type 1 diabetes. The 6-step APP development pathway serves as JDRF's APP strategic funding plan and defines the priorities of product research and development. Each step in the plan represents incremental advances in automation beginning with devices that shut off insulin delivery to prevent episodes of low blood sugar and progressing ultimately to a fully automated ``closed loop'' system that maintains blood glucose at a target level without the need to bolus for meals or adjust for exercise.

  7. Organ Facts: Pancreas

    MedlinePlus

    ... Home / Before The Transplant / Organ Facts / Pancreas Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Pancreas Facts The pancreas is a five to six inch ...

  8. Exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with pancreatic adenocarcinoma.

    PubMed

    Ritchey, J W; Degernes, L A; Brown, T T

    1997-01-01

    This report describes exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with complete effacement of the pancreas by a pancreatic adenocarcinoma. The bird presented with a 3-month history of weight loss and voluminous, foul-smelling droppings. Clinically, routine hematologic findings were normal and fecal tests were performed to evaluate exocrine pancreatic function. The fecal function tests were positive for neutral and split fats and negative for trypsin. Oral administration of corn oil did not result in elevation of blood triglyceride levels. Two days later, the triglyceride tolerance test was repeated using corn oil mixed with pancreatic enzymes. This time, there was a 70% elevation of blood triglyceride levels. Because of a poor prognosis, the bird was euthanatized. At necropsy, the pancreas was diffusely enlarged, white, nodular, and firm. The liver contained multiple, 1-2-mm-diameter, randomly located, tan nodules. Microscopically, the pancreas was effaced by numerous lobules of neoplastic ductular structures surrounded by abundant fibrous connective tissue. In the liver, the hepatic parenchyma was replaced by multiple, well-demarcated, nonencapsulated foci of neoplastic tissue similar to that in the pancreas. PMID:9150549

  9. Pancreatic exocrine insufficiency after pancreatic surgery.

    PubMed

    Goess, Ruediger; Ceyhan, Güralp O; Friess, Helmut

    2016-06-01

    Pancreatic exocrine insufficiency is an often-underestimated complication following pancreatic surgery. After recent advances in managing acute postoperative complications the focus of current research is now shifting onto the long-term complications following pancreatectomy. Weight loss and steatorrhea as typical symptoms have high influence on the quality of life in the postoperative period. Malnutrition-related symptoms occur late and are often misinterpreted. Enzyme replacement therapy is more or less the only possible treatment option, even though not many controlled trials have been performed in this field. In this review we summarized the pathophysiology, diagnosis, risk factors and treatment options of exocrine insufficiency and focus mainly on patients with pancreaticoduodenectomy (classical Whipple), pylorus-preserving pancreaticoduodenectomy (ppWhipple) or distal pancreatectomy. Incidence of pancreatic exocrine insufficiency after surgery depends mainly on the initial diagnosis, the preoperative exocrine function and is associated with the extent of parenchyma resection. Diagnosing exocrine failure after surgery can be difficult and specific function tests are commonly not routinely performed. Starting and monitoring of enzyme replacement treatment is more based on clinical symptoms, than on objective markers. To improve the performance status of postsurgical patients it is important to consider pancreatic exocrine function as one aspect of quality of life. Further clinical trials should be initiated to gain more specific knowledge about the influence of the different pancreatic resections on pancreatic exocrine function to initialize proper treatment even before major clinical symptoms occur. PMID:27058237

  10. Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight

    NASA Technical Reports Server (NTRS)

    Spooner, B. S.; Hardman, P.; Paulsen, A.

    1994-01-01

    Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

  11. Alford pleas in the age of innocence.

    PubMed

    Redlich, Allison D; Ozdoğru, Asil Ali

    2009-01-01

    In 1970, the Supreme Court handed down a decision in North Carolina v. Alford that has since allowed defendants who do not wish to risk their fates at trial to plead guilty while simultaneously asserting their innocence. Although "Alford pleas" have remained unexamined by researchers, the increasing number of identified wrongful convictions of those factually innocent highlights the need for an in-depth examination of them. In the present study, using the Department of Justice 2004 State Survey of Inmates in Correctional Facilities dataset, we examined the likelihood of entering Alford pleas over traditional guilty, no contest, and not guilty pleas for those convicted of murder/manslaughter. Although we generally found few differences between the three guilty plea types, interesting differences between Alford and not guilty pleas emerged. Implications for actual innocence are discussed. PMID:19405036

  12. Implication of epigenetics in pancreas development and disease.

    PubMed

    Quilichini, Evans; Haumaitre, Cécile

    2015-12-01

    Pancreas development is controlled by a complex interaction of signaling pathways and transcription factor networks that determine pancreatic specification and differentiation of exocrine and endocrine cells. Epigenetics adds a new layer of gene regulation. DNA methylation, histone modifications and non-coding RNAs recently appeared as important epigenetic factors regulating pancreas development. In this review, we report recent findings obtained by analyses in model organisms as well as genome-wide approaches that demonstrate the role of these epigenetic regulators in the control of exocrine and endocrine cell differentiation, identity, function, proliferation and regeneration. We also highlight how altered epigenetic processes contribute to pancreatic disorders: diabetes and pancreatic cancer. Uncovering these epigenetic events can help to better understand these diseases, provide novel therapeutical targets for their treatment, and improve cell-based therapies for diabetes. PMID:26696517

  13. Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells

    PubMed Central

    Matsumoto, Masanari; Miki, Takashi; Shibasaki, Tadao; Kawaguchi, Miho; Shinozaki, Hidehiro; Nio, Junko; Saraya, Atsunori; Koseki, Haruhiko; Miyazaki, Masaru; Iwanaga, Toshihiko; Seino, Susumu

    2004-01-01

    Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an important role in exocytosis. Several potential effectors of Rab3, including rabphilin3 and Rims (Rim1 and Rim2), have been isolated and characterized. Noc2 was identified originally in endocrine pancreas as a molecule homologous to rabphilin3, but its role in exocytosis is unclear. To clarify the physiological function of Noc2 directly, we have generated Noc2 knockout (Noc2-/-) mice. Glucose intolerance with impaired insulin secretion was induced in vivo by acute stress in Noc2-/- mice, but not in wild-type (Noc2+/+) mice. Ca2+-triggered insulin secretion from pancreatic isles of Noc2-/- mice was markedly impaired, but was completely restored by treatment with pertussis toxin, which inhibits inhibitory G protein Gi/o signaling. In addition, the inhibitory effect of clonidine, an α2-adrenoreceptor agonist, on insulin secretion was significantly greater in Noc2-/- islets than in Noc2+/+ islets. Impaired Ca2+-triggered insulin secretion was rescued by adenovirus gene transfer of wild-type Noc2 but not by that of mutant Noc2, which does not bind to Rab3. Accordingly, Noc2 positively regulates insulin secretion from endocrine pancreas by inhibiting Gi/o signaling, and the interaction of Noc2 and Rab3 is required for the effect. Interestingly, we also found a marked accumulation of secretory granules in various exocrine cells of Noc2-/- mice, especially in exocrine pancreas with no amylase response to stimuli. Thus, Noc2, a critical effector of Rab3, is essential in normal regulation of exocytosis in both endocrine and exocrine cells. PMID:15159548

  14. Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells.

    PubMed

    Matsumoto, Masanari; Miki, Takashi; Shibasaki, Tadao; Kawaguchi, Miho; Shinozaki, Hidehiro; Nio, Junko; Saraya, Atsunori; Koseki, Haruhiko; Miyazaki, Masaru; Iwanaga, Toshihiko; Seino, Susumu

    2004-06-01

    Rab3 is a subfamily of the small GTP-binding protein Rab family and plays an important role in exocytosis. Several potential effectors of Rab3, including rabphilin3 and Rims (Rim1 and Rim2), have been isolated and characterized. Noc2 was identified originally in endocrine pancreas as a molecule homologous to rabphilin3, but its role in exocytosis is unclear. To clarify the physiological function of Noc2 directly, we have generated Noc2 knockout (Noc2(-/-)) mice. Glucose intolerance with impaired insulin secretion was induced in vivo by acute stress in Noc2(-/-) mice, but not in wild-type (Noc2(+/+)) mice. Ca(2+)-triggered insulin secretion from pancreatic isles of Noc2(-/-) mice was markedly impaired, but was completely restored by treatment with pertussis toxin, which inhibits inhibitory G protein Gi/o signaling. In addition, the inhibitory effect of clonidine, an alpha(2)-adrenoreceptor agonist, on insulin secretion was significantly greater in Noc2(-/-) islets than in Noc2(+/+) islets. Impaired Ca(2+)-triggered insulin secretion was rescued by adenovirus gene transfer of wild-type Noc2 but not by that of mutant Noc2, which does not bind to Rab3. Accordingly, Noc2 positively regulates insulin secretion from endocrine pancreas by inhibiting Gi/o signaling, and the interaction of Noc2 and Rab3 is required for the effect. Interestingly, we also found a marked accumulation of secretory granules in various exocrine cells of Noc2(-/-) mice, especially in exocrine pancreas with no amylase response to stimuli. Thus, Noc2, a critical effector of Rab3, is essential in normal regulation of exocytosis in both endocrine and exocrine cells. PMID:15159548

  15. Normal Pancreas Anatomy

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Pancreas Anatomy Add to My Pictures View /Download : Small: ... 1586x1534 View Download Large: 3172x3068 View Download Title: Pancreas Anatomy Description: Anatomy of the pancreas; drawing shows ...

  16. Aryne Compatible Solvents are not Always Innocent.

    PubMed

    Suh, Sung-Eun; Chenoweth, David M

    2016-08-19

    Arynes are important and versatile intermediates in a variety of transformations. Commonly used solvents for aryne chemistry include acetonitrile and dichloromethane. Although rarely reported, the reactive nature of aryne intermediates makes them prone to side reactions, which sometimes involve solvent participation. Acetonitrile and dichloromethane are not always innocent solvents and can participate in aryne-based reactions. These results are presented in the context of ongoing mechanistic investigations of the triple aryne-tetrazine reaction. PMID:27486792

  17. CERCLA's innocent landowner defense -- Consultants beware

    SciTech Connect

    Nijman, J.T. )

    1994-05-01

    Consultant liability is an area of the innocent landowner defense under CERCLA that is not often discussed. The only reasonable way to protect consultants hired by innocent purchasers'' is for Congress or state legislatures to establish standardized, regulated audit guidelines. However, even standardized guidelines do not protect consultants completely, because standards cannot specify all activity necessary to perform a particular task. Each project has unique circumstances, and standards arguably can become per se determinants of liability. CERCLA provides three defenses to its basic strict, joint and several liability provisions -- an act of God, an act of war, and an act or omission of a third party not in a contractual relationship with the current owner. Congress amended the third-party not in a contractual relationship with the current owner. Congress amended the third-party defense in SARA by redefining contractual relationship'' to exclude from liability owners who acquired the real property following disposal or placement of hazardous material, and established satisfactorily that the owner at the time of purchase neither knew nor had reason to know hazardous substances were disposed on the property -- the innocent landowner defense.

  18. Use of the Electronic Medical Record to Assess Pancreas Size in Type 1 Diabetes

    PubMed Central

    Virostko, John; Hilmes, Melissa; Eitel, Kelsey; Moore, Daniel J.; Powers, Alvin C.

    2016-01-01

    Aims This study harnessed the electronic medical record to assess pancreas volume in patients with type 1 diabetes (T1D) and matched controls to determine whether pancreas volume is altered in T1D and identify covariates that influence pancreas volume. Methods This study included 25 patients with T1D and 25 age-, sex-, and weight-matched controls from the Vanderbilt University Medical Center enterprise data warehouse. Measurements of pancreas volume were made from medical imaging studies using magnetic resonance imaging (MRI) or computed tomography (CT). Results Patients with T1D had a pancreas volume 47% smaller than matched controls (41.16 ml vs. 77.77 ml, P < 0.0001) as well as pancreas volume normalized by subject body weight, body mass index, or body surface area (all P < 0.0001). Pancreatic volume was smaller with a longer duration of T1D across the patient population (N = 25, P = 0.04). Additionally, four individual patients receiving multiple imaging scans displayed progressive declines in pancreas volume over time (~ 6% of volume/year), whereas five controls scanned a year apart did not exhibit a decline in pancreas size (P = 0.03). The pancreas was uniformly smaller on the right and left side of the abdomen. Conclusions Pancreas volume declines with disease duration in patients with T1D, suggesting a protracted pathological process that may include the exocrine pancreas. PMID:27391588

  19. The epistemic innocence of motivated delusions.

    PubMed

    Bortolotti, Lisa

    2015-05-01

    Delusions are defined as irrational beliefs that compromise good functioning. However, in the empirical literature, delusions have been found to have some psychological benefits. One proposal is that some delusions defuse negative emotions and protect one from low self-esteem by allowing motivational influences on belief formation. In this paper I focus on delusions that have been construed as playing a defensive function (motivated delusions) and argue that some of their psychological benefits can convert into epistemic ones. Notwithstanding their epistemic costs, motivated delusions also have potential epistemic benefits for agents who have faced adversities, undergone physical or psychological trauma, or are subject to negative emotions and low self-esteem. To account for the epistemic status of motivated delusions, costly and beneficial at the same time, I introduce the notion of epistemic innocence. A delusion is epistemically innocent when adopting it delivers a significant epistemic benefit, and the benefit could not be attained if the delusion were not adopted. The analysis leads to a novel account of the status of delusions by inviting a reflection on the relationship between psychological and epistemic benefits. PMID:25459652

  20. Getting a New Pancreas: Facts about Pancreas Transplants

    MedlinePlus

    ... 2003 December 2006 March 2012 Getting A New Pancreas Facts About Pancreas Transplants American Society of Transplantation 1120 Route 73, ... the views of the Society. _________________________________________________________________ Getting a New Pancreas Facts About Pancreas Transplants When you get a ...

  1. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    PubMed

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. PMID:26822093

  2. Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis

    PubMed Central

    Charchaflie, R. J.; Fernandez, L. Bustos; Perec, C. J.; Gonzalez, E.; Marzi, A.

    1974-01-01

    Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested. PMID:4852110

  3. Pancreas transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100129.htm Pancreas transplant - series—Normal anatomy To use the sharing ... to slide 6 out of 6 Overview The pancreas resides in the back of the abdomen. It ...

  4. Annular pancreas (image)

    MedlinePlus

    Annular pancreas is an abnormal ring or collar of pancreatic tissue that encircles the duodenum (the part of the ... intestine that connects to stomach). This portion of pancreas can constrict the duodenum and block or impair ...

  5. Pancreas transplant - series (image)

    MedlinePlus

    The pancreas resides in the back of the abdomen. It functions to produce digestive enzymes which are delivered to ... of the most important hormones produced by the pancreas is insulin. Insulin is produced by specialized cells ...

  6. Innocent until Primed: Mock Jurors' Racially Biased Response to the Presumption of Innocence

    PubMed Central

    Young, Danielle M.; Levinson, Justin D.; Sinnett, Scott

    2014-01-01

    Background Research has shown that crime concepts can activate attentional bias to Black faces. This study investigates the possibility that some legal concepts hold similar implicit racial cues. Presumption of innocence instructions, a core legal principle specifically designed to eliminate bias, may instead serve as an implicit racial cue resulting in attentional bias. Methodology/Principal findings The experiment was conducted in a courtroom with participants seated in the jury box. Participants first watched a video of a federal judge reading jury instructions that contained presumption of innocence instructions, or matched length alternative instructions. Immediately following this video a dot-probe task was administered to assess the priming effect of the jury instructions. Presumption of innocence instructions, but not the alternative instructions, led to significantly faster response times to Black faces when compared with White faces. Conclusions/Significance These findings suggest that the core principle designed to ensure fairness in the legal system actually primes attention for Black faces, indicating that this supposedly fundamental protection could trigger racial stereotypes. PMID:24643050

  7. Pancreas transplantation: review

    PubMed Central

    Meirelles, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID:26154551

  8. Pancreas preservation for pancreas and islet transplantation

    PubMed Central

    Iwanaga, Yasuhiro; Sutherland, David E.R.; Harmon, James V.; Papas, Klearchos K.

    2010-01-01

    Purpose of review To summarize advances and limitations in pancreas procurement and preservation for pancreas and islet transplantation, and review advances in islet protection and preservation. Recent findings Pancreases procured after cardiac death, with in-situ regional organ cooling, have been successfully used for islet transplantation. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are comparable to University of Wisconsin solution when used for cold storage before pancreas transplantation. Colloid-free preservation solutions are inferior to University of Wisconsin solution for pancreas preservation prior to islet isolation and transplantation. Clinical reports on pancreas and islet transplants suggest that the two-layer method may not offer significant benefits over cold storage with the University of Wisconsin solution: improved oxygenation may depend on the graft size; benefits in experimental models may not translate to human organs. Improvements in islet yield and quality occurred from pancreases treated with inhibitors of stress-induced apoptosis during procurement, storage, isolation or culture. Pancreas perfusion may be desirable before islet isolation and transplantation and may improve islet yields and quality. Methods for real-time, noninvasive assessment of pancreas quality during preservation have been implemented and objective islet potency assays have been developed and validated. These innovations should contribute to objective evaluation and establishment of improved pancreas preservation and islet isolation strategies. Summary Cold storage may be adequate for preservation before pancreas transplants, but insufficient when pancreases are processed for islets or when expanded donors are used. Supplementation of cold storage solutions with cytoprotective agents and perfusion may improve pancreas and islet transplant outcomes. PMID:18685343

  9. Change of Both Endocrine and Exocrine Insufficiencies After Acute Pancreatitis in Non-Diabetic Patients: A Nationwide Population-Based Study.

    PubMed

    Ho, Te-Wei; Wu, Jin-Ming; Kuo, Ting-Chun; Yang, Ching-Yao; Lai, Hong-Shiee; Hsieh, Su-Hua; Lai, Feipei; Tien, Yu-Wen

    2015-07-01

    Acute pancreatitis (AP) is the most common pancreatic disease and consists of an acute inflammation of the pancreas. AP can contribute to endocrine and exocrine insufficiencies in survivors as a result of the key role of the pancreas in both glucose metabolism and nutritional digestion. The aim of this population-based study was to determine the endocrine or exocrine insufficiencies in patients after initial AP with biliary or alcohol-associated causes.We conducted a nationwide cohort study using data from Taiwan's National Health Insurance Research Database collected between 2001 and 2010. A total of 12,284 patients with AP were identified.Alcohol-associated AP (odds ratio, 1.894; 95% CI, 1.520-2.268; P < 0.001) and ≥2 admissions for AP (odds ratio, 1.937; 95% CI, 1.483-2.391; P < 0.001) were significantly associated with newly diagnosed diabetes mellitus after AP. Further, only alcohol-associated AP (odds ratio, 1.215; 95% CI, 1.133-1.297; P < 0.001) was significantly associated with pancreatic exocrine insufficiency after AP. Additionally, alcohol-associated AP (odds ratio, 1.804; 95% CI, 1.345-2.263; P < 0.001) and ≥2 readmissions for AP (odds ratio, 3.190; 95% CI, 2.317-4.063; P < 0.001) were significantly associated with both exocrine and endocrine insufficiencies after AP.Our data showed that alcohol-associated AP, rather than a biliary cause, contributed to a higher extent to exocrine or endocrine insufficiencies. Furthermore, recurrent AP also led to endocrine insufficiency. PMID:26166112

  10. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    PubMed Central

    Rana, Surinder S.; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K.

    2016-01-01

    Background Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Methods Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Results Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. Conclusion EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet. PMID:27366039

  11. Polyamine biosynthesis is critical for growth and differentiation of the pancreas

    PubMed Central

    Mastracci, Teresa L.; Robertson, Morgan A.; Mirmira, Raghavendra G.; Anderson, Ryan M.

    2015-01-01

    The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. Moreover, we demonstrate that inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine synthase (DHS). These data identify that the pancreatic requirement for polyamine biosynthesis is largely mediated through a requirement for spermidine for the downstream posttranslational modification of eIF5A by its enzymatic activator DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role for polyamine biosynthesis in pancreatic organogenesis and identified that it may be possible to exploit polyamine biosynthesis to manipulate pancreatic cell differentiation. PMID:26299433

  12. Reporter islets in the eye reveal the plasticity of the endocrine pancreas

    PubMed Central

    Ilegems, Erwin; Dicker, Andrea; Speier, Stephan; Sharma, Aarti; Bahow, Alan; Edlund, Patrick Karlsson; Leibiger, Ingo B.; Berggren, Per-Olof

    2013-01-01

    The islets of Langerhans constitute the endocrine part of the pancreas and are responsible for maintenance of blood glucose homeostasis. They are deeply embedded in the exocrine pancreas, limiting their accessibility for functional studies. Understanding regulation of function and survival and assessing the clinical outcomes of individual treatment strategies for diabetes requires a monitoring system that continuously reports on the endocrine pancreas. We describe the application of a natural body window that successfully reports on the properties of in situ pancreatic islets. As proof of principle, we transplanted “reporter islets” into the anterior chamber of the eye of leptin-deficient mice. These islets displayed obesity-induced growth and vascularization patterns that were reversed by leptin treatment. Hence, reporter islets serve as optically accessible indicators of islet function in the pancreas, and also reflect the efficacy of specific treatment regimens aimed at regulating islet plasticity in vivo. PMID:24248353

  13. An immunohistochemical study of the endocrine pancreas in raptors.

    PubMed

    Palmieri, C; Shivaprasad, H L

    2014-12-01

    The cytoarchitecture of the endocrine pancreas of 10 raptors (golden eagles, peregrine falcons, Saker falcon, turkey vultures, red-tailed hawk and unspecified falcon) was examined by immunohistochemistry. Three islet types were identified: type A mixed islets composed mainly by glucagon (A)-secreting cells, type B mixed islets with predominantly insulin (B)-secreting cell component and type M mixed islets (type M) consisting of variable number of glucagon-, insulin- and somatostatin (D)-secreting cells. The latter were further characterized into Type I, II or III according to the cell distribution of the three cell types. A and D cells were also randomly scattered within the exocrine pancreas. The results of this study suggest that the classical concept in birds of a segregation of A and B cells in well-defined and distinct islets is not applicable in raptors, reflecting an evolutionary adaptation to different dietary habits and variation in developmental mechanisms. PMID:25468799

  14. Ontogeny, postnatal development and ageing of endocrine pancreas in Bubalus bubalis

    PubMed Central

    LUCINI, C.; CASTALDO, L.; LAI, O.; DE VICO, G.

    1998-01-01

    The ontogenesis, postnatal development and ageing of the endocrine pancreas in mammals have not been extensively studied. In order to improve understanding of this organ, we studied the buffalo pancreas during fetal and postnatal development. Glucagon, insulin and somatostatin immunoreactive cells (i.c.) were first seen in 2-mo-old embryos. Pancreatic polypeptide (PP) i.c. were observed during the 3rd month of gestation. The early embryo pancreas was almost totally composed of endocrine tissue. The endocrine portion only slightly increased in mass with animal growth, whereas the exocrine portion noticeably increased in mass during the late fetal and postnatal periods. In adults, therefore, the exocrine portion was more evident than the endocrine portion. Three types of islet were observed in fetal and young buffalos: small, large and PP-islets. The small islets were composed of insulin, glucagon, somatostatin and PP i.c. The large islets were primarily composed of insulin i.c. and a few glucagon, somatostatin and PP i.c. The PP islets were mostly composed of PP i.c. with a few somatostatin, insulin and glucagon i.c. The number of large islets greatly diminished by adulthood. Glucagon, insulin, somatostatin and PP i.c. were also seen scattered in the exocrine parenchyma and along the duct epithelium. In the duct epithelium, these cells were either single or grouped, and they sometimes formed a protrusion projecting towards the connective tissue. These morphological features were primarily observed in fetuses and young buffalos. PMID:9688507

  15. Cryosurgery: ultrastructural changes in pancreas tissue after low temperature exposure.

    PubMed

    Korpan, N N

    2007-04-01

    A number of theoretical and experimental studies, both in vitro and in vivo, have been performed to explain the action of low temperatures on tissue. It is now evident that the thermal parameters used in the past for freezing during cryosurgery were not precise; this may have resulted in the failure of treatment. For the first time, this report describes the early ultrastructural features of pancreatic parenchyma after low temperature exposure, i.e., cryosurgery, in vivo. We demonstrate the effect of freeze-thawing processes using temperatures of various intensities. The cryosurgical response of pancreas parenchyma, i.e., ultrastructural cellular changes in pancreas tissue, was investigated. The electronic microscopic analysis showed that, after local cryodestruction at temperatures of -80 degrees C and -180 degrees C, similar processes occurred within the pancreas tissue in the early postcryosurgical phase -- immediately and up to 24 hours after low temperature exposure on tissue. The exocrine pancreatic cells in the center of the cryozone changed upon thawing. Ultrastructural changes in the exocrine pancreatic cells, where the first signs of dystrophic processes had been noticed, were increased. These ultrastructural changes in the pancreatic cells provide a platform to better understand the mechanisms of damage and the pathogenesis of frostbite after cryosurgery. The properties of the pancreas parenchyma response after low temperature exposure provide important insights into the mechanisms of damage and the cryogenic lesion immediately after thawing in cryosurgery. Our new insights prove on the cell level that suddenly and progressively damaged pancreatic cells in the postcryosurgical zone lead to aseptic cryonecrosis and then to aseptic cryoapoptosis of vital normal tissue. The vascular capillary changes and circulatory stagnation demonstrate the anti-angiogenesis mechanism, which, together with cryoaponecrosis and cryoapoptosis, are some of the main mechanisms

  16. Body image and the innocent eye.

    PubMed

    Sirridge, M; Welch, K

    2002-06-01

    This paper describes the development, content, teaching experience, and impact of the course "The body image in medicine and the arts" which is offered annually in a one-month format for medical students and other upper division students at the University of Missouri-Kansas City (UMKC). Literature, photography, art, anthropology, art history, cultural studies, feminism, modernism, and medicine are all employed in the course as a way of encouraging students to consider the broader cultural interpretations of the human body. Any medical humanities instructor wishing to explore new ideas and themes related to teaching students about past and present body image issues and their impact on contemporary biomedical culture can gain insight through an overview of this course. The purpose of the course is to allow medical students a forum for talking more personally and metaphorically about the body as a cultural concept. The teaching faculty involved in this course believe that the majority of students who participate in this class complete it more acutely aware than before of the fact that no single human being, even a "good, caring" doctor, can see with an "innocent eye". The accomplishment of this goal alone justifies faculty participation in the course. PMID:23671049

  17. Pheromones and exocrine glands in Isoptera.

    PubMed

    Costa-Leonardo, Ana Maria; Haifig, Ives

    2010-01-01

    Termites are eusocial insects that have a peculiar and intriguing system of communication using pheromones. The termite pheromones are composed of a blend of chemical substances and they coordinate different social interactions or activities, including foraging, building, mating, defense, and nestmate recognition. Some of these sociochemicals are volatile, spreading in the air, and others are contact pheromones, which are transmitted by trophallaxis and grooming. Among the termite semiochemicals, the most known are alarm, trail, sex pheromones, and hydrocarbons responsible for the recognition of nestmates. The sources of the pheromones are exocrine glands located all over the termite body. The principal exocrine structures considered pheromone-producing glands in Isoptera are the frontal, mandibular, salivary or labial, sternal, and tergal glands. The frontal gland is the source of alarm pheromone and defensive chemicals, but the mandibular secretions have been little studied and their function is not well established in Isoptera. The secretion of salivary glands involves numerous chemical compounds, some of them without pheromonal function. The worker saliva contains a phagostimulating pheromone and probably a building pheromone, while the salivary reservoir of some soldiers contains defensive chemicals. The sternal gland is the only source of trail-following pheromone, whereas sex pheromones are secreted by two glandular sources, the sternal and tergal glands. To date, the termite semiochemicals have indicated that few molecules are involved in their chemical communication, that is, the same compound may be secreted by different glands, different castes and species, and for different functions, depending on the concentration. In addition to the pheromonal parsimony, recent studies also indicate the occurrence of a synergic effect among the compounds involved in the chemical communication of Isoptera. PMID:20831960

  18. Why people waive their Miranda rights: the power of innocence.

    PubMed

    Kassin, Saul M; Norwick, Rebecca J

    2004-04-01

    In a laboratory experiment, 72 participants who were guilty or innocent of a mock theft were apprehended for investigation. Motivated to avoid prosecution and trial, they were confronted by a neutral, sympathetic, or hostile male "detective" who sought a waiver of their Miranda rights. Later, 72 other participants watched videotapes of these sessions and answered questions about the detective and suspect. Strikingly, results showed that although the detective's demeanor had no effect, participants who were truly innocent were significantly more likely to sign a waiver than those who were guilty. Naively believing in the power of their innocence to set them free, most waived their rights even in the hostile detective condition, where the risk of interrogation was apparent. The conceptual and policy implications of these results are discussed. PMID:15141779

  19. Exocrine and endocrine modulation in common gastric carcinoma.

    PubMed

    Canzonieri, Vincenzo; Colarossi, Cristina; Del Col, Laura; Perin, Tiziana; Talamini, Renato; Sigon, Roberto; Cannizzaro, Renato; Aiello, Eleonora; Buonadonna, Angela; Italia, Fabrizio; Massi, Daniela; Carbone, Antonino; Memeo, Lorenzo

    2012-05-01

    Diagnostic and prognostic implications of endocrine differentiation were evaluated in 103 common gastric adenocarcinomas and undifferentiated carcinomas. Maturely differentiated exocrine and endocrine phenotypes were evaluated by using gastric exocrine and endocrine markers along with intestinal exocrine and endocrine markers. Immunohistochemical analysis revealed that 66 tumors (64%) were positive for generic endocrine markers such as chromogranin A and/or synaptophysin. The 14 patients with more than 20% tumor cells positive for at least 1 endocrine marker experienced a poorer prognosis than patients with no (n = 37) or 1% to 20% (n = 52) positivity. The 16 carcinomas expressing the maturely differentiated exocrine gastric phenotype significantly correlated with poorer outcome compared with carcinomas with mature exocrine intestinal (n = 22) or mixed/gastrointestinal (n = 64) phenotypes. Among tumors expressing chromogranin A and/or synaptophysin, the maturely differentiated endocrine gastric phenotype (n = 26) was a negative prognostic factor compared with mature endocrine intestinal (n = 21) and mixed/gastrointestinal (n = 5) phenotypes. Endocrine differentiation and maturely exocrine/endocrine gastric phenotypes are associated with an unfavorable prognosis and may identify subsets of patients for tailored therapy. PMID:22523208

  20. Secretin is not necessary for exocrine pancreatic development and growth in mice

    PubMed Central

    Sans, Maria Dolors; Sabbatini, Maria Eugenia; Ernst, Stephen A.; D'Alecy, Louis G.; Nishijima, Ichiko

    2011-01-01

    Adaptive exocrine pancreatic growth is mediated primarily by dietary protein and the gastrointestinal hormone cholecystokinin (CCK). Feeding trypsin inhibitors such as camostat (FOY-305) is known to induce CCK release and stimulate pancreatic growth. However, camostat has also been reported to stimulate secretin release and, because secretin often potentiates the action of CCK, it could participate in the growth response. Our aim was to test the role of secretin in pancreatic development and adaptive growth through the use of C57BL/6 mice with genetic deletion of secretin or secretin receptor. The lack of secretin in the intestine or the secretin receptor in the pancreas was confirmed by RT-PCR. Other related components, such as vasoactive intestinal polypeptide (VIP) receptors (VPAC1 and VPAC2), were not affected. Secretin increased cAMP levels in acini from wild-type (WT) mice but had no effect on acini from secretin receptor-deleted mice, whereas VIP and forskolin still induced a normal response. Secretin in vivo failed to induce fluid secretion in receptor-deficient mice. The pancreas of secretin or secretin receptor-deficient mice was of normal size and histology, indicating that secretin is not necessary for normal pancreatic differentiation or maintenance. When WT mice were fed 0.1% camostat in powdered chow, the pancreas doubled in size in 1 wk, accompanied by parallel increases in protein and DNA. Camostat-fed littermate secretin and secretin receptor-deficient mice had similar pancreatic mass to WT mice. These results indicate that secretin is not required for normal pancreatic development or adaptive growth mediated by CCK. PMID:21852360

  1. Assessment of pancreas cells

    NASA Technical Reports Server (NTRS)

    Vanoss, C. J.

    1978-01-01

    Pancreatic islets were obtained from guinea pig pancreas by the collagenase method and kept alive in tissue culture prior to further studies. Pancreas cell morphology was studied by standard histochemical techniques using light microscopy. Preparative vertical electrophoresis-levitation of dispersed fetal guinea pig pancreas cells was conducted in phosphate buffer containing a heavy water (D20) gradient which does not cause clumping of cells or alter the osmolarity of the buffers. The faster migrating fractions tended to be enriched in beta-cell content. Alpha and delta cells were found to some degree in most fractions. A histogram showing the cell count distribution is included.

  2. [Exocrine pancreatic insufficiency and diabetes mellitus].

    PubMed

    Weitgasser, Raimund; Abrahamian, Heidemarie; Clodi, Martin; Zlamal-Fortunat, Sandra; Hammer, Heinz F

    2016-04-01

    Exocrine pancreatic insufficiency (EPI) in diabetic patients is frequent. Studies based on fecal elastase-1 measurement give prevalence rates of 10‒30 % of severe and 22‒56 % of moderate EPI in type 1 and rates of 5‒46 % in type 2 diabetic patients. Nevertheless, not all patients report typical symptoms like diarrhea, steatorrhea and weight loss. For noninvasive testing the determination of fecal elastase-1 has the highest sensitivity and specificity. This test should be performed at least in all symptomatic patients. As differential diagnosis celiac disease (with a prevalence of about 3-5 % of type 1 diabetic patients), autonomic neuropathy, but also diseases like irritable bowel syndrome and gastrointestinal tumors have to be taken into account. Patients with symptoms and a fecal elastase-1 < 100 µg/g should be treated with pancreatic enzymes in adequate daily doses administered at main meals. Treatment improves symptoms significantly, supply with fat soluble vitamins is normalised, risk for osteoporosis is reduced. However, improvement of glucose metabolism has not been demonstrated consistently. A pancreatogenic diabetes, also termed as type 3c diabetes, has not necessarily to be treated with insulin, often-at least initially-treatment with oral antidiabetic drugs is sufficient. PMID:27052236

  3. The Power of Innocence: From Politeness to Politics.

    ERIC Educational Resources Information Center

    Baddeley, Simon; James, Kim

    1991-01-01

    Etiquette serves as a defense of the social order while hiding that purpose from its beneficiaries. Although people believe their manners guarantee integrity, politically "innocent" powerful people are often unintentionally offensive to people of a different class, ethnicity, or gender. (SK)

  4. Visualizing the Politics of Innocence in the Age of AIDS

    ERIC Educational Resources Information Center

    Mitchell, Claudia; Walsh, Shannon; Larkin, June

    2004-01-01

    We are concerned with the ways in which social constructions of age can contribute to reducing or exacerbating the vulnerability of young people, and for this reason we refer to the issue as one of "the politics of innocence". The focus of this paper is on gender, youth and HIV prevention/AIDS awareness in the context of South Africa and…

  5. 33 CFR 151.2020 - Vessels in innocent passage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Vessels in innocent passage. 151.2020 Section 151.2020 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL...

  6. Preschoolers' Understanding of Lies and Innocent and Negligent Mistakes.

    ERIC Educational Resources Information Center

    Siegal, Michael; Peterson, Candida C.

    1998-01-01

    Examined preschoolers' ability to distinguish innocent and negligent mistakes from lies. Found that, when asked to identify a mistake or lie about a food's contact with contaminants and identify a bystander's reaction, children distinguished mistakes from lies; they could also discriminate between lies and both negligent mistakes that generate…

  7. Innocent heart murmurs in children. Taking a diagnostic approach.

    PubMed Central

    Saunders, N. R.

    1995-01-01

    Nearly all pediatric murmurs are heard in normal hearts and are not due to cardiac disorders. These murmurs usually can be classified by distinctive features and distinguished from organic murmurs by skillful clinical examination. This article reviews the various types of innocent heart murmurs in children, discusses their differential diagnoses, and suggests an approach to sorting out pediatric murmurs. PMID:8520239

  8. Organ Facts: Kidney / Pancreas

    MedlinePlus

    ... the kidneys is to remove waste from the body through the production of urine. They also help to regulate blood pressure, blood volume and the chemical (electrolyte) composition of the blood. The pancreas is a five ...

  9. Cystic Lymphangioma of Pancreas.

    PubMed

    Bihari, Chhagan; Rastogi, Archana; Rajesh, S; Arora, Ankur; Arora, Asit; Kumar, Nikhil

    2016-03-01

    Lymphangiomas are benign hamartomatous malformations which can arise either from congenitally sequestered lymphatic channels or due to acquired obstruction caused by fibrosis of lymph channels. They are common in the pediatric age group in the soft tissue of neck and the axilla. Abdominal lymphangiomas are rare; even rarer is the primary involvement of pancreas. It occurs more frequently in females and is often located in the distal pancreas. The authors report the case of cystic lymphangioma of pancreas in a 26-year old female presenting with recurrent episodes of upper abdominal pain that was treated with laparoscopic cyst excision. Although exceptionally rare, lymphangioma of the pancreas should be considered in the differential diagnosis of pancreatic cystic lesions, especially in young women. PMID:27065694

  10. Tissue-specific deletion of c-Jun in the pancreas has limited effects on pancreas formation

    SciTech Connect

    Yamamoto, Kaoru; Miyatsuka, Takeshi; Tanaka, Ayako; Toyoda, Shuichi; Kato, Ken; Shiraiwa, Toshihiko; Fujitani, Yoshio; Yamasaki, Yoshimitsu; Hori, Masatsugu; Matsuhisa, Munehide; Matsuoka, Taka-aki; Kaneto, Hideaki

    2007-11-30

    It is well known that activating protein-1 (AP-1) is involved in a variety of cellular functions such as proliferation, differentiation, apoptosis, and oncogenesis. AP-1 is a dimer complex consisting of different subunits, and c-Jun is known to be one of its major components. In addition, it has been shown that mice lacking c-Jun are embryonic lethal and that c-Jun is essential for liver and heart development. However, the role of c-Jun in the pancreas is not well known. The aim of this study was to examine the possible role of c-Jun in the pancreas. First, c-Jun was strongly expressed in pancreatic duct-like structures at an embryonic stage, while a lower level of expression was observed in some part of the adult pancreas, implying that c-Jun might play a role during pancreas development. Second, to address this point, we generated pancreas-specific c-Jun knock-out mice (Ptf1a-Cre; c-Jun{sup flox/flox} mice) by crossing Ptf1a-Cre knock-in mice with c-Jun floxed mice. Ptf1a is a pancreatic transcription factor and its expression is confined to pancreatic stem/progenitor cells, which give rise to all three types of pancreatic tissue: endocrine, exocrine, and duct. Contrary to our expectation, however, there was no morphological difference in the pancreas between Ptf1a-Cre; c-Jun{sup flox/flox} and control mice. In addition, there was no difference in body weight, pancreas weight, and the expression of various pancreas-related factors (insulin, glucagon, cytokeratin, and amylase) between the two groups. Furthermore, there was no difference in glucose tolerance between Ptf1a-Cre; c-Jun{sup flox/flox} and control mice. Taken together, although we cannot exclude the possibility that c-Jun ablation is compensated by some unknown factors, c-Jun appears to be dispensable for pancreas development at least after ptf1a gene promoter is activated.

  11. Cyclosporine pharmacokinetics in pancreas transplant recipients.

    PubMed

    Munda, R; Schroeder, T J; Pedersen, S A; Clardy, C W; Wadhwa, N K; Myre, S A; Stephens, G W; Pesce, A J; Alexander, J W; First, M R

    1988-04-01

    Ten CsA pharmacokinetic studies were performed on five pancreas transplant recipients to determine proper doses and dosing intervals. These cadaver pancreas transplants were performed with exocrine ductal drainage into the urinary tract through a bladder anastomosis in four cases and into the bowel in one case. Four CsA pharmacokinetic studies were performed on diabetic renal transplant recipients and an additional six studies were performed while with pancreas transplant patients taking metoclopramide in an effort to enhance absorption of CsA. Mean CsA dose was 3.7 mg/kg/dose (range 2.1 to 7.5 mg/kg/dose). All patients but one were on twice daily dosing intervals yielding an average daily dose of 7.4 mg/kg/d. Noncompartmental pharmacokinetic analyses were used. The adequacy of a 1-, 2-, or 3-exponential model was determined by breakpoint analysis of the log concentration v time curve using the F statistic. The terminal rate constant was calculated by nonlinear regression analysis. The AUC and AUMC were calculated by the trapezoidal method with exponential extrapolation and these were used to calculate the MRT and Vdss. The unknown fractional absorption, F, was used to correct the oral data. The average CsA concentration maximum (Cmax) was 528 ng/mL with an average time to maximum concentration (Tmax) of 4.7 hours, a mean residence time of 7.75 hours, with a Vdss/%F of 9.61 L/kg in the pancreas transplant recipients. Additional studies of six patients receiving metoclopramide with CsA revealed an average Cmax of 723 ng/mL, an average Tmax of 2.3 hours, an average MRT of 6.08 hours, and an average Vdss/%F of 5.7% L/kg. These results indicate that coexistent gastroparesis in diabetic recipients of either pancreatic or renal transplants may result in reduced bioavailability of CsA. PMID:3284095

  12. Pancreas and cyst segmentation

    NASA Astrophysics Data System (ADS)

    Dmitriev, Konstantin; Gutenko, Ievgeniia; Nadeem, Saad; Kaufman, Arie

    2016-03-01

    Accurate segmentation of abdominal organs from medical images is an essential part of surgical planning and computer-aided disease diagnosis. Many existing algorithms are specialized for the segmentation of healthy organs. Cystic pancreas segmentation is especially challenging due to its low contrast boundaries, variability in shape, location and the stage of the pancreatic cancer. We present a semi-automatic segmentation algorithm for pancreata with cysts. In contrast to existing automatic segmentation approaches for healthy pancreas segmentation which are amenable to atlas/statistical shape approaches, a pancreas with cysts can have even higher variability with respect to the shape of the pancreas due to the size and shape of the cyst(s). Hence, fine results are better attained with semi-automatic steerable approaches. We use a novel combination of random walker and region growing approaches to delineate the boundaries of the pancreas and cysts with respective best Dice coefficients of 85.1% and 86.7%, and respective best volumetric overlap errors of 26.0% and 23.5%. Results show that the proposed algorithm for pancreas and pancreatic cyst segmentation is accurate and stable.

  13. MFng Is Dispensable for Mouse Pancreas Development and Function▿ †

    PubMed Central

    Svensson, Per; Bergqvist, Ingela; Norlin, Stefan; Edlund, Helena

    2009-01-01

    Notch signaling regulates pancreatic cell differentiation, and mutations of various Notch signaling components result in perturbed pancreas development. Members of the Fringe family of β1,3-N-acetylglucosaminyltransferases, Manic Fringe (MFng), Lunatic Fringe (LFng), and Radical Fringe (RFng), modulate Notch signaling, and MFng has been suggested to regulate pancreatic endocrine cell differentiation. We have characterized the expression of the three mouse Fringe genes in the developing mouse pancreas between embryonic days 9 and 14 and show that the expression of MFng colocalized with the proendocrine transcription factor Ngn3. In contrast, the expression of LFng colocalized with the exocrine marker Ptf1a, whereas RFng was not expressed. Moreover, we show that expression of MFng is lost in Ngn3 mutant mice, providing evidence that MFng is genetically downstream of Ngn3. Gain- and loss-of-function analyses of MFng by the generation of mice that overexpress MFng in early pancreatic progenitor cells and mice with a targeted deletion of MFng provide, however, evidence that MFng is dispensable for pancreas development and function, since no pancreatic defects in these mice were observed. PMID:19223466

  14. Epidemiology of pancreas cancer in Los Angeles

    SciTech Connect

    Mack, T.M.; Paganini-Hill, A.

    1981-03-15

    The characteristics of the 3614 Los Angeles County residents in whom cancer of the exocrine pancreas was diagnosed during the period 1972-1977 were compared with those of all county residents and patients in whom any cancer was diagnosed during the same period. Seventy-nine percent of the diagnoses had been pathologically verified. This disease still preferentially afflicts the old, the black, and men, although the differences in risk with factors other than age are modest. The disease is not evenly distributed by social class, or over time, although it is not clear that the observed differences reflect etiology. The distributions with respect to important categories of occupation and industry, religion, marital status, geography of residence, and birthplace were rather uniform. Although there is no obvious explanation for any of several unexpected minor inequities in the pattern of incidence, there is no compelling evidence to support any specific environmental cause. There is substantial evidence which is inconsistent with those environmental hypotheses that have been proposed previously.

  15. Portal Annular Pancreas

    PubMed Central

    Harnoss, Jonathan M.; Harnoss, Julian C.; Diener, Markus K.; Contin, Pietro; Ulrich, Alexis B.; Büchler, Markus W.; Schmitz-Winnenthal, Friedrich H.

    2014-01-01

    Abstract Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF). On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered. In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery). Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option. PMID:25207658

  16. Calcium and magnesium in exocrine secretion--an X-ray microanalytical study

    SciTech Connect

    Roomans, G.M.; Barnard, T.

    1982-01-01

    Calcium and magnesium distribution in mammalian exocrine glands under resting, stimulated and pathological conditions was investigated by X-ray microanalysis of thick and ultrathin cryosections. Ultrathin sections were cut from tissue frozen in the presence of a polymer cryoprotectant, dextran. The effect of this treatment on isolated rabbit pancreas. Dextran caused a disturbance in water and ion transport, partly due to an osmotic effect and the impermeability of the pancreatic epithelium to dextran; this does, however, not necessarily invalidate intracellular measurements on frozen-dried sections. Cholinergic stimulation of the rat pancreas caused a change of Ca distribution from the basal to the apical part of the cell; this may be a component of the secretory Ca flux. Kinetic considerations make a significant Ca movement via the ER-Golgi endomembrane space less likely. The mitochondrial Ca concentration is low, and not significantly changed by cholinergic stimulation. X-ray microanalysis was carried out on submandibular glands of rats after chronic treatment with reserpin and/or isoproterenol (an animal model for cystic fibrosis, CF). The acinar cells had elevated Mg and Ca and lowered K concentrations. Analysis of ultrathin cryosections showed high levels of Ca and Mg in secretory granules, mucus globules and the ER. Ca and Mg in the ER may be transported intracellularly with secretory proteins to secretion granules or mucus globules. The decrease in cell K may be due to efflux of K caused by elevated cytoplasmic Ca levels. A similar decrease in cell K was caused by incubation of rat salivary glands with diluted serum from CF patients, a treatment which has been reported to mimic the effect of a rise in cytoplasmic Ca.

  17. EXOCRINE PANCREATIC CARCINOGENESIS IN THE GUPPY POECILIA RETICULATA

    EPA Science Inventory

    Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following exposure to the direct acting carcinogen, methylazoxymethanol acetate (MAM-Ac). Fish 6- to 10-days old were exposed to nominal, nontoxic concentrations of 4 and 10 mg MAM-Ac 1-1 for 2 h and then tr...

  18. EXOCRINE PANCREATIC CARCINOGENESIS IN THE GUPPY (POECILIA RETICULATA).

    EPA Science Inventory

    Exocrine pancreatic neoplasms developed in the guppy (Poecilia reticulata) following exposure to the direct acting carcinogen, methylazoxymethanol acetate (MAM-Ac). Fish 6- to 10-days old were exposed to nominal, nontoxic concentrations of 4 and 10 mg MAM-Ac/L for 2 hr and then t...

  19. Endocrine and exocrine function of the bovine testis. Chapter 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter is devoted to the endocrine and exocrine function of the normal bovine male testes. The discussion begins with a historical review of the literature dating back to Aristotle’s (300 BC) initial description of the anatomy of the mammalian testes. The first microscopic examination of the t...

  20. Exocrine Glands of Schwarziana quadripunctata (Hymenoptera, Apinae, Meliponini).

    PubMed

    Cruz-Landim, C; Reginato, R D

    2001-08-01

    This article 'describes the location, anatomy, histology and ontogeny of adult Schwarziana quadripunctata exocrine glands. These glands appear either as individualized organs (salivary gland system and Dufour gland) or as epidermis differentiation (tegumentary glands). Variations in the occurrence and degree of development among colony components with regard to their degree of maturity are also described. PMID:11706578

  1. Association of DLA-DQB1 alleles with exocrine pancreatic insufficiency in Pembroke Welsh Corgis.

    PubMed

    Evans, J M; Tsai, K L; Starr-Moss, A N; Steiner, J M; Clark, L A

    2015-08-01

    Exocrine pancreatic insufficiency (EPI) is a digestive disorder resulting from the insufficient secretion of enzymes from the pancreas. In dogs, this condition is often attributed to pancreatic acinar atrophy, wherein the enzyme-producing acinar cells are believed to be destroyed through an autoimmune process. Although EPI affects many diverse breeds, to date, molecular studies have been limited to the German Shepherd dog. A recent study of major histocompatibility genes in diseased and healthy German Shepherd dogs identified both risk and protective haplotypes. Herein, we genotyped DLA-DQB1 in Pembroke Welsh Corgis to determine whether dog leukocyte antigen alleles contribute to the pathogenesis of EPI across dog breeds. We evaluated 14 affected and 43 control Pembroke Welsh Corgis, which were selected based on an age of onset similar to German Shepherd dogs. We identified one protective allele (odds ratio = 0.13, P-value = 0.044) and one risk allele (odds ratio = 3.8, P-value = 0.047). As in German Shepherd dogs, the risk allele is a duplication of DLA-DQB1 (alleles DQB1*013:03 and 017:01); however, Pembroke Welsh Corgis have acquired a single polymorphism on DQB1*017:01. Thus, the DLA-DQB1 duplication is a risk allele for EPI in at least two breeds. PMID:26095904

  2. X-ray microanalysis of exocrine glands in animal models for cystic fibrosis

    SciTech Connect

    Mueller, R.M.R.; Roomans, G.M.

    1985-01-01

    Elemental distribution and ultrastructure of the submandibular gland, the parotid gland and the pancreas were investigated in three suggested animal models of the disease cystic fibrosis: the chronically reserpinized rat, the chronically isoproterenol-treated rat, and the chronically pilocarpine-treated rat. To elucidate the cellular mechanism underlying the effects of these treatments, chronic effects of specific alpha - and beta -adrenergic agonists, as well as acute effects of reserpine and various agonists were also investigated. Reserpine, isoproterenol, and pilocarpine cause an increase in the calcium concentration in submandibular gland acinar cells, due to an increased calcium content of the intracellular mucus. In the parotid gland, reserpine and isoproterenol cause a decrease of the calcium concentration in acinar cells, due to a lower calcium content of the zymogen granules. In the submandibular gland, a decreased cellular Na concentration was noted after chronic treatment with isoproterenol or pilocarpine, and after a single dose of reserpine or isoproterenol. Ultrastructural changes in the exocrine glands investigated included excessive accumulation of intracellular secretory material and formation of abnormal uncondensed secretion granules. A common pattern in the animal models appears to be (1) inhibition of secretion resulting in intracellular accumulation of secretory material, (2) synthesis of secretory macromolecules with altered cation-binding properties.

  3. National Pancreas Foundation

    MedlinePlus

    ... NPF raises and directs funds to support exemplary research projects in the field of pancreas disease Fellows Symposium A three-day symposium pairing together world class physicians and scientists with medical fellows. ... Research Grant Application Research History Grant Review Committee ...

  4. ALDH1B1 is a potential stem / progenitor marker for multiple pancreas progenitor pools

    PubMed Central

    Ioannou, Marilia; Serafimidis, Ioannis; Arnes, Luis; Sussel, Lori; Singh, Surendra; Vasiliou, Vasilis; Gavalas, Anthony

    2013-01-01

    Aldehyde Dehydrogenase (ALDH) genes are increasingly associated with stem / progenitor cell status but their role in the maintenance of pluripotency remains uncertain. In a screen conducted for downstream Ngn3 target genes using ES derived pancreas progenitors we identified Aldh1b1, encoding a mitochondrial enzyme, as one of the genes strongly up regulated in response to Ngn3 expression. We found both by in situ hybridization and immunofluorescence using a specific antibody that ALDH1B1 is exclusively expressed in the emerging pancreatic buds of the early embryo (9.5 dpc) in a Pdx1 dependent manner. Around the time of secondary transition, ALDH1B1 expression was restricted in the tip tripotent progenitors of the branching epithelium and in a subset of the trunk epithelium. Expression in the latter was Ngn3 dependent. Subsequently, ALDH1B1 expression persisted only in the tip cells that become restricted to the exocrine lineage and declined rapidly as these cells mature. In the adult pancreas we identified rare ALDH1B1+ cells that become abundant following pancreas injury in either the caerulein or streptozotocin paradigms. Blocking ALDH catalytic activity in pancreas embryonic explants resulted in reduced size of the explants and accelerated differentiation suggesting for the first time that ALDH activity may be necessary in the developing pancreas for the maintenance and expansion of progenitor pools. PMID:23142317

  5. ECM signaling regulates collective cellular dynamics to control pancreas branching morphogenesis

    PubMed Central

    Shih, Hung Ping; Panlasigui, Devin; Cirulli, Vincenzo; Sander, Maike

    2015-01-01

    Summary During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; as well, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells, and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis. PMID:26748698

  6. Ectopic Ptf1a expression in murine ESCs potentiates endocrine differentiation and models pancreas development in vitro

    PubMed Central

    Nair, Gopika; Vincent, Robert K.; Odorico, Jon S.

    2014-01-01

    Besides its role in exocrine differentiation, pancreas-specific transcription factor 1a (PTF1a) is required for pancreas specification from the foregut endoderm and ultimately for endocrine cell formation. Examining the early role of PTF1a in pancreas development has been challenging due to limiting amounts of embryonic tissue material for study. Embryonic stem cells (ESCs) which can be differentiated in vitro, and without limit to the amount of experimental material, can serve as a model system to study these early developmental events. To this end, we derived and characterized a mouse ESC line with tetracycline-inducible expression of PTF1a (tet-Ptf1a mESCs). We found that transient ectopic expression of PTF1a initiated the pancreatic program in differentiating ESCs causing cells to activate PDX1 expression in bud-like structures resembling pancreatic primordia in vivo. These bud-like structures also expressed progenitor markers characteristic of a developing pancreatic epithelium. The epithelium differentiated to generate a wave of NGN3+ endocrine progenitors, and further formed cells of all three pancreatic lineages. Notably, the insulin+ cells in the cultures were monohormonal, and expressed PDX1 and NKX6.1. PTF1a-induced cultures differentiated into significantly more endocrine and exocrine cells and the ratio of endocrine-to-exocrine cell differentiation could be regulated by retinoic acid and nicotinamide signaling. Moreover, induced cultures treated with RA and Nic exhibited a modest glucose response. Thus, this tet-Ptf1a ESC-based in vitro system is a valuable new tool for interrogating the role of PTF1a in pancreas development and in directing differentiation of ESCs to endocrine cells. PMID:24375815

  7. Retinoids in the pancreas

    PubMed Central

    Brun, Pierre-Jacques; Wongsiriroj, Nuttaporn

    2016-01-01

    Retinoids (vitamin A and its natural and synthetic analogs) are required by most tissues for maintaining the normal health of the tissue. This is certainly true for the pancreas. The recent literature is convincing that retinoids are needed by the adult to assure normal pancreatic endocrine functions, especially those of the α- and β-cells. It is also well established that retinoids are required to insure normal pancreas development in utero, including the development of the endocrine pancreas. The actions of retinoids for maintaining normal pancreatic islet functions has drawn considerable research interest from investigators interested in understanding and treating metabolic disease. Pancreatic retinoids are also of interest to investigators studying the origins of pancreatic disease, including the development of pancreatic fibrosis and its sequelae. This research interest is focused on pancreatic stellate cells (PSCs) which store retinoids and possess the metabolic machinery needed to metabolize retinoids. The literature on pancreatic disease and retinoids suggests that there is an association between impairments in pancreatic retinoid storage and metabolism and the development of pancreatic disease. These topics will be considered in this review. PMID:26904552

  8. Structural similarities and differences between the human and the mouse pancreas

    PubMed Central

    Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

    2015-01-01

    Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application. PMID:26030186

  9. Double papillary fibroelastoma: beautiful, innocent flowers in the left heart.

    PubMed

    Floria, Mariana; Gerard, Marina; Louagie, Yves; Weynand, Birgit; Schroeder, Erwin

    2014-01-01

    Papillary fibroelastoma is a rare, benign tumor, and multiple papillary fibroelastomas are even more uncommon. In an asymptomatic patient scheduled for carotid endarterectomy, transthoracic echocardiography discovered a fibroelastoma on the mitral valve. Then, transesophageal echocardiography showed another fibroelastoma on the aortic valve. Because he also needed a right coronary artery bypass, the patient underwent surgical excision of both masses. Fibroelastomas are not always as innocent as they seem, and surgical excision is necessary because of their potential for systemic or coronary embolization. Transoesophageal echocardiography may improve the diagnosis of multiple papillary fibroelastomas. PMID:24796685

  10. Noc-king out exocrine and endocrine secretion.

    PubMed

    Cheviet, Séverine; Waselle, Laurent; Regazzi, Romano

    2004-10-01

    The Rab GTPase effector Noc2 was brought into the limelight by a recent publication that demonstrated its requirements at different stages of regulated exocytosis. Noc2 knockout resulted in distinct abnormalities in endocrine and exocrine cells, ranging from the accumulation of secretory granules of increased size to impairments in the regulated release of their secretory products. Explanations for these defects are beginning to emerge and they promise to reveal some of the most jealously kept secrets of regulated exocytosis. PMID:15450973

  11. White Innocence and Mexican Americans as Perpetrators in the School-to-Prison Pipeline

    ERIC Educational Resources Information Center

    Orozco, Richard

    2013-01-01

    This essay discusses white innocence as a mechanism that may contribute to perceptions of Mexican Americans as perpetrators. These perceptions are crucial to ways teachers and administrators respond to student actions as the initial steps in the school-to-prison pipeline. Specifically, this work reviews the rhetoric of white innocence in a high…

  12. Brilliance of a Fire: Innocence, Experience and the Theory of Childhood

    ERIC Educational Resources Information Center

    Davis, Robert A.

    2011-01-01

    This essay offers an extensive rehabilitation and reappraisal of the concept of childhood innocence as a means of testing the boundaries of some prevailing constructions of childhood. It excavates in detail some of the lost histories of innocence in order to show that these are more diverse and more complex than established and pejorative…

  13. Role of Connexins and Pannexins in the Pancreas.

    PubMed

    Cigliola, Valentina; Allagnat, Florent; Berchtold, Lukas Adrian; Lamprianou, Smaragda; Haefliger, Jacques-Antoine; Meda, Paolo

    2015-11-01

    The pancreas produces enzymes with a digestive function and hormones with a metabolic function, which are produced by distinct cell types of acini and islets, respectively. Within these units, secretory cells coordinate their functioning by exchanging information via signals that flow in the intercellular spaces and are generated either at distance (several neural and hormonal inputs) or nearby the pancreatic cells themselves (inputs mediated by membrane ionic-specific channels and by ionic- and metabolite-permeant pannexin channels and connexin "hemichannels"). Pancreatic secretory cells further interact via the extracellular matrix of the pancreas (inputs mediated by integrins) and directly with neighboring cells, by mechanisms that do not require extracellular mediators (inputs mediated by gap and tight junction channels). Here, we review the expression and function of the connexins and pannexins that are expressed by the main secretory cells of the exocrine and endocrine pancreatic cells. Available data show that the patterns of expression of these proteins differ in acini and islets, supporting distinct functions in the physiological secretion of pancreatic enzymes and hormones. Circumstantial evidence further suggests that alterations in the signaling provided by these proteins are involved in pancreatic diseases. PMID:26465951

  14. Endothelium-derived essential signals involved in pancreas organogenesis

    PubMed Central

    Talavera-Adame, Dodanim; Dafoe, Donald C

    2015-01-01

    Endothelial cells (ECs) are essential for pancreas differentiation, endocrine specification, and endocrine function. They are also involved in the physiopathology of type 1 and type 2 diabetes. During embryogenesis, aortic ECs provide specific factors that maintain the expression of key genes for pancreas development such as pancreatic and duodenal homeobox-1. Other unknown factors are also important for pancreatic endocrine specification and formation of insulin-producing beta cells. Endocrine precursors proliferate interspersed with ductal cells and exocrine precursors and, at some point of development, these endocrine precursors migrate to pancreatic mesenchyme and start forming the islets of Langerhans. By the end of the gestation and close to birth, these islets contain immature beta cells with the capacity to express vascular endothelial growth factor and therefore to recruit ECs from the surrounding microenvironment. ECs in turn produce factors that are essential to maintain insulin secretion in pancreatic beta cells. Once assembled, a cross talk between endocrine cells and ECs maintain the integrity of islets toward an adequate function during the whole life of the adult individual. This review will focus in the EC role in the differentiation and maturation of pancreatic beta cells during embryogenesis as well as the current knowledge about the involvement of endothelium to derive pancreatic beta cells in vitro from mouse or human pluripotent stem cells. PMID:25992319

  15. The essence of innocence: consequences of dehumanizing Black children.

    PubMed

    Goff, Phillip Atiba; Jackson, Matthew Christian; Di Leone, Brooke Allison Lewis; Culotta, Carmen Marie; DiTomasso, Natalie Ann

    2014-04-01

    The social category "children" defines a group of individuals who are perceived to be distinct, with essential characteristics including innocence and the need for protection (Haslam, Rothschild, & Ernst, 2000). The present research examined whether Black boys are given the protections of childhood equally to their peers. We tested 3 hypotheses: (a) that Black boys are seen as less "childlike" than their White peers, (b) that the characteristics associated with childhood will be applied less when thinking specifically about Black boys relative to White boys, and (c) that these trends would be exacerbated in contexts where Black males are dehumanized by associating them (implicitly) with apes (Goff, Eberhardt, Williams, & Jackson, 2008). We expected, derivative of these 3 principal hypotheses, that individuals would perceive Black boys as being more responsible for their actions and as being more appropriate targets for police violence. We find support for these hypotheses across 4 studies using laboratory, field, and translational (mixed laboratory/field) methods. We find converging evidence that Black boys are seen as older and less innocent and that they prompt a less essential conception of childhood than do their White same-age peers. Further, our findings demonstrate that the Black/ape association predicted actual racial disparities in police violence toward children. These data represent the first attitude/behavior matching of its kind in a policing context. Taken together, this research suggests that dehumanization is a uniquely dangerous intergroup attitude, that intergroup perception of children is underexplored, and that both topics should be research priorities. PMID:24564373

  16. β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.

    PubMed

    Kim, Hyo-Sup; Lee, Moon-Kyu

    2016-05-01

    Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues. To overcome this limitation, the use of pancreatic progenitor cells is gaining more attention. In particular, pancreatic exocrine cells, such as duct epithelial cells and acinar cells, are attractive candidates for β-cell regeneration because of their differentiation potential and pancreatic lineage characteristics. It has been assumed that β-cell neogenesis from pancreatic progenitor cells could occur in pancreatic ducts in the postnatal stage. Several studies have shown that insulin-producing cells can arise in the duct tissue of the adult pancreas. Acinar cells also might have the potential to differentiate into insulin-producing cells. The present review summarizes recent progress in research on the transdifferentiation of pancreatic exocrine cells into insulin-producing cells, especially duct and acinar cells. PMID:27330712

  17. The types of endocrine cells in the pancreas of Sunda porcupine (Hystrix javanica)

    PubMed Central

    Budipitojo, Teguh; Fibrianto, Yuda Heru; Mulyani, Guntari Titik

    2016-01-01

    Aim: To identify the types of endocrine cells in the pancreas of the Sunda porcupine (Hystrix javanica) and its immunolocalization. Materials and Methods: Five adult H. javanica were used without sexual distinction. The presences of endocrine cells (glucagon, insulin, somatostatin, and pancreatic polypeptide [PP]) in pancreatic tissues were detected using the avidin-biotin-peroxidase complex method. Results: The fusiform, round, and oval form endocrine cells were detected in the islets of Langerhans and exocrine parts. Most of the insulin cells were found in the central area, glucagon cells were identified in the central and peripheral areas, and somatostatin and PP cells were detected in the mantle area of the islets of Langerhans. Glucagon and somatostatin cells were also detected in smaller numbers of peripheral parts of the islet. In all of the islet parts, glucagon endocrine cells were most prevalent cell type and then, somatostatin, insulin, and PP. In the exocrine parts, PP, somatostatin, glucagon, and insulin endocrine cells were found in the inter-acinus part with moderate, moderate, a few and rare numbers, in that order. In the pancreatic duct, glucagon and somatostatin cells were found between epithelial cells in rare numbers. Conclusion: The pancreas of Sunda porcupine (H. javanica) contains four types of major pancreatic endocrine cells with approximately similar distribution patterns to the other rodents, except for abundant glucagon cells in the peripheral area of the islets of Langerhans. PMID:27397977

  18. Human pancreas development.

    PubMed

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes. PMID:26395141

  19. Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review

    PubMed Central

    Borazanci, Erkut; Millis, Sherri Z; Korn, Ron; Han, Haiyong; Whatcott, Clifford J; Gatalica, Zoran; Barrett, Michael T; Cridebring, Derek; Von Hoff, Daniel D

    2015-01-01

    Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient’s tumor. Further work should be pursued to better characterize this disease. PMID:26380056

  20. Cystic lesions of the pancreas

    PubMed Central

    Hruban, Ralph H.; Fukushima, Noriyoshi

    2008-01-01

    Summary In contrast to the relatively uniform pathology and the unyielding dismal outcome associated with infiltrating ductal adenocarcinoma of the pancreas, cystic lesions have a broad spectrum of gross and microscopic pathologies, and a range of clinical outcomes. The common cystic lesions of the pancreas are reviewed with emphasis on practical tips for distinguishing between the main entities. PMID:20953247

  1. Clinical experience in pancreas transplantation in Lyon: long-term survival of duct injected pancreatic grafts.

    PubMed

    Melandri, M; Lefrancois, N; La Rocca, E; Martin, X; Sanseverino, R; Camozzi, L; Faure, J L; Secchi, A; Gelet, A; Bottani, G

    1988-01-01

    Ninety-seven pancreatic grafts in 92 insulin-dependent diabetic patients were performed during the last 11 years. Eighty-three of these grafts were carried out after neoprene duct injection, the other patients underwent pancreato-duodenal transplantation. In 80 cases, a double pancreas and kidney graft was performed. Five different immunosuppressive protocols were subsequently applied. Actuarial survival of patients and pancreata was 75.1% and 47%, after one year and 54.6% and 22.1%, respectively, 4 years after transplantation. Slightly better results were observed in double pancreas and kidney transplantation. The survival of both patients and pancreas improved when the most recent immunosuppressive protocols including cyclosporin A and only small doses of steroids were applied. The main causes of loss of the pancreatic graft were rejection, vascular thrombosis and death of the patient with functioning organ. Metabolic studies showed good insulin secretion with normal or impaired glucose tolerance as well as good short and half-term glycemic control. Whole pancreas grafts with enteric diversion yielded prompter and higher insulin secretion but the incidence of surgical complications was increased. In comparison to the data recorded at 6 months after pancreas transplantation, 5 patients of our series with still functioning organ showed an equally satisfactory and unchanged glycemic control after more than 4 years from surgery. In these patients, the previously high insulinemic values decreased to normal levels. However, 3 of these patients showed a decrease in post-prandial peaks as confirmed also by OGTT. However, mean blood glucose level was not altered. In our series the suppression of exocrine pancreatic secretion by neoprene duct injection did not appear to represent a relevant cause of decrease in endocrine function. The results obtained do not yet allow us to draw definite conclusions as to the efficacy of pancreas transplantation in the treatment of

  2. Characterization of integrin expression in islets isolated from hamster, canine, porcine, and human pancreas.

    PubMed

    Wang, R N; Paraskevas, S; Rosenberg, L

    1999-04-01

    The reasons for the failure of clinical islet transplantation remain obscure. Islet isolation, however, exposes the islet to variety of cellular stresses, including disruption of the cell-matrix relationship, an event associated with apoptosis. The cell-matrix relationship is characterized by an interaction between cell surface integrin receptors and matrix molecules of the surrounding basement membrane (BM). The purpose of this study was to characterize integrin expression and the distribution of the peri-insular BM in human, porcine, canine, and hamster pancreas, and after routine islet isolation. Whereas islets in the porcine pancreas do not have a demonstrable BM, islets in the human, canine, and hamster pancreas have an almost continuous BM with very little direct exocrine to endocrine cell-cell contact. After islet isolation, the BM was destroyed, only to be reestablished during the period of culture. In the pancreas of all four species, integrin alpha3 was expressed only on islet cells, and integrin alpha5 was present on islet cells as well as on acinar, centroacinar, and duct cells. Integrin alphaV was detected only in human and canine pancreas. Integrin beta1 was demonstrated only in the human pancreas. In isolated islets, integrin alpha3, alpha5, and alphaV expression decreased during the culture period and the intensity of the staining was observed to be coincident with the distribution of the BM. In summary, this is the first report of integrin expression in hamster, canine, porcine, and human islets. After islet isolation, the altered islet cell-matrix relationship is reflected both in the decrease in integrin expression and in the destruction of the peri-insular BM. These profound changes will need to be considered as the process of islet isolation for transplantation is refined. (J Histochem Cytochem 47:499-506, 1999) PMID:10082751

  3. Positron emission tomography ligand [11C]5-hydroxy-tryptophan can be used as a surrogate marker for the human endocrine pancreas.

    PubMed

    Eriksson, Olof; Espes, Daniel; Selvaraju, Ram K; Jansson, Emma; Antoni, Gunnar; Sörensen, Jens; Lubberink, Mark; Biglarnia, Ali-Reza; Eriksson, Jan W; Sundin, Anders; Ahlström, Håkan; Eriksson, Barbro; Johansson, Lars; Carlsson, Per-Ola; Korsgren, Olle

    2014-10-01

    In humans, a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of β-cells, with healthy volunteers (HVs). C-peptide-negative (i.e., insulin-deficient) T1D subjects (n = 10) and HVs (n = 9) underwent dynamic positron emission tomography with the radiolabeled serotonin precursor [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP). A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HVs, with large interindividual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where β-cells normally are the major constituent of the islets. [(11)C]5-HTP retention in the pancreas was reduced in T1D compared with nondiabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HVs and subjects with T1D was in agreement with previously reported morphological observations on the β-cell volume, implying that [(11)C]5-HTP retention is a useful noninvasive surrogate marker for the human endocrine pancreas. PMID:24848067

  4. Cyclic AMP-dependent protein kinase (cAPK) regulatory subunits are packaged and secreted by many exocrine and endocrine cells

    SciTech Connect

    Mednieks, M.I.; Hand, A.R.

    1986-05-01

    Regulatory (R) subunits of cAPK were identified by us as components of rat and human saliva by photoaffinity labeling with (/sup 32/P)-8-azido cyclic AMP. Photoaffinity labeling of purified rat parotid granule contents and immunogold labeling of thin sections with monoclonal antibodies showed the presence of R subunits in granules. The authors now report that cAPK R subunits are present in secretory granules and are apparently secreted by many exocrine and endocrine cell types. Labeling of thin sections of rat tissues with antibody to R subunits and protein A-gold shows gold particles over secretory granules of endocrine cells of the pituitary, pancreas and intestine. Zymogen granules of exocrine pancreatic acinar cells, the dense cores of secretory granules of seminal vesicle epithelial cells and secretory product in the seminal vesicle lumina were prominently labeled with gold. Photoaffinity labeling shows that pancreatic secretions and seminal vesicle contents have cAPK components. Phosphorylative modification of cellular proteins by cAMP controls hormonally stimulated protein secretion by many cell types. Although no catalytic activity was detected, identification of R subunits in granules and as secretory products indicates that they may have multiple roles in cellular mechanisms of action of cyclic AMP-mediated events in secretory cells.

  5. Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation12

    PubMed Central

    Drosos, Yiannis; Neale, Geoffrey; Ye, Jianming; Paul, Leena; Kuliyev, Emin; Maitra, Anirban; Means, Anna L; Washington, M Kay; Rehg, Jerold; Finkelstein, David B; Sosa-Pineda, Beatriz

    2016-01-01

    The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness. PMID:26992918

  6. Effects of coping and cooperative instructions on guilty and informed innocents' physiological responses to concealed information.

    PubMed

    Zvi, Liza; Nachson, Israel; Elaad, Eitan

    2012-05-01

    Previous research on the Concealed Information Test indicates that knowledge of the critical information of a given event is sufficient for the elicitation of strong physiological reactions, thus facilitating detection by the test. Other factors that affect the test's efficacy are deceptive verbal responses to the test's questions and motivation of guilty examinees to avoid detection. In the present study effects of coping and cooperative instructions - delivered to guilty and innocent participants - on detection were examined. In a mock-theft experiment guilty participants who actually committed a mock-crime, and informed innocent participants who handled the critical items of the crime in an innocent context, were instructed to adopt either a coping or a cooperative attitude toward the polygraph test. Results indicated that both, guilt and coping behavior, were associated with enhanced physiological responses to the critical information, whereas innocence and cooperative behavior attenuated physiological responses. Theoretical and applied implications of the results are discussed. PMID:22330977

  7. Adenylyl cyclase 6 mediates the action of cyclic AMP-dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation

    PubMed Central

    Sabbatini, Maria E; D’Alecy, Louis; Lentz, Stephen I; Tang, Tong; Williams, John A

    2013-01-01

    Both secretin and vasoactive intestinal polypeptide (VIP) receptors are responsible for the activation of adenylyl cyclases (ACs), which increase intracellular cyclic AMP (cAMP) levels in the exocrine pancreas. There are nine membrane-associated isoforms, each with its own pattern of expression and regulation. In this study we sought to establish which AC isoforms play a regulatory role in pancreatic exocrine cells. Using RT-PCR, AC3, AC4, AC6, AC7 and AC9 were found to be expressed in the pancreas. AC3, AC4, AC6 and AC9 were expressed in both pancreatic acini and ducts, whereas AC7 was expressed only in pancreatic ducts. Based on known regulation by intracellular signals, selective inhibitors and stimulators were used to suggest which isoforms play an important role in the induction of cAMP formation. AC6 appeared to be an important isoform because protein kinase A (PKA), PKC and calcium all inhibited VIP-induced cAMP formation, whereas calcineurin or calmodulin did not modify the response to VIP. Mice with genetically deleted AC6 were studied and showed reduced cAMP formation and PKA activation in both isolated pancreatic acini and duct fragments. The absence of AC6 reduced cAMP-dependent secretagogue-stimulated amylase secretion, and abolished fluid secretion in both in vivo and isolated duct fragments. In conclusion, several AC isoforms are expressed in pancreatic acini and ducts. AC6 mediates a significant part of pancreatic amylase and fluid secretion in response to secretin, VIP and forskolin through cAMP/PKA pathway activation. PMID:23753526

  8. Common Disorders of the Pancreas

    MedlinePlus

    ... the disease becomes more chronic, patients can develop malnutrition and weight loss. If the pancreas becomes destroyed ... with these disorders may have chronic pain, diarrhea, malnutrition, or diabetes. Treatment focuses on pain control and ...

  9. Allograft pancreas: pale acinar nodules.

    PubMed

    Troxell, Megan L; Drachenberg, Cinthia

    2016-08-01

    Microscopic pale-staining acinar nodules were characterized in native pancreas in the 1980s under a variety of names but have been infrequently reported since. We retrospectively studied the frequency and characteristics of pale acinar nodules in allograft pancreas biopsies, as compared to a sampling of native pancreas specimens at our center. Pale acinar nodules were present in 13% (9/69) of allograft biopsies from 22% (7/32) of transplant patients, and 23% (5/22) of native pancreas surgical specimens, although more nodules per pancreas area were present in allograft needle biopsies. Acinar nodules had size of 100 to 700 μm, were periodic acid-Schiff pale, were synaptophysin negative, stained more weakly with keratin CAM 5.2 compared to surrounding parenchyma, and had a low proliferative rate. Ultrastructural evaluation revealed paucity of zymogen granules with dilated cistern-like structures. In our experience, pale acinar nodules have similar features in allograft and native pancreas specimens, yet remain of uncertain etiology and significance. PMID:27063474

  10. Pancreas Cell Fate

    PubMed Central

    Guney, Michelle A.; Gannon, Maureen

    2009-01-01

    Diabetes is characterized by decreased function of insulin-producing insulin β cells and insufficient insulin output resulting from an absolute (Type 1) or relative (Type 2) inadequate functional β cell mass. Both forms of the disease would greatly benefit from treatment strategies that could enhance β cell regeneration and/or function. Successful and reliable methods of generatingβ cells or whole islets from progenitor cells in vivo or in vitro could lead to restoration of β cell mass in individuals with Type 1 diabetes and enhanced β cell compensation in Type 2 patients. A thorough understanding of the normal developmental processes that occur during pancreatic organogenesis, e.g., transcription factors, cell signaling molecules, and cell-cell interactions that regulate endocrine differentiation from the embryonic pancreatic epithelium, is required in order to successfully reach these goals. This review summarizes our current understanding of pancreas development, with particular emphasis on factors intrinsic or extrinsic to the pancreatic epithelium that are involved in regulating the development and differentiation of the various pancreatic cell types. We also discuss the recent progress in generating insulin-producing cells from progenitor sources. PMID:19750517

  11. [Intraoperative pancreas puncture cytology].

    PubMed

    Eggert, A; Lattmann, E; Kopf, R; Pfeiffer, M; Klöppel, G

    1984-01-01

    In the case of 10 to 15% of surgical patients with a pancreatic disorder an intraoperative diagnosis had to be made when a preoperative diagnosis had not yielded a definite result. Fine needle aspiration biopsy ( FNAB ) of the pancreas provided the basis for intraoperative differentiation of malignant and benign pancreatic processes. 244 pancreatic biopsies were carried out in 100 patients. It was possible to make a statement in 99% of the cases, with 65 malignant and 35 benign changes. In 83% the cytological diagnosis was correct; the method yielded incorrect-negative results in 7% of the cases. In 9% the presence of tumour cells was only suspected. There were no incorrect positive cancer diagnoses. FNAB caused no postoperative complications. Intraoperative bleeding after FBAB had to be stopped with a suture in one case. Transitory, asymptomatic hyperamylasemy must be expected in 25% of the patients after FNAB . This diagnostic technique is recommended in preference to the histological tissue removal methods because of its low risk factor. At least 2 biopsies of the suspect area with 2 smears are required, as a training in this diagnostic technique. PMID:6730761

  12. [Change in pancreatic exocrine function in acute appendicitis].

    PubMed

    Ivanov, Iu A

    1979-10-01

    In order to study changes in the functional state of the pancreas 1572 investigations of the blood and urine amylase, atoxylresistant lipase of the blood serum before operation were performed in different postoperative periods in 131 patients with acute appendicitis. The enzyme activity was established to increase, especially in destructive forms of appendicitis and in elderly patients. PMID:505800

  13. Pancreas Transplantation From Living Donors: A Single Center Experience of 20 Cases.

    PubMed

    Choi, J Y; Jung, J H; Kwon, H; Shin, S; Kim, Y H; Han, D J

    2016-08-01

    Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage-related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK. PMID:26833623

  14. Innocent Bystanders and Smoking Guns: Dwarf Carbon Stars

    NASA Astrophysics Data System (ADS)

    Green, Paul J.

    2014-01-01

    As far as we know, most carbon throughout the Universe is created and dispersed by AGB stars. So it was at first surprising to find that the carbon stars most prevalent in the Galaxy are in fact dwarfs. We suspect that dC stars are most likely innocent bystanders in post-mass transfer binaries, and may be predominantly metal-poor. Among 1200 C stars found in the SDSS (Green 2013), we confirm 724 dCs, of which a dozen are DA/dC stars in composite spectrum binaries, quadrupling the total sample of these "smoking guns" for AGB binary mass transfer. The dCs likely span absolute magnitudes M_i from about 6.5 to 10.5. G-type dC stars with weak CN and relatively blue colors are probably the most massive dCs still cool enough to show C_2 bands. Eleven very red C stars with strong red CN bands appear to be N-type AGB stars at large Galactocentric distances, one likely a new discovery in the dIrr galaxy Le A. Two such stars within 30arcmin of each other may trace a previously unidentified dwarf galaxy or tidal stream at ~40 kpc. We describe follow-up projects to study the spatial, kinematic, and binary properties of these C-enriched dwarfs.

  15. Characteristics and Outcomes of Adenosquamous Carcinoma of the Pancreas

    PubMed Central

    Simone, Christine G.; Zuluaga Toro, Tania; Chan, Ellie; Feely, Michael M.; Trevino, Jose G.

    2013-01-01

    ABSTRACT BACKGROUND: Adenosquamous carcinoma of the pancreas (ASCAP) is a rare histologic type of pancreatic carcinoma that constitutes 1% to 4% of all pancreatic exocrine malignancies. It has a clinical presentation similar to that of adenocarcinoma of the pancreas (ACP), but may have a worse overall prognosis, with most patients surviving for less than 2 years. METHODS: This was an institutional, retrospective, cohort analysis of 237 patients who underwent resection of pancreatic cancer with curative intent. RESULTS: Of the 237 cases examined, we identified 7 (2.9%) with histologically confirmed ASCAP. Demographics, comorbidities, risk factors, presenting symptoms, survival data, tumor characteristics, and types of treatment for each patient were included in the analysis. Risk factors for development of ASCAP were not conclusive. Although human papilloma virus (HPV) has been implicated in other squamous cell cancers, in our cohort, its involvement in ASCAP was 0%. Presurgical fine-needle aspiration failed to identify the invasive squamous cell component in all cases. In this cohort analysis, overall survival ranged from 3 to 25 months, with 2 patients surviving more than 20 months after surgical resection. With a median follow-up of 2.9 years, our data demonstrate a trend to worse median overall survival for ASCAP than for ACP (8.2 vs. 20.4 months; P = .23), with a limited number of long-term survivors. CONCLUSIONS: Although recommended, adjuvant treatment was inconsistently provided for patients in this ASCAP cohort. Published data show variability in overall survival, but our findings support that surgical resection is one of the few options for control of this rare, poorly understood pancreatic malignancy. Further research is necessary to define risk factors and adjuvant and neoadjuvant treatments, to help improve patient outcomes. PMID:23936547

  16. Ethanol diversely alters palmitate, stearate and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer

    PubMed Central

    Boros, Laszlo G.; Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu; Go, Vay Liang W.; Lee, Wai-Nang Paul

    2015-01-01

    Objective To determine tissue specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods Tissue fatty acid profile, and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and GC/MS. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results Fatty acid ratios in the liver indicated that there was an over two-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas there was a 17% decrease in the stearate to palmitate ratio, while oleate to palmitate ratio was increased by 30%. The fractions of deuterium labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas consistent with the oleate/stearate ratios in these tissues. Conclusions Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. PMID:19248221

  17. Differential ability of Ptf1a and Ptf1a-VP16 to convert stomach, duodenum and liver to pancreas

    PubMed Central

    Jarikji, Zeina H.; Vanamala, Sandeep; Beck, Caroline W.; Wright, Chris V.E.; Leach, Steven D.; Horb, Marko E.

    2014-01-01

    Summary Determining the functional attributes of pancreatic transcription factors is essential to understand how the pancreas is specified distinct from other endodermal organs, such as liver, stomach and duodenum, and to direct the differentiation of other cell types into pancreas. Previously, we demonstrated that Pdx1-VP16 was sufficient to convert liver to pancreas. In this paper we characterize the functional ability of another pancreatic transcription factor, Ptf1a, in promoting ectopic pancreatic fates at early stages throughout the endoderm and later in during organogenesis. Using the transthyretin promoter to drive expression in the early liver region/bud of transgenic Xenopus tadpoles, we find that Ptf1a-VP16 is able to convert liver to pancreas. Overexpression of the unmodified Ptf1a on the other hand, has no effect in liver, but is able to convert stomach and duodenum to pancreas. When overexpressed at earlier embryonic stages throughout the endoderm, Ptf1a activity is similarly limited, whereas Ptf1a-VP16 has increased activity. Interestingly, in all instances we find that Ptf1a-VP16 is only capable of promoting acinar cell fates, whereas Ptf1a promotes both acinar and endocrine fates. Lastly, we demonstrate that, similar to mouse and zebrafish, Xenopus Ptf1a is essential for the initial specification of both endocrine and exocrine cells during normal pancreas development. PMID:17320068

  18. [Neuroendocrine system of the pancreas and gastrointestinal tract: origin and development].

    PubMed

    Díaz Pérez, José Angel

    2009-04-01

    Gastroenteropancreatic neuroendocrine tumours (GEP NETs) originate from the neuroendocrine cells through the gastrointestinal tract and endocrine pancreas. The embryologic development of the pancreas is a complex process that begins with the "stem cell" that come from the endodermus. These cells go through two phases: in the first transition the "stem cell" differentiates in exocrine and endocrine cells. This process is regulated by transcription factors such as Pdx1 ("insulin promoter factor 1"), Hlxb6 and SOX9. In the second transition the neuroendocrine cell differentiates in the 5 cell types (alpha, beta, delta, PP y epsilon.). This process is regulated through the balance between factors favoring differentiation (mainly neurogenin 3) and inhibitor factors which depend on Notch signals. The existence of a third transition in postnatal pancreas is hypothesized. The "stem cell" from pancreatic ducts would become adult beta cells, through autoduplication and neogenesis. In the small gut of the adult the stem cell are placed in the intestinal crypts and develop to villi in secretor lines (enterocytes, globet and Paneths cells) or neuroendocrine cells from which at least 10 cell types depend. This process is regulated by transcription factors: Math1, neurogenina 3 and NeuroD. PMID:19627763

  19. Immunocytochemical localization of progesterone receptors in endocrine cells of the human pancreas.

    PubMed Central

    Doglioni, C.; Gambacorta, M.; Zamboni, G.; Coggi, G.; Viale, G.

    1990-01-01

    Progesterone receptors (PgR) have been immunocytochemically localized in the nuclei of several (40% to 75%) endocrine cells of the human pancreas and in a more variable number of neoplastic cells of 7 of 18 endocrine pancreatic tumors. Conversely the exocrine epithelial cells of the pancreas did not exhibit any PgR immunoreactivity in normal as well as in different pathologic conditions, including pancreatic adenocarcinomas. Estrogen receptors were not detected in any of the pancreatic samples investigated. Double immunocytochemical experiments have documented that PgR immunoreactivity in normal Langerhans islets is a consistent feature of most (75%) glucagon-producing A cells, of approximately 5% to 20% of insulin-producing B cells, and of a variable percentage of pancreatic polypeptide (PP)-producing cells, ranging from 5% to 70%. These figures were not affected by the sex, age, or underlying disease of the patients. The reported findings corroborate previous clinical and experimental evidence indicating that sex steroid hormones may have some regulatory effects on the functional activity of the endocrine pancreas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2240168

  20. Hydrogen Sulfide Regulates Ca2+ Homeostasis Mediated by Concomitantly Produced Nitric Oxide via a Novel Synergistic Pathway in Exocrine Pancreas

    PubMed Central

    Moustafa, Amira

    2014-01-01

    Abstract Aim: The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca2+ homeostasis in rat pancreatic acini. Results: Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The NaHS-induced [Ca2+]i elevation persisted with an EC50 of 73.3 μM in the absence of extracellular Ca2+ but was abolished by thapsigargin, indicating that both Ca2+ entry and Ca2+ release contributed to the increase. The [Ca2+]i increase was markedly inhibited in the presence of NG-monomethyl L-arginine or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), and diaminofluorescein-2/diaminofluorescein-2 triazole (DAF-2/DAF-2T) fluorometry demonstrated that nitric oxide (NO) was also produced by H2S in a dose-dependent manner with an EC50 of 64.8 μM, indicating that NO was involved in the H2S effect. The H2S-induced [Ca2+]i increase was inhibited by pretreatment with U73122, xestospongin C, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, KT5823, and GP2A, indicating that phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3) receptor, soluble guanylate cyclase (sGC), protein kinase G (PKG), and Gq-protein play roles as intermediate components in the H2S-triggered intracellular signaling. Innovation: To our knowledge, our study is the first one highlighting the effect of H2S on intracellular Ca2+ dynamics in pancreatic acinar cells. Moreover, a novel cascade was presumed to function via the synergistic interaction between H2S and NO. Conclusion: We conclude that H2S affects [Ca2+]i homeostasis that is mediated by H2S-evoked NO production via an endothelial nitric oxide synthase (eNOS)-NO-sGC-cyclic guanosine monophosphate-PKG-Gq-protein-PLC-IP3 pathway to induce Ca2+ release, and this pathway is identical to the one we recently proposed for a sole effect of NO and the two gaseous molecules synergistically function to regulate Ca2+ homeostasis. Antioxid. Redox Signal. 20, 747–758. PMID:24138560

  1. Cytosolic Ca2+ and Ca2+-activated Cl− current dynamics: insights from two functionally distinct mouse exocrine cells

    PubMed Central

    Giovannucci, David R; Bruce, Jason I. E; Straub, Stephen V; Arreola, Jorge; Sneyd, James; Shuttleworth, Trevor J; Yule, David I

    2002-01-01

    The dynamics of Ca2+ release and Ca2+-activated Cl− currents in two related, but functionally distinct exocrine cells, were studied to gain insight into how the molecular specialization of Ca2+ signalling machinery are utilized to produce different physiological endpoints: in this case, fluid or exocytotic secretion. Digital imaging and patch-clamp methods were used to monitor the temporal and spatial properties of changes in cytosolic Ca2+ concentration ([Ca2+]c) and Cl− currents following the controlled photolytic release of caged-InsP3 or caged-Ca2+. In parotid and pancreatic acinar cells, changes in [Ca2+]c and activation of a Ca2+-activated Cl− current occurred with close temporal coincidence. In parotid, a rapid global Ca2+ signal was invariably induced, even with low-level photolytic release of threshold amounts of InsP3. In pancreas, threshold stimulation generated an apically delimited [Ca2+]c signal, while a stronger stimulus induced a global [Ca2+]c signal which exhibited characteristics of a propagating wave. InsP3 was more effective in parotid, where [Ca2+]c signals initiated with shorter latency and exhibited a faster time-to-peak than in pancreas. The increased potency of InsP3 in parotid probably results from a four-fold higher number of InsP3 receptors as measured by radiolabelled InsP3 binding and western blot analysis. The Ca2+ sensitivity of the Cl− channels in parotid and pancreas was determined from the [Ca2+]-current relationship measured during a dynamic ‘Ca2+ ramp’ produced by the continuous, low-level photolysis of caged-Ca2+. In addition to a greater number of InsP3 receptors, the Cl− current density of parotid acinar cells was more than four-fold greater than that of pancreatic cells. Whereas activation of the current was tightly coupled to increases in Ca2+ in both cell types, local Ca2+ clearance was found to contribute substantially to the deactivation of the current in parotid. These data reveal specializations of

  2. Clinical imaging of the pancreas

    SciTech Connect

    May, G.; Gardiner, R.

    1987-01-01

    Featuring more than 300 high-quality radiographs and scan images, clinical imaging of the pancreas systematically reviews all appropriate imaging modalities for diagnosing and evaluating a variety of commonly encountered pancreatic disorders. After presenting a succinct overview of pancreatic embryology, anatomy, and physiology, the authors establish the clinical indications-including postoperative patient evaluation-for radiologic examination of the pancreas. The diagnostic capabilities and limitations of currently available imaging techniques for the pancreas are thoroughly assessed, with carefully selected illustrations depicting the types of images and data obtained using these different techniques. The review of acute and chronic pancreatitis considers the clinical features and possible complications of their variant forms and offers guidance in selecting appropriate imaging studies.

  3. Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2014-03-28

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  4. Juvenile Diabetes Mellitus and Concurrent Exocrine Pancreatic Insufficiency in a Labrador Retriever: Long-Term Management.

    PubMed

    Alvarez, Maria Saiz; Herrería-Bustillo, Vicente; Utset, Artur Font; Martínez, Jorge

    2015-01-01

    A 3 mo old, female, entire Labrador retriever presented with vomiting, diarrhea, polyuria, polydipsia, polyphagia, and stunted growth. Diagnostics revealed the presence of juvenile diabetes mellitus and concurrent exocrine pancreatic insufficiency. Pancreatic histopathology showed severe pancreatic atrophy. Successful treatment was achieved with a combination of insulin and pancreatic enzymes. This report describes successful long-term treatment of juvenile diabetes mellitus and concurrent exocrine pancreatic insufficiency in a dog. PMID:26535463

  5. Additional Resection of the Pancreas Body Prevents Postoperative Pancreas Fistula in Patients with Portal Annular Pancreas Who Undergo Pancreaticoduodenectomy

    PubMed Central

    Muto, Jun; Mano, Yohei; Harada, Noboru; Uchiyama, Hideaki; Yoshizumi, Tomoharu; Taketomi, Akinobu; Shirabe, Ken; Maehara, Yoshihiko

    2012-01-01

    Portal annular pancreas (PAP) is a rare variant in which the uncinate process of the pancreas extends to the dorsal surface of the pancreas body and surrounds the portal vein or superior mesenteric vein. Upon pancreaticoduodenectomy (PD), when the pancreas is cut at the neck, two cut surfaces are created. Thus, the cut surface of the pancreas becomes larger than usual and the dorsal cut surface is behind the portal vein, therefore pancreatic fistula after PD has been reported frequently. We planned subtotal stomach-preserving PD in a 45-year-old woman with underlying insulinoma of the pancreas head. When the pancreas head was dissected, the uncinate process was extended and fused to the dorsal surface of the pancreas body. Additional resection of the pancreas body 1 cm distal to the pancreas tail to the left side of the original resection line was performed. The new cut surface became one and pancreaticojejunostomy was performed as usual. No postoperative complications such as pancreatic fistula occurred. Additional resection of the pancreas body may be a standardized procedure in patients with PAP in cases of pancreas cut surface reconstruction. PMID:22532811

  6. Immunohistochemical expression of rabphilin -3A-like (Noc2) in normal and tumor tissues of human endocrine pancreas

    PubMed Central

    Shanmugam, C; Katkoori, VR; Jhala, NC; Grizzle, WE; Manne, U

    2009-01-01

    Involvement of rabphilin-3A-like (RPH3AL), or Noc2, the potential effector of Ras-associated binding proteins Rab3A and Rab27A in the regulation of exocytotic processes in the endocrine pancreas has been demonstrated in experimental models. Noc2 expression together with other regulatory molecules of the exocytotic machinery in human tissues, however, has not been studied. We evaluated immunohistochemical expression of the key molecules of the exocytotic machinery, Noc2, Rab3A, Rab27A, and RIM2, together with the characteristic islet cell hormones, insulin and glucagon in normal and endocrine tumor tissues of human pancreas. Normal pancreatic islets were stained for all of these proteins and showed strong cytoplasmic localization. A similar pattern of strong cytoplasmic expression of these proteins was observed in the majority of endocrine tumors. By contrast, the exocrine portions of normal appearing pancreas completely lacked Rab27A staining and showed decreased expression of the proteins, Noc2, Rab3A, and RIM2. The staining pattern of Noc2 and Rab27A was similar to the staining pattern of glucagon-producing cells within the islets. The concomitant expression of Noc2 with these molecules suggests that Noc2 may serve as an effector for Rab3A and Rab27A and that it is involved in the regulation of exocytosis of the endocrine pancreas in humans. PMID:19212825

  7. Immunohistochemical expression of rabphilin-3A-like (Noc2) in normal and tumor tissues of human endocrine pancreas.

    PubMed

    Shanmugam, C; Katkoori, V R; Jhala, N C; Grizzle, W E; Manne, U

    2009-04-01

    Involvement of rabphilin-3A-like (RPH3AL), or Noc2, the potential effector of Ras-associated binding proteins Rab3A and Rab27A in the regulation of exocytotic processes in the endocrine pancreas has been demonstrated in experimental models. Noc2 expression together with other regulatory molecules of the exocytotic machinery in human tissues, however, has not been studied. We evaluated immunohistochemical expression of the key molecules of the exocytotic machinery, Noc2, Rab3A, Rab27A, and RIM2, together with the characteristic islet cell hormones, insulin and glucagon in normal and endocrine tumor tissues of human pancreas. Normal pancreatic islets were stained for all of these proteins and showed strong cytoplasmic localization. A similar pattern of strong cytoplasmic expression of these proteins was observed in the majority of endocrine tumors. By contrast, the exocrine portions of normal appearing pancreas completely lacked Rab27A staining and showed decreased expression of the proteins, Noc2, Rab3A, and RIM2. The staining pattern of Noc2 and Rab27A was similar to the staining pattern of glucagon-producing cells within the islets. The concomitant expression of Noc2 with these molecules suggests that Noc2 may serve as an effector for Rab3A and Rab27A and that it is involved in the regulation of exocytosis of the endocrine pancreas in humans. PMID:19212825

  8. Lymphoepithelial Cyst of the Pancreas

    PubMed Central

    Arumugam, Prabhu; Fletcher, Natalie; Kyriakides, Charis; Mears, Lisa; Kocher, Hemant M.

    2016-01-01

    Lymphoepithelial cyst (LEC) of the pancreas is an extremely rare, benign pancreatic cystic lesion that is difficult to differentiate preoperatively from other cystic pancreatic lesions. LEC may have malignant potential. Here, we describe a case of LEC of the pancreas – initially suspected to be a mucinous cyst neoplasm – in an elderly man presenting with abdominal pain, who went on to have a distal pancreatectomy and splenectomy. We also review the relevant literature and discuss implications for the diagnosis and management of this rare lesion. PMID:27403123

  9. Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection

    PubMed Central

    Lim, Pei-Wen; Dinh, Kate H.; Sullivan, Mary; Wassef, Wahid Y.; Zivny, Jaroslav; Whalen, Giles F.; LaFemina, Jennifer

    2016-01-01

    Background Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. Methods Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. Results 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. Conclusion Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency. PMID:27037206

  10. Diabetes and Pancreas: Why So Difficult? Potential Mechanisms of Elevated Serum Pancreatic Enzymes.

    PubMed

    Matteucci, Elena; Giampietro, Ottavio

    2016-01-01

    Diabetes mellitus has been associated with a higher risk of exocrine pancreas disorders despite inconsistencies among studies, presumably due to the presence of several (often unmeasured) confounding factors. As a direct consequence of this uncertainty, the relationship between anti-diabetic therapies and pancreatic adverse reactions is difficult to evaluate and remains far from being clarified. Indeed, the on going debate on the safety of incretin-based therapies does not lie in any definite conclusion. Serum level of amylases and lipase reflects the balance between production from different tissues and clearance, but it may be also influenced by numerous molecular, cellular, and systems mechanisms. The present review tries to provide an overview of potential biochemical pathways that may underlie pancreatic hyperenzymemia in health and diabetes mellitus. PMID:26639098

  11. Derivation of ductlike cell lines from a transplantable acinar cell carcinoma of the rat pancreas.

    PubMed Central

    Pettengill, O. S.; Faris, R. A.; Bell, R. H.; Kuhlmann, E. T.; Longnecker, D. S.

    1993-01-01

    Two cell lines were derived from a transplantable acinar cell carcinoma that had been established from a primary carcinoma of the pancreas in an azaserine-treated Lewis rat. The cultured tumor cells initially produced amylase, but production of exocrine enzymes ceased after 1-2 weeks in culture. The cultured cells were tumorigenic in Lewis rats, and one line produced solid tumors composed of ductlike structures surrounded by dense fibrous tissue. The second cell line produced partially solid and partially cystic tumors with a mixed phenotype of squamous, mucinous, and glandular areas when it grew in vivo following regrafting. Both cell lines lost structural and immunohistochemical acinar cell markers while acquiring duct cell markers during culture and regrafting. These studies provide strong support for the hypothesis that ductlike carcinomas can arise from neoplastic pancreatic acinar cells in rats. Images Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:8391218

  12. What difference exists in the pancreas of mammals with sanguivorous diet? A morphological, stereological and immunohistochemical study of the pancreatic islets of the hematophagous bat Diphylla ecaudata.

    PubMed

    Machado-Santos, Clarice; Aquino, Júlio César Fraulob; Mikalauka, Jefferson Simanas; Abidu-Figueiredo, Marcelo; Mendes, Rosa Maria Marcos; Sales, Armando

    2013-05-10

    Diphylla ecaudata is a vampire bat that mainly feeds on the blood of birds. This highly specialized diet - hematophagy - is accompanied by a series of morphological changes in the gastro-entero-pancreatic system, since the distribution and relative proportions of different pancreatic endocrine cell types can vary between species due to different physiological conditions and eating habits. The aim of this study was to examine for the first time the pancreas of the vampire bat D. ecaudata using morphological, stereological and immunohistochemical techniques. The pancreas of the D. ecaudata has an exocrine acinar portion in which the highest concentration of pancreatic islets is scattered. These pancreatic islets have irregular size and a mean diameter of 56.94 μm. The total number of islets in the pancreas was 23,900, with a volumetric density of 4.1%. Insulin-immunoreactive (IR) cells were located in the central pancreatic islet region and had the largest density (54.8%). Glucagon-IR cells were located mainly in the peripheral mantle region (16.2%), along with somatostatin-IR (SS) cells (14.3%). Cells immunoreactive to insulin, glucagon and somatostatin were also observed to have spread in isolated places in the exocrine pancreas. In the connective tissue near the pancreatic ducts, a high concentration was identified of insulin-IR cells and a low concentration of glucagon-IR and somatostatin-IR cells. These results indicate that although the pancreas of D. ecaudata has morphological similarities with that of other mammals, it has a differentiated islet structure, because there were a large number of islets and different volumetric densities of α, β and δ cells. PMID:23500834

  13. Nom1 Mediates Pancreas Development by Regulating Ribosome Biogenesis in Zebrafish

    PubMed Central

    Qin, Wei; Chen, Zelin; Zhang, Yihan; Yan, Ruibin; Yan, Guanrong; Li, Song; Zhong, Hanbing; Lin, Shuo

    2014-01-01

    Ribosome biogenesis is an important biological process for proper cellular function and development. Defects leading to improper ribosome biogenesis can cause diseases such as Diamond-Blackfan anemia and Shwachman-Bodian-Diamond syndrome. Nucleolar proteins are a large family of proteins and are involved in many cellular processes, including the regulation of ribosome biogenesis. Through a forward genetic screen and positional cloning, we identified and characterized a zebrafish line carrying mutation in nucleolar protein with MIF4G domain 1 (nom1), which encodes a conserved nulceolar protein with a role in pre-rRNA processing. Zebrafish nom1 mutants exhibit major defects in endoderm development, especially in exocrine pancreas. Further studies revealed that impaired proliferation of ptf1a-expressing pancreatic progenitor cells mainly contributed to the phenotype. RNA-seq and molecular analysis showed that ribosome biogenesis and pre-mRNA splicing were both affected in the mutant embryos. Several defects of ribosome assembly have been shown to have a p53-dependent mechanism. In the nom1 mutant, loss of p53 did not rescue the pancreatic defect, suggesting a p53-independent role. Further studies indicate that protein phosphatase 1 alpha, an interacting protein to Nom1, could partially rescue the pancreatic defect in nom1 morphants if a human nucleolar localization signal sequence was artificially added. This suggests that targeting Pp1α into the nucleolus by Nom1 is important for pancreatic proliferation. Altogether, our studies revealed a new mechanism involving Nom1 in controlling vertebrate exocrine pancreas formation. PMID:24967912

  14. Perioperative Computed Tomography Assessments of the Pancreas Predict Nonalcoholic Fatty Liver Disease After Pancreaticoduodenectomy

    PubMed Central

    Ohgi, Katsuhisa; Okamura, Yukiyasu; Yamamoto, Yusuke; Ashida, Ryo; Ito, Takaaki; Sugiura, Teiichi; Aramaki, Takeshi; Uesaka, Katsuhiko

    2016-01-01

    Abstract Nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has become a clinically important issue. Although pancreatic exocrine insufficiency has been reported to be a main cause of NAFLD after PD, a clinically practical examination to assess the pancreatic exocrine function has not been established. The aim of this study was to evaluate risk factors for NAFLD after PD with a focus on perioperative computed tomography (CT) assessments of the pancreas. A retrospective review of 245 patients followed for more than 6 months after PD was conducted. We evaluated several pancreatic CT parameters, including the pancreatic parenchymal thickness, pancreatic duct-to-parenchymal ratio, pancreatic attenuation, and remnant pancreatic volume (RPV) on pre- and/or postoperative CT around 6 months after surgery. The variables, including the pancreatic CT parameters, were compared between the groups with and without NAFLD after PD. The incidence of NAFLD after PD was 19.2%. A multivariate analysis identified 5 independent risk factors for NAFLD after PD: a female gender (odds ratio [OR] 5.66, P < 0.001), RPV < 12 mL (OR 4.73, P = 0.001), preoperative pancreatic attenuation of <30 Hounsfield units (OR 4.50, P = 0.002), dissection of the right-sided nerve plexus around the superior mesenteric artery (OR 3.02, P = 0.017) and a preoperative serum carbohydrate antigen 19–9 level of ≥70 U/mL (OR 2.58, P = 0.029). Our results showed that 2 pancreatic CT parameters, the degree of preoperative pancreatic attenuation and RPV, significantly influence the development of NAFLD after PD. Perioperative CT assessments of the pancreas may be helpful for predicting NAFLD after PD. PMID:26871772

  15. Cholecystokinin receptors: Biochemical demonstration and autoradiographical localization in rat brain and pancreas using (/sup 3/H) cholecystokinin8 as radioligand

    SciTech Connect

    Van Dijk, A.; Richards, J.G.; Trzeciak, A.; Gillessen, D.; Moehler, H.

    1984-04-01

    Since cholecystokinin8 (CCK8) seems to be the physiological ligand of CCK receptors in the brain, it would be the most suitable probe for the characterization of CCK receptors in radioligand binding studies. (/sup 3/H)CCK8 was synthetized with a specific radioactivity sufficient for the detection of high affinity binding sites. (/sup 3/H)CCK8 binds saturably and reversibly to distinct sites in rat brain and pancreas with nanomolar affinity. While the C-terminal tetrapeptide of CCK is the minimal structure required for nanomolar affinity in the brain, the entire octapeptide sequence is required for binding affinity in pancreas. Desulfated CCK8 and several gastrin-I peptides, which are likewise unsulfated, show virtually no affinity to the binding sites in pancreas but high affinity in cerebral cortex. The ligand specificity of the CCK peptides corresponds to their electrophysiological potency in the brain and their stimulation of secretion in pancreas, respectively. Autoradiographically, high densities of (/sup 3/H)CCK8 binding sites were found in cerebral cortex and olfactory bulb, medium levels in nucleus accumbens, hippocampus, dentate gyrus, and striatum with virtually no labeling in cerebellum. This pattern is similar to the distribution of CCK-like immunoreactivity in the brain. In pancreas, equally high levels of (/sup 3/H)CCK8 labeling were found in the exocrine and endocrine region. (/sup 3/H)CCK8 binding sites differ from those identified previously with (/sup 125/I)Bolton-Hunter-CCK33 by their sensitivity to guanyl nucleotides in the brain, their ion dependency in the brain, and pancreas, and their different autoradiographical localization in some parts of the brain. The distribution of CCK binding sites labeled with (/sup 3/H)CCK8 appears to correlate better with the CCK immunoreactivity than those labeled with (/sup 125/I)Bolton-Hunter-CCK33. Thus, (/sup 3/H)CCK8 appears to be the radioligand of choice for the investigation of CCK receptors.

  16. Purification and Characterization of a Population of EGFP-Expressing Cells from the Developing Pancreas of a Neurogenin3/EGFP Transgenic Mouse

    PubMed Central

    Barrow, J; Bernardo, A S; Hay, C W; Blaylock, M; Duncan, L; MacKenzie, A; McCreath, K; Kind, A J; Schnieke, A E; Colman, A; Hart, A W

    2005-01-01

    Neurogenin 3 (ngn3) is a basic helix loop helix transcription factor that is transiently expressed in the developing mouse pancreas with peak expression around E15. In mice lacking the ngn3 gene the endocrine cells of the pancreas fail to develop suggesting that the ngn3-positive cell may represent a progenitor cell for the endocrine pancreas. In order to purify and characterize this cell in detail we have generated a transgenic mouse, in which the ngn3 promoter drives expression of enhanced green fluorescent protein (EGFP). In the E15.5 embryo EGFP was expressed in the dorsal and ventral pancreas, the duodenum, and lower intestine as well as in the brain. This pattern of expression was in keeping with the known expression profile of the endogenous ngn3 gene. Within the pancreas EGFP was localized in close proximity to cells that stained positive for ngn3, insulin, and glucagon, but was absent from regions of the pancreas that stained positive for amylase. EGFP was also present in the pancreas at E18.5, although there was no detectable expression of ngn3. At this stage EGFP did not colocalize with any of the hormones or exocrine markers. EGFP+ cells were FACS purified (96%) from the E15 pancreas yielding ∼ 10,000 cells or 1.6% of the total pancreatic cells from one litter. RT/PCR analysis confirmed that the purified cells expressed EGFP, ngn3, insulin, glucagon, somatostatin and pancreatic polypeptide. The ability to purify ngn3+ cells provides an invaluable source of material for charactering in detail their properties. PMID:19521525

  17. Morphology of the pancreas of some species belonging to the genera Phelsuma and Gecko (family Gekkonidae): evidence of apoptotic process during the seasonal cycle.

    PubMed

    Buono, S; Odierna, G; Putti, R

    2006-10-01

    In this study we investigated comparative morphology of the endocrine pancreas of several species belonging to the family Gekkonidae and apoptotic processes of the pancreas which may be correlated to the seasonal cycle. The following species of the family Gekkonidae were studied: Phelsuma lineata, P. madagascariensis, P. dubia, P. abotti, Gekko gecko, G. vittatus, and Geckonia chazaliae. In all these species the pancreas consisted of large and medium islets as well as endocrine cells which were scattered throughout the acinar cells. Exocrine parenchyma consisted of tubuli-acini. Four mayor cell types were identified in the endocrine pancreas, using immunocytochemistry: glucagon-immunoreactive (A) cells, insulin-immunoreactive (B) cells, somatostatin-immunoreactive (D) cells, and pancreatic polypeptide immunoreactive (PP) cells. In the endocrine pancreas the amount of A cells and B cells was either equal or a prevalence of A cells was observed. In the wet season the pancreatic morphology presented normal features with very rare apoptotic cells. The animals belonging to the genus Phelsuma taken in the dry season (July) showed numerous vacuolated, Caspase 3, 9 and 11-immunoreactive acinar and some endocrine cells containing picnotic nuclei which were positive to tunel reaction. The animals belonging to the genus Gekko taken at the end of the dry season (October) exhibited strongly vacuolated, Caspase 3, 9 and 11-immunoreactive endocrine and some acinar cells containing nuclei which were positive to tunel reaction. These apoptosis events could be a reaction in response to stress mechanisms, such as a starvation period during the dry season. PMID:16763810

  18. VAMP8/Endobrevin as a General Vesicular SNARE for Regulated Exocytosis of the Exocrine System

    PubMed Central

    Wang, Cheng-Chun; Shi, Hong; Guo, Ke; Ng, Chee Peng; Li, Jie; Qi Gan, Bin; Chien Liew, Hwee; Leinonen, Jukka; Rajaniemi, Hannu; Hong Zhou, Zhi; Zeng, Qi

    2007-01-01

    The molecular mechanism governing the regulated secretion of most exocrine tissues remains elusive, although VAMP8/endobrevin has recently been shown to be the major vesicular SNARE (v-SNARE) of zymogen granules of pancreatic exocrine acinar cells. In this article, we have characterized the role of VAMP8 in the entire exocrine system. Immunohistochemical studies showed that VAMP8 is expressed in all examined exocrine tissues such as salivary glands, lacrimal (tear) glands, sweat glands, sebaceous glands, mammary glands, and the prostate. Severe anomalies were observed in the salivary and lacrimal glands of VAMP8-null mice. Mutant salivary glands accumulated amylase and carbonic anhydrase VI. Electron microscopy revealed an accumulation of secretory granules in the acinar cells of mutant parotid and lacrimal glands. Pilocarpine-stimulated secretion of saliva proteins was compromised in the absence of VAMP8. Protein aggregates were observed in mutant lacrimal glands. VAMP8 may interact with syntaxin 4 and SNAP-23. These results suggest that VAMP8 may act as a v-SNARE for regulated secretion of the entire exocrine system. PMID:17215514

  19. Guilty Knowledge versus Innocent Associations: Effects of Trait Anxiety and Stimulus Context on Skin Conductance.

    ERIC Educational Resources Information Center

    Giesen, Martin; Rollison, Michael A.

    1980-01-01

    Simulated lie detection procedure investigated skin conductance responsivity among self-reported skin responders. Subjects grouped by trait anxiety engaged in mock crime providing "guilty knowledge" or in neutral activity providing "innocent associations" and were interrogated using Lykken's Guilty Knowledge technique. Substantial relationship was…

  20. 33 CFR 151.2015 - Is a vessel in innocent passage exempt from the mandatory requirements?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Is a vessel in innocent passage exempt from the mandatory requirements? 151.2015 Section 151.2015 Navigation and Navigable Waters COAST... SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control...

  1. Redefining the Legacy of Mina Shaughnessy: A Critique of the Politics of Linguistic Innocence.

    ERIC Educational Resources Information Center

    Lu, Min-zhan

    1991-01-01

    Argues that Mina Shaughnessy's view of language as a politically innocent vehicle of meaning overlooks basic writers' need to confront the dissonance they experience between academic and other discourses. Suggests educators need to abandon the limitations of the essentialist view of language informing their pedagogy. (KEH)

  2. Too Late for Luck: A Comparison of Post-Furman Exonerations and Executions of the Innocent

    ERIC Educational Resources Information Center

    Harmon, Talia Roitberg; Lofquist, William S.

    2005-01-01

    This study is a quantitative analysis designed to compare two groups of factually innocent capital defendants: those who were exonerated and those who were executed. There are a total of 97 cases in the sample, including 81 exonerations and 16 executions. The primary objective of the authors is to identify factors that may predict case outcomes…

  3. Literature and the Teaching of Culture: The Example of Roger Ikor's "Le Tourniquet des innocents."

    ERIC Educational Resources Information Center

    Hodgson, Richard G.

    1983-01-01

    Roger Ikor's 1972 novel "Le Tourniquet des innocents" is proposed for advanced university-level French culture courses, illustrating how the study of a contemporary novel can be integrated into cultural education. Classroom activities suggested include text analyses, study of cultural themes, and preparation of a lexicon featuring cultural…

  4. The penology of racial innocence: the erasure of racism in the study and practice of punishment.

    PubMed

    Murakawa, Naomi; Beckett, Katherine

    2010-01-01

    In post–civil rights America, the ascendance of “law-and-order” politics and “postracial” ideology have given rise to what we call the penology of racial innocence. The penology of racial innocence is a framework for assessing the role of race in penal policies and institutions, one that begins with the presumption that criminal justice is innocent of racial power until proven otherwise. Countervailing sociolegal changes render this framework particularly problematic. On the one hand, the definition of racism has contracted in antidiscrimination law and in many social scientific studies of criminal justice, so that racism is defined narrowly as intentional and causally discrete harm. On the other hand, criminal justice institutions have expanded to affect historically unprecedented numbers of people of color, with penal policies broadening in ways that render the identification of racial intent and causation especially difficult. Analyses employing the penology of racial innocence examine the ever-expanding criminal justice system with limited definitions of racism, ultimately contributing to the erasure of racial power. Both racism and criminal justice operate in systemic and serpentine ways; our conceptual tools and methods, therefore, need to be equally systemic and capacious. PMID:21132957

  5. Responding to "Innocent" Racism: Educating Teachers in Politically Reflexive and Dialogic Engagement in Local Communities

    ERIC Educational Resources Information Center

    Pirbhai-Illich, Fatima; Austin, Theresa; Paugh, Patricia; Farino, Yvonne

    2011-01-01

    This article develops the construct of "innocent racism" and argues for keeping questions of race central in teacher education. The authors report three cases in which they, teacher educators working within a school/university alliance, identified and addressed racism in their courses. We situate our analyses within antiracist research informed by…

  6. Lost Innocent and Sacrificial Delegate: The JonBenet Ramsey Murder.

    ERIC Educational Resources Information Center

    Conrad, Joann

    1999-01-01

    Analyzes murder case of 6-year-old JonBenet Ramsey as emblematic of American cultural fascination with images of the innocence of children and the perfect family, and of a change in cultural self-awareness as these images prove illusionary. Considers the role of mass media in marketing a cultural fascination with sexualized images of children and…

  7. Pancreas donation for islet transplantation.

    PubMed

    Frutos, M A; Ruiz, P; Mansilla, J J

    2005-04-01

    Islet transplantation, though still in the experimental phase, is a therapeutic option that has opened new expectations for the control of diabetes mellitus. Initial results are encouraging for the significant advantages compared with whole pancreas transplantation for selected patients with type 1 diabetes mellitus, with or without kidney failure. However, the success of transplantation, both at centers with more experience and others with less, is limited by the difficulty in obtaining a suitable number of donors and by laboratory isolation techniques. Significant advances require changes in donor selection, perfusion, oxygenation, and transfer of the pancreas, and in the process of isolation, purification, and culture in the laboratory. Of the 32 pancreases sent to the islet isolation laboratory from different hospitals in Andalusia, a viable percentage of islets was finally available in 19. However, in only 4 (18%) procedures were the preparations considered optimal for implantation in 2 recipients. PMID:15866673

  8. Wearable and implantable pancreas substitutes.

    PubMed

    Ricotti, Leonardo; Assaf, Tareq; Dario, Paolo; Menciassi, Arianna

    2013-03-01

    A lifelong-implanted and completely automated artificial or bioartificial pancreas (BAP) is the holy grail for type 1 diabetes treatment, and could be a definitive solution even for other severe pathologies, such as pancreatitis and pancreas cancer. Technology has made several important steps forward in the last years, providing new hope for the realization of such devices, whose feasibility is strictly connected to advances in glucose sensor technology, subcutaneous and intraperitoneal insulin pump development, the design of closed-loop control algorithms for mechatronic pancreases, as well as cell and tissue engineering and cell encapsulation for biohybrid pancreases. Furthermore, smart integration of the mentioned components and biocompatibility issues must be addressed, bearing in mind that, for mechatronic pancreases, it is most important to consider how to recharge implanted batteries and refill implanted insulin reservoirs without requiring periodic surgical interventions. This review describes recent advancements in technologies and concepts related to artificial and bioartificial pancreases, and assesses how far we are from a lifelong-implanted and self-working pancreas substitute that can fully restore the quality of life of a diabetic (or other type of) patient. PMID:22990986

  9. Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection

    PubMed Central

    Hölldobler, Bert

    2016-01-01

    The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents. PMID:26986740

  10. Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection.

    PubMed

    Hölldobler, Bert

    2016-01-01

    The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents. PMID:26986740

  11. Application of Rotating Wall Vessel (RWV) Cell Culture for Pancreas Islet Cell Transplantation

    NASA Technical Reports Server (NTRS)

    Rutzky, Lynne P.

    1998-01-01

    Type I insulin-dependent diabetes mellitus (IDDM) remains a major cause of morbidity and mortality in both pediatric and adult populations, despite significant advances in medical management. While insulin therapy treats symptoms of acute diabetes, it fails to prevent chronic complications such as microvascular disease, blindness, neuropathy, and chronic renal failure. Strict control of blood glucose concentrations delays but does not prevent the onset and progression of secondary complications. Although, whole pancreas transplantation restores physiological blood glucose levels, a continuous process of allograft rejection causes vascular and exocrine-related complications. Recent advances in methods for isolation and purification of pancreatic islets make transplantation of islet allografts an attractive alternative to whole pancreas transplantation. However, immunosuppressive drugs are necessary to prevent rejection of islet allografts and many of these drugs are known to be toxic to the islets. Since auto-transplants of isolated islets following total pancreatectomy survive and function in vivo, it is apparent that a major obstacle to successful clinical islet transplantation is the immunogenicity of the islet allografts.

  12. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages.

    PubMed

    Seaberg, Raewyn M; Smukler, Simon R; Kieffer, Timothy J; Enikolopov, Grigori; Asghar, Zeenat; Wheeler, Michael B; Korbutt, Gregory; van der Kooy, Derek

    2004-09-01

    The clonal isolation of putative adult pancreatic precursors has been an elusive goal of researchers seeking to develop cell replacement strategies for diabetes. We report the clonal identification of multipotent precursor cells from the adult mouse pancreas. The application of a serum-free, colony-forming assay to pancreatic cells enabled the identification of precursors from pancreatic islet and ductal populations. These cells proliferate in vitro to form clonal colonies that coexpress neural and pancreatic precursor markers. Upon differentiation, individual clonal colonies produce distinct populations of neurons and glial cells, pancreatic endocrine beta-, alpha- and delta-cells, and pancreatic exocrine and stellate cells. Moreover, the newly generated beta-like cells demonstrate glucose-dependent Ca(2+) responsiveness and insulin release. Pancreas colonies do not express markers of embryonic stem cells, nor genes suggestive of mesodermal or neural crest origins. These cells represent a previously unidentified adult intrinsic pancreatic precursor population and are a promising candidate for cell-based therapeutic strategies. PMID:15322557

  13. Monitoring of canine pancreas allograft function with measurements of urinary amylase.

    PubMed

    Ekberg, H; Deane, S A; Allen, R D; Hawthorne, W J; Williamson, P; Grierson, J M; Stewart, G J; Little, J M

    1988-07-01

    A canine model of whole pancreas transplantation with pancreaticocystostomy was studied for predictability of graft rejection using urinary amylase (UA) monitoring. Six pancreatectomized dogs were transplanted without immunosuppression and with acute rejection occurring at a median of 9.5 days (range 7-12 days). A differential loss of allograft exocrine and endocrine function was demonstrated, with a gradual decrease in UA after transplantation but maintenance of fasting blood glucose levels (FBGL) till the day before complete loss of graft structure. Another 13 dogs treated with cyclosporin (25 mg/kg per day) had prolonged graft survival (P less than 0.01) with an actuarial median survival of 91 days (range 8-159 days). Five allografts were lost because of rejection and eight dogs died with functioning grafts. Fasting spot levels of UA less than 5000 iu/l or less than 10,000 iu/l had a positive predictivity of graft failure of 71% or 31%, respectively. Falls of UA levels of greater than 75% in 24 h and 48 h were seen equally in both rejecting and functioning allografts. This study confirmed the role of UA as an earlier marker of rejection than FBGL. The clinical role of UA will be important, but its use as a predictor of pancreas rejection may be dependent on a fall to a predetermined level rather than the rate of fall. PMID:2473736

  14. ATP release, generation and hydrolysis in exocrine pancreatic duct cells.

    PubMed

    Kowal, J M; Yegutkin, G G; Novak, I

    2015-12-01

    -inactivating and nucleotide-phosphorylating ecto-enzymes. We suggest that extracellular ATP homeostasis in pancreatic ducts may be important in pancreas physiology and potentially in pancreas pathophysiology. PMID:26431833

  15. Exocrine pancreatic response to intraduodenal fatty acids and fats in rabbits.

    PubMed

    Navas, J M; Calvo, J J; López, M A; De Dios, I

    1993-05-01

    1. The exocrine pancreatic secretion in rabbits after intraduodenal perfusion of, respectively, a short-chain fatty acid (propionate), a long-chain fatty acid (oleate) and a neutral fat (intralipid) has been studied. 2. Only the neutral fat and the long-chain fatty acid stimulated the hydroelectrolyte fraction of exocrine pancreatic secretion in a dose-related fashion, but this response was not mediated by secretin release. 3. Acinar secretion was more effectively stimulated after propionate perfusion than by oleate and this was governed by different mechanisms. 4. Neutral fat, without predigestion, stimulated the pancreatic enzyme secretion in the rabbit. PMID:8099868

  16. Differences in the readiness of guilty and informed innocent examinees to cooperate on the Guilty Action Test.

    PubMed

    Elaad, Eitan

    2014-01-01

    A mock crime experiment was designed in which 100 participants were randomly assigned to five conditions: four experimental conditions in a 2 × 2 factorial design (two guilt conditions-guilty or informed innocents, crossed with two incentive level conditions-with or without a promised reward for proving innocence), and one control condition of uninformed innocents. Along with the common dependent polygraph measures, attitudes towards cooperating with the test were assessed. Results indicated that the informed innocents preferred to cooperate whereas guilty participants preferred to try and obstruct the test. These tendencies were amplified among participants who were promised a reward. The cooperative choice attenuated electrodermal responses to the critical items. Respiration measures were sensitive to the incentive level manipulation. Implications of the results for future research and for actual detection of information tests were discussed. PMID:24020868

  17. Cybersecurity in Artificial Pancreas Experiments.

    PubMed

    O'Keeffe, Derek T; Maraka, Spyridoula; Basu, Ananda; Keith-Hynes, Patrick; Kudva, Yogish C

    2015-09-01

    Medical devices have transformed modern health care, and ongoing experimental medical technology trials (such as the artificial pancreas) have the potential to significantly improve the treatment of several chronic conditions, including diabetes mellitus. However, we suggest that, to date, the essential concept of cybersecurity has not been adequately addressed in this field. This article discusses several key issues of cybersecurity in medical devices and proposes some solutions. In addition, it outlines the current requirements and efforts of regulatory agencies to increase awareness of this topic and to improve cybersecurity. PMID:25923544

  18. Cybersecurity in Artificial Pancreas Experiments

    PubMed Central

    O'Keeffe, Derek T.; Maraka, Spyridoula; Basu, Ananda; Keith-Hynes, Patrick

    2015-01-01

    Abstract Medical devices have transformed modern health care, and ongoing experimental medical technology trials (such as the artificial pancreas) have the potential to significantly improve the treatment of several chronic conditions, including diabetes mellitus. However, we suggest that, to date, the essential concept of cybersecurity has not been adequately addressed in this field. This article discusses several key issues of cybersecurity in medical devices and proposes some solutions. In addition, it outlines the current requirements and efforts of regulatory agencies to increase awareness of this topic and to improve cybersecurity. PMID:25923544

  19. Design of a bioartificial pancreas+

    PubMed Central

    Opara, Emmanuel C.; Mirmalek-Sani, Sayed-Hadi; Khanna, Omaditya; Moya, Monica L; Brey, Eric M.

    2010-01-01

    Introduction In Type 1 diabetes, the β-cells that secrete insulin have been destroyed such that daily exogenous insulin administration is required for the control of blood sugar in individuals afflicted with the disease. Following the development of reliable techniques for the isolation of islets from the human pancreas, islet transplantation has emerged as a therapeutic option, albeit, for only a few selected patients largely because there are not enough islets for the millions of patients requiring the treatment, and there is also the need to use immunosuppressive drugs to prevent transplant rejection. In 1980, the concept of islet immunoisolation by microencapsulation was introduced as a technique to overcome these two major barriers to islet transplantation. Microencapsulation of islets and transplantation in the peritoneal cavity was then described as a bioartificial pancreas. However, it is difficult to retrieve encapsulated islets transplanted in the peritoneal cavity, thus making it difficult to meet all the criteria for a bioartificial pancreas. A new design of a bioartificial pancreas comprising islets co-encapsulated with angiogenic protein in perm-selective multilayer alginate-poly-L-ornithine-alginate (APA) microcapsules and transplanted in an omentum pouch is described in this paper. Materials & Methods The multilayer APA microcapsules are made with ultrapure alginate using poly-L-ornithine as a semi-permeable membrane separating the two alginate layers. The inner alginate layer is used to encapsulate the islets and the outer layer is used to encapsulate angiogenic protein, which would induce neovascularization around the graft within the omentum pouch. Results In in vitro studies, we found that both the wild-type and the heparin binding-growth associated molecule (HBGAM)-FGF-1 chimera can be encapsulated and released in a controlled and sustained manner from the outer alginate layer with a mean diameter in the range of 113–164 microns when 1

  20. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    PubMed

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells. PMID:26235267

  1. ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children.

    PubMed

    Taylor, Christopher J; Chen, Kathy; Horvath, Karoly; Hughes, David; Lowe, Mark E; Mehta, Devendra; Orabi, Abrahim I; Screws, Jeremy; Thomson, Mike; Van Biervliet, Stephanie; Verkade, Henkjan J; Husain, Sohail Z; Wilschanski, Michael

    2015-07-01

    The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis. PMID:25915425

  2. EXOCRINE PANCREATIC NEOPLASMS IN THE MUMMICHOG (FUNDULUS HETEROCLITUS) FROM A CREOSOTE-CONTAMINATED SITE

    EPA Science Inventory

    A high prevalence of exocrine pancreatic neoplasms occurred in mummichog, Fundulus heteroclitus, from a creosote-contaminated site in the Elizabeth River, Virginia. otal of 20 neoplasms occurred in a group of about 1 100 fish evaluated histologically. f 240 adult fish collected d...

  3. Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

    SciTech Connect

    Cameron, R.S.; Cameron, P.L.; Castle, J.D.

    1986-10-01

    A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion.

  4. Molecular therapeutics in pancreas cancer

    PubMed Central

    Narayanan, Vignesh; Weekes, Colin D

    2016-01-01

    The emergence of the “precision-medicine” paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  5. Molecular therapeutics in pancreas cancer.

    PubMed

    Narayanan, Vignesh; Weekes, Colin D

    2016-04-15

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  6. Solid pseudopapillary tumor of the pancreas in a patient with cervical cancer: relation of E-cadherin/β-catenin adhesion complex in their carcinogenesis

    PubMed Central

    Vijay, Adarsh; Ram, Lakshmi; Mathew, Renol Koshy; Chawdhery, Muhammad Zafar

    2015-01-01

    Solid pseudopapillary tumor (SPT) of the pancreas is one of the most uncommon histotypes of all exocrine pancreatic neoplasms. Disorganization of E-cadherin and β-catenin mutations, two key components of the Wnt signal transduction pathway, has been implicated in the development of SPT, but not other pancreatic tumors. Loss of E-cadherin/β-catenin proteins and tyrosine phosphorylation of E-cadherin/β-catenin have been postulated in cervical carcinogenesis and cancer invasion. A 38-year-old married woman, who had undergone brachytherapy, radiotherapy and chemotherapy for cervical cancer in Philippines in 2011, was admitted to our hospital after follow-up CT scan of abdomen in 2012 revealed a lesion in the tail of pancreas. The patient underwent distal pancreatectomy and splenectomy. The pathological diagnosis was SPT of pancreas. We suspect that the concurrent SPT pancreas and cervical cancer in this woman were triggered by a primary insult, a process in which E-cadherin/β-catenin/Wnt-signaling pathway played important roles. PMID:25848087

  7. Pancreas Transplantation: An Alarming Crisis in Confidence.

    PubMed

    Stratta, R J; Gruessner, A C; Odorico, J S; Fridell, J A; Gruessner, R W G

    2016-09-01

    In the past decade, the annual number of pancreas transplantations performed in the United States has steadily declined. From 2004 to 2011, the overall number of simultaneous pancreas-kidney (SPK) transplantations in the United States declined by 10%, whereas the decreases in pancreas after kidney (PAK) and pancreas transplant alone (PTA) procedures were 55% and 34%, respectively. Paradoxically, this has occurred in the setting of improvements in graft and patient survival outcomes and transplanting higher-risk patients. Only 11 centers in the United States currently perform ≥20 pancreas transplantations per year, and most centers perform <5 pancreas transplantations annually; many do not perform PAKs or PTAs. This national trend in decreasing numbers of pancreas transplantations is related to a number of factors including lack of a primary referral source, improvements in diabetes care and management, changing donor and recipient considerations, inadequate training opportunities, and increasing risk aversion because of regulatory scrutiny. A national initiative is needed to "reinvigorate" SPK and PAK procedures as preferred transplantation options for appropriately selected uremic patients taking insulin regardless of C-peptide levels or "type" of diabetes. Moreover, many patients may benefit from PTAs because all categories of pancreas transplantation are not only life enhancing but also life extending procedures. PMID:27232750

  8. Possible link between ectopic pancreas and holoprosencephaly

    PubMed Central

    Kin, Tatsuya; Korbutt, Gregory S.; Shapiro, A.M. James

    2012-01-01

    We report on the incidental observation of ectopic pancreas in a donor for islet cell transplantation. The donor’s clinical and imaging presentation was definitive for holoprosencephaly. This case report discusses a possible link between ectopic pancreas and holoprosencephaly. PMID:22688061

  9. The innocent landowner defense under CERCLA should be transferable to subsequent purchasers

    SciTech Connect

    Spertus, J.W.

    1993-12-31

    Under CERCLA, landowners are held strictly liable for cleaning up hazardous substances on their property. Purchasers who acquire title to contaminated property become liable for cleanup costs by virtue of their status as the current owner. Although liability under the Act is strict, joint, and several, a few limited defenses enable some landowners to avoid liability altogether. One such defense, known as the innocent landowner defense, is the subject of this article.

  10. Solitary fibrous tumor of the pancreas.

    PubMed

    Baxter, Andrew R; Newman, Elliot; Hajdu, Cristina H

    2015-01-01

    Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms of fibroblastic origin. Most commonly they affect the pleura but they been described in other viscera. SFT of the pancreas is extremely rare, and only eight cases have been reported to date. We perform a literature review and report a ninth case. The patient is a 54-year-old African-American female who presented with several months of abdominal pain. Abdominal radiography demonstrated a lesion in the head of the pancreas, and she underwent a Whipple operation. Pathology demonstrated SFT of the pancreas. She is alive and well 1 year post-operatively. SFT of the pancreas predominately affects middle-aged women. These tumors are difficult to distinguish radiologically from neuroendocrine tumors. While SFT of the pancreas tend to have an indolent course, there is the potential for malignancy. We recommend complete surgical excision. PMID:26628714

  11. Solitary fibrous tumor of the pancreas

    PubMed Central

    Baxter, Andrew R.; Newman, Elliot; Hajdu, Cristina H.

    2015-01-01

    Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms of fibroblastic origin. Most commonly they affect the pleura but they been described in other viscera. SFT of the pancreas is extremely rare, and only eight cases have been reported to date. We perform a literature review and report a ninth case. The patient is a 54-year-old African-American female who presented with several months of abdominal pain. Abdominal radiography demonstrated a lesion in the head of the pancreas, and she underwent a Whipple operation. Pathology demonstrated SFT of the pancreas. She is alive and well 1 year post-operatively. SFT of the pancreas predominately affects middle-aged women. These tumors are difficult to distinguish radiologically from neuroendocrine tumors. While SFT of the pancreas tend to have an indolent course, there is the potential for malignancy. We recommend complete surgical excision. PMID:26628714

  12. Glucagon in the Artificial Pancreas

    PubMed Central

    2014-01-01

    The use of glucagon, in conjunction with insulin, in a dual chamber pump (artificial pancreas, AP) is a working goal for multiple companies and researchers. However, capital investment to create, operate, and maintain facilities with sufficient scale to produce enough glucagon to treat millions of patients, at a level of profit that makes it feasible, will be substantial. It can be assumed that the marketplace will expect the daily cost of glucagon (to the consumer) to be similar to the daily cost of insulin. After one subtracts wholesaler and pharmacy markup, there may be very few dollars remaining for the drug company to cover profit, capital expenditures, marketing, burden, and other costs. Without the potential for adequate margins, manufacturers may not be willing to take the risk. Assuming that the projections discussed in this article are in the right ballpark, advance planning for the supply for glucagon needs to start today and not wait for the AP to come to market. PMID:25139825

  13. Robotic surgery of the pancreas

    PubMed Central

    Joyce, Daniel; Morris-Stiff, Gareth; Falk, Gavin A; El-Hayek, Kevin; Chalikonda, Sricharan; Walsh, R Matthew

    2014-01-01

    Pancreatic surgery is one of the most challenging and complex fields in general surgery. While minimally invasive surgery has become the standard of care for many intra-abdominal pathologies the overwhelming majority of pancreatic surgery is performed in an open fashion. This is attributed to the retroperitoneal location of the pancreas, its intimate relationship to major vasculature and the complexity of reconstruction in the case of pancreatoduodenectomy. Herein, we describe the application of robotic technology to minimally invasive pancreatic surgery. The unique capabilities of the robotic platform have made the minimally invasive approach feasible and safe with equivalent if not better outcomes (e.g., decreased length of stay, less surgical site infections) to conventional open surgery. However, it is unclear whether the robotic approach is truly superior to traditional laparoscopy; this is a key point given the substantial costs associated with procuring and maintaining robotic capabilities. PMID:25356035

  14. Impact of high dietary zinc on zinc accumulation, enzyme activity and proteomic profiles in the pancreas of piglets.

    PubMed

    Pieper, R; Martin, L; Schunter, N; Villodre Tudela, C; Weise, C; Klopfleisch, R; Zentek, J; Einspanier, R; Bondzio, A

    2015-04-01

    The exocrine pancreas plays an important role in zinc homeostasis. Feeding very high (2000-3000mgzinc/kg diet) levels of zinc oxide to piglets for short periods is a common practice in the swine industry to improve performance and prevent diseases. The impact on pancreatic function and possible side effects during long-term feeding of high dietary zinc levels are still poorly understood. A total of 54 weaned piglets were either fed with low (57mg/kg, LZn), normal (164mg/kg, NZn) or high (2425mg/kg, HZn) zinc concentration in the diets. After 4 weeks of feeding, ten piglets per treatment were euthanized and pancreas samples were taken. Tissue zinc concentration and metallothionein abundance was greater with HZn compared with NZn and LZn (P<0.05). Similarly, activity of α-amylase, lipase, trypsin and chymotrypsin was higher with HZn as compared with NZn and LZn diets (P<0.05), whereas elastase activity was unchanged. Total trolox equivalent antioxidative capacity of pancreas tissue was higher with HZn diets compared with the other treatments (P<0.05). Pancreatic protein profiles of NZn and HZn fed piglets were obtained by 2D-DIGE technique and revealed 15 differentially expressed proteins out of 2100 detected spots (P<0.05). The differentially expressed proteins aldose reductase, eukaryotic elongation factor II and peroxiredoxin III were confirmed by immunoblotting. Identified proteins include zinc finger-containing transcription factors and proteins mainly associated with oxidative stress response and signal transduction in HZn compared with NZn pigs. Histologic examination however showed no morphologic changes. The results suggest that long-term supply of very high dietary zinc increases zinc and metallothionein concentration, and digestive enzyme activity, but also triggers oxidative stress reactions in the pancreas of young pigs. The data provide new insights into pancreatic function under outbalanced zinc homeostasis. PMID:25744507

  15. [Surgical treatment of benign, premalignant and low-risk tumors of the pancreas : Standard resection or parenchyma preserving, local extirpation].

    PubMed

    Beger, H G

    2016-07-01

    Cystic neoplasms and neuroendocrine adenomas of the pancreas are detected increasingly more frequently and in up to 50 % as asymptomatic tumors. Intraductal papillary mucinous neoplasms, mucinous cystic neoplasms and solid pseudopapillary neoplasms are considered to be premalignant lesions with different rates of malignant transformation. The most frequent neuroendocrine adenomas are insulinomas. Neuroendocrine adenomas are considered to be potentially malignant, inherent to the lesion and development is unpredictable. Standard surgical treatment for pancreatic tumors are the Kausch-Whipple resection, left hemipancreatectomy and total pancreatectomy depending on the location; however, the application of standard surgical procedures, which are usually multiorgan resections for benign, premalignant and low-risk cancers of the pancreas have to be balanced against the risk for early postoperative morbidity, hospital mortality of 1.5-7 % and loss of endocrine and exocrine pancreatic functions in 12-30 %. Tumor enucleation, pancreatic middle segment resection and duodenum-preserving total pancreatic head (DPPHR-T/S) resection are parenchyma-preserving, local resection procedures, which are associated with a low early postoperative rate of severe complications, hospital mortality up to 1.3 % and maintenance of exocrine and endocrine pancreatic functions in more than 90 %. Tumor enucleation bears the risk of pancreatic fistulas (<33 %) and a limitation is proximity to the pancreatic main duct. The main risk for pancreatic middle segment resection is early postoperative pancreatic fistulas (up to 40 %), early postoperative intra-abdominal hemorrhage and a reintervention frequency up to 15 %. The DPPHR-T/S resection is applied for cystic neoplastic lesions in 90 %, severe postoperative complications are below 15 % and the 90-day hospital mortality is 0.5 %. Pancreatic fistulas are observed in less than 20 % with a recurrence rate of <1 %. These

  16. What You Need to Know about Cancer of the Pancreas

    MedlinePlus

    ... You Need To Know About™ Cancer of the Pancreas This booklet is about cancer of the pancreas, also called pancreatic cancer. There are two main ... care. This booklet covers: The anatomy of the pancreas and basics about cancer of the pancreas Treatments ...

  17. How Innocent are Potentially Redox Non-Innocent Ligands? Electronic Structure and Metal Oxidation States in Iron-PNN Complexes as a Representative Case Study.

    PubMed

    Butschke, Burkhard; Fillman, Kathlyn L; Bendikov, Tatyana; Shimon, Linda J W; Diskin-Posner, Yael; Leitus, Gregory; Gorelsky, Serge I; Neidig, Michael L; Milstein, David

    2015-05-18

    Herein we present a series of new α-iminopyridine-based iron-PNN pincer complexes [FeBr2LPNN] (1), [Fe(CO)2LPNN] (2), [Fe(CO)2LPNN](BF4) (3), [Fe(F)(CO)2LPNN](BF4) (4), and [Fe(H)(CO)2LPNN](BF4) (5) with formal oxidation states ranging from Fe(0) to Fe(II) (LPNN = 2-[(di-tert-butylphosphino)methyl]-6-[1-(2,4,6-mesitylimino)ethyl]pyridine). The complexes were characterized by a variety of methods including (1)H, (13)C, (15)N, and (31)P NMR, IR, Mössbauer, and X-ray photoelectron spectroscopy (XPS) as well as electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy, SQUID magnetometry, and X-ray crystallography, focusing on the assignment of the metal oxidation states. Ligand structural features suggest that the α-iminopyridine ligand behaves as a redox non-innocent ligand in some of these complexes, particularly in [Fe(CO)2LPNN] (2), in which it appears to adopt the monoanionic form. In addition, the NMR spectroscopic features ((13)C, (15)N) indicate the accumulation of charge density on parts of the ligand for 2. However, a combination of spectroscopic measurements that more directly probe the iron oxidation state (e.g., XPS), density functional theory (DFT) calculations, and electronic absorption studies combined with time-dependent DFT calculations support the description of the metal atom in 2 as Fe(0). We conclude from our studies that ligand structural features, while useful in many assignments of ligand redox non-innocence, may not always accurately reflect the ligand charge state and, hence, the metal oxidation state. For complex 2, the ligand structural changes are interpreted in terms of strong back-donation from the metal center to the ligand as opposed to electron transfer. PMID:25918944

  18. Murine nonvolatile pheromones: isolation of exocrine-gland secreting Peptide 1.

    PubMed

    Kimoto, Hiroko; Touhara, Kazushige

    2013-01-01

    Our search for a substance recognized by the vomeronasal neurons revealed that the extra-orbital lacrimal gland (ELG) isolated from adult male mice produced the male-specific peptide pheromone exocrine gland-secreting peptide 1 (ESP1). The following protocol reveals how ESP1 may be extracted from the ELG, purified using anion-exchange and reverse-phase high-performance liquid chromatography (HPLC), and analyzed by mass spectrometry. This protocol has been specifically designed for the purification of ESP1, but may be modified to isolate a variety of peptides from the exocrine glands. Peptides purified in this manner may help further define the molecular mechanisms underlying pheromone communication in the vomeronasal system. PMID:24014353

  19. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis

    PubMed Central

    Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  20. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.

    PubMed

    Jin, Yuepeng; Bai, Yongyu; Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  1. Cystic lesions of the pancreas

    PubMed Central

    Karoumpalis, Ioannis; Christodoulou, Dimitrios K.

    2016-01-01

    Different types of benign or malignant cystic lesions can be observed in the pancreas. Pancreatic cystic lesions are classified under pathology terms into simple retention cysts, pseudocysts and cystic neoplasms. Mucinous cystic neoplasm is a frequent type of cystic neoplasm and has a malignant potential. Serous cystadenoma follows in frequency and is usually benign. Intraductal papillary mucinous neoplasms are the most commonly resected cystic pancreatic neoplasms characterized by dilated segments of the main pancreatic duct and/or side branches, the wall of which is covered by mucus secreting cells. These neoplasms can occupy the pancreatic head or any part of the organ. Solid pseudopapillary tumor is rare, has a low tendency for malignancy, and is usually located in the pancreatic body or tail. Endoscopic ultrasound with the use of fine-needle aspiration and cytology permits discrimination of those lesions. In this review, the main characteristics of those lesions are presented, as well as recommendations regarding their follow up and management according to recent guidelines. PMID:27065727

  2. Cystic lesions of the pancreas.

    PubMed

    Karoumpalis, Ioannis; Christodoulou, Dimitrios K

    2016-01-01

    Different types of benign or malignant cystic lesions can be observed in the pancreas. Pancreatic cystic lesions are classified under pathology terms into simple retention cysts, pseudocysts and cystic neoplasms. Mucinous cystic neoplasm is a frequent type of cystic neoplasm and has a malignant potential. Serous cystadenoma follows in frequency and is usually benign. Intraductal papillary mucinous neoplasms are the most commonly resected cystic pancreatic neoplasms characterized by dilated segments of the main pancreatic duct and/or side branches, the wall of which is covered by mucus secreting cells. These neoplasms can occupy the pancreatic head or any part of the organ. Solid pseudopapillary tumor is rare, has a low tendency for malignancy, and is usually located in the pancreatic body or tail. Endoscopic ultrasound with the use of fine-needle aspiration and cytology permits discrimination of those lesions. In this review, the main characteristics of those lesions are presented, as well as recommendations regarding their follow up and management according to recent guidelines. PMID:27065727

  3. Pancreas Transplantation: Past, Present, Future.

    PubMed

    Dholakia, Shamik; Mittal, Shruti; Quiroga, Isabel; Gilbert, James; Sharples, Edward J; Ploeg, Rutger J; Friend, Peter J

    2016-07-01

    Diabetes is the pandemic disease of the modern era, with 10% of these patients having type 1 diabetes mellitus. Despite the prevalence, morbidities, and associated financial burden, treatment options have not changed since the introduction of injectable insulin. To date, over 40,000 pancreas transplants have been performed globally. It remains the only known method for restoring glycemic control and thus curing type 1 diabetes mellitus. The aim of this review is to bring pancreatic transplantation out of the specialist realm, informing practitioners about this important procedure, so that they feel better equipped to refer suitable patients for transplantation and manage, counsel, and support when encountering them within their own specialty. This study was a narrative review conducted in October 2015, with OVID interface searching EMBASE and MEDLINE databases, using Timeframe: Inception to October 2015. Articles were assessed for clinical relevance and most up-to-date content, with articles written in English as the only inclusion criterion. Other sources used included conference proceedings/presentations and unpublished data from our institution (Oxford Transplant Centre). Pancreatic transplantation is growing and has quickly become the gold standard of care for patients with type 1 diabetes mellitus and renal failure. Significant improvements in quality of life and life expectancy make pancreatic transplant a viable and economically feasible intervention. It remains the most effective method of establishing and maintaining euglycemia, halting and potentially reversing complications associated with diabetes. PMID:26965300

  4. The protection of innocent suspects: a comment on Palmatier and Rovner (2015).

    PubMed

    Vrij, Aldert

    2015-01-01

    Palmatier and Rovner (2015) should be applauded for their efforts to examine whether CQT and CIT polygraph testing methods can be reconciled by common theory. They (understandably) focus on liars in their article, however, liars are only part of the equation. Lie detection tests also involve truth tellers, and the ways in which truth tellers are protected against a false accusation is where the CQT and CIT differ. This important point is not addressed by Palmatier and Rovner (2015), but the concern expressed by CQT opponents that innocent suspects are not well protected in a CQT test needs to be addressed head on by CQT supporters. PMID:25224520

  5. Catalysis by aluminum(III) complexes of non-innocent ligands.

    PubMed

    Berben, Louise A

    2015-02-01

    Non-Innocent ligand complexes of aluminum are described in this Concept article, beginning with a discussion of their synthesis, and then structural and electronic characterization. The main focus concerns the ability of the ligands in these complexes to mediate proton transfer reactions. As examples, aluminum-ligand cooperation in the activation of polar bonds is described, as is the importance of hydrogen bonding to stabilization of a transition state for β-hydride abstraction. Taken together these reactions enable catalytic processes such as the dehydrogenation of formic acid. PMID:25429760

  6. Blaming for a better future: future orientation and associated intolerance of personal uncertainty lead to harsher reactions toward innocent victims.

    PubMed

    Bal, Michèlle; van den Bos, Kees

    2012-07-01

    People are often encouraged to focus on the future and strive for long-term goals. This noted, the authors argue that this future orientation is associated with intolerance of personal uncertainty, as people usually cannot be certain that their efforts will pay off. To be able to tolerate personal uncertainty, people adhere strongly to the belief in a just world, paradoxically resulting in harsher reactions toward innocent victims. In three experiments, the authors show that a future orientation indeed leads to more negative evaluations of an innocent victim (Study 1), enhances intolerance of personal uncertainty (Study 2), and that experiencing personal uncertainty leads to more negative evaluations of a victim (Study 3). So, while a future orientation enables people to strive for long-term goals, it also leads them to be harsher toward innocent victims. One underlying mechanism causing these reactions is intolerance of personal uncertainty, associated with a future orientation. PMID:22492551

  7. Accumulation of Extracellular Matrix and Developmental Dysregulation in the Pancreas by Transgenic Production of Transforming Growth Factor-β1

    PubMed Central

    Lee, Myung-Shik; Gu, Danling; Feng, Lili; Curriden, Scott; Arnush, Marc; Krahl, Troy; Gurushanthaiah, Deepak; Wilson, Curtis; Loskutoff, David L.; Fox, Howard; Sarvetnick, Nora

    1995-01-01

    Transgenic mice expressing transforming growth factor-β1 (TGF-β1) in the pancreatic β-islet cells directed by human insulin promoter were produced to study in vivo effects of TGF-β1. Fibroblast proliferation and abnormal deposition of extracellular matrix were observed from birth onward, finally replacing almost all the exocrine pancreas. Cellular infiltrates comprising macrophages and neutrophils were also observed. Plasminogen activator inhibitor was induced in the transgenic pancreas as well as fibronectin and laminin, partly explaining accumulation of extracellular matrix. TGF-β1 inhibited proliferation of acinar cells in vivo as evidenced by decreased bromodeoxyuridine incorporation. Development of pancreatic islets was dysregulated, resulting in small islet cell clusters without formation of normal adult islets; however, the overall islet cell mass was not signfifcantly diminished. Additional transgenic lines with less pronounced phenotypes had less expression of TGF-β1 transgene. These findings suggest that TGF-β1 might be a mediator of diseases associated with extracellular matrix deposition such as chronic pancreatitis, and this mouse model will be useful for further analysis of the in vivo effects of TGF-β1, including its potential for immunosuppression. Imagesp43-aFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:7604884

  8. Results of Pancreas Transplantation Alone with Special Attention to Native Kidney Function and Proteinuria in Type 1 Diabetes Patients

    PubMed Central

    Boggi, Ugo; Vistoli, Fabio; Amorese, Gabriella; Giannarelli, Rosa; Coppelli, Alberto; Mariotti, Rita; Rondinini, Lorenzo; Barsotti, Massimiliamo; Piaggesi, Alberto; Tedeschi, Anna; Signori, Stefano; De Lio, Nelide; Occhipinti, Margherita; Mangione, Emanuela; Cantarovich, Diego; Del Prato, Stefano; Mosca, Franco; Marchetti, Piero

    2011-01-01

    We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience. PMID:22189549

  9. Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.

    PubMed

    Zhou, Jing; Jin, Jun-O; Patel, Ekta S; Yu, Qing

    2015-12-01

    Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions. PMID:26255211

  10. Characterization of human brain nicotinamide 5'-mononucleotide adenylyltransferase-2 and expression in human pancreas.

    PubMed Central

    Yalowitz, Joel A; Xiao, Suhong; Biju, Mangatt P; Antony, Aśok C; Cummings, Oscar W; Deeg, Mark A; Jayaram, Hiremagalur N

    2004-01-01

    NMNAT (nicotinamide 5'-mononucleotide adenylyltransferase; EC 2.7.7.1) catalyses the transfer of the adenylyl group from ATP to NMN to form NAD. We have cloned a novel human NMNAT cDNA, designated hNMNAT-2, from human brain. The cDNA contains a 924 bp open reading frame that encodes a 307 amino acid peptide that was expressed as a histidine-patch-containing thioredoxin fusion protein. Expressed hNMNAT-2 shared only 35% amino acid sequence homology with the human NMNAT enzyme (hNMNAT-1), but possessed enzymic activity comparable with hNMNAT-1. Using human genomic databases, hNMNAT-2 was localized to chromosome 1q25 within a 171 kb gene, whereas hNMNAT-1 is on chromosome 1p32-35. Northern blot analysis revealed highly restricted expression of hNMNAT-2 to brain, heart and muscle tissues, which contrasts with the wide tissue expression of hNMNAT-1; different regions of the brain exhibited differential expression of hNMNAT-2. Substitution mutations of either of two invariant residues, His-24 or Trp-92, abolished enzyme activity. Anti-peptide antibody to a unique epitope within hNMNAT-2 was produced, and immunohistochemical analysis of sections of normal adult human pancreas revealed that hNMNAT-2 protein was markedly expressed in the islets of Langerhans. However, the pancreatic exocrine cells exhibited weak expression of hNMNAT-2 protein. Sections of pancreas from insulinoma patients showed strong expression of hNMNAT-2 protein in the insulin-producing tumour cells, whereas acinar cells exhibited relatively low expression of hNMNAT-2 protein. These data suggest that the unique tissue-expression patterns of hNMNAT-2 reflect distinct functions for the isoforms in the regulation of NAD metabolism. PMID:14516279

  11. Acute pancreatitis decreases the sensitivity of pancreas-projecting dorsal motor nucleus of the vagus neurones to group II metabotropic glutamate receptor agonists in rats

    PubMed Central

    Babic, Tanja; Travagli, R Alberto

    2014-01-01

    Recent studies have shown that pancreatic exocrine secretions (PES) are modulated by dorsal motor nucleus of the vagus (DMV) neurones, whose activity is finely tuned by GABAergic and glutamatergic synaptic inputs. Group II metabotropic glutamate receptors (mGluR) decrease synaptic transmission to pancreas-projecting DMV neurones and increase PES. In the present study, we used a combination of in vivo and in vitro approaches aimed at characterising the effects of caerulein-induced acute pancreatitis (AP) on the vagal neurocircuitry modulating pancreatic functions. In control rats, microinjection of bicuculline into the DMV increased PES, whereas microinjections of kynurenic acid had no effect. Conversely, in AP rats, microinjection of bicuculline had no effect, whereas kynurenic acid decreased PES. DMV microinjections of the group II mGluR agonist APDC and whole cell recordings of excitatory currents in identified pancreas-projecting DMV neurones showed a reduced functional response in AP rats compared to controls. Moreover, these changes persisted up to 3 weeks following the induction of AP. These data demonstrate that AP increases the excitatory input to pancreas-projecting DMV neurones by decreasing the response of excitatory synaptic terminals to group II mGluR agonist. PMID:24445314

  12. Melatonin, endocrine pancreas and diabetes.

    PubMed

    Peschke, Elmar

    2008-01-01

    Melatonin influences insulin secretion both in vivo and in vitro. (i) The effects are MT(1)-and MT(2)-receptor-mediated. (ii) They are specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the cAMP-pathway and decrease of insulin release. [Correction added after online publication 4 December 2007: in the preceding sentence, 'increase of insulin release' was changed to 'decrease of insulin release'.] Furthermore, melatonin inhibits the cGMP-pathway, possibly mediated by MT(2) receptors. In this way, melatonin likely inhibits insulin release. A third system, the IP(3)-pathway, is mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from intracellular stores, with a resultant increase in insulin. (iii) Insulin secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm. This rhythm, which is apparently generated within the islets, is influenced by melatonin, which induces a phase shift in insulin secretion. (iv) Observation of the circadian expression of clock genes in the pancreas could possibly be an indication of the generation of circadian rhythms in the pancreatic islets themselves. (v) Melatonin influences diabetes and associated metabolic disturbances. The diabetogens, alloxan and streptozotocin, lead to selective destruction of beta-cells through their accumulation in these cells, where they induce the generation of ROS. Beta-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. Results suggest that melatonin in pharmacological doses provides protection against ROS. (vi) Finally, melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans. In contrast, in the pineal gland, the AANAT mRNA is increased and the insulin receptor mRNA is decreased, which indicates a close interrelationship between insulin and melatonin. PMID:18078445

  13. A novel method for discrimination between innocent and pathological heart murmurs.

    PubMed

    Gharehbaghi, Arash; Borga, Magnus; Sjöberg, Birgitta Janerot; Ask, Per

    2015-07-01

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM. PMID:26003286

  14. Pluripotency of adult stem cells derived from human and rat pancreas

    NASA Astrophysics Data System (ADS)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  15. Progressive Metaplastic and Dysplastic Changes in Mouse Pancreas Induced by Cyclooxygenase-2 Overexpression1

    PubMed Central

    Colby, Jennifer KL; Klein, Russell D; McArthur, Mark J; Conti, Claudio J; Kiguchi, Kaoru; Kawamoto, Toru; Riggs, Penny K; Pavone, Amy I; Sawicki, Janet; Fischer, Susan M

    2008-01-01

    Cyclooxygenase-2 (COX-2) overexpression is an established factor linking chronic inflammation with metaplastic and neoplastic change in various tissues. We generated transgenic mice (BK5.COX-2) in which elevation of COX-2 and its effectors trigger a metaplasia-dysplasia sequence in exocrine pancreas. Histologic evaluation revealed a chronic pancreatitis-like state characterized by acinar-to-ductal metaplasia and a well-vascularized fibroinflammatory stroma that develops by 3 months. By 6 to 8 months, strongly dysplastic features suggestive of pancreatic ductal adenocarcinoma emerge in the metaplastic ducts. Increased proliferation, cellular atypia, and loss of normal cell/tissue organization are typical features in transgenic pancreata. Alterations in biomarkers associated with human inflammatory and neoplastic pancreatic disease were detected using immunohistochemistry. The abnormal pancreatic phenotype can be completely prevented by maintaining mice on a diet containing celecoxib, a well-characterized COX-2 inhibitor. Despite the high degree of atypia, only limited evidence of invasion to adjacent tissues was observed, with no evidence of distant metastases. However, cell lines derived from spontaneous lesions are aggressively tumorigenic when injected into syngeneic or nude mice. The progressive nature of the metaplastic/dysplastic changes observed in this model make it a valuable tool for examining the transition from chronic inflammation to neoplasia. PMID:18670639

  16. Mixed acinar-neuroendocrine carcinoma of the pancreas with neuroendocrine predominance.

    PubMed

    Ogbonna, Onyekachi Henry; Garcon, Marie Carmel; Syrigos, Kostas N; Saif, Muhammad Wasif

    2013-01-01

    Background. Pancreatic tumors are rare and could arise from either the exocrine (ductal and acinar cells) or the endocrine (neuroendocrine cells) components of the pancreas. In some instances, the occurrence of pancreatic tumors comprising both acinar cells and neuroendocrine cells, with neuroendocrine cells making up more than 30% of the tumor, has been identified. This unique entity has been referred to as mixed acinar-neuroendocrine carcinoma (MANEC). Only about 20 such cases have been reported in the literature. Case Report. We report an interesting case of MANEC with neuroendocrine cell predominance in a woman presenting with epigastric pain secondary to a pancreatic mass with acinar and endocrine differentiation. She underwent surgical resection of the tumor and was offered adjuvant treatment chemotherapy with carboplatin, etoposide, and radiotherapy for positive tumor resection margins. Conclusions. Given the paucity of the cases of MANEC, continuous reporting of these cases when identified should be encouraged to aid oncologists in understanding the disease and help establish standardized management. PMID:24348574

  17. Mixed Acinar-Neuroendocrine Carcinoma of the Pancreas with Neuroendocrine Predominance

    PubMed Central

    Ogbonna, Onyekachi Henry; Syrigos, Kostas N.; Saif, Muhammad Wasif

    2013-01-01

    Background. Pancreatic tumors are rare and could arise from either the exocrine (ductal and acinar cells) or the endocrine (neuroendocrine cells) components of the pancreas. In some instances, the occurrence of pancreatic tumors comprising both acinar cells and neuroendocrine cells, with neuroendocrine cells making up more than 30% of the tumor, has been identified. This unique entity has been referred to as mixed acinar-neuroendocrine carcinoma (MANEC). Only about 20 such cases have been reported in the literature. Case Report. We report an interesting case of MANEC with neuroendocrine cell predominance in a woman presenting with epigastric pain secondary to a pancreatic mass with acinar and endocrine differentiation. She underwent surgical resection of the tumor and was offered adjuvant treatment chemotherapy with carboplatin, etoposide, and radiotherapy for positive tumor resection margins. Conclusions. Given the paucity of the cases of MANEC, continuous reporting of these cases when identified should be encouraged to aid oncologists in understanding the disease and help establish standardized management. PMID:24348574

  18. Severe pancreas hypoplasia and multicystic renal dysplasia in two human fetuses carrying novel HNF1beta/MODY5 mutations.

    PubMed

    Haumaitre, Cécile; Fabre, Mélanie; Cormier, Sarah; Baumann, Clarisse; Delezoide, Anne-Lise; Cereghini, Silvia

    2006-08-01

    Heterozygous mutations in the HNF1beta/vHNF1/TCF2 gene cause maturity-onset diabetes of the young (MODY5), associated with severe renal disease and abnormal genital tract. Here, we characterize two fetuses, a 27-week male and a 31.5-week female, carrying novel mutations in exons 2 and 7 of HNF1beta, respectively. Although these mutations were predicted to have different functional consequences, both fetuses displayed highly similar phenotypes. They presented one of the most severe phenotypes described in HNF1beta carriers: bilateral enlarged polycystic kidneys, severe pancreas hypoplasia and abnormal genital tract. Consistent with this, we detected high levels of HNF1beta transcripts in 8-week human embryos in the mesonephros and metanephric kidney and in the epithelium of pancreas. Renal histology and immunohistochemistry analyses of mutant fetuses revealed cysts derived from all nephron segments with multilayered epithelia and dysplastic regions, accompanied by a marked increase in the expression of beta-catenin and E-cadherin. A significant proportion of cysts still expressed the cystic renal disease proteins, polycystin-1, polycystin-2, fibrocystin and uromodulin, implying that cyst formation may result from a deregulation of cell-cell adhesion and/or the Wnt/beta-catenin signaling pathway. Both fetuses exhibited a severe pancreatic hypoplasia with underdeveloped and disorganized acini, together with an absence of ventral pancreatic-derived tissue. beta-catenin and E-cadherin were strongly downregulated in the exocrine and endocrine compartments, and the islets lacked the transporter essential for glucose-sensing GLUT2, indicating a beta-cell maturation defect. This study provides evidence of differential gene-dosage requirements for HNF1beta in normal human kidney and pancreas differentiation and increases our understanding of the etiology of MODY5 disorder. PMID:16801329

  19. Karyotypic abnormalities in tumours of the pancreas.

    PubMed Central

    Bardi, G.; Johansson, B.; Pandis, N.; Mandahl, N.; Bak-Jensen, E.; Andrén-Sandberg, A.; Mitelman, F.; Heim, S.

    1993-01-01

    Short-term cultures from 20 pancreatic tumours, three endocrine and 17 exocrine, were cytogenetically analysed. All three endocrine tumours had a normal chromosome complement. Clonal chromosome aberrations were detected in 13 of the 17 exocrine tumours: simple karyotypic changes were found in five carcinomas and numerous numerical and/or structural changes in eight. When the present findings and those previously reported by our group were viewed in conjunction, the most common numerical imbalances among the 22 karyotypically abnormal pancreatic carcinomas thus available for evaluation turned out to be, in order of falling frequency, -18, -Y, +20, +7, +11 and -12. Imbalances brought about by structural changes most frequently affected chromosomes 1 (losses in 1p but especially gains of 1q), 8 (in particular 8q gains but also 8p losses), and 17 (mostly 17q gain but also loss of 17p). Chromosomal bands 1p32, 1q10, 6q21, 7p22, 8p21, 8q11, 14p11, 15q10-11, and 17q11 were the most common breakpoint sites affected by the structural rearrangements. Abnormal karyotypes were detected more frequently in poorly differentiated and anaplastic carcinomas than in moderately and well differentiated tumours. Images Figure 1 PMID:8494707

  20. Multipotent pancreas progenitors: Inconclusive but pivotal topic.

    PubMed

    Jiang, Fang-Xu; Morahan, Grant

    2015-12-26

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  1. Three-dimensional pancreas organogenesis models.

    PubMed

    Grapin-Botton, A

    2016-09-01

    A rediscovery of three-dimensional culture has led to the development of organ biogenesis, homeostasis and disease models applicable to human tissues. The so-called organoids that have recently flourished serve as valuable models bridging between cell lines or primary cells grown on the bottom of culture plates and experiments performed in vivo. Though not recapitulating all aspects of organ physiology, the miniature organs generated in a dish are useful models emerging for the pancreas, starting from embryonic progenitors, adult cells, tumour cells and stem cells. This review focusses on the currently available systems and their relevance to the study of the pancreas, of β-cells and of several pancreatic diseases including diabetes. We discuss the expected future developments for studying human pancreas development and function, for developing diabetes models and for producing therapeutic cells. PMID:27615129

  2. Intraductal Oncocytic Papillary Neoplasms of the Pancreas.

    PubMed

    Kallen, Michael E; Naini, Bita V

    2016-09-01

    Intraductal oncocytic papillary neoplasms (IOPNs) are cystic neoplasms with intraductal growth and complex papillae composed of oncocytic cells. IOPNs have been reported both in the pancreas and biliary tree, and are most likely closely related in these 2 locations. In the pancreas, these rare tumors are now considered 1 of the 4 histologic subtypes of intraductal papillary mucinous neoplasm (IPMN). Significant differences in histology, immunophenotype, and molecular genetics have been reported between IOPNs and other IPMN subtypes. However, there are limited data regarding the clinical behavior and prognosis of IOPNs in comparison to other subtypes of IPMN. We review features of pancreatic IOPNs and discuss the differential diagnosis of other intraductal lesions in the pancreas. PMID:27575268

  3. Multipotent pancreas progenitors: Inconclusive but pivotal topic

    PubMed Central

    Jiang, Fang-Xu; Morahan, Grant

    2015-01-01

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  4. Progenitor cells in the adult pancreas.

    PubMed

    Holland, Andrew M; Góñez, L Jorge; Harrison, Leonard C

    2004-01-01

    The beta-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or beta-cell progenitors and the molecular mechanisms underlying beta-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, beta-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of beta-cells. PMID:14737742

  5. Conservative Pancreas Graft Preservation at the Extreme.

    PubMed

    Laurence, Jerome Martin; Sapisochin, Gonzalo; Selzner, Markus; Norgate, Andrea; Kumar, Deepali; McGilvary, Ian D; Preig, Paul D; Schiff, Jeffrey; Cattral, Mark S

    2016-01-01

    Because of the value some patients place in remaining insulin-independent after pancreas transplantation, they may be reluctant to undergo graft pancreatectomy, even in the face of extreme complications, such as graft thrombosis and duodenal segment leak. Partly, for this reason, a variety of complex salvage techniques have been described to save the graft in such circumstances. We report a case of a series of extreme complications related to a leak from the duodenal segment after a simultaneous pancreas and kidney transplant. These included infected thrombosis of the inferior vena cava associated with a graft venous thrombosis and a retroperitoneal fistula. The patient retained graft function with insulin independence and repeatedly declined graft pancreatectomy against the advice of the transplant team. Conservative treatment with percutaneous drainage, antibiotics, and anticoagulation was eventually successful. This outcome is unique in our experience and may be instructive to teams caring for pancreas transplant recipients. PMID:27500244

  6. An Investigative Study of Pancreatic Exocrine Biomarkers, Histology, and Histomorphometry in Male Zucker Diabetic Fatty (ZDF) Rats Given Dulaglutide by Subcutaneous Injection Twice Weekly for 13 Weeks.

    PubMed

    Usborne, Amy; Byrd, Richard A; Meehan, James; Blackbourne, Jamie L; Sullivan, John; Poitout-Belissent, Florence; Prefontaine, Annick; Martin, Jennifer A; Vahle, John L

    2015-12-01

    Glucagon-like peptide-1 (GLP-1) receptor agonist therapy has been implicated as a possible risk factor for acute pancreatitis in patients with type 2 diabetes. Dulaglutide is a long-acting GLP-1 receptor agonist in development for treatment of type 2 diabetes. The effects of dulaglutide were evaluated in male Zucker diabetic fatty (ZDF) rats to examine whether dulaglutide may induce or modulate pancreatitis. Rats were randomized to dose groups receiving twice-weekly subcutaneously administered dulaglutide 0.5, 1.5, and 5.0 mg/kg/dose (corresponding human plasma exposures following twice-weekly dosing are 3-, 8-, and 30-fold, respectively) for 13 weeks or to vehicle control. Following termination, serially trimmed sections of pancreases were stained with hematoxylin and eosin or co-stained with an epithelial marker and a marker of either proliferation or apoptosis. Efficacious reductions in glucose and hemoglobin A1c occurred at all dulaglutide doses. Lipase activity was unaffected, and there were modest increases in total and pancreatic amylase activities at all doses without individual microscopic inflammatory correlates. Microscopic dulaglutide-related pancreatic changes included increased interlobular ductal epithelium without ductal cell proliferation (≥0.5 mg/kg), increased acinar atrophy with/without inflammation (≥1.5 mg/kg), and increased incidence/severity of neutrophilic acinar pancreatic inflammation (5.0 mg/kg). In summary, dulaglutide treatment was associated with mild alterations in ductal epithelium and modest exacerbation of spontaneous lesions of the exocrine pancreas typically found in the ZDF rat model. PMID:26269615

  7. Calcium-dependent photodynamic action of di- and tetrasulphonated aluminium phthalocyanine on normal and tumour-derived rat pancreatic exocrine cells.

    PubMed Central

    al-Laith, M.; Matthews, E. K.

    1994-01-01

    Important differences exist in the responses to photodynamic agents of normal and tumour-derived pancreatic acinar cells. In the present study amylase release has been used to assess the mechanisms by which the photodynamic drugs tetra- and disulphonated aluminium phthalocyanine (A1PcS4, A1PcS2) act on pancreatic cells via energy and calcium-dependent activation and transduction pathways. The photodynamic release of amylase was found to be energy dependent and inhibited by the chelation of free cytoplasmic calcium but not by the removal of extracellular calcium. In contrast to their effects on normal acinar cells, the photodynamic action of A1PcS4 and A1PcS2 was to inhibit amylase secretion from pancreatoma AR4-2J cells. Removal of extracellular calcium reversed this inhibitory effect on AR4-2J cells and produced a significant increase in amylase release, but chelation of free cytoplasmic calcium did not affect the inhibitory photodynamic action of the phthalocyanines on amylase release from the tumour cells. Overall, these results demonstrate further important distinctions between the photodynamic action of sulphonated aluminium phthalocyanines on normal versus tumour exocrine cells of the pancreas and indicate that calcium plays an important role in photodynamic drug action, since these agents affected intracellular calcium mobilisation at some distal point in the membrane signal transduction pathway for regulated secretion. Furthermore, the photodynamic inhibition of constitutive secretion in tumour cells may involve a calcium-dependent membrane target site or modulation of membrane calcium channels by activation of protein kinase C. PMID:7524603

  8. [Ectopic pancreas imitating gastric neoplasm -- a case report].

    PubMed

    Buczek, Tomasz; Puzdrowski, Witold; Lenekowski, Radosław; Kruszewski, Wiesław Janusz

    2013-01-01

    Ectopic pancreas is a rare developmental disorder. Usually is asymptomatic. Most frequently is diagnosed in its gastric location accidentally during endoscopy. A patient with ectopic pancreas was described manifesting as a gastric tumor arousing oncological concern. PMID:24455840

  9. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

    PubMed Central

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-01-01

    AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful. PMID:25561813

  10. Quantitative assessment of fat absorption and its diagnostic value in exocrine pancreatic insufficiency.

    PubMed

    Simpson, J W; Doxey, D L

    1983-09-01

    A new method of quantifying fat absorption based on the estimation of serum triglyceride levels is described. When long chain triglyceride (LCT) was fed to normal dogs a significant elevation of serum triglyceride concentration was recorded which was not observed in dogs with exocrine pancreatic insufficiency. When the test was repeated on the dogs with pancreatic insufficiency using the LCT together with lipase the serum triglyceride concentration increased, suggesting the failure in the initial test was caused by a deficiency in pancreatic lipase. Feeding medium chain triglyceride (MCT) did not raise the serum triglyceride levels in normal dogs. PMID:6635347