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Sample records for inherited pancreatic endocrine

  1. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management and controversies

    PubMed Central

    Jensen, Robert T.; Berna, Marc J.; Bingham, David B; Norton, Jeffrey A.

    2008-01-01

    Pancreatic endocrine tumors (PETs) can occur in as part of four inherited disorders including: Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis 1(NF-1) [von Recklinghausen’s disease] and the tuberous sclerosis complex (TSC). The relative frequency with which patients with these disorders develop PETs is MEN1>VHL>NF-1>TSC. Over the last few years there have been major advances in the understanding of the genetics and molecular pathogenesis of these disorders as well in the localization, medical and surgical treatment of the PETs in these patients. The study of the PETs in these disorders has not only provided insights into the possible pathogenesis of sporadic PETs, but have also presented a number of unique management and treatment issues, some of which are applicable to patients with sporadic PETs. Therefore the study of PETs in these uncommon disorders has provided valuable insights that in many cases are applicable to the general group of patients with sporadic PETs. In this article these areas are briefly reviewed as well as the current state of knowledge of the PETs in these disorders and the controversies that exist in their management are briefly summarized and discussed. PMID:18798544

  2. Pancreatic endocrine tumors: recent advances.

    PubMed

    Jensen, R T

    1999-01-01

    Pancreatic endocrine tumors (PET's) can be divided on a clinical and pathologic basis into ten classes [insulinomas, gastrinomas (Zollinger-Ellison syndrome), VIPomas (Verner-Morrison syndrome, WDHA, pancreatic cholera), glucagonomas, somatostatinomas, ACTH-releasing tumors (ACTHomas), growth hormone-releasing factor secreting tumors (GRFomas), nonfunctioning or pancreatic polypeptide secreting tumors (non-functioning PET), PET's causing carcinoid syndrome and PET's causing hypercalcemia)]. Recent reports suggest calcitonin-secreting PET's also rarely occur but whether they cause a distinct clinical syndrome is unclear. PET's resemble carcinoid tumors histologically; in their ability to synthesize and frequently secrete multiple peptides such as neuroendocrine cell markers (chromogranins); their biologic behavior and their tumor growth patterns. Both groups of tumors are highly vascular, have high densities of somatostatin receptors and similar tumor localization studies including somatostatin receptor scintigraphy are used for both. PET's, similar to carcinoids causing the carcinoid syndrome, require two separate treatment options be considered: treatment directed against the hormone-excess state and treatment directed against the tumor per se because of their malignant nature. In the last few years there have been advances in tumor diagnosis, localization methods, treatment approaches particularly related to the use of synthetic somatostatin analogues, and the definition of the role of surgical procedures in these diseases. Important other advances include insights into the long-term natural history of PET's particularly from studies of gastrinomas, which allow prognostic factors to be identified and the timing of treatment options to better planned, as well as insights into the molecular basis of these disorders. The latter includes both a description of the molecular basis of the genetic inherited syndromes associated with PET's or carcinoid tumors, as well as

  3. Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

    PubMed

    Skinner, Michael K

    2014-12-01

    Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease.

  4. Endocrine Disruptor Induction of Epigenetic Transgenerational Inheritance of Disease

    PubMed Central

    Skinner, Michael K.

    2014-01-01

    Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. PMID:25088466

  5. Endocrine disruptor induction of epigenetic transgenerational inheritance of disease.

    PubMed

    Skinner, Michael K

    2014-12-01

    Environmental exposures such as toxicants, nutrition and stress have been shown to promote the epigenetic transgenerational inheritance of disease susceptibility. Endocrine disruptors are one of the largest groups of specific toxicants shown to promote this form of epigenetic inheritance. These environmental compounds that interfere with normal endocrine signaling are one of the largest classes of toxicants we are exposed to on a daily level. The ability of ancestral exposures to promote disease susceptibility significantly increases the potential biohazards of these toxicants. Therefore, what your great-grandmother was exposed to during pregnancy may influence your disease development, even in the absence of any exposure, and you are going to pass this on to your grandchildren. This non-genetic form of inheritance significantly impacts our understanding of biology from the origins of disease to evolutionary biology. The current review will describe the previous studies and endocrine disruptors shown to promote the epigenetic transgenerational inheritance of disease. PMID:25088466

  6. Minireview: transgenerational epigenetic inheritance: focus on endocrine disrupting compounds.

    PubMed

    Rissman, Emilie F; Adli, Mazhar

    2014-08-01

    The idea that what we eat, feel, and experience influences our physical and mental state and can be transmitted to our offspring and even to subsequent generations has been in the popular realm for a long time. In addition to classic gene mutations, we now recognize that some mechanisms for inheritance do not require changes in DNA. The field of epigenetics has provided a new appreciation for the variety of ways biological traits can be transmitted to subsequent generations. Thus, transgenerational epigenetic inheritance has emerged as a new area of research. We have four goals for this minireview. First, we describe the topic and some of the nomenclature used in the literature. Second, we explain the major epigenetic mechanisms implicated in transgenerational inheritance. Next, we examine some of the best examples of transgenerational epigenetic inheritance, with an emphasis on those produced by exposing the parental generation to endocrine-disrupting compounds (EDCs). Finally, we discuss how whole-genome profiling approaches can be used to identify aberrant epigenomic features and gain insight into the mechanism of EDC-mediated transgenerational epigenetic inheritance. Our goal is to educate readers about the range of possible epigenetic mechanisms that exist and encourage researchers to think broadly and apply multiple genomic and epigenomic technologies to their work.

  7. The Role of ARX in Human Pancreatic Endocrine Specification.

    PubMed

    Gage, Blair K; Asadi, Ali; Baker, Robert K; Webber, Travis D; Wang, Rennian; Itoh, Masayuki; Hayashi, Masaharu; Miyata, Rie; Akashi, Takumi; Kieffer, Timothy J

    2015-01-01

    The in vitro differentiation of human embryonic stem cells (hESCs) offers a model system to explore human development. Humans with mutations in the transcription factor Aristaless Related Homeobox (ARX) often suffer from the syndrome X-linked lissencephaly with ambiguous genitalia (XLAG), affecting many cell types including those of the pancreas. Indeed, XLAG pancreatic islets lack glucagon and pancreatic polypeptide-positive cells but retain somatostatin, insulin, and ghrelin-positive cells. To further examine the role of ARX in human pancreatic endocrine development, we utilized genomic editing in hESCs to generate deletions in ARX. ARX knockout hESCs retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. ARX knockout somatostatin-positive cells shared expression patterns with human fetal and adult δ-cells. Differentiated ARX knockout cells upregulated PAX4, NKX2.2, ISL1, HHEX, PCSK1, PCSK2 expression while downregulating PAX6 and IRX2. Re-expression of ARX in ARX knockout pancreatic progenitors reduced HHEX and increased PAX6 and insulin expression following differentiation. Taken together these data suggest that ARX plays a key role in pancreatic endocrine fate specification of pancreatic polypeptide, somatostatin, glucagon and insulin positive cells from hESCs. PMID:26633894

  8. A differential diagnosis of inherited endocrine tumors and their tumor counterparts

    PubMed Central

    Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

    2013-01-01

    Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

  9. Transcriptional control of pancreatic endocrine cell development.

    PubMed

    Gasa, Rosa

    2005-11-01

    In diabetes mellitus, insulin-producing beta cells in the pancreas are lost (type 1) or dysfunctional (type 2). Cell replacement therapy has emerged as a promising alternative to insulin injection for treatment of diabetic patients. Given the scarcity and difficulty in obtaining pancreatic beta cells from cadaveric donors, current research is aiming at the generation of functional beta cells from non-beta-cell sources or from pluripotent progenitors such as adult or embryonic stem cells. However, to achieve this, we first need to understand how beta cells are formed during normal development. Knowledge of the molecular and genetic pathways that direct cells along their differentiation pathway will be instrumental if we aim to engineer new beta cells for clinical use. This article reviews pancreatic development from a gene expression point of view and discusses our current understanding of the transcription factors that rule pancreatic morphogenesis during ontogeny.

  10. Demographics, epidemiology, and inheritance of pancreatic ductal adenocarcinoma.

    PubMed

    Yeo, Theresa Pluth

    2015-02-01

    Pancreatic cancer (PC) will affect 48,960 persons in the United States and will result in 40,560 deaths in 2015, according to the American Cancer Society. On a global basis, at least 337,000 persons will be diagnosed with PC. The incidence of PC has increased slightly in the United States, though worldwide cases are likely to increase substantially due to the influence of cigarette smoking, rising obesity and type II diabetes. The development of PC is related to a state of chronic inflammation and insulin resistance. Well-established environmental and personal risk factors for PC include advancing age, cigarette smoking, second-hand tobacco smoke exposure, obesity, inherited familial cancer syndromes, Ashkenazi Jewish heritage, chronic pancreatitis, dietary factors, and diabetes. Other identified associations are human immunodeficiency virus infection, ABO blood group polymorphisms, hepatitis B virus, and Helicobacter pylori.

  11. Demographics, epidemiology, and inheritance of pancreatic ductal adenocarcinoma.

    PubMed

    Yeo, Theresa Pluth

    2015-02-01

    Pancreatic cancer (PC) will affect 48,960 persons in the United States and will result in 40,560 deaths in 2015, according to the American Cancer Society. On a global basis, at least 337,000 persons will be diagnosed with PC. The incidence of PC has increased slightly in the United States, though worldwide cases are likely to increase substantially due to the influence of cigarette smoking, rising obesity and type II diabetes. The development of PC is related to a state of chronic inflammation and insulin resistance. Well-established environmental and personal risk factors for PC include advancing age, cigarette smoking, second-hand tobacco smoke exposure, obesity, inherited familial cancer syndromes, Ashkenazi Jewish heritage, chronic pancreatitis, dietary factors, and diabetes. Other identified associations are human immunodeficiency virus infection, ABO blood group polymorphisms, hepatitis B virus, and Helicobacter pylori. PMID:25726048

  12. REST represses a subset of the pancreatic endocrine differentiation program.

    PubMed

    Martin, David; Kim, Yung-Hae; Sever, Dror; Mao, Chai-An; Haefliger, Jacques-Antoine; Grapin-Botton, Anne

    2015-09-15

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3(+) progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1(+) progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program. PMID:26156633

  13. REST represses a subset of the pancreatic endocrine differentiation program

    PubMed Central

    Martin, David; Kim, Yung-Hae; Sever, Dror; Mao, Chai-An; Haefiiger, Jacques-Antoine; Grapin-Botton, Anne

    2016-01-01

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1+ progenitors impairs the differentiation of endocrine-committed Neurog3+ progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1+ progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program. PMID:26156633

  14. REST represses a subset of the pancreatic endocrine differentiation program.

    PubMed

    Martin, David; Kim, Yung-Hae; Sever, Dror; Mao, Chai-An; Haefliger, Jacques-Antoine; Grapin-Botton, Anne

    2015-09-15

    To contribute to devise successful beta-cell differentiation strategies for the cure of Type 1 diabetes we sought to uncover barriers that restrict endocrine fate acquisition by studying the role of the transcriptional repressor REST in the developing pancreas. Rest expression is prevented in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3(+) progenitors, decreases beta and alpha cell mass by E18.5, and triggers diabetes in adulthood. Conditional inactivation of Rest in Pdx1(+) progenitors is not sufficient to trigger endocrine differentiation but up-regulates a subset of differentiation genes. Our results show that the transcriptional repressor REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program.

  15. IMPAN cells: a pancreatic model for differentiation into endocrine cells.

    PubMed

    Klein, T; Frandsen, U; Heller, R S; Serup, P

    2001-11-15

    It is currently believed that pancreatic progenitor or stem cells exist in the ductal cell population and that these cells have the ability to be grown and differentiated into endocrine cells for the treatment of diabetes. In this study, we have examined this potential in IMPAN (Immortalized Pancreatic) cells. These cells are derived from the adult H-2K(b)-tsA58 transgenic mouse. We observed an increased mRNA expression of insulin, proendocrine gene neurogenin 3, and beta-cell transcription factor Pdx1 when the cells were grown on bovine collagen I gels. The induction profile of these three genes was similar under the tested conditions. No glucagon or other endocrine-specific transcription factors were detectable. Application of GIP, GLP-1 derivative NN2211, and activin-A/betacellulin to IMPAN cells in normal culture did not lead to endocrine differentiation. In conclusion, it appears that the ability of IMPAN cells to mature to endocrine cells is limited. PMID:11697865

  16. In vivo imaging of pancreatic endocrine islets

    NASA Astrophysics Data System (ADS)

    Villiger, Martin; Goulley, Joan; Pache, Christophe; Friedrich, Michael; Grapin-Botton, Anne; Meda, Paolo; Leitgeb, Rainer; Lasser, Theo

    2009-07-01

    Extended focus optical coherence microscope (xfOCM) circumvents the compromise between lateral resolution and depth of field by us of a Bessel-like illumination beam. The high sensitivity and parallel depth profiling of Fourier domain optical coherence tomography are preserved, and combined with high isotropic resolution of 1.5 - 2 μm. To comply with the requirements for in vivo measurements, beam scanning had to be implemented. We then performed measurements, first of excised pancreas, validated by standard immunohistochemistry, to investigate the structures that can be observed. For a quantitative analysis, a semi-automatic islet detection algorithm evaluated the islet size, position, contrast and homogeneity. The influence of streptozotocin on the signature of the islets was investigated in a next step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo, visualizing pancreatic lobules, ducts, blood vessels and individual islets of Langerhans.

  17. Fundamental differences in the neural invasion behavior of pancreatic endocrine tumors: relevance for local recurrence rates?

    PubMed

    Bergmann, Frank; Ceyhan, Güralp O; Rieker, Ralf J; Esposito, Irene; Fischer, Lars; Herpel, Esther; Friess, Helmut; Schirmacher, Peter; Kern, Michael A

    2009-01-01

    Neural invasion represents an important prognostic factor in pancreatic cancer, and it is thought to be one of the main causes for the high rate of postoperative local recurrences in pancreatic ductal adenocarcinomas. In contrast to the latter, systematic investigations of the mode and extent of neural invasion in pancreatic endocrine tumors have not yet been carried out, although this process represents an important feature in the classification of these tumors. In the present study, a total of 48 pancreatic endocrine tumors were analyzed including 10 well-differentiated endocrine tumors of uncertain behavior, 33 well-differentiated endocrine carcinomas, and 5 poorly differentiated endocrine carcinomas. Neural invasion was found in a large subset (73%) of pancreatic endocrine tumors. The frequency of neural invasion correlated with the grade of malignancy but occurred irrespective of functional activity, hormone phenotype, or histomorphology. Analogous to pancreatic ductal adenocarcinoma, the expression of epidermal growth factor receptor and nerve growth factor, which were expressed in 50% and 100% of the tumors, respectively, seemed to be associated with the frequency of neural invasion. However, in contrast to pancreatic ductal adenocarcinoma, neural invasion in pancreatic endocrine tumors was only detected within the tumor boundaries and did not reach beyond the tumor invasion front. This phenomenon may explain the low rate of local relapses after tumor resection in pancreatic endocrine tumors despite the high frequency of neural invasion.

  18. Endocrine manifestations related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

  19. Immunohistochemical localization of polypeptide hormones in pancreatic endocrine cells of a dipnoan fish, Protopterus aethiopicus.

    PubMed

    Scheuermann, D W; Adriaensen, D; Timmermans, J P; De Groodt-Lasseel, M H

    1991-01-01

    Light microscopical immunohistochemistry was used to demonstrate the regulatory peptides present in the endocrine pancreas of Protopterus aethiopicus. The peptides studied included insulin, glucagon, pancreatic polypeptide and somatostatin. The results showed that the 4 regulatory peptides commonly detected in the mammalian endocrine pancreas were immunologically discernible in this dipnoan fish. Large amounts of insulin-immunoreactive cells, in the centre of the pancreatic islets, were surrounded by a small rim of glucagon-or pancreatic polypeptide-immunoreactive cells. In addition, adjacent sections stained with anti-glucagon and anti-pancreatic polypeptide revealed that these hormones could be found in the same cells. Somatostatin-positive cells were scattered throughout the islets. Their processes were seen to contact many different endocrine pancreatic cells, suggesting that the somatostatin-immunoreactive cells control the functions of other endocrine pancreatic cells. PMID:1687100

  20. Pancreatic exocrine and endocrine function after subtotal pancreatectomy for nesidioblastosis.

    PubMed

    Dunger, D B; Burns, C; Ghale, G K; Muller, D P; Spitz, L; Grant, D B

    1988-02-01

    Pancreatic exocrine and endocrine function was assessed in seven patients 1 to 2 years after 95% pancreatectomy (group A) and three patients 9 to 11 years after 75% pancreatectomy (group B). In all cases surgery was undertaken for the treatment of hyperinsulinism and the histologic diagnosis was nesidioblastosis. The activities of pancreatic enzymes and bicarbonate concentrations were generally normal in group B, but were reduced in approximately half the children in group A. One child in group A had significant exocrine failure and poor weight gain. Blood glucose levels and fasting insulin levels were normal during a standard glucose tolerance test in all of the group B patients. One had a low fasting blood glucose level. In the group A patients three had low fasting glucose levels and one a frankly diabetic glucose tolerance test. C peptide and insulin levels were comparable but inappropriate insulin levels were noted in one patient, suggesting that the control of glucose-stimulated insulin release may remain abnormal. The results suggest that pancreatic function is not seriously impaired in the majority of patients 1 to 2 years after 95% pancreatectomy and that it is comparable to that noted in 75% pancreatectomy patients followed over a longer period of time.

  1. sept7b is required for the differentiation of pancreatic endocrine progenitors

    PubMed Central

    Dash, Surjya Narayan; Hakonen, Elina; Ustinov, Jarkko; Otonkoski, Timo; Andersson, Olov; Lehtonen, Sanna

    2016-01-01

    Protection or restoration of pancreatic β-cell mass as a therapeutic treatment for type 1 diabetes requires understanding of the mechanisms that drive the specification and development of pancreatic endocrine cells. Septins are filamentous small GTPases that function in the regulation of cell division, cytoskeletal organization and membrane remodeling, and are involved in various tissue-specific developmental processes. However, their role in pancreatic endocrine cell differentiation remains unknown. Here we show by functional manipulation techniques in transgenic zebrafish lines that suppression of sept7b, the zebrafish ortholog of human SEPT7, profoundly increases the number of endocrine progenitors but limits their differentiation, leading to reduction in β- and α-cell mass. Furthermore, we discovered that shh (sonic hedgehog) expression in the endoderm, essential for the development of pancreatic progenitors of the dorsal pancreatic bud, is absent in larvae depleted of sept7b. We also discovered that sept7b is important for the differentiation of ventral pancreatic bud-derived cells: sept7b-depleted larvae exhibit downregulation of Notch receptors notch1a and notch1b and show precocious differentiation of NeuroD-positive endocrine cells in the intrapancreatic duct and gut epithelium. Collectively, this study provides a novel insight into the development of pancreatic endocrine progenitors, revealing an essential role for sept7b in endocrine progenitor differentiation. PMID:27114183

  2. Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration

    PubMed Central

    Manfroid, Isabelle; Ghaye, Aurelie; Naye, François; Detry, Nathalie; Palm, Sarah; Pan, Luyuan; Ma, Taylur P.; Huang, Wei; Rovira, Meritxell; Martial, Joseph A.; Parsons, Michael J.; Moens, Cecilia B.; Voz, Marianne L.; Peers, Bernard

    2012-01-01

    Recent zebrafish studies have shown that the late appearing pancreatic endocrine cells derive from pancreatic ducts but the regulatory factors involved are still largely unknown. Here, we show that the zebrafish sox9b gene is expressed in pancreatic ducts where it labels the pancreatic Notch-responsive cells previously shown to be progenitors. Inactivation of sox9b disturbs duct formation and impairs regeneration of beta cells from these ducts in larvae. sox9b expression in the midtrunk endoderm appears at the junction of the hepatic and ventral pancreatic buds and, by the end of embryogenesis, labels the hepatopancreatic ductal system as well as the intrapancreatic and intrahepatic ducts. Ductal morphogenesis and differentiation are specifically disrupted in sox9b mutants, with the dysmorphic hepatopancreatic ducts containing misdifferentiated hepatocyte-like and pancreatic-like cells. We also show that maintenance of sox9b expression in the extrapancreatic and intrapancreatic ducts requires FGF and Notch activity, respectively, both pathways known to prevent excessive endocrine differentiation in these ducts. Furthermore, beta cell recovery after specific ablation is severely compromised in sox9b mutant larvae. Our data position sox9b as a key player in the generation of secondary endocrine cells deriving from pancreatic ducts in zebrafish. PMID:22537488

  3. Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

    PubMed Central

    Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

    2013-01-01

    Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

  4. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation.

    PubMed

    Valdez, Ivan Achel; Dirice, Ercument; Gupta, Manoj K; Shirakawa, Jun; Teo, Adrian Kee Keong; Kulkarni, Rohit N

    2016-04-19

    A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity-the ability of pancreatic cells to undergo cellular interconversions-a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD) mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT) as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration. PMID:27068459

  5. Effect of octreotide acetate on pancreatic exocrine and endocrine functions after pancreatoduodenal resection.

    PubMed

    Petrin, P; Antoniutti, M; Zaramella, D; Da Lio, C; Basso, D; Plebani, M; Panozzo, M P; Costantino, V; Pedrazzoli, S

    1995-01-01

    In view of forecasting the effect of octreotide acetate (Sandostatin) in preventing fistula formation after pancreatic surgery, 9 patients, who had pancreatoduodenectomy 8-12 days before, underwent a 2-day study. The first day, by means of a catheter located in the jejunal loop separately anastomosed to the pancreatic remnant, basal and after secretin stimulation pancreatic secretion was evaluated. During the 2nd day the possible inhibitory effect of octreotide on basal and stimulated secretion was investigated. Under the experimental conditions of the study Sandostatin showed little effect on the water and bicarbonate increase as stimulated by secretin. A greater hormone inhibitory effect on amylase production and pancreatic endocrine function was seen. On the basis of these results the use of Sandostatin can hardly be seen as useful in preventing fistula formation after pancreatic resection.

  6. Multiple, temporal-specific roles for HNF6 in pancreatic endocrine and ductal differentiation

    PubMed Central

    Zhang, Hongjie; Ables, Elizabeth Tweedie; Pope, Christine F.; Washington, M. Kay; Hipkens, Susan; Means, Anna L.; Path, Gunter; Costa, Robert H.; Seufert, Jochen; Leiter, Andrew B.; Magnuson, Mark A.; Gannon, Maureen

    2009-01-01

    Within the developing pancreas Hepatic Nuclear Factor 6 (HNF6) directly activates the pro-endocrine transcription factor, Ngn3. HNF6 and Ngn3 are each essential for endocrine differentiation and HNF6 is also required for embryonic duct development. Most HNF6−/− animals die as neonates, making it difficult to study later aspects of HNF6 function. Here, we describe, using conditional gene inactivation, that HNF6 has specific functions at different developmental stages in different pancreatic lineages. Loss of HNF6 from Ngn3-expressing cells (HNF6Δendo) resulted in fewer multipotent progenitor cells entering the endocrine lineage, but had no effect on β cell terminal differentiation. Early, pancreas-wide HNF6 inactivation (HNF6Δpanc) resulted in endocrine and ductal defects similar to those described for HNF6 global inactivation. However, all HNF6Δpanc animals survived to adulthood. HNF6Δpanc pancreata displayed increased ductal cell proliferation and metaplasia, as well as characteristics of pancreatitis, including up-regulation of CTGF, MMP7, and p8/Nupr1. Pancreatitis was most likely caused by defects in ductal primary cilia. In addition, expression of Prox1, a known regulator of pancreas development, was decreased in HNF6Δpanc pancreata. These data confirm that HNF6 has both early and late functions in the developing pancreas and is essential for maintenance of Ngn3 expression and proper pancreatic duct morphology. PMID:19766716

  7. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes.

    PubMed

    Pasini, B; Stratakis, C A

    2009-07-01

    A genetic predisposition for paragangliomas and adrenal or extra-adrenal phaeochromocytomas was recognized years ago. Beside the well-known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel 'paraganglioma-phaeochromocytoma syndrome' caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest-derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent-of-origin effect for SDHD mutations. Life-time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation. PMID:19522823

  8. Dimethyl Fumarate Protects Pancreatic Islet Cells and Non-Endocrine Tissue in L-Arginine-Induced Chronic Pancreatitis

    PubMed Central

    Robles, Lourdes; Vaziri, Nosratola D.; Li, Shiri; Masuda, Yuichi; Takasu, Chie; Takasu, Mizuki; Vo, Kelly; Farzaneh, Seyed H.; Stamos, Michael J.; Ichii, Hirohito

    2014-01-01

    Background Chronic pancreatitis (CP) is a progressive disorder resulting in the destruction and fibrosis of the pancreatic parenchyma which ultimately leads to impairment of the endocrine and exocrine functions. Dimethyl Fumarate (DMF) was recently approved by FDA for treatment of patients with multiple sclerosis. DMF's unique anti-oxidant and anti-inflammatory properties make it an interesting drug to test on other inflammatory conditions. This study was undertaken to determine the effects of DMF on islet cells and non-endocrine tissue in a rodent model of L-Arginine-induced CP. Methods Male Wistar rats fed daily DMF (25 mg/kg) or vehicle by oral gavage were given 5 IP injections of L-Arginine (250 mg/100 g×2, 1 hr apart). Rats were assessed with weights and intra-peritoneal glucose tolerance tests (IPGTT, 2 g/kg). Islets were isolated and assessed for islet mass and viability with flow cytometry. Non-endocrine tissue was assessed for histology, myeloperoxidase (MPO), and lipid peroxidation level (MDA). In vitro assessments included determination of heme oxygenase (HO-1) protein expression by Western blot. Results Weight gain was significantly reduced in untreated CP group at 6 weeks. IPGTT revealed significant impairment in untreated CP group and its restoration with DMF therapy (P <0.05). Untreated CP rats had pancreatic atrophy, severe acinar architectural damage, edema, and fatty infiltration as well as elevated MDA and MPO levels, which were significantly improved by DMF treatment. After islet isolation, the volume of non-endocrine tissue was significantly smaller in untreated CP group. Although islet counts were similar in the two groups, islet viability was significantly reduced in untreated CP group and improved with DMF treatment. In vitro incubation of human pancreatic tissue with DMF significantly increased HO-1 expression. Conclusion Administration of DMF attenuated L-Arginine-induced CP and islet function in rats. DMF treatment could be a possible

  9. Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window

    PubMed Central

    Cras-Méneur, Corentin; Li, Lin; Kopan, Raphael; Permutt, M. Alan

    2009-01-01

    Canonical Notch signaling is thought to control the endocrine/exocrine decision in early pancreatic progenitors. Later, RBP-Jκ interacts with Ptf1a and E12 to promote acinar differentiation. To examine the involvement of Notch signaling in selecting specific endocrine lineages, we deregulated this pathway by targeted deletion of presenilin1 and presenilin2, the catalytic core of γ-secretase, in Ngn3- or Pax6-expressing endocrine progenitors. Surprisingly, whereas Pax6+ progenitors were irreversibly committed to the endocrine fate, we discovered that Ngn3+ progenitors were bipotential in vivo and in vitro. When presenilin amounts are limiting, Ngn3+ progenitors default to an acinar fate; subsequently, they expand rapidly to form the bulk of the exocrine pancreas. γ-Secretase inhibitors confirmed that enzymatic activity was required to block acinar fate selection by Ngn3 progenitors. Genetic interactions identified Notch2 as the substrate, and suggest that γ-secretase and Notch2 act in a noncanonical titration mechanism to sequester RBP-Jκ away from Ptf1a, thus securing selection of the endocrine fate by Ngn3 progenitors. These results revise the current view of pancreatic cell fate hierarchy, establish that Ngn3 is not in itself sufficient to commit cells to the endocrine fate in the presence of Ptf1a, reveal a noncanonical action for Notch2 protein in endocrine cell fate selection, and demonstrate that acquisition of an endocrine fate by Ngn3+ progenitors is γ-secretase-dependent until Pax6 expression begins. PMID:19723764

  10. Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis.

    PubMed

    Ludvigsen, Eva

    2007-01-01

    Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of

  11. β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.

    PubMed

    Abdellatif, Ahmed M; Oishi, Hisashi; Itagaki, Takahiro; Jung, Yunshin; Shawki, Hossam H; Okita, Yukari; Hasegawa, Yoshikazu; Suzuki, Hiroyuki; El-Morsy, Salah E; El-Sayed, Mesbah A; Shoaib, Mahmoud B; Sugiyama, Fumihiro; Takahashi, Satoru

    2016-01-01

    The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas. PMID:26901059

  12. β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development

    PubMed Central

    Abdellatif, Ahmed M.; Oishi, Hisashi; Itagaki, Takahiro; Jung, Yunshin; Shawki, Hossam H.; Okita, Yukari; Hasegawa, Yoshikazu; Suzuki, Hiroyuki; El-Morsy, Salah E.; El-Sayed, Mesbah A.; Shoaib, Mahmoud B.; Sugiyama, Fumihiro; Takahashi, Satoru

    2016-01-01

    The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas. PMID:26901059

  13. Prognostic markers in smear preparations for pancreatic endocrine neoplasms: A cytomorphologic study and statistical analysis of 20 potential prognostic features

    PubMed Central

    Layfield, Lester J.; Schmidt, Robert L.; Campbell, Jack; Esebua, Magda

    2016-01-01

    Background: Papanicolaou Society of Cytopathology guidelines place low- and intermediate-grade pancreatic endocrine tumors into the “neoplastic, other” category whereas high-grade pancreatic endocrine tumors are placed in the “malignant” category. No attempt was made to stratify pancreatic endocrine tumors in the “neoplastic, other” category by likelihood for metastases. Histologically, pancreatic endocrine tumors are divided into well, intermediate, and poorly differentiated examples based on mitotic count and Ki-67 proliferation index (PI). PI has been used in the evaluation of cytologic specimens utilizing cell block material. Unfortunately, cell block material may not always be available for analysis, and little data exists as to cytomorphologic features in smear preparations which might distinguish between low- and intermediate-grade endocrine neoplasms and predict metastases. Methods: We studied 36 cases of Diff-Quik stained smear preparations for 20 morphologic features to determine which best-classified cases into poor and not poor outcome categories. Hierarchical logistic regression analysis was used to determine associations between the morphologic features and outcomes. Results: Absolute agreement between raters ranged from 51% to 97% across the 20 morphologic features. About 12 of the 20 morphologic features showed statistically significant associations with poor outcome. Mitoses, irregular nuclear membranes, and 3-fold variation in nuclear size are the best discriminators between poor and not poor outcomes. Conclusions: A scoring system was developed utilizing mitoses, irregular nuclear membranes, and 3-fold variation in nuclear size to divide smears of pancreatic endocrine tumors into poor and not poor outcome groups. The scoring system achieved 84% accuracy in separating cases into poor and not poor outcomes.

  14. Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests.

    PubMed

    Cavallini, G; Bovo, P; Zamboni, M; Bosello, O; Filippini, M; Riela, A; Brocco, G; Rossi, L; Pelle, C; Chiavenato, A

    1992-01-01

    Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

  15. Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

    PubMed

    Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

    2013-11-19

    Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

  16. Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

    PubMed Central

    Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

    2013-01-01

    Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001 PMID:24252877

  17. Pituitary prolactinoma, pancreatic glucagonomas, and aldosterone-producing adrenal cortical adenoma: a suggested variant of multiple endocrine neoplasia type I.

    PubMed

    Gould, E; Albores-Saavedra, J; Shuman, J

    1987-12-01

    A case of a pituitary prolactinoma, pancreatic glucagonoma, and an aldosterone-producing adrenal cortical adenoma coexisting in a 65-year-old man is reported. This case may represent a sporadic variant of the multiple endocrine neoplasia syndrome type I first manifested by hyperaldosteronism.

  18. Concomitant pancreatic endocrine neoplasm and intraductal papillary mucinous neoplasm: a case report and literature review.

    PubMed

    Kadota, Yoshie; Shinoda, Masahiro; Tanabe, Minoru; Tsujikawa, Hanako; Ueno, Akihisa; Masugi, Yohei; Oshima, Go; Nishiyama, Ryo; Tanaka, Masayuki; Mihara, Kisho; Abe, Yuta; Yagi, Hiroshi; Kitago, Minoru; Itano, Osamu; Kawachi, Shigeyuki; Aiura, Koichi; Tanimoto, Akihiro; Sakamaoto, Michiie; Kitagawa, Yuko

    2013-03-21

    We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.

  19. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2013-01-01

    Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP) at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries) were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR) in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  20. Prognostic Significance of p27, Ki-67, and Topoisomerase lla Expression in Clinically Nonfunctioning Pancreatic Endocrine Tumors.

    PubMed

    Chang, Hee Jin; Batts, Kenneth P.; Lloyd, Ricardo V.; Sebo, Thomas J.; Thompson, Geoffrey B.; Lohse, Christine M.; Pankratz, Shane V.

    2000-01-01

    Nonfunctioning islet cell tumors or pancreatic endocrine tumors are the most common type of malignant islet cell tumor. Although previously detected usually at an advanced stage because of mass effect, the early detection rate of small localized disease has been increasing. To date it has been difficult to predict the clinical behavior in localized regional nonfunctioning tumors. To investigate potential markers predicting malignancy and poor prognosis in nonfunctioning pancreatic endocrine tumors, we analyzed the expression of Ki-67, topoisomerase Ila (Topolla), and p27, as well as a variety of clinicopathologic parameters in 76 cases of nonfunctioning islet cell tumors (23 benign cases and 53 malignant cases). Ki-67, Topolla. and p27 labeling indices were significantly different between benign and malignant tumors. Expression of Ki-67, Topolla, and p27 were associated with survival in patients with a malignant tumor in a univariate setting. However, only p27 and Topolla were jointly associated with survival in multivariate analysis. Immunohistochemical staining for p27, Topolla, and Ki-67 can be helpful in the diagnosis of nonfunctioning pancreatic endocrine tumor. Analysis of p27 and Topolla may also have potential utility as prognostic factors for malignant tumors.

  1. Parental effects of endocrine disrupting compounds in aquatic wildlife: Is there evidence of transgenerational inheritance?

    PubMed

    Schwindt, Adam R

    2015-08-01

    The effects of endocrine disrupting compounds (EDCs) on aquatic wildlife are increasingly being recognized for their complexity. Investigators have detected alterations at multiple levels of biological organization in offspring exposed to EDCs through the blood or germ line of the parents, suggesting that generational consequences of EDCs are evident. Exposure to EDCs through the parents is concerning because if the resulting phenotype of the offspring is heritable and affects fitness, then evolutionary consequences may be evident. This review summarizes the evidence for transgenerational effects of EDCs in aquatic wildlife and illustrates cases where alterations appear to be transmitted maternally, paternally, or parentally. The literature indicates that EDC exposure to the parents induces developmental, physiological, endocrinological, and behavioral changes as well as increased mortality of offspring raised in clean environments. What is lacking, however, is a clear demonstration of heritable transgenerational effects in aquatic wildlife. Therefore, it is not known if the parental effects are the result of developmental or phenotypic plasticity or if the altered phenotypes are durably passed to subsequent generations. Epigenetic changes to gene regulation are discussed as a possible mechanism responsible for EDC induced parental effects. Additional research is needed to evaluate if heritable effects of EDCs are evident in aquatic wildlife, as has been demonstrated for terrestrial mammals.

  2. Ductulo-insular pancreatic endocrine tumor with amyloid deposition: report of a case.

    PubMed

    Shintaku, Masayuki; Tado, Hiroki; Inayama, Kumiko; Murakami, Takaaki; Suzuki, Takahisa

    2015-04-01

    We report a case of ductulo-insular pancreatic endocrine tumor (DI-PET) in a 50-year-old woman. The patient presented with symptoms and signs of hypoglycemia, and a small tumor in the uncus of the pancreas was extirpated. The tumor predominantly consisted of a neuroendocrine tumor (NET) of grade 2, which surrounded a minor component of ductular proliferation accompanied by a desmoplastic stroma. Both components were largely juxtaposed but admixed with each other in small areas. The NET component was immunoreactive for insulin and accompanied by the marked deposition of amyloid in the stroma. The ductular component consisted of a haphazard proliferation of ductules showing mildly atypical cytological features and immunoreactivities for cytokeratins 7 and 19. DI-PET is a rare composite neoplasm that should be distinguished from mixed ductal-neuroendocrine carcinoma because of the marked differences in treatment modalities and prognoses between the tumors. DI-PET associated with stromal amyloid deposition has not been reported to date. The 'transdifferentiation' of NET cells into ductular cells is considered as the most plausible histogenetic mechanism of this tumor, although other possibilities, such as an origin from a primitive endodermal stem cell or the induction of ductular proliferation by stimulation with NET-derived humoral factors, cannot be excluded. PMID:25684418

  3. The Mechanism of Environmental Endocrine Disruptors (DEHP) Induces Epigenetic Transgenerational Inheritance of Cryptorchidism.

    PubMed

    Chen, Jinjun; Wu, Shengde; Wen, Sheng; Shen, Lianju; Peng, Jinpu; Yan, Chao; Cao, Xining; Zhou, Yue; Long, Chunlan; Lin, Tao; He, Dawei; Hua, Yi; Wei, Guanghui

    2015-01-01

    Discussion on the role of DEHP in the critical period of gonadal development in pregnant rats (F0), studied the evolution of F1-F4 generation of inter-generational inheritance of cryptorchidism and the alteration of DNA methylation levels in testis. Pregnant SD rats were randomly divided into two groups: normal control group and DEHP experimental group. From pregnancy 7 d to 19 d, experimental group was sustained to gavage DEHP 750 mg/kg bw/day, observed the incidence of cryptorchidism in offspring and examined the pregnancy rate of female rats through mating experiments. Continuous recording the rat's weight and AGD value, after maturation (PND80) recording testis and epididymis' size and weight, detected the sperm number and quality. Subsequently, we examined the evolution morphological changes of testicular tissue for 4 generation rats by HE staining and Western Blot. Completed the MeDIP-sequencing analysis of 6 samples (F1 generation, F4 generation and Control). DEHP successfully induced cryptorchidism occurrence in offspring during pregnancy. The incidence of cryptorchidism in F1 was 30%, in F2 was 12.5%, and there was no cryptorchidism coming up in F3 and F4. Mating experiment shows conception rate 50% in F1, F2 generation was 75%, the F3 and F4 generation were 100%. HE staining showed that the seminiferous epithelium of F1 generation was atrophy and with a few spermatogenic cell, F2 generation had improved, F3 and F4 generation were tend to be normal. The DNA methyltransferase expression was up-regulated with the increase of generations by Real Time-PCR, immunohistochemistry and Western Blot. MeDIP-seq Data Analysis Results show many differentially methylated DNA sequences between F1 and F4. DEHP damage male reproductive function in rats, affect expression of DNA methyltransferase enzyme, which in turn leads to genomic imprinting methylation pattern changes and passed on to the next generation, so that the offspring of male reproductive system critical role

  4. In vitro generation of pancreatic endocrine cells from human adult fibroblast-like limbal stem cells.

    PubMed

    Criscimanna, Angela; Zito, Giovanni; Taddeo, Annalisa; Richiusa, Pierina; Pitrone, Maria; Morreale, Daniele; Lodato, Gaetano; Pizzolanti, Giuseppe; Citarrella, Roberto; Galluzzo, Aldo; Giordano, Carla

    2012-01-01

    Stem cells might provide unlimited supply of transplantable cells for β-cell replacement therapy in diabetes. The human limbus is a highly specialized region hosting a well-recognized population of epithelial stem cells, which sustain the continuous renewal of the cornea, and the recently identified stromal fibroblast-like stem cells (f-LSCs), with apparent broader plasticity. However, the lack of specific molecular markers for the identification of the multipotent limbal subpopulation has so far limited the investigation of their differentiation potential. In this study we show that the human limbus contains uncommitted cells that could be potentially harnessed for the treatment of diabetes. Fourteen limbal biopsies were obtained from patients undergoing surgery for ocular diseases not involving the conjunctiva or corneal surface. We identified a subpopulation of f-LSCs characterized by robust proliferative capacity, expressing several pluripotent stem cell markers and exhibiting self-renewal ability. We then demonstrated the potential of f-LSCs to differentiate in vitro into functional insulin-secreting cells by developing a four-step differentiation protocol that efficiently directed f-LSCs towards the pancreatic endocrine cell fate. The expression of specific endodermal, pancreatic, islet, and β-cell markers, as well as functional properties of f-LSC-derived insulin-producing cells, were evaluated during differentiation. With our stage-specific approach, up to 77% of f-LSCs eventually differentiated into cells expressing insulin (also assessed as C-peptide) and exhibited phenotypic features of mature β-cells, such as expression of critical transcription factors and presence of secretory granules. Although insulin content was about 160-fold lower than what observed in adult islets, differentiated cells processed ∼98% of their proinsulin content, similar to mature β-cells. Moreover, they responded in vitro in a regulated manner to multiple secretory stimuli

  5. TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes

    PubMed Central

    Vinagre, João; Nabais, Joana; Pinheiro, Jorge; Batista, Rui; Oliveira, Rui Caetano; Gonçalves, António Pedro; Pestana, Ana; Reis, Marta; Mesquita, Bárbara; Pinto, Vasco; Lyra, Joana; Cipriano, Maria Augusta; Ferreira, Miguel Godinho; Lopes, José Manuel; Sobrinho-Simões, Manuel; Soares, Paula

    2016-01-01

    One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes. PMID:27411289

  6. TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes.

    PubMed

    Vinagre, João; Nabais, Joana; Pinheiro, Jorge; Batista, Rui; Oliveira, Rui Caetano; Gonçalves, António Pedro; Pestana, Ana; Reis, Marta; Mesquita, Bárbara; Pinto, Vasco; Lyra, Joana; Cipriano, Maria Augusta; Ferreira, Miguel Godinho; Lopes, José Manuel; Sobrinho-Simões, Manuel; Soares, Paula

    2016-01-01

    One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes. PMID:27411289

  7. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. PMID:27555793

  8. Hereditary pancreatitis: current perspectives

    PubMed Central

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. PMID:27555793

  9. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

  10. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice.

    PubMed

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-Ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  11. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice

    PubMed Central

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  12. An overview of hereditary pancreatitis.

    PubMed

    Rebours, Vinciane; Lévy, Philippe; Ruszniewski, Philippe

    2012-01-01

    Hereditary pancreatitis is a rare cause of chronic pancreatitis. The prevalence was evaluated to 0.3/100000 in Western Countries. Genetic disorders are due to mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). Since 1996, more than 30 mutations were found. The three more common mutations are R122H, N29I and A16V. First symptoms begin since childhood, mainly before 10 years old. Main symptoms are pancreatic pain and acute pancreatitis (>70%). CP morphological changes as pancreatic calcifications are diagnosed at a median age of 22-25 years. Exocrine and endocrine pancreatic insufficiency occurred in 34% and 26% at a median age of 29 and 38 years. No clinical differences exist according to the mutation type. No excess of mortality in hereditary pancreatitis population compared to general population was found, despite a real risk of cancer. The cumulative risks of pancreatic cancer at 50, 60 and, 75 years are 10%, 18.7% and, 53.5%, respectively. The relative risk of cancer increases in smokers and is evaluated to 8.55. Hereditary pancreatitis diagnosis permits to propose an adapted management in expert centres.

  13. An inhibitor of fibroblast growth factor receptor-1 (FGFR1) promotes late-stage terminal differentiation from NGN3+ pancreatic endocrine progenitors

    PubMed Central

    Yamashita-Sugahara, Yzumi; Matsumoto, Masahito; Ohtaka, Manami; Nishimura, Ken; Nakanishi, Mahito; Mitani, Kohnosuke; Okazaki, Yasushi

    2016-01-01

    Human induced pluripotent stem cells (hiPSCs) provide a potential resource for regenerative medicine. To identify the signalling pathway(s) contributing to the development of functional β cells, we established a tracing model consisting of dual knock-in hiPSCs (INS-Venus/NGN3-mCherry) (hIveNry) expressing the fluorescent proteins Venus and mCherry under the control of intrinsic insulin (INS) and neurogenin 3 (NGN3) promoters, respectively. hIveNry iPSCs differentiated into NGN3- and mCherry-positive endocrine progenitors and then into Venus-positive β cells expressing INS, PDX1, NKX6.1, and glucokinase (GCK). Using these cells, we conducted high-throughput screening of chemicals and identified a specific kinase inhibitor of fibroblast growth factor receptor 1 (FGFR1) that acted in a stage-dependent manner to promote the terminal differentiation of pancreatic endocrine cells, including β cells, from the intermediate stage of pancreatic endocrine progenitors while blocking the early development of pancreatic progenitors. This FGFR1 inhibitor augmented the expression of functional β cell markers (SLC30A8 and ABCC8) and improved glucose-stimulated INS secretion. Our findings indicate that the hIveNry model could provide further insights into the mechanisms of hiPS-derived β cell differentiation controlled by FGFR1-mediated regulatory pathways in a temporal-dependent fashion. PMID:27786288

  14. Threshold-dependent cooperativity of Pdx1 and Oc1 in pancreatic progenitors establishes competency for endocrine differentiation and β-cell function

    PubMed Central

    Wright, Christopher V.E.; Won, Kyoung-Jae

    2016-01-01

    Summary Pdx1 and Oc1 are co-expressed in multipotent pancreatic progenitors and regulate the pro-endocrine gene Neurog3. Their expression diverges in later organogenesis, with Oc1 absent from hormone+ cells and Pdx1 maintained in mature β cells. In a classical genetic test for cooperative functional interactions, we derived mice with combined Pdx1 and Oc1 heterozygosity. Endocrine development in double-heterozygous pancreata was normal at embryonic day (e)13.5, but defects in specification and differentiation were apparent at e15.5, the height of the second wave of differentiation. Pancreata from double heterozygotes showed alterations in the expression of genes crucial for β-cell development and function, decreased numbers and altered allocation of Neurog3-expressing endocrine progenitors, and defective endocrine differentiation. Defects in islet gene expression and β-cell function persisted in double heterozygous neonates. These results suggest that Oc1 and Pdx1 cooperate prior to their divergence, in pancreatic progenitors, to allow for proper differentiation and functional maturation of β cells. PMID:27292642

  15. Stereological estimation and morphological assessment of the endocrine pancreatic components in relation to sex in hen

    PubMed Central

    Fatahian Dehkordi, Rahmat Allah; Moradi, Hamid

    2015-01-01

    In pancreatic survey, quantitative and morphological characteristics could be fundamental variables for the evaluation of some structures. The aim of this study was the application of stereological methods for estimation of quantitative parameters and morphological evaluation of the pancreas in chickens. Ten adult male and ten adult female native chickens were used in this study. Routine tissue processing was carried out for all samples. The sections were stained with hematoxylin and eosin and Gomori's aldehyde-fuchsin. Stereological examinations were performed according to systemic uniform random sampling as well as Cavalieri and point counting method. The morphological results showed that in both sexes, pancreas of chickens was composed of four main pancreatic lobes and contained two distinct islet types. Alpha islets consisted of alpha and a few delta cells and beta islets contained beta and seldom delta cells. Stereological results showed that in both sexes, there were significantly distinctive regional differences in the volume of islet and the numerical density of cells among some lobes with highest values in third and splenic lobes, respectively (p < 0.05). The nuclear volume was lowest in ventral lobe either males (80.60 ± 33.50) or females (84.20 ± 44.10). Beside, in the islets diameter of splenic lobe, there were significant differences in males as compared with females (p < 0.05). In splenic lobe, a significant difference was observed in the nuclear diameter in males than to females (p < 0.05). The results indicated that although there were not morphological changes between sexes in pancreatic lobes, however, some stereological parameters could be affected by sex. PMID:25992251

  16. Pancreatitis.

    PubMed

    Mitchell, R M S; Byrne, M F; Baillie, J

    2003-04-26

    In the past decade, our understanding of the genetic basis, pathogenesis, and natural history of pancreatitis has grown strikingly. In severe acute pancreatitis, intensive medical support and non-surgical intervention for complications keeps patients alive; surgical drainage (necrosectomy) is reserved for patients with infected necrosis for whom supportive measures have failed. Enteral feeding has largely replaced the parenteral route; controversy remains with respect to use of prophylactic antibiotics. Although gene therapy for chronic pancreatitis is years away, our understanding of the roles of gene mutations in hereditary and sporadic pancreatitis offers tantalising clues about the disorder's pathogenesis. The division between acute and chronic pancreatitis has always been blurred: now, genetics of the disorder suggest a continuous range of disease rather than two separate entities. With recognition of pancreatic intraepithelial neoplasia, we see that chronic pancreatitis is a premalignant disorder in some patients. Magnetic resonance cholangiopancreatography and endoscopic ultrasound are destined to replace endoscopic retrograde cholangiopancreatography for many diagnostic indications in pancreatic disease.

  17. Pancreatitis

    MedlinePlus

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  18. Incorporation of Bone Marrow Cells in Pancreatic Pseudoislets Improves Posttransplant Vascularization and Endocrine Function

    PubMed Central

    Wittig, Christine; Laschke, Matthias W.; Scheuer, Claudia; Menger, Michael D.

    2013-01-01

    Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×103 cells. To create bone marrow cell-enriched pseudoislets 2×103 islet cells were co-cultured with 2×103 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation. PMID:23875013

  19. Ketosis resistant diabetes of the young: a profile of its exocrine and endocrine pancreatic dysfunction.

    PubMed

    Sidhu, S S; Shah, P; Srikant, S; Tandon, R K

    1994-10-01

    A subset of insulin requiring diabetes in the young (IRDY) is ketosis resistant. Its pathogenesis and pathophysiology remain ill defined. The current study was done to evaluate the exocrine and endocrine dysfunction in ketosis resistant young diabetics. Fecal chymotrypsin (unit/G), basal & stimulated c-peptide levels (pmol/ml) and sonographic evaluation of the pancreas were done in 59 IRDY patients: 34 ketosis resistant (KR) and 24 ketosis prone (KP). Fecal chymotrypsin levels in KR (11.1 +/- 3.4) and KP (10.3 +/- 5.1) were lower than in controls (22.4 +/- 7.3) (P < 0.01). KR subjects had better endogenous insulin reserves than KP subjects: the basal and stimulated c-peptide levels in KR patients (0.12 & 0.17) were higher than in KP subjects (0.06 and 0.07) (P < 0.05). A strong correlation was noted between the exocrine and beta cell dysfunction in KR subjects (r = 0.7, P < 0.05). Pancreas was smaller in KR and KP patients than in controls (P < 0.05) on sonography. Thus the resistance to ketosis is a reflection of the better preserved beta cell reserves in the KR patients. Loss of the trophic effect of insulin and associated malnutrition is responsible for their exocrine dysfunction.

  20. Developing a multivariable prognostic model for pancreatic endocrine tumors using the clinical data warehouse resources of a single institution.

    PubMed

    Botsis, Taxiarchis; Anagnostou, Valsamo K; Hartvigsen, Gunnar; Hripcsak, George; Weng, Chunhua

    2010-01-01

    OBJECTIVE: Current staging systems are not accurate for classifying pancreatic endocrine tumors (PETs) by risk. Here, we developed a prognostic model for PETs and compared it to the WHO classification system. METHODS: We identified 98 patients diagnosed with PET at NewYork-Presbyterian Hospital/Columbia University Medical Center (1999 to 2009). Tumor and clinical characteristics were retrieved and associations with survival were assessed by univariate Cox analysis. A multivariable model was constructed and a risk score was calculated; the prognostic strength of our model was assessed with the concordance index. RESULTS: Our cohort had median age of 60 years and consisted of 61.2% women; median follow-up time was 10.4 months (range: 0.1-99.6) with a 5-year survival of 61.5%. The majority of PETs were non-functional and no difference was observed between functional and non-functional tumors with respect to WHO stage, age, pathologic characteristics or survival. Distant metastases, aspartate aminotransferase-AST and surgical resection (HR=3.39, 95% CI: 1.38-8.35, p=0.008, HR=3.73, 95% CI: 1.20-11.57, p=0.023 and HR=0.20, 95% CI: 0.08-0.51, p<0.001 respectively) were the strongest predictors in the univariate analysis. Age, perineural and/or lymphovascular invasion, distant metastases and AST were the independent prognostic factors in the final multivariable model; a risk score was calculated and classified patients into low (n=40), intermediate (n=48) and high risk (n=10) groups. The concordance index of our model was 0.93 compared to 0.72 for the WHO system. CONCLUSION: Our prognostic model was highly accurate in stratifying patients by risk; novel approaches as such could thus be incorporated into clinical decisions.

  1. Childhood pancreatitis.

    PubMed

    Uretsky, G; Goldschmiedt, M; James, K

    1999-05-01

    Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.

  2. The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells

    PubMed Central

    Kang, Hong Soon; Takeda, Yukimasa; Jeon, Kilsoo

    2016-01-01

    The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis. PMID:27270601

  3. The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells.

    PubMed

    Kang, Hong Soon; Takeda, Yukimasa; Jeon, Kilsoo; Jetten, Anton M

    2016-01-01

    The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis. PMID:27270601

  4. Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the "Apact" Study)

    ClinicalTrials.gov

    2016-10-24

    Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Digestive System Diseases; Endocrine System Diseases; Gemcitabine; Antimetabolites, Antineoplastic

  5. Dynamics of genomic H3K27me3 domains and role of EZH2 during pancreatic endocrine specification.

    PubMed

    Xu, Cheng-Ran; Li, Lin-Chen; Donahue, Greg; Ying, Lei; Zhang, Yu-Wei; Gadue, Paul; Zaret, Kenneth S

    2014-10-01

    Endoderm cells undergo sequential fate choices to generate insulin-secreting beta cells. Ezh2 of the PRC2 complex, which generates H3K27me3, modulates the transition from endoderm to pancreas progenitors, but the role of Ezh2 and H3K27me3 in the next transition to endocrine progenitors is unknown. We isolated endoderm cells, pancreas progenitors, and endocrine progenitors from different staged mouse embryos and analyzed H3K27me3 genome-wide. Unlike the decline in H3K27me3 domains reported during embryonic stem cell differentiation in vitro, we find that H3K27me3 domains increase in number during endocrine progenitor development in vivo. Genes that lose the H3K27me3 mark typically encode transcriptional regulators, including those for pro-endocrine fates, whereas genes that acquire the mark typically are involved in cell biology and morphogenesis. Deletion of Ezh2 at the pancreas progenitor stage enhanced the production of endocrine progenitors and beta cells. Inhibition of EZH2 in embryonic pancreas explants and in human embryonic stem cell cultures increased endocrine progenitors in vitro. Our studies reveal distinct dynamics in H3K27me3 targets in vivo and a means to modulate beta cell development from stem cells.

  6. Pancreatitis

    MedlinePlus

    ... to the abdomen. In 1 out of 4 childhood cases, a cause is never found. What are the symptoms of pancreatitis? Inflammation of the pancreas is often associated with pain in the upper abdomen and/or the back which may develop slowly, ...

  7. Cross talk between the extracellular matrix and the immune system in the context of endocrine pancreatic islet transplantation. A review article.

    PubMed

    Kuehn, C; Vermette, P; Fülöp, T

    2014-04-01

    This review aims to highlight the importance of the bidirectional influence of the extracellular matrix (ECM) and immune cells in the context of type 1 diabetes mellitus (T1DM) and endocrine pancreatic islet transplantation. We introduced the main classes of molecules and proteins constituting the ECM as well as cells and cytokines of the immune system with the aim to further examine their roles in T1DM and islet transplantation. Integrins expressed by immune cells and their functions are detailed. Finally, this article reviews the roles of the ECM and the immune system in islet transplantation as well as ECM-related cytokines and their influence on the ECM and immune cells. PMID:24679589

  8. 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

    2015-08-07

    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.

  9. Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide.

    PubMed

    Teitelman, G; Alpert, S; Polak, J M; Martinez, A; Hanahan, D

    1993-08-01

    The early progenitor cells to the pancreatic islets in the mouse have been characterized so as to re-examine their possible lineage relationships to the four islet cell types found in mature islets. Insulin and glucagon were both first expressed at embryonic day 9.5, and many cells coexpressed these two markers, as shown by light and electron microscopic analysis using double-label immunohistochemistry. Incubation of embryonic pancreas with 1% glutaraldehyde, a fixative commonly used by electron microscopists, abolished this reactivity, thereby explaining reported difficulties in detecting these precursor cells. Using antisera specific for neuropeptide Y (NPY) a peptide with considerable homology to pancreatic polypeptide (PP), we show that NPY first appears with insulin and glucagon immunoreactivity at E9.5, and is co-expressed with glucagon in a majority of adult alpha cells. As we have previously reported, PP itself is first detectable immunocytochemically at postnatal day 1 with PP-specific antibodies. However, antibodies raised against bovine PP are shown by dot blotting to recognize NPY with comparable avidity, indicating that a recent report of islet progenitor cells containing PP at E9.5 (Herrera, P. L., Huarte, J., Sanvito, F., Meda, P., Orci, L. and Vassalli, J. D. (1991) Development 113, 1257-1265), actually represents cross-reactivity to NPY. The data support a model in which early precursor cells to the endocrine pancreas co-activate and co-express a set of islet cell hormone and neural genes, whose expression is both selectively increased and extinguished as development proceeds, concomitant with a restriction to the patterns of expression characteristic of mature islet cell types.

  10. [Clinical characteristics of multiple endocrine neoplasia].

    PubMed

    Conte-Devolx, Bernard; Niccoli, Patricia

    2010-01-01

    Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are autosomal dominant inherited multiglandular diseases with familial and individual age-related penetrance and variable expression. The most frequent endocrine features of MEN1 are parathyroid involvement (> 95%), duodeno-pancreatic endocrine tissue involvement (80%), pituitary adenoma (30%), and adrenal cortex tumors (25%), with no clear syndromic variants. Identification of the germline MEN1 mutation confirms the diagnosis, but there is no phenotype-genotype correlation. All patients with MEN2 have medullary thyroid carcinoma (MTC). The most distinctive MEN2 variants are MEN2A (MTC+pheochromocytoma+hyperparathyroidism), MEN2B (MTC+pheo), and isolated familial MTC (FMTC). The prognosis of MEN2 is linked to the progression of MTC, which depends mainly on the stage at diagnosis and the quality of initial surgical treatment. This emphasizes the need for early diagnosis and management. The specific RET codon mutation correlates with the MEN2 syndromic variant and with the age of onset and aggressiveness of MTC. Consequently, RET mutational status should guide major management decisions, such as whether and when to perform thyroidectomy. PMID:20669560

  11. Second Giessen International Workshop on Interactions of Exocrine and Endocrine Pancreatic Diseases. Castle of Rauischholzhausen of the Justus-Liebig-university, Giessen (Rauischholzhausen), Germany. March 7-8, 2008.

    PubMed

    Andren-Sandberg, Ake; Hardt, Philip D

    2008-07-10

    The 'Second Giessen International Workshop on Interactions of Exocrine and Endocrine Pancreatic Diseases' was organized in order to reflect and discuss recent developments in the field, especially the progress that has been achieved since the first meeting in March 2005. About thirty international specialists were invited to share their experience and thoughts covering the main topics of: A) pancreatic diabetes (type 3c); B) chronic inflammation of the pancreas. The presentations of session A covered an overview about the frequency of exocrine dysfunction in diabetes mellitus, the relation between diabetes, celiac disease and the exocrine pancreas, the prevalence of type 3c diabetes, damage to the pancreas caused by genes, the role of incretins in type 2 and type 3 diabetes, the role of exocrine tissue in beta cell homeostasis, peculiarities in the treatment of type 3c diabetes and a lecture on incretins: from concept to treatment. Session B included presentations about the frequency of chronic inflammation of the pancreas and therapeutical implications, the role of ACE in the pancreas, genomics and the metabolic hypothesis of chronic pancreatitis, nutritional aspects of pancreatic diseases, the stellate cell concept, autoimmunity, genetic background of chronic pancreatitis and the hypothesis of chronic obstruction induced by gallstone disease. The meeting resulted in several new projects that will be started by the participants in the near future.

  12. What Is Pancreatic Cancer?

    MedlinePlus

    ... very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have ... are by far the most common type of pancreas cancer. If you are told you have pancreatic cancer, ...

  13. PTCH 1 staining of pancreatic neuroendocrine tumor (PNET) samples from patients with and without multiple endocrine neoplasia (MEN-1) syndrome reveals a potential therapeutic target.

    PubMed

    Gurung, Buddha; Hua, Xianxin; Runske, Melissa; Bennett, Bonita; LiVolsi, Virginia; Roses, Robert; Fraker, Douglas A; Metz, David C

    2015-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare, indolent tumors that may occur sporadically or develop in association with well-recognized hereditary syndromes, particularly multiple endocrine neoplasia type 1 (MEN-1). We previously demonstrated that the hedgehog (HH) signaling pathway was aberrantly up-regulated in a mouse model that phenocopies the human MEN-1 syndrome, Men1l/l;RipCre, and that inhibition of this pathway suppresses MEN-1 tumor cell proliferation. We hypothesized that the HH signaling pathway is similarly upregulated in human PNETs. We performed immunohistochemical (IHC) staining for PTCH1 in human fresh and archival PNET specimens to examine whether human sporadic and MEN-1-associated PNETs revealed similar abnormalities as in our mouse model and correlated the results with clinical and demographic factors of the study cohort. PTCH1 staining was positive in 12 of 22 PNET patients (55%). Four of 5 MEN-1 patients stained for PTCH1 (p = 0.32 as compared with sporadic disease patients). Nine of 16 patients with metastatic disease stained for PTCH1 as compared with zero of 3 with localized disease only (p = 0.21). No demographic or clinical features appeared to be predictive of PTCH 1 positivity and PTCH 1 positivity per se was not predictive of clinical outcome. PTCH1, a marker of HH pathway up regulation, is detectable in both primary and metastatic tumors in more than 50% of PNET patients. Although no clinical or demographic factors predict PTCH1 positivity and PTCH1 positivity does not predict clinical outcome, the frequency of expression alone indicates that perturbation of this pathway with agents such as Vismodegib, an inhibitor of Smoothened (SMO), should be examined in future clinical trials. PMID:25482929

  14. [Hereditary pancreatitis].

    PubMed

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-02-01

    Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed. PMID:27000817

  15. Endocrine glands

    MedlinePlus

    Endocrine glands release (secrete) hormones into the bloodstream. The endocrine glands include: Adrenal Hypothalamus Islets of Langerhans in the pancreas Ovaries Parathyroid Pineal Pituitary Testes Thyroid

  16. [Inherited thrombophilia].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-02-01

    Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to Leiden factor V mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dysfibrinogenemia and elevated factor VIII levels. In this review we briefly analyze, from an epidemiologic, clinic and diagnostic point of view, the main inherited prothrombotic risk factors. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in some conditions such as pregnancy and cardiovascular diseases.

  17. [The epidemiology of pancreatic cancer].

    PubMed

    Lakatos, Gábor; Tulassay, Zsolt

    2010-10-31

    Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.

  18. Wilson's disease: An endocrine revelation

    PubMed Central

    Kapoor, Nitin; Shetty, Sahana; Thomas, Nihal; Paul, Thomas Vizhalil

    2014-01-01

    Wilson's disease is an inherited disorder of copper metabolism. The affected patients, who otherwise have a near normal life span, may often suffer from some potentially treatable and under recognized endocrine disorders that may hinder their quality of life. We explored previously published literature on the various endocrine aspects of this disease with their probable underlying mechanisms, highlighting the universal need of research in this area. PMID:25364683

  19. Wilson's disease: An endocrine revelation.

    PubMed

    Kapoor, Nitin; Shetty, Sahana; Thomas, Nihal; Paul, Thomas Vizhalil

    2014-11-01

    Wilson's disease is an inherited disorder of copper metabolism. The affected patients, who otherwise have a near normal life span, may often suffer from some potentially treatable and under recognized endocrine disorders that may hinder their quality of life. We explored previously published literature on the various endocrine aspects of this disease with their probable underlying mechanisms, highlighting the universal need of research in this area. PMID:25364683

  20. Endocrine causes of calcium disorders.

    PubMed

    Greco, Deborah S

    2012-11-01

    Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients.

  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.

  2. A Possible New Multiple Endocrine Neoplasia Mutation in a Patient with a Prototypic Multiple Endocrine Neoplasia Presentation

    PubMed Central

    Buzzola, Rino; Kurukulasuriya, Lilamani Romayne; Touza, Mariana; Litofsky, Norman S.; Brietzke, Stephen; Sowers, James R.

    2016-01-01

    Background Multiple endocrine neoplasia (MEN) type 1 syndrome is an uncommon inherited disorder characterized by the occurrence of tumors involving two or more endocrine glands. These tumors include pheochromocytoma, adrenal cortical and neuroendocrine tumors including (bronchopulmonary, thymic, gastric), lipomas, angiofibromas, collagenomas, and meningiomas. MEN-4 is very rare and has been characterized by the occurrence of parathyroid and anterior pituitary tumors in association with tumors of the adrenals, kidneys, and reproductive organs. Summary We report the case of a 40-year-old male without significant family history of endocrine disease who was found to have primary hyperparathyroidism, a pituitary tumor causing acromegaly, thyroid cancer, renal cell carcinoma, and pancreatic cysts. We posit that this represents a new version of MEN-4. While renal tumors (angiomyolipoma) have been reported as part of the MEN-4 phenotype, to our knowledge, this is the first case reported of the association of MEN-1 and/or MEN-4 phenotype with this unique constellation of tumors, including renal cell carcinoma. Interestingly, this patient tested negative (DNA sequencing/deletion) for MEN-1 (menin), MEN-4 (CDKN1B) and VHL genes. Key Message Thus, while this case has clinical characteristics consistent with either MEN-1 or MEN-4, it may represent a unique genetic variant. PMID:26989398

  3. Natural course of acute pancreatitis.

    PubMed

    Beger, H G; Rau, B; Mayer, J; Pralle, U

    1997-02-01

    Acute pancreatitis comprises, in terms of clinical, pathologic, biochemical, and bacteriologic data, four entities. Interstitial edematous pancreatitis and necrotizing pancreatitis are the most frequent clinical manifestations; pancreatic pseudocyst and pancreatic abscess are late complications after necrotizing pancreatitis, developing after 3 to 5 weeks. Determinants of the natural course of acute pancreatitis are pancreatic parenchymal necrosis, extrapancreatic retroperitoneal fatty tissue necrosis, biologically active compounds in pancreatic ascites, and infection of necrosis. Early in the course of acute pancreatitis multiple organ failure is the consequence of various inflammatory mediators that are released from the inflammatory process and from activated leukocytes attracted by pancreatic injury. During the late course, starting the second week, local and systemic septic complications are dominant. Around 80% of deaths in acute pancreatitis are caused by septic complications. The infection of pancreatic necrosis occurs in 8% to 12% of acute pancreatitis and in 30% to 40% of patients with necrotizing pancreatitis. Bacteriologic analysis of intraoperative smears and aspirates reveals predominantly gram-negative germs deriving from the intestine, most frequently Escherichia coli. It has been confirmed that after necrotizing pancreatitis a considerable large group of patients suffer long-lasting exocrine and endocrine insufficiency.

  4. Microchimerism in endocrine pathology.

    PubMed

    Rust, Daniel W; Bianchi, Diana W

    2009-01-01

    Chimerism in an individual refers to the coexistence of cells arising from two distinct organisms. It can arise iatrogenically via transplant or blood transfusion, and physiologically via twin to twin transfer, or from trafficking between mother and fetus during pregnancy. Many of the diseases associated with microchimerism affect the endocrine system (e.g., autoimmune thyroid disease and diabetes mellitus type 1). Microchimerism is relevant to endocrine pathology because (a) it is associated with pregnancy, a condition of complex endocrine physiology; (b) materno-fetal and feto-maternal cellular migration must involve the placenta, itself an endocrine organ; and (c) in some species, chimerism results in states of intersexuality, a condition intimately involved with endocrine physiology. Studies of feto-maternal microchimerism in the thyroid have documented the presence of fetal cells in association with Hashimoto thyroiditis, Graves' disease, thyroid adenoma, and papillary thyroid carcinoma. Studies of materno-fetal microchimerism have documented the presence of maternal cells in juvenile diabetes and other pediatric conditions. Microchimerism plays a potential role in the repair of diseased thyroid and pancreatic tissues.

  5. Endocrine glands

    MedlinePlus

    The endocrine system is primarily composed of glands that produce chemical messengers called hormones. Glands of the endocrine system include the pituitary gland, the thyroid gland, the parathyroid glands, the thymus, ...

  6. Hereditary pancreatitis for the endoscopist.

    PubMed

    Patel, Milan R; Eppolito, Amanda L; Willingham, Field F

    2013-03-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68-81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) are also associated with hereditary pancreatitis. While chronic alcoholic pancreatitis may develop in the fourth or fifth decades, patients with hereditary pancreatitis may develop symptoms in the first or second decades of life. Hereditary pancreatitis is diagnosed either by detecting a causative gene mutation or by the presence of chronic pancreatitis in two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes. Patients with hereditary pancreatitis may have recurrent acute pancreatitis and may develop pancreatic exocrine and endocrine insufficiency. Hereditary pancreatitis may involve premature trypsinogen activation or decreased control of trypsin. Recurrent inflammation can lead to acute pancreatitis and subsequently to chronic pancreatitis with parenchymal calcification. There is a markedly increased risk of pancreatic carcinoma compared with the general population. Patients are often referred for evaluation of pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and for evaluation for malignancy. Medical treatment includes pancreatic enzyme supplementation, nutritional supplementation, diabetes management, and palliation of pain. Patients should avoid tobacco use and alcohol exposure. Hereditary pancreatitis is reviewed and recommendations for

  7. Pancreatic Cancer Genetics

    PubMed Central

    Amundadottir, Laufey T.

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS). PMID:26929738

  8. Inherited Neuropathies

    PubMed Central

    Li, Jun

    2013-01-01

    With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases, collectively called Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurologic disorders. Patients with CMT typically present with chronic muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and foot deformities. Clinical similarities between patients often require genetic testing to achieve a precise diagnosis. In this article, the author reviews the clinical and pathologic features of CMT, and demonstrates how electrodiagnostic and genetic tools are used to assist in the diagnosis and symptomatic management of the diseases. Several cases are presented to illustrate the diagnostic processes. PMID:23117945

  9. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  10. Pancreatic alpha-cells from female mice undergo morphofunctional changes during compensatory adaptations of the endocrine pancreas to diet-induced obesity.

    PubMed

    Merino, Beatriz; Alonso-Magdalena, Paloma; Lluesma, Mónica; Ñeco, Patricia; Gonzalez, Alejandro; Marroquí, Laura; García-Arévalo, Marta; Nadal, Angel; Quesada, Ivan

    2015-06-25

    Obesity is frequently associated with insulin resistance. To compensate for this situation and maintain normoglycaemia, pancreatic beta-cells undergo several morphofunctional adaptations, which result in insulin hypersecretion and hyperinsulinaemia. However, no information exists about pancreatic alpha-cells during this compensatory stage of obesity. Here, we studied alpha-cells in mice fed a high-fat diet (HFD) for 12 weeks. These animals exhibited hyperinsulinaemia and normoglycaemia compared with control animals in addition to hypoglucagonaemia. While the in vivo response of glucagon to hypoglycaemia was preserved in the obese mice, the suppression of glucagon secretion during hyperglycaemia was impaired. Additionally, in vitro glucagon release at low glucose levels and glucagon content in isolated islets were decreased, while alpha-cell exocytosis remained unchanged. Assessment of morphological parameters revealed that alpha-cell area was reduced in the pancreas of the obese mice in association with alpha-cell hypotrophy, increased apoptosis and decreased proliferation. HFD feeding for 24 weeks led to significant deterioration in beta-cell function and glucose homeostasis. Under these conditions, the majority of alpha-cell changes were reversed and became comparable to controls. These findings indicate that pancreatic compensatory adaptations during obesity may also involve pancreatic alpha-cells. Additionally, defects in alpha-cell function during obesity may be implicated in progression to diabetes.

  11. Fibrocalculous pancreatic diabetes.

    PubMed

    Goundan, Poorani; Junqueira, Ana; Kelleher-Yassen, Donna; Steenkamp, Devin

    2016-03-01

    The aim of this paper is to review the relevant literature related to the epidemiology, pathophysiology, natural history, clinical features and treatment of fibrocalculous pancreatic diabetes (FCPD). We review the English-language literature on this topic published between 1956 and 2014. FCPD is a form of diabetes usually associated with chronic calcific pancreatitis. It has been predominantly, though not exclusively, described in lean, young adults living in tropical developing countries. Historically linked to malnutrition, the etiology of this phenotype has not been clearly elucidated, nor has there been a clear consensus on specific diagnostic criteria or clinical features. Affected individuals usually present with a long-standing history of abdominal pain, which may begin as early as childhood. Progressive pancreatic endocrine and exocrine dysfunction, consistent with chronic pancreatitis is expected. Common causes of chronic pancreatitis, such as alcohol abuse, are usually absent. Typical radiographic and pathological features include coarse pancreatic calcifications, main pancreatic duct dilation, pancreatic fibrosis and atrophy. Progressive microvascular complications are common, but diabetic ketoacidosis is remarkably unusual. Pancreatic carcinoma is an infrequently described long term complication. FCPD is an uncommon diabetes phenotype characterized by early onset non-alcoholic chronic pancreatitis with hyperglycemia, insulin deficiency and a striking resistance to ketosis. PMID:26472503

  12. Granulomatous Insulitis as a Cause of Acute-Onset Insulin-Dependent Diabetes Mellitus in a Patient With a Pancreatic Endocrine Carcinoma.

    PubMed

    Saab, Jad; Qin, Lihui; Jessurun, Jose

    2016-10-01

    Autoimmune destruction of β cells is the cause of most cases of type 1 diabetes mellitus. Lymphocytic insulitis has been documented in the early phases of this disease as well as in recurrent diabetes after pancreas transplantation and in certain viral infections. We report a unique case of granulomatous insulitis in a patient with an endocrine tumor of the pancreas that clinically manifested as acute-onset insulin-dependent diabetes mellitus. Granulomata were present in islets with complete disappearance of β cells, as well as in the primary tumor, metastases, and lymph nodes. We postulate that these granulomata represent a sarcoid-like reaction to the tumor with secondary injury to nonneoplastic endocrine cells through a mechanism of molecular mimicry.

  13. Endocrine Disorders in Cystic Fibrosis.

    PubMed

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. PMID:27469183

  14. Endocrine Diseases

    MedlinePlus

    ... high or too low, you may have an endocrine disease or disorder. Endocrine diseases and disorders also occur if your body does not respond to hormones the way it is supposed to. Featured Topics Adrenal Insufficiency ... Topics Research Discoveries & News Children with Cushing ...

  15. Immunoreactivity to peptides belonging to the pancreatic polypeptide family (NPY, aPY, PP, PYY) and to glucagon-like peptide in the endocrine pancreas and anterior intestine of adult lampreys, Petromyzon marinus: an immunohistochemical study.

    PubMed

    Cheung, R; Andrews, P C; Plisetskaya, E M; Youson, J H

    1991-01-01

    Immunoreactivity of antisera directed against human neuropeptide Y (NPY), anglerfish polypeptide YG (aPY), bovine pancreatic polypeptide (bPP), salmon pancreatic polypeptide (sPP), porcine peptide tyrosine tyrosine (PYY), and salmon glucagon-like peptide (GLP) was investigated in the endocrine pancreas and anterior intestine of adult lampreys, Petromyzon marinus, by immunohistochemical analysis. There was no immunoreactivity to anti-sPP and anti-bPP in any tissue and anti-GLP immunostaining was only present in the anterior intestine. The immunoreactivity to antisera raised against NPY, aPY, and PYY was colocalized within the same small number of cells in the caudal and cranial pancreas of juveniles and the caudal pancreas of upstream migrant adults. These antibodies did not immunostain B- or D-cells and thus, NPY, aPY, and PYY were likely localized in a third cell type (3a) in the lamprey pancreas. Immunostaining of a few cells with only anti-aPY suggested the possibility of a fourth cell type (3b). Immunoreactivity was similar in the cranial and caudal pancreas of male upstream migrants; however, in the female cranial pancreas, a few cells demonstrated intense immunoreaction to anti-aPY, while weaker immunostaining with this antiserum was observed in B-cells. In the intestine of juvenile and upstream migrant lampreys, positive immunostaining to GLP, NPY, aPY, and PYY antibodies was colocalized within the same cell. We believe that this cell may contain PYY/glucagon family peptides. Other intestinal cells immunostained with either GLP or somatostatin-34 antiserum. PMID:2026316

  16. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  17. Epidemiologic and etiologic factors of pancreatic cancer.

    PubMed

    Lowenfels, Albert B; Maisonneuve, Patrick

    2002-02-01

    Ranking fourth as a cause of death from cancer for men and women in the United States, pancreatic cancer represents a significant challenge for physicians and surgeons. In addition to the elderly, high-risk groups include blacks, men, smokers, and patients with certain preexisting diseases such as pancreatitis and long-standing diabetes. Various inherited genetic disorders cause approximately 5% to 10% of the total cases of pancreatic cancer. Smoking doubles the risk of pancreatic cancer. Control of smoking offers the best available strategy for reducing the incidence of this disease. Dietary measures to reduce the risk of pancreatic cancer include maintenance of normal body weight and consumption of a well balanced diet with adequate amounts of fruits and vegetables. Chronic pancreatitis caused by heavy alcohol consumption or, rarely, by an underlying inherited disorder is another strong risk factor, but because this benign disease is uncommon, elimination of this underlying cause would have minimal impact on the frequency of pancreatic cancer.

  18. Inherited or acquired metabolic disorders.

    PubMed

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series. PMID:27432685

  19. Notch Signaling in Pancreatic Development

    PubMed Central

    Li, Xu-Yan; Zhai, Wen-Jun; Teng, Chun-Bo

    2015-01-01

    The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion that Notch signaling specifies the endocrine lineage. Here, we review the current knowledge of the Notch signaling pathway in pancreatic development and its crosstalk with the Wingless and INT-1 (Wnt) and fibroblast growth factor (FGF) pathways. PMID:26729103

  20. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... fluids through an intravenous (IV) tube in your vein and nutrition through a feeding tube or IV. ...

  1. Inherit Space

    NASA Technical Reports Server (NTRS)

    Giarratano, Joseph C.; Jenks, K. C.

    1997-01-01

    The objective of the proposed research was to begin development of a unique educational tool targeted at educating and inspiring young people 12-16 years old about NASA and the Space Program. Since these young people are the future engineers, scientists and space pioneers, the nurturing of their enthusiasm and interest is of critical importance to the Nation. This summer the basic infrastructure of the tool was developed in the context of an educational game paradigm. The game paradigm has achieved remarkable success in maintaining the interest of young people in a self-paced, student-directed learning environment. This type of environment encourages student exploration and curiosity which are exactly the traits that future space pioneers need to develop to prepare for the unexpected. The Inherit Space Educational Tool is an open-ended learning environment consisting of a finite-state machine classic adventure game paradigm. As the young person explores this world, different obstacles must be overcome. Rewards will be offered such as using the flight simulator to fly around and explore Titan. This simulator was modeled on conventional Earth flight simulators but has been considerably enhanced to add texture mapping of Titan's atmosphere utilizing the latest information from the NASA Galileo Space Probe. Additional scenery was added to provide color VGA graphics of a futuristic research station on Titan as well as an interesting story to keep the youngster's attention. This summer the game infrastructure has been developed as well as the Titan Flight Simulator. A number of other enhancements are planned.

  2. Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours

    PubMed Central

    Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

    2014-01-01

    Objective(s): The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). Methods: 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). Conclusion: 99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options. PMID:27408857

  3. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    SciTech Connect

    Rossi, R.L.; Braasch, J.W.; O'Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  4. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

  5. Inherited platelet disorders.

    PubMed

    Franchini, Massimo; Lippi, Giuseppe; Veneri, Dino; Targher, Giovanni; Zaffanello, Marco; Guidi, Gian Cesare

    2008-01-01

    Inherited platelet disorders are a rare, but probably underdiagnosed, cause of symptomatic bleeding. They are characterized by abnormalities of platelet number (inherited thrombocytopenias), function (inherited disorders of platelet function) or both. This review briefly discusses the inherited platelet disorders with respect to molecular defects, diagnostic evaluation and treatment strategies.

  6. Tropical chronic pancreatitis

    PubMed Central

    Barman, K; Premalatha, G; Mohan, V

    2003-01-01

    Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non-alcoholic pancreatitis, seen almost exclusively in the developing countries of the tropical world. The classical triad of TCP consists of abdominal pain, steatorrhoea, and diabetes. When diabetes is present, the condition is called fibrocalculous pancreatic diabetes (FCPD) which is thus a later stage of TCP. Some of the distinctive features of TCP are younger age at onset, presence of large intraductal calculi, more aggressive course of the disease, and a high susceptibility to pancreatic cancer. Pancreatic calculi are the hallmark for the diagnosis of TCP and in non-calcific cases ductal dilation on endoscopic retrograde cholangiopancreatography, computed tomography, or ultrasound helps to identify the disease. Diabetes is usually quite severe and of the insulin requiring type, but ketosis is rare. Microvascular complications of diabetes occur as frequently as in type 2 diabetes but macrovascular complications are uncommon. Pancreatic enzyme supplements are used for relief of abdominal pain and reducing the symptoms related to steatorrhoea. Early diagnosis and better control of the endocrine and exocrine dysfunction could help to ensure better survival and improve the prognosis and quality of life of TCP patients. PMID:14654569

  7. Nutrition in pancreatic diseases.

    PubMed

    Meier, Rémy F; Beglinger, Christoph

    2006-01-01

    The pancreas plays a major role in nutrient digestion. Therefore, in both acute and chronic pancreatitis, exocrine and endocrine pancreatic insufficiency can develop, impairing digestive and absorptive processes. These changes can lead to malnutrition over time. In parallel to these changes, decreased caloric intake and increased metabolic activity are often present. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. In severe acute pancreatitis, enteral nutrition with a naso-jejunal feeding tube and a low molecular diet displays clear advantages compared to parenteral nutrition. Infectious complications, length of hospital stay and the need for surgery are reduced. Furthermore, enteral nutrition is less costly than parenteral nutrition. Parenteral nutrition is reserved for patients who do not tolerate enteral nutrition. Abstinence from alcohol, dietary modifications and pancreatic enzyme supplementation is sufficient in over 80% of patients with chronic pancreatitis. In addition, oral supplements are helpful. Enteral nutrition can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis.

  8. Familial pancreatic cancer.

    PubMed

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  9. Growing new endocrine pancreas in situ.

    PubMed

    Hammerman, Marc R

    2006-03-01

    Type 1 diabetes mellitus is a major cause of endstage renal disease in young adults. Maintenance of normoglycemia in type 1 diabetics using exogenous insulin is difficult under the best of circumstances. Transplantation therapies are limited by the scarcity of human donor organs, rendering a priority the identification of an alternative source for replacing insulin-secreting cells. Embryonic pancreatic primordia transplanted into diabetic animal hosts undergo selective endocrine differentiation in situ and normalize glucose tolerance. Pancreatic primordia can be transplanted across isogeneic, allogeneic, and both concordant (rat-to-mouse) and highly disparate (pig-to-rodent) xenogeneic barriers. Successful transplantation of pancreatic primordia depends on obtaining them at defined windows during embryonic development within which the risk of teratogenicity is eliminated, growth potential is maximized, and immunogenicity is reduced. Here we review studies exploring the potential for pancreatic organogenesis post-transplantation of embryonic primordia as a therapy for type 1 diabetes.

  10. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2013-10-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern knowledge of the etiopathogenesis of the disease, the pharmacological treatment of pain, and knowledge of the natural history of autoimmune pancreatitis. New evidence supports the relatively low prevalence of chronic alcoholic pancreatitis, and the role of tobacco in triggering the etiopathogenic mechanisms of chronic pancreatitis is better understood. Some studies have identified certain factors that are associated with having a positive genetic test in adults with chronic idiopathic pancreatitis, which should help to select those patients who should undergo genetic studies. Antioxidant therapy has been shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Finally, the development of exocrine and endocrine pancreatic insufficiency is a very common finding during the long-term follow-up of patients with autoimmune pancreatitis. Smoking also seems to play a role in this type of pancreatitis.

  11. Pancreatic Cancer

    MedlinePlus

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  12. Endocrine Tumor: Overview

    MedlinePlus

    ... a roadmap to this full guide. About the endocrine system The endocrine system is made up of cells that produce hormones. ... of sugar in the blood. Part of the endocrine system is the neuroendocrine system, which is made up ...

  13. [Endocrine hypertension].

    PubMed

    Takeda, R

    1993-03-01

    Endocrine Hypertension, is, in a narrow sense, defined as adrenal hypertension, including mainly pheochromocytoma, Cushing's syndrome, a syndrome of primary aldosteronism and it's related mineralocorticoid excess disorders. In memory of a great contribution to hypertensiology by the late Prof. Murakami, who was the first author to write on pheochromocytoma in Japan, this paper is dedicated to reviewing the current status of adrenal hypertension in Japan from the epidemiological viewpoint, putting emphasis upon the clinical characteristics of aged patients with adrenal hypertension. Secondly, some topics in the research field of each adrenal hypertension are briefly introduced. Thirdly, our recent data are presented, showing 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) mRNA expression in resistance vessels and decreased 11 beta-HSD activities in vessels in SHR which supports the hypothesis that there might exist a subtype identified as partial impairment of 11 beta-HSD in patients with essential hypertension. PMID:8331819

  14. Chronic pancreatitis.

    PubMed

    Chari, S T; DiMagno, E P

    2000-09-01

    In the past year, there has been at least one important clinical paper that sheds light on the character and natural history of painful chronic pancreatitis, which has important clinical implications. In addition, several novel mutations have been described in the cationic trypsinogen gene in patients with hereditary pancreatitis. The mechanism by which these mutations cause pancreatic disease remains speculative. The diagnosis of early chronic pancreatitis is controversial. A novel noninvasive pancreatic function test (measurement of postprandial APOB-48) was reported but is unlikely to be a sensitive test of pancreatic function. Pancreatic fibrosis is frequently seen in alcoholics without chronic pancreatitis, and this makes it difficult to interpret the findings on endoscopic ultrasonogram. Recent studies highlight the difficulty in abolishing pancreatic steatorrhea. Recently fibrosing colonopathy in adult patients has been reported. Extracorporeal shockwave lithotripsy combined with endoscopic therapy failed to benefit patients with calcific chronic pancreatitis.

  15. Purification of monolayer cell cultures of the endocrine pancreas.

    PubMed

    Braaten, J T; Järlfors, U; Smith, D S; Mintz, D H

    1975-01-01

    Experimental use of primary cultures of endocrine pancreas is constrained by early, vigorous proliferation of fibroblastoid cells. The addition of heavy metals, sodium ethylmercurithiosalicylate, phenyl mercuric acetate, phenyl mercuric nitrate and sodium aurothiomalate to the culture media selectively destroys these fibroblastoid cells yielding highly enriched, morphologically intact, functionally competent endocrine cells that are capable of cell replication. This action of heavy metals appears to be due to reversible inhibition of sulfhydryl enzymes since glutathione and thioglycolate were demonstrated to completely inhibit the cytotoxic effects of the mercury and gold containing agents, respectively. Certain variables in the application of the mercurial agents to pancreatic endocrine cell cultures were defined, most notably the enhanced sensitivity of fetal vs. neonatal tissue, and in inverse relationship of cell density to effective toxicity. After removal of the heavy metal agent from the culture media, many pancreatic islets send out cytoplasmic projections, containing large numbers of oriented microtubules which serve as bridging units to adjacent endocrine cells. The sustained availability of virtually pure pancreatic endocrine cell cultures, which results from the application of mercury to the culture media will undoubtedly permit many aspects of the cell biology of the endocrine pancreas to be directly and sequentially assailed. PMID:1239830

  16. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas

    PubMed Central

    Gradwohl, Gérard; Dierich, Andrée; LeMeur, Marianne; Guillemot, François

    2000-01-01

    In the mammalian pancreas, the endocrine cell types of the islets of Langerhans, including the α-, β-, δ-, and pancreatic polypeptide cells as well as the exocrine cells, derive from foregut endodermal progenitors. Recent genetic studies have identified a network of transcription factors, including Pdx1, Isl1, Pax4, Pax6, NeuroD, Nkx2.2, and Hlxb9, regulating the development of islet cells at different stages, but the molecular mechanisms controlling the specification of pancreatic endocrine precursors remain unknown. neurogenin3 (ngn3) is a member of a family of basic helix–loop–helix transcription factors that is involved in the determination of neural precursor cells in the neuroectoderm. ngn3 is expressed in discrete regions of the nervous system and in scattered cells in the embryonic pancreas. We show herein that ngn3-positive cells coexpress neither insulin nor glucagon, suggesting that ngn3 marks early precursors of pancreatic endocrine cells. Mice lacking ngn3 function fail to generate any pancreatic endocrine cells and die postnatally from diabetes. Expression of Isl1, Pax4, Pax6, and NeuroD is lost, and endocrine precursors are lacking in the mutant pancreatic epithelium. Thus, ngn3 is required for the specification of a common precursor for the four pancreatic endocrine cell types. PMID:10677506

  17. Endocrine Labomas

    PubMed Central

    Dutta, Deep; Chowdhury, Subhankar

    2012-01-01

    Laboratory endocrinology forms an integral part of 21st century endocrinology. Perhaps, no other specialty of medicine is as closely associated with laboratory as endocrinology. This review intends to highlight the challenges faced by an endocrinologist before interpreting a hormone assay report. This review by no means is holistic but intends to highlight some of the pitfalls of laboratory endocrinology and arouse further interest in this important but neglected section of endocrinology. Lack of standardization, as well as rigorous implementation is some of the major challenges facing endocrine assays in our country. It is essential to be aware not only of the details of the method of analysis of a hormone, the pre-analytical requisites, but also disease-specific analytical issues to prevent unnecessary concern both for the patient, as well as the treating physician, as well as needless investigations. Problems with interpretation of serum prolactin, thyroglobulin, steroid hormone assays, rennin assay and vitamin-D assay have been highlighted. PMID:23565398

  18. Endocrine Disruptors

    PubMed Central

    2015-01-01

    Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices. PMID:26740809

  19. [Pancreatic Diseases].

    PubMed

    Schöfl, Rainer

    2016-06-22

    The author presents his personal choice of practical relevant papers of pancreatic diseases from 2014 to 2015. Nutritional factors and hypertriglycidemia are discussed as causes of acute pancreatitis. Tools to avoid post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis are described and the natural course of fluid collections and pseudocysts is demonstrated. The value of secretin-MRCP(magnetic resonance cholangiopancreatography) for diagnosis of chronic pancreatitis is illustrated. Data help to choose the minimally effective prednisolone dose in autoimmune pancreatitis. The increased prevalence of fractures in patients with chronic pancreatitis highlights the necessity of screening for bone density loss. The association of vitamin D intake with pancreatic cancer is described. The probability of cancer in IPNM is shown and innovative surgical concepts to reduce the loss of pancreatic function are presented. Finally neoadjuvant concepts for the treatment of pancreatic cancer are highlighted. PMID:27329710

  20. Inherited thrombophilia: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-01-01

    Inherited thrombophilia can be defined as a genetically determined predisposition to develop thromboembolic complications. Inherited prothrombotic risk factors include antithrombin deficiency, protein C and protein S deficiencies, activated protein C resistance due to factor V Leiden mutation, inherited hyperhomocysteinemia, prothrombin G20210A variant, dys- and hyperfibrinogenemia and elevated factor VIII levels. In this review we briefly analyze, from an epidemiologic, laboratory and clinical point of view, the main inherited prothrombotic risk factors. Finally, we discuss the synergism between genetic and acquired prothrombotic risk factors in some conditions such as pregnancy and cardiovascular diseases.

  1. Endotherapy in chronic pancreatitis.

    PubMed

    Tandan, Manu; Nageshwar Reddy, D

    2013-10-01

    Chronic pancreatitis (CP) is a progressive disease with irreversible changes in the pancreas. Patients commonly present with pain and with exocrine or endocrine insufficiency. All therapeutic efforts in CP are directed towards relief of pain as well as the management of associated complications. Endoscopic therapy offers many advantages in patients with CP who present with ductal calculi, strictures, ductal leaks, pseudocyst or associated biliary strictures. Endotherapy offers a high rate of success with low morbidity in properly selected patients. The procedure can be repeated and failed endotherapy is not a hindrance to subsequent surgery. Endoscopic pancreatic sphincterotomy is helpful in patients with CP with minimal ductal changes while minor papilla sphincterotomy provides relief in patients with pancreas divisum and chronic pancreatitis. Extracorporeal shock wave lithotripsy is the standard of care in patients with large pancreatic ductal calculi. Long term follow up has shown pain relief in over 60% of patients. A transpapillary stent placed across the disruption provides relief in over 90% of patients with ductal leaks. Pancreatic ductal strictures are managed by single large bore stents. Multiple stents are placed for refractory strictures. CP associated benign biliary strictures (BBS) are best treated with multiple plastic stents, as the response to a single plastic stent is poor. Covered self expanding metal stents are increasingly being used in the management of BBS though further long term studies are needed. Pseudocysts are best drained endoscopically with a success rate of 80%-95% at most centers. Endosonography (EUS) has added to the therapeutic armamentarium in the management of patients with CP. Drainage of pseudcysts, cannulation of inaccessible pancreatic ducts and celiac ganglion block in patients with intractable pain are all performed using EUS. Endotherapy should be offered as the first line of therapy in properly selected patients with CP

  2. Nutrition in chronic pancreatitis

    PubMed Central

    Rasmussen, Henrik Højgaard; Irtun, Øivind; Olesen, Søren Schou; Drewes, Asbjørn Mohr; Holst, Mette

    2013-01-01

    The pancreas is a major player in nutrient digestion. In chronic pancreatitis both exocrine and endocrine insufficiency may develop leading to malnutrition over time. Maldigestion is often a late complication of chronic pancreatic and depends on the severity of the underlying disease. The severity of malnutrition is correlated with two major factors: (1) malabsorption and depletion of nutrients (e.g., alcoholism and pain) causes impaired nutritional status; and (2) increased metabolic activity due to the severity of the disease. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. Good nutritional practice includes screening to identify patients at risk, followed by a thoroughly nutritional assessment and nutrition plan for risk patients. Treatment should be multidisciplinary and the mainstay of treatment is abstinence from alcohol, pain treatment, dietary modifications and pancreatic enzyme supplementation. To achieve energy-end protein requirements, oral supplementation might be beneficial. Enteral nutrition may be used when patients do not have sufficient calorie intake as in pylero-duodenal-stenosis, inflammation or prior to surgery and can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis and should only be used in case of GI-tract obstruction or as a supplement to enteral nutrition. PMID:24259957

  3. Individual susceptibility to alcoholic pancreatitis.

    PubMed

    Apte, Minoti V; Pirola, Romano C; Wilson, Jeremy S

    2008-03-01

    The observation that only a minority of heavy drinkers develop pancreatitis has prompted an intensive search for a trigger factor/cofactor/susceptibility factor that may precipitate a clinical attack. Putative susceptibility factors examined so far include diet, smoking, amount and type of alcohol consumed, the pattern of drinking and lipid intolerance. In addition, a range of inherited factors have been assessed including blood group antigens, human leukocyte antigen serotypes, alpha-1-antitrypsin phenotypes and several genotypes. The latter group comprises mutations/polymorphisms in genes related to alcohol-metabolizing enzymes, detoxifying enzymes, pancreatic digestive enzymes, pancreatic enzyme inhibitors, cystic fibrosis and cytokines. Disappointingly, despite this concerted research effort, no clear association has been established between the above factors and alcoholic pancreatitis. Experimentally, the secretagogue cholecystokinin (CCK) has been investigated as a candidate 'trigger' for alcoholic pancreatitis. However, the clinical relevance of CCK as a trigger factor has to be questioned, as it is difficult to envisage a situation in humans where abnormally high levels of CCK would be released into the circulation to trigger pancreatitis in alcoholics. In contrast, bacterial endotoxemia is a candidate cofactor that does have relevance to the clinical situation. Plasma lipopolysaccharide (LPS, an endotoxin) levels are significantly higher in drinkers (either after chronic alcohol intake or a single binge) compared to non-drinkers. We have recently shown that alcohol-fed animals challenged with otherwise innocuous doses of LPS exhibit significant pancreatic injury. Moreover, repeated LPS exposure in alcohol-fed rats leads to progressive injury to the gland characterized by significant pancreatic fibrosis. These studies support the concept that endotoxin may be an important factor in the initiation and progression of alcoholic pancreatitis. Scope remains for

  4. Epidemiology and prevention of pancreatic cancer.

    PubMed

    Lowenfels, Albert B; Maisonneuve, Patrick

    2004-05-01

    Pancreatic cancer is an uncommon tumor, but because the mortality rate approaches 100%, this form of cancer has now become a common cause of cancer mortality. In the United States it is the fourth most frequent cause of cancer mortality; in Japan it ranks as the fifth commonest cause of death from cancer. Smoking is the major known risk factor for pancreatic cancer, accounting for approximately 25-30% of all cases. Some of the time-dependent changes in the frequency of pancreatic cancer can be explained by smoking trends. Aggressive public health measures to control smoking would substantially reduce the burden of pancreatic cancer. Dietary factors are less important for pancreatic cancer than for other digestive tract tumors, but consumption of a diet with adequate quantities of fruits and vegetables, plus control of calories either by dietary measures or by exercise will help to prevent this lethal tumor. There are more than a dozen inherited germline mutations that increase the risk of pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. In addition to germline defects, there are several common polymorphisms in genes that control detoxification of environmental carcinogens that may alter the risk of pancreatic cancer. More research will be needed in this area, to explain and to clarify the interaction between genes and environmental factors.

  5. Endocrine Glands & Their Hormones

    MedlinePlus

    ... Home » Cancer Registration & Surveillance Modules » Anatomy & Physiology » Endocrine System » Endocrine Glands & Their Hormones Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

  6. Endocrine system and obesity.

    PubMed

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients.

  7. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by ... This Article Generic Name Select Brand Names corticotropin H.P. ACTHAR GEL epinephrine ADRENALIN Multiple Endocrine Neoplasia ...

  8. Epidemiology of pancreatic cancer: an update.

    PubMed

    Maisonneuve, Patrick; Lowenfels, Albert B

    2010-01-01

    Pancreatic cancer, although infrequent, has a very poor prognosis, making it one of the 4 or 5 most common causes of cancer mortality in developed countries. Its incidence varies greatly across regions, which suggests that lifestyle factors such as diet, and environmental factors, such as vitamin D exposure, play a role. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer in the coming decades. Smoking is the most common known risk factor, causing 20-25% of all pancreatic tumors. Although a common cause of pancreatitis, heavy alcohol intake is associated only with a modest increased risk of pancreatic cancer. While viruses do not represent a major risk factor, people infected with Helicobacter pylori appeared to be at high risk of pancreatic cancer. Many factors associated with the metabolic syndrome, including overweight and obesity, impaired glucose tolerance, and long-standing diabetes also increase the risk disease, while atopic allergy and use of metformin as a treatment for diabetes have been associated with a reduced risk of pancreatic cancer. A family history of pancreatic cancer is associated with an increased risk of pancreatic cancer and it is estimated that 5-10% of patients with pancreatic cancer have an underlying germline disorder. Having a non-O blood group, another inherited characteristic, has also been steadily associated with an increased risk of pancreatic cancer. While many risk factors for pancreatic cancer are not modifiable, adopting a healthy lifestyle could substantially reduce pancreatic cancer risk. PMID:21088417

  9. Conservation of pancreatic tissue by combined gastric, biliary, and pancreatic duct drainage for pain from chronic pancreatitis.

    PubMed

    Warshaw, A L

    1985-04-01

    In patients with chronic pancreatitis, the sclerosing process of the pancreas may constrict not only the pancreatic duct for also the bile duct and duodenum. This study analyzes the prevalence of these obstructive lesions in 58 consecutive patients with chronic pancreatitis requiring surgery for either pain (57 patients) or for painless jaundice (1 patient). There was significant biliary obstruction in 21, 4 of whom also had symptomatic duodenal obstruction. All 21 patients with biliary and duodenal obstruction were among the 38 with a dilated pancreatic duct suitable for pancreaticojejunostomy (modified Puestow procedure). None of the 20 patients with small duct pancreatitis had biliary or duodenal obstruction. Pseudocysts were distributed evenly between the two groups (9 of 38 patients with a dilated duct versus 4 of 20 patients with small duct pancreatitis). Pancreaticojejunostomy combined with choledochoenterostomy and gastrojejunostomy in appropriately selected patients provided good to excellent long-term (mean 3.6 years) relief of pain in 30 of 36 patients (83 percent). There was no correlation between successful relief of pain and development of pancreatic exocrine or endocrine insufficiency or calcification. Stenosis of the bile duct developed some years subsequent to pancreaticojejunostomy in four patients and required a second operation for choledochoenterostomy in three. Three other patients required secondary pancreatic resections due to failure of the pancreaticojejunostomy to relieve pain. It is often possible to effect excellent relief of symptoms with maximal conservation of remaining pancreatic functions despite sclerotic obstruction of multiple organ systems.

  10. PEDIATRIC PANCREATITIS

    PubMed Central

    Pohl, John F.; Uc, Aliye

    2015-01-01

    Purpose of Review The purpose of this review is to describe recent developments in pediatric pancreatitis and to discuss etiologies and current management. Recent Findings Although recent studies have estimated the annual incidence of pediatric acute pancreatitis approaching that of adults, there are no established guidelines about its diagnosis and treatment in children. Genetic and structural/congenital abnormalities are emerging as the primary risk factors for pediatric acute recurrent and chronic pancreatitis. Specifically, chronic pancreatitis is associated with a significant socioeconomic burden in children. Both medical and surgical therapies are proposed for pediatric chronic pancreatitis, but there is little evidence that they are beneficial. Summary Acute, acute recurrent and chronic pancreatitis create significant health issues in the pediatric population. Medical and surgical therapies exist to potentially treat these conditions, but the pediatric data is limited and the cohorts are small. A multidisciplinary and multicenter approach is necessary to better determine pancreatic disease processes and treatment options in children. PMID:26181572

  11. Endocrine tumors of the pancreas.

    PubMed

    Meko, J B; Norton, J A

    1994-01-01

    Pancreatic endocrine tumors are rare, yet can cause significant morbidity due to excessive secretion of hormones. Octreotide is effective in reducing the plasma concentrations of many of these hormones. The availability of potent H2-receptor antagonists and omeprazole has altered the emphasis in patients with Zollinger-Ellison syndrome away from total gastrectomy and towards resection of the gastrinoma for potential cure. Fifty percent of insulinomas and gastrinomas are not evident on preoperative imaging studies, despite their sophistication. Calcium angiography, endoscopic ultrasonography, isotope-labeled octreotide scanning, and injection of methylene blue during secretin angiography are recent imaging modalities that have shown promise in the localization of these tumors. Intraoperative ultrasound has emerged as the best method for operative detection of insulinomas. Duodenotomy and intraoperative endoscopic transillumination are especially important in the surgical management of Zollinger-Ellison syndrome because 30% to 40% of gastrinomas are located in the duodenum. The management of patients with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome continues to be controversial. Some advocate an aggressive surgical approach, whereas others have had little success in rendering patients eugastrinemic.

  12. Demographics and epidemiology of pancreatic cancer.

    PubMed

    Yeo, Theresa Pluth; Lowenfels, Albert B

    2012-01-01

    Pancreatic cancer affects 44,000 Americans and at least 250,000 individuals worldwide annually. The incidence is slowly increasing after a recent period of decline. Cases are predicted to increase globally because of increased longevity and the widespread adoption of cancer-causing behaviors, such as cigarette smoking, dietary indiscretion, and a global increase in diabetes. Well-known risk factors for pancreatic cancer are advancing age, tobacco smoking, obesity, certain inherited familial disorders, second-hand smoke exposure, chronic pancreatitis, and diabetes. Associations with human immunodeficiency virus, ABO blood group, hepatitis B virus, human immunodeficiency virus, and Helicobacter pylori have also been identified.

  13. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  14. Chronic pancreatitis.

    PubMed

    Majumder, Shounak; Chari, Suresh T

    2016-05-01

    Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. PMID:26948434

  15. [Diagnosis of inherited thrombocytopenia].

    PubMed

    Baccini, V; Alessi, M C

    2016-02-01

    Inherited thrombocytopenias are rare, heterogenous and probably under-diagnosed because often classified as autoimmune thrombocytopenia. About 20 genes were described responsible for these thrombocytopenias. Precise diagnosis is necessary because the prognosis is different and some of them can evolve into hemopathies. First of all, it is important to gather a body of evidence to orientate towards an inherited cause: presence of the thrombocytopenia since childhood and of other family cases is a strong argument. Secondly, it is difficult to target the genetic investigations that settle the precise diagnosis. Genetic variants responsible for inherited thrombocytopenias affect different stage during megakaryocytopoiesis and cause thrombocytopenias with distinct characteristics. Presence of extra-hematological features, platelets' size measurement and evaluation of bone marrow megakaryocyte morphology when it is possible allow a primary orientation. We propose a diagnostic approach considering extra-hematological features, mode of inheritance, morphology, molecular and functional platelets' studies and bone marrow megakaryocyte morphology in order to better target genetic study. Nevertheless, despite this approach, some inherited thrombocytopenias remain still unexplained and could benefit from new methods of new generation sequencing in the future. PMID:26617290

  16. Chronic pancreatitis.

    PubMed

    Chari, S T; DiMagno, E P

    2001-09-01

    An increasing number of novel mutations are associated with chronic pancreatitis. Some cause a high-penetrance, autosomal dominant type of clinical picture (eg, mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others have a low penetrance or are frequent in the general population (eg, mutations in Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen gene) and act as disease modifiers. The results of recent studies indicate that smoking adversely affects the course and complications of chronic pancreatitis (more frequent and faster rate of calcification and higher risk of development of pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients with this condition should not smoke. Using current diagnostic criteria, the accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is not good. For example, 39% of dyspeptic persons without any other evidence of chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not prevented or increased by pancreatic surgery. Islet cell autotransplantation holds promise for the prevention of diabetes in patients requiring total pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein occlusion is present in 7% of patients undergoing surgery for chronic pancreatitis, but fewer than one fifth of these patients have variceal bleeding before or after surgery.

  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. Multi-step pancreatic carcinogenesis and its clinical implications.

    PubMed

    Sakorafas, G H; Tsiotou, A G

    1999-12-01

    The poor prognosis of pancreatic cancer relates mainly to its delayed diagnosis. It has been repeatedly shown that earlier diagnosis of pancreatic cancer is associated with a better outcome. Molecular diagnostic methods (mainly detection of K-ras mutations in pure pancreatic or duodenal juice, on specimens obtained by percutaneous fine-needle aspirations or in stool specimens) can achieve earlier diagnosis in selected subgroups of patients, such as patients with chronic pancreatitis (especially hereditary), adults with recent onset of non-insulin-dependent diabetes mellitus and patients with some inherited disorders that predispose to the development of pancreatic cancer. There is increasing evidence that pancreatic carcinogenesis is a multi-step phenomenon. Screening procedures for precursor lesions in these selected subgroups of patients may reduce the incidence and mortality from pancreatic cancer.

  19. Male endocrine dysfunction.

    PubMed

    Hotaling, James M; Patel, Zamip

    2014-02-01

    Evaluation for endocrine function is a pivotal part of the male infertility workup. Endocrine dysfunction may result from endogenous and exogenous sources. This article describes the traditional roles that the hypothalamic-pituitary-gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as well as other insults that may contribute to hypospermatogenesis. Recent research into the role alternative hormonal axes play in spermatogenesis and promising new technologies that may correct inborn or acquired endocrinopathies leading to impaired sperm growth and maturation are discussed.

  20. Organs as inheritable property?

    PubMed

    Voo, Teck Chuan; Holm, Soren

    2014-01-01

    It has been argued that organs should be treated as individual tradable property like other material possessions and assets, on the basis that this would promote individual freedom and increase efficiency in addressing the shortage of organs for transplantation. If organs are to be treated as property, should they be inheritable? This paper seeks to contribute to the idea of organs as inheritable property by providing a defence of a default of the family of a dead person as inheritors of transplantable organs. In the course of discussion, various succession rules for organs and their justifications will be suggested. We then consider two objections to organs as inheritable property. Our intention here is to provoke further thought on whether ownership of one's body parts should be assimilated to property ownership.

  1. Endocrine system: part 1.

    PubMed

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  2. Animal models for investigating chronic pancreatitis

    PubMed Central

    2011-01-01

    Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

  3. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  4. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed. PMID:26972038

  5. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  6. Sleep and the endocrine system.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  7. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  8. Epigenetic inheritance of centromeres.

    PubMed

    Henikoff, S; Furuyama, T

    2010-01-01

    Centromeres of higher eukaryotes are epigenetically maintained; however, the mechanism that underlies centromere inheritance is unknown. Centromere identity and inheritance require the assembly of nucleosomes containing the CenH3 histone variant in place of canonical H3. Work from our laboratory has led to the proposal that epigenetic inheritance of centromeres evolved as adaptations of CenH3 and other centromere proteins to resist drive of selfish centromeres during female meiosis. Our molecular studies have revealed that the Drosophila CenH3 nucleosome is equivalent to half of the canonical H3 nucleosome and induces positive supercoils, as opposed to the negative supercoils induced by an H3 nucleosome. CenH3 likewise induces positive supercoils in functional yeast centromeres in vivo. The right-handed wrapping of DNA around the histone core implied by positive supercoiling indicates that centromeric nucleosomes are unlikely to be octameric and that the exposed surfaces holding the nucleosome together would be available for kinetochore protein recruitment. The mutual incompatibility of nucleosomes with opposite topologies could explain how centromeres are efficiently maintained as unique loci on chromosomes. We propose that the opposite wrapping of DNA around a half-nucleosome core particle facilitates a mode of inheritance that does not depend on DNA sequence, DNA modification or protein conformation.

  9. Pancreatic injury.

    PubMed

    Ahmed, Nasim; Vernick, Jerome J

    2009-12-01

    Injury to the pancreas, because of its retroperitoneal location, is a rare occurrence, most commonly seen with penetrating injuries (gun shot or stab wounds). Blunt trauma to the pancreas accounts for only 25% of the cases. Pancreatic injuries are associated with high morbidity and mortality due to accompanying vascular and duodenal injuries. Pancreatic injuries are not always easy to diagnose resulting in life threatening complications. Physical examination as well as serum amylase is not diagnostic following blunt trauma. Computed tomography (CT) scan can delineate the injury or transaction of the pancreas. Endoscopic retrograde pancreaticography (ERCP) is the main diagnostic modality for evaluation of the main pancreatic duct. Unrecognized ductal injury leads to pancreatic pseudocyst, fistula, abscess, and other complications. Management depends upon the severity of the pancreatic injury as well as associated injuries. Damage control surgery in hemodynamic unstable patients reduces morbidity and mortality.

  10. The endocrine quiz

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Nagesh, V. Sri

    2014-01-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject. PMID:24944922

  11. Endocrine diseases of rodents.

    PubMed

    Collins, Bobby R

    2008-01-01

    The frequency of documented endocrine diseases in rodents and other small mammals varies considerably among the species maintained as pets, biomedical research animals, or display animals in zoos. The clinical diagnosis of endocrine diseases almost never occurs in free-ranging animals in their native habitat. Feral animals that have clinical endocrine disease, such as neoplasia, adrenal cortical hyperplasia, or diabetes, would exhibit clinical signs of altered behavior that would result in their removal by predators. The diagnosis of endocrine disease thus takes place in the relatively protective environment of captivity. This observation should forewarn pet owners and clinicians caring for these animals that the environment contributes to the development of endocrine diseases in these animals.

  12. Chronic pancreatitis: A surgical disease? Role of the Frey procedure

    PubMed Central

    Roch, Alexandra; Teyssedou, Jérome; Mutter, Didier; Marescaux, Jacques; Pessaux, Patrick

    2014-01-01

    Although medical treatment and endoscopic interventions are primarily offered to patients with chronic pancreatitis, approximately 40% to 75% will ultimately require surgery during the course of their disease. Although pancreaticoduodenectomy has been considered the standard surgical procedure because of its favorable results on pain control, its high postoperative complication and pancreatic exocrine or/and endocrine dysfunction rates have led to a growing enthusiasm for duodenal preserving pancreatic head resection. The aim of this review is to better understand the rationale underlying of the Frey procedure in chronic pancreatitis and to analyze its outcome. Because of its hybrid nature, combining both resection and drainage, the Frey procedure has been conceptualized based on the pathophysiology of chronic pancreatitis. The short and long-term outcome, especially pain relief and quality of life, are better after the Frey procedure than after any other surgical procedure performed for chronic pancreatitis. PMID:25068010

  13. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP. PMID:22782018

  14. Pancreatic mixed ductal-islet tumors. Is this an entity?

    PubMed

    Permert, J; Mogaki, M; Andrén-Sandberg, A; Kazakoff, K; Pour, P M

    1992-02-01

    Thirty-eight human pancreatic cancer specimens were studied for the reactivity of cancer cells with monoclonal antibodies against insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, calcitonin, and with argyrophilic reactivity. Immunoreactivity with one or several antibodies or argyrophilic reactivity were found in 30 (79%) cases. In 17 cases, the number of endocrine cells was excessive and morphologically consistent with the mixed ductal-islet tumor. Although most immunoreactive cells were located at the base of the malignant glands, some had intraepithelial location and were also present in the invasive portion of cancers, indicating their malignant nature. Endocrine cell proliferation were found in the pancreatic tissue adjacent to the carcinoma in 8 out of 12 specimens examined. In these cases, the immunoreactive cells were either distributed among the acinar cells or ductal cells. More endocrine cells were found in the hyperplastic ducts; however, no correlation was found between the degree of hyperplasia and the occurrence of any type of immunoreactive cells. Although several types of endocrine cells occurred in different pancreatic regions (head, body, and tail), PP cells were restricted to tissues taken from the head of the pancreas. Experimental data and similar observations by other investigators led us to conclude that participation of endocrine cells in ductal-type carcinomas is a general phenomenon and does not justify the classification of these lesions to mixed ductal-islet entity. However, because immunoreactive cells were more common and numerous in well-differentiated carcinomas, they may have some prognostic values. PMID:1316418

  15. Epigenetic inheritance in ciliates.

    PubMed

    Nowacki, Mariusz; Landweber, Laura F

    2009-12-01

    2009 marks not only the 200th anniversary of Darwin's birth but also publication of the first scientific evolutionary theory, Lamarck's Philosophie Zoologique. While Lamarck embraced the notion of the inheritance of acquired characters, he did not invent it (Burkhardt, 1984). New phenomena discovered recently offer molecular pathways for the transmission of several acquired characters. Ciliates have long provided model systems to study phenomena that bypass traditional modes of inheritance. RNA, normally thought of as a conduit in gene expression, displays a novel mode of action in ciliated protozoa. For example, maternal RNA templates provide both an organizing guide for DNA rearrangements in Oxytricha and a template that can transmit spontaneous mutations that may arise during somatic growth to the next generation, providing two such mechanisms of so-called Lamarckian inheritance. This suggests that the somatic ciliate genome is really an 'epigenome', formed through templates and signals arising from the previous generation. This review will discuss these new biological roles for RNA, including non-coding 'template' RNA molecules. The evolutionary consequences of viable mechanisms in ciliates to transmit acquired characters may create an additional store of heritable variation that contributes to the cosmopolitan success of this diverse lineage of microbial eukaryotes.

  16. [Endocrine emergencies during pregnancy].

    PubMed

    Harbeck, B; Schütt, M; Sayk, F

    2012-03-01

    Endocrine emergencies during pregnancy can become life-threatening for both mother and fetus. In addition to some pregnancy-linked endocrine disorders, several pre-existing forms of endocrinopathy, such as Grave's disease, type 1 diabetes and adrenal insufficiency might deteriorate acutely during pregnancy. Early diagnosis and management are challenging because the classical symptoms are often modified by pregnancy. Laboratory tests are subject to altered physiological ranges and pharmacological options are limited while therapeutic goals are stricter than in the non-pregnant patient. This article focuses on endocrine emergencies complicating pregnancy. PMID:22349529

  17. Acute pancreatitis

    MedlinePlus

    ... rate Lab tests that show the release of pancreatic enzymes will be done. These include: Increased blood amylase level Increased serum blood lipase level Increased urine amylase ... swelling of the pancreas include: CT scan of the abdomen MRI of ...

  18. Pancreatitis - children

    MedlinePlus

    ... perform lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase level Blood lipase level Urine amylase level Other blood tests ... the pancreas include: Ultrasound of the abdomen (most common) CT ...

  19. Pancreatic abscess.

    PubMed Central

    Gartell, P C

    1982-01-01

    Three cases of pancreatic abscess are described to show the difficulties in diagnosis and that inadequate treatment is invariably fatal. Early recognition and prompt surgical drainage, together with biliary decompression if indicated, are advised. PMID:7069670

  20. Hereditary Pancreatitis.

    PubMed

    Rivera Rivera, Edgardo D; Chugh, Ankur; Cordova, Jonathon; Young, Sona

    2016-02-01

    A 13-year-old boy with a strong family history of hereditary pancreatitis was found to have a PRSS1 mutation after being tested at age 5 years during his first documented incident of pancreatitis. Since then, a multidisciplinary team has been treating him for the diagnosis of hereditary pancreatitis. His pain episodes increased in severity over the past several months such that the pain began to severely interfere with his daily life. After extensive discussion, a total pancreatectomy with auto islet cell transplant was performed. He is now pain free and does not require any insulin. This leads us to the questions of what is hereditary pancreatitis and how is it diagnosed? What are the management and follow-up strategies needed for these patients? This article addresses these questions and informs the reader about this diagnosis and the importance of having a high index of clinical suspicion. PMID:26878183

  1. Chronic pancreatitis and pancreatic cancer.

    PubMed

    Maisonneuve, Patrick; Lowenfels, Albert B

    2002-01-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention.

  2. CCAR1 is required for Ngn3-mediated endocrine differentiation

    SciTech Connect

    Lu, Chung-Kuang; Lai, Yi-Chyi; Lin, Yung-Fu; Chen, Hau-Ren; Chiang, Ming-Ko

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer We identify CCAR1 to directly interact with Ngn3. Black-Right-Pointing-Pointer CCAR1 is co-localized with Ngn3 in the nucleus. Black-Right-Pointing-Pointer CCAR1 cooperates with Ngn3 in activating NeuroD expression. Black-Right-Pointing-Pointer CCAR1 is required for Ngn3-mediated PANC-1 transdifferentiation. -- Abstract: Neurogenin3 (Ngn3) is a basic helix-loop-helix transcription factor that specifies pancreatic endocrine cell fates during pancreas development. It can also initiate a transdifferentiation program when expressed in pancreatic exocrine and ductal cells. However, how Ngn3 initiates a transcriptional cascade to achieve endocrine differentiation is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which is a transcriptional coactivator for nuclear receptors, also interacts with Ngn3. The association between Ngn3 and CCAR1 was verified by pull-down assays and co-immunoprecipitation analyses. Using gene reporter assays, we found that CCAR1 is essential for Ngn3 to activate the expression of the reporter genes containing the NeuroD promoter. Moreover, down-regulation of endogenous CCAR1 in the PANC-1 pancreatic ductal cell line inhibits the transdifferentiation program initiated by Ngn3. CCAR1 is, therefore, a novel partner of Ngn3 in mediating endocrine differentiation.

  3. Autoimmune pancreatitis.

    PubMed

    Omiyale, Ayodeji Oluwarotimi

    2016-06-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  4. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  5. Pancreatic Cancer Early Detection Program

    ClinicalTrials.gov

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  6. Effect of octreotide acetate on pancreatic exocrine function.

    PubMed

    Williams, S T; Woltering, E A; O'Dorisio, T M; Fletcher, W S

    1989-05-01

    Somatostatin and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.

  7. Endocrine system: part 2.

    PubMed

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

    2014-06-01

    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  8. Exercise and Inherited Arrhythmias.

    PubMed

    Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D

    2016-04-01

    Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise.

  9. Exercise and Inherited Arrhythmias.

    PubMed

    Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D

    2016-04-01

    Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise. PMID:26927864

  10. The Current Role of Venous Sampling in the Localization of Endocrine Disease

    SciTech Connect

    Lau, Jeshen H. G. Drake, William; Matson, Matthew

    2007-07-15

    Endocrine venous sampling plays a specific role in the diagnosis of endocrine disorders. In this article, we cover inferior petrosal sinus sampling, selective parathyroid venous sampling, hepatic venous sampling with arterial stimulation, adrenal venous sampling, and ovarian venous sampling. We review their indications and the scientific evidence justifying these indications in the diagnosis and management of Cushing's syndrome, hyperparathyroidism, pancreatic endocrine tumors, Conn's syndrome, primary hyperaldosteronism, pheochromocytomas, and androgen-secreting ovarian tumors. For each sampling technique, we compare its diagnostic accuracy with that of other imaging techniques and, where possible, look at how it impacts patient management. Finally, we incorporate venous sampling into diagnostic algorithms used at our institution.

  11. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

    PubMed Central

    Guo, Wen-yi; Zhao, Liang; Xiang, Ming-wei; Mei, Fang-chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment.

  12. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

    PubMed Central

    Guo, Wen-yi; Zhao, Liang; Xiang, Ming-wei; Mei, Fang-chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID:27656209

  13. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis.

    PubMed

    Hong, Yu-Pu; Guo, Wen-Yi; Wang, Wei-Xing; Zhao, Liang; Xiang, Ming-Wei; Mei, Fang-Chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-Hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID:27656209

  14. Conservative management of pediatric pancreatic pseudocyst using octreotide acetate.

    PubMed

    Mulligan, C; Howell, C; Hatley, R; Martindale, R; Clark, J

    1995-03-01

    Pancreatic pseudocysts in children are rare. A total of 213 cases have been reported in the literature, the majority secondary to trauma (65%). Treatment options range from conservative, non-operative management to operative drainage. Octreotide acetate, a long-acting analog of somatostatin, is a synthetic peptide with a variety of endocrine and gastrointestinal functions. Octreotide has been successfully used following pancreatic surgery to reduce exocrine function and most recently in the management of adult pancreatic pseudocysts. We report the efficacy of octreotide, as an adjunct to treatment, in two children with pancreatic pseudocyst. Each child was treated conservatively with bowel rest, hyperalimentation, and octreotide acetate (2.5 micrograms/kg SQ QD). Complete resolution of the pseudocysts occurred within 5 weeks. We conclude that octreotide acetate is a safe and potentially effective adjunct in the treatment of pediatric pancreatic pseudocyst, and should be added to the management of pseudocyst before drainage procedures.

  15. The inheritance of obesity.

    PubMed

    Savona-Ventura, Charles; Savona-Ventura, Stephanie

    2015-04-01

    Syndromic adiposity appears to have a predisposition to run in families suggesting a hereditary element in its transmission. Purely genetic defects and DNA sequence variants have been directly associated with the development of adiposity; however, these account for a very small proportion of cases. A stronger association has been made between the intrauterine and early childhood nutritional environment of the foetus and young child and the predisposition of childhood and subsequent adulthood obesity. The nutritional environments include both a situation of nutritional deprivation or excess working through the interplay of epigenetic changes, and pancreatic and hypothalamic development. This is further compounded by the nutritional and lifestyle attitudes of the particular at-risk family. Adiposity prevention measures must include reenforced intervention strategies stating with lifestyle education schemes during pregnancy followed through until infancy and early childhood especially in those families/individuals identified as being at a risk of developing significant adiposity.

  16. [Pancreatic ultrasonography].

    PubMed

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%.

  17. [Pancreatic pseudocysts].

    PubMed

    Stăncescu, M; Ciurea, S

    1989-01-01

    Clinical, evolutive and therapeutical aspects were studied, of 66 cases of patients with pancreatic pseudocysts hospitalized in the clinic over a period of 27 years. Particular modalities of onset were, those of patients with duodenal stenosis, mechanical jaundice, ascites and pleurisy, those in whom symptomatology suggested kidney or cholecystic disease. The intraoperative diagnosis raises the problem of differentiating a retroperitoneal tumor, identifying the possible association with a pancreatic cancer, and the condition when the pseudocysts are found at a certain distance from the pancreas itself. The therapeutical methods are codified, but recidives are possible. Cholecystectomy removes the biliary cause of pancreatitis which can determine the development of pseudocysts. The death rate of these cases was 6.3%.

  18. Transpapillary biliary stenting is a risk factor for pancreatic stones in patients with autoimmune pancreatitis

    PubMed Central

    Matsubayashi, Hiroyuki; Kishida, Yoshihiro; Iwai, Tomohiro; Murai, Katsuyuki; Yoshida, Masao; Imai, Kenichiro; Yamamoto, Yusuke; Kikuyama, Masataka; Ono, Hiroyuki

    2016-01-01

    Background and study aim: Pancreatic stones occasionally develop in autoimmune pancreatitis (AIP), often worsen endocrine and exocrine functions, and occasionally cause pain attacks. However, the risks of pancreatic stones in AIP have been poorly studied. The aim of this study was to analyze the risk factors associated with pancreatic stone formation in cases of AIP. Patients and methods: In total, 50 patients with AIP (39 males, 11 females; mean age 64.0 years), followed up for at least a year, were analyzed for their demographic and clinical findings and pancreatic stone occurrence. Results: In total, 50 patients were followed up for an average of 59.7 (12 – 120) months, with steroid treatment in 44 patients (88 %); pancreatic stones occurred in 14 (28 %) patients after the diagnosis of AIP and endoscopic treatment was needed in one patient with pain attack. The pancreatic stones appeared only in patients with long follow-up period (P < 0.001, 83.9 months vs. 49.6 months), biliary stenting (odds ratio [OR]: 8.40, P = 0.010), relapse (OR: 6.20, P = 0.023), jaundice (OR: 5.40, P = 0.019), and swelling of the duodenal major papilla (OR: 4.67, P = 0.040). Biliary stenting was placed for an average of 9.9 months in 27 patients. Multivariate analysis revealed a significant association only with biliary stenting (P = 0.011). The stones appeared relatively earlier in patients with stones in the main pancreatic duct or Santorini duct (22.1 months) than in patients where pancreatic stones developed elsewhere (53.4 months) (P = 0.018). Conclusions: The risk of pancreatic stone development should be taken into account when a biliary stent is placed in patients with AIP. PMID:27540582

  19. Long-term outcomes of autoimmune pancreatitis.

    PubMed

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-09-14

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  20. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  1. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.

  2. Inherited Colorectal Cancer Syndromes

    PubMed Central

    Kastrinos, Fay; Syngal, Sapna

    2011-01-01

    Colorectal cancer is the most common gastrointestinal malignancy and the second leading cause of cancer death in both men and women in the United States. Most colorectal cancer cases diagnosed annually are due to sporadic events but up to 5% are attributed to known monogenic disorders including Lynch syndrome, Familial Adenomatous Polyposis, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. These inherited colorectal cancer syndromes confer a markedly increased risk for the development of multiple cancers and predictive genetic testing is available to identify mutation carriers and at-risk family members. Through personalized strategies for diagnosis and management, a substantial reduction in morbidity and mortality has been appreciated among patients at highest risk for the development of colorectal cancer. PMID:22157284

  3. Computed Tomography of Pancreatitis and Pancreatic Cancer.

    PubMed

    Furlow, Bryant

    2015-01-01

    Pancreatic disease often is asymptomatic until tissue damage and complications occur or until malignancies have reached advanced stages and have metastasized. Contrast-enhanced multidetector computed tomography plays a central role in diagnosing, staging, and treatment planning for pancreatitis and pancreatic cancer. This article introduces the functional anatomy of the pancreas and common bile duct and the epidemiology, pathobiology, and computed tomography imaging of pancreatitis, calculi, and pancreatic cancer.

  4. Interactions between the endocrine and exocrine pancreas and their clinical relevance.

    PubMed

    Czakó, László; Hegyi, Péter; Rakonczay, Zoltán; Wittmann, Tibor; Otsuki, Makoto

    2009-01-01

    In consequence of the close anatomical and functional links between the exocrine and endocrine pancreas, any disease affecting one of these parts will inevitably affect the other. Pancreatic conditions which might cause diabetes mellitus include acute and chronic pancreatitis, pancreatic surgery, cystic fibrosis and pancreatic cancer. The development of diabetes greatly influences the prognosis and quality of life of patients with exocrine pancreatic diseases. It may cause life-threatening complications, such as hypoglycemia, due to the lack of glucagon and the impaired absorption of nutrients, or the micro- and macrovascular complications may impair the organ functions. Diabetes mellitus is an independent risk factor of mortality in those with exocrine pancreatic diseases. The treatment of pancreatic diabetes, a distinct metabolic and clinical form of diabetes, requires special knowledge. Diet and pancreatic enzyme replacement therapy may be sufficient in the early stages. Oral antidiabetic drugs are not recommended. If the diet proves inadequate to reach the glycemic goals, insulin treatment with multiple injections is required. Impairments of the exocrine pancreatic function and morphology in diabetic patients are frequent and well known. Atrophy of the exocrine tissue may be caused by the lack of trophic insulin, whereas pancreatic fibrosis can result from activation of stellate cells by hyperglycemia, or from microangiopathy and neuropathy. The regulation of the exocrine pancreatic function is also damaged because of the impaired effect of islet hormones. In the event of a proven impairment of the pancreatic exocrine function in diabetes mellitus, pancreatic enzyme replacement therapy is indicated. This may improve the nutritional condition of the patient and decrease the metabolic instability.

  5. Endocrine Problems After Childhood Cancer: Precocious Puberty

    MedlinePlus

    ... cancer Precocious Puberty Version 3.0 - 10/08 Endocrine Problems after Childhood Cancer: Precocious Puberty Children treated ... the complex system of glands known as the endocrine system. What is the endocrine system? The endocrine ...

  6. 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

  7. What Is Women's Endocrine Health?

    MedlinePlus

    ... healthy lifestyle and harness the power to prevent endocrine disorders, the Power of Prevention. Childhood Childhood is a ... frequent at this time. Learning how to prevent endocrine disorders during this age is pivotal. Young Women At ...

  8. [Pancreatic choristoma in the gallbladder: report of two cases].

    PubMed

    Beltrán, Marcelo A; Barría, Carlos; Naquira, Cecilia; Almonacid, Jorge; Cruces, Karina S

    2007-10-01

    Pancreatic choristoma is the occurrence of normal pancreatic tissue in an abnormal location without any anatomic continuity with the main body of the gland. Although heterotopia is uncommon in the gallbladder and biliary tract, anecdotic cases of gastric mucosa, liver, adrenal gland and pancreas among other tissues have been described. We report an eight year-old male and a 22 year-old female, electively operated for symptomatic cholelithiasis. On pathology, a nodule identified as a pancreatic endocrine and exocrine choristoma, was found in the gallbladder wall of both patients. We employed immunohistochemistry to characterize this choristoma. Tubular and epithelial structures were immunoreactive to cytokeratins 7, 8, 18, 19 and 20 and to CA19-9. Exocrine activity was documented by immunoreactivity to al-antitrypsin and al-chemotrypsin. Other immunohistochemical markers such as insulin and somatostatin were positive identifying endocrine activity.

  9. Staining Protocols for Human Pancreatic Islets

    PubMed Central

    Campbell-Thompson, Martha L.; Heiple, Tiffany; Montgomery, Emily; Zhang, Li; Schneider, Lynda

    2012-01-01

    Estimates of islet area and numbers and endocrine cell composition in the adult human pancreas vary from several hundred thousand to several million and beta mass ranges from 500 to 1500 mg 1-3. With this known heterogeneity, a standard processing and staining procedure was developed so that pancreatic regions were clearly defined and islets characterized using rigorous histopathology and immunolocalization examinations. Standardized procedures for processing human pancreas recovered from organ donors are described in part 1 of this series. The pancreas is processed into 3 main regions (head, body, tail) followed by transverse sections. Transverse sections from the pancreas head are further divided, as indicated based on size, and numbered alphabetically to denote subsections. This standardization allows for a complete cross sectional analysis of the head region including the uncinate region which contains islets composed primarily of pancreatic polypeptide cells to the tail region. The current report comprises part 2 of this series and describes the procedures used for serial sectioning and histopathological characterization of the pancreatic paraffin sections with an emphasis on islet endocrine cells, replication, and T-cell infiltrates. Pathology of pancreatic sections is intended to characterize both exocrine, ductular, and endocrine components. The exocrine compartment is evaluated for the presence of pancreatitis (active or chronic), atrophy, fibrosis, and fat, as well as the duct system, particularly in relationship to the presence of pancreatic intraductal neoplasia4. Islets are evaluated for morphology, size, and density, endocrine cells, inflammation, fibrosis, amyloid, and the presence of replicating or apoptotic cells using H&E and IHC stains. The final component described in part 2 is the provision of the stained slides as digitized whole slide images. The digitized slides are organized by case and pancreas region in an online pathology database

  10. The inheritance of centromere identity.

    PubMed

    Niikura, Yohei; Kitagawa, Risa; Kitagawa, Katsumi

    2016-07-01

    CENP-A (Centromere protein A) is a histone H3 variant that epigenetically determines the centromere position, but the mechanism of its centromere inheritance is obscure. We propose that CENP-A ubiquitylation, which is inherited through dimerization between rounds of cell division, is a candidate for the epigenetic mark of centromere identity. PMID:27652331

  11. Screening and surveillance approaches in familial pancreatic cancer.

    PubMed

    Canto, Marcia Irene

    2008-07-01

    Screening and surveillance for pancreatic cancer and its precursors is a relatively new indication for endoscopic ultrasound. It provides an alternative approach to the ineffective treatment of mostly incurable symptomatic pancreatic cancer. It is currently reserved for individuals with an increased risk for pancreatic ductal adenocarcinoma, such as those who have inherited genetic syndromes (eg, patients who have Peutz-Jeghers syndrome or hereditary pancreatitis, germline mutation carriers of p16 and BRCA2) and at-risk relatives of patients who have familial pancreatic cancer. This article discusses the rationale for performing screening and surveillance, the types of patients who are eligible for screening, the diagnostic modalities and technique for screening, the diagnostic yield of screening, and the ongoing research.

  12. Your Endocrine System (For Kids)

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Your Endocrine System KidsHealth > For Kids > Your Endocrine System Print A A A Text Size en español ... a pea, is the "master gland" of the endocrine system. It makes and releases a bunch of hormones ...

  13. Pancreatic Cancer Stage 3

    MedlinePlus

    ... historical Searches are case-insensitive Pancreatic Cancer Stage 3 Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing shows cancer ...

  14. Pancreatic enzyme replacement therapy during pancreatic insufficiency.

    PubMed

    Berry, Amy J

    2014-06-01

    Pancreatic stimulation and therefore digestion is a tightly controlled and hormonally mediated process. Any alterations affecting any of the systematic steps for successful digestion and absorption to occur will impair appropriate pancreatic enzymatic secretion, entry into the bowel lumen, functionality once inside the lumen, and thus appropriate mixing with foods and nutrients. Many causes of pancreatic insufficiency may require the initiation of pancreatic enzyme therapy, including but not limited to cystic fibrosis, pancreatic cancer, acute and chronic pancreatitis, and pancreatic surgery. This purpose of this article is to help clarify the conditions that cause pancreatic insufficiency, how to determine if the patient is malabsorbing, and the best use of pancreatic enzyme replacement therapy for treatment in these conditions. The first step in determining if pancreatic enzyme therapy is appropriate is to determine if the patient is malabsorbing specifically due to pancreatic exocrine insufficiency. An overview of the methods used to determine pancreatic insufficiency is provided, as well as appropriate treatment methods. Recent Food and Drug Administration regulations require a more thorough process, including randomized controlled trials to prove the safety and efficacy of pancreatic enzymes, to approve them for use. The studies used to verify efficacy also are examined. Last, dosing guidelines and some unconventional ways to administer pancreatic enzymes, such as during enteral feedings, are reviewed.

  15. Endocrine investigation and therapy.

    PubMed

    McClure, R D

    1987-08-01

    The most commonly investigated testicular disorder is male infertility. Although endocrine causes are uncommon, they are potentially curable. A careful history and examination for subtle features of hypogonadism are important initiating steps. Understanding the appropriate use of both baseline and dynamic testing of the hypothalamic-pituitary-gonadal axis (and, in certain instances, the adrenal and thyroid glands) is extremely important.

  16. The Endocrine Machinery.

    ERIC Educational Resources Information Center

    Fillman, David

    1987-01-01

    Promotes a reductionist approach to teaching about the endocrine system in high school biology and anatomy courses. Encourages the study of how hormones travel to the cells and affect them. Provides suggestions for activities and discussion questions, along with sample diagrams and flow charts. (TW)

  17. ENDOCRINE DISRUPTORS: LESSONS LEARNED

    EPA Science Inventory

    For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

  18. Genomic analyses identify molecular subtypes of pancreatic cancer.

    PubMed

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development. PMID:26909576

  19. Genomic analyses identify molecular subtypes of pancreatic cancer.

    PubMed

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  20. Endocrine dysfunction in hereditary hemochromatosis.

    PubMed

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies. PMID:26951056

  1. Endocrine dysfunction in hereditary hemochromatosis.

    PubMed

    Pelusi, C; Gasparini, D I; Bianchi, N; Pasquali, R

    2016-08-01

    Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

  2. Hypothalamic-endocrine aspects in Huntington's disease.

    PubMed

    Petersén, Asa; Björkqvist, Maria

    2006-08-01

    Huntington's disease (HD) is a hereditary and fatal disorder caused by an expanded CAG triplet repeat in the HD gene, resulting in a mutant form of the protein huntingtin. Wild-type and mutant huntingtin are expressed in most tissues of the body but the normal function of huntingtin is not fully known. In HD, the neuropathology is characterized by intranuclear and cytoplasmic inclusions of huntingtin aggregates, and cell death primarily in striatum and cerebral cortex. However, hypothalamic atrophy occurs at early stages of HD with loss of orexin- and somatostatin-containing cell populations. Several symptoms of HD such as sleep disturbances, alterations in circadian rhythm, and weight loss may be due to hypothalamic dysfunction. Endocrine changes including increased cortisol levels, reduced testosterone levels and increased prevalence of diabetes are found in HD patients. In HD mice, alterations in the hypothalamic-pituitary-adrenal axis occurs as well as pancreatic beta-cell and adipocyte dysfunction. Increasing evidence points towards important pathology of the hypothalamus and the endocrine system in HD. As many neuroendocrine factors are secreted into the cerebrospinal fluid, blood and urine, it is possible that their levels may reflect the disease state in the central nervous system. Investigating neuroendocrine changes in HD opens up the possibility of finding biomarkers to evaluate future therapies for HD, as well as of identifying novel targets for therapeutic interventions.

  3. [Nutrition, probiotics, antibiotics, antioxidative therapy, endoscopy in chronic pancreatitis].

    PubMed

    Mössner, J

    2006-10-18

    Treatment of chronic pancreatitis is dependent on the stage of the disease and consists of several arms: treatment of pain when ever possible according to its pathogenesis; treatment of complications primarily by interventional endoscopy, in cases of failure by surgery; therapy of exocrine insufficiency with porcine pancreatic extracts; treatment of endocrine insufficiency with insulin. Pseudocysts can be drained according to their location by either the transgastric, transduodenal, transpapillary or transcutaneous route. Distal prepapillary stenoses of the main pancreatic duct can be handled by placement of a plastic stent; similarily to treatment of biliary strictures. Stones leading to obstruction of the main pancreatic duct can be disintegrated by extracorporeal shock wave lithotripsy (ESWL) and the fragments removed by endoscopy after papillotomy. Transgastral endoscopic drainage of retroperitoneal necroses is still experimental. Prospective randomized multicenter trials comparing surgery with interventional endoscopy are still lacking. Failure of endoscopic therapy or suspicion of tumor is clearly an indication for surgery. There is no need for a specific diet in patients with chronic pancreatitis without having diabetes. In severe attacks, clinically similar to acute pancreatitis, enteral nutrition via a jejunal tube is replacing parenteral nutrition. However, prospective comparative trials are still mandatory. Prophylactic application of antibiotics in patients with pancreatic necrosis is again under debate. Whether probiotics are capable to decrease the risk of secondary pancreatic infection of necrosis has not been thoroughly studied. The hypothesis that capture of oxygen free radicals by drugs such as selenium may prevent frequency and severity of acute relapses has also not been proven.

  4. Opioids and endocrine dysfunction

    PubMed Central

    Hester, Joan

    2012-01-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist. PMID:26516462

  5. Endocrine disrupters as obesogens.

    PubMed

    Grün, Felix; Blumberg, Bruce

    2009-05-25

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity.

  6. Opioids and endocrine dysfunction.

    PubMed

    Seyfried, Oliver; Hester, Joan

    2012-02-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist.

  7. Endocrine disorders in pregnancy.

    PubMed

    Sipes, S L; Malee, M P

    1992-12-01

    Disorders of the pituitary gland such as diabetes insipidus, pituitary adenomas, and hyperprolactinemia, disorders of the thyroid gland such as Graves' disease and hypothyroidism, and diseases of the adrenal gland such as adrenocortical insufficiency and Cushing's syndrome can complicate pregnancy. The goals of this article were to provide a basic scientific understanding of the normal function of these endocrine glands, their pregnancy-related changes, and suggestions for diagnosis and treatment of maternal and fetal endocrine disorders during pregnancy. Antenatal recognition and appropriate management of the disorders that especially affect the fetus (i.e., maternal Graves' disease, fetal hypothyroidism, and congenital adrenal hyperplasia) is essential in order to prevent fetal and neonatal morbidity and mortality.

  8. Endocrine disruptors and obesity.

    PubMed

    Heindel, Jerrold J; Newbold, Retha; Schug, Thaddeus T

    2015-11-01

    The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development. These chemicals, so-called 'obesogens' might predispose some individuals to gain weight despite their efforts to limit caloric intake and increase levels of physical activity. This Review discusses the role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action. The research reviewed here provides knowledge that health scientists can use to inform their research and decision-making processes. PMID:26391979

  9. Pancreatic islet plasticity: Interspecies comparison of islet architecture and composition

    PubMed Central

    Steiner, Donald J.; Kim, Abraham; Miller, Kevin; Hara, Manami

    2010-01-01

    The pancreatic islet displays diverse patterns of endocrine cell arrangement. The prototypic islet, with insulin-secreting β-cells forming the core surrounded by other endocrine cells in the periphery, is largely based on studies of normal rodent islets. Recent reports on large animals, including humans, show a difference in islet architecture, in which the endocrine cells are randomly distributed throughout the islet. This particular species difference has raised concerns regarding the interpretation of data based on rodent studies to humans. On the other hand, further variations have been reported in marsupials and some nonhuman primates, which possess an inverted ratio of β-cells to other endocrine cells. This review discusses the striking plasticity of islet architecture and cellular composition among various species including changes in response to metabolic states within a single species. We propose that this plasticity reflects evolutionary acquired adaptation induced by altered physiological conditions, rather than inherent disparities between species. PMID:20657742

  10. Autoimmune pancreatitis can develop into chronic pancreatitis

    PubMed Central

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  11. The Epidemiology of Pancreatitis and Pancreatic Cancer

    PubMed Central

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

  12. Nuclear receptors in transgenerational epigenetic inheritance.

    PubMed

    Ozgyin, Lilla; Erdős, Edina; Bojcsuk, Dóra; Balint, Balint L

    2015-07-01

    Nuclear Receptors are ligand-activated transcription factors that translate information about the lipid environment into specific genetic programs, a property that renders them good candidates to be mediators of rapid adaptation changes of a species. Lipid-based morphogens, endocrine hormones, fatty acids and xenobiotics might act through this class of transcription factors making them regulators able to fine-tune physiological processes. Here we review the basic concepts and current knowledge on the process whereby small molecules act through nuclear receptors and contribute to transgenerational changes. Several molecules shown to cause transgenerational changes like phthalates, BPA, nicotine, tributylin bind and activate nuclear receptors like ERs, androgen receptors, glucocorticoid receptors or PPARγ. A specific subset of observations involving nuclear receptors has focused on the effects of environmental stress or maternal behaviour on the development of transgenerational traits. While these effects do not involve environmental ligands, they change the expression levels of Estrogen and glucocorticoid receptors of the second generation and consequently initiate an altered genetic program in the second generation. In this review we summarize the available literature about the role of nuclear receptors in transgenerational inheritance.

  13. [Endocrine problems during pregnancy].

    PubMed

    Mann, Klaus; Hintze, Gerhard

    2016-09-01

    Endocrine disorders may have an important influence on fertility, the course of a pregnancy and fetal development. For example, fertility is decreased and the risk of miscarriage is increased in women with autoimmune disorders, such as Addison's disease or autoimmune thyroiditis. Treatment of endocrine diseases in many cases has to be adapted during the course of a pregnancy. In patients with Addison's disease the dosage of hydrocortisone necessarily has to be increased. This is also valid for the time of delivery. Disorders of the thyroid gland are of great importance during pregnancy. If hypothyroidism is diagnosed in early pregnancy, immediate treatment with levothyroxine should be initiated. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Treatment of Graves's disease will be performed during the first trimenon with propylthiouracile, afterwards with methimazole (thiamazole). In contrast, thyrotoxicosis due to hCG should not be treated with methimazole. In this paper, we present an overview on the most important endocrine disorders during pregnancy. PMID:27598917

  14. Endocrine disrupting chemicals

    PubMed Central

    Yeung, Bonnie HY; Wan, Hin T; Law, Alice YS

    2011-01-01

    In the past 200 years, an enormous number of synthetic chemicals with diverse structural features have been produced for industrial, medical and domestic purposes. These chemicals, originally thought to have little or no biological toxicity, are widely used in our daily lives as well as are commonly present in foods. It was not until the first World Wildlife Federation Wingspread Conference held in 1994 were concerns about the endocrine disrupting (ED) effects of these chemicals articulated. The potential hazardous effects of endocrine disrupting chemicals (EDCs) on human health and ecological well-being are one of the global concerns that affect the health and propagation of human beings. Considerable numbers of studies indicated that endocrine disruption is linked to “the developmental basis of adult disease,” highlighting the significant effects of EDC exposure on a developing organism, leading to the propensity of an individual to develop a disease or dysfunction in later life. In this review, we intend to provide environmental, epidemiological and experimental data to associate pollutant exposure with reproductive disorders, in particular on the development and function of the male reproductive system. Possible effects of pollutant exposure on the processes of embryonic development, like sex determination and masculinization are described. In addition, the effects of pollutant exposure on hypothalamus-pituitary-gonadal axis, testicular signaling, steroidogenesis and spermatogenesis are also discussed. PMID:22319671

  15. Endocrine taste cells.

    PubMed

    Kokrashvili, Zaza; Yee, Karen K; Ilegems, Erwin; Iwatsuki, Ken; Li, Yan; Mosinger, Bedrich; Margolskee, Robert F

    2014-06-01

    In taste cells, taste receptors, their coupled G proteins and downstream signalling elements mediate the detection and transduction of sweet, bitter and umami compounds. In some intestinal endocrine cells, taste receptors and gustducin contribute to the release of glucagon-like peptide 1 (GLP-1) and other gut hormones in response to glucose and non-energetic sweeteners. Conversely, taste cells have been found to express multiple hormones typically found in intestinal endocrine cells, e.g. GLP-1, glucagon, somatostatin and ghrelin. In the present study, by immunohistochemistry, multiple subsets of taste cells were found to express GLP-1. The release of GLP-1 from 'endocrine taste cells' into the bloodstream was examined. In wild-type mice, even after oesophagectomy and vagotomy, oral stimulation with glucose induced an elevation of GLP-1 levels in the bloodstream within 10 min. Stimulation of taste cell explants from wild-type mice with glucose led to the release of GLP-1 into the medium. Knocking out of the Tas1r3 gene did not eliminate glucose-stimulated GLP-1 release from taste cells in vivo. The present results indicate that a portion of the cephalic-phase rise in circulating GLP-1 levels is mediated by the direct release of GLP-1 from taste cells into the bloodstream.

  16. Immunocytochemical study of the distribuition of endocrine cells in the pancreas of the Brazilian sparrow species Zonotrichia Capensis Subtorquata (Swaison, 1837).

    PubMed

    Nascimento, A A; Sales, A; Cardoso, T R D; Pinheiro, N L; Mendes, R M M

    2007-11-01

    In the present study, we investigated types of pancreatic endocrine cells and its respective peptides in the Brazilian sparrow species using immunocytochemistry. The use of polyclonal specific antisera for somatostatin, glucagon, avian pancreatic polypeptide (APP), YY polypeptide (PYY) and insulin, revealed a diversified distribution in the pancreas. All these types of immunoreactive cells were observed in the pancreas with different amounts. Insulin-Immunoreactive cells to (B cells) were most numerous, preferably occupying the central place in the pancreatic islets. Somatostatin, PPA, PYY and glucagon immunoreactive cells occurred in a lower frequency in the periphery of pancreatic islets.

  17. The Human Endocrine Pancreas: New Insights on Replacement and Regeneration.

    PubMed

    Domínguez-Bendala, Juan; Lanzoni, Giacomo; Klein, Dagmar; Álvarez-Cubela, Silvia; Pastori, Ricardo L

    2016-03-01

    Islet transplantation is an effective cell therapy for type 1 diabetes (T1D) but its clinical application is limited due to shortage of donors. After a decade-long period of exploration of potential alternative cell sources, the field has only recently zeroed in on two of them as the most likely to replace islets. These are pluripotent stem cells (PSCs) (through directed differentiation) and pancreatic non-endocrine cells (through directed differentiation or reprogramming). Here we review progress in both areas, including the initiation of Phase I/II clinical trials using human embryonic stem cell (hESc)-derived progenitors, advances in hESc differentiation in vitro, novel insights on the developmental plasticity of the pancreas, and groundbreaking new approaches to induce β cell conversion from the non-endocrine compartment without genetic manipulation. PMID:26774512

  18. Growth-hormone-releasing factor immunoreactivity in human endocrine tumors.

    PubMed Central

    Bostwick, D. G.; Quan, R.; Hoffman, A. R.; Webber, R. J.; Chang, J. K.; Bensch, K. G.

    1984-01-01

    Seventy-three human tumors and adjacent nonneoplastic tissues were analyzed immunohistochemically for the presence of growth-hormone-releasing factor (GRF). Four of 9 pancreatic endocrine tumors, 2 of 3 appendiceal carcinoids, and 1 of 5 cecal carcinoids were immunoreactive for GRF. One of the GRF-containing pancreatic tumors was associated with acromegaly. Histologically, the growth patterns of these tumors were variable, and the distribution of immunoreactive cells was patchy and irregular. There were no normal cells that contained GRF. These results indicate that GRF production by human tumors is more common than previously thought, although clinical acromegaly may not be apparent in patients who harbor such neoplasms. Images Figure 1 PMID:6093542

  19. Pancreatic stellate cells--multi-functional cells in the pancreas.

    PubMed

    Masamune, Atsushi; Shimosegawa, Tooru

    2013-01-01

    There is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. In addition, we have seen great progress in our understanding of the cell biology of PSCs and the interactions between PSCs and other cell types in the pancreas. In response to pancreatic injury or inflammation, quiescent PSCs are activated to myofibroblast-like cells. Recent studies have shown that the activation of intracellular signaling pathways such as mitogen-activated protein kinases plays a role in the activation of PSCs. microRNAs might also play a role, because the microRNA expression profiles are dramatically altered in the process of activation. In addition to producing extracellular matrix components such as type I collagen, PSCs have a wide variety of cell functions related to local immunity, inflammation, angiogenesis, and exocrine and endocrine functions in the pancreas. From this point of view, the interactions between PSCs and other cell types such as pancreatic exocrine cells, endocrine cells, and cancer cells have attracted increasing attention of researchers. PSCs might regulate exocrine functions in the pancreas through the cholecystokinin-induced release of acetylcholine. PSCs induce apoptosis and decrease insulin expression in β-cells, suggesting a novel mechanism of diabetes in diseased pancreas. PSCs promote the progression of pancreatic cancer by multiple mechanisms. Recent studies have shown that PSCs induce epithelial-mesenchymal transition and enhance the stem-cell like features of pancreatic cancer cells. In conclusion, PSCs should now be recognized as not only profibrogenic cells but as multi-functional cells in the pancreas.

  20. Pancreatic panniculitis associated with pancreatic carcinoma

    PubMed Central

    Zhang, Guannan; Cao, Zhe; Yang, Gang; Wu, Wenming; Zhang, Taiping; Zhao, Yupei

    2016-01-01

    Abstract Introduction: Pancreatic panniculitis is a very rare complication of pancreatic cancer, most often accompanying rare acinar cell carcinoma. We herein report a case of pancreatic panniculitis that was associated with pancreatic mucinous adenocarcinoma. Patient information: A 57-year-old male was referred to our hospital for weight loss. A physical examination revealed subcutaneous nodules on his lower extremities. The blood test showed abnormal increases in amylase, lipase, and carbohydrate antigen 19–9 levels. A computed tomography scan detected a hypodense 2 × 1.5 cm solid mass with an unclear margin in the head of the pancreas. The biopsy of subcutaneous nodules on the lower extremities was conducted and revealed lobular panniculitis. Pancreatic cancer and pancreatic panniculitis were strongly suspected. After the administration of octreotide acetate and the Whipple procedure, the serous amylase and lipase levels returned to normal, and the pancreatic panniculitis had almost resolved by 4 weeks later. Conclusion: Pancreatic panniculitis is a rare complication of pancreatic cancer. However, in the presence of a pancreatic mass, as in this case, clinicians should be aware that panniculitis may be the sentinel of pancreatic carcinoma. PMID:27495045

  1. Do endocrine disruptors cause hypospadias?

    PubMed Central

    Botta, Sisir; Cunha, Gerald R.

    2014-01-01

    Introduction Endocrine disruptors or environmental agents, disrupt the endocrine system, leading to various adverse effects in humans and animals. Although the phenomenon has been noted historically in the cases of diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT), the term “endocrine disruptor” is relatively new. Endocrine disruptors can have a variety of hormonal activities such as estrogenicity or anti-androgenicity. The focus of this review concerns on the induction of hypospadias by exogenous estrogenic endocrine disruptors. This has been a particular clinical concern secondary to reported increased incidence of hypospadias. Herein, the recent literature is reviewed as to whether endocrine disruptors cause hypospadias. Methods A literature search was performed for studies involving both humans and animals. Studies within the past 5 years were reviewed and categorized into basic science, clinical science, epidemiologic, or review studies. Results Forty-three scientific articles were identified. Relevant sentinel articles were also reviewed. Additional pertinent studies were extracted from the reference of the articles that obtained from initial search results. Each article was reviewed and results presented. Overall, there were no studies which definitely stated that endocrine disruptors caused hypospadias. However, there were multiple studies which implicated endocrine disruptors as one component of a multifactorial model for hypospadias. Conclusions Endocrine disruption may be one of the many critical steps in aberrant development that manifests as hypospadias. PMID:26816789

  2. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals.

    PubMed

    Wei, Yanchang; Yang, Cai-Rong; Wei, Yan-Ping; Zhao, Zhen-Ao; Hou, Yi; Schatten, Heide; Sun, Qing-Yuan

    2014-02-01

    The global prevalence of prediabetes and type 2 diabetes (T2D) is increasing, and it is contributing to the susceptibility to diabetes and its related epidemic in offspring. Although the impacts of paternal impaired fasting blood glucose and glucose intolerance on the metabolism of offspring have been well established, the exact molecular and mechanistic basis that mediates these impacts remains largely unclear. Here we show that paternal prediabetes increases the susceptibility to diabetes in offspring through gametic epigenetic alterations. In our findings, paternal prediabetes led to glucose intolerance and insulin resistance in offspring. Relative to controls, offspring of prediabetic fathers exhibited altered gene expression patterns in the pancreatic islets, with down-regulation of several genes involved in glucose metabolism and insulin signaling pathways. Epigenomic profiling of offspring pancreatic islets revealed numerous changes in cytosine methylation depending on paternal prediabetes, including reproducible changes in methylation over several insulin signaling genes. Paternal prediabetes altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapping with that of pancreatic islets in offspring. Our study uniquely revealed that prediabetes can be inherited transgenerationally through the mammalian germ line by an epigenetic mechanism.

  3. [Hypotension from endocrine origin].

    PubMed

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie

    2012-11-01

    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  4. Diabetic and endocrine emergencies

    PubMed Central

    Kearney, T; Dang, C

    2007-01-01

    Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004–5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population. PMID:17308209

  5. [Endocrine disorders and osteoporosis].

    PubMed

    Kinoshita, Yuka

    2015-10-01

    Secondary osteoporosis is a bone disease characterized by decreased bone mass that predisposes fractures due to underlying disorders or medication. Disorders of the endocrine system, such as primary hyperparathyroidism, hyperthyroidism, hypogonadism, growth hormone deficiency, Cushing's syndrome, and anorexia nervosa frequently cause secondary osteoporosis. In those diseases, hormone excess or deficiency affects functions of osteoblasts, osteocyte, and osteoclasts, leading to aberrant bone remodeling. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in most patients with secondary osteoporosis along with treatment of the underlying disease. PMID:26529938

  6. Type I interferons mediate pancreatic toxicities of PERK inhibition.

    PubMed

    Yu, Qiujing; Zhao, Bin; Gui, Jun; Katlinski, Kanstantsin V; Brice, Angela; Gao, Yan; Li, ChangHong; Kushner, Jake A; Koumenis, Constantinos; Diehl, J Alan; Fuchs, Serge Y

    2015-12-15

    The great preclinical promise of the pancreatic endoplasmic reticulum kinase (PERK) inhibitors in neurodegenerative disorders and cancers is marred by pancreatic injury and diabetic syndrome observed in PERK knockout mice and humans lacking PERK function and suffering from Wolcott-Rallison syndrome. PERK mediates many of the unfolded protein response (UPR)-induced events, including degradation of the type 1 interferon (IFN) receptor IFNAR1 in vitro. Here we report that whole-body or pancreas-specific Perk ablation in mice leads to an increase in IFNAR1 protein levels and signaling in pancreatic tissues. Concurrent IFNAR1 deletion attenuated the loss of PERK-deficient exocrine and endocrine pancreatic tissues and prevented the development of diabetes. Experiments using pancreas-specific Perk knockouts, bone marrow transplantation, and cultured pancreatic islets demonstrated that stabilization of IFNAR1 and the ensuing increased IFN signaling in pancreatic tissues represents a major driver of injury triggered by Perk loss. Neutralization of IFNAR1 prevented pancreatic toxicity of PERK inhibitor, indicating that blocking the IFN pathway can mitigate human genetic disorders associated with PERK deficiency and help the clinical use of PERK inhibitors.

  7. Bariatric Surgery and the Endocrine System

    MedlinePlus

    ... Endocrine System Fact Sheet Bariatric Surgery and the Endocrine System February, 2012 Download PDFs English Espanol Editors John ... could have both benefits and risks for your endocrine system—the network of glands that produce, store, and ...

  8. Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment

    PubMed Central

    Ro, Cynthia; Chai, Wanxing; Yu, Victoria E.; Yu, Run

    2013-01-01

    Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized. PMID:23237225

  9. Inherited thrombophilia and reproductive disorders

    PubMed Central

    Liatsikos, Spyros A.; Tsikouras, Panagiotis; Manav, Bachar; Csorba, Roland; von Tempelhoff, Georg Friedrich; Galazios, Georgios

    2016-01-01

    Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia. PMID:27026779

  10. [Inherited bone marrow failure syndromes].

    PubMed

    Okuno, Yusuke

    2016-02-01

    Inherited bone marrow failure syndromes comprise a series of disorders caused by various gene mutations. Genetic tests were formerly difficult to perform because of the large size and number of causative genes. However, recent advances in next-generation sequencing has enabled simultaneous testing of all causative genes to be performed at an acceptable cost. We collaboratively conducted a series of whole-exome sequencing studies of patients with inherited bone marrow failure syndromes and discovered RPS27/RPL27 and FANCT as causative genes of Diamond-Blackfan anemia and Fanconi anemia, respectively. Furthermore, we established a target gene sequencing system to cover 189 genes associated with pediatric blood diseases to assist genetic diagnoses in clinical practice. In this review, discovery of new causative genes and possible roles of next-generation sequencing in the genetic diagnosis of inherited bone marrow failure syndromes are discussed. PMID:26935625

  11. Nongenetic inheritance and transgenerational epigenetics.

    PubMed

    Szyf, Moshe

    2015-02-01

    The idea that inherited genotypes define phenotypes has been paramount in modern biology. The question remains, however, whether stable phenotypes could be also inherited from parents independently of the genetic sequence per se. Recent data suggest that parental experiences can be transmitted behaviorally, through in utero exposure of the developing fetus to the maternal environment, or through either the male or female germline. The challenge is to delineate a plausible mechanism. In the past decade it has been proposed that epigenetic mechanisms are involved in multigenerational transmission of phenotypes and transgenerational inheritance. The prospect that ancestral experiences are written in our epigenome has immense implications for our understanding of human behavior, health, and disease. PMID:25601643

  12. Nongenetic inheritance and transgenerational epigenetics.

    PubMed

    Szyf, Moshe

    2015-02-01

    The idea that inherited genotypes define phenotypes has been paramount in modern biology. The question remains, however, whether stable phenotypes could be also inherited from parents independently of the genetic sequence per se. Recent data suggest that parental experiences can be transmitted behaviorally, through in utero exposure of the developing fetus to the maternal environment, or through either the male or female germline. The challenge is to delineate a plausible mechanism. In the past decade it has been proposed that epigenetic mechanisms are involved in multigenerational transmission of phenotypes and transgenerational inheritance. The prospect that ancestral experiences are written in our epigenome has immense implications for our understanding of human behavior, health, and disease.

  13. Are specific allergen sensitivities inherited?

    PubMed

    Misiak, Rana Tawil; Wegienka, Ganesa; Zoratti, Edward

    2010-09-01

    A family history of an allergic condition is a well-accepted risk factor for the development of an allergic condition in an individual, particularly for allergic disorders such as asthma, eczema, and allergic rhinitis. However, the question of whether specific allergen sensitization is inherited requires a complicated answer, as environmental exposure plays an important role in the development of allergen-specific IgE. This article summarizes the findings of recent studies in the literature regarding what is known about the inheritance of specific allergens. Overall, properly collected and analyzed data appear to both support and refute the hypothesis that specific allergen sensitization is inherited, even when attempting to account for the complexities of varying study methodologies and the evaluation of diverse populations and communities. PMID:20574668

  14. An immunohistochemical study of the endocrine cells in the gastrointestinal mucosa of the Caiman latirostris.

    PubMed

    Yamada, J; Campos, V J; Kitamura, N; Pacheco, A C; Yamashita, T; Yanaihara, N

    1987-05-01

    Twelve endocrine cell types immunoreactive for either 5-hydroxytryptamine (5-HT), somatostatin, gastrin, motilin, neurotensin, bovine pancreatic polypeptide (BPP), avian pancreatic polypeptide (APP), pancreatic glucagon, enteroglucagon, glicentin, secretin or cholecystokinin (CCK) were found in gastrointestinal mucosa of Caiman latirostris. Moderate numbers of enteroglucagon-immunoreactive cells, a few 5-HT-, somatostatin- and motilin-immunoreactive cells and rare pancreatic glucagon-immunoreactive cells were found in the fundic stomach. Numerous gastrin-immunoreactive cells and moderate numbers of somatostatin- and motilin-immunoreactive cells were seen in the pyloric stomach. Moderate numbers of 5-HT-, gastrin-, motilin- and enteroglucagon-immunoreactive cells, a few somatostatin-, neurotensin- and BPP-immunoreactive cells, and rare APP-, pancreatic glucagon-, glicentin-, secretin- and CCK-immunoreactive cells were observed in the proximal intestine. Moderate numbers of 5-HT-immunoreactive cells, small to moderate numbers of neurotensin- and enteroglucagon-immunoreactive cells and occasional somatostatin-, motilin- and BPP-immunoreactive cells were seen in the distal intestine. Moderate numbers of neurotensin-immunoreactive cells and a few 5-HT-immunoreactive cells were found also in the cloaca. Cells immunoreactive for gastrin releasing polypeptide, bombesin and gastric inhibitory peptide were not observed in the caiman gastrointestinal epithelium. The differences in endocrine cell types between the caiman and alligator are discussed in terms of their topographic distribution.

  15. Data on morphometric analysis of the pancreatic islets from C57BL/6 and BALB/c mice.

    PubMed

    da Silva, Thiago Aparecido; Lemes, Robertha Mariana; Oliveira, Carlo Jose Freire; Almeida, Aline da Silva; Chica, Javier Emílio Lazo

    2016-09-01

    The endocrine portion of the pancreas, which is characterized by pancreatic islets, has been widely investigated among different species. The BALB/c and C57BL/6 mice are extensively used in experimental research, and the morphometric differences in the pancreatic islets of these animals have not been evaluated so far. Thus, our data have a comparative perspective related to the morphometric analysis of area, diameters, circularity, and density of pancreatic islets from BALB/c and C57BL/6 mice. The data presented here are focused to evaluate the differences in morphology of pancreatic islets of two common laboratory mouse strains.

  16. Diabetic Ketoacidosis with Concurrent Pancreatitis, Pancreatic β Islet Cell Tumor, and Adrenal Disease in an Obese Ferret (Mustela putorius furo)

    PubMed Central

    Phair, Kristen A; Carpenter, James W; Schermerhorn, Thomas; Ganta, Chanran K; DeBey, Brad M

    2011-01-01

    A 5.5-y-old spayed female ferret (Mustela putorius furo) with a history of adrenal disease, respiratory disease, and chronic obesity was evaluated for progressive lethargy and ataxia, diminished appetite, and possible polyuria and polydipsia. Physical examination revealed obesity, lethargy, tachypnea, dyspnea, a pendulous abdomen, significant weakness and ataxia of the hindlimbs, prolonged skin tenting, and mild tail-tip alopecia. Clinicopathologic analysis revealed severe hyperglycemia, azotemia, an increased anion gap, glucosuria, ketonuria, proteinuria, and hematuria. Abdominal ultrasonography showed hyperechoic hepatomegaly, bilateral adrenomegaly, splenic nodules, mild peritoneal effusion, and thickened and mildly hypoechoic limbs of the pancreas with surrounding hyperechoic mesentery. Fine-needle aspirates of the liver were highly suggestive of hepatic lipidosis. In light of a diagnosis of concurrent diabetic ketoacidosis and pancreatitis, the ferret was treated with fluid therapy, regular and long-acting insulin administration, and pain medication. However, electrolyte derangements, metabolic acidosis, dyspnea, and the clinical appearance of the ferret progressively worsened despite treatment, and euthanasia was elected. Necropsy revealed severe hepatic lipidosis, severe suppurative pancreatitis and vacuolar degeneration of pancreatic islet cells, a pancreatic β islet cell tumor, bilateral adrenal cortical adenomas, and myocardial fibrosis. To our knowledge, this case represents the first report of concurrent diabetes mellitus, pancreatitis, pancreatic β islet cell tumor (insulinoma), and adrenal disease in a domestic ferret. The simultaneous existence of 3 endocrine diseases, pancreatitis, and their associated complications is a unique and clinically challenging situation. PMID:21838985

  17. Notch signaling differentially regulates the cell fate of early endocrine precursor cells and their maturing descendants in the mouse pancreas and intestine.

    PubMed

    Li, Hui Joyce; Kapoor, Archana; Giel-Moloney, Maryann; Rindi, Guido; Leiter, Andrew B

    2012-11-15

    Notch signaling inhibits differentiation of endocrine cells in the pancreas and intestine. In a number of cases, the observed inhibition occurred with Notch activation in multipotential cells, prior to the initiation of endocrine differentiation. It has not been established how direct activation of Notch in endocrine precursor cells affects their subsequent cell fate. Using conditional activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the effects of Notch in both organs, on cell fate of early endocrine precursors and maturing endocrine-restricted cells, respectively. Notch did not preclude the differentiation of a limited number of endocrine cells in either organ when activated in Ngn3(+) precursor cells. In addition, in the pancreas most Ngn3(+) cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3(+) cells, Notch favored enterocyte and goblet cell fates, while selecting against endocrine and Paneth cell differentiation. A small fraction of NeuroD1(+) cells in the pancreas retain plasticity to respond to Notch, giving rise to intraislet ductules as well as cells with no detectable pancreatic lineage markers that appear to have limited ultrastructural features of both endocrine and duct cells. These results suggest that Notch directly regulates cell fate decisions in multipotential early endocrine precursor cells. Some maturing endocrine-restricted NeuroD1(+) cells in the pancreas switch to the duct lineage in response to Notch, indicating previously unappreciated plasticity at such a late stage of endocrine differentiation.

  18. [Surgery for pancreatic neuroendocrine tumors].

    PubMed

    Shibata, Chikashi; Egawa, Shin-Ichi; Motoi, Fuyuhiko; Morikawa, Takanori; Naitoh, Takeshi; Unno, Michiaki; Sasaki, Iwao

    2012-11-01

    Approximately half of pancreatic neuroendocrine tumors (PNETs) are nonfunctioning, and insulinoma and gastrinoma are frequent forms of functioning tumors. The treatment of patients with PNETs should be based on the consideration that more than half are malignant except for insulinomas. Multiple endocrine neoplasia type 1 (MEN1) is often complicated with gastrinoma. Endoscopic ultrasound and somatostain receptor scintigraphy are useful in diagnosing PNETs, and the selective arterial secretagogue injection test is performed if necessary. WHO2010 is available as a histopathologic grading system of malignancy. Although surgical resection should first be considered as a treatment for PNETs, liver metastasis is a major factor hindering resection. In Japan, the choices of drugs to treat liver metastases are too few. In patients with MEN1 in whom PNETS are frequently multiple, we should perform procedures that preserve pancreatic function, although some patients may require total pancreatectomy for the complete resection of tumors. The indications for total pancreatectomy should be determined individually based on the tumor status and patient age. PMID:23330458

  19. Male infertility. 3. Endocrine causes.

    PubMed

    McNally, M R

    1987-02-01

    Endocrine causes of male infertility range from easily manageable disorders such as hypothyroidism to complex problems such as pituitary tumors. Proper management requires a thorough understanding of the hypothalamic-pituitary-testicular axis. Hormonal evaluation is performed only when the patient's history and results of physical examination indicate an endocrine problem. With proper identification and treatment, most of these problems can be successfully managed.

  20. Trauma and the endocrine system.

    PubMed

    Mesquita, Joana; Varela, Ana; Medina, José Luís

    2010-12-01

    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma.

  1. Imaging of Acute Pancreatitis.

    PubMed

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist.

  2. [Dementia due to Endocrine Diseases].

    PubMed

    Matsunaga, Akiko; Yoneda, Makoto

    2016-04-01

    Endocrine diseases affecting various organs, such as the pituitary gland, the thyroid, the parathyroid, the adrenal glands and the pancreas, occasionally cause dementia. While Alzheimer's disease (AD) is the main cause of dementia in the elderly and is untreatable, dementia caused by endocrine diseases is treatable in most cases. However, patients with dementia associated with endocrine diseases show memory impairments similar to those found in AD, often leading to misdiagnoses. Patients with endocrine diseases often present with other characteristic systemic and neuropsychiatric symptoms caused by altered hormone levels. Such neuropsychiatric symptoms include involuntary movements, depression, seizures, and muscle weakness. In these cases, abnormalities in imaging and blood or urine tests are helpful in making a differential diagnosis. As delays in the diagnosis and treatment of these patients may cause irreversible brain damage, it is imperative for clinicians to carefully exclude the possibility of latent endocrine diseases when treating patients with dementia.

  3. Pancreatic-pleural fistula in chronic pancreatitis.

    PubMed

    Elkaoui, Hakim; Atoini, Fouad; Bouchentouf, Sidi Mohamed; El Omari, Fatima; Mahi, Mohamed; Ait Ali, Abdelmounaim; Bounaim, Ahmed; Sair, Khalid; Zentar, Aziz

    2012-03-01

    Pancreatic-pleural fistula is a rare condition and few data related to its diagnosis and treatment are available. A fistulous connection linking the pancreas with the pleura via the diaphragm or mediastinum through the retroperitoneal area is formed. We report on a case with pancreatic-pleural fistula at its early stages in an alcoholic male patient aged 45 years with known chronic pancreatitis. The operation by Roux-en-Y jejuno-pseudocystostomy was followed by chest tube drainage. PMID:22560825

  4. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  5. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  6. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  7. Pancreatic blood flow in experimental acute pancreatitis

    SciTech Connect

    Berry, A.R.; Millar, A.M.; Taylor, T.V.

    1982-05-01

    The etiology and pathogenesis of acute necrotizing hemorrhagic pancreatitis remain controversial. Recent work has suggested that an early fall in pancreatic blood flow, causing ischemia, may be the initiating factor. Using an established rat model of hemorrhagic pancreatitis and the fractional indicator distribution technique with /sup 86/RbCl, pancreatic blood flow and tissue perfusion have been measured at various times in the condition. Six groups of ten rats were studied: control sham operation and pancreatitis groups were sacrificed at 1, 6, and 24 hr. Pancreatic blood flow (% of cardiac output) and perfusion (blood flow/g tissue) were measured. Blood flow was increased by a maximum of 53% at 1 hr (P less than 0.001) and remained elevated for 24 hr, and perfusion was increased by a maximum of 70% (P less than 0.001) at 1 hr and remained elevated at 6 hr. Pancreatic perfusion declines after 6 hr due to increasing gland edema. The results demonstrate a significant increase in pancreatic blood flow and perfusion in experimentally induced acute pancreatitis, suggesting a primary inflammatory response, and refute the ischemic etiological theory.

  8. English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

    PubMed

    Hoffmeister, A; Mayerle, J; Beglinger, C; Büchler, M W; Bufler, P; Dathe, K; Fölsch, U R; Friess, H; Izbicki, J; Kahl, S; Klar, E; Keller, J; Knoefel, W T; Layer, P; Loehr, M; Meier, R; Riemann, J F; Rünzi, M; Schmid, R M; Schreyer, A; Tribl, B; Werner, J; Witt, H; Mössner, J; Lerch, M M

    2015-12-01

    Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.

  9. Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.

    PubMed

    Delaspre, Fabien; Beer, Rebecca L; Rovira, Meritxell; Huang, Wei; Wang, Guangliang; Gee, Stephen; Vitery, Maria del Carmen; Wheelan, Sarah J; Parsons, Michael J

    2015-10-01

    Diabetes is associated with a paucity of insulin-producing β-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in β-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch-responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors. To test our hypothesis that adult CACs are also progenitors, we took two complementary approaches: 1) We established the transcriptome for adult CACs. Using gene ontology, transgenic lines, and in situ hybridization, we found that the CAC transcriptome is enriched for progenitor markers. 2) Using lineage tracing, we demonstrated that CACs do form new endocrine cells after β-cell ablation or partial pancreatectomy. We concluded that CACs and their larval predecessors are the same cell type and represent an opportune model to study both β-cell neogenesis and β-cell regeneration. Furthermore, we show that in cftr loss-of-function mutants, there is a deficiency of larval CACs, providing a possible explanation for pancreatic complications associated with cystic fibrosis. PMID:26153247

  10. Ectopic apudocarcinomas and associated endocrine hyperplasias of the foregut.

    PubMed Central

    Friesen, S R; McGuigan, J E

    1975-01-01

    Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become "arrested" in the mesoderm or in other ectopic locations. They may become hyperplastic, adenomatous or malignant. Eight illustrative patients are reported. One patient had "pancreatic hyperparathyroidism" with hypercalcemic crises, pancreatic apudocarcinoma, normal parathyroids, biologically active parathormone, but inert immunochemically to the usual parathyroid antisera. Two had gastrin-secreting malignancies in the mesoderm. Remission after excision, but eventual recurrence of the syndrome due to islet cell hyperplasia required total gastrectomy. One patient had a gastric corpus apudocarcinoma found prospectively with hypergastrinemia which required excision of the tumor. One patient had acromegaly with hypergastrinemia and antral gastrinosis treated by pituitary irradiation, One patient had the antral or intermediary type of the Zollinger-Ellison syndrome with moderate hypergastrinemia, duodenal ulcer and antral gastrinosis, treated by vagotomy and antrectomy. One patient had hyperparathyroidism with antral gastrinosis, treated by parathyroidectomy. One patient had malignant Zollinger-Ellison syndrome and developed associated thyroid parafollicular cell hyperplasia and parathyroid chief cell hyperplasia, treated by total gastrectomy and multiple endocrine excisions. These investigative observations demonstrate ectopic loci and associated hyperplasias which support the concept of migration and bizarre potentiality of polypeptide-secreting cells of the foregut. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. PMID:241302

  11. Advances in the etiology of chronic pancreatitis.

    PubMed

    Lerch, Markus M; Mayerle, Julia; Aghdassi, Ali A; Budde, Christoph; Nitsche, Claudia; Sauter, Gabriele; Persike, Maria; Günther, Annett; Simon, Peter; Weiss, F Ulrich

    2010-01-01

    In the past, chronic pancreatitis has been regarded as a fairly uniform and largely untreatable disorder that most commonly affects patients who both lack gainful employment or adequate insurance coverage and have a tendency to smoke and drink. Large clinical trials suggest that this perception is not only misguided and discriminatory but also not based on facts. We forgot that the perception of chronic liver disease was similar before World War II, and just like liver cirrhosis the fibrosis and cirrhosis of the pancreas--i.e. chronic pancreatitis--is the end result of a range of environmental, inflammatory, infectious and genetic disorders. A growing number of these have only recently been recognized as a distinct entity and several of which are becoming truly treatable. A large proportion of the risk for developing pancreatitis is conveyed by genetic risk factors, and we estimate that less than half of those have been identified so far. The same holds true for protective factors that can prevent pancreatitis, even in the face of excessive alcohol abuse. Various gene mutations and polymorphisms appear to determine an individual's susceptibility for developing pancreatic disease, for the severity of the disease, and for the disease progression. The spectrum of genotype/phenotype associations ranges from straightforward autosomal dominant traits with near-complete penetrance, as for the most common mutations in the cationic trypsinogen gene (PRSS1), to moderate risks factors without mendelian inheritance patterns, as for SPINK1 and CFTR mutations, to very subtle risk associations and disease modifiers that can only be identified in large cohort studies, as for the chymotrypsin C, calcium-sensing receptor and the anionic trypsin (PRSS2) mutations. Only a better understanding of the disease mechanisms that underlie these changes will make an individualized therapy of pancreatic disorders a realistic option.

  12. Pancreatitis - series (image)

    MedlinePlus

    ... common bile duct and block the flow of pancreatic enzymes out of the pancreas into the intestine. Pancreatitis ... three to five days, to prevent secretion of enzymes by the pancreas. He will also receive pain medication to control ...

  13. Endocrine effects of marijuana.

    PubMed

    Brown, Todd T; Dobs, Adrian S

    2002-11-01

    In the 35 years since the active compound of marijuana, delta9-tetrahydrocannabinol, was isolated, the psychological and physiological impact of marijuana use has been actively investigated. Animal models have demonstrated that cannabinoid administration acutely alters multiple hormonal systems, including the suppression of the gonadal steroids, growth hormone, prolactin, and thyroid hormone and the activation of the hypothalamic-pituitary-adrenal axis. These effects are mediated by binding to the endogenous cannabinoid receptor in or near the hypothalamus. Despite these findings in animals, the effects in humans have been inconsistent, and discrepancies are likely due in part to the development of tolerance. The long-term consequences of marijuana use in humans on endocrine systems remain unclear.

  14. Endocrine activation in tachycardias.

    PubMed

    Lukac, P; Lukacova, S; Vigas, M; Hatala, R

    2001-01-01

    This article reviews the complex character of neuroendocrine response to paroxysmal tachycardia. While the endocrine influences in arrhythmogenesis are well perceived by the cardiologists, less attention has been paid to influence of tachycardia on neuroendocrine activation. However, this may significantly alter the clinical course of tachycardias and its responses to pharmacotherapeutic interventions. Main characteristics of hormones with direct relationship to cardiovascular system (ANP, AVP, catecholamines, angiotensin and others) are listed with description of regulation of their secretion and main biological effects, especially with regard to regulation of circulation. Changes in hemodynamics during tachycardia with accompanying changes in ANP, AVP renin-angiotensin-aldosterone system, sympatho-neural and sympatho-adrenal activation are reviewed. Further research and understanding require more complex approach and concentration on interrelationship of different regulatory hormones in tachycardia. (Fig. 2, Ref. 96.) PMID:11763674

  15. Real-time detection of acetylcholine release from the human endocrine pancreas.

    PubMed

    Rodriguez-Diaz, Rayner; Dando, Robin; Huang, Y Anthony; Berggren, Per-Olof; Roper, Stephen D; Caicedo, Alejandro

    2012-05-03

    Neurons, sensory cells and endocrine cells secrete neurotransmitters and hormones to communicate with other cells and to coordinate organ and system function. Validation that a substance is used as an extracellular signaling molecule by a given cell requires a direct demonstration of its secretion. In this protocol we describe the use of biosensor cells to detect neurotransmitter release from endocrine cells in real-time. Chinese hamster ovary cells expressing the muscarinic acetylcholine (ACh) receptor M3 were used as ACh biosensors to record ACh release from human pancreatic islets. We show how ACh biosensors loaded with the Ca(2+) indicator Fura-2 and pressed against isolated human pancreatic islets allow the detection of ACh release. The biosensor approach is simple; the Ca(2+) signal generated in the biosensor cell reflects the presence (release) of a neurotransmitter. The technique is versatile because biosensor cells expressing a variety of receptors can be used in many applications. The protocol takes ∼3 h.

  16. Real-time detection of acetylcholine release from the human endocrine pancreas

    PubMed Central

    Rodriguez-Diaz, Rayner; Dando, Robin; Huang, Y Anthony; Berggren, Per-Olof; Roper, Stephen D; Caicedo, Alejandro

    2012-01-01

    Neurons, sensory cells and endocrine cells secrete neurotransmitters and hormones to communicate with other cells and to coordinate organ and system function. Validation that a substance is used as an extracellular signaling molecule by a given cell requires a direct demonstration of its secretion. In this protocol we describe the use of biosensor cells to detect neurotransmitter release from endocrine cells in real-time. Chinese hamster ovary cells expressing the muscarinic acetylcholine (ACh) receptor M3 were used as ACh biosensors to record ACh release from human pancreatic islets. We show how ACh biosensors loaded with the Ca2+ indicator Fura-2 and pressed against isolated human pancreatic islets allow the detection of ACh release. The biosensor approach is simple; the Ca2+ signal generated in the biosensor cell reflects the presence (release) of a neurotransmitter. The technique is versatile because biosensor cells expressing a variety of receptors can be used in many applications. The protocol takes ~3 h. PMID:22555241

  17. Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

    ClinicalTrials.gov

    2016-02-16

    Pancreatic Adenocarcinoma; Poorly Differentiated Malignant Neoplasm; Resectable Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Undifferentiated Pancreatic Carcinoma

  18. Psychological aspects of endocrine disease.

    PubMed

    Sonino, N; Guidi, J; Fava, G A

    2015-03-01

    This review illustrates how an innovative psychoneuroendocrine approach to endocrine patients may improve their management. Important psychological issues pertain to all the different phases of an endocrine disorder. Before disease onset, stressful life events may play a pathogenetic role and, together with chronic stress, may contribute to a cumulative burden also called allostatic load; psychological and psychiatric symptoms are common both in the prodromal and in the active phase of illness; after cure or remission, there could be residual symptoms and impaired quality of life that deserve attention. All these aspects should be taken into consideration and introduced in current endocrine care and practice.

  19. Endocrine Proxies Can Simplify Endocrine Complexity to Enable Evolutionary Prediction.

    PubMed

    Davidowitz, Goggy

    2016-08-01

    It is well understood that much of evolutionary change is mediated through the endocrine system with growing interest to identify how this occurs. This however, causes a conflict of sorts. To understand endocrine mechanism, a focus on detail is required. In contrast, to understand evolutionary change, reduction to a few key traits is essential. Endocrine proxies, measurable traits that accurately reflect specific hormonal titers or the timing of specific hormonal events, can reduce endocrine complexity to a few traits that enable predictions of how the endocrine system regulates evolutionary change. In the tobacco hornworm (Manduca sexta, Sphingidae), three endocrine proxies, measured on 5470 individuals, were used to test explicit predictions of how the endocrine system regulates the response to 10 generations of simultaneous selection on body size and development time. The critical weight (CW) reflects the variation in the cessation of juvenile hormone (JH) secretion in the last larval instar, the interval to cessation of growth (ICG) reflects the variation in prothoracicotropic hormone and 20-hydroxyecdysone (20E). Growth rate (GR) reflects the nutrient signaling pathways, primarily the insulin and TOR This is a standard identity similar to DNA signaling pathways. These three endocrine proxies explained 99% and 93% of the variation in body size and development time, respectively, following the 10 generations of simultaneous selection. When the two focal traits, body size and development time, were selected in the same direction, both to either increase or both to decrease, the response to selection was determined primarily by the CW and the ICG, proxies for the developmental hormones JH and 20E, and constrained by GR. In contrast, when the two focal traits were selected in opposite directions, one to increase and the other to decrease, the response to selection was determined primarily by the insulin and TOR signaling pathways as measured by their proxy, GR, and

  20. Endocrine Proxies Can Simplify Endocrine Complexity to Enable Evolutionary Prediction.

    PubMed

    Davidowitz, Goggy

    2016-08-01

    It is well understood that much of evolutionary change is mediated through the endocrine system with growing interest to identify how this occurs. This however, causes a conflict of sorts. To understand endocrine mechanism, a focus on detail is required. In contrast, to understand evolutionary change, reduction to a few key traits is essential. Endocrine proxies, measurable traits that accurately reflect specific hormonal titers or the timing of specific hormonal events, can reduce endocrine complexity to a few traits that enable predictions of how the endocrine system regulates evolutionary change. In the tobacco hornworm (Manduca sexta, Sphingidae), three endocrine proxies, measured on 5470 individuals, were used to test explicit predictions of how the endocrine system regulates the response to 10 generations of simultaneous selection on body size and development time. The critical weight (CW) reflects the variation in the cessation of juvenile hormone (JH) secretion in the last larval instar, the interval to cessation of growth (ICG) reflects the variation in prothoracicotropic hormone and 20-hydroxyecdysone (20E). Growth rate (GR) reflects the nutrient signaling pathways, primarily the insulin and TOR This is a standard identity similar to DNA signaling pathways. These three endocrine proxies explained 99% and 93% of the variation in body size and development time, respectively, following the 10 generations of simultaneous selection. When the two focal traits, body size and development time, were selected in the same direction, both to either increase or both to decrease, the response to selection was determined primarily by the CW and the ICG, proxies for the developmental hormones JH and 20E, and constrained by GR. In contrast, when the two focal traits were selected in opposite directions, one to increase and the other to decrease, the response to selection was determined primarily by the insulin and TOR signaling pathways as measured by their proxy, GR, and

  1. Notch-mediated patterning and cell fate allocation of pancreatic progenitor cells

    PubMed Central

    Afelik, Solomon; Qu, Xiaoling; Hasrouni, Edy; Bukys, Michael A.; Deering, Tye; Nieuwoudt, Stephan; Rogers, William; MacDonald, Raymond J.; Jensen, Jan

    2012-01-01

    Early pancreatic morphogenesis is characterized by the transformation of an uncommitted pool of pancreatic progenitor cells into a branched pancreatic epithelium that consists of ‘tip’ and ‘trunk’ domains. These domains have distinct molecular signatures and differentiate into distinct pancreatic cell lineages. Cells at the branched tips of the epithelium develop into acinar cells, whereas cells in the trunk subcompartment differentiate into endocrine and duct cells. Recent genetic analyses have highlighted the role of key transcriptional regulators in the specification of these subcompartments. Here, we analyzed in mice the role of Notch signaling in the patterning of multipotent pancreatic progenitor cells through mosaic overexpression of a Notch signaling antagonist, dominant-negative mastermind-like 1, resulting in a mixture of wild-type and Notch-suppressed pancreatic progenitor cells. We find that attenuation of Notch signaling has pronounced patterning effects on multipotent pancreatic progenitor cells prior to terminal differentiation. Relative to the wild-type cells, the Notch-suppressed cells lose trunk marker genes and gain expression of tip marker genes. The Notch-suppressed cells subsequently differentiate into acinar cells, whereas duct and endocrine populations are formed predominantly from the wild-type cells. Mechanistically, these observations could be explained by a requirement of Notch for the expression of the trunk determination gene Nkx6.1. This was supported by the finding of direct binding of RBP-jκ to the Nkx6.1 proximal promoter. PMID:22461559

  2. Surgical and interventional management of complications caused by acute pancreatitis

    PubMed Central

    Karakayali, Feza Y

    2014-01-01

    Acute pancreatitis is one of the most common gastrointestinal disorders worldwide. It requires acute hospitalization, with a reported annual incidence of 13 to 45 cases per 100000 persons. In severe cases there is persistent organ failure and a mortality rate of 15% to 30%, whereas mortality of mild pancreatitis is only 0% to 1%. Treatment principles of necrotizing pancreatitis and the role of surgery are still controversial. Despite surgery being effective for infected pancreatic necrosis, it carries the risk of long-term endocrine and exocrine deficiency and a morbidity and mortality rate of between 10% to 40%. Considering high morbidity and mortality rates of operative necrosectomy, minimally invasive strategies are being explored by gastrointestinal surgeons, radiologists, and gastroenterologists. Since 1999, several other minimally invasive surgical, endoscopic, and radiologic approaches to drain and debride pancreatic necrosis have been described. In patients who do not improve after technically adequate drainage, necrosectomy should be performed. When minimal invasive management is unsuccessful or necrosis has spread to locations not accessible by endoscopy, open abdominal surgery is recommended. Additionally, surgery is recognized as a major determinant of outcomes for acute pancreatitis, and there is general agreement that patients should undergo surgery in the late phase of the disease. It is important to consider multidisciplinary management, considering the clinical situation and the comorbidity of the patient, as well as the surgeons experience. PMID:25309073

  3. Preoperative glucose abnormalities in patients with pancreatic tumours

    PubMed Central

    Durlik, Marek; Kałuża, Bernadetta; Milczarczyk, Alicja; Franek, Edward

    2014-01-01

    Introduction Pancreatic cancer is a neoplasm characterised by poor prognosis. The only effective, possible treatment is radical surgery, but most patients do not qualify for surgery because of delayed diagnosis. Aim To determine if assessment of endocrine pancreatic function could serve as a means of screening for pancreatic cancer. Material and methods This prospective study was conducted on a group of 50 patients diagnosed with pancreatic tumour, who were qualified for surgery. Results From 1.07.2010 to 4.07.2011 a further 50 patients were added to the study group. They had been admitted to the hospital with pancreatic tumours. During the preoperative period, nine of these people had been treated for diabetes, 14 were newly diagnosed with diabetes and 15 had been diagnosed with impaired glucose tolerance, but only 12 had a normal glucose profile. Afterwards, patients underwent the surgical treatment. Histopathological examination revealed that out of the 50 operated patients, 36 suffered from malignant disease, and of these only four had no impaired glucose tolerance before treatment. Conclusions In most cases, patients with pancreatic tumours have impaired glucose tolerance. Screening patients over 50 years of age could speed up diagnosis and surgical treatment. PMID:25061491

  4. Symmetry inheritance of scalar fields

    NASA Astrophysics Data System (ADS)

    Smolić, Ivica

    2015-07-01

    Matter fields do not necessarily have to share the symmetries with the spacetime they live in. When this happens, we speak of the symmetry inheritance of fields. In this paper we classify the obstructions of symmetry inheritance by the scalar fields, both real and complex, and look more closely at the special cases of stationary and axially symmetric spacetimes. Since the symmetry noninheritance is present in the scalar fields of boson stars and may enable the existence of the black hole scalar hair, our results narrow the possible classes of such solutions. Finally, we define and analyse the symmetry noninheritance contributions to the Komar mass and angular momentum of the black hole scalar hair.

  5. [Radionuclide therapy of endocrine-related cancer].

    PubMed

    Kratochwil, C; Giesel, F L

    2014-10-01

    This article gives an overview of the established radionuclide therapies for endocrine-related cancer that already have market authorization or are currently under evaluation in clinical trials. Radioiodine therapy is still the gold standard for differentiated iodine-avid thyroid cancer. In patients with bone and lung metastases (near) total remission is seen in approximately 50% and the 15-year survival rate for these patients is approximately 90%. In contrast to the USA, meta-iodobenzylguanidine (MIBG) therapy has market approval in Europe. According to the current literature, in the setting of advanced stage neuroblastoma and malignant pheochromocytoma or paraganglioma, radiological remission can be achieved in >30% and symptom control in almost 80% of the treated patients. Somatostatin receptor targeted radionuclide therapies (e.g. with DOTATATE or DOTATOC) demonstrated promising results in phase 2 trials, reporting progression-free survival in the range of 24-36 months. A first phase 3 pivotal trial for intestinal carcinoids is currently recruiting and another trial for pancreatic neuroendocrine tumors is planned. Radiopharmaceuticals based on glucagon-like peptide 1 (GLP1) or minigastrins are in the early evaluation stage for application in the treatment of insulinomas and medullary thyroid cancer. In general, radiopharmaceutical therapy belongs to the group of so-called theranostics which means that therapy is tailored for individual patients based on molecular imaging diagnostics to stratify target positive or target negative tumor phenotypes.

  6. Utilizing inheritance in requirements engineering

    NASA Technical Reports Server (NTRS)

    Kaindl, Hermann

    1994-01-01

    The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

  7. 62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis.

    PubMed

    Fujibayashi, Y; Saji, H; Yomoda, I; Kawai, K; Horiuchi, K; Adachi, H; Torizuka, K; Yokoyama, A

    1986-01-01

    As Zn is closely associated with the exocrine and endocrine functions of the pancreas, exploitation of Zn metabolism for anatomical and functional diagnosis was conceived, namely with the recent availability of positron emitting 62Zn (t1/2 = 9 h). In the present paper, response changes in Zn biodistribution (mice) and Zn excretion through the pancreatic duct (rats) due to the stimulation of gastro-intestinal hormones like secretin, CCK-PZ (exocrine stimulation) and glucose (endocrine stimulation) were studied. Under these stimuli, the pancreatic secretion of radioactive Zn through cannulated pancreatic duct showed increased Zn secretion only under the CCK-PZ effect, 3 h post 65Zn (t1/2 = 270 d) injection. Tissue biodistribution in mice pre-injected with 65Zn showed pancreas specific decrease of radioactive Zn whenever a gastro-intestinal hormone was post-administered, whereas the glucose effect was negligible. Thus, the effective mobilization of the injected radioactive Zn, upon exocrine stimulation, represented by CCK-PZ, favored the exploration of a functional study of the pancreas with the positron computed tomograph (PCT) using short lived nuclide labeled 62Zn-EDDA in dog. Evidence of the applicability of this system in regional function studies of the pancreas was obtained. Demonstration of Zn participation in the exocrine function of the pancreas in-vivo holds considerable promise for diagnosis of pancreatic diseases. PMID:3086246

  8. Pancreatitis in children.

    PubMed

    Winchester, M

    1992-12-01

    The pathophysiology of pancreatic autodigestion is poorly understood. Pancreatitis affects all age groups, and the diagnosis is sometimes missed when serum amylase and lipase activities are not measured in the child with abdominal pain. Acute pancreatitis in children has become a more commonly seen condition and the causes have varied. Laboratory and radiological studies play an important role in determining the diagnosis and prognosis. Family history is important in the diagnosis of idiopathic hereditary pancreatitis. Most acute episodes resolve with supportive care, but the mortality in acute pancreatitis is currently about 15% (Hadorn et al., 1980). Endoscopic retrograde cholangiopancreatography or an endoscopic retrograde pancreatogram may be necessary to investigate relapses of pancreatitis. Chronic pancreatitis can be a life-threatening condition requiring lifetime medical management.

  9. Effect of ionizing radiation on the primate pancreas: an endocrine and morphologic study

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Zuurmond, T.; Louw, G.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; Du Toit, L.B.

    1987-01-01

    In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.

  10. 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

  11. 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

  12. [Endocrine disease in adrenoleukodystrophy].

    PubMed

    Girard, S; Bruckert, E; Turpin, G

    2001-02-01

    X-linked adrenoleukodysrophy is the most frequent genetic disorder affecting central and peripheral nervous system myelin. One of the biochemical abnormalities is the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids subsequent to defective catabolism in the peroxysomes. The principal characteristic of the disease is an association between a neurological disorder and an endocrine disorder: primary adrenal insufficiency and testicular failure. Clinical manifestations are variable. There are two main forms, one affecting boys between the age of 5 and 10 years with severe rapidly fatal cerebral involvement, and the other affecting young adults between the age of 20 and 30 years with degeneration of the anterior and posterior long spinal cord tracts, similar to the disorders observed in multiple sclerosis. About 20% of the heterozygous women may develop a syndrome which resembles adrenomyeloneuropathy, rarely adrenal insufficiency. Adrenal insufficiency is present in 85% of the childhood cerebral forms and in about 70% of the adult forms. It may occur before, after or at the same time as the neurological disease but is not correlated with the severity of the neurological disorder. Careful screening is required to avoid missing subclinical forms. Adrenoleukodystrophy should be envisaged in young boys with primary adrenal insufficiency, accounting for about 30% of the cases of primary adrenal insufficiency in children under 3 years of age and about 13% of those in adults. Experience with dietary therapy (low-VLCFA diet and supplementation with unsaturated fatty acids such as glyceryl trioleate (GTO) and glyceryl trierucate (GTE), commonly called Lorenzo's oil) has not demonstrated any clinical improvement in the cerebral forms. Bone marrow transplantation is recommended for children who show early evidence of cerebral involvement. Gene therapy is a promising perspective. Lovastatin and 4-phenlbutyrate have recently been shown to normalize

  13. Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3

    PubMed Central

    Osipovich, Anna B.; Long, Qiaoming; Manduchi, Elisabetta; Gangula, Rama; Hipkens, Susan B.; Schneider, Judsen; Okubo, Tadashi; Stoeckert, Christian J.; Takada, Shinji; Magnuson, Mark A.

    2014-01-01

    Insulinoma associated 1 (Insm1) plays an important role in regulating the development of cells in the central and peripheral nervous systems, olfactory epithelium and endocrine pancreas. To better define the role of Insm1 in pancreatic endocrine cell development we generated mice with an Insm1GFPCre reporter allele and used them to study Insm1-expressing and null populations. Endocrine progenitor cells lacking Insm1 were less differentiated and exhibited broad defects in hormone production, cell proliferation and cell migration. Embryos lacking Insm1 contained greater amounts of a non-coding Neurog3 mRNA splice variant and had fewer Neurog3/Insm1 co-expressing progenitor cells, suggesting that Insm1 positively regulates Neurog3. Moreover, endocrine progenitor cells that express either high or low levels of Pdx1, and thus may be biased towards the formation of specific cell lineages, exhibited cell type-specific differences in the genes regulated by Insm1. Analysis of the function of Ripply3, an Insm1-regulated gene enriched in the Pdx1-high cell population, revealed that it negatively regulates the proliferation of early endocrine cells. Taken together, these findings indicate that in developing pancreatic endocrine cells Insm1 promotes the transition from a ductal progenitor to a committed endocrine cell by repressing a progenitor cell program and activating genes essential for RNA splicing, cell migration, controlled cellular proliferation, vasculogenesis, extracellular matrix and hormone secretion. PMID:25053427

  14. Drugs Approved for Pancreatic Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Pancreatic Cancer This page lists cancer ... in pancreatic cancer that are not listed here. Drugs Approved for Pancreatic Cancer Abraxane (Paclitaxel Albumin-stabilized ...

  15. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  16. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  17. Plate tectonics, damage and inheritance

    NASA Astrophysics Data System (ADS)

    Bercovici, David; Ricard, Yanick

    2014-04-01

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

  18. Plate tectonics, damage and inheritance

    NASA Astrophysics Data System (ADS)

    Bercovici, D. A.; Ricard, Y. R.

    2013-12-01

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto subduction about 4Ga, evident in geochemical analysis from ancient cratons, to global tectonics by 3-2.7Ga, suggests that plates and plate boundaries spread globally over a 1Gyr period. We hypothesize that when sufficient lithospheric damage, which promotes shear-localization and long-lived weak zones, combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of plate boundaries and eventually fully formed tectonic plates driven by subduction alone. We demonstrate this process with an idealized model of pressure-driven flow (wherein a low pressure zone is equivalent to downwelling suction or slab pull) in a lithosphere that self-weakens according to a mylonitic-type polycrystalline grain-damage mechanism (Bercovici and Ricard, Phys. Earth Planet. Int. v.202-203, pp27-55, 2012). In the simplest case, for Earth-like conditions, four successive orthogonal rotations of the driving pressure field yield relic damage zones that are inherited to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even as flow is only driven by subduction. For Venus' hotter surface conditions, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which is compatible with observations. After plates are developed, continued changes in driving forces combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor and micro plates.

  19. Plate tectonics, damage and inheritance.

    PubMed

    Bercovici, David; Ricard, Yanick

    2014-04-24

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates. PMID:24717430

  20. Plate tectonics, damage and inheritance.

    PubMed

    Bercovici, David; Ricard, Yanick

    2014-04-24

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

  1. Human pancreatic cell autotransplantation following total pancreatectomy.

    PubMed Central

    Traverso, L W; Abou-Zamzam, A M; Longmire, W P

    1981-01-01

    During total pancreaticoduodenectomy for chronic pancreatitis, four patients received an intraportal pancreatic mixed-cell autograft prepared by collagenase digestion. The technique of this autotransplantation procedure was successfully developed using a normal canine pancreas, but has proved difficult to apply in the human chronic pancreatitis model. Our four patients became insulin-dependent, with proof of intrahepatic insulin production in only one patient. Three factors have contributed to the lack of graft success: 1) the preoperative endocrine status, 2) systemic hypotension and portal hypertension secondary to graft infusion, and 3) difficulty applying the successful technique in a normal dog pancreas to an extensively scarred human pancreas. The preoperative insulin response during a glucose tolerance test was blunted or delayed in the three patients tested. An immediate decrease in blood pressure and rise in portal pressure occurred in every patient and prevented infusion of the entire graft (30-50%) in three patients. Unfortunately, the patient with the most compromised insulin status was the only patient able to receive the entire graft. Our experience would indicate that further refinements in technique are necessary to prevent the vascular reaction and allow infusion of the entire graft. Furthermore, normal islet cell function is necessary before a successful graft can be expected. PMID:6781424

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

    PubMed

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

    2014-05-01

    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 (RA) and nicotinamide (Nic) 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.

  3. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  4. Inherited disorders of bilirubin clearance.

    PubMed

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-03-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  5. Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

    PubMed Central

    Canto, Marcia Irene; Hruban, Ralph H.; Fishman, Elliot K.; Kamel, Ihab R.; Schulick, Richard; Zhang, Zhe; Topazian, Mark; Takahashi, Naoki; Fletcher, Joel; Petersen, Gloria; Klein, Alison P.; Axilbund, Jennifer; Griffin, Constance; Syngal, Sapna; Saltzman, John R.; Mortele, Koenraad J.; Lee, Jeffrey; Tamm, Eric; Vikram, Raghunandan; Bhosale, Priya; Margolis, Daniel; Farrell, James; Goggins, Michael

    2012-01-01

    BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, non-invasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRI). METHODS We screened 225 asymptomatic adult HRI at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRI (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n=5) by any of the imaging modalities. Fifty-one of the 84 HRI with a cyst (60.7%) had multiple lesions, typically small (mean 0.55 cm, range 2–39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects <50 years old, 34% of subjects 50–59 years old, and 53% of subjects 60–69 years old (P<.0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRI, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRI (82 intraductal papillary mucinous neoplasms [IPMN] and 3 pancreatic endocrine tumors). Three of 5 HRI who underwent pancreatic resection had high-grade dysplasia in <3 cm IPMNs and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRI frequently detects small pancreatic cysts, including curable, non-invasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT. PMID:22245846

  6. Endocrine disruption in aquatic vertebrates.

    PubMed

    Kloas, Werner; Urbatzka, Ralph; Opitz, Robert; Würtz, Sven; Behrends, Thomas; Hermelink, Björn; Hofmann, Frauke; Jagnytsch, Oana; Kroupova, Hana; Lorenz, Claudia; Neumann, Nadja; Pietsch, Constanze; Trubiroha, Achim; Van Ballegooy, Christoph; Wiedemann, Caterina; Lutz, Ilka

    2009-04-01

    Environmental compounds can interfere with endocrine systems of wildlife and humans. The main sink of such substances, called endocrine disrupters (ED), are surface waters. Thus, aquatic vertebrates, such as fish and amphibians, are most endangered. ED can adversely affect reproductive biology and the thyroid system. ED act by (anti)estrogenic and (anti)androgenic modes of action, resulting in abnormal sexual differentiation and impaired reproduction. These effects are mainly driven by direct interferences of ED with sex steroid receptors rather than indirectly by impacting synthesis and bioavailability of sex steroids, which in turn might affect the hypothalamic-pituitary-gonadal axis. Recent findings reveal that, in addition to the human-produced waste of ED, natural sources, such as parasites and decomposition of leaves, also might act as ED, markedly affecting sexual differentiation and reproduction in fish and amphibians. Although the thyroid system has essential functions in both fish and amphibians, amphibian metamorphosis has been introduced as the most sensitive model to detect thyroidal ED; no suitable fish model exists. Whereas ED may act primarily on only one specific endocrine target, all endocrine systems will eventually be deregulated as they are intimately connected to each other. The recent ecotoxicological issue of pharmaceutically active compounds (PhACs) present in the aquatic environment indicates a high potential for further endocrine modes of action on aquatic vertebrates by ED derived from PhACs, such as glucocorticoids, progestins, and beta-agonists.

  7. Chronobiology in the endocrine system.

    PubMed

    Haus, Erhard

    2007-08-31

    Biological signaling occurs in a complex web with participation and interaction of the central nervous system, the autonomous nervous system, the endocrine glands, peripheral endocrine tissues including the intestinal tract and adipose tissue, and the immune system. All of these show an intricate time structure with rhythms and pulsatile variations in multiple frequencies. Circadian (about 24-hour) and circannual (about 1-year) rhythms are kept in step with the cyclic environmental surrounding by the timing and length of the daily light span. Rhythmicity of many endocrine variables is essential for their efficacy and, even in some instances, for the qualitative nature of their effects. Indeed, the continuous administration of certain hormones and their synthetic analogues may show substantially different effects than expected. In the design of drug-delivery systems and treatment schedules involving directly or indirectly the endocrine system, consideration of the human time organization is essential. A large amount of information on the endocrine time structure has accumulated, some of which is discussed in this review.

  8. Paternal inheritance of mitochondria in Chlamydomonas.

    PubMed

    Nakamura, Soichi

    2010-03-01

    To analyze mitochondrial DNA (mtDNA)inheritance, differences in mtDNA between Chlamydomonas reinhardtii and Chlamydomonas smithii, respiration deficiency and antibiotic resistance were used to distinguish mtDNA origins. The analyses indicated paternal inheritance. However, these experiments raised questions regarding whether paternal inheritance occurred normally.Mitochondrial nucleoids were observed in living zygotes from mating until 3 days after mating and then until progeny formation. However, selective disappearance of nucleoids was not observed. Subsequently, experimental serial backcrosses between the two strains demonstrated strict paternal inheritance. The fate of mt+ and mt- mtDNA was followed using the differences in mtDNA between the two strains. The slow elimination of mt+ mtDNA through zygote maturation in darkness was observed, and later the disappearance of mt+ mtDNA was observed at the beginning of meiosis. To explain the different fates of mtDNA, methylation status was investigated; however, no methylation was detected. Variously constructed diploid cells showed biparental inheritance. Thus, when the mating process occurs normally, paternal inheritance occurs. Mutations disrupting mtDNA inheritance have not yet been isolated. Mutations that disrupt maternal inheritance of chloroplast DNA (cpDNA) do not disrupt inheritance of mtDNA. The genes responsible for mtDNA inheritance are different from those of chloroplasts.

  9. Atypical mitochondrial inheritance patterns in eukaryotes.

    PubMed

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  10. Nutrition in acute pancreatitis.

    PubMed

    Nompleggi, D J

    1999-08-01

    Pancreatitis is a common disorder. Numerous factors have been implicated in the pathogenesis of acute and chronic pancreatitis, but the exact mechanisms of these conditions are still poorly understood. Depending on the cause of the disorder, patients who have pancreatitis are usually not malnourished and are able to eat within 5 to 7 days of disease onset. In these patients, nutritional support is unnecessary. However, severe disease induces a catabolic state similar to that seen in trauma and sepsis, resulting in rapid weight loss and increased morbidity and mortality. Thus, vigorous nutritional support may be useful in the treatment of severe pancreatitis. Studies have shown that parenteral and enteral nutritional support are well tolerated and can maintain or improve nutritional status in patients with pancreatitis. This article reviews nutritional assessment and therapy in pancreatitis.

  11. Quantification of endocrine cells and ultrastructural study of insulin granules in the large intestine of opossum Didelphis aurita (Wied-Neuwied, 1826).

    PubMed

    dos Santos, Daiane Cristina Marques; Cupertino, Marli do Carmo; Fialho, Maria do Carmo Queiroz; Barbosa, Alfredo Jose Afonso; Fonseca, Cláudio Cesar; Sartori, Sirlene Souza Rodrigues; da Matta, Sérgio Luis Pinto

    2014-02-01

    This study aimed to investigate the distribution of argyrophil, argentaffin, and insulin-immunoreactive endocrine cells in the large intestine of opossums (Didelphis aurita) and to describe the ultrastructure of the secretory granules of insulin-immunoreactive endocrine cells. Fragments of the large intestine of 10 male specimens of D. aurita were collected, processed, and subjected to staining, immunohistochemistry, and transmission electron microscopy. The argyrophil, the argentaffin, and the insulin-immunoreactive endocrine cells were sparsely distributed in the intestinal glands of the mucous layer, among other cell types of the epithelium in all regions studied. Proportionally, the argyrophil, the argentaffin, and the insulin-immunoreactive endocrine cells represented 62.75%, 36.26%, and 0.99% of the total determined endocrine cells of the large intestine, respectively. Quantitatively, there was no difference between the argyrophil and the argentaffin endocrine cells, whereas insulin-immunoreactive endocrine cells were less numerous. The insulin-immunoreactive endocrine cells were elongated or pyramidal, with rounded nuclei of irregularly contoured, and large amounts of secretory granules distributed throughout the cytoplasm. The granules have different sizes and electron densities and are classified as immature and mature, with the mature granules in predominant form in the overall granular population. In general, the granule is shown with an external electron-lucent halo and electron-dense core. The ultrastructure pattern in the granules of the insulin-immunoreactive endocrine cells was similar to that of the B cells of pancreatic islets in rats.

  12. Digenic inheritance in medical genetics

    PubMed Central

    Schäffer, Alejandro A

    2013-01-01

    Digenic inheritance (DI) is the simplest form of inheritance for genetically complex diseases. By contrast with the thousands of reports that mutations in single genes cause human diseases, there are only dozens of human disease phenotypes with evidence for DI in some pedigrees. The advent of high-throughput sequencing (HTS) has made it simpler to identify monogenic disease causes and could similarly simplify proving DI because one can simultaneously find mutations in two genes in the same sample. However, through 2012, I could find only one example of human DI in which HTS was used; in that example, HTS found only the second of the two genes. To explore the gap between expectation and reality, I tried to collect all examples of human DI with a narrow definition and characterise them according to the types of evidence collected, and whether there has been replication. Two strong trends are that knowledge of candidate genes and knowledge of protein–protein interactions (PPIs) have been helpful in most published examples of human DI. By contrast, the positional method of genetic linkage analysis, has been mostly unsuccessful in identifying genes underlying human DI. Based on the empirical data, I suggest that combining HTS with growing networks of established PPIs may expedite future discoveries of human DI and strengthen the evidence for them. PMID:23785127

  13. Mitochondrial DNA inheritance after SCNT.

    PubMed

    Hiendleder, Stefan

    2007-01-01

    Mitochondrial biogenesis and function is under dual genetic control and requires extensive interaction between biparentally inherited nuclear genes and maternally inherited mitochondrial genes. Standard SCNT procedures deprive an oocytes' mitochondrial DNA (mtDNA) of the corresponding maternal nuclear DNA and require it to interact with an entirely foreign nucleus that is again interacting with foreign somatic mitochondria. As a result, most SCNT embryos, -fetuses, and -offspring carry somatic cell mtDNA in addition to recipient oocyte mtDNA, a condition termed heteroplasmy. It is thus evident that somatic cell mtDNA can escape the selective mechanism that targets and eliminates intraspecific sperm mitochondria in the fertilized oocyte to maintain homoplasmy. However, the factors responsible for the large intra- and interindividual differences in heteroplasmy level remain elusive. Furthermore, heteroplasmy is probably confounded with mtDNA recombination. Considering the essential roles of mitochondria in cellular metabolism, cell signalling, and programmed cell death, future experiments will need to assess the true extent and impact of unorthodox mtDNA transmission on various aspects of SCNT success.

  14. Smoking and Pancreatic Disease.

    PubMed

    Edderkaoui, Mouad; Thrower, Edwin

    2013-11-01

    Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.

  15. Recessive transmission of a multiple endocrine neoplasia syndrome in the rat.

    PubMed

    Fritz, Andreas; Walch, Axel; Piotrowska, Kamilla; Rosemann, Michael; Schäffer, Ekkehard; Weber, Karin; Timper, Andreas; Wildner, Gerhild; Graw, Jochen; Höfler, Heinz; Atkinson, Michael J

    2002-06-01

    We describe a novel hereditary cancer syndrome in the rat that is transmitted by a recessive gene mutation. Animals exhibiting the mutant phenotype develop multiple neuroendocrine malignancies within the first year of life. The endocrine neoplasia is characterized by bilateral adrenal pheochromocytoma, multiple extra-adrenal pheochromocytoma, bilateral medullary thyroid cell neoplasia, bilateral parathyroid hyperplasia, and pituitary adenoma. The appearance of neoplastic disease is preceded by the development of bilateral juvenile cataracts. Although the spectrum of affected tissues is reminiscent of human forms of multiple endocrine neoplasia (MEN), no germ-line mutations were detected in the Ret or Menin genes that are responsible for the dominantly inherited MEN syndromes in humans. Segregation studies in F1 and F2 crosses yielded frequencies of affected animals entirely consistent with a recessive autosomal mode of inheritance. The lack of the phenotype in F1 animals effectively excludes a germ-line tumor suppressor gene mutation as the causal event. The absence of mutation of known MEN genes and the unique constellation of affected tissues, plus the recessive mode of inheritance, lead us to conclude that the mutation of an as yet unknown gene is responsible for this syndrome of inherited neuroendocrine cancer.

  16. [Endocrine tumors of the testis].

    PubMed

    Loy, V; Linke, J

    2003-07-01

    The most characteristic endocrine tumours of the testis are germ cell tumours and sex cord/gonadal stromal tumours. They include the primary carcinoid, the relation of which to teratomas is still unclear. In general, gonadal stromal tumours are rare, however, endocrine activity occurs in at least 10%-20%. Among gonadal stromal tumours, only Leydig cell tumours and Sertoli cell tumours are of practical importance. Endocrine disorders are mostly related to Leydig cell tumours (gynaecomastia, pubertas praecox). Although less frequent than the other gonadal stromal tumours, they can, in principle, occur. The large cell calcifying Sertoli cell tumour occurs in association with other complex disorders (i.e. Peutz-Jeghers syndrome). Valuable markers are: inhibin, calretinin, cytokeratin, melan-A, CD-99, Ki-67, androgen receptor and p53. As the conventional morphology and immunohistological markers frequently overlap, unclear cases should be referred to specialised centres. PMID:14513279

  17. Age and the endocrine system.

    PubMed

    Noth, R H; Mazzaferri, E L

    1985-02-01

    The pattern of age-induced changes in each endocrine system is unique. Both hormone levels and target organ responsivity are altered in the aging endocrine-cardiovascular system. Serum levels of vasopressor hormones both increase (norepinephrine) and decrease (renin, aldosterone). Target organ responses to beta-adrenergic stimulation in the heart and probably also in vascular smooth muscle decrease due to postreceptor changes. These effects contribute to the clinical problems of hypertension and orthostatic hypotension which characterize the elderly. Aging produces mild carbohydrate intolerance and a minimal increase in fasting serum glucose in healthy, nonobese individuals, primarily due to decreasing postreceptor responsiveness to insulin. Aging decreases the metabolism of thyroxine, including its conversion to triiodothyronine, but clinically significant alterations of thyroid hormone levels do not occur. Changes in the end-organ response to thyroid hormones, however, significantly alter the clinical presentation of thyroid diseases. Aging shifts the serum vasopressin-serum osmolality relationship toward higher serum vasopressin levels probably due to altered baroreceptor input, probably contributing to the tendency toward hyponatremia in the elderly. Aging slows the metabolism of cortisol, but glucocorticoid levels in the human are essentially unaltered by age. However, recent data indicate that delta-5 adrenal steroids decrease markedly in both men and women. Nodules in the anterior pituitary, the thyroid, and the adrenal increase in frequency with aging. Finally, the reproductive system is primarily altered by endocrine cell death, by unknown mechanisms, resulting in decreased estrogen and testosterone levels in women and men. This most obvious age-related endocrine change turns out to be incompletely understood and is not representative of most age-related endocrine changes. Despite characterization of these many age-related alterations in endocrine systems

  18. Epigenetic inheritance: a contributor to species differentiation?

    PubMed

    Boffelli, Dario; Martin, David I K

    2012-10-01

    Multiple epigenetic states can be associated with the same genome, and transmitted through the germline for generations, to create the phenomenon of epigenetic inheritance. This form of inheritance is mediated by complex and highly diverse components of the chromosome that associate with DNA, control its transcription, and are inherited alongside it. But, how extensive, and how stable, is the information carried in the germline by the epigenome? Several known examples of epigenetic inheritance demonstrate that it has the ability to create selectable traits, and thus to mediate Darwinian evolution. Here we discuss the possibility that epigenetic inheritance is responsible for some stable characteristics of species, focusing on a recent comparison of the human and chimpanzee methylomes which reveals that somatic methylation states are related to methylation states in the germline. Interpretation of this finding highlights the potential significance of germline epigenetic states, as well as the challenge of investigating a form of inheritance with complex and unfamiliar rules.

  19. Epigenetic Inheritance: A Contributor to Species Differentiation?

    PubMed Central

    Boffelli, Dario

    2012-01-01

    Multiple epigenetic states can be associated with the same genome, and transmitted through the germline for generations, to create the phenomenon of epigenetic inheritance. This form of inheritance is mediated by complex and highly diverse components of the chromosome that associate with DNA, control its transcription, and are inherited alongside it. But, how extensive, and how stable, is the information carried in the germline by the epigenome? Several known examples of epigenetic inheritance demonstrate that it has the ability to create selectable traits, and thus to mediate Darwinian evolution. Here we discuss the possibility that epigenetic inheritance is responsible for some stable characteristics of species, focusing on a recent comparison of the human and chimpanzee methylomes which reveals that somatic methylation states are related to methylation states in the germline. Interpretation of this finding highlights the potential significance of germline epigenetic states, as well as the challenge of investigating a form of inheritance with complex and unfamiliar rules. PMID:22966965

  20. INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

    PubMed Central

    KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

    2014-01-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

  1. Hereditary pancreatic hypoplasia, diabetes mellitus, and congenital heart disease: a new syndrome?

    PubMed Central

    Yorifuji, T; Matsumura, M; Okuno, T; Shimizu, K; Sonomura, T; Muroi, J; Kuno, C; Takahashi, Y; Okuno, T

    1994-01-01

    We report on a Japanese family with hereditary pancreatic hypoplasia, diabetes mellitus, and congenital heart disease. The disease was apparently inherited as an autosomal dominant trait. The patients in this family had no major anomalies other than those of the heart and pancreas. To our knowledge, this combination has not previously been reported. Images PMID:8071961

  2. Musculoskeletal manifestations of endocrine disorders.

    PubMed

    Boswell, Stephanie B; Patel, Dakshesh B; White, Eric A; Gottsegen, Christopher J; Forrester, Deborah M; Masih, Sulabha; Matcuk, George R

    2014-01-01

    Endocrine disorders can lead to disturbances in numerous systems within the body, including the musculoskeletal system. Radiological evaluation of these conditions can demonstrate typical appearances of the bones and soft tissues. Knowledge of these patterns can allow the radiologist to suggest a diagnosis that may not be clinically apparent. This review will highlight the typical musculoskeletal findings of acromegaly, hypercortisolism, hyperthyroidism, hypothyroidism, hyperparathyroidism, pseudo- and pseudopseudohypoparathyroidism, and diabetes mellitus. The radiological manifestations of each of these endocrine disorders, along with a brief discussion of the pathophysiology and clinical implications, will be discussed. PMID:24642251

  3. Endocrine hypertension in small animals.

    PubMed

    Reusch, Claudia E; Schellenberg, Stefan; Wenger, Monique

    2010-03-01

    Hypertension is classified as idiopathic or secondary. In animals with idiopathic hypertension, persistently elevated blood pressure is not caused by an identifiable underlying or predisposing disease. Until recently, more than 95% of cases of hypertension in humans were diagnosed as idiopathic. New studies have shown, however, a much higher prevalence of secondary causes, such as primary hyperaldosteronism. In dogs and cats, secondary hypertension is the most prevalent form and is subclassified into renal and endocrine hypertension. This review focuses on the most common causes of endocrine hypertension in dogs and cats.

  4. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer

    PubMed Central

    Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gallinger, Steven; Gross, Myron; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Mandelson, Margaret T.; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J.Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hoffman Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay-Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Shu, Xiao-Ou; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Watters, Joanne; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.

    2012-01-01

    Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case–control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10−6, 1.6 × 10−5, 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10−5), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H. pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. PMID:22523087

  5. Long non-coding RNAs as regulators of the endocrine system

    PubMed Central

    Knoll, Marko; Lodish, Harvey F.; Sun, Lei

    2015-01-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers. PMID:25560704

  6. Long non-coding RNAs as regulators of the endocrine system.

    PubMed

    Knoll, Marko; Lodish, Harvey F; Sun, Lei

    2015-03-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

  7. Endocrine pancreas development in zebrafish.

    PubMed

    Tehrani, Zahra; Lin, Shuo

    2011-10-15

    Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic β cells. Current efforts to cure diabetes are aimed at replenishing damaged cells by generating a new supply of β cells in vitro. The most promising strategy for achieving this goal is to differentiate embryonic stem (ES) cells by sequentially exposing them to signaling molecules that they would normally encounter in vivo. This approach requires a thorough understanding of the temporal sequence of the signaling events underlying pancreatic β-cell induction during embryonic development. The zebrafish system has emerged as a powerful tool in the study of pancreas development. In this review, we provide a temporal summary of pancreas development in zebrafish with a special focus on the formation of pancreatic β cells.

  8. Endocrine and Nutritional Management After Bariatric Surgery

    MedlinePlus

    Endocrine and Nutritional Management After Bariatric Surgery A Patient’s Guide Bariatric (weight loss) surgery is a treatment ... This guide for patients is based on The Endocrine Society’s practice guidelines for physicians that focus on ...

  9. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

  10. ANALYTICAL CHALLENGES OF ENVIRONMENTAL ENDOCRINE DISRUPTOR MONITORING

    EPA Science Inventory

    Reported increases in the incidence of endocrine-related conditions have led to speculation about environmental causes. Environmental scientists are focusing increased research effort into understanding the mechanisms by which endocrine disruptors affect human and ecological h...

  11. Calbindin 28 kDa in endocrine cells of known or putative calcium-regulating function. Thyro-parathyroid C cells, gastric ECL cells, intestinal secretin and enteroglucagon cells, pancreatic glucagon, insulin and PP cells, adrenal medullary NA cells and some pituitary (TSH?) cells.

    PubMed

    Buffa, R; Mare, P; Salvadore, M; Solcia, E; Furness, J B; Lawson, D E

    1989-01-01

    The distribution of calbindin in some endocrine glands (thyroid, parathyroid, ultimobranchial body, pituitary and adrenals) and in the diffuse endocrine cells of the gut and pancreas has been investigated immunohistochemically using an antiserum raised against the 28 kDa calbindin from chicken duodenum. The identity of calbindin-immunoreactive cells in a number of avian and mammalian species was ascertained by comparison with hormone-reactive cells in consecutive sections or by double immunostaining of the same section with both calbindin and hormone antibodies. Calcitonin-producing C cells of the mammalian and avian thyroid, parathyroid or ultimobranchial body, PP, glucagon and insulin cells of the mammalian and avian pancreas, enteroglucagon cells of the avian intestine, secretin cells of the mammalian duodenum, histamine-producing ECL cells of the mammalian stomach, as well as noradrenaline-producing cells of the adrenal medulla and some (TSH?) cells of the adenohypophysis were among the calbindin-immunoreactive cells. Although some species variability has been observed in the intensity and distribution of the immunoreactivity, especially in the pancreas and the gut, a role for calbindin in the mechanisms of calcium-mediated endocrine cell stimulation or of intracellular and extracellular calcium homeostasis is suggested. PMID:2737922

  12. Inheritance of goat coat colors.

    PubMed

    Adalsteinsson, S; Sponenberg, D P; Alexieva, S; Russel, A J

    1994-01-01

    Goat color inheritance was evaluated based on color description of 218 kids and their parents (10 sires, 178 dams) from mixed crosses between several goat populations in an experiment on cashmere fiber production. Altogether 10 color patterns were observed. They were postulated to be caused by 10 alleles at the Agouti locus, with the allele for white or tan color being the top dominant allele, and the nine others codominant. The bottom recessive allele, for nonagouti color, was the 11th allele at this locus. The postulated alleles are white or tan (A(wt)), black mask (A(blm)), bezoar (A(bz)), badgerface (A(b)), grey (A(g)), lightbelly (A(lb)), swiss markings (A(sm)), lateral stripes (A(ls)), mahogany (A(mh)), red cheek (A(rc)), and nonagouti (Aa). Two types of eumelanin pigment were observed, black and light brown, the latter being dominant. Recessive brown was not observed.

  13. Inheritance of epigenetic chromatin silencing

    PubMed Central

    David-Rus, Diana; Mukhopadhyay, Swagatam; Lebowitz, Joel L.; Sengupta, Anirvan M.

    2010-01-01

    Maintenance of alternative chromatin states through cell divisions pose some fundamental constraints on the dynamics of histone modifications. In this paper, we study the systems biology of epigenetic inheritance by defining and analyzing general classes of mathematical models. We discuss how the number of modification states involved plays an essential role in the stability of epigenetic states. In addition, DNA duplication and the consequent dilution of marked histones act as a large perturbation for a stable state of histone modifications. The requirement that this large perturbation falls into the basin of attraction of the original state sometimes leads to additional constraints on effective models. Two such models, inspired by two different biological systems, are compared in their fulfilling the requirements of multistability and of recovery after DNA duplication. We conclude that in the presence of multiple histone modifications that characterize alternative epigenetic stable states, these requirements are more easily fulfilled. PMID:19174167

  14. Calcium Ions in Inherited Cardiomyopathies.

    PubMed

    Deftereos, Spyridon; Papoutsidakis, Nikolaos; Giannopoulos, Georgios; Angelidis, Christos; Raisakis, Konstantinos; Bouras, Georgios; Davlouros, Periklis; Panagopoulou, Vasiliki; Goudevenos, John; Cleman, Michael W; Lekakis, John

    2016-01-01

    Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis. PMID:26411603

  15. Pancreatic stem cells remain unresolved.

    PubMed

    Jiang, Fang-Xu; Morahan, Grant

    2014-12-01

    Diabetes mellitus is caused by absolute (type 1) or relative (type 2) deficiency of insulin-secreting islet β cells. An ideal treatment of diabetes would, therefore, be to replace the lost or deficient β cells, by transplantation of donated islets or differentiated endocrine cells or by regeneration of endogenous islet cells. Due to their ability of unlimited proliferation and differentiation into all functional lineages in our body, including β cells, embryonic stem cells and induced pluripotent stem cells are ideally placed as cell sources for a diabetic transplantation therapy. Unfortunately, the inability to generate functional differentiated islet cells from pluripotent stem cells and the poor availability of donor islets have severely restricted the broad clinical use of the replacement therapy. Therefore, endogenous sources that can be directed to becoming insulin-secreting cells are actively sought after. In particular, any cell types in the developing or adult pancreas that may act as pancreatic stem cells (PSC) would provide an alternative renewable source for endogenous regeneration. In this review, we will summarize the latest progress and knowledge of such PSC, and discuss ways that facilitate the future development of this often controversial, but crucial research.

  16. Palliation in pancreatic cancer.

    PubMed

    Kruse, E James

    2010-04-01

    Pancreatic cancer is rarely curable, and because of its location causes significant symptoms for patients in need of palliation. The common problems of incurable pancreatic cancer are biliary obstruction, duodenal obstruction, and pain. Approaches include surgical, endoscopic and radiologic interventions. This article discusses the palliative options and controversies related to these symptoms.

  17. Pancreatitis in cats.

    PubMed

    Armstrong, P Jane; Williams, David A

    2012-08-01

    Pancreatitis was considered a rare disease in the cat until a couple of decades ago when several retrospective studies of severe acute pancreatitis were published. It was apparent that few of the diagnostic tests of value in the dog were helpful in cats. With increasing clinical suspicion, availability of abdominal ultrasonography, and introduction of pancreas-specific blood tests of increasing utility, it is now accepted that acute pancreatitis is probably almost as common in cats as it is in dogs, although the etiology(s) remain more obscure. Pancreatitis in cats often co-exists with inflammatory bowel disease, less commonly with cholangitis, and sometimes with both. Additionally, pancreatitis may trigger hepatic lipidosis, while other diseases, such as diabetes mellitus, may be complicated by pancreatitis. Therapy is similar to that used in dogs, with added emphasis on early nutritional support to prevent hepatic lipidosis. Less is known about chronic pancreatitis than the acute form, but chronic pancreatitis is more common in cats than it is in dogs and may respond positively to treatment with corticosteroids.

  18. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

  19. [Endocrine abnormalities in HIV infections].

    PubMed

    Verges, B; Chavanet, P; Desgres, J; Kisterman, J P; Waldner, A; Vaillant, G; Portier, H; Brun, J M; Putelat, R

    The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.

  20. [Environmental contaminants and endocrine disruptors].

    PubMed

    Fontenele, Eveline Gadelha Pereira; Martins, Manoel Ricardo Alves; Quidute, Ana Rosa Pinto; Montenegro, Renan Magalhães

    2010-02-01

    The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages. PMID:20414542

  1. GATA factors in endocrine neoplasia.

    PubMed

    Pihlajoki, Marjut; Färkkilä, Anniina; Soini, Tea; Heikinheimo, Markku; Wilson, David B

    2016-02-01

    GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted.

  2. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

    EPA Science Inventory

    For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

  3. The Vitamin D Endocrine System.

    ERIC Educational Resources Information Center

    Norman, Anthony W.

    1985-01-01

    Discusses the physiology and biochemistry of the vitamin D endocrine system, including role of biological calcium and phosphorus, vitamin D metabolism, and related diseases. A 10-item, multiple-choice test which can be used to obtain continuing medical education credit is included. (JN)

  4. Plasticity of renal endocrine function.

    PubMed

    Kurt, Birgül; Kurtz, Armin

    2015-03-15

    The kidneys are important endocrine organs. They secrete humoral factors, such as calcitriol, erythropoietin, klotho, and renin into the circulation, and therefore, they are essentially involved in the regulation of a variety of processes ranging from bone formation to erythropoiesis. The endocrine functions are established by cells, such as proximal or distal tubular cells, renocortical interstitial cells, or mural cells of afferent arterioles. These endocrine cells are either fixed in number, such as tubular cells, which individually and gradually upregulate or downregulate hormone production, or they belong to a pool of cells, which display a recruitment behavior, such as erythropoietin- and renin-producing cells. In the latter case, regulation of humoral function occurs via (de)recruitment of active endocrine cells. As a consequence renin- and erythropoietin-producing cells in the kidney show a high degree of plasticity by reversibly switching between distinct cell states. In this review, we will focus on the characteristics of renin- and of erythropoietin-producing cells, especially on their origin and localization, their reversible transformations, and the mediators, which are responsible for transformation. Finally, we will discuss a possible interconversion of renin and erythropoietin expression. PMID:25608752

  5. Review of idiopathic pancreatitis

    PubMed Central

    Lee, Jason Kihyuk; Enns, Robert

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted. PMID:18081217

  6. Clinical nutrition in pancreatitis.

    PubMed

    McClave, S A; Snider, H; Owens, N; Sexton, L K

    1997-10-01

    In patients with acute pancreatitis or an acute flare of chronic pancreatitis, a discrepancy exists between increased protein/calorie requirements induced by a hypermetabolic stress state and reduced ingestion/assimilation of exogenous nutrients, which promotes progressive nutritional deterioration. Patients with severe pancreatitis (defined by > or =3 Ranson criteria, an APACHE II score of > or =10, development of major organ failure, and/or presence of pancreatic necrosis) are more likely to require aggressive nutritional support than patients with mild disease. The type of formula and level of the gastrointestinal tract into which nutrients are infused determine the degree to which pancreatic exocrine secretion is stimulated. Animal studies and early prospective randomized controlled trials in humans suggest that total enteral nutrition via jejunal feeding may be the preferred route to parenteral alimentation in this disease setting.

  7. A small molecule that directs differentiation of human ESCs into the pancreatic lineage.

    PubMed

    Chen, Shuibing; Borowiak, Malgorzata; Fox, Julia L; Maehr, René; Osafune, Kenji; Davidow, Lance; Lam, Kelvin; Peng, Lee F; Schreiber, Stuart L; Rubin, Lee L; Melton, Douglas

    2009-04-01

    Stepwise differentiation from embryonic stem cells (ESCs) to functional insulin-secreting beta cells will identify key steps in beta-cell development and may yet prove useful for transplantation therapy for diabetics. An essential step in this schema is the generation of pancreatic progenitors--cells that express Pdx1 and produce all the cell types of the pancreas. High-content chemical screening identified a small molecule, (-)-indolactam V, that induces differentiation of a substantial number of Pdx1-expressing cells from human ESCs. The Pdx1-expressing cells express other pancreatic markers and contribute to endocrine, exocrine and duct cells, in vitro and in vivo. Further analyses showed that (-)-indolactam V works specifically at one stage of pancreatic development, inducing pancreatic progenitors from definitive endoderm. This study describes a chemical screening platform to investigate human ESC differentiation and demonstrates the generation of a cell population that is a key milepost on the path to making beta cells. PMID:19287398

  8. Copper deficiency in rats increases pancreatic enkephalin-containing peptides and insulin.

    PubMed

    Recant, L; Voyles, N R; Timmers, K I; Zalenski, C; Fields, M; Bhathena, S J

    1986-01-01

    Free enkephalins (enk) and higher molecular weight enkephalin-containing peptides (enk-c-p) are present in the endocrine pancreas of rats, presumably in B cells. To determine whether these opioid peptides show dynamic alterations as insulin content of pancreas changes, we utilized a copper deficient rat model, in which the exocrine pancreas atrophies and the endocrine pancreas is "intact" and insulin (IRI) content increases. Dietary copper deficiency (-C) was produced in weanling male rats for 4 and 7 weeks. The deficient and copper supplemented (+C) groups were further subdivided to receive all dietary carbohydrate as either 62% fructose (F) or 62% starch (S). -CF rats showed the most severe deficiency. After 7 weeks, total units of pancreatic IRI in -CF were 7.5 +CF 2.1, -CS 7.9 and in +CS 2.8 (p less than 0.001). Pancreatic content of Met5- and Leu5-enk was measured in extracts which were purified on C-18 Seppaks with and without prior treatment with trypsin and carboxypeptidase B. -C animals showed progressive, significant increases in pancreatic content of Leu-enk-c-p, with a decrease in free Leu- and Met-enk (p less than 0.02-0.01). The pancreatic findings are compatible with a co-localization of enkephalins and insulin in the endocrine pancreas and are suggestive of co-regulation. PMID:3550724

  9. Light scattering as an intrinsic indicator for pancreatic islet cell mass and secretion.

    PubMed

    Ilegems, E; van Krieken, P P; Edlund, P K; Dicker, A; Alanentalo, T; Eriksson, M; Mandic, S; Ahlgren, U; Berggren, P-O

    2015-01-01

    The pancreatic islet of Langerhans is composed of endocrine cells producing and releasing hormones from secretory granules in response to various stimuli for maintenance of blood glucose homeostasis. In order to adapt to a variation in functional demands, these islets are capable of modulating their hormone secretion by increasing the number of endocrine cells as well as the functional response of individual cells. A failure in adaptive mechanisms will lead to inadequate blood glucose regulation and thereby to the development of diabetes. It is therefore necessary to develop tools for the assessment of both pancreatic islet mass and function, with the aim of understanding cellular regulatory mechanisms and factors guiding islet plasticity. Although most of the existing techniques rely on the use of artificial indicators, we present an imaging methodology based on intrinsic optical properties originating from mature insulin secretory granules within endocrine cells that reveals both pancreatic islet mass and function. We demonstrate the advantage of using this imaging strategy by monitoring in vivo scattering signal from pancreatic islets engrafted into the anterior chamber of the mouse eye, and how this versatile and noninvasive methodology permits the characterization of islet morphology and plasticity as well as hormone secretory status.

  10. Acute Obstructive Suppurative Pancreatic Ductitis

    PubMed Central

    Palakodeti, Sandeep; Munroe, Craig

    2016-01-01

    Acute obstructive suppurative pancreatic ductitis (AOSPD) is a rare clinical entity defined as suppuration from the pancreatic duct without concomitant pancreatic cyst, abscess, or necrosis. We describe a case of AOSPD in a woman with a past medical history of type 2 diabetes and chronic pancreatitis who presented with abdominal sepsis, which resolved only after therapeutic endoscopic retrograde cholangiopancreatography. Our case highlights the importance of considering AOSPD as a cause of abdominal sepsis particularly in patients with chronic pancreatitis or any recent pancreatic duct instrumentation and demonstrates that treatment requires prompt drainage and decompression of the pancreatic duct.

  11. Transgenerational inheritance of heart disorders caused by paternal bisphenol A exposure.

    PubMed

    Lombó, Marta; Fernández-Díez, Cristina; González-Rojo, Silvia; Navarro, Claudia; Robles, Vanesa; Herráez, María Paz

    2015-11-01

    Bisphenol A (BPA) is an endocrine disruptor used in manufacturing of plastic devices, resulting in an ubiquitous presence in the environment linked to human infertility, obesity or cardiovascular diseases. Both transcriptome and epigenome modifications lie behind these disorders that might be inherited transgenerationally when affecting germline. To assess potential effects of paternal exposure on offspring development, adult zebrafish males were exposed to BPA during spermatogenesis and mated with non-treated females. Results showed an increase in the rate of heart failures of progeny up to the F2, as well as downregulation of 5 genes involved in cardiac development in F1 embryos. Moreover, BPA causes a decrease in F0 and F1 sperm remnant mRNAs related to early development. Results reveal a paternal inheritance of changes in the insulin signaling pathway due to downregulation of insulin receptor β mRNAs, suggesting a link between BPA male exposure and disruption of cardiogenesis in forthcoming generations. PMID:26322593

  12. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  13. Legal Portion in Russian Inheritance Law

    ERIC Educational Resources Information Center

    Inshina, Roza; Murzalimova, Lyudmila

    2013-01-01

    In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

  14. Inherited factor XI deficiency: a concise review.

    PubMed

    Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe

    2006-10-01

    Inherited factor XI (FXI) deficiency, also called Hemophilia C, is an uncommon autosomal recessive disorder, which is associated with a variable bleeding tendency that usually manifests after trauma or surgery. This concise report reviews current knowledge regarding the pathogenesis, genetics, diagnosis, clinical manifestations and management of this inherited bleeding disorder.

  15. Hereditary pancreatitis in England and Wales.

    PubMed Central

    Sibert, J R

    1978-01-01

    Information from 72 patients from 7 families in England and Wales confirms that hereditary pancreatitis is inherited as an autosomal dominant conditions with limited penetrance. The degree of penetrance is approximately 80%. These patients have had recurrent attacks of abdominal pain starting from childhood or young adult life. The mean age of onset in the 7 families studied was 13.6 years. There were two peaks, with maximum numbers at 5 years and 17 years. The second peak was thought to represent genetically susceptible individuals having pain brought on by alcohol rather than representing evidence of genetic heterogeneity. Five of the 7 families had members with both childhood and adult ages of onset. Only 4 patients out of 72 had life-threatening disease and in the majority of cases the attacks of pain were of nuisance value only. Hereditary pancreatitis was implicated in only 1 patient's death and this was not definite. Patients appear to get better after a period of symptoms usually as they approach middle age, or after a severe attack. In older patients alcohol, emotional upsets, and fatty food appear to precipitate attacks. Pancreatic insufficiency (5.5%), diabetes mellitus (12.5%), pseudocysts (5.5%), and haemorrhagic pleural effusion are uncommon complications. Portal vein thrombosis occurred definitely in 2 patients and was suspected in 3 others. Carcinoma of the pancreas was not found in any of 72 patients studied in detail; however, 2 members from a family not visited personally had chronic pancreatitis and malabsorption going on to carcinoma. They may have suffered from a different disease. Genetic linkage information was too slight for many definite conclusions. However, there was no suggestion of linkage with any of the markers tested. PMID:671483

  16. Hereditary pancreatitis of 3 Chinese children

    PubMed Central

    Dai, Li-Na; Chen, Ying-Wei; Yan, Wei-Hui; Lu, Li-Na; Tao, Yi-Jing; Cai, Wei

    2016-01-01

    Abstract Background: Hereditary pancreatitis (HP) is quite rare and is distinguished by incomplete penetrance presentation as early-onset relapsing pancreatitis, usually beginning in childhood. HP is now known to be commonly relevant to mutations in the PRSS1 (gene-encoding cationic trypsinogen), SPINK1 (serine protease inhibitor, Kazal type 1), CFTR (cystic fibrosis), carboxypeptidase A1 (CPA1), and chymotrypsin C (CTRC) genes as reported in some Caucasian studies. HP has a variable spectrum of severity and may develop complications. Methods & Results: We describe the clinical course of 3 preschool children, hospitalized with postprandial abdominal pain, whose laboratory tests showed high serum amylase. Similar episodes of abdominal pain led to readmission, and the patients recovered quickly after using symptomatic therapy. The condition of the first boy, who developed a pancreatic tail pseudocyst and splenic infarction, was especially complicated. The boy underwent 2 endoscopic retrograde cholangiopancreatographies and stenting, along with a surgical procedure that completely relieved his symptoms for 3 months. The 3 patients and their parents were given genetic testing. All of the patients carried 1 or more gene mutations inherited from their mothers, fathers, or both parents; however, none of the parents were affected. Conclusion: For children with repeated pancreatitis, clinicians should consider HP in the differential diagnosis. It is reliable to perform gene sequencing on suspicious patients and their parents. Multidisciplinary and comprehensive treatment should be recommended to manage HP and its complications. Cholangiopancreatography and stenting is a relatively minimally invasive approach when compared with surgery and can be tried as an early intervention. Surgical procedures should be reserved for patients with complications. PMID:27603351

  17. Transgenerational inheritance of stress pathology.

    PubMed

    Matthews, Stephen G; Phillips, David I

    2012-01-01

    It is becoming increasingly evident that maternal exposure to adversity during pregnancy leads to life-long effects in offspring. While there appears to be some commonality in the effects of maternal stress on endocrine and behavioral outcomes in the first generation offspring, it is clear that effects are highly dependent on species, sex and age, as well as on the time in pregnancy when stress is experienced. Recent studies have identified that the effects of maternal stress are not confined to the first generation and that they can extend over multiple generations. These effects are also evident in humans. While our understanding of the potential mechanisms by which transgenerational programming of the stress response occurs remain largely undetermined, recent studies have begun to identify potential mechanisms of transfer. These include modified maternal adaptations to pregnancy, altered maternal behavior and transgenerational epigenetic programming. Such transgenerational programming of stress responses and pathologies has important societal consequences as it could provide a biological explanation for the generational persistence of human behaviors in populations exposed to adversity.

  18. Transgenerational epigenetic inheritance in health and disease.

    PubMed

    Whitelaw, Nadia C; Whitelaw, Emma

    2008-06-01

    Over the past century, patterns of phenotypic inheritance have been observed that are not easily rationalised by Mendel's rules of inheritance. Now that we have begun to understand more about non-DNA based, or 'epigenetic', control of phenotype at the molecular level, the idea that the transgenerational inheritance of these epigenetic states could explain non-Mendelian patterns of inheritance has become attractive. There is a growing body of evidence that abnormal epigenetic states, termed epimutations, are associated with disease in humans. For example, in several cases of colorectal cancer, epimutations have been identified that silence the human mismatch repair genes, MLH1 and MSH2. But strong evidence that the abnormal epigenetic states are primary events that occur in the absence of genetic change and are inherited across generations is still absent.

  19. IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas

    PubMed Central

    Mellitzer, Georg; Bonné, Stefan; Luco, Reini F; Van De Casteele, Mark; Lenne-Samuel, Nathalie; Collombat, Patrick; Mansouri, Ahmed; Lee, Jacqueline; Lan, Michael; Pipeleers, Daniel; Nielsen, Finn C; Ferrer, Jorge; Gradwohl, Gérard; Heimberg, Harry

    2006-01-01

    Neurogenin 3 (Ngn3) is key for endocrine cell specification in the embryonic pancreas and induction of a neuroendocrine cell differentiation program by misexpression in adult pancreatic duct cells. We identify the gene encoding IA1, a zinc-finger transcription factor, as a direct target of Ngn3 and show that it forms a novel branch in the Ngn3-dependent endocrinogenic transcription factor network. During embryonic development of the pancreas, IA1 and Ngn3 exhibit nearly identical spatio-temporal expression patterns. However, embryos lacking Ngn3 fail to express IA1 in the pancreas. Upon ectopic expression in adult pancreatic duct cells Ngn3 binds to chromatin in the IA1 promoter region and activates transcription. Consistent with this direct effect, IA1 expression is normal in embryos mutant for NeuroD1, Arx, Pax4 and Pax6, regulators operating downstream of Ngn3. IA1 is an effector of Ngn3 function as inhibition of IA1 expression in embryonic pancreas decreases the formation of insulin- and glucagon-positive cells by 40%, while its ectopic expression amplifies neuroendocrine cell differentiation by Ngn3 in adult duct cells. IA1 is therefore a novel Ngn3-regulated factor required for normal differentiation of pancreatic endocrine cells. PMID:16511571

  20. [Etiological factors of acute pancreatitis].

    PubMed

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  1. Pancreatic islet blood flow and its measurement

    PubMed Central

    Jansson, Leif; Barbu, Andreea; Bodin, Birgitta; Drott, Carl Johan; Espes, Daniel; Gao, Xiang; Grapensparr, Liza; Källskog, Örjan; Lau, Joey; Liljebäck, Hanna; Palm, Fredrik; Quach, My; Sandberg, Monica; Strömberg, Victoria; Ullsten, Sara; Carlsson, Per-Ola

    2016-01-01

    Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting β-cells, endothelium-derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future. PMID:27124642

  2. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

    PubMed Central

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

    2009-01-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

  3. Leading the Team You Inherit.

    PubMed

    Watkins, Michael D

    2016-06-01

    Most leaders don't have the luxury of building their teams from scratch. Instead they're put in charge of an existing group, and they need guidance on the best way to take over and improve performance. Watkins, an expert on transitions, suggests a three-step approach: Assess. Act quickly to size up the personnel you've inherited, systematically gathering data from one-on-one chats, team meetings, and other sources. Reflect, too, on the business challenges you face, the kinds of people you want in various roles, and the degree to which they need to collaborate. Reshape. Adjust the makeup of the team by moving people to new positions, shifting their responsibilities, or replacing them. Make sure that everyone is aligned on goals and how to achieve them--you may need to change the team's stated direction. Consider also making changes in the way the team operates (reducing the frequency of meetings, for example, or creating new subteams). Then establish ground rules and processes to sustain desired behaviors, and revisit those periodically. Accelerate team development. Set your people up for some early wins. Initial successes will boost everyone's confidence and reinforce the value of your new operating model, thus paving the way for ongoing growth.

  4. Inherited disorders of blood coagulation.

    PubMed

    Lippi, Giuseppe; Franchini, Massimo; Montagnana, Martina; Favaloro, Emmanuel J

    2012-08-01

    Hemostasis is traditionally defined as a physiological response to blood vessel injury and bleeding, which entails a co-ordinated process involving the blood vessel, platelets, and blood clotting proteins (i.e. coagulation factors). Hemostasis can be divided into primary and secondary components. The former rapidly initiates after endothelial damage and is characterized by vascular contraction, platelet adhesion, and formation of a soft aggregate plug. The latter is initiated following the release of tissue factor and involves a complex sequence of events known as the blood coagulation cascade, encompassing serial steps where each coagulation factor activates another in a chain reaction that culminates in the conversion of fibrinogen to fibrin. Patients carrying abnormalities of the coagulation cascade (i.e. deficiencies of coagulation factors) have an increased bleeding tendency, where the clinical severity is mostly dependent upon the type and the plasma level of the factor affected. These disorders also impose a heavy medical and economic burden on individual patients and society in general. The aim of this article is to provide a general overview on the pathophysiology, clinics, diagnostics, and therapy of inherited disorders of coagulation factors.

  5. Leading the Team You Inherit.

    PubMed

    Watkins, Michael D

    2016-06-01

    Most leaders don't have the luxury of building their teams from scratch. Instead they're put in charge of an existing group, and they need guidance on the best way to take over and improve performance. Watkins, an expert on transitions, suggests a three-step approach: Assess. Act quickly to size up the personnel you've inherited, systematically gathering data from one-on-one chats, team meetings, and other sources. Reflect, too, on the business challenges you face, the kinds of people you want in various roles, and the degree to which they need to collaborate. Reshape. Adjust the makeup of the team by moving people to new positions, shifting their responsibilities, or replacing them. Make sure that everyone is aligned on goals and how to achieve them--you may need to change the team's stated direction. Consider also making changes in the way the team operates (reducing the frequency of meetings, for example, or creating new subteams). Then establish ground rules and processes to sustain desired behaviors, and revisit those periodically. Accelerate team development. Set your people up for some early wins. Initial successes will boost everyone's confidence and reinforce the value of your new operating model, thus paving the way for ongoing growth. PMID:27491196

  6. [Inherited thrombopathia in Simmental cattle].

    PubMed

    Aebi, M; Wiedemar, N; Drögemüller, C; Zanolari, R

    2016-02-01

    During the years 2012 to 2014, a total of 5 affected Simmental cattle showing persistent bleeding after minor or unknown trauma, were presented at the Clinic for Ruminants or at the Institute for Genetics of the Vetsuisse-Faculty, University of Berne. The homozygous mutation RASGRP2, initially reported in 2007, was present in all these cases and all available parents were heterozygous carriers thus confirming the recessive mode of inheritance. Three affected animals died as a result of persistent bleeding. One animal was stabilized at the Clinic for Ruminants and was slaughtered one month later. Another case showing persistent bleeding and several hematomas was euthanized after genotyping. A frequency of 10% carriers for the associated mutation was detected in a sample of 145 Simmental sires which were used 2013 for artificial insemination in Switzerland. These bulls are designated as TP carriers and should not be used uncontrolled. Breeding organizations in Switzerland make use of the gene test to select bulls which do not carry the mutation. PMID:27145685

  7. The inheritance of fingerprint patterns.

    PubMed Central

    Slatis, H M; Katznelson, M B; Bonné-Tamir, B

    1976-01-01

    Analysis of the fingerprints of 571 members of the Habbanite isolate suggest inherited patterns and pattern sequences. A genetic theory has been developed; it assumes that the basic fingerprint pattern sequence is all ulnar loops and that a variety of genes cause deviations from this pattern sequence. Genes that have been proposed include: (1) a semidominant gene for whorls on the thumbs (one homozygote has whorls on both thumbs, the other has ulnar loops on both thumbs and the heterozygote usually has two ulnar loops or one ulnar loop and one whorl); (2) a semidominant gene for whorls on the ring fingers which acts like the gene for whorls on the thumbs; (3) a dominant gene for arches on the thumbs and often on other fingers; (4) one or more dominant genes for arches on the fingers; (5) a dominant gene for whorls on all fingers except for an ulnar loop on the middle finger; (6) a dominant gene for radial loops on the index fingers, frequently associated with an arch on the middle fingers; and (7) a recessive gene for radial loops on the ring and little fingers. These genes may act independently or may show epistasis. PMID:1266855

  8. Coalgebraic structure of genetic inheritance.

    PubMed

    Tian, Jianjun; Li, Bai-Lian

    2004-09-01

    Although in the broadly defined genetic algebra, multiplication suggests a forward direction of from parents to progeny, when looking from the reverse direction, it also suggests to us a new algebraic structure-coalge- braic structure, which we call genetic coalgebras. It is not the dual coalgebraic structure and can be used in the construction of phylogenetic trees. Math- ematically, to construct phylogenetic trees means we need to solve equations x([n]) = a, or x([n]) = b. It is generally impossible to solve these equations inalgebras. However, we can solve them in coalgebras in the sense of tracing back for their ancestors. A thorough exploration of coalgebraic structure in genetics is apparently necessary. Here, we develop a theoretical framework of the coalgebraic structure of genetics. From biological viewpoint, we defined various fundamental concepts and examined their elementary properties that contain genetic significance. Mathematically, by genetic coalgebra, we mean any coalgebra that occurs in genetics. They are generally noncoassociative and without counit; and in the case of non-sex-linked inheritance, they are cocommutative. Each coalgebra with genetic realization has a baric property. We have also discussed the methods to construct new genetic coalgebras, including cocommutative duplication, the tensor product, linear combinations and the skew linear map, which allow us to describe complex genetic traits. We also put forward certain theorems that state the relationship between gametic coalgebra and gametic algebra. By Brower's theorem in topology, we prove the existence of equilibrium state for the in-evolution operator. PMID:20369970

  9. Paternity and inheritance of wealth

    NASA Astrophysics Data System (ADS)

    Hartung, John

    1981-06-01

    One of the oldest conjectures in anthropology is that men transfer wealth to their sister's son when the biological paternity of their `own' children is in doubt1-12. Because maternity is certain, a man is necessarily related to his sister's son and his brother (see Fig. 1). It is argued here that relatedness to male heirs can be assured by passing wealth to sister's sons or down a line of brothers, whether the prevailing kinship system reckons those brothers matrilineally or patrilineally. It is also argued that when several transfers of wealth are considered, a man's likelihood of being cuckolded need not be unrealistically high13 for his successive matrilineal heirs to be more related to him than his successive patrilineal heirs (see Fig. 2). Cross-cultural data on sister's son/brother inheritance14 and frequency of extramarital sex for females15 support the hypothesis that men tend to transmit wealth to their sister's son and/or brother when the probability that their putative children are their genetic children is relatively low.

  10. Inherited bleeding syndromes in Iraq.

    PubMed

    Al-Mondhiry, H A

    1977-06-30

    This paper presents data on the occurence and pattern of inherited bleeding syndromes (IBS) in Iraq, a hitherto unexplored problem. During the first fourteen months of a prospective on-going study at a major university center, 116 patients from 62 families were diagnosed as having IBS. All patients were referred because of moderate to severe bleeding diatheses. They included 62 haemophiliacs 32 patients with von Willebrand's disease (VWD), 9 with Christmas disease (CD), 6 with afibrinogenemia, 1 with prothrombin deficiency, and 6 were thought to have platelet dysfunction. 32 other bleeders (16 hemophiliacs, 14 VWD, and 2 CD) were also recognized among the pedigrees studied but were not available for full investigations. The clinical and laboratory features of the patients observed in Iraq do not seem to be significantly different from those of patients in Western Europe or North America. Although the absolute incidence and relative distribution of these disorders in the entire population cannot yet be determined, the rate of occurence per segment population is likely to be high, most likely due to the high rate of consanguinity and large number of births per family, phenomena still prevalent in this country.

  11. Early pancreatic islet fate and maturation is controlled through RBP-Jκ

    PubMed Central

    Cras-Méneur, Corentin; Conlon, Megan; Zhang, Yaqing; Pasca Di Magliano, Marina; Bernal-Mizrachi, Ernesto

    2016-01-01

    Notch signaling is known to control early pancreatic differentiation through Ngn3 repression. In later stages, downstream of Notch, the Presenilins are still required to maintain the endocrine fate allocation. Amongst their multiple targets, it remains unclear which one actually controls the maintenance of the fate of the early islets. Conditional deletions of the Notch effector RBP-Jκ with lineage tracing in Presenilin-deficient endocrine progenitors, demonstrated that this factor is central to the control of the fate through a non-canonical Notch mechanism. RBP-Jκ mice exhibit normal islet morphogenesis and function, however, a fraction of the progenitors fails to differentiate and develop into disorganized masses resembling acinar to ductal metaplasia and chronic pancreatitis. A subsequent deletion of RBP-Jκ in forming β-cells led to the transdifferentiation into the other endocrine cells types, indicating that this factor still mediates the maintenance of the fate within the endocrine lineage itself. These results highlight the dual importance of Notch signaling for the endocrine lineage. Even after Ngn3 expression, Notch activity is required to maintain both fate and maturation of the Ngn3 progenitors. In a subset of the cells, these alterations of Notch signaling halt their differentiation and leads to acinar to ductal metaplasia. PMID:27240887

  12. Wnt9a deficiency discloses a repressive role of Tcf7l2 on endocrine differentiation in the embryonic pancreas.

    PubMed

    Pujadas, G; Cervantes, S; Tutusaus, A; Ejarque, M; Sanchez, L; García, A; Esteban, Y; Fargas, L; Alsina, B; Hartmann, C; Gomis, R; Gasa, R

    2016-01-14

    Transcriptional and signaling networks establish complex cross-regulatory interactions that drive cellular differentiation during development. Using microarrays we identified the gene encoding the ligand Wnt9a as a candidate target of Neurogenin3, a basic helix-loop-helix transcription factor that functions as a master regulator of pancreatic endocrine differentiation. Here we show that Wnt9a is expressed in the embryonic pancreas and that its deficiency enhances activation of the endocrine transcriptional program and increases the number of endocrine cells at birth. We identify the gene encoding the endocrine transcription factor Nkx2-2 as one of the most upregulated genes in Wnt9a-ablated pancreases and associate its activation to reduced expression of the Wnt effector Tcf7l2. Accordingly, in vitro studies confirm that Tcf7l2 represses activation of Nkx2-2 by Neurogenin3 and inhibits Nkx2-2 expression in differentiated β-cells. Further, we report that Tcf7l2 protein levels decline upon initiation of endocrine differentiation in vivo, disclosing the downregulation of this factor in the developing endocrine compartment. These findings highlight the notion that modulation of signalling cues by lineage-promoting factors is pivotal for controlling differentiation programs.

  13. Wnt9a deficiency discloses a repressive role of Tcf7l2 on endocrine differentiation in the embryonic pancreas

    PubMed Central

    Pujadas, G.; Cervantes, S.; Tutusaus, A.; Ejarque, M.; Sanchez, L.; García, A.; Esteban, Y.; Fargas, L.; Alsina, B.; Hartmann, C.; Gomis, R.; Gasa, R.

    2016-01-01

    Transcriptional and signaling networks establish complex cross-regulatory interactions that drive cellular differentiation during development. Using microarrays we identified the gene encoding the ligand Wnt9a as a candidate target of Neurogenin3, a basic helix-loop-helix transcription factor that functions as a master regulator of pancreatic endocrine differentiation. Here we show that Wnt9a is expressed in the embryonic pancreas and that its deficiency enhances activation of the endocrine transcriptional program and increases the number of endocrine cells at birth. We identify the gene encoding the endocrine transcription factor Nkx2-2 as one of the most upregulated genes in Wnt9a-ablated pancreases and associate its activation to reduced expression of the Wnt effector Tcf7l2. Accordingly, in vitro studies confirm that Tcf7l2 represses activation of Nkx2-2 by Neurogenin3 and inhibits Nkx2-2 expression in differentiated β-cells. Further, we report that Tcf7l2 protein levels decline upon initiation of endocrine differentiation in vivo, disclosing the downregulation of this factor in the developing endocrine compartment. These findings highlight the notion that modulation of signalling cues by lineage-promoting factors is pivotal for controlling differentiation programs. PMID:26771085

  14. Diagnosis of autoimmune pancreatitis

    PubMed Central

    Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

    2014-01-01

    Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

  15. Pleuropulmonary complications of pancreatitis

    PubMed Central

    Kaye, Michael D.

    1968-01-01

    Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and—if long standing—may be complicated by a bronchopleural fistula. Images PMID:4872925

  16. Autoimmune pancreatitis and cholangitis

    PubMed Central

    Jani, Niraj; Buxbaum, James

    2015-01-01

    Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings. PMID:26558153

  17. Fatal Pancreatic Panniculitis Associated with Acute Pancreatitis: A Case Report

    PubMed Central

    Lee, Woo Sun; Kim, Mi Yeon; Kim, Sang Woo; Paik, Chang Nyol; Kim, Hyung Ok

    2007-01-01

    Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic diseases; these diseases include acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, and other pancreatic diseases. This malady is manifested as tender erythematous nodules on the legs, buttock, or trunk. Histopathologically, it shows the pathognomonic findings of focal subcutaneous fat necrosis and ghost-like anucleated cells with a thick shadowy wall. We herein report a case of fatal pancreatic panniculitis that was associated with acute pancreatitis in a 50-yr-old man. He presented with a 3-week history of multiple tender skin nodules, abdominal pain and distension. Laboratory and radiologic findings revealed acute pancreatitis, and skin biopsy showed pancreatic panniculitis. Despite intensive medical care, he died of multi-organ failure 3 weeks after presentation. PMID:17982246

  18. [Primary pancreatic plasmacytoma].

    PubMed

    Sánchez Acevedo, Z; Pomares Rey, B; Alpera Tenza, M R; Andrada Becerra, E

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma. PMID:22738942

  19. A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase.

    PubMed

    Feng, Zhi-Chao; Riopel, Matthew; Popell, Alex; Wang, Rennian

    2015-04-01

    The interactions between c-Kit and its ligand, stem cell factor (SCF), play an important role in haematopoiesis, pigmentation and gametogenesis. c-Kit is also found in the pancreas, and recent studies have revealed that c-Kit marks a subpopulation of highly proliferative pancreatic endocrine cells that may harbour islet precursors. c-Kit governs and maintains pancreatic endocrine cell maturation and function via multiple signalling pathways. In this review we address the importance of c-Kit signalling within the pancreas, including its profound role in islet morphogenesis, islet vascularisation, and beta cell survival and function. We also discuss the impact of c-Kit signalling in pancreatic disease and the use of c-Kit as a potential target for the development of cell-based and novel drug therapies in the treatment of diabetes.

  20. Multiple endocrine neoplasia type 2.

    PubMed

    Lodish, Maya

    2013-01-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter.

  1. Classical endocrine diseases causing obesity.

    PubMed

    Weaver, Jolanta U

    2008-01-01

    Obesity is associated with several endocrine diseases, including common ones such as hypothyroidism and polycystic ovarian syndrome to rare ones such as Cushing's syndrome, central hypothyroidism and hypothalamic disorders. The mechanisms for the development of obesity vary in according to the endocrine condition. Hypothyroidism is associated with accumulation of hyaluronic acid within various tissues, additional fluid retention due to reduced cardiac output and reduced thermogenesis. The pathophysiology of obesity associated with polycystic ovarian syndrome remains complex as obesity itself may simultaneously be the cause and the effect of the syndrome. Net excess of androgen appears to be pivotal in the development of central obesity. In Cushing's syndrome, an interaction with thyroid and growth hormones plays an important role in addition to an increased adipocyte differentiation and adipogenesis. This review also describes remaining rare cases: hypothalamic obesity due to central hypothyroidism and combined hormone deficiencies. PMID:18230905

  2. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  3. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  4. SEL1L deficiency impairs growth and differentiation of pancreatic epithelial cells

    PubMed Central

    2010-01-01

    Background The vertebrate pancreas contains islet, acinar and ductal cells. These cells derive from a transient pool of multipotent pancreatic progenitors during embryonic development. Insight into the genetic determinants regulating pancreatic organogenesis will help the development of cell-based therapies for the treatment of diabetes mellitus. Suppressor enhancer lin12/Notch 1 like (Sel1l) encodes a cytoplasmic protein that is highly expressed in the developing mouse pancreas. However, the morphological and molecular events regulated by Sel1l remain elusive. Results We have characterized the pancreatic phenotype of mice carrying a gene trap mutation in Sel1l. We show that Sel1l expression in the developing pancreas coincides with differentiation of the endocrine and exocrine lineages. Mice homozygous for the gene trap mutation die prenatally and display an impaired pancreatic epithelial morphology and cell differentiation. The pancreatic epithelial cells of Sel1l mutant embryos are confined to the progenitor cell state throughout the secondary transition. Pharmacological inhibition of Notch signaling partially rescues the pancreatic phenotype of Sel1l mutant embryos. Conclusions Together, these data suggest that Sel1l is essential for the growth and differentiation of endoderm-derived pancreatic epithelial cells during mouse embryonic development. PMID:20170518

  5. Is Pancreatic Cancer Hereditary?

    MedlinePlus

    ... Trials Pain Management Nutrition and Exercise Holistic Care Pathology Intraductal Papillary Mucinous Neoplasms Islet Cell Tumors & Endocrine ... 410-933-7262 Site Map Policies & Credits News Pathology Home Goldman Center © 2016 Johns Hopkins University

  6. Surgical Approaches to Chronic Pancreatitis

    PubMed Central

    Hartmann, Daniel; Friess, Helmut

    2015-01-01

    Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ-preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients. PMID:26681935

  7. Age-Related Impairment of Pancreatic Beta-Cell Function: Pathophysiological and Cellular Mechanisms

    PubMed Central

    De Tata, Vincenzo

    2014-01-01

    The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions. PMID:25232350

  8. Endocrine manifestations in celiac disease

    PubMed Central

    Freeman, Hugh James

    2016-01-01

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison’s disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet. PMID:27784959

  9. [Contamination, endocrine disruptors and cancer].

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-03-01

    Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations. PMID:27382804

  10. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis. PMID:26520201

  11. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis.

  12. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly. PMID:27281924

  13. Law & psychiatry: Murder, inheritance, and mental illness.

    PubMed

    Gold, Azgad; Appelbaum, Paul S

    2011-07-01

    Should a murderer be allowed to inherit the victim's estate? The question dates from biblical times, but most jurisdictions today have statutes in place that bar inheritance by convicted murderers. However, a special problem arises when the killer has a severe mental illness and has been found not guilty by reason of insanity. Should such people, who have not been convicted of a crime, be permitted to collect their inheritance? Jurisdictions vary in their responses, with the rules reflecting a mix of practical and moral considerations influenced by different perspectives about what determines the behavior of persons with mental illness.

  14. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly.

  15. The Ontogeny of the Endocrine Pancreas in the Fetal/Newborn Baboon

    PubMed Central

    Quinn, Amy R.; Blanco, Cynthia L.; Perego, Carla; Finzi, Giovanna; La Rosa, Stefano; Capella, Carlo; Guardado-Mendoza, Rodolfo; Casiraghi, Francesca; Gastaldelli, Amalia; Johnson, Marney; Dick, Edward J.; Folli, Franco

    2013-01-01

    Background Erratic regulation of glucose metabolism including hyperglycemia is a common condition of premature infants and is associated with increased morbidity and mortality. Objective To examine histological and ultra-structural differences in the endocrine pancreas in fetal (throughout gestation) and neonatal baboons. Methods Twelve fetal baboons were delivered at 125 days (d) gestational age (GA), 140dGA, or 175dGA. Eight animals were delivered at term (185dGA); half were fed for 5d. Seventy-three non-diabetic adult baboons were used for comparison. Pancreatic tissue was studied utilizing light microscopy, confocal imaging and electron microscopy. Results The fetal and neonatal endocrine pancreas islet architecture became more organized as GA advanced. The percent areas of α-β-δ-cell type were similar within each fetal and newborn GA (NS), but were higher than the adults (P<0.05) regardless of GA. The ratio of β-cells within the islet (whole and core) increased with gestation (P<0.01). Neonatal baboons who survived for 5 days (feeding), had a 2.5-fold increase in pancreas weight compared to their counterparts euthanized at birth (P=0.01). Endocrine cells were found amongst exocrine ductal and acinar cells in 125,140 and 175dGA fetuses. Subpopulation of cells that co-expressed trypsin and glucagon/insulin show the presence of cells with mixed endo-exocrine lineage in fetuses. Conclusions The fetal endocrine pancreas has no prevalence of a of α-β-δ-cell type with larger endocrine cell percent areas than adults. Cells with mixed endocrine/exocrine phenotype occur during fetal development. Developmental differences may play a role in glucose homeostasis during the neonatal period and may have long term implications. PMID:22723715

  16. Pancreatic Cancer Risk Factors

    MedlinePlus

    ... age at the time of diagnosis is 71. Gender Men are slightly more likely to develop pancreatic ... of these syndromes can be found by genetic testing. For more information on genetic testing, see Can ...

  17. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... sudden inflammation of the pancreas manifested clinically by abdominal pain, nausea and dehydration that is usually self-limiting ... room for evaluation should they develop any abnormal abdominal pain symptoms. Conclusions While a rare event, acute pancreatitis ...

  18. Acute Pancreatitis in Children

    MedlinePlus

    ... are the symptoms of pancreatitis? Common symptoms include abdominal pain, nausea, and vomiting. However, not every patient with ... help the pancreas to recover. Patients who have abdominal pain can be treated with pain medications. Some patients ...

  19. Nutrition support in pancreatitis.

    PubMed

    Marulendra, S; Kirby, D F

    1995-04-01

    Nutrition support in patients with pancreatitis has created a challenge for clinicians. Because the pancreas is normally stimulated by the ingestion of food, particularly fat, patients are often denied oral nutrition. This reduction in the ingestion of food, together with the increased metabolic demands of this disease, often results in a negative energy balance and occasionally undernutrition or malnutrition. This review summarizes the etiologies and methods for staging pancreatitis, the physiology of pancreatic exocrine secretion and the response of the pancreas to different methods of nutrition support. The results of clinical trials, which examine both parenteral and enteral nutrition in animals and humans with this disease, are reviewed. Recommendations for nutrition management of patients with acute and chronic pancreatitis and areas for future research are discussed.

  20. Management of necrotizing pancreatitis

    PubMed Central

    Slavin, John; Ghaneh, Paula; Sutton, Robert; Hartley, Mark; Rowlands, Peter; Garvey, Conall; Hughes, Mark; Neoptolemos, John

    2001-01-01

    Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. Patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be non-operative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB, and the role of enteral feeding. PMID:11819813

  1. Surgery for Pancreatic Cancer

    MedlinePlus

    ... the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy ... pancreatic cancers appear to be confined to the pancreas at the time they are found. Even then, ...

  2. Pancreatic enzyme pharmacotherapy.

    PubMed

    Ferrone, Marcus; Raimondo, Massimo; Scolapio, James S

    2007-06-01

    Supplemental pancreatic enzyme preparations are provided to patients with conditions of pancreatic exocrine deficiency such as chronic pancreatitis and cystic fibrosis. These patients frequently experience steatorrhea, which occurs from inadequate fat absorption. The delivery of sufficient enzyme concentrations into the duodenal lumen simultaneously with meals can reduce nutrient malabsorption, improve the symptoms of steatorrhea, and in some cases alleviate the pain associated with chronic pancreatitis. Current clinical practices dictate administration of lipase 25,000-40,000 units/meal by using pH-sensitive pancrelipase microspheres, along with dosage increases, compliance checks, and differential diagnosis in cases of treatment failure. Despite the large number of specialty enzyme replacements available commercially, many patients remain dissatisfied with standard therapy, and future developments are needed to optimize treatment in these individuals.

  3. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  4. Cytokines and acute pancreatitis.

    PubMed

    Brady, M; Christmas, S; Sutton, R; Neoptolemos, J; Slavin, J

    1999-07-01

    Cytokines have been shown to play a pivotal role in multiple organ dysfunction, a major cause of death in severe acute pancreatitis. Moreover, the two-hit hypothesis of the cytokine-induced systemic inflammatory response syndrome explains the variable individual response to severe acute pancreatitis and the impact of secondary events such as sepsis or therapeutic intervention. Many experimental anti-cytokine therapies have been administered following induction of experimental pancreatitis, and have proved to be therapeutic. Patients with severe pancreatitis present early because of pain. Clearly then a window for therapeutic intervention is available between onset of symptoms and peak pro-inflammatory cytokine expression. It is this fundamental observation that convinces many in the field that the treatment of AP will be one of the first clinical successes for novel drugs or therapy that seek to modulate the inflammatory response.

  5. Perspectives in Pancreatic Pain

    PubMed Central

    1997-01-01

    This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described. PMID:9298380

  6. [Hereditary aspects of pancreatitis].

    PubMed

    Bak, Daniel; Sobczyńska-Tomaszewska, Agnieszka; Bal, Jerzy

    2003-01-01

    Pancreatitis presents clinically as acute and chronic form. A common characteristic of these two forms is enzymatic autodigestion of pancreas in the course of the disease. It results from premature activation of pancreatic digestive enzymes and disturbance of subtle balance between proteolytic enzymes and their inhibitors. The way to understand the character of mechanisms leading to development of pancreatitis has been simplified by discovery of genetic factors, which are able to initiate pathological changes at tissue level. Mutations in the PRSS1 gene (first of all R122H and N29I mutations), which encodes for cationic trypsin, cause trypsin to be protected from autodegradation. These mutations also cause precursor of trypsin - trypsinogen, to be activated easier. On the other hand mutations in the SPINK1 gene have been identified. SPINK1 gene encodes for the most important protease inhibitor of the pancreatic fluid. The most frequent mutation, namely N34S, decrease SPINK1 protein in its activity. The link between the genotype and phenotype is not clear in every case. It is probable that pancreatitis will be recognized as poligenic with many genes engaged in the disease development. Pancreatic cancer is a frequent consequence of pancreatitis. It is a very invasive cancer with high mortality. In the course of pancreatic inflammation intensive cell proliferation takes place for regeneration of pancreas damage. It is the chance for amplification of pathological changes in DNA, which have arisen as a ROS's (Reactive Oxygen Species) and RNOS's (Reactive Nitrogen Oxide Species) action effect. ROS and RNOS are generated in the course of pancreas inflammation.

  7. microRNAs in Pancreatic β-Cell Physiology.

    PubMed

    Özcan, Sabire

    2015-01-01

    The β-cells within the pancreas are responsible for production and secretion of insulin. Insulin is released from pancreatic β-cells in response to increasing blood glucose levels and acts on insulin-sensitive tissues such as skeletal muscle and liver in order to maintain normal glucose homeostasis. Therefore, defects in pancreatic β-cell function lead to hyperglycemia and diabetes mellitus. A new class of molecules called microRNAs has been recently demonstrated to play a crucial role in regulation of pancreatic β-cell function under normal and pathophysiological conditions. miRNAs have been shown to regulate endocrine pancreas development, insulin biosynthesis, insulin exocytosis, and β-cell expansion. Many of the β-cell enriched miRNAs have multiple functions and regulate pancreas development as well as insulin biosynthesis and exocytosis. Furthermore, several of the β-cell specific miRNAs have been shown to accumulate in the circulation before the onset of diabetes and may serve as potential biomarkers for prediabetes. This chapter will focus on miRNAs that are enriched in pancreatic β-cells and play a critical role in modulation of β-cell physiology and may have clinical significance in the treatment of diabetes. PMID:26662988

  8. Developmental origins of epigenetic transgenerational inheritance

    PubMed Central

    Hanson, Mark A.; Skinner, Michael K.

    2016-01-01

    Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

  9. Center for Inherited Disease Research (CIDR)

    Cancer.gov

    The Center for Inherited Disease Research (CIDR) Program at The Johns Hopkins University provides high-quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to common diseases.

  10. [Arterial hypertension secondary to endocrine disorders].

    PubMed

    Minder, Anna; Zulewski, Henryk

    2015-06-01

    Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

  11. Phosphatonins: new hormones involved in numerous inherited bone disorders

    PubMed Central

    Masi, Laura

    2011-01-01

    Summary Phosphate (Pi) homeostasis is under control of several endocrine factors that play effects on bone, kidney and intestine. The control of Pi homeostasis has a significant biological importance, as it relates to numerous cellular mechanisms involved in energy metabolism, cell signaling, nucleic acid synthesis, membrane function, as well as skeletal health and integrity. Pi is essential for diverse biological processes, and negative Pi balance resulting from improperly regulated intestinal absorption, systemic utilization, and renal excretion. As results of these functions, chronic Pi deprivation causes several biological alterations, such as bone demineralization with unmineralized osateoid typical of osteomalacia in adults and rickets in developing animals and humans (1). Phosphatonins are new hormones playing an important role in the control of Pi homeostasis together with parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D3. Most insight into the underlying mechanisms was established by defining the molecular basis of different inherited disorders that are characterized by an abnormal regulation of Pi homeostasis. PMID:22461821

  12. Hnf1b controls pancreas morphogenesis and the generation of Ngn3+ endocrine progenitors.

    PubMed

    De Vas, Matias G; Kopp, Janel L; Heliot, Claire; Sander, Maike; Cereghini, Silvia; Haumaitre, Cécile

    2015-03-01

    Heterozygous mutations in the human HNF1B gene are associated with maturity-onset diabetes of the young type 5 (MODY5) and pancreas hypoplasia. In mouse, Hnf1b heterozygous mutants do not exhibit any phenotype, whereas the homozygous deletion in the entire epiblast leads to pancreas agenesis associated with abnormal gut regionalization. Here, we examine the specific role of Hnf1b during pancreas development, using constitutive and inducible conditional inactivation approaches at key developmental stages. Hnf1b early deletion leads to a reduced pool of pancreatic multipotent progenitor cells (MPCs) due to decreased proliferation and increased apoptosis. Lack of Hnf1b either during the first or the secondary transitions is associated with cystic ducts. Ductal cells exhibit aberrant polarity and decreased expression of several cystic disease genes, some of which we identified as novel Hnf1b targets. Notably, we show that Glis3, a transcription factor involved in duct morphogenesis and endocrine cell development, is downstream Hnf1b. In addition, a loss and abnormal differentiation of acinar cells are observed. Strikingly, inactivation of Hnf1b at different time points results in the absence of Ngn3(+) endocrine precursors throughout embryogenesis. We further show that Hnf1b occupies novel Ngn3 putative regulatory sequences in vivo. Thus, Hnf1b plays a crucial role in the regulatory networks that control pancreatic MPC expansion, acinar cell identity, duct morphogenesis and generation of endocrine precursors. Our results uncover an unappreciated requirement of Hnf1b in endocrine cell specification and suggest a mechanistic explanation of diabetes onset in individuals with MODY5.

  13. [Disperse endocrine system and APUD concept].

    PubMed

    Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A

    2011-01-01

    This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

  14. Anatomical and functional imaging in endocrine hypertension

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2012-01-01

    In endocrine hypertension, hormonal excess results in clinically significant hypertension. The functional imaging (such as radionuclide imaging) complements anatomy-based imaging (such as ultrasound, computed tomography, and magnetic resonance imaging) to facilitate diagnostic localization of a lesion causing endocrine hypertension. The aim of this review article is to familiarize general radiologists, endocrinologists, and clinicians with various anatomical and functional imaging techniques used in patients with endocrine hypertension. PMID:23087854

  15. Epigenetic alterations caused by nutritional stress during fetal programming of the endocrine pancreas.

    PubMed

    Sosa-Larios, Tonantzin C; Cerbón, Marco A; Morimoto, Sumiko

    2015-02-01

    Nutrition during critical periods of development is one of the pivotal factors in establishing a lifelong healthy metabolism. Different nutritional deficiencies such as a low availability of proteins in the maternal diet produce alterations in offspring that include changes in insulin and glucose metabolism, a decrease in the size and number of cells of pancreatic islets of Langerhans, and premature ageing of the secretory function of pancreatic β cells. Moreover, it has been reported that chronic nutritional stress is associated with epigenetic alterations in mechanisms of gene regulation during pancreatic development and function. These alterations can lead to dysfunctional states in pancreatic β cells, which in the long run are responsible for the onset of metabolic diseases like type 2 diabetes. The present review summarizes the most important evidence in relation to the participation of epigenetic mechanisms in the regulation of gene expression during the intrauterine programming of the endocrine pancreas in animal models. Such mechanisms include DNA methylation as well as modifications of histones and microRNAs (miRNAs).

  16. Total Pancreatectomy with Islet Autologous Transplantation: The Cure for Chronic Pancreatitis?

    PubMed Central

    Kesseli, Samuel J; Smith, Kerrington A; Gardner, Timothy B

    2015-01-01

    Chronic pancreatitis (CP) is a debilitating disease that leads to varying degrees of pancreatic endocrine and exocrine dysfunction. One of the most difficult symptoms of CP is severe abdominal pain, which is often challenging to control with available analgesics and therapies. In the last decade, total pancreatectomy with autologous islet cell transplantation has emerged as a promising treatment for the refractory pain of CP and is currently performed at approximately a dozen centers in the United States. While total pancreatectomy is not a new procedure, the endocrine function-preserving autologous islet cell isolation and re-implantation have made the prospect of total pancreatectomy more acceptable to patients and clinicians. This review will focus on the current status of total pancreatectomy with autologous islet cell transplant including patient selection, technical considerations, and outcomes. As the procedure is performed at an increasing number of centers, this review will highlight opportunities for quality improvement and outcome optimization. PMID:25630865

  17. Hereditary pancreatitis and secondary screening for early pancreatic cancer.

    PubMed

    Vitone, L J; Greenhalf, W; Howes, N R; Neoptolemos, J P

    2005-01-01

    Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

  18. Effect of Endocrine Disruptor Pesticides: A Review

    PubMed Central

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-01-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. PMID:21776230

  19. Effect of endocrine disruptor pesticides: a review.

    PubMed

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-06-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  20. Basic mechanisms of ovarian endocrine function

    PubMed Central

    Schomberg, David W.

    1978-01-01

    This review outlines the current understanding of ovarian endocrine development and regulation with both physiological and biochemical background to provide a framework applicable to problems concerning environmental agents and ovarian endocrine function. Two approaches are used. First, the endocrine regulation of follicle development and corpus luteum function is considered in the classical sense, i.e., viewing these structures as gonadotropin-responsive units undergoing a programmed sequence of development and differentiation. Secondly, a relatively new area of ovarian physiology concerned with intra-ovarian regulation is explored, since this area holds potential for exploration of the direct effects of toxicological or environmental agents upon gonadal endocrine cells. PMID:17539154

  1. Genetics Home Reference: multiple endocrine neoplasia

    MedlinePlus

    ... Tumor Encyclopedia: Pheochromocytoma Encyclopedia: Pituitary Tumor Health Topic: Endocrine Diseases Health Topic: Parathyroid Disorders Health Topic: Pheochromocytoma Health Topic: Thyroid Cancer Genetic ...

  2. Type 1 autoimmune pancreatitis.

    PubMed

    Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki

    2011-12-07

    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed

  3. Pain in chronic pancreatitis and pancreatic cancer.

    PubMed

    Fasanella, Kenneth E; Davis, Brian; Lyons, John; Chen, Zongfu; Lee, Kenneth K; Slivka, Adam; Whitcomb, David C

    2007-06-01

    Chronic, debilitating abdominal pain is arguably the most important component of chronic pancreatitis, leading to significant morbidity and disability. Attempting to treat this pain, which is too often unsuccessful, is a frustrating experience for physician and patient. Multiple studies to improve understanding of the pathophysiology that causes pain in some patients but not in others have been performed since the most recent reviews on this topic. In addition, new treatment modalities have been developed and evaluated in this population. This review discusses new advances in neuroscience and the study of visceral pain mechanisms, as well as genetic factors that may play a role. Updates of established therapies, as well as new techniques used in addressing pain from chronic pancreatitis, are reviewed. Lastly, outcome measures, which have been highly variable in this field over the years, are addressed. PMID:17533083

  4. General Information about Pancreatic Cancer

    MedlinePlus

    ... Research Pancreatic Cancer Treatment (PDQ®)–Patient Version General Information About Pancreatic Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

    Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

    2013-01-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

  6. Pancreatic trauma: A concise review

    PubMed Central

    Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar

    2013-01-01

    Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma. PMID:24379625

  7. Pathophysiology of autoimmune pancreatitis

    PubMed Central

    Pezzilli, Raffaele; Pagano, Nico

    2014-01-01

    Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related disease. In addition, the pancreas of a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP. From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that the polymorphic genes encoding cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses. PMID:24891971

  8. Endocrine causes of male infertility.

    PubMed

    Jarow, Jonathan P

    2003-02-01

    Although endocrinopathies are not often seen in infertile men, these disorders are clinically significant; they often have potentially serious medical significance, regardless of fertility issues. Correction of these disorders represents a possible way to restore normal fertility for the male partner. Male fertility is critically dependent upon a normal hormonal milieu. The hypothalamic-pituitary-gonadal axis is quite sensitive to disruption by endocrine disorders and other generalized medical disorders. Thus, male infertility is occasionally the presenting sign for significant underlying medical disease; it is important to properly evaluate these patients.

  9. Endocrine Disease in Aged Horses.

    PubMed

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. PMID:27449391

  10. Endocrine problems of adolescent pregnancy.

    PubMed

    Molitch, M E

    1993-09-01

    A number of changes in renal and endocrine physiology occur during pregnancy that alter hormone levels and affect a number of disease processes. Increased glomerular filtration causes an increase in hormone and substrate clearance. Increased placental steroid production causes an increase in hormone-binding globulin production, insulin resistance, and prolactinoma growth. Production of peptide hormones may cause changes in normal physiology and alter dynamic hormone testing. Placental vasopressinase increases vasopressin clearance. A number of diseases of hormone overproduction and underproduction affect pregnancy outcome and must be treated promptly by therapeutic modalities that also may affect the fetus.

  11. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists.

  12. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists. PMID:27376795

  13. Nutrition, Inflammation, and Acute Pancreatitis

    PubMed Central

    Petrov, Max

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

  14. Clinical pancreatic disorder I: Acute pancreatitis.

    PubMed

    Andrén-Sandberg, Ake

    2011-07-01

    The Annual American Pancreas Club is an important event for communicating around clinical pancreatic disorders, just as the European, Japanese, Indian, and the International Pancreatic association. Even though the meeting is only 1½ day there were 169 different abstracts and a "How do I do it session." Among all these abstracts on the pancreas there are some real pearls, but they are almost always well hidden, never highlighted - all abstracts are similarly presented - and will too soon be forgotten. The present filing of the abstracts is one way (not the way) to get the pancreatic abstracts a little more read and a little more remembered - and perhaps a little more cited. It should also be understood that most of the abstracts are short summaries of hundreds of working hours (evenings, nights, weekends, holidays, you name them …) in the laboratory or in the clinic, often combined with blood, sweat and tears. The authors should be shown at least some respect, and their abstracts should not only be thought of as "just another little abstract" - and the best respect they can be shown are that they will be remembered to be another brick in our scientific wall.Now the pancreatic abstracts of American Pancreas Club 2011 are gathered and filed with the aim to give them a larger audience than they have had in their original abstract book. However, it is obvious that most of clinical fellows do not have time to read all the abstracts. For them I have made a "clinical highlight section" of 10 percent of all the pancreatic abstracts. If someone else should have done some collection of abstract, there should probably have been other selections, but as this is not the case, the editor's choices are the highlighted ones.The article as series I of clinical highlight section is present, and more series will be present in the following issues. If readers will remember some of the abstracts better after reading this "abstract of abstracts", it was worth the efforts - and without

  15. The global gene expression profile of the secondary transition during pancreatic development.

    PubMed

    Willmann, Stefanie J; Mueller, Nikola S; Engert, Silvia; Sterr, Michael; Burtscher, Ingo; Raducanu, Aurelia; Irmler, Martin; Beckers, Johannes; Sass, Steffen; Theis, Fabian J; Lickert, Heiko

    2016-02-01

    Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF(+) pancreatic epithelium from the FVF(−) surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5-15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with them RNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation. PMID:26643664

  16. The global gene expression profile of the secondary transition during pancreatic development.

    PubMed

    Willmann, Stefanie J; Mueller, Nikola S; Engert, Silvia; Sterr, Michael; Burtscher, Ingo; Raducanu, Aurelia; Irmler, Martin; Beckers, Johannes; Sass, Steffen; Theis, Fabian J; Lickert, Heiko

    2016-02-01

    Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF(+) pancreatic epithelium from the FVF(−) surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5-15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with them RNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation.

  17. Production of islet-like structures from neonatal porcine pancreatic tissue in suspension bioreactors.

    PubMed

    Chawla, Meera; Bodnar, Cheryl A; Sen, Arindom; Kallos, Michael S; Behie, Leo A

    2006-01-01

    The aim of this study was to develop a scaleable process to expand pancreatic endocrine tissue (i.e., aggregates or islet-like structures) in suspension bioreactors. Key issues addressed included (i) serum-free media, (ii) cell inoculation density, (iii) medium pH, and (iv) aggregate dissociation. Suspension bioreactors were inoculated with pancreatic neonatal tissue and operated under controlled conditions for a 9-day period. Medium studies showed that a new serum-free medium developed in our laboratory was capable of supporting endocrine cell expansion. An inoculation density of 127,000 cells/mL resulted in more than a 7.5-fold increase in the number of insulin-positive cells after 9 days. The resulting population consisted of single cells and many islet-like aggregates that contained all of the endocrine cell types (including insulin-positive, glucagon-positive, somatostatin-positive, and pancreatic polypeptide-positive cells). Furthermore, the cell aggregates exhibited a glucose-responsive behavior. This study represents a significant milestone on the path to the effective expansion of human islet-like tissue in bioreactors that may be used for cell therapy to treat Type 1 diabetes.

  18. Multiple Endocrine Neoplasia: A Genetically Diverse Group of Familial Tumor Syndromes.

    PubMed

    Pacheco, M Cristina

    2016-06-01

    Multiple endocrine neoplasia (MEN) syndrome is a familial cancer syndrome characterized by neuroendocrine tumors. The syndrome encompasses four major subtypes: MEN1, MEN2A, MEN2B, and MEN4. MEN1 is caused by mutations in the MEN1 gene, MEN2A and MEN2B are caused by mutations in RET, and MEN4 is caused by mutations in CDKNB1. All are inherited in an autosomal dominant pattern, but de novo cases do arise. While all subtypes are associated with neuroendocrine tumors, each has characteristic organ involvement. Identifying patients with the syndrome can aid in proper screening and treatment. PMID:27617149

  19. Hepatobiliary and pancreatic ascariasis

    PubMed Central

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  20. Hepatobiliary and pancreatic ascariasis.

    PubMed

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  1. Pharmacogenetics in pancreatic cancer.

    PubMed

    Tourkantonis, Ioannis S; Peponi, Evangelia; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2014-07-01

    Pancreatic cancer is an aggressive malignancy with a poor overall survival rate. Given advances in pharmacogenomics, numerous gene mutations have been identified that could be potential targets for drug development. Therefore, future research strategies may identify prognostic and predictive markers aiming to improve outcome by maximizing efficacy whilst lowering toxicity. In this commentary, we summarize several interesting results regarding pancreatic cancer pharmacogenetics that have been presented in the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. In particular, we focus on Abstract #4124, which investigated the potential predictive role of human equilibrative nucleoside transporter 1 (hENT1) in patients treated with adjuvant gemcitabine for pancreatic cancer, on Abstract #4125, which examined the tolerability of a modified FOLFORINOX study based on UGT1A1*28 genotype guided dosing of IRI in patients with advanced pancreatic cancer, and on Abstract #4130, which confirmed the predictive role of circulating tumor and invasive cells (CTICs) from patients with unresectable pancreatic cancer in second-line chemotherapy treatment setting. PMID:25076337

  2. Borderline resectable pancreatic cancer.

    PubMed

    Hackert, Thilo; Ulrich, Alexis; Büchler, Markus W

    2016-06-01

    Surgery followed by adjuvant chemotherapy remains the only treatment option for pancreatic ductal adenocarcinoma (PDAC) with the chance of long-term survival. If a radical tumor resection is possible, 5-year survival rates of 20-25% can be achieved. Pancreatic surgery has significantly changed during the past years and resection approaches have been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), which has recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), has become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. Preoperative diagnostic accuracy to define resectability of PDAC is a keypoint in this context as well as the surgical and interdisciplinary expertise to perform advanced pancreatic surgery and manage complications. The present mini-review summarizes the current state of definition, management and outcome of BR-PDAC. Furthermore, the topic of ongoing and future studies on neoadjuvant treatment which is closely related to borderline resectability in PDAC is discussed. PMID:26970276

  3. Hepatobiliary and pancreatic ascariasis

    PubMed Central

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.

  4. Sleep apnoea in endocrine diseases.

    PubMed

    Rosenow, F; McCarthy, V; Caruso, A C

    1998-03-01

    The pertinent literature on the prevalence, clinical manifestations and pathogenic mechanisms of sleep apnoea (SA) in endocrine diseases, namely acromegaly, Cushing syndrome, hypothyroidism and diabetes mellitus was reviewed. An increased prevalence is well documented in patients with active and treated acromegaly. While most authors report peripheral obstruction, due to hypertrophy of tongue and pharyngeal tissues, to be the cause of SA in acromegaly, some findings argue for a role of hormone-induced changes of central respiratory control. SA is also more common in hypothyroidism, especially when myxedema is present. The associated edema and myopathy appear to be of pathogenic importance. Thyroxin substitution is frequently effective for the treatment of SA but nCPAP can be necessary initially and in some patients even after remission of clinical signs of hypothyroidism. In Cushing disease and syndrome, parapharyngeal fat accumulation can cause SA, but no epidemiological information is available. In non insulin dependent diabetes (NIDDM), obesity is the common risk factor for both, nocturnal hypoxia and insulin resistance. In IDDM, the development of autonomic neuropathy may predispose to SA. Where treatment of the underlying endocrine disease is unable cure the associated SA, nCPAP is usually the treatment of first choice. More prospective studies are clearly needed to establish prevalences and resolve the controversies regarding pathogenesis. PMID:9613423

  5. Endocrine response to brain injury.

    PubMed

    Chioléro, R; Berger, M

    1994-11-01

    The neuroendocrine response (NER) is an essential component of the adaptive process to trauma, brain injury, and major surgery. While receiving additive humoral and neural afferent inputs, the brain nuclei responsible for the NER act mainly by efferent pathways to the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, the activations of which induce subsequent circulatory and metabolic responses. The NER to brain injury is similar to the response observed in patients with extracerebral injury, even if the response after brain injury is extremely variable. Generally, there is a biphasic pattern, with a sympathoadrenal storm associated with variable and altered stimulation of the HPA during the ebb phase. The first phase is followed by a decrease in both responses while other endocrine changes develop, involving mainly the counter-regulatory, gonadal, and thyroid hormones. The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome. Alterations of the thyroid hormones are largely related to a reduction in peripheral deiodination of thyroxin. Recent research shows that increased free-radical production and decreased selenium (an antioxidant) serum levels play an important role in thyroid metabolism. Two major issues remain unsolved: a) the precise definition of cerebral death, since endocrine brain function is not abolished in the state currently defined as brain death; and b) the question of whether substitutive hormone therapy should be applied in severe brain injury.

  6. Management of fetal endocrine disorders.

    PubMed

    Hughes, I A

    2003-08-01

    A number of maternal endocrine disorders, when active during pregnancy, can have adverse effects on the newborn. Frequently, these affects can be anticipated as in Graves' disease, or the adverse effect can be prevented as in macrosomia in the infant of the diabetic mother. Occasionally, there are opportunities for prenatal treatment of a fetal endocrine disorder. For instance, a large goitre that may cause problems during delivery can be treated with thyroid hormones administered intra-amniotically or as analogues that cross the placenta. A uniquely effective form of treatment for prevention of a major birth defect is administration of dexamethasone to the mother to avoid virilisation of a female fetus with congenital adrenal hyperplasia (CAH). However, such treatment should only be conducted within the framework of a clinical trial as the long-term effects of exposure to potent glucocorticoids in utero are unknown. Intrauterine growth retardation, which affects about 5% of newborns, is currently not amenable to direct pharmacological treatment before birth. However, there are more practical options for managing this condition, including improved maternal nutrition and avoidance of toxins injurious to fetal growth.

  7. [The vitamin D endocrine system].

    PubMed

    Castro, Luiz Claudio Gonçalves de

    2011-11-01

    The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)(2)D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)(2)D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)(2)D directly or indirectly modulates about 3% of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.

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

    PubMed Central

    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.

    2015-01-01

    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

  9. Transient expression of Ngn3 in Xenopus endoderm promotes early and ectopic development of pancreatic beta and delta cells

    PubMed Central

    Oropeza, Daniel; Horb, Marko

    2012-01-01

    Promoting ectopic development of pancreatic beta cells from other cell types is one of the strategies being pursued for the treatment of diabetes. To achieve this, a detailed outline of the molecular lineage that operates in pancreatic progenitor cells to generate beta cells over other endocrine cell types is necessary. Here, we demonstrate that early transient expression of the endocrine progenitor bHLH protein Neurogenin 3 (Ngn3) favors the promotion of pancreatic beta and delta cell fates over an alpha cell fate, while later transient expression promotes ectopic development of all three endocrine cell fates. We found that short-term activation of Ngn3 in Xenopus laevis endoderm just after gastrulation was sufficient to promote both early and ectopic development of beta and delta cells. By examining gene expression changes four hours after Ngn3 activation we identified several new downstream targets of Ngn3. We show that several of these are required for the promotion of ectopic beta cells by Ngn3 as well as for normal beta cell development. These results provide new detail regarding the Ngn3 transcriptional network operating in endocrine progenitor cells to specify a beta cell phenotype and should help define new approaches to promote ectopic development of beta cells for diabetes therapy. PMID:22121111

  10. The effects of nanomaterials as endocrine disruptors.

    PubMed

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-08-14

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.

  11. The Effects of Nanomaterials as Endocrine Disruptors

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-01-01

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

  12. The effects of nanomaterials as endocrine disruptors.

    PubMed

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-01-01

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

  13. Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy

    PubMed Central

    Itoh, Nobuyuki; Ohta, Hiroya; Konishi, Morichika

    2015-01-01

    The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs are secreted signaling molecules by acting via cell-surface FGF receptors (FGFRs). Paracrine FGFs require heparan sulfate as a cofactor for FGFRs. In contrast, endocrine FGFs, comprising FGF19, FGF21, and FGF23, require α-Klotho or β-Klotho as a cofactor for FGFRs. Endocrine FGFs, which are specific to vertebrates, lost heparan sulfate-binding affinity and acquired a systemic signaling system with α-Klotho or β-Klotho during early vertebrate evolution. The phenotypes of endocrine FGF knockout mice indicate that they play roles in metabolism including bile acid, energy, and phosphate/active vitamin D metabolism. Accumulated evidence for the involvement of endocrine FGFs in human genetic and metabolic diseases also indicates their pathophysiological roles in metabolic diseases, potential risk factors for metabolic diseases, and useful biomarkers for metabolic diseases. The therapeutic utility of endocrine FGFs is currently being developed. These findings provide new insights into the physiological and pathophysiological roles of endocrine FGFs and potential diagnostic and therapeutic strategies for metabolic diseases. PMID:26483756

  14. Skin manifestations of endocrine and neuroendocrine tumors.

    PubMed

    Leventhal, Jonathan S; Braverman, Irwin M

    2016-06-01

    The skin signs of benign and malignant endocrine and neuroendocrine tumors are manifold and early identification of these dermatologic features is crucial in initiating timely diagnosis and management. This article reviews the salient cutaneous features of these tumors that arise in the classic endocrine glands, lung and gastrointestinal tract either as individual neoplasms or as part of a syndrome.

  15. Diagnosis and pathology of endocrine diseases

    SciTech Connect

    Shriver, B.D.

    1988-01-01

    This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands.

  16. [Genetic diagnostic testing in inherited retinal dystrophies].

    PubMed

    Kohl, S; Biskup, S

    2013-03-01

    Inherited retinal dystrophies are clinically and genetically highly heterogeneous. They can be divided according to the clinical phenotype and course of the disease, as well as the underlying mode of inheritance. Isolated retinal dystrophies (i.e., retinitis pigmentosa, Leber's congenital amaurosis, cone and cone-rod dystrophy, macular dystrophy, achromatopsia, congenital stationary nightblindness) and syndromal forms (i.e., Usher syndrome, Bardet-Biedl syndrome) can be differentiated. To date almost 180 genes and thousands of distinct mutations have been identified that are responsible for the different forms of these blinding illnesses. Until recently, there was no adequate diagnostic genetic testing available. With the development of the next generation sequencing technologies, a comprehensive genetic screening analysis for all known genes for inherited retinal dystrophies has been established at reasonable costs and in appropriate turn-around times. Depending on the primary clinical diagnosis and the presumed mode of inheritance, different diagnostic panels can be chosen for genetic testing. Statistics show that in 55-80 % of the cases the genetic defect of the inherited retinal dystrophy can be identified with this approach, depending on the initial clinical diagnosis. The aim of any genetic diagnostics is to define the genetic cause of a given illness within the affected patient and family and thereby i) confirm the clinical diagnosis, ii) provide targeted genetic testing in family members, iii) enable therapeutic intervention, iv) give a prognosis on disease course and progression and v) in the long run provide the basis for novel therapeutic approaches and personalised medicine.

  17. Histopathologically Proven Autoimmune Pancreatitis Mimicking Neuroendocrine Tumor or Pancreatic Cancer

    PubMed Central

    Onda, Shinji; Okamoto, Tomoyoshi; Kanehira, Masaru; Fujioka, Shuichi; Harada, Tohru; Hano, Hiroshi; Fukunaga, Masaharu; Yanaga, Katsuhiko

    2012-01-01

    Autoimmune pancreatitis (AIP) can be difficult to distinguish from pancreatic cancer. We report a case of histopathologically proven AIP mimicking neuroendocrine tumor (NET) or pancreatic cancer in a 53-year-old man. He was referred to our hospital for further evaluation of a pancreatic mass detected on ultrasonography at a medical check-up. Abdominal ultrasonography showed a 15-mm hypoechoic mass located in the pancreatic body. Computed tomography revealed a tumor without any contrast enhancement, and magnetic resonance imaging demonstrated the mass to be hyperintense on diffusion-weighted image. Endoscopic retrograde cholangiopancreatography revealed slight dilatation of a branch of the pancreatic duct without stricture of the main pancreatic duct. The common bile duct seemed intact. Under suspicion of a non-functioning NET or malignant neoplasm, laparotomy was performed. At laparotomy, an elastic firm and well-circumscribed mass was found suggestive of a non-functioning NET, thus enucleation was performed. Histopathologically, the lesion corresponded to AIP. PMID:22423237

  18. Primary Pancreatic Head Tuberculosis: Great Masquerader of Pancreatic Adenocarcinoma

    PubMed Central

    Gupta, Dhaval; Patel, Jatin; Rathi, Chetan; Ingle, Meghraj; Sawant, Prabha

    2015-01-01

    Isolated pancreatic tuberculosis (TB) is considered an extremely rare condition, even in the developing countries. Most reported cases of pancreatic TB are diagnosed after exploratory laparotomy or autopsy. Pancreatic TB is a potential mimic of invasive pancreatic malignancy and the presence of vascular invasion does not distinguish one condition from the other. Every effort should be made for the earliest diagnosis of this condition as TB is a treatable condition and it avoids unnecessary management of pancreatic carcinoma. Here we report a rare case of primary pancreatic head TB in a 58-year-old male who presented with hypodense lesion in head of pancreas with double duct sign and portal vein invasion mimicking non-resectable pancreatic carcinoma.

  19. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.

    PubMed

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-03-28

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

  20. Pancreatic calculi superimposed upon slow growing pancreatic cancer.

    PubMed

    Noda, A; Takeuchi, K; Ibuki, E; Murayama, H; Kobayashi, T; Nonogaki, T

    1996-01-01

    We report on a 59 year old male patient with cancer of the head of the pancreas, upon which pancreatic calculi were superimposed during the 3 year clinical course. Pancreatic calculi were noted in the main pancreatic duct (MPD) on both computed tomographic scans and ultrasonographs of the abdomen approximately 10 months after the recognizable dilatation of the MPD. Existence of the calculi was confirmed by autopsy. Elemental analysis and infrared spectrophotometry of the calculi demonstrated that the main constituent of the calculi was calcium carbonate. Histopathological examination showed that the pancreatic cancer was moderately differentiated adenocarcinoma. Immunohistochemical studies revealed that pancreatic stone protein (lithostathine) was present in the cytoplasm of tumour cells. In this case, pancreatic cancer progressed to obstruct the MPD unusually slowly, resulting in stagnation of pancreatic secretion and subsequent formation of the calculi.

  1. Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreas.

    PubMed

    Yoshida, Tetsu; Shiraki, Nobuaki; Baba, Hideo; Goto, Mizuki; Fujiwara, Sakuhei; Kume, Kazuhiko; Kume, Shoen

    2008-07-01

    Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the plakin genes are known to function in interconnecting cytoskeletal filaments and anchoring them at plasma membrane-associated adhesive junction. Here we analyzed the expression patterns of Eppk1 in the developing and adult pancreas in the mice. In the embryonic pancreas, Eppk1+/Pdx1+ and Eppk1+/Sox9+ pancreatic progenitor cells were observed in early pancreatic epithelium. Since Pdx1 expression overlapped with that of Sox9 at this stage, these multipotent progenitor cells are Eppk1+/Pdx1+/Sox9+ cells. Then Eppk1 expression becomes confined to Ngn3+ or Sox9+ endocrine progenitor cells, and p48+ exocrine progenitor cells, and then restricted to the duct cells and a cells at birth. In the adult pancreas, Eppk1 is expressed in centroacinar cells (CACs) and in duct cells. Eppk1 is observed in pancreatic intraepithelial neoplasia (PanIN), previously identified as pancreatic ductal adenocarcinoma (PDAC) precursor lesions. In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. Furthermore, in the partial pancreatectomy (Px) regeneration model using mice, Eppk1 is expressed in "ducts in foci", a tubular structure transiently induced. These results suggest that Eppk1 serves as a useful marker for detecting pancreatic progenitor cells in developing and regenerating pancreas.

  2. Vitamin D receptor activation induces peptide YY transcription in pancreatic islets.

    PubMed

    Choi, Mihwa; Ozeki, Jun; Hashizume, Masami; Kato, Shigeaki; Ishihara, Hisamitsu; Makishima, Makoto

    2012-11-01

    Peptide YY (PYY) is a peptide hormone secreted from L cells in the intestine after food intake and regulates appetite and intestinal function. PYY is also expressed in the pancreas, but the mechanisms of regulation of pancreatic PYY expression have not been elucidated. The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D(3) and regulates numerous physiological processes. Because VDR is expressed in the pancreas, we investigated the role of pancreatic VDR activation and found that Pyy is a VDR target gene in the mouse pancreas. Treatment of mice with 1α-hydroxyvitamin D(3) increased plasma PYY levels. VDR activation increased mRNA and protein expression of PYY in the pancreatic islets of mice and pancreatic endocrine cell lines but did not change intestinal PYY expression. 1α-Hydroxyvitamin D(3)-dependent induction of pancreatic and plasma PYY was abolished in VDR-null mice. We identified a functional vitamin D-responsive element in the mouse Pyy promoter using chromatin immunoprecipitation assay, EMSA, and luciferase promoter assay. Thus, Pyy is a tissue-specific VDR target gene. The pancreatic VDR-PYY pathway may mediate a regulatory function of vitamin D in the neuroendocrine system.

  3. Genetic testing by cancer site: endocrine system.

    PubMed

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  4. The molecular classification of hereditary endocrine diseases.

    PubMed

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  5. Interaction between diet and gastrointestinal endocrine cells

    PubMed Central

    EL-SALHY, MAGDY; MAZZAWI, TAREK; HAUSKEN, TRYGVE; HATLEBAKK, JAN GUNNAR

    2016-01-01

    The gastrointestinal endocrine cells are essential for life. They regulate the gastrointestinal motility, secretion, visceral sensitivity, absorption, local immune defense, cell proliferation and appetite. These cells act as sensory cells with specialized microvilli that project into the lumen that sense the gut contents (mostly nutrients and/or bacteria byproducts), and respond to luminal stimuli by releasing hormones into the lamina propria. These released hormones exert their actions by entering the circulating blood and reaching distant targets (endocrine mode), nearby structures (paracrine mode) or via afferent and efferent synaptic transmission. The mature intestinal endocrine cells are capable of expressing several hormones. A change in diet not only affects the release of gastrointestinal hormones, but also alters the densities of the gut endocrine cells. The interaction between ingested foodstuffs and the gastrointestinal endocrine cells can be utilized for the clinical management of gastrointestinal and metabolic diseases, such as irritable bowel syndrome, obesity and diabetes. PMID:27284402

  6. [Acute pancreatitis in children].

    PubMed

    Rottier, B L; Holl, R A; Draaisma, J M

    1998-02-21

    Acute pancreatitis is probably commoner in children than was previously thought. In children it is most commonly associated with trauma or viral infection. The presentation may be subtler than in adults, requiring a high index of suspicion in the clinician. In three children, two boys aged 4 and 10 and a girl of 15 years, acute pancreatitis was suspected because of the findings at ultrasonography and endoscopic retrograde cholangiopancreatography performed when the disease recurred (the boy aged 4), apathy and immobility without dehydration or other obvious causes (the boy aged 10), and severe abdominal pain in combination with vomiting (the girl). All three patients had severely increased (urinary) amylase levels. Most often, acute pancreatitis in children tends to be a self-limiting disease which responds well to conservative treatment.

  7. Nutrition support in pancreatitis.

    PubMed

    Curtis, Caitlin S; Kudsk, Kenneth A

    2007-12-01

    Nutrition support is especially important in patients who have pancreatitis, as these patients have high metabolic needs and are usually unable to ingest sufficient calories from an oral diet because of pain or intestinal dysfunction. Clinicians must assess severity of the disease carefully, as initiation and timing of nutrition support are crucial. Depending on the severity, early nutrition support may be unnecessary, while late support ultimately may lead to worse outcomes. Route of nutrition support also plays an important role in treatment. The clinician has many alternatives from which to choose, including enteral nutrition given nasogastrically or nasojejunally, or parenteral nutrition given through a central line. This article explores the role of nutrition support in the outcome of pancreatitis and provides guidelines to aid the clinician in caring for patients who have acute and chronic pancreatitis.

  8. [Acute pancreatitis and pregnancy].

    PubMed

    Laraki, M; Harti, A; Bouderka, M A; Barrou, H; Matar, N; Benaguida, M

    1993-10-01

    Acute pancreatitis during pregnancy is a serious condition and diagnosis is often difficult. The authors report the case of a 32-year-old woman in the 32nd week of her fifth pregnancy, in which the outcome was fatal for both mother and child. The cause of pancreatitis during pregnancy has been attributed to many factors, chiefly cholelithiasis. A number of recent studies have shown the relationship existing between the role played by pregnancy in predisposing to gallbladder disease with lithiasis. Many diagnosis errors are made in this condition. Thus modern treatment methods have improved the prognosis in acute pancreatitis but, when it occurs during pregnancy, diagnostic delays often lead to a gloomy outlook. PMID:8248696

  9. Incidental isolated pancreatic hydatid cyst.

    PubMed

    Kısaoğlu, Abdullah; Özoğul, Bünyami; Atamanalp, Sabri Selçuk; Pirimoğlu, Berhan; Aydınlı, Bülent; Korkut, Ercan

    2015-03-01

    Isolated pancreatic hydatid cysts are a rare parasitic disease even in endemic areas. It is difficult to discriminate primary pancreatic hydatid cysts from other cystic and solid lesions of the pancreas. This is a case report of an incidental isolated pancreatic hydatid cyst. A heterogeneous cystic lesion in the body of the pancreas was identified on magnetic resonance imaging of a patient previously diagnosed patient with cholelithiasis, and because of the malignant possibility of the lesion, splenectomy with distal pancreatectomy and cholecystectomy was performed. The histopathologic diagnosis was reported as a hydatid cyst. Pancreatic hydatid cysts should be kept in mind in the differential diagnosis of pancreatic pseudocysts and cystic malignancies.

  10. [Pancreatic abscess and infected pseudocyst].

    PubMed

    Trinidad, E E; Ramírez-Ronda, C H

    1994-01-01

    Acute pancreatitis is a sterile inflammatory process caused by a chemical auto digestion of the pancreas. The pancreatic abscess and infected pseudocyst are complications of acute pancreatitis of a high mortality rate that require a prompt diagnosis. The pseudocyst is defined as a localized collection of pancreatic juices confine to a retroperitoneal area by a fibrous membrane without epithelium; an abscess is a collection of pus and necrotic tissue. This illnesses should be suspected when patients with acute pancreatitis develop fever, tachycardia, abdominal distention or mass after 14-22 days after the initial attack. These entities require different treatment. The definite treatment is surgical intervention.

  11. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    PubMed Central

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  12. Environmental stress and epigenetic transgenerational inheritance.

    PubMed

    Skinner, Michael K

    2014-09-05

    Previous studies have shown a wide variety of environmental toxicants and abnormal nutrition can promote the epigenetic transgenerational inheritance of disease. More recently a number of studies have indicated environmental stress can also promote epigenetic alterations that are transmitted to subsequent generations to induce pathologies. A recent study by Yao and colleagues demonstrated gestational exposure to restraint stress and forced swimming promoted preterm birth risk and adverse newborn outcomes generationally. This ancestral stress promoted the epigenetic transgenerational inheritance of abnormalities in the great-grand offspring of the exposed gestating female. Several studies now support the role of environmental stress in promoting the epigenetic transgenerational inheritance of disease. Observations suggest ancestral environmental stress may be a component of disease etiology in the current population.

  13. Transgenerational epigenetic inheritance: an open discussion.

    PubMed

    Nagy, Corina; Turecki, Gustavo

    2015-08-01

    Much controversy surrounds the idea of transgenerational epigenetics. Recent papers argue that epigenetic marks acquired through experience are passed to offspring, but as in much of the field of epigenetics, there is lack of precision in the definitions and perhaps too much eagerness to translate animal research to humans. Here, we review operational definitions of transgenerational inheritance and the processes of epigenetic programing during early development. Subsequently, based on this background, we critically examine some recent findings of studies investigating transgenerational inheritance. Finally, we discuss possible mechanisms that may explain transgenerational inheritance, including transmission of an epigenetic blueprint, which may predispose offspring to specific epigenetic patterning. Taken together, we conclude that presently, the evidence suggesting that acquired epigenetic marks are passed to the subsequent generation remains limited.

  14. Transgenerational epigenetic inheritance: an open discussion.

    PubMed

    Nagy, Corina; Turecki, Gustavo

    2015-08-01

    Much controversy surrounds the idea of transgenerational epigenetics. Recent papers argue that epigenetic marks acquired through experience are passed to offspring, but as in much of the field of epigenetics, there is lack of precision in the definitions and perhaps too much eagerness to translate animal research to humans. Here, we review operational definitions of transgenerational inheritance and the processes of epigenetic programing during early development. Subsequently, based on this background, we critically examine some recent findings of studies investigating transgenerational inheritance. Finally, we discuss possible mechanisms that may explain transgenerational inheritance, including transmission of an epigenetic blueprint, which may predispose offspring to specific epigenetic patterning. Taken together, we conclude that presently, the evidence suggesting that acquired epigenetic marks are passed to the subsequent generation remains limited. PMID:26344807

  15. Maternal inheritance of mitochondria in Eucalyptus globulus.

    PubMed

    Vaillancourt, R E; Petty, A; McKinnon, G E

    2004-01-01

    It is important to verify mitochondrial inheritance in plant species in which mitochondrial DNA (mtDNA) will be used as a source of molecular markers. We used a polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) approach to amplify mitochondrial introns from subunits 1, 4, 5, and 7 of NADH dehydrogenase (nad) and cytochrome oxidase subunit II (cox2) in Eucalyptus globulus. PCR fragments were then either sequenced or cut with restriction enzymes to reveal polymorphism. Sequencing cox2 showed that eucalypts lack the intron between exons 1 and 2. One polymorphism was found in intron 2-3 of nad7 following restriction digests with HphI. Fifty-four F1 progeny from seven families with parents distinguishable in their mitochondrial nad7 were screened to show that mitochondria were maternally inherited in E. globulus. These results constitute the first report of mitochondrial inheritance in the family Myrtaceae.

  16. Pancreatic cystic neoplasms: Review of current knowledge, diagnostic challenges, and management options

    PubMed Central

    Jana, Tanima; Shroff, Jennifer; Bhutani, Manoop S.

    2015-01-01

    Pancreatic cystic lesions are being detected with increasing frequency, largely due to advances in cross-sectional imaging. The most common neoplasms include serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms, and cystic pancreatic endocrine neoplasms. Computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are currently used as imaging modalities. EUS-guided fine needle aspiration has proved to be a useful diagnostic tool, and enables an assessment of tumor markers, cytology, chemistries, and DNA analysis. Here, we review the current literature on pancreatic cystic neoplasms, including classification, diagnosis, treatment, and recommendations for surveillance. Data for this manuscript was acquired via searching the literature from inception to December 2014 on PubMed and Ovid MEDLINE. PMID:25821410

  17. Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849+10kbC>T: Significance for geneticists

    SciTech Connect

    Gilbert, F.; Li, Zhen; Arzimanoglou, I.

    1995-09-25

    We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kbC>T as homozygotes or compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic-sufficient and sweat test-negative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negative/inconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+10kbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possibly for CF carrier screening in the general population. 19 refs., 1 tab.

  18. [Infectious complications in necrotizing pancreatitis].

    PubMed

    Werner, J; Büchler, M W

    2007-10-01

    Patients with CT evidence of more than 50 % necrosis, or an increased CRP or procalcitonin are at risk of developing severe pancreatitis and septic complications and should be monitored in an intensive care unit. ERCP and sphincterotomy are indicated in patients with biliary pancreatitis and impacted gall stones, biliary sepsis, or obstructive jaundice. In septic patients with necrotizing pancreatitis, a FNA should be performed for differentiation of sterile and infected pancreatic necrosis. Adequate volume resuscitation and analgesic treatment are the most important treatment of acute pancreatitis. Antibiotic prophylaxis reduces septic complications in severe necrotizing pancreatitis and should be started early. Surgical therapy is indicated in patients with infected pancreatic necrosis. The surgical technique of choice is open necrosectomy with postoperative closed lavage of the lesser sac.

  19. Medical treatment of acute pancreatitis.

    PubMed

    Mayerle, Julia; Simon, Peter; Lerch, Markus M

    2004-12-01

    Eighty percent of all cases of acute pancreatitis are linked etiologically to gallstone disease or caused by immoderate alcohol consumption. No specific causal treatment for acute pancreatitis exists. Early prognostic factors that indicate severe disease are three or more signs on organ failure scores according to Ranson, Imrie, or Acute Physiology and Chronic Health Evaluation (APACHE) 11, extrapancreatic complications of the disease, or the detection of pancreatic necrosis on CT scans. Elevated CRP levels above 130 mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Moreover, relief of often severe visceral pain is a high priority. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis, or other infectious complications. Enteral nutrition has no adverse effect compared with parenteral nutrition during the course of acute pancreatitis, and is probably beneficial in regard to outcome.

  20. Pancreatic disorders in inflammatory bowel disease

    PubMed Central

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  1. Pancreatic disorders in inflammatory bowel disease.

    PubMed

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-08-15

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  2. Transgenerational epigenetic inheritance: how important is it?

    PubMed

    Grossniklaus, Ueli; Kelly, William G; Kelly, Bill; Ferguson-Smith, Anne C; Pembrey, Marcus; Lindquist, Susan

    2013-03-01

    Much attention has been given to the idea of transgenerational epigenetic inheritance, but fundamental questions remain regarding how much takes place and the impact that this might have on organisms. We asked five leading researchers in this area--working on a range of model organisms and in human disease--for their views on these topics. Their responses highlight the mixture of excitement and caution that surrounds transgenerational epigenetic inheritance and the wide gulf between species in terms of our knowledge of the mechanisms that may be involved.

  3. Inherited epidermolysis bullosa: clinical and therapeutic aspects*

    PubMed Central

    Boeira, Vanessa Lys Simas Yamakawa; Souza, Erica Sales; Rocha, Bruno de Oliveira; Oliveira, Pedro Dantas; de Oliveira, Maria de Fátima Santos Paim; Rêgo, Vitória Regina Pedreira de Almeida; Follador, Ivonise

    2013-01-01

    Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages. PMID:23739692

  4. Expression of the beacon gene in endocrine glands of the rat.

    PubMed

    Ziolkowska, Agnieszka; Rucinski, Marcin; Di Liddo, Rosa; Nussdorfer, Gastone G; Malendowicz, Ludwik K

    2004-01-01

    Beacon gene has been recently identified in the rat hypothalamus, and reported to be overexpressed in obese animals. This pattern of expression suggests that beacon may be involved in the functional regulation of neuroendocrine axes. Hence, we have investigated the expression of beacon in the endocrine system of the rat. Reverse transcription-polymerase chain reaction showed the expression of beacon mRNA in the hypothalamus, adenohypophysis, thyroid gland, adrenal gland, testis, ovary and pancreatic islets. Immunocytochemistry demonstrated the presence of the beacon immunoreactivity in all tissues studied, the staining being very intense in the neurons of paraventricular and supraoptic nuclei, the basophils of adenohypophysis, the parathyroid gland, adrenocortical cells, testis Leydig cells, ovary thecal, granulosa and lutein cells, and pancreatic islets. Due the fact that beacon has been included in the ubiquitin-like protein family, its widespread expression in rat endocrine tissues is not astonishing. The in vivo administration of beacon[47-73] (3.5 nmol/100 body weight) elicited within 60 min a marked decrease in the plasma concentration of ACTH, aldosterone and corticosterone, and a moderate lowering of the blood levels of testosterone and estradiol. This finding suggests that beacon exerts a negative modulatory action on the pituitary-adrenal axis and gonad secretory activity, whose physiological relevance remains, however, to be established.

  5. Serine Protease Inhibitor Kazal Type 1 (SPINK1) c.194+2T > C Mutation May Predict Long-term Outcome of Endoscopic Treatments in Idiopathic Chronic Pancreatitis

    PubMed Central

    Sun, Chang; Liu, Mu-Yun; Liu, Xiao-Gang; Hu, Liang-Hao; Xia, Tian; Liao, Zhuan; Li, Zhao-Shen

    2015-01-01

    Abstract Endoscopic interventional is a commonly used treatment method for idiopathic chronic pancreatitis. Serine protease inhibitor Kazal type 1 (SPINK1) 194+2T>C mutation is most frequently observed in Chinese pancreatitis patients and influences the clinical course of idiopathic chronic pancreatitis patients. We conducted this study to determine the impacts of this mutation on the outcome of endoscopic treatments. In this study, we enrolled 423 patients. Among them, 101 idiopathic chronic pancreatitis patients without other relevant mutations had a successful endoscopic procedure and completed follow-up. Clinical characteristics including Izbicki pain score, exocrine and endocrine function, were evaluated. Genetic sequencing was conducted to detect SPINK1 194+2T>C mutations. The c.194+2T>C mutation was found in 58 (57.43%) patients. Factors relevant to pain relief are c.194+2T>C mutation (P = 0.011), severe pain before treatment (P = 0.005), and necessary subsequent endoscopic treatments (P < 0.001). More patients with the intronic mutation had deteriorated endocrine function (P = 0.001) relative to those patients without the mutation. Patients carrying the c.194+2T>C mutation were less likely to achieve pain relief through endoscopic treatments. They also have a higher risk of endocrine function deterioration. SPINK1 c.194+2T>C mutation may be applied as a pretreatment predictor in idiopathic chronic pancreatitis patients. PMID:26632706

  6. [Cardiac failure in endocrine diseases].

    PubMed

    Hashizume, K

    1993-05-01

    Several endocrine diseases show the symptoms of cardiac failure. Among them, patients with acromegaly show a specific cardiomyopathy which results in a severe left-sided cardiac failure. Hypoparathyroidism also induces cardiac failure, which is resulted from hypocalcemia and low levels of serum parathyroid hormone. In the cases of hypothyroidism, the patients with myxedemal coma show a severe cardiac failure, which is characterized by disturbance of central nervous system, renal function, and cardiac function. In the patients with thyroid crisis (storm), the cardiac failure comes from the great reduction of cardiac output with dehydration. The reduction of circulation volume, observed in the patients with pheochromocytoma easily induces cardiac failure (shock) just after the removal of adrenal tumor. In patients with malignant carcinoid syndrome, right-sided ventricular failure which may be occurred through the actions of biogenic amines is observed. PMID:8331806

  7. Endocrine Consequences of Anorexia Nervosa

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Summary Anorexia nervosa (AN) is prevalent in adolescents and young adults, and endocrine changes include hypothalamic amenorrhea, a nutritionally acquired growth hormone resistance with low insulin like growth factor-1 (IGF-1), relative hypercortisolemia, decreases in leptin, insulin, amylin and incretins, and increases in ghrelin, PYY and adiponectin. These changes in turn have deleterious effects on bone, and may affect neurocognition, anxiety, depression and eating disorder psychopathology. Low bone density is particularly concerning; clinical fractures occur and changes in both bone microarchitecture and strength estimates have been reported. Recovery causes improvement of many, but not all, hormonal changes, and deficits in bone accrual may persist despite recovery. Physiologic, primarily transdermal, estrogen replacement increases bone density in adolescents, although catch-up is incomplete. In adults, oral estrogen co-administered with rhIGF-1 in one study, and bisphosphonates in another increased bone density, though not to normal. More studies are necessary to determine the optimal therapeutic approach in AN. PMID:24731664

  8. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    PubMed

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke.

  9. Octreotide acetate decreases pancreatic complications after pancreatic trauma.

    PubMed

    Amirata, E; Livingston, D H; Elcavage, J

    1994-10-01

    Octreotide acetate (Sandostatin) has been reported to decrease pancreatic related morbidity after pancreatic resections. This study examined the use of octreotide after pancreatic trauma. The charts of all patients treated for pancreatic injuries from June 1988 to February 1992 were reviewed (n = 28). The mean age of the patients was 29 years (range 16 to 61). The mechanism of injury was motor vehicle accident in 7 patients, gunshot wounds in 14, and stab wounds in 7. The mean (+/- SD) abdominal trauma index (ATI) was 33 +/- 14 and injury severity score (ISS) was 22 +/- 12. Pancreatic injuries were graded as grade I (contusion) in 6 patients, grade II (parenchymal injury) in 18, and grade III (ductal injury) in 4. Seven patients (6 grade II and 1 grade III) were treated with prophylactic octreotide acetate, 150 micrograms to 300 micrograms per day, beginning on day 1. There were no pancreatic complications in this group. Of the remaining 21 patients, 6 (29%) developed 9 pancreatic complications: fluid collections in 3, fistula in 4, pseudocyst in 1, and pancreatitis in 1. Three patients had grade III, 1 had grade II, and 2 had grade I injuries. There were no differences in ATI, ISS, or grade of pancreatic injury between patients who were treated with octreotide and those who were not. No complications were associated with the use of octreotide. In conclusion, pancreatic complications occurred frequently (21%) following pancreatic trauma and resulted in significant morbidity. In this nonrandomized series of patients with equivalent ATI, ISS, and pancreatic grade injuries, the prophylactic use of octreotide was associated with no pancreatic complications and no negative sequelae.

  10. Doubly uniparental inheritance: two mitochondrial genomes, one precious model for organelle DNA inheritance and evolution.

    PubMed

    Passamonti, Marco; Ghiselli, Fabrizio

    2009-02-01

    Eukaryotes have exploited several mechanisms for organelle uniparental inheritance, so this feature arose and evolved independently many times in their history. Metazoans' mitochondria commonly experience strict maternal inheritance; that is, they are only transmitted by females. However, the most noteworthy exception comes from some bivalve mollusks, in which two mitochondrial lineages (together with their genomes) are inherited: one through females (F) and the other through males (M). M and F genomes show up to 30% sequence divergence. This inheritance mechanism is known as doubly uniparental inheritance (DUI), because both sexes inherit uniparentally their mitochondria. Here, we review what we know about this unusual system, and we propose a model for evolution of DUI that might account for its origin as sex determination mechanism. Moreover, we propose DUI as a choice model to address many aspects that should be of interest to a wide range of biological subfields, such as mitochondrial inheritance, mtDNA evolution and recombination, genomic conflicts, evolution of sex, and developmental biology. Actually, as research proceeds, mitochondria appear to have acquired a central role in many fundamental processes of life, which are not only in their metabolic activity as cellular power plants, such as cell signaling, fertilization, development, differentiation, ageing, apoptosis, and sex determination. A function of mitochondria in the origin and maintenance of sex has been also proposed.

  11. Ecological risk assessment of endocrine disruptors.

    PubMed Central

    Hutchinson, T H; Brown, R; Brugger, K E; Campbell, P M; Holt, M; Länge, R; McCahon, P; Tattersfield, L J; van Egmond, R

    2000-01-01

    The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna. PMID:11102288

  12. Analyzing endocrine system conservation and evolution.

    PubMed

    Bonett, Ronald M

    2016-08-01

    Analyzing variation in rates of evolution can provide important insights into the factors that constrain trait evolution, as well as those that promote diversification. Metazoan endocrine systems exhibit apparent variation in evolutionary rates of their constituent components at multiple levels, yet relatively few studies have quantified these patterns and analyzed them in a phylogenetic context. This may be in part due to historical and current data limitations for many endocrine components and taxonomic groups. However, recent technological advancements such as high-throughput sequencing provide the opportunity to collect large-scale comparative data sets for even non-model species. Such ventures will produce a fertile data landscape for evolutionary analyses of nucleic acid and amino acid based endocrine components. Here I summarize evolutionary rate analyses that can be applied to categorical and continuous endocrine traits, and also those for nucleic acid and protein-based components. I emphasize analyses that could be used to test whether other variables (e.g., ecology, ontogenetic timing of expression, etc.) are related to patterns of rate variation and endocrine component diversification. The application of phylogenetic-based rate analyses to comparative endocrine data will greatly enhance our understanding of the factors that have shaped endocrine system evolution.

  13. Endocrine complications following pediatric bone marrow transplantation.

    PubMed

    Ho, Josephine; Lewis, Victor; Guilcher, Gregory M T; Stephure, David K; Pacaud, Danièle

    2011-01-01

    Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly. PMID:21823531

  14. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    PubMed

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7838348

  15. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    PubMed

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Chronic Pancreatitis in Children

    MedlinePlus

    ... fewer than 10 grams of fat. About 20 potato chips contain 10 grams of fat, so it takes discipline to make sure to stay within this range. Patients who have lost the ability to digest food will be prescribed pills containing pancreatic enzymes to help with digestion. They may also be ...

  17. Pancreatic Cancer: A Review.

    PubMed

    Yabar, Cinthya S; Winter, Jordan M

    2016-09-01

    Pancreatic cancer is now the third leading cause of cancer related deaths in the United States, yet advances in treatment options have been minimal over the past decade. In this review, we summarize the evaluation and treatments for this disease. We highlight molecular advances that hopefully will soon translate into improved outcomes. PMID:27546841

  18. Pancreatic Cancer Stage 4

    MedlinePlus

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  19. Pancreatic Cystic Neoplasms

    PubMed Central

    Limaiem, Faten; Khalfallah, Tahar; Farhat, Leila Ben; Bouraoui, Saâdia; Lahmar, Ahlem; Mzabi, Sabeh

    2014-01-01

    Background: Cystic neoplasms of the pancreas are rare and constitute approximately 0.5% of all pancreatic neoplasms. Aims: The study was to describe clinicopathological features of pancreatic cystic tumors. Patients and Methods: In our retrospective study, we reviewed 10 cases of pancreatic cystic neoplasms that were diagnosed at the pathology department of Mongi Slim hospital over a 14-year period (2000-2013). We adopted the latest World Health Organization (WHO) classification (2010) in grouping all tumors. Results: There were one male and nine female patients (sex ratio M/F = 1:9) aged between 21 and 68 years (mean = 37.5 years). The most common clinical presentation was epigastric and abdominal pain (n = 6) followed by vomiting (n = 3). Abdominal computed tomography (CT) scan disclosed a cystic lesion of the pancreas ranging in size between 2 and 10 cm (mean = 6.75 cm). All patients underwent surgical treatment. Histopathological examination of the surgical specimen established the diagnosis of solid pseudopapillary neoplasm (n = 2), serous cystic neoplasm (n = 2), mucinous cystadenoma (n = 4), mucinous cystadenocarcinoma (n = 1), and intraductal papillary mucinous neoplasm with invasive carcinoma (n = 1). Conclusion: Better understanding of pancreatic cystic neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients. PMID:25210676

  20. Acute and chronic pancreatitis.

    PubMed

    Vlodov, J; Tenner, S M

    2001-09-01

    Acute pancreatitis has multiple causes, an unpredictable course, and myriad complications. The diagnosis relies on a combination of history, physical examination, serologic markers, and radiologic findings. The mainstay of therapy includes aggressive hydration, maintenance of NPO, and adequate analgesia with narcotics. Antibiotic and nutritional support with total parenteral nutrition should be used when appropriate.

  1. Minimally invasive pancreatic surgery.

    PubMed

    Yiannakopoulou, E

    2015-12-01

    Minimally invasive pancreatic surgery is feasible and safe. Laparoscopic distal pancreatectomy should be widely adopted for benign lesions of the pancreas. Laparoscopic pancreaticoduodenectomy, although technically demanding, in the setting of pancreatic ductal adenocarcinoma has a number of advantages including shorter hospital stay, faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. Furthermore, it seems that progression-free survival is longer in patients undergoing laparoscopic pancreaticoduodenectomy in comparison with those undergoing open pancreaticoduodenectomy. Minimally invasive middle pancreatectomy seems appropriate for benign or borderline tumors of the neck of the pancreas. Technological advances including intraoperative ultrasound and intraoperative fluorescence imaging systems are expected to facilitate the wide adoption of minimally invasive pancreatic surgery. Although, the oncological outcome seems similar with that of open surgery, there are still concerns, as the majority of relevant evidence comes from retrospective studies. Large multicenter randomized studies comparing laparoscopic with open pancreatectomy as well as robotic assisted with both open and laparoscopic approaches are needed. Robotic approach could be possibly shown to be less invasive than conventional laparoscopic approach through the less traumatic intra-abdominal handling of tissues. In addition, robotic approach could enable the wide adoption of the technique by surgeon who is not that trained in advanced laparoscopic surgery. A putative clinical benefit of minimally invasive pancreatic surgery could be the attenuated surgical stress response leading to reduced morbidity and mortality as well as lack of the detrimental immunosuppressive effect especially for the oncological patients. PMID:26530291

  2. Epigenetic inheritance of proteostasis and ageing

    PubMed Central

    Li, Cheryl; Casanueva, Olivia

    2016-01-01

    Abundant evidence shows that the genome is not as static as once thought and that gene expression can be reversibly modulated by the environment. In some cases, these changes can be transmitted to the next generation even if the environment has reverted. Such transgenerational epigenetic inheritance requires that information be stored in the germline in response to exogenous stressors. One of the most elusive questions in the field of epigenetic inheritance is the identity of such inherited factor(s). Answering this question would allow us to understand how the environment can shape human populations for multiple generations and may help to explain the rapid rise in obesity and neurodegenerative diseases in modern society. It will also provide clues on how we might be able to reprogramme the epigenome to prevent transmission of detrimental phenotypes and identify individuals who might be at increased risk of disease. In this article, we aim to review recent developments in this field, focusing on research conducted mostly in the nematode Caenorhabditis elegans and mice, that link environmental modulators with the transgenerational inheritance of phenotypes that affect protein-folding homoeostasis and ageing. PMID:27744335

  3. Phylogenetics Exercise Using Inherited Human Traits

    ERIC Educational Resources Information Center

    Tuimala, Jarno

    2006-01-01

    A bioinformatics laboratory exercise based on inherited human morphological traits is presented. It teaches how morphological characters can be used to study the evolutionary history of humans using parsimony. The exercise can easily be used in a pen-and-paper laboratory, but if computers are available, a more versatile analysis can be carried…

  4. Fractional populations in sex-linked inheritance

    NASA Astrophysics Data System (ADS)

    Pyo Lee, Seung; Chung, Myung-Hoon; Koo Kim, Chul; Nahm, Kyun

    2001-03-01

    We study the fractional populations in chromosome inherited diseases. The governing equations for the fractional populations are found and solved in the presence of mutation and selection. The physical fixed points obtained are used to discuss the cases of color blindness and hemophilia.

  5. Prenatal diagnosis of inherited metabolic diseases.

    PubMed Central

    Diukman, R; Goldberg, J D

    1993-01-01

    Advances in the prenatal diagnosis of inherited metabolic disease have provided new reproductive options to at-risk couples. These advances have occurred in both sampling techniques and methods of analysis. In this review we present an overview of the currently available prenatal diagnostic approaches for the diagnosis of metabolic disease in a fetus. Images PMID:8236980

  6. Ethnogenetics: Interpreting Ideas about Diabetes and Inheritance.

    ERIC Educational Resources Information Center

    Weiner, Diane

    1999-01-01

    Interviews with American Indian tribal members in California and Arizona and their physicians revealed different beliefs about the causes and inheritance of diabetes. These differences in understanding are examined in terms of differences between physician and client communication practices and between professional medical education and lay health…

  7. Understanding Genetics and Inheritance in Rural Schools

    ERIC Educational Resources Information Center

    Kibuka-Sebitosi, Esther

    2007-01-01

    Conducted in urban and rural schools in two provinces of South Africa, the present study reports biology learners' understanding of concepts about genetics and inheritance. Participants were Grade 11 and 12 learners, aged 15-16 years. The tools included a written questionnaire, interviews, pre- and post-paper and pencil tests and focus group…

  8. Difficulties in Learning Inheritance and Polymorphism

    ERIC Educational Resources Information Center

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  9. Epigenetic Inheritance of Disease and Disease Risk

    PubMed Central

    Bohacek, Johannes; Mansuy, Isabelle M

    2013-01-01

    Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated. PMID:22781843

  10. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    ClinicalTrials.gov

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  11. Amphibians as model to study endocrine disrupters.

    PubMed

    Kloas, Werner; Lutz, Ilka

    2006-10-13

    Environmental compounds can interfere with endocrine systems of wildlife and humans. These so-called endocrine disrupters (ED) are known to affect reproductive biology and thyroid system. The classical model species for these endocrine systems are amphibians and therefore they can serve as sentinels for detection of the modes of action (MOAs) of ED. Recently, amphibians are being reviewed as suitable models to assess (anti)estrogenic and (anti)androgenic MOAs influencing reproductive biology as well as (anti)thyroidal MOAs interfering with the thyroid system. The development of targeted bioassays in combination with adequate chemical analyses is the prerequisite for a concise risk assessment of ED.

  12. Endocrine scintigraphy with hybrid SPECT/CT.

    PubMed

    Wong, Ka Kit; Fig, Lorraine M; Youssef, Ehab; Ferretti, Alice; Rubello, Domenico; Gross, Milton D

    2014-10-01

    Nuclear medicine imaging of endocrine disorders takes advantage of unique cellular properties of endocrine organs and tissues that can be depicted by targeted radiopharmaceuticals. Detailed functional maps of biodistributions of radiopharmaceutical uptake can be displayed in three-dimensional tomographic formats, using single photon emission computed tomography (CT) that can now be directly combined with simultaneously acquired cross-sectional anatomic maps derived from CT. The integration of function depicted by scintigraphy and anatomy with CT has synergistically improved the efficacy of nuclear medicine imaging across a broad spectrum of clinical applications, which include some of the oldest imaging studies of endocrine dysfunction.

  13. Laparoscopic pancreatic surgery.

    PubMed

    Mori, Toshiyuki; Abe, Nobutsugu; Sugiyama, Masanori; Atomi, Yutaka

    2005-01-01

    In the past, in the pancreas, a minimally invasive technique was only used for diagnostic laparoscopy in evaluating periampullary malignancy. Recent advances in operative techniques and instrumentation have empowered surgeons to perform virtually all procedures in the pancreas, including the Whipple procedure. Some of these procedures represent the most sophisticated application of minimally invasive surgery, and their outcomes are reportedly better than those of conventional open approaches. In addition to the evaluation of resectability in periampullary malignancy, palliative procedures, including biliary bypasses and gastrojejunostomy, can be performed laparoscopically. Although it is reportedly feasible to perform a Whipple procedure laparescopically, no benefit of the laparoscopic approach over the conventional open approach has been documented. Laparoscopic distal pancreatectomy, with or without preserving the spleen, is technically easier than the Whipple procedure, and is more widely accepted. Indications for laparoscopic distal pancreatectomy include cystic neoplasms and islet-cell tumors located in the pancreatic body or tail. Complications of acute and chronic pancreatitis may be treated with the use of surgical laparoscopy. When infected necrotizing pancreatitis is identified, surgical intervention for drainage and debridement is required. According to the type and location of infected necrotizing pancreatitis, three laparoscopic operative approaches have been reported: infracolic debridement, retroperitoneal debridement, and laparoscopic transgastric pancreatic necrosectomy. When internal drainage is indicated for a pseudocyst, a minimally invasive technique is a promising option. Laparoscopic pseudocyst gastrostomy, cyst jejunostomy, or cyst duodenostomy can be performed, depending on the size and location of the pseudocyst. Especially when a pseudocyst is located in close contact with the posterior wall of the stomach, it is best drained by a

  14. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis.

    PubMed

    Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E; Krenn, Veit; Mayerle, Julia; Lerch, Markus M; Schett, Georg; Wirtz, Stefan; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-03-11

    Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts.

  15. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

    PubMed Central

    Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E.; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L.; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E.; Krenn, Veit; Mayerle, Julia; Lerch, Markus M.; Schett, Georg; Wirtz, Stefan; Neurath, Markus F.; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts. PMID:26964500

  16. Acute pancreatitis: clinical vs. CT findings

    SciTech Connect

    Hill, M.C.; Barkin, J.; Isikoff, M.B.; Silver stein, W.; Kalser, M.

    1982-08-01

    In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months.

  17. RNA-sequencing of WFS1-deficient pancreatic islets.

    PubMed

    Ivask, Marilin; Hugill, Alison; Kõks, Sulev

    2016-04-01

    Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in theWFS1gene.WFS1encodes an endoplasmic reticulum resident transmembrane protein. TheWfs1-null mice exhibit progressive insulin deficiency and diabetes. The aim of this study was to describe the insulin secretion and transcriptome of pancreatic islets inWFS1-deficient mice.WFS1-deficient (Wfs1KO) mice had considerably less pancreatic islets than heterozygous (Wfs1HZ) or wild-type (WT) mice. Wfs1KOpancreatic islets secreted less insulin after incubation in 2 and 10 mmol/L glucose and with tolbutamide solution compared toWTand Wfs1HZislets, but not after stimulation with 20 mmol/L glucose. Differences in proinsulin amount were not statistically significant although there was a trend that Wfs1KOhad an increased level of proinsulin. After incubation in 2 mmol/L glucose solution the proinsulin/insulin ratio in Wfs1KOwas significantly higher than that ofWTand Wfs1HZRNA-seq from pancreatic islets found melastatin-related transient receptor potential subfamily member 5 protein gene (Trpm5) to be downregulated inWFS1-deficient mice. Functional annotation ofRNAsequencing results showed thatWFS1 deficiency influenced significantly the pathways related to tissue morphology, endocrine system development and function, molecular transport network. PMID:27053292

  18. Chronic pancreatitis: role of oxidative stress and antioxidants.

    PubMed

    Bhardwaj, P; Yadav, R K

    2013-11-01

    Chronic pancreatitis (CP) is characterized by pain, and exocrine and endocrine insufficiency of pancreas. Several hypotheses have been put forward to explain the hitherto partially understood pathophysiology of CP. In the past decade, animal and clinical studies have suggested that an increased chronic oxidative stress (OS) plays a key role in pathophysiology of CP and perpetuates its clinical and histological symptoms (pain and fibrosis-necrosis, respectively). Mounting OS in pancreatic acinar cells is a result of overproduction of free radicals (FR) during xenobiotic metabolism. It has been shown that Phase I cytochrome P450 enzymes of xenobiotic pathway are induced when exposed to a xenobiotic overload including alcohol, tobacco, smoke and other dietary toxins, which exceeds the capacity of Phase II conjugation due to limited glutathione availability. Consequently, there is an overload of toxic metabolites as well as FR. Additionally, bioactivation of subsequently entering compounds may occur increasing their toxicity. Such an imbalance overwhelms the antioxidant capacity of the body resulting in undefended chronic OS that derails the normal physiology of pancreatic acinar cells since FR act as second messengers controlling the cellular signaling. OS hypothesis is further supported by the studies that demonstrated that antioxidant supplementation ameliorated pain. Moreover, animal studies have demonstrated a cessation of fibrotic cascade with antioxidant supplementation. In a recent large randomized controlled trial, it was demonstrated that antioxidant supplementation led to a significant reduction in pain, and also lowered the OS in patients with alcoholic or idiopathic CP.

  19. Regulation of pancreatic somatostatin gene expression by insulin and glucagon.

    PubMed

    Ehrman, Melissa M; Melroe, Gregory T; Kittilson, Jeffrey D; Sheridan, Mark A

    2005-05-12

    Rainbow trout were used as a model system to study the effects of insulin and glucagon on the expression of preprosomatostatins (PPSS). We previously showed that the endocrine pancreas of trout contains three mRNAs that encode for distinct somatostatin-containing peptides: PPSS I, which contains somatostain-14 (SS-14) at its C-terminus, and two separate PPSS IIs, PPSS II' and PPSS II'', each containing [Tyr7, Gly10]-SS-14 at their C-terminus. Rainbow trout injected (100 ng/g body weight) with insulin displayed elevated expression of PPSS II' and PPSS II'' mRNAs. Glucagon-injected (100 ng/g body weight) animals displayed elevated pancreatic expression of all PPSS mRNAs compared to saline-injected control animals. Insulin directly stimulated the expression of pancreatic PPSS II' and PPSS II'' mRNAs in vitro in a dose-dependent manner in the presence of 4mM glucose. Glucagon, in the presence of 10mM glucose, directly stimulated the expression of all PPSS mRNAs in a dose-dependent manner in vitro. These results indicate that the pancreatic expression of PPSS mRNAs is differentially regulated by insulin and glucagon and that the regulatory pattern is dependent on glucose concentration. PMID:15866425

  20. Fetal endocannabinoids orchestrate the organization of pancreatic islet microarchitecture

    PubMed Central

    Malenczyk, Katarzyna; Keimpema, Erik; Piscitelli, Fabiana; Calvigioni, Daniela; Björklund, Peyman; Mackie, Kenneth; Di Marzo, Vincenzo; Hökfelt, Tomas G. M.; Dobrzyn, Agnieszka; Harkany, Tibor

    2015-01-01

    Endocannabinoids are implicated in the control of glucose utilization and energy homeostasis by orchestrating pancreatic hormone release. Moreover, in some cell niches, endocannabinoids regulate cell proliferation, fate determination, and migration. Nevertheless, endocannabinoid contributions to the development of the endocrine pancreas remain unknown. Here, we show that α cells produce the endocannabinoid 2-arachidonoylglycerol (2-AG) in mouse fetuses and human pancreatic islets, which primes the recruitment of β cells by CB1 cannabinoid receptor (CB1R) engagement. Using subtractive pharmacology, we extend these findings to anandamide, a promiscuous endocannabinoid/endovanilloid ligand, which impacts both the determination of islet size by cell proliferation and α/β cell sorting by differential activation of transient receptor potential cation channel subfamily V member 1 (TRPV1) and CB1Rs. Accordingly, genetic disruption of TRPV1 channels increases islet size whereas CB1R knockout augments cellular heterogeneity and favors insulin over glucagon release. Dietary enrichment in ω-3 fatty acids during pregnancy and lactation in mice, which permanently reduces endocannabinoid levels in the offspring, phenocopies CB1R−/− islet microstructure and improves coordinated hormone secretion. Overall, our data mechanistically link endocannabinoids to cell proliferation and sorting during pancreatic islet formation, as well as to life-long programming of hormonal determinants of glucose homeostasis. PMID:26494286