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Sample records for endocrine cell types

  1. Abnormal gastrointestinal endocrine cells in patients with diabetes type 1: relationship to gastric emptying and myoelectrical activity.

    Science.gov (United States)

    El-Salhy, M; Sitohy, B

    2001-11-01

    Gastrointestinal symptoms in patients with diabetes are believed to be caused by gastrointestinal dysmotility and secretion/absorption disturbances, and the gut endocrine cells play an important part in regulating these two functions. Studies on animal models of human diabetes type I revealed abnormality in these cells, but it is unknown whether abnormality also occurs in patients with diabetes. Eleven patients with long duration of diabetes type I and organ complications, as well as gastrointestinal symptoms, were studied. Endocrine cells in different segments of the gastrointestinal tract were detected by immunocytochemistry and quantified by computerized image analysis. Gastric emptying was measured by scintigraphy and gastric myoelectric activity was determined by electrogastrography. An abnormal density of gastrointestinal endocrine cells was found in patients with diabetes. This abnormality occurred in all segments of the upper and lower gastrointestinal tract investigated, and included most of the endocrine cell types. The patients showed delayed gastric emptying, which correlated closely with the acute glucose level, but did not correlate with HbA1c. Gastric emptying also correlated closely with the density of duodenal serotonin and secretin cells. The patients exhibited bradygastrias and tachygastrias. These dysrhythmias, however, did not differ significantly from controls. The endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. The abnormality in density of the gastrointestinal endocrine cells may contribute to the development of gastrointestinal dysmotility and the symptoms encountered in patients with diabetes.

  2. Specifying pancreatic endocrine cell fates.

    Science.gov (United States)

    Collombat, Patrick; Hecksher-Sørensen, Jacob; Serup, Palle; Mansouri, Ahmed

    2006-07-01

    Cell replacement therapy could represent an attractive alternative to insulin injections for the treatment of diabetes. However, this approach requires a thorough understanding of the molecular switches controlling the specification of the different pancreatic cell-types in vivo. These are derived from an apparently identical pool of cells originating from the early gut endoderm, which are successively specified towards the pancreatic, endocrine, and hormone-expressing cell lineages. Numerous studies have outlined the crucial roles exerted by transcription factors in promoting the cell destiny, defining the cell identity and maintaining a particular cell fate. This review focuses on the mechanisms regulating the morphogenesis of the pancreas with particular emphasis on recent findings concerning the transcription factor hierarchy orchestrating endocrine cell fate allocation.

  3. Multiple endocrine neoplasia type I

    International Nuclear Information System (INIS)

    Fischer, H.J.; Lois, J.F.; Gomes, A.S.

    1985-01-01

    A case of multiple endocrine neoplasia (Men) consisting of an unusual combination of an insulin-producing islet cell tumour and an adrenal adenoma is reported. CT clearly demonstrated the adrenal mass whereas the pancreatic lesion remained questionable. Conversely angiography located the pancreatic tumour but the adrenal findings were subtle. (orig.)

  4. The Relationship between the Ionic Composition of the Environment and the Secretory Activity of the Endocrine Cell Types of Stannius Corpuscles in the Teleost Gasterosteus aculeatus

    NARCIS (Netherlands)

    Wendelaar Bonga, S.E.; Greven, J.A.A.; Veenhuis, M.

    1976-01-01

    The corpuscles of Stannius of threespined sticklebacks contain two glandular cell types of presumed endocrine nature. To elucidate the function of both cell types the secretory activity of the cells was studied in fully adapted seawater and freshwater fishes and in specimens transferred from sea

  5. Intestinal endocrine cells in radiation enteritis

    NARCIS (Netherlands)

    Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were

  6. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  7. Intestinal endocrine cells in radiation enteritis

    International Nuclear Information System (INIS)

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

    1989-01-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis

  8. Duodenal endocrine cells in adult coeliac disease.

    Science.gov (United States)

    Sjölund, K; Alumets, J; Berg, N O; Håkanson, R; Sundler, F

    1979-01-01

    Using immunohistochemical techniques we studied duodenal biopsies from 18 patients with coeliac disease and 24 patients with normal duodenal morphology. We had access to antisera against the following gastrointestinal peptides: cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin-17, glucagon-enteroglucagon, motilin, neurotensin, pancreatic peptide (PP), secretin, somatostatin, substance P and vasoactive intestinal peptide (VIP). The somatostatin, GIP, CCK, and glucagon cells were increased in number in coeliac disease. The number of motilin cells was slightly increased, while secretin cells were reduced. Cells storing gastrin-17, substance P, or neurotensin were rare in all patients regardless of diagnosis. No PP immunoreactive cells were found and VIP was localised to neurons only. In biopsies from patients having a mucosa with ridging of villi the number of the various endocrine cell types did not differ from that in the control group. Images Fig. 2 PMID:385455

  9. Immunohistochemical study on gastrointestinal endocrine cells of four reptiles

    Science.gov (United States)

    Huang, Xu-Gen; Wu, Xiao-Bing

    2005-01-01

    AIM: To clarify the types, regional distributions and distribution densities as well as morphological features of gastrointestinal (GI) endocrine cells in various parts of the gastrointestinal track (GIT) of four reptiles, Gekko japonicus, Eumeces chinensis, Sphenomorphus indicus and Eumeces elegans. METHODS: Paraffin-embedded sections (5 μm) of seven parts (cardia, fundus, pylorus, duodenum, jejunum, ileum, rectum) of GIT dissected from the four reptiles were prepared. GI endocrine cells were revealed by using immunohistochemical techniques of streptavidin-peroxidase (S-P) method. Seven types of antisera against 5-hydroxy-tryptamine (5-HT), somatostatin (SS), gastrin (GAS), glucagon (GLU), substance P (SP), insulin and pancreatic polypeptide were identified and then GI endocrine cells were photomicrographed and counted. RESULTS: The GI endocrine system of four reptiles was a complex structure containing many endocrine cell types similar in morphology to those found in higher vertebrates. Five types of GI endocrine cells, namely 5-HT, SS, GAS, SP and GLU immunoreactive (IR) cells were identified in the GIT of G. japonicus, E. chinensis and S. indicus; while in the GIT of E. elegans only the former three types of endocrine cells were observed. No PP- and INS- IR cells were found in all four reptiles. 5-HT-IR cells, which were most commonly found in the pylorus or duodenum, distributed throughout the whole GIT of four reptiles. However, their distribution patterns varied from each other. SS-IR cells, which were mainly found in the stomach especially in the pylorus and/or fundus, were demonstrated in the whole GIT of E. chinensis, only showed restricted distribution in the other three species. GAS-IR cells, with a much restricted distribution, were mainly demonstrated in the pylorus and/or the proximal small intestine of four reptiles. GLU-IR cells exhibited a limited and species-dependent variant distribution in the GIT of four reptiles. SP-IR cells were found

  10. Chronology of endocrine differentiation and beta-cell neogenesis.

    Science.gov (United States)

    Miyatsuka, Takeshi

    2016-01-01

    Diabetes is a chronic and incurable disease, which results from absolute or relative insulin insufficiency. Therefore, pancreatic beta cells, which are the only type of cell that expresses insulin, is considered to be a potential target for the cure of diabetes. Although the findings regarding beta-cell neogenesis during pancreas development have been exploited to induce insulin-producing cells from non-beta cells, there are still many hurdles towards generating fully functional beta cells that can produce high levels of insulin and respond to physiological signals. To overcome these problems, a solid understanding of pancreas development and beta-cell formation is required, and several mouse models have been developed to reveal the unique features of each endocrine cell type at distinct developmental time points. Here I review our understanding of pancreas development and endocrine differentiation focusing on recent progresses in improving temporal cell labeling in vivo.

  11. Radiation pathomorphology of the gastrointestinal endocrine cells

    International Nuclear Information System (INIS)

    Yuzhakov, V.V.; Yakovleva, N.D.; Kvetnoj, I.M.; Ulitina, E.D.

    1994-01-01

    The paper presents the results of histochemical, electronmicroscopic and radioautographic analysis of the effects of a total single gamma irradiation on the functional morphology of cells of the diffuse endocrine system of the gastrointestinal tract of rats and mice. Irradiation in dosses from 5 to 20 Gy results in reduction of the detectability of argyrophilic and argentaffine cells. Changes in these cells counts are related to the irradiation dose. The reaction observed early after the irradiation is related to changes in the endocrine and endoplasmatic reticulum

  12. Multiple endocrine neoplasia type 2: achievements and current challenges

    Directory of Open Access Journals (Sweden)

    Andreas Machens

    2012-01-01

    Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

  13. Ultrastructure of the midgut endocrine cells in Melipona quadrifasciata anthidioides (Hymenoptera, Apidae

    Directory of Open Access Journals (Sweden)

    C. A. Neves

    Full Text Available In this study we describe the ultrastructure of the endocrine cells observed in the midgut of M. quadrifasciata anthidioides. This bee has two types of endocrine cells, which are numerous on the posterior midgut region. Cells of the closed type are smaller and have irregular secretory granules with lower electrondensity than those of the open cell type. The open cell type has elongated mitochondria mainly on the basal area, where most of the secretory granules are also found. Besides the secretion granules and mitochondria, endocrine cells in this species have well-developed autophagic vacuoles and Golgi complex elements.

  14. Endocrine cells in the denervated intestine

    Science.gov (United States)

    Santos, Gilda C; Zucoloto, Sérgio; Garcia, Sérgio B

    2000-01-01

    This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group − the proximal jejunal serosa was treated with 2 mm BAC for 30 min, and the control group − treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. PMID:10971748

  15. Nuclear Receptors and Multiple Endocrine Neoplasia type 1 (MEN1)

    NARCIS (Netherlands)

    Dreijerink, K.M.A.

    2009-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome that is characterized by the occurrence of tumours of the parathyroid glands, gastroenteropancreatic tumours, pitui-tary gland adenomas, as well as adrenal adenomas and neuro-endocrine tumours, often at a young age. MEN1 tumours can

  16. Molecular diagnosis of multiple endocrine neoplasia type 2A ...

    African Journals Online (AJOL)

    Molecular diagnosis of multiple endocrine neoplasia type 2A. RJ Pegoraro, DJ Hacking, RH Buck, L Rom, PA Lanning, GMB Berger. Abstract. Objective. To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. Subjects.

  17. Endocrine Disruptors and Leydig Cell Function

    Directory of Open Access Journals (Sweden)

    K. Svechnikov

    2010-01-01

    Full Text Available During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

  18. Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells

    Science.gov (United States)

    Bechard, Matthew E.; Bankaitis, Eric D.; Hipkens, Susan B.; Ustione, Alessandro; Piston, David W.; Yang, Yu-Ping; Magnuson, Mark A.; Wright, Christopher V.E.

    2016-01-01

    The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9+ bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3TA.LO cell population, defined as Neurog3 transcriptionally active and Sox9+ and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9+ Neurog3TA.LO progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3HI cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9+ Neurog3TA.LO progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9+ Neurog3TA.LO endocrine-biased progenitors feed production of Neurog3HI endocrine-committed cells during pancreas organogenesis. PMID:27585590

  19. Imaging Finding of Multiple Endocrine Neoplasia Type 1: Case Report

    International Nuclear Information System (INIS)

    Yum, Tae Jun; Cho, Hee Woo

    2012-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome with characteristic clinical and radiological manifestations. Many reports on MEN1 have been published; however, no cases of radiologically diagnosed MEN1 have been reported. Therefore, we report on a radiologically diagnosed case of MEN1 with clinical symptoms of gastroduodenal ulcer.

  20. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    International Nuclear Information System (INIS)

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-01-01

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause

  1. Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs.

    Science.gov (United States)

    Iser, Wendy B; Gami, Minaxi S; Wolkow, Catherine A

    2007-03-15

    In C. elegans, insulin signaling affects development, lifespan and stress resistance. Several studies have shown that insulin signaling affects lifespan in an endocrine-like manner from different cells, while the major downstream target of insulin, the FOXO transcription factor encoded by daf-16, may act preferentially in intestinal cells to prolong lifespan. This discrepancy raised the possibility that insulin may have both endocrine and cell-intrinsic outputs. Here, we further investigated the types of cells capable of producing endocrine outputs of insulin and also identified a new cell-intrinsic insulin output. We found that insulin signaling within groups of neurons promoted wildtype lifespan, showing that the endocrine outputs of insulin were not restricted to specific cells. In contrast, DAF-16 appeared to have a greater effect on lifespan when expressed in a combination of tissues. These results suggest that insulin signaling may regulate DAF-16 through cell-intrinsic and endocrine pathways. We also found that an insulin-dependent response to fasting in intestinal cells was preferentially regulated by intestinal insulin signaling and was less responsive to insulin signaling from non-intestinal cells. Together, these results show that C. elegans insulin signaling has endocrine as well as tissue-specific outputs which could influence lifespan in a combinatorial fashion.

  2. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Directory of Open Access Journals (Sweden)

    Grzegorz Piecha

    2010-01-01

    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  3. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.

    Science.gov (United States)

    D'Amour, Kevin A; Bang, Anne G; Eliazer, Susan; Kelly, Olivia G; Agulnick, Alan D; Smart, Nora G; Moorman, Mark A; Kroon, Evert; Carpenter, Melissa K; Baetge, Emmanuel E

    2006-11-01

    Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synthesizing the pancreatic hormones insulin, glucagon, somatostatin, pancreatic polypeptide and ghrelin. This process mimics in vivo pancreatic organogenesis by directing cells through stages resembling definitive endoderm, gut-tube endoderm, pancreatic endoderm and endocrine precursor--en route to cells that express endocrine hormones. The hES cell-derived insulin-expressing cells have an insulin content approaching that of adult islets. Similar to fetal beta-cells, they release C-peptide in response to multiple secretory stimuli, but only minimally to glucose. Production of these hES cell-derived endocrine cells may represent a critical step in the development of a renewable source of cells for diabetes cell therapy.

  4. Review: the role of neural crest cells in the endocrine system.

    Science.gov (United States)

    Adams, Meghan Sara; Bronner-Fraser, Marianne

    2009-01-01

    The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

  5. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

  6. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  7. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  8. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

  9. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors.

    Science.gov (United States)

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami; Ripoche, Doriane; Leteurtre, Emmanuelle; Chen, Yuan-Jia; Rehfeld, Jens F; Lepinasse, Florian; Hervieu, Valérie; Pattou, François; Vantyghem, Marie-Christine; Scoazec, Jean-Yves; Bertolino, Philippe; Zhang, Chang Xian

    2015-10-01

    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have migrated from the duodenum. In the current study, we further characterized previously described transient pancreatic gastrin-expressing cells using cell lineage tracing in a pan-pancreatic progenitor and a pancreatic endocrine progenitor model. We provide evidence showing that pancreatic gastrin-expressing cells, found from embryonic day 12.5 until postnatal day 7, are derived from pancreatic Ptf1a(+) and neurogenin 3-expressing (Ngn3(+)) progenitors. Importantly, the majority of them coexpress glucagon, with 4% coexpressing insulin, indicating that they are a temporary subpopulation of both alpha and beta cells. Interestingly, Men1 disruption in both Ngn3 progenitors and beta and alpha cells resulted in the development of pancreatic gastrin-expressing tumors, suggesting that the latter developed from islet cells. Finally, we detected gastrin expression using three human cohorts with pancreatic endocrine tumors (pNETs) that have not been diagnosed as gastrinomas (in 9/34 pNETs from 6/14 patients with multiple endocrine neoplasia type 1, in 5/35 sporadic nonfunctioning pNETs, and in 2/20 sporadic insulinomas), consistent with observations made in mouse models. Our work provides insight into the histogenesis of pancreatic gastrin-expressing tumors. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Endocrine function over time in patients with myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Ørngreen, M C; Witting, N

    2015-01-01

    BACKGROUND AND PURPOSE: Patients with myotonic dystrophy type 1 (DM1) have an increased incidence of endocrine dysfunction. In this study, the temporal evolution of endocrine dysfunction in patients with DM1 was investigated. METHODS: Endocrine function was assessed in 68 patients with DM1, in whom...... endocrine function had been followed, on average, for 8 years. The endocrine function was assessed by measuring the concentration of hormones and metabolites in blood and by validating libido with questionnaires. RESULTS: At baseline, 30 of the 68 patients presented with at least one hormonal dysfunction....... When re-evaluated after 8 years, 57 of 68 patients had endocrine dysfunction. Diabetic patients had increased from one to four. At follow-up, hyperparathyroidism occurred in 25% and abnormal thyroid-stimulating hormone in 21%, compared with 14% and 9% at baseline. Sixteen of 33 men had increased...

  11. Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1

    OpenAIRE

    Tomita, Masaki; Ichiki, Nobuhiko; Ayabe, Takanori; Tanaka, Hiroyuki; Kataoka, Hiroaki; Nakamura, Kunihide

    2017-01-01

    Abstract Thymic epithelial tumors occur in 1?5% of patients with multiple endocrine neoplasia type 1 (MEN 1). Majority of these thymic epithelial tumors are thymic carcinoids and patients with thymoma in MEN 1 is rare. Furthermore, thymoma with neuroendocrine differentiation was also rarely reported. Herein, we report a 68-year-old man having type B3 thymoma with neuroendocrine differentiation in MEN 1 and to the best of our knowledge this is the first such case ever reported.

  12. Gastric Endocrine Cell Carcinoma with Long-Term Survival Developing Metachronous Remnant Cancer

    Directory of Open Access Journals (Sweden)

    Tomoyuki Abe

    2011-04-01

    Full Text Available A rare case of primary gastric endocrine cell carcinoma in a 79-year-old man is reported. Upper gastrointestinal endoscopy showed a large Bormann’s type 2 tumour located in the middle of the stomach. On computed tomography, the gastric wall was thickened by the large tumour, and there were no distant metastases. Distal gastrectomy, lymph node dissection, and partial resection of the transverse colon were performed because the tumour involved the transverse mesocolon. The final pathological diagnosis was endocrine cell carcinoma, with tumour infiltration up to the subserous layer. Adjuvant chemotherapy was given, but metachronous remnant gastric cancer developed 2 years after surgery. Endoscopic submucosal dissection was performed for the early 0-IIc type gastric cancer, and the surgical margin was preserved. The patient has survived for 5 years after the primary surgery, remaining disease-free so far.

  13. Endocrine function in 97 patients with myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Ørngreen, Mette Cathrine; Arlien-Søborg, P.; Duno, M

    2012-01-01

    . Correlation with CTG(n) expansion size was investigated with the Pearson correlation test. Eighteen percent of the DM1 patients had hyperparathyroidism with increased PTH compared with 0.5% in the background population. Of these, 16% had normocalcemia and 2% had hypercalcemia. An additional 3% had...... LH, but normal testosterone levels, indicating relative insufficiency. Numbers of CTG repeats correlated directly with plasma PTH, phosphate, LH, and tended to correlate with plasma testosterone for males. This is the largest study of endocrine dysfunction in a cohort of Caucasian patients with DM1....... We found that patients with DM1 have an increased risk of abnormal endocrine function, particularly calcium metabolism disorders. However, the endocrine dysfunction appears not to be of clinical significance in all of the cases. Finally, we found correlations between CTG(n) expansion size and plasma...

  14. In vitro reprogramming of rat bmMSCs into pancreatic endocrine-like cells.

    Science.gov (United States)

    Li, Hong-Tu; Jiang, Fang-Xu; Shi, Ping; Zhang, Tao; Liu, Xiao-Yu; Lin, Xue-Wen; San, Zhong-Yan; Pang, Xi-Ning

    2017-02-01

    Islet transplantation provides curative treatments to patients with type 1 diabetes, but donor shortage restricts the broad use of this therapy. Thus, generation of alternative transplantable cell sources is intensively investigated worldwide. We previously showed that bone marrow-derived mesenchymal stem cells (bmMSCs) can be reprogrammed to pancreatic-like cells through simultaneously forced suppression of Rest/Nrsf (repressor element-1 silencing transcription factor/neuronal restrictive silencing factor) and Shh (sonic hedgehog) and activation of Pdx1 (pancreas and duodenal transcription factor 1). We here aimed to reprogram bmMSCs further along the developmental pathway towards the islet lineages by improving our previous strategy and by overexpression of Ngn3 (neurogenin 3) and NeuroD1 (neurogenic differentiation 1), critical regulators of the development of endocrine pancreas. We showed that compared to the previous protocol, the overexpression of only Pdx1 and Ngn3 reprogrammed bmMSCs into cells with more characteristics of islet endocrine lineages verified with bioinformatic analyses of our RNA-Seq datasets. These analyses indicated 2325 differentially expressed genes including those involved in the pancreas and islet development. We validated with qRT-PCR analysis selective genes identified from the RNA-Seq datasets. Thus, we reprogrammed bmMSCs into islet endocrine-like cells and advanced the endeavor to generate surrogate functional insulin-secreting cells.

  15. Frequency and Risk Factors of Endocrine Complications in Turkish Children and Adolescents with Sickle Cell Anemia

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    Samim Özen

    2013-03-01

    Full Text Available Objective: To define frequency and risk factors of abnormalities in growth, puberty, thyroid function, and bone and carbohydrate metabolisms in children and adolescents with sickle cell disease (SCD. Materials and Methods: Endocrine problems including short stature, puberty and thyroid disorders, and carbohydrate and bone metabolisms in 50 Turkish children and adolescents with SCD were evaluated. Relationships among sex, disease type, blood transfusions, exchange and exacerbation frequency, ferritin levels, and endocrine pathologies were investigated. Results: The mean age of the study group was 13.1±2.9 years. Weights and heights of 12 participants (24% were below -2 standard deviations and 4 participants (8% had malnutrition. Mean difference (±standard deviation between bone and chronological age of patients was -1.73±1.86 years. Fifty percent of patients had at least one endocrine abnormality other than vitamin D deficiency and insufficiency. Hypergonadotropic hypogonadism in 3 patients (6%, hypogonadotropic hypogonadism in 1 female patient (2%, and small testicular volume in respect to age in 3 male patients (8.5% were seen. Growth hormone deficiency was detected in 1 (2% female patient, and hypothyroidism was diagnosed in 3 patients (6%; 1 central case, 2 cases of primary hypothyroidism. At vertebral level, 5 patients (11.1% had osteopenia and 1 patient (2.2% had osteoporosis, while 5 patients (11.1% had osteopenia at femur neck level. The most common endocrine abnormality was vitamin D deficiency. 25-Hydroxyvitamin D was deficient in 63.2% and insufficient in 18.4% of patients. Sex, disease type, blood transfusion frequency, exacerbation frequency, and ferritin levels were not related to endocrine pathologies. As the age was increased, standard deviation scores of femur neck bone mineral density was decreased (r =-0.56; p<0.05. Vitamin D was lower in patients whose weights and/or heights were below -2 standard deviations from the mean

  16. Scintigraphic Evaluation of Multiple Endocrine Neoplasia Type 2 ( MEN Type 2 )

    International Nuclear Information System (INIS)

    Lee, Jae Tae; Lee, Kyu Bo; Whang, Kee Suk; Kim, Bo Wan; Lee, In Kyu

    1991-01-01

    Multiple endocrine neoplasia type 2 (MEN type 2, Sipple's syndrome) is a rare disorder characterized by the association of medullary carcinoma of the thyroid, parathyroid hyperplasia and can be diagnosed in early stage of the disease by meticulous screening tests of the family. This case report describes the location and categorization of tumors using 99m Tc-pertechnetate, I -NaI, 99m Tc-pentavalent(V) DMSA, 131 I -MIBG scans in two cases of MEN type 2 occurred in a 32 year old women and her 29-year old brother. In MEN type 2, we think, combined use of 99m Tc-(V)-DMSA, 99m Tc-pertechnetate and 1 '3 1 I -MIBG may be useful for the categorization of tumor mass lesions and planning appropriate therapy.

  17. Insulin-Producing Endocrine Cells Differentiated In Vitro From Human Embryonic Stem Cells Function in Macroencapsulation Devices In Vivo.

    Science.gov (United States)

    Agulnick, Alan D; Ambruzs, Dana M; Moorman, Mark A; Bhoumik, Anindita; Cesario, Rosemary M; Payne, Janice K; Kelly, Jonathan R; Haakmeester, Carl; Srijemac, Robert; Wilson, Alistair Z; Kerr, Justin; Frazier, Mauro A; Kroon, Evert J; D'Amour, Kevin A

    2015-10-01

    The PEC-01 cell population, differentiated from human embryonic stem cells (hESCs), contains pancreatic progenitors (PPs) that, when loaded into macroencapsulation devices (to produce the VC-01 candidate product) and transplanted into mice, can mature into glucose-responsive insulin-secreting cells and other pancreatic endocrine cells involved in glucose metabolism. We modified the protocol for making PEC-01 cells such that 73%-80% of the cell population consisted of PDX1-positive (PDX1+) and NKX6.1+ PPs. The PPs were further differentiated to islet-like cells (ICs) that reproducibly contained 73%-89% endocrine cells, of which approximately 40%-50% expressed insulin. A large fraction of these insulin-positive cells were single hormone-positive and expressed the transcription factors PDX1 and NKX6.1. To preclude a significant contribution of progenitors to the in vivo function of ICs, we used a simple enrichment process to remove remaining PPs, yielding aggregates that contained 93%-98% endocrine cells and 1%-3% progenitors. Enriched ICs, when encapsulated and implanted into mice, functioned similarly to the VC-01 candidate product, demonstrating conclusively that in vitro-produced hESC-derived insulin-producing cells can mature and function in vivo in devices. A scaled version of our suspension culture was used, and the endocrine aggregates could be cryopreserved and retain functionality. Although ICs expressed multiple important β cell genes, the cells contained relatively low levels of several maturity-associated markers. Correlating with this, the time to function of ICs was similar to PEC-01 cells, indicating that ICs required cell-autonomous maturation after delivery in vivo, which would occur concurrently with graft integration into the host. Type 1 diabetes (T1D) affects approximately 1.25 million people in the U.S. alone and is deadly if not managed with insulin injections. This paper describes the production of insulin-producing cells in vitro and a new

  18. Endocrine complications after busulphan and cyclophosphamide based hematopoietic stem cell transplant: A single tertiary care centre experience

    Directory of Open Access Journals (Sweden)

    Abhay Gundgurthi

    2013-01-01

    Full Text Available Introduction: Endocrine complications are common after hematopoietic stem cell transplant (HSCT. Although HSCT is performed at various centers in India, no study is available for endocrine dysfunctions among them. This study was carried out with the objective to evaluate endocrine dysfunction among patients undergone HSCT in the past. Materials and Methods: We carried out a cross-sectional study in a 50 post-HSCT recipients (39 allogenic, 11 autologous. All relevant data were collected from patient′s records. Samples for hormonal estimation were collected and stimulation tests for cortisol and growth hormone were interpreted based on peak values achieved during insulin tolerance test. Results: The mean age of patients was 26.3 ± 16.9 years (range 4-74. Adrenal insufficiency (AI was present in 60%, hypergonadotropic hypogonadism (HH in 60%, growth hormone deficiency (GHD in 54%, hypothyroidism in 4%, hyperprolactinemia in 4%, new onset diabetes after transplant in 4%, and impaired fasting glucose in 6%. Multiple endocrine complications were common. GHD was present in 77% of children (n = 22 although height standard deviation score was not statistically different compared to those who didn′t have GHD. HH was present in 36% of children. In adults (n = 28, 36% had GHD, all females had HH, and 89% of males had HH. Germ cell dysfunction with compensated Leydig cell dysfunction was the most common pattern of HH in males. Fifteen patients had graft versus host disease (GVHD. GVHD had no bearing on development of endocrine deficiencies. AI was related to duration after and type of transplant, but was unrelated to steroid intake. Conclusions: Endocrine manifestations are common after HSCT; they can occur as early or late complications. All HSCT recipients should have endocrine evaluation as per prevailing guidelines.

  19. GLUT4 in the endocrine pancreas--indicating an impact in pancreatic islet cell physiology?

    Science.gov (United States)

    Bähr, I; Bazwinsky-Wutschke, I; Wolgast, S; Hofmann, K; Streck, S; Mühlbauer, E; Wedekind, D; Peschke, E

    2012-06-01

    The glucose transporter GLUT4 is well known to facilitate the transport of blood glucose into insulin-sensitive muscle and adipose tissue. In this study, molecular, immunohistochemical, and Western blot investigations revealed evidence that GLUT4 is also located in the mouse, rat, and human endocrine pancreas. In addition, high glucose decreased and insulin elevated the GLUT4 expression in pancreatic α-cells. In contrast, high glucose increased GLUT4 expression, whereas insulin led to a reduced expression level of the glucose transporter in pancreatic β-cells. In vivo experiments showed that in pancreatic tissue of type 2 diabetic rats as well as type 2 diabetic patients, the GLUT4 expression is significantly increased compared to the nondiabetic control group. Furthermore, type 1 diabetic rats exhibited reduced GLUT4 transcript levels in pancreatic tissue, whereas insulin treatment of type 1 diabetic animals enhanced the GLUT4 expression back to control levels. These data provide evidence for the existence of GLUT4 in the endocrine pancreas and indicate a physiological relevance of this glucose transporter as well as characteristic changes in diabetic disease. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  1. CXCL14-like Immunoreactivity Exists in Somatostatin-containing Endocrine Cells, and in the Lamina Propria and Submucosal Somatostatinergic Nervous System of Mouse Alimentary Tract.

    Science.gov (United States)

    Suzuki, Hirohumi; Yamada, Kentaro; Matsuda, Yasuhiro; Onozuka, Minoru; Yamamoto, Toshiharu

    2017-12-26

    In the present study, we investigated the distribution of CXCL14 immunoreactive endocrine cells and neurons in mouse alimentary tract by immunohistochemistry. CXCL14 immunoreactive endocrine cells were found as closed-type cells in the stomach and open-type cells in the small intestine. The immunostaining of these endocrine cells corresponded with that of the somatostatin-containing endocrine cells. Only a few CXCL14 immunoreactive endocrine cells were seen in the large intestine. CXCL14 immunoreactive fibers were observed in the muscular layer from the stomach to the rectum with most abundance in the rectum. Many CXCL14 immunoreactive fibers were observed in the lamina propria and submucosal layer from the duodenum to the rectum with most abundance in the rectum; these fibers corresponded to the somatostatin-containing nerve fibers. Some CXCL14 immunoreactive neuronal somata that were also immuno-positive for somatostatin, were noted in the submucosal layer of the rectum. However, the remaining parts of the alimentary tract presented with almost negligible immunoreactive somata. The co-localization of CXCL14 and somatostatin suggests that CXCL14 contributes to the function of somatostatin, which include the inhibition of other endocrine and exocrine cells and the enteric nervous systems.

  2. Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy

    Directory of Open Access Journals (Sweden)

    Francesco Tonelli

    2012-01-01

    Full Text Available Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1 correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2 avoid persistent hypoparathyroidism; and 3 facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1 subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2 total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1 the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2 the surgeon's experience; 3 the timing of surgery; 4 the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay of the curative potential of the surgical procedure; and, 5 the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

  3. Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.

    Science.gov (United States)

    Hayden, Melvin R; Patel, Kamlesh; Habibi, Javad; Gupta, Deepa; Tekwani, Seema S; Whaley-Connell, Adam; Sowers, James R

    2008-01-01

    Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.

  4. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

    2017-02-01

    The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

  5. A rare presentation of multiple endocrine neoplasia (MEN type 2A syndrome

    Directory of Open Access Journals (Sweden)

    Elroy Patrick Weledji

    2016-02-01

    Full Text Available Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease.

  6. Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Luis Sarmiento

    2017-01-01

    Full Text Available Human enteroviruses (HEV, especially coxsackievirus serotype B (CVB and echovirus (E, have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1, 2'-5'-oligoadenylate synthetase 1 (OAS1, interferon-β (IFN-β, chemokine (C–X–C motif ligand 10 (CXCL10 and chemokine (C–C motif ligand 5 (CCL5. Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV.

  7. Pernicious anaemia and mucosal endocrine cell proliferation of the non-antral stomach.

    OpenAIRE

    Rode, J; Dhillon, A P; Papadaki, L; Stockbrügger, R; Thompson, R J; Moss, E; Cotton, P B

    1986-01-01

    There is a recognised association between pernicious anaemia and the development of gastric carcinoma, endocrine cell hyperplasia, and carcinoid tumour. Multiple endoscopic biopsies from the body mucosa of seven patients with pernicious anaemia showed small intestinal metaplasia with varying degrees of inflammation, fibrosis, and expansion of the lamina propria. Using conventional silver and lead stains, endocrine cells were inconspicuous. Staining for the general neural and neuroendocrine ma...

  8. Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

    Science.gov (United States)

    Telander, R L; Zimmerman, D; van Heerden, J A; Sizemore, G W

    1986-12-01

    Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. A case of gastric endocrine cell carcinoma which was significantly reduced in size by radiotherapy

    International Nuclear Information System (INIS)

    Azakami, Kiyoshi; Nishida, Kouji; Tanikawa, Ken

    2016-01-01

    In 2010, the World Health Organization classified gastric neuroendocrine tumors (NETs) into three types: NET grade (G) 1, NET G2 and neuroendocrine carcinoma (NEC). NECs are associated with a very poor prognosis. The patient was an 84-year-old female who was initially diagnosed by gastrointestinal endoscope with type 3 advanced gastric cancer with stenosis of the gastric cardia. Her overall status and performance status did not allow for operations or intensive chemotherapy. Palliative radiotherapy was performed and resulted in a significant reduction in the size of the tumor as well as the improvement of the obstructive symptoms. She died 9 months after radiotherapy. An autopsy provided a definitive diagnosis of gastric endocrine cell carcinoma, and the effectiveness of radiotherapy was pathologically-confirmed. Palliative radiotherapy may be a useful treatment option for providing symptom relief, especially for old patients with unresectable advanced gastric neuroendocrine carcinoma. (author)

  10. [The relative analysis of clinical endocrine features and pathological types of pituitary microadenomas].

    Science.gov (United States)

    Yan, Qing; Zhang, Hua-qiu; Wang, He-ping; Guo, Dong-sheng; Lei, Ting; Li, Ling

    2010-06-15

    To study the relationship between the clinical presentation, endocrinal findings and pathological types in patients with pituitary microadenomas, so as to improve the accuracy of clinical diagnosis and choose the best therapy strategy before the operation. From January 2007 to June 2009, the clinical data of 94 patients who were surgically removed pituitary microadenomas were obtained, including the clinical presentation, endocrinal findings and pathological diagnosis. The analysis was accomplished with Chi-square test. Hormonal symptoms were found in 86 patients (91.5%), it occurred more frequently in immunopositive patients (85/92, 92.4%) than in immunonegative patients (1/2, 50.0%) (P gigantism or acromegaly in growth hormone (GH) positive group. The coincidence of endocrinal findings and immunohistochemistry diagnosis was 69.0%; 87.7% patients had high level of blood PRL in PRL positive group and 21.9% patients had high level of blood GH in GH positive group. There is an obvious relationship between the clinical presentation, endocrinal findings and pathological diagnosis in patients with pituitary microadenomas, which may contribute to the clinical diagnosis and treatment of pituitary secreting microadenomas.

  11. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  12. Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

    Science.gov (United States)

    Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

    2017-06-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

  13. Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes.

    Science.gov (United States)

    Singh, Vijay Pratap; Khandelwal, Bidita; Sherpa, Namgyal T

    2015-01-01

    Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti

  14. Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland

    OpenAIRE

    Vierimaa, O. (Outi)

    2008-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by parathyroid, gastroenteropancreatic and pituitary neuroendocrine tumours. In Northern Finland, two founder mutations of the MEN1 gene (1466del12, 1657insC) accounting for the majority of the MEN1 cases, have common ancestors born in the 18th and 19th centuries, respectively. Three small clusters of familial pituitary adenoma have also been detected, two of which could be linked by genealogy to a ...

  15. FGF-2b and h-PL Transform Duct and Non-Endocrine Human Pancreatic Cells into Endocrine Insulin Secreting Cells by Modulating Differentiating Genes

    Directory of Open Access Journals (Sweden)

    Giulia Donadel

    2017-10-01

    Full Text Available Background: Diabetes mellitus (DM is a multifactorial disease orphan of a cure. Regenerative medicine has been proposed as novel strategy for DM therapy. Human fibroblast growth factor (FGF-2b controls β-cell clusters via autocrine action, and human placental lactogen (hPL-A increases functional β-cells. We hypothesized whether FGF-2b/hPL-A treatment induces β-cell differentiation from ductal/non-endocrine precursor(s by modulating specific genes expression. Methods: Human pancreatic ductal-cells (PANC-1 and non-endocrine pancreatic cells were treated with FGF-2b plus hPL-A at 500 ng/mL. Cytofluorimetry and Immunofluorescence have been performed to detect expression of endocrine, ductal and acinar markers. Bromodeoxyuridine incorporation and annexin-V quantified cells proliferation and apoptosis. Insulin secretion was assessed by RIA kit, and electron microscopy analyzed islet-like clusters. Results: Increase in PANC-1 duct cells de-differentiation into islet-like aggregates was observed after FGF-2b/hPL-A treatment showing ultrastructure typical of islets-aggregates. These clusters, after stimulation with FGF-2b/hPL-A, had significant (p < 0.05 increase in insulin, C-peptide, pancreatic and duodenal homeobox 1 (PDX-1, Nkx2.2, Nkx6.1, somatostatin, glucagon, and glucose transporter 2 (Glut-2, compared with control cells. Markers of PANC-1 (Cytokeratin-19, MUC-1, CA19-9 were decreased (p < 0.05. These aggregates after treatment with FGF-2b/hPL-A significantly reduced levels of apoptosis. Conclusions: FGF-2b and hPL-A are promising candidates for regenerative therapy in DM by inducing de-differentiation of stem cells modulating pivotal endocrine genes.

  16. Single-Cell Gene Expression Analysis of a Human ESC Model of Pancreatic Endocrine Development Reveals Different Paths to β-Cell Differentiation.

    Science.gov (United States)

    Petersen, Maja Borup Kjær; Azad, Ajuna; Ingvorsen, Camilla; Hess, Katja; Hansson, Mattias; Grapin-Botton, Anne; Honoré, Christian

    2017-10-10

    The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells. We uncover several similarities and differences with mouse development and reveal that cells can take multiple paths to the same differentiation state, a principle that could be relevant to other systems. Notably, activation of the key β-cell transcription factor NKX6.1 can be initiated before or after endocrine commitment. The single-cell temporal resolution we provide can be used to improve the production of functional β cells. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Characteristics of the Danish families with multiple endocrine neoplasia type 1

    DEFF Research Database (Denmark)

    Jäger, Anne Charlotte; Friis-Hansen, Lennart; Hansen, Thomas v.O.

    2006-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier...... reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five...... mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were...

  18. WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines.

    Science.gov (United States)

    Sikora, Matthew J; Jacobsen, Britta M; Levine, Kevin; Chen, Jian; Davidson, Nancy E; Lee, Adrian V; Alexander, Caroline M; Oesterreich, Steffi

    2016-09-20

    Invasive lobular carcinoma (ILC) of the breast typically presents with clinical biomarkers consistent with a favorable response to endocrine therapies, and over 90 % of ILC cases express the estrogen receptor (ER). However, a subset of ILC cases may be resistant to endocrine therapies, suggesting that ER biology is unique in ILC. Using ILC cell lines, we previously demonstrated that ER regulates a distinct gene expression program in ILC cells, and we hypothesized that these ER-driven pathways modulate the endocrine response in ILC. One potential novel pathway is via the Wnt ligand WNT4, a critical signaling molecule in mammary gland development regulated by the progesterone receptor. The ILC cell lines MDA-MB-134-VI, SUM44PE, and BCK4 were used to assess WNT4 gene expression and regulation, as well as the role of WNT4 in estrogen-regulated proliferation. To assess these mechanisms in the context of endocrine resistance, we developed novel ILC endocrine-resistant long-term estrogen-deprived (ILC-LTED) models. ILC and ILC-LTED cell lines were used to identify upstream regulators and downstream signaling effectors of WNT4 signaling. ILC cells co-opted WNT4 signaling by placing it under direct ER control. We observed that ER regulation of WNT4 correlated with use of an ER binding site at the WNT4 locus, specifically in ILC cells. Further, WNT4 was required for endocrine response in ILC cells, as WNT4 knockdown blocked estrogen-induced proliferation. ILC-LTED cells remained dependent on WNT4 for proliferation, by either maintaining ER function and WNT4 regulation or uncoupling WNT4 from ER and upregulating WNT4 expression. In the latter case, WNT4 expression was driven by activated nuclear factor kappa-B signaling in ILC-LTED cells. In ILC and ILC-LTED cells, WNT4 led to suppression of CDKN1A/p21, which is critical for ILC cell proliferation. CDKN1A knockdown partially reversed the effects of WNT4 knockdown. WNT4 drives a novel signaling pathway in ILC cells, with a

  19. Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

    Science.gov (United States)

    Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

    2016-01-01

    The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

  20. Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

    Science.gov (United States)

    Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

    2014-03-01

    Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

  1. [Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

    Science.gov (United States)

    Ueki, H

    1987-11-01

    We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

  2. Spexin peptide is expressed in human endocrine and epithelial tissues and reduced after glucose load in type 2 diabetes.

    Science.gov (United States)

    Gu, Liping; Ma, Yuhang; Gu, Mingyu; Zhang, Ying; Yan, Shuai; Li, Na; Wang, Yufan; Ding, Xiaoying; Yin, Jiajing; Fan, Nengguang; Peng, Yongde

    2015-09-01

    Spexin mRNA and protein are widely expressed in rat tissues and associate with weight loss in rodents of diet-induced obesity. Its location in endocrine and epithelial cells has also been suggested. Spexin is a novel peptide that involves weight loss in rodents of diet-induced obesity. Therefore, we aimed to examine its expression in human tissues and test whether spexin could have a role in glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). The expression of the spexin gene and immunoreactivity in the adrenal gland, skin, stomach, small intestine, liver, thyroid, pancreatic islets, visceral fat, lung, colon, and kidney was higher than that in the muscle and connective tissue. Immunoreactive serum spexin levels were reduced in T2DM patients and correlated with fasting blood glucose (FBG, r=-0.686, Pepithelial tissues, indicating that spexin may be involved in physiological functions of endocrine and in several other tissues. Circulating spexin levels are low in T2DM patients and negatively related to blood glucose and lipids suggesting that the peptide may play a role in glucose and lipid metabolism in T2DM. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Mouse Pancreas Tissue Slice Culture Facilitates Long-Term Studies of Exocrine and Endocrine Cell Physiology in situ

    OpenAIRE

    Marciniak, Anja; Selck, Claudia; Friedrich, Betty; Speier, Stephan

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To ove...

  4. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

    2012-01-01

    necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both...

  5. ANGPTL4 is produced by entero-endocrine cells in the human intestinal tract

    NARCIS (Netherlands)

    Alex, S.; Lichtenstein, L.L.; Dijk, W.; Mensink, R.P.; Tan, N.S.; Kersten, A.H.

    2014-01-01

    Gut hormones produced by entero-endocrine cells (EEC) located throughout the gastrointestinal tract play a major role in the regulation of glucose and energy homeostasis. Angiopoietin-like 4 (ANGPTL4, also referred to as fasting induced adipose factor) is a secreted factor involved in regulation of

  6. Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

    DEFF Research Database (Denmark)

    Kim, Yung Hae; Larsen, Hjalte List; Rué, Paul

    2015-01-01

    Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine...

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

    Science.gov (United States)

    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.

  8. Klinefelter's Syndrome with Seizure, Pseudohypoparathyroidism Type Ib and Multiple Endocrine Dysfunctions

    Directory of Open Access Journals (Sweden)

    Chwen-Yi Yang

    2005-12-01

    Full Text Available Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47, XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.

  9. Preliminary study of the role of gastrointestinal endocrine cells in the maintenance of villous structure following X-irradiation

    International Nuclear Information System (INIS)

    Wyatt, M.G.; Hume, S.P.; Carr, K.E.; Marigold, J.C.

    1987-01-01

    The mechanism of gastrointestinal villous damage following ionizing irradiation is complex. Various compartments within the gastrointestinal tract have in turn been considered important for the maintenance of normal villous structure. To date, however, evidence for a single overriding regulator of epithelial well-being is lacking. In this study, the role of the gastro-intestinal (enteroendocrine) cells is explored and comparison made between endocrine cell number and villous structure. Experiments were organized using both control and irradiated groups of mice. Two time points (1 and 3 days) and three radiation doses (6, 10 and 18Gy) were employed. A simple method for endocrine cell identification and subsequent quantification is described. Endocrine cell number was then compared with villous surface detail, as seen with a scanning electron microscope (SEM). Results indicated a decrease in the endocrine cell number at all three radiation doses. Whereas at low doses endocrine cell recovery occurred between 1 and 3 days, at medium and high doses further decline was noticed. A similar pattern was seen when considering villous surface structure. It is suggested that both scanning electron microscopy and endocrine cell number provide a more sensitive indicator of gastrointestinal radiation damage than do current crypt counting techniques. In addition, a link between endocrine cell number and villous structure is proposed

  10. A possible role for the canonical Wnt pathway in endocrine cell development in chicks

    International Nuclear Information System (INIS)

    Pedersen, Anna Hauntoft; Heller, R. Scott

    2005-01-01

    Wnt signalling is involved in many developmental processes such as proliferation, differentiation, cell fate decisions, and morphogenesis. However, little is known about Wnt signalling during pancreas development. Multiple Wnt ligands and Frizzled receptors are expressed in the embryonic mouse pancreas, the surrounding mesenchyme, and have also been detected in the chicken endoderm during development. The aim of this study was to investigate the role of canonical Wnt signalling on endocrine cell development by use of the in ovo electroporation of the chicken endoderm. Overexpression with a constitutive active form of β-catenin in combination with Ngn3 resulted in reduced numbers of glucagon cells. dnLEF-1 or naked-1 did not alter endocrine cell differentiation when co-expressed with Ngn3, but dnLEF-1 appeared to have some potential for inhibiting delamination of Ngn3 cells. In addition, neuronal β-III-tubulin, which had previously been considered a specific marker for neuronal cells, was observed in the pancreas and was upregulated in the electroporated Ngn3 cells and thus may be a new endocrine marker in the chicken

  11. `Full fusion' is not ineluctable during vesicular exocytosis of neurotransmitters by endocrine cells

    Science.gov (United States)

    Oleinick, Alexander; Svir, Irina; Amatore, Christian

    2017-01-01

    Vesicular exocytosis is an essential and ubiquitous process in neurons and endocrine cells by which neurotransmitters are released in synaptic clefts or extracellular fluids. It involves the fusion of a vesicle loaded with chemical messengers with the cell membrane through a nanometric fusion pore. In endocrine cells, unless it closes after some flickering (`Kiss-and-Run' events), this initial pore is supposed to expand exponentially, leading to a full integration of the vesicle membrane into the cell membrane-a stage called `full fusion'. We report here a compact analytical formulation that allows precise measurements of the fusion pore expansion extent and rate to be extracted from individual amperometric spike time courses. These data definitively establish that, during release of catecholamines, fusion pores enlarge at most to approximately one-fifth of the radius of their parent vesicle, hence ruling out the ineluctability of `full fusion'.

  12. Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.

    Science.gov (United States)

    Lima, Aline Dt; Alves, Vanessa R; Rocha, Andressa R; Martinhago, Ana C; Martinhago, Ciro; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Gebrim, Luiz H

    2018-03-01

    Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive βHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.

  13. Financial burden is associated with worse health-related quality of life in adults with multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Peipert, Benjamin J; Goswami, Sneha; Helenowski, Irene; Yount, Susan E; Sturgeon, Cord

    2017-12-01

    Health-related quality of life and financial burden among patients with multiple endocrine neoplasia type 1 is poorly described. It is not known how financial burden influences health-related quality of life in this population. We hypothesized that the financial burden attributable to multiple endocrine neoplasia type 1 is associated with worse health-related quality of life. United States adults (≥18 years) with multiple endocrine neoplasia type 1 were recruited from the AMENSupport MEN online support group. Patient demographics, clinical characteristics, and financial burden were assessed via an online survey. The instrument Patient-Reported Outcomes Measurement Information System 29-item profile measure was used to assess health-related quality of life. Multivariable linear regression was used to identify significant variables in each Patient-Reported Outcomes Measurement Information System domain. Out of 1,378 members in AMENSupport, our survey link was accessed 449 times (33%). Of 153 US respondents who completed our survey, 84% reported financial burden attributable to multiple endocrine neoplasia type 1. The degree of financial burden had a linear relationship with worse health-related quality of life across all Patient-Reported Outcomes Measurement Information System domains (r = 0.36-0.55, P financial event(s). Borrowing money from friends/family (30%), unemployment (13%), and spending >$100/month out-of-pocket on prescription medications (46%) were associated consistently with impaired health-related quality of life (ß = 3.75-6.77, P times more likely to be unemployed and declare bankruptcy than the US population, respectively. This study characterizes the financial burden in patients with multiple endocrine neoplasia type 1. Individuals with multiple endocrine neoplasia type 1 report a high degree of financial burden, negative financial events, and unemployment. Each of these factors was associated with worse health-related quality of life

  14. Effects of acute exercise on pancreatic endocrine function in subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Winding, Kamilla

    2015-01-01

    We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in type 2 diabetic (T2D) subjects and examined the influence of the diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with GLP-1 infusion and arginine injection, the morning after a one.......05-P arginine (P = 0.08). The same trends were seen for low HbA1c subjects. Furthermore, exercise increased GLP-1- and arginine-stimulated insulin secretion (P diabetic......-hour walk or no exercise. Subjects were stratified by high and low quantiles of fasting plasma glucose (FPG) and HbA1c as well as current use/non-use of anti-diabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (P 

  15. Reproductive endocrine issues in men with sickle cell anemia.

    Science.gov (United States)

    Huang, A W; Muneyyirci-Delale, O

    2017-07-01

    In patients with sickle cell anemia, the sickling of red blood cells is known to cause end-organ damage by infarction. In some men who are affected by sickle cell anemia, the obstruction of venous outflow of the penis causes priapism, which could lead to erectile dysfunction. There is also evidence that the disease is linked to other reproductive issues in men-specifically delayed puberty, low testosterone, and sperm abnormalities-although the causes of these problems are less clear. Treatment of sickle cell anemia can have effects on the reproductive system as well. This review summarizes the findings from various publications pertaining to reproductive endocrinology, along with their conclusions and discrepancies. © 2017 American Society of Andrology and European Academy of Andrology.

  16. GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine

    DEFF Research Database (Denmark)

    Mortensen, Kristine; Christensen, Louise Lundby; Holst, Jens Juul

    2003-01-01

    BACKGROUND: The incretin hormones GIP and GLP-1 are thought to be produced in separate endocrine cells located in the proximal and distal ends of the mammalian small intestine, respectively. METHODS AND RESULTS: Using double immunohistochemistry and in situ hybridization, we found that GLP-1 was ....... CONCLUSIONS: Our results provide a morphological basis to suggest simultaneous, rather than sequential, secretion of these hormones by postprandial luminal stimulation....

  17. Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells

    Czech Academy of Sciences Publication Activity Database

    Brieno-Enriguez, M. A.; García-López, J.; Cárdenas, D.B.; Guibert, S.; Cleroux, E.; Děd, Lukáš; de Dios Hourcade, J.; Pěknicová, Jana; Weber, M.; del Mazo, J.

    2015-01-01

    Roč. 10, č. 4 (2015) E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP503/12/1834; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : endocrine disruptor * epigenetic s * primordial germ cells * vinclozolin * TUNEL analysis * methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  18. Radiological surveillance in multiple endocrine neoplasia type 1: a double-edged sword?

    Directory of Open Access Journals (Sweden)

    Ruth Therese Casey

    2017-03-01

    Full Text Available Context: Multiple endocrine neoplasia type 1 (MEN1 is a hereditary condition characterised by the predisposition to hyperplasia/tumours of endocrine glands. MEN1-related disease, moreover, malignancy related to MEN1, is increasingly responsible for death in up to two-thirds of patients. Although patients undergo radiological and biochemical surveillance, current recommendations for radiological monitoring are based on non-prospective data with little consensus or evidence demonstrating improved outcome from this approach. Here, we sought to determine whether cumulative radiation exposure as part of the recommended radiological screening programme posed a distinct risk in a cohort of patients with MEN1.Patients and study design: A retrospective review of 43 patients with MEN1 attending our institution between 2007 and 2015 was performed. Demographic and clinical information including phenotype was obtained for all patients. We also obtained details regarding all radiological procedures performed as part of MEN1 surveillance or disease localisation. An estimated effective radiation dose (ED for each individual patient was calculated.Results: The mean ED for the total patient cohort was 121 mSv, and the estimated mean lifetime risk of cancer secondary to radiation exposure was 0.49%. Patients with malignant neuroendocrine tumours (NETS had significantly higher ED levels compared to patients without metastatic disease (P < 0.0022.Conclusions: In MEN1, radiological surveillance is associated with clinically significant exposure to ionising radiation. In patients with MEN1, multi-modality imaging strategies designed to minimise this exposure should be considered.

  19. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    S Birla

    2016-01-01

    Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

  20. Exocrine dysfunction correlates with endocrinal impairment of pancreas in Type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    H R Prasanna Kumar

    2018-01-01

    Full Text Available Background: Diabetes mellitus (DM is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1 is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. Aim: The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. Methodology: A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics. Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t-test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Results: Statistically nonsignificant (P = 0.5051 relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation (P = 0.003 between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy (P = 0.001 and peripheral pulses (P = 0.001 with FE-1 levels were found to be statistically significant. Conclusion: This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  1. Exocrine Dysfunction Correlates with Endocrinal Impairment of Pancreas in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Prasanna Kumar, H R; Gowdappa, H Basavana; Hosmani, Tejashwi; Urs, Tejashri

    2018-01-01

    Diabetes mellitus (DM) is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1) is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM) by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics). Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t -test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Statistically nonsignificant ( P = 0.5051) relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation ( P = 0.003) between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy ( P = 0.001) and peripheral pulses ( P = 0.001) with FE-1 levels were found to be statistically significant. This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  2. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development

    OpenAIRE

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2011-01-01

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends o...

  3. Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients

    NARCIS (Netherlands)

    de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

    2013-01-01

    Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

  4. Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

    NARCIS (Netherlands)

    de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

    2013-01-01

    Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

  5. Endocrine disrupting activities and immunomodulatory effects in lymphoblastoid cell lines of diclofenac, 4-hydroxydiclofenac and paracetamol.

    Science.gov (United States)

    Klopčič, Ivana; Markovič, Tijana; Mlinarič-Raščan, Irena; Dolenc, Marija Sollner

    2018-05-16

    A critical literature review reveals that knowledge of side effects of pharmaceuticals diclofenac and paracetamol is extremely important because of their widespread use and occurrence in the environment. In order to delineate whether these compounds have endocrine activity and influence on the immune system, we assessed the potential endocrine disrupting and immunomodulatory activities of: diclofenac (DIC), its metabolite 4-hydroxydiclofenac (4-HD) and paracetamol (PAR). Herein, we report on their impact on estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR) and thyroid hormone receptor (TR). The endocrine disrupting effects were assessed in vitro in MDA-kb2 and GH3.TRE-Luc cell lines and by the XenoScreen YES/YAS assay. Moreover, binding affinity to nuclear receptors (GR and AR) was also measured. Immunomodulatory properties of the compounds were evaluated in lymphoblastoid cell lines. All the tested compounds showed endocrine disrupting and immunomodulatory activities. The results revealed that both DIC and its metabolite 4-HD exhibited significant estrogenic, anti-androgenic (in YAS assay), (anti)-androgenic, (anti)-glucocorticoid and anti-thyroid hormonal activities (in luciferase reporter gene assays). DIC showed direct binding to the GR, while its metabolite 4-HD to the GR and AR. Only metabolite 4-HD showed estrogenic, androgenic (in YAS assay) and thyroid-hormonal activities. PAR had anti-androgenic activity and anti-thyroid hormonal activity. PAR displayed GR agonist activity with competition to its receptor and agonistic activity to AR. All of the compounds significantly modulated pro-inflammatory and immunoregulatory cytokine production in lymphoblastoid cell lines and were thus proven immunomodulatory. The study is useful in determining toxicological effects and contributes to the knowledge of possible side effects of diclofenac, its metabolite and paracetamol. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Single Cell Assay for Analyzing Single Cell Exosome and Endocrine Secretion and Cancer Markers

    Science.gov (United States)

    Chiu, Yu-Jui

    To understand the inhomogeneity of cells in biological systems, there is a growing demand for the capability to characterize the properties of individual single cells. Since single cell studies require continuous monitoring of the cell behaviors instead of a snapshot test at a single time point, an effective single-cell assay that can support time lapsed studies in a high throughput manner is desired. Most currently available single-cell technologies cannot provide proper environments to sustain cell growth and cannot provide, for appropriate cell types, proliferation of single cells and convenient, non-invasive tests of single cell behaviors from molecular markers. In this dissertation, I present a highly versatile single-cell assay that can accommodate different cellular types, enable easy and efficient single cell loading and culturing, and be suitable for the study of effects of in-vitro environmental factors in combination with drug screening. The salient features of the assay are the non-invasive collection and surveying of single cell secretions at different time points and massively parallel translocation of single cells by user defined criteria, producing very high compatibility to the downstream process such as single cell qPCR and sequencing. Above all, the acquired information is quantitative -- for example, one of the studies is measured by the number of exosomes each single cell secretes for a given time period. Therefore, our single-cell assay provides a convenient, low-cost, and enabling tool for quantitative, time lapsed studies of single cell properties.

  7. Enteroendocrine cell types revisited

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Egerod, Kristoffer Lihme; Lund, Mari L

    2013-01-01

    The GI-tract is profoundly involved in the control of metabolism through peptide hormones secreted from enteroendocrine cells scattered throughout the gut mucosa. A large number of recently generated transgenic reporter mice have allowed for direct characterization of biochemical and cell...... biological properties of these previously highly elusive enteroendocrine cells. In particular the surprisingly broad co-expression of six functionally related hormones in the intestinal enteroendocrine cells indicates that it should be possible to control not only the hormone secretion but also the type...... and number of enteroendocrine cells. However, this will require a more deep understanding of the factors controlling differentiation, gene expression and specification of the enteroendocrine cells during their weekly renewal from progenitor cells in the crypts of the mucosa....

  8. Surgical strategies in endocrine tumors

    NARCIS (Netherlands)

    Schreinemakers, J.M.J.

    2010-01-01

    Endocrine surgery has become more custom-made throughout the years. Endocrine tumors can be sporadic or develop as part of familial syndromes. Several familial syndromes are known to cause endocrine tumors. The most common are multiple endocrine neoplasia (MEN) syndromes type 1, 2A and 2B. This

  9. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Brieño-Enríquez

    Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  10. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    International Nuclear Information System (INIS)

    Erdas, Enrico; Mariotti, Stefano; Pomata, Mariano; Aste, Nicola; Pilloni, Luca; Nicolosi, Angelo; Licheri, Sergio; Cappai, Antonello; Mastinu, Marco; Cetani, Filomena; Pardi, Elena

    2012-01-01

    Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99m Tc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

  11. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Directory of Open Access Journals (Sweden)

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  12. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    Energy Technology Data Exchange (ETDEWEB)

    Biemann, Ronald, E-mail: ronald.biemann@medizin.uni-halle.de [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Navarrete Santos, Anne [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Navarrete Santos, Alexander [Department of Cardiothoracic Surgery, Martin Luther University, Faculty of Medicine, Halle (Germany); Riemann, Dagmar [Department of Immunology, Martin Luther University, Faculty of Medicine, Halle (Germany); Knelangen, Julia [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany); Blueher, Matthias [Department of Medicine, University of Leipzig, Leipzig (Germany); Koch, Holger [Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Ruhr-University Bochum, Bochum (Germany); Fischer, Bernd [Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Germany)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  13. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

    International Nuclear Information System (INIS)

    Biemann, Ronald; Navarrete Santos, Anne; Navarrete Santos, Alexander; Riemann, Dagmar; Knelangen, Julia; Blüher, Matthias; Koch, Holger; Fischer, Bernd

    2012-01-01

    Highlights: ► Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). ► The adipogenic impact depends strongly on the window of exposure. ► Bisphenol A reduces the potential of MSC to differentiate into adipocytes. ► DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. ► BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPARγ2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 μM) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 μM) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

  14. Distribution of Pancreatic Polypeptide-secreting Endocrine Cells in Nondiabetic and Diabetic Cases.

    Science.gov (United States)

    Śliwińska-Mossoń, Mariola; Milnerowicz, Halina

    2017-07-01

    The aim of the study was to demonstrate the effects of cigarette smoking and ongoing inflammation in chronic pancreatitis on the functioning of pancreatic polypeptide (PP)-secreting cells and to determine the relationship between the occurrence of an increased number of PP cells in the pancreas, the change in their location, and the intensity of their inflammatory changes in the course of pancreatitis and diabetes. Samples of tissues from healthy persons and from patients were verified histopathologically, and then PP was localized by immunohistochemical staining using the monoclonal anti-human PP antibody. The histopathologic evaluation of the hormone expression intensity in tissue sections was carried out using the semiquantitative method and was calculated with digital image analysis. The present study showed a very strong PP expression in the pancreatic tissue (especially in the head of the pancreas) derived from smoking patients with diabetes. The increase in the percentage of cells in the PP islets, between the acinar cells in smoking patients with diabetes and a statistically significant increase in the expression of PP, indicates a pancreatic endocrine dysfunction and suggests that cigarette smoking has a negative impact on the organ's efficiency. Because of its properties, the PP appears to be a useful marker of the endocrine insufficiency of the pancreas and a specific prognostic parameter of developing diabetes due to chronic pancreatitis.

  15. Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development.

    Science.gov (United States)

    Beucher, Anthony; Martín, Mercè; Spenle, Caroline; Poulet, Martine; Collin, Caitlin; Gradwohl, Gérard

    2012-01-15

    During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends on pancreas developmental stage. Using temporal genetic labeling approaches we examined the dynamic of endocrine progenitor differentiation and explored the plasticity of Neurog3-induced cells throughout development. We found that Neurog3(+) progenitors develop into hormone-expressing cells in a fast process taking less then 10h. Furthermore, fate-mapping studies in heterozygote (Neurog3(CreERT/+)) and Neurog3-deficient (Neurog3(CreERT/CreERT)) embryos revealed that Neurog3-induced cells have different potential over time. At the early bud stage, failed endocrine progenitors can adopt acinar or ductal fate, whereas later in the branching pancreas they do not contribute to the acinar lineage but Neurog3-deficient cells eventually differentiate into duct cells. Thus these results provide evidence that the plasticity of Neurog3-induced cells becomes restricted during development. Furthermore these data suggest that during the secondary transition, endocrine progenitor cells arise from bipotent precursors already committed to the duct/endocrine lineages and not from domain of cells having distinct potentialities. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Endocrine Therapy of Estrogen Receptor-Positive Breast Cancer Cells: Early Differential Effects on Stem Cell Markers

    Directory of Open Access Journals (Sweden)

    Euphemia Y. Leung

    2017-09-01

    Full Text Available IntroductionEndocrine therapy of breast cancer, which either deprives cancer tissue of estrogen or prevents estrogen pathway signaling, is the most common treatment after surgery and radiotherapy. We have previously shown for the estrogen-responsive MCF-7 cell line that exposure to tamoxifen, or deprivation of estrogen, leads initially to inhibition of cell proliferation, followed after several months by the emergence of resistant sub-lines that are phenotypically different from the parental line. We examined the early responses of MCF-7 cells following either exposure to 4-hydroxytamoxifen or deprivation of estrogen for periods of 2 days–4 weeks.MethodsEndocrine-sensitive or -resistant breast cancer cell lines were used to examine the expression of the stem cell gene SOX2, and the Wnt effector genes AXIN2 and DKK1 using quantitative PCR analysis. Breast cancer cell lines were used to assess the anti-proliferative effects (as determined by IC50 values of Wnt pathway inhibitors LGK974 and IWP-2.ResultsHormone therapy led to time-dependent increases of up to 10-fold in SOX2 expression, up to threefold in expression of the Wnt target genes AXIN2 and DKK1, and variable changes in NANOG and OCT4 expression. The cells also showed increased mammosphere formation and increased CD24 surface protein expression. Some but not all hormone-resistant MCF-7 sub-lines, emerging after long-term hormonal stress, showed up to 50-fold increases in SOX2 expression and smaller increases in AXIN2 and DKK1 expression. However, the increase in Wnt target gene expression was not accompanied by an increase in sensitivity to Wnt pathway inhibitors LGK974 and IWP-2. A general trend of lower IC50 values was observed in 3-dimensional spheroid culture conditions (which allowed enrichment of cells with cancer stem cell phenotype relative to monolayer cultures. The endocrine-resistant cell lines showed no significant increase in sensitivity to Wnt inhibitors

  17. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Science.gov (United States)

    Marciniak, Anja; Selck, Claudia; Friedrich, Betty; Speier, Stephan

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  18. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Directory of Open Access Journals (Sweden)

    Anja Marciniak

    Full Text Available Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  19. Clinical and Genetic Analysis of Multiple Endocrine Neoplasia Type 1-Related Primary Hyperparathyroidism in Chinese.

    Directory of Open Access Journals (Sweden)

    Jing Kong

    Full Text Available Multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT differs in many aspects from sporadic PHPT (SHPT. The aims of this study were to summarize the clinical features and genetic background of Chinese MHPT patients and compare the severity of the disease with those of SHPT.A total of 40 MHPT (27 sporadic, 7 families and 169 SHPT cases of Chinese descent were retrospectively analyzed. X-rays and ultrasound were used to assess the bone and urinary system. Dual energy x-ray absorptiometry (DXA were performed to measure bone mineral density (BMD. Besides direct sequencing of the MEN1 and CDKN1B genes, multiplex ligation-dependent probe amplification (MLPA was used to screen gross deletion for the MEN1 gene.Compared with SHPT patients, MHPT patients showed lower prevalence of typical X-ray changes related to PHPT (26.3% vs. 55.7%, P = 0.001 but higher prevalence of urolithiasis/renal calcification (40.2% vs. 60.0%, P = 0.024. MHPT patients showed higher phosphate level (0.84 vs. 0.73mmol/L, P<0.05 but lower ALP (103.0 vs. 174.0U/L, P<0.001 and PTH (4.0 vs. 9.8×upper limit, P<0.001 levels than SHPT patients. There were no significant differences in BMD Z-scores at the lumbar spine and femoral neck between the two groups. Mutations in the MEN1 gene were detected in 27 MHPT cases. Among the nine novel mutations were novel, one of them involved the deletion of exon 5 and 6.MHPT patients experienced more common kidney complications but less skeletal issues, and a milder biochemical manifestation compared with SHPT patients. MEN1 mutation detection rate was 79.4% and 9 of the identified mutations were novel.

  20. Celiac disease and endocrine autoimmunity.

    Science.gov (United States)

    Kahaly, George J; Schuppan, Detlef

    2015-01-01

    Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

  1. Endocrine Regulation of T-cell Development and Peripheral T-cell Maturation

    NARCIS (Netherlands)

    K. van der Weerd (Kim)

    2013-01-01

    markdownabstract__Abstract__ During the last century a large number of studies have demonstrated that complex interplay exists between the immune and the neuro-endocrine systems. This interplay, via shared cytokines, hormones and their respective receptors and nervous innervations, results in a

  2. Retinol dehydrogenase-10 regulates pancreas organogenesis and endocrine cell differentiation via paracrine retinoic acid signalling

    DEFF Research Database (Denmark)

    Arregi, Igor; Climent, Maria; Iliev, Dobromir

    2016-01-01

    Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here we show that Retinol dehydrogenase-10 (Rdh......10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme. Rdh10 null mutant mouse embryos exhibited dorsal pancreas agenesis...... and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Conditional disruption of Rdh10 from the endoderm caused increased mortality, reduced body weight and lowered blood glucose levels after birth. Endodermal Rdh10 deficiency led to a smaller dorsal pancreas with a reduced density of early...

  3. [The immuno-endocrine system. A new endocrine theory: the problem of the packed transport].

    Science.gov (United States)

    Csaba, György

    2011-05-15

    Since the eighties of the last century hormone content was justified in immune cells (lymphocytes, granulocytes, monocytes, macrophages and mast cells), which produce, store and secrete these hormones. Although the amount of these materials in immune cells is relatively small, the mass of the producers (immune cells) is so large, that the phenomenon must be considered from endocrinological point of view, underlying the important differences between the "classical" and immuno-endocrine systems. Cells of the classic (built-in) endocrine system are mono-producers, while immune cells can synthesize many types of hormones (polyproducers). In addition, these cells can transport the whole hormone-producing machinery to the site of need, producing a local effect. This can be observed, for example, in the case of endorphin producing immune cells during inflammation and during early pregnancy around the chorionic villi. Hormone producing immune cells also have receptors for many hormones, so that they are poly-receivers. Via hormone producing and receiving capacity there is a bidirectional connection between the neuro-endocrine and immuno-endocrine systems. In addition, there is a network inside the immuno-endocrine system. The packed transport theory attempts to explain the mechanism and importance of the immuno-endocrine system.

  4. Effects of the Endocrine-Disrupting Chemical DDT on Self-Renewal and Differentiation of Human Mesenchymal Stem Cells

    Science.gov (United States)

    Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F.B.; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth P.

    2014-01-01

    Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear. Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology. Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs. Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells. Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs. Citation: Strong AL, Shi Z, Strong MJ, Miller DF, Rusch DB, Buechlein AM, Flemington EK

  5. Stimulatory effects of combined endocrine disruptors on MA-10 Leydig cell steroid production and lipid homeostasis

    International Nuclear Information System (INIS)

    Jones, Steven; Boisvert, Annie; Naghi, Andrada; Hullin-Matsuda, Françoise; Greimel, Peter; Kobayashi, Toshihide; Papadopoulos, Vassilios; Culty, Martine

    2016-01-01

    Previous work in our laboratory demonstrated that in-utero exposure to a mixture of the phytoestrogen Genistein (GEN), and plasticizer DEHP, induces short- and long-term alterations in testicular gene and protein expression different from individual exposures. These studies identified fetal and adult Leydig cells as sensitive targets for low dose endocrine disruptor (ED) mixtures. To further investigate the direct effects and mechanisms of toxicity of GEN and DEHP, MA-10 mouse tumor Leydig cells were exposed in-vitro to varying concentrations of GEN and MEHP, the principal bioactive metabolite of DEHP. Combined 10 μM GEN + 10 μM MEHP had a stimulatory effect on basal progesterone production. Consistent with increased androgenicity, the mRNA of steroidogenic and cholesterol mediators Star, Cyp11a, Srb1 and Hsl, as well as upstream orphan nuclear receptors Nr2f2 and Sf1 were all significantly increased uniquely in the mixture treatment group. Insl3, a sensitive marker of Leydig endocrine disruption and cell function, was significantly decreased by combined GEN + MEHP. Lipid analysis by high-performance thin layer chromatography demonstrated the ability of combined 10 μM combined GEN + MEHP, but not individual exposures, to increase levels of several neutral lipids and phospholipid classes, indicating a generalized deregulation of lipid homeostasis. Further investigation by qPCR analysis revealed a concomitant increase in cholesterol (Hmgcoa) and phospholipid (Srebp1c, Fasn) mediator mRNAs, suggesting the possible involvement of upstream LXRα agonism. These results suggest a deregulation of MA-10 Leydig function in response to a combination of GEN + MEHP. We propose a working model for GEN + MEHP doses relevant to human exposure involving LXR agonism and activation of other transcription factors. Taken more broadly, this research highlights the importance of assessing the impact of ED mixtures in multiple toxicological models across a range of environmentally

  6. Endocrine Regulation of T-cell Development and Peripheral T-cell Maturation

    OpenAIRE

    Weerd, Kim

    2013-01-01

    markdownabstract__Abstract__ During the last century a large number of studies have demonstrated that complex interplay exists between the immune and the neuro-endocrine systems. This interplay, via shared cytokines, hormones and their respective receptors and nervous innervations, results in a highly organized integrated surveillance system capable of preserving homeostasis of the body to a large numbers of disturbances. Within this surveillance system the immune system recognizes external (...

  7. Endocrine system: part 1.

    Science.gov (United States)

    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.

  8. Androgen receptor expression in Circulating Tumor Cells from castration-resistant prostate cancer patients with novel endocrine agents

    NARCIS (Netherlands)

    Crespo, M.; van Dalum, Guus; Ferraldeschi, R.; Zafeiriou, Z.; Sideris, S.; Lorente, D.; Bianchini, D.; Rodrigues, D.N.; Rijsnaes, R.; Miranda, S.; Figueiredo, I.; Flohr, P.; Nowakowska, K.; de Bono, J.S.; Terstappen, Leonardus Wendelinus Mathias Marie; Attard, G.

    2015-01-01

    Background: Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated

  9. Prolactin-secreting adenoma as part of the multiple endocrine neoplasia--type I (MEN-I) syndrome.

    Science.gov (United States)

    Levine, J H; Sagel, J; Rosebrock, G; Gonzalez, J J; Nair, R; Rawe, S; Powers, J M

    1979-06-01

    Two patients presented with the galactorrhea-amenorrhea syndrome. One patient had previously had parathyroid hyperplasia and the other an insulinoma. Preoperative evaluation of each patient revealed hyperprolactinemia and radiological evidence of an abnormal sella turcica. Pituitary adenomas were identified and removed at surgery. Immunostaining techniques confirmed the presence of prolactin-containing cells in both tumors. We propose that prolactin-secreting tumors be considered as part of the MEN-I syndrome, and that patients presenting with the galactorrhea-amenorrhea syndrome be screened and followed sequentially for evidence of other endocrine neoplasia.

  10. Endocrine system and obesity.

    Science.gov (United States)

    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. Copyright © 2010. Published by Elsevier Inc.

  11. Regeneration of pancreatic non-β endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin.

    Directory of Open Access Journals (Sweden)

    Yanqing Zhang

    Full Text Available The non-β endocrine cells in pancreatic islets play an essential counterpart and regulatory role to the insulin-producing β-cells in the regulation of blood-glucose homeostasis. While significant progress has been made towards the understanding of β-cell regeneration in adults, very little is known about the regeneration of the non-β endocrine cells such as glucagon-producing α-cells and somatostatin producing δ-cells. Previous studies have noted the increase of α-cell composition in diabetes patients and in animal models. It is thus our hypothesis that non-β-cells such as α-cells and δ-cells in adults can regenerate, and that the regeneration accelerates in diabetic conditions. To test this hypothesis, we examined islet cell composition in a streptozotocin (STZ-induced diabetes mouse model in detail. Our data showed the number of α-cells in each islet increased following STZ-mediated β-cell destruction, peaked at Day 6, which was about 3 times that of normal islets. In addition, we found δ-cell numbers doubled by Day 6 following STZ treatment. These data suggest α- and δ-cell regeneration occurred rapidly following a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling techniques, we demonstrated α- and δ-cell regeneration involved cell proliferation. Co-staining of the islets with the proliferating cell marker Ki67 showed α- and δ-cells could replicate, suggesting self-duplication played a role in their regeneration. Furthermore, Pdx1(+/Insulin(- cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. This is further confirmed by the detection of Pdx1(+/glucagon(+ cells and Pdx1(+/somatostatin(+ cells following STZ treatment. Taken together, our study demonstrated adult α- and δ-cells could regenerate, and both self-duplication and regeneration from endocrine precursor cells were involved in their regeneration.

  12. Reporter cell lines for the characterization of the interactions between nuclear receptors and endocrine disruptors

    Directory of Open Access Journals (Sweden)

    marina egrimaldi

    2015-05-01

    Full Text Available Endocrine-disrupting chemicals (EDCs are exogenous substances interfering with hormone biosynthesis, metabolism, or action, and consequently causing disturbances in the endocrine system. Various pathways are activated by EDCs, including interactions with nuclear receptors (NRs which are primary targets of numerous environmental contaminants.The main NRs targeted by environmental contaminants are the estrogen (ER α, β and the androgen (AR receptors. ERs and AR have pleiotropic regulatory roles in a diverse range of tissues, notably in the mammary gland, the uterus and the prostate. Thus, dysfunctional ERs and AR signaling due to inappropriate exposure to environmental pollutants may lead to hormonal cancers and infertility. The pregnane X receptor (PXR is also recognized by many environmental molecules. PXR has a protective role of the body through its ability to regulate proteins involved in the metabolism, the conjugation and the transport of many exogenous and endogenous compounds. However, the permanent activation of this receptor by xenobiotics may lead to premature drug metabolism, the formation and accumulation of toxic metabolites and defects in hormones homeostasis. The activity of other NRs can also be affected by environmental molecules. Compounds capable of inhibiting or activating the estrogen related (ERRγ, the thyroid hormone (TRα, β, the retinoid X receptors (RXRα, β, γ and peroxisome proliferator-activated (PPAR α, γ receptors have been identified and are highly suspected to promote developmental, reproductive, neurological, or metabolic diseases in humans and wildlife.In this review we provide an overview of reporter cell lines established to characterize the human NR activities of a large panel of EDCs including natural as well as industrial compounds such as pesticides, plasticizers, surfactants, flame retardants and cosmetics.

  13. Circadian rhythm of the Leydig cells endocrine function is attenuated during aging.

    Science.gov (United States)

    Baburski, Aleksandar Z; Sokanovic, Srdjan J; Bjelic, Maja M; Radovic, Sava M; Andric, Silvana A; Kostic, Tatjana S

    2016-01-01

    Although age-related hypofunction of Leydig cells is well illustrated across species, its circadian nature has not been analyzed. Here we describe changes in circadian behavior in Leydig cells isolated from adult (3-month) and aged (18- and 24-month) rats. The results showed reduced circadian pattern of testosterone secretion in both groups of aged rats despite unchanged LH circadian secretion. Although arrhythmic, the expression of Insl3, another secretory product of Leydig cells, was decreased in both groups. Intracellular cAMP and most important steroidogenic genes (Star, Cyp11a1 and Cyp17a1), together with positive steroidogenic regulator (Nur77), showed preserved circadian rhythm in aging although rhythm robustness and expression level were attenuated in both aged groups. Aging compromised cholesterol mobilization and uptake by Leydig cells: the oscillatory transcription pattern of genes encoding HDL-receptor (Scarb1), hormone sensitive lipase (Lipe, enzyme that converts cholesterol esters from lipid droplets into free cholesterol) and protein responsible for forming the cholesterol esters (Soat2) were flattened in 24-month group. The majority of examined clock genes displayed circadian behavior in expression but only a few of them (Bmal1, Per1, Per2, Per3 and Rev-Erba) were reduced in 24-month-old group. Furthermore, aging reduced oscillatory expression pattern of Sirt1 and Nampt, genes encoding key enzymes that connect cellular metabolism and circadian network. Altogether circadian amplitude of Leydig cell's endocrine function decreased during aging. The results suggest that clock genes are more resistant to aging than genes involved in steroidogenesis supporting the hypothesis about peripheral clock involvement in rhythm maintenance during aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Immunocytochemical detection of glucagon and insulin cells in endocrine pancreas and cyclic disparity of plasma glucose in the turtle Melanochelys trijuga.

    Science.gov (United States)

    Chandavar, Vidya R; Naik, Prakash R

    2008-06-01

    The present investigation was carried out to know the seasonal variation in plasma glucose,insulin and glucagon cells during the reproductive cycle of untreated Melanochelys trijuga. Pancreatic endocrine cells were immunochemically localized.Insulin-immunoreactive (IR) cells occurred in groups of 3-20 and were in close apposition, while glucagon-IR cells were distributed individually between the exocrine pancreas or formed anastomosing cords where cells were not intimately attached. Whenever both IR cell types were present together forming an islet,insulin-IR cells formed clusters in the centre with glucagon-IR cells being scattered at the periphery. Glucagon-IR cells seemed to be secretory throughout the pancreas during the reproductive cycle,while insulin-IR cells were found to be pulsating in their secretion. Mean size of the islet was 1.306, 0.184 and 2.558 mm in the regenerative, reproductive and regressive periods,respectively. In general,insulin-IR cells measured 5.18 (mu)m and glucagon-IR cells 5.22 (mu)m in their longest axis. Invariably, glucagon-IR cells were more in number than insulin-IR cells. The fasting plasma glucose level was 69.97 mg% during the regenerative period, which increased to 97.96 mg% during the reproductive period,and reached a peak value of 113.52 mg% in the regressive period.

  15. Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution.

    Science.gov (United States)

    Yoshitomi, Munetake; Ohta, Keisuke; Kanazawa, Tomonoshin; Togo, Akinobu; Hirashima, Shingo; Uemura, Kei-Ichiro; Okayama, Satoko; Morioka, Motohiro; Nakamura, Kei-Ichiro

    2016-10-31

    Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

  16. Corticosteroid production in H295R cells during exposure to 3 endocrine disrupters analyzed with LC-MS/MS

    DEFF Research Database (Denmark)

    Winther, Christina S; Nielsen, Frederik K; Hansen, Martin

    2013-01-01

    295R cell line. The method was applied by studying the effects of 2 model endocrine disrupters, ketoconazole and prochloraz, the pharmaceutical budesonide, and the inducer forskolin on the steroid production in this cell line. Dose-response curves were obtained for the correlation between hormone...... concentrations and the concentration of the individual disruptors. Exposing cells to ketoconazole resulted in a decrease in cortisol and corticosterone concentrations in a dose-dependent manner with EC₅₀ values of 0.24 and 0.40 μmol/L, respectively. The same applied for cells exposed to prochloraz with EC₅₀...

  17. Generation of hepatocyte- and endocrine pancreatic-like cells from human induced endodermal progenitor cells

    NARCIS (Netherlands)

    Sambathkumar, Rangarajan; Akkerman, Renate; Dastidar, Sumitava; Roelandt, Philip; Kumar, Manoj; Bajaj, Manmohan; Mestre Rosa, Ana Rita; Helsen, Nicky; Vanslembrouck, Veerle; Kalo, Eric; Khurana, Satish; Laureys, Jos; Gysemans, Conny; Faas, Marijke M; de Vos, Paul; Verfaillie, Catherine M

    2018-01-01

    Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14

  18. Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of Regenerating Gene (REG protein in fulminant type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Kaoru Aida

    Full Text Available BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs, extracellular matrix (ECM, and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. RESULT: Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. CONCLUSION: The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.

  19. [A Case of Endocrine Cell Carcinoma of the Transverse Colon with Very Poor Prognosis, Onset with Bowel Obstruction].

    Science.gov (United States)

    Yabe, Sakiko; Yamamoto, Eisuke; Masuda, Taiki; Sugimoto, Hitoshi; Koshiishi, Haruya; Yoshimura, Tetsunori

    2018-01-01

    We report a case of endocrine cell carcinoma of the colon with very poor prognosis, onset with bowel obstruction and multiple liver metastases. The patient was a 77-year-old man who underwent left hemicolectomy after a colon stent treatment for bowel obstruction due to cancer of the transverse colon with unresectable multiple liver metastases. Chemotherapy was not initiated because of his poor health. He died of primary cancer 52 days after the surgery. Endocrine cell carcinoma of the large intestine has a poor prognosis due to an early onset of liver and lymph node metastases, as well as peritoneal dissemination. A large-scale clinical study is needed to establish an effective adjuvant chemotherapy.

  20. The Acid-Secreting Parietal Cell as an Endocrine Source of Sonic Hedgehog During Gastric Repair

    Science.gov (United States)

    Engevik, Amy C.; Feng, Rui; Yang, Li

    2013-01-01

    Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Despite its known function in tissue regeneration, the role of Shh secreted from the gastric epithelium during tissue repair in the stomach remains unknown. Here we tested the hypothesis that Shh secreted from the acid-secreting parietal cell is a fundamental circulating factor that drives gastric repair. A mouse model expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated using animals bearing loxP sites flanking exon 2 of the Shh gene (Shhflx/flx) and mice expressing a Cre transgene under the control of the H+,K+-ATPase β-subunit promoter. Shhflx/flx, the H+,K+-ATPase β-subunit promoter, and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury. At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood samples were collected. Parabiosis experiments were used to establish the effect of circulating Shh on ulcer repair. Control mice exhibited an increased expression of Shh in the gastric tissue and plasma that correlated with the repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis experiment whereby a control mouse was paired with a PC-ShhKO littermate and both animals subjected to gastric injury, a significant increase in the circulating Shh was measured in both parabionts. Elevated circulating Shh concentrations correlated with the repair of gastric ulcers in the PC-ShhKO parabionts. Therefore, the acid-secreting parietal cell within the stomach acts as an endocrine source of Shh during repair. PMID:24092639

  1. Endocrine dysfunction in Taiwanese children with human chorionic gonadotropin-secreting germ cell tumors

    Directory of Open Access Journals (Sweden)

    Chien-Ming Lin

    2014-02-01

    Conclusion: Taiwanese children with HCG-secreting GCTs often have clinical manifestations related to endocrine dysfunction. High index of suspicion is important to avoid delayed diagnosis in these children.

  2. Ghrelin – a pleiotropic hormone secreted from endocrine X/A-like cells of the stomach

    Directory of Open Access Journals (Sweden)

    Andreas eStengel

    2012-02-01

    Full Text Available The gastric X/A-like endocrine cell receives growing attention due it its peptide products with ghrelin being the best characterized. This peptide hormone was identified a decade ago as a stimulator of food intake and to date remains the only known peripherally produced and centrally acting orexigenic hormone. In addition, subsequent studies identified numerous other functions of this peptide including the modulation of gastrointestinal motility, the maintenance of energy homeostasis and an impact on reproduction. Moreover, ghrelin is also involved in the response to stress and assumed to play a role in coping functions and exert a modulatory action on immune pathways. Our knowledge on the regulation of ghrelin has markedly advanced during the past years by the identification of the ghrelin acylating enzyme, ghrelin-O-acyltransferase, and by the description of changes in expression, activation and release under different metabolic as well as physically and psychically challenging conditions. However, our insight on regulatory processes of ghrelin at the cellular and subcellular levels is still very limited and warrants further investigation.

  3. Simultaneous effects of endocrine disruptor bisphenol A and flavonoid fisetin on progesterone production by granulosa cells.

    Science.gov (United States)

    Bujnakova Mlynarcikova, Alzbeta; Scsukova, Sona

    2018-04-01

    In the present study, we aimed to examine effects of different concentrations of the endocrine disruptor Bisphenol A (BPA; 1 nM, 1 μM, 100 μM) and the flavonoid fisetin (1, 10, 25, 50 μM), individually and in combinations, on steroidogenic function of porcine ovarian granulosa cells (GCs) represented by progesterone production. We confirmed that BPA inhibited progesterone production by GCs at the highest concentration. Fisetin reduced gonadotropin-stimulated progesterone synthesis dose-dependently, and in this manner, fisetin impaired progesterone production when added to BPA-treated GCs. The mechanisms of the inhibitory effects of the combinations included a significant down-regulation of the key steroidogenesis-related genes (STAR, CYP11A1, HSD3B). Our findings suggest for the first time that fisetin might interfere with ovarian steroidogenesis, and might not have beneficial but rather aggravating effects in terms of modulating progesterone synthesis altered by high concentrations of BPA. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Purinergic signaling pathways in endocrine system.

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

    2015-09-01

    Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

  5. Purinergic Signaling Pathways in Endocrine System

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

    2015-01-01

    Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

  6. Islet Cells Serve as Cells of Origin of Pancreatic Gastrin-Positive Endocrine Tumors

    DEFF Research Database (Denmark)

    Bonnavion, Rémy; Teinturier, Romain; Jaafar, Rami

    2015-01-01

    The cells of origin of pancreatic gastrinomas remain an enigma, since no gastrin-expressing cells are found in the normal adult pancreas. It was proposed that the cellular origin of pancreatic gastrinomas may come from either the pancreatic cells themselves or gastrin-expressing cells which have ...

  7. Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

    International Nuclear Information System (INIS)

    Peppa, Melpomeni; Brountzos, Elias; Economopoulos, Nicolaos; Boutati, Eleni; Pikounis, Vasilios; Patapis, Paul; Economopoulos, Theofanis; Raptis, Sotirios A.; Hadjidakis, Dimitrios

    2009-01-01

    Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.

  8. Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Dhalapathy Sadacharan

    2013-01-01

    Full Text Available Thymic neuroendocrine (NE tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1. They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT at the time of parathyroid surgery for primary hyperparathyroidism (PHPT in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.

  9. Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells

    International Nuclear Information System (INIS)

    Drooge, Barend L. van; Marqueño, Anna; Grimalt, Joan O.; Fernández, Pilar; Porte, Cinta

    2017-01-01

    Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. - Highlights: • Organic extracts of outdoor ambient air PM1 showed aromatase activity inhibition in exposed human placental JEG-3 cells. • Cytotoxicity and strongest endocrine disruption was observed in rural winter samples, while lowest inhibition was observed in urban background site 50 m above a busy street. • Cytotoxicity and aromatase activity inhibition in the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning. - Organic extracts from ambient air PM 1 related to biomass burning are more cytotoxic and have stronger endocrine disruption potential than urban PM 1 .

  10. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

    Directory of Open Access Journals (Sweden)

    Christine Wittig

    Full Text Available 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 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 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.

  11. The cell-specific pattern of cholecystokinin peptides in endocrine cells versus neurons is governed by the expression of prohormone convertases 1/3, 2, and 5/6

    DEFF Research Database (Denmark)

    Bundgaard, J.R.; Hannibal, J.; Zhu, X.

    2008-01-01

    Most peptide hormone genes are, in addition to endocrine cells, also expressed in neurons. The peptide hormone cholecystokinin (CCK) is expressed in different molecular forms in cerebral neurons and intestinal endocrine cells. To understand this difference, we examined the roles of the neuroendoc...

  12. Interaction of fast and slow dynamics in endocrine control systems with an application to β-cell dynamics.

    Science.gov (United States)

    Wang, Yi-Fang; Khan, Michael; van den Berg, Hugo A

    2012-01-01

    Endocrine dynamics spans a wide range of time scales, from rapid responses to physiological challenges to with slow responses that adapt the system to the demands placed on it. We outline a non-linear averaging procedure to extract the slower dynamics in a way that accounts properly for the non-linear dynamics of the faster time scale and is applicable to a hierarchy of more than two time scales, although we restrict our discussion to two scales for the sake of clarity. The procedure is exact if the slow time scale is infinitely slow (the dimensionless ε-quantity is the period of the fast time scale fluctuation times an upper bound to the slow time scale rate of change). However, even for an imperfect separation of time scales we find that this construction provides an excellent approximation for the slow-time dynamics at considerably reduced computational cost. Besides the computation advantage, the averaged equation provided a qualitative insight into the interaction of the time scales. We demonstrate the procedure and its advantages by applying the theory to the model described by Tolić et al. [I.M. Tolić, E. Mosekilde, J. Sturis, Modeling the insulin-glucose feedback system: the significance of pulsatile insulin secretion, J. Theor. Biol. 207 (2000) 361-375.] for ultradian dynamics of the glucose-insulin homeostasis feedback system, extended to include β-cell dynamics. We find that the dynamics of the β-cell mass are dependent not only on the glycemic load (amount of glucose administered to the system), but also on the way this load is applied (i.e. three meals daily versus constant infusion), effects that are lost in the inappropriate methods used by the earlier authors. Furthermore, we find that the loss of the protection against apoptosis conferred by insulin that occurs at elevated levels of insulin has a functional role in keeping the β-cell mass in check without compromising regulatory function. We also find that replenishment of β-cells from a

  13. Enucleation and limited pancreatic resection provide long-term cure for insulinoma in multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Bartsch, Detlef K; Albers, Max; Knoop, Richard; Kann, Peter H; Fendrich, Volker; Waldmann, Jens

    2013-01-01

    To assess the characteristics and long-term outcome after surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated insulinoma. Retrospective analysis of prospectively collected data of MEN1 patients with organic hyperinsulinism at a tertiary referral center. Thirteen (17%) of 74 patients with MEN1 had organic hyperinsulinism. The median age at diagnosis was 27 (range 9-48) years. In 7 patients insulinoma was the first manifestation of the syndrome. All patients had at least one pancreatic neuroendocrine neoplasm (pNEN) upon imaging, including CT, MRI or endoscopic ultrasonography. Seven patients had solitary lesions upon imaging, 4 patients had one dominant tumor with coexisting multiple small pNENs, and 2 patients had multiple lesions without dominance. Eight patients had limited resections (1 segmental resection, 7 enucleations), 4 subtotal distal pancreatectomies, and 1 patient a partial duodenopancreatectomy. There was no postoperative mortality. Six patients experienced complications, including pancreatic fistula in 5 patients. Pathological examination revealed median three (range 1-14) macro-pNENs sized between 6 and 40 mm, and a total of 14 potentially benign insulinomas were detected in the 13 patients. After median follow-up of 156 months, only 1 patient developed recurrent hyperinsulinism after initial enucleation. Twelve patients developed new pNENs in the pancreatic remnant and 4 patients underwent reoperations (3 for metastatic ZES, 1 for recurrent hyperinsulinism). One of 5 patients with an initial extended pancreatic resection developed insulin-dependent diabetes mellitus. Enucleation and limited resection provide long-term cure for MEN1 insulinoma in patients with solitary or dominant tumors. Subtotal distal pancreatectomy should thus be preserved for patients with multiple pNENs without dominance given the risk of exocrine and endocrine pancreas insufficiency in the mostly young patients. © 2013 S. Karger AG, Basel.

  14. Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2

    Science.gov (United States)

    Kluijfhout, Wouter P.; van Beek, Dirk-Jan; Verrijn Stuart, Annemarie A.; Lodewijk, Lutske; Valk, Gerlof D.; van der Zee, David C.; Vriens, Menno R.; Borel Rinkes, Inne H.M.

    2015-01-01

    Abstract The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients. Hardly any literature exists on complications in the very young. A retrospective single-center analysis was performed on the outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy after January 1993 and at least 6 months of follow-up were included, subdivided in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients older than 6 years. Postoperative hypocalcemia and other complications were registered. Twelve (27%) patients developed transient hypocalcemia and 9 (20%) patients suffered from permanent hypocalcemia, with a nonsignificant trend toward higher incidence with decreasing age. Three (7%) patients had other complications, of whom 2 were younger than 3 years. For patients younger than 3 years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days, respectively, for the older patient groups (P < 0.05). Patients with complications had a longer LOS compared with patients without (5.0 vs 2.0, P < 0.01). None of the patients had clinical signs of recurrent MTC after a mean follow-up of 10.5 years. Prophylactic thyroidectomy in very young children is associated with a higher rate of complications, causing a significant increased LOS. Irrespective age of surgery, MTC did not recur in any patient. In planning optimal timing of surgery, clinicians should take the risk of complications into account. We advise not to perform total

  15. Endocrine Disrupting Chemicals (EDCs)

    Science.gov (United States)

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

  16. A Review of Fatigue Condition in Patients with Type II Diabetes in Isfahan Endocrine and Metabolism Research Center

    Directory of Open Access Journals (Sweden)

    Nasim Vard

    2016-07-01

    Full Text Available Complications of Diabetes such as Fatigue is a serious obstacle hindering the enhancement of health behaviors, including participation in Diabetes self-care programs, and is considered as a challenging problem for nurses and health-care providers in the process of diseases’ treatments and therapies. These complications not only influence the patients’ quality of life, but also, increases the risk of complications. Hence, regarding the importance of the role of fatigue and its subsequent effects on Diabetes’ control as well as the paucity of studies carried out in this field, the current research intended to review fatigue condition in patients with type II Diabetes in Isfahan Endocrine and Metabolism Research Center. The nature of this study is a Quantitative-Descriptive research. For the purpose of the present study, 195 patients with type II Diabetes were selected as the target sample population, based on Non-probability Convenience Sampling Method, from Isfahan Endocrine and Metabolism Research Center. To collect the research data, the researcher used a two-part written questionnaire encompassing Personal Information and Multidimensional Fatigue Symptom Inventory- Short Form (MFSI-SF as the data collection tool. Each of the participants in the present research were briefly advised about the nature and objectives of the research and they were interviewed by the researcher to complete the questionnaire after consent reached with the patients. The collected data was analyzed by SPSS16 statistical analysis software; accordingly the significance level of all the tests was estimated as P˂0.05. The results of the data analysis showed that %85.1 of the patients suffered from fatigue. There was a statistically significant difference between the mean of the severity of fatigue condition between female and male patients in the present study, i.e.23.22 ± 17.49 for women and 13.24 ± 17.73 for men, indexing a significance level of P˂0

  17. Relationship of visfatin level to pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index in overweight women who performed hydraulic resistance exercise

    OpenAIRE

    Ha, Chang Ho; Swearingin, Brenda; Jeon, Yong Kyun

    2015-01-01

    [Purpose] This study aimed to examine the correlation of visfatin level to pancreatic endocrine hormone level, homeostasis model assessment of insulin resistance (HOMA-IR) index, and HOMA β-cell index in hydraulic resistance exercise. Furthermore, it investigated the relationship between visfatin level and other variables affected by exercise in overweight women. [Subjects and Methods] The exercise group trained for 12 weeks, 70 minutes/day, 5 days/week. Visfatin level, pancreatic endocrine h...

  18. Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.

    Science.gov (United States)

    Pyarokhil, Asadullah Hamid; Ishihara, Miyuki; Sasaki, Motoki; Kitamura, Nobuo

    2012-04-10

    The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Circelli, Luisa; Ramundo, Valeria; Marotta, Vincenzo; Sciammarella, Concetta; Marciello, Francesca; Del Prete, Michela; Sabatino, Lina; Pasquali, Daniela; Izzo, Francesco; Scala, Stefania; Colao, Annamaria; Faggiano, Antongiulio; Colantuoni, Vittorio

    2015-07-01

    CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype-phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. Endocrine Diseases

    Science.gov (United States)

    ... Syndrome (PCOS) Pregnancy and Thyroid Disease Primary Hyperparathyroidism Prolactinoma Thyroid Tests Turner Syndrome Contact Us The National ... Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...

  1. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  2. Application of the thiocarbohydrazide method for vicinal glycol group detection to the study of gastric mucosa endocrine cells.

    Science.gov (United States)

    Lefranc, G; Chung, Y T; Barrière, P; Pradal, G

    1980-01-01

    The thiocarbohydrazide-silver proteinate (TCH SP) method was applied to the study of cat, rabbit and mouse gastric mucosa endocrine cells. After 24-h treatment with thiocarbohydrazide (TCH), glycogen was seen in the hyaloplasm of X, D, P, A and O cells but not in EC, EC-like or D1 cells. With flotation times as short as 30 to 40 min glycogen was readily detected in X cells. Secretory granules of EC cells were constantly stained, while those of D1 cells failed to react. In most experiments granules of X, A and O cells showed peripheral "staining", while in others staining of variable intensity affected the entire granular cross-section in X, D and P cells. With 72-h exposure to TCH, EC and EC-like cells showed particles resembling glycogen, even staining or only peripheral staining of certain EC cell granules. From the results of this and previous studies, EC cell staining is believed to be due wholly or partly, according to exposure times, to the action of silver proteinate, while that of certain non-EC cells is probably a specific indicator of complexed carbohydrates.

  3. Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634).

    Science.gov (United States)

    Jesić, Maja D; Tancić-Gajić, Milina; Jesić, Milos M; Zivaljević, Vladan; Sajić, Silvija; Vujović, Svetlana; Damjanović, Svetozar

    2014-01-01

    The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. This is a case report of 3-year-old boy from the MEN 2A family (the boy's father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is < 2 pg/ml (normal < 13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

  4. Proliferative endocrine effects of adipose tissue from obese animals on MCF7 cells are ameliorated by resveratrol supplementation.

    Science.gov (United States)

    Theriau, Christopher F; Sauvé, O'Llenecia S; Beaudoin, Marie-Soleil; Wright, David C; Connor, Michael K

    2017-01-01

    Obesity is clearly associated with an increased risk of breast cancer in postmenopausal women. The purpose was to determine if obesity alters the adipocyte adipokine secretion profile, thereby altering the adipose-dependent paracrine/endocrine growth microenvironment surrounding breast cancer cells (MCF7). Additionally, we determined whether resveratrol (RSV) supplementation can counteract any obesity-dependent effects on breast cancer tumor growth microenvironment. Obese ZDF rats received standard chow diet or diet supplemented with 200 mg/kg body weight RSV. Chow-fed Zucker rats served as lean controls. After 6 weeks, conditioned media (CM) prepared from inguinal subcutaneous adipose tissue (scAT) was added to MCF7 cells for 24 hrs. Experiments were also conducted using purified isolated adipocytes to determine whether any endocrine effects could be attributed specifically to the adipocyte component of adipose tissue. scAT from ZDF rats promoted cell cycle entry in MCF7 cells which was counteracted by RSV supplementation. RSV-CM had a higher ratio of ADIPO:LEP compared to ZDF-CM. This altered composition of the CM led to increased levels of pAMPKT172, p27, p27T198 and AdipoR1 while decreasing pAktT308 in MCF7 cells grown in RSV-CM compared to ZDF-CM. RSV-CM increased number of cells in G0/G1 and decreased cells in S-phase compared to ZDF-CM. Co-culture experiments revealed that these obesity-dependent effects were driven by the adipocyte component of the adipose tissue. Obesity decreased the ratio of adiponectin:leptin secreted by adipocytes, altering the adipose-dependent growth microenvironment resulting in increased breast cancer cell proliferation. Supplementation with RSV reversed these adipose-dependent effects suggesting a potential for RSV as a nutritional supplementation to improve breast cancer treatment in obese patients.

  5. Proliferative endocrine effects of adipose tissue from obese animals on MCF7 cells are ameliorated by resveratrol supplementation.

    Directory of Open Access Journals (Sweden)

    Christopher F Theriau

    Full Text Available Obesity is clearly associated with an increased risk of breast cancer in postmenopausal women. The purpose was to determine if obesity alters the adipocyte adipokine secretion profile, thereby altering the adipose-dependent paracrine/endocrine growth microenvironment surrounding breast cancer cells (MCF7. Additionally, we determined whether resveratrol (RSV supplementation can counteract any obesity-dependent effects on breast cancer tumor growth microenvironment. Obese ZDF rats received standard chow diet or diet supplemented with 200 mg/kg body weight RSV. Chow-fed Zucker rats served as lean controls. After 6 weeks, conditioned media (CM prepared from inguinal subcutaneous adipose tissue (scAT was added to MCF7 cells for 24 hrs. Experiments were also conducted using purified isolated adipocytes to determine whether any endocrine effects could be attributed specifically to the adipocyte component of adipose tissue. scAT from ZDF rats promoted cell cycle entry in MCF7 cells which was counteracted by RSV supplementation. RSV-CM had a higher ratio of ADIPO:LEP compared to ZDF-CM. This altered composition of the CM led to increased levels of pAMPKT172, p27, p27T198 and AdipoR1 while decreasing pAktT308 in MCF7 cells grown in RSV-CM compared to ZDF-CM. RSV-CM increased number of cells in G0/G1 and decreased cells in S-phase compared to ZDF-CM. Co-culture experiments revealed that these obesity-dependent effects were driven by the adipocyte component of the adipose tissue. Obesity decreased the ratio of adiponectin:leptin secreted by adipocytes, altering the adipose-dependent growth microenvironment resulting in increased breast cancer cell proliferation. Supplementation with RSV reversed these adipose-dependent effects suggesting a potential for RSV as a nutritional supplementation to improve breast cancer treatment in obese patients.

  6. Management of endocrine orbitopathy

    International Nuclear Information System (INIS)

    Kahaly, G.J.

    2001-01-01

    Endocrine orbitopathy is the most common extrathyroidal manifestation of Basedow's disease and is characterized by a lymphocyte infiltration of the peribulbar space. Infiltrating and activated T cells react with orbital target cells and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema, and enlargement of the extra ocular muscels. Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with endocrine orbitopathy. Immunosuppressive treatment is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of thyroid eye disease. (orig.) [de

  7. Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.

    Science.gov (United States)

    Moon, Heejung; Song, Jieun; Shin, Jeong-Oh; Lee, Hankyu; Kim, Hong-Kyung; Eggenschwiller, Jonathan T; Bok, Jinwoong; Ko, Hyuk Wan

    2014-06-10

    Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome. Here, we generated Ick knockout mice to elucidate the precise role of ICK in mammalian development and to examine the pathological mechanisms of ECO syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase-dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally localized in the proximal region of cilia near the basal bodies, whereas kinase-dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips. Consistent with these observations in cultured cells, Ick knockout mouse embryos displayed elongated cilia and reduced Shh signaling during limb digit patterning. Taken together, these results indicate that ICK plays a crucial role in controlling ciliary length and that ciliary defects caused by a lack of functional ICK leads to abnormal Shh signaling, resulting in congenital disorders such as ECO syndrome.

  8. Tumors of the endocrine/neuroendocrine system: an overview.

    Science.gov (United States)

    Erlandson, R A; Nesland, J M

    1994-01-01

    For the sake of discussion, the markedly diversified tumors of the endocrine/neuroendocrine system are classified as those originating in classic epithelial endocrine organs (eg, adrenal cortical adenomas), from the diffuse endocrine cells (eg, jejunal carcinoid tumors), or from clusters of these cells (eg, islet cell tumors); and those arising from neurosecretory neurons (eg, neuroblastoma) or paraganglia (eg, carotid body tumor). Although traditional transmission electron microscopy is useful for identifying neurosecretory or endosecretory granules as such, with few exceptions (eg, insulin-containing granules with a complex paracrystalline core) it is not possible to ascribe a granule type (size, shape, or ultrastructure) to a distinct nosologic entity or secretory product because of their overlapping fine structures in different cell types. Immunoelectron microscopy methods utilizing colloidal gold-labeled secondary antibodies can be used to localize virtually any antigen (peptide or neuroamine) to a specific neurosecretory or endosecretory granule or other cell structure. General endocrine/neuroendocrine cell markers such as neuron-specific enolase, the chromogranins, and synaptophysin are useful in identifying neuroendocrine differentiation in a neoplasm using routine immunohistochemical procedures. The current relevance of the APUD concept of Pearse as well as the biologic importance of endocrine/neuroendocrine secretory products such as bombesin and insulinlike growth factors also are discussed.

  9. Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells.

    Science.gov (United States)

    van Drooge, Barend L; Marqueño, Anna; Grimalt, Joan O; Fernández, Pilar; Porte, Cinta

    2017-11-01

    Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Cytochemical identification of endocrine thymus of chicken in relation to aging

    Directory of Open Access Journals (Sweden)

    Uma Kanta Mishra

    2013-09-01

    Full Text Available Age related cytochemical changes of thymic endocrine cells were studied in 78 day old chicks at five day interval to age of day 60 employing a panel of cytochemical stains. Methenamine silver revealed cell morphology including cell processes distinctly while diamine silver revealed a stronger argentaffinity in these cells. The cells had greater affinity for diamine silver compared to methenamine silver (Argentaffin, followed by formaldehyde induced auto- fluorescence, argyrophilia, lead hematoxylin and HCl-toluidine. The chromaffin reaction was the weakest. Cytochemically, three different endocrine cell populations i.e. argentaffin cells, argyrophilic cells and amine precursor uptake and decarboxylation series (APUD/chromaffin cells, formed the resident population of thymic endocrine cells. Occurrence of numerous serotonin storing cells, moderately frequent APUD cells, and fewer chromaffin as well as mast cells suggests for a conspicuous reservoir of amine storing cells in thymus. Morphologically argentaffin cells were of four types i.e. the peripherally granulated spherical cells (Type-I, densely granulated oval cells (Type-II, pyramidal argentaffin cells (Type-III and diffusely granulated elongated cells (Type-IV. The type-II argentaffin cells were most frequent in the medulla followed by the type-I cells and the type-III cells. The type-IV cells were least in frequency. The age related changes in frequency of these cells are also discussed.

  11. Assessment of Depression, Anxiety, Quality of Life, and Coping in Long-Standing Multiple Endocrine Neoplasia Type 2 Patients.

    Science.gov (United States)

    Rodrigues, Karine C; Toledo, Rodrigo A; Coutinho, Flavia L; Nunes, Adriana B; Maciel, Rui M B; Hoff, Ana O; Tavares, Marcos C; Toledo, Sergio P A; Lourenço, Delmar M

    2017-05-01

    Data on psychological harm in multiple endocrine neoplasia type 2 (MEN2) are scarce. The aim of this study was to assess anxiety, depression, quality of life, and coping in long-standing MEN2 patients. Patients were 43 adults (age ≥18 years) with clinical and genetic diagnosis of MEN2 and long-term follow-up (10.6 ± 8.2 years; range 1-33 years). This was a cross-sectional study with qualitative and quantitative psychological assessment using semi-directed interviews and HADS, EORTC QLQ C30, and MINI-MAC scales. Adopting clinical criteria from 2015 ATA Guidelines on MEN2, biochemical cure (39%; 16/41), persistence/recurrence (61%; 25/41), and stable chronic disease (22/41) of medullary thyroid carcinoma (MTC) were scored. Pheochromocytoma affected 19 (44%) patients, with previous adrenalectomy in 17 of them. Overall, anxiety (42%; mean score 11 ± 2.9; range 8-18; anxiety is defined as a score ≥8) and depression (26%; mean score 11 ± 3.8; range 8-20; depression is defined as a score ≥8) symptoms were frequent. Patients who transmitted RET mutations to a child had higher scores for weakness-discouragement/anxious preoccupation and lower scores for cognitive, emotional, and physical functioning (p emotional functioning were noticed in 33 patients who were well-informed about their disease (p stress-inducing factors had lower scores for fighting spirit and cognitive functioning and higher scores for insomnia and dyspnea (p stress-inducing factors, and cure) interfering positively or negatively with the results of the psychometrics scales. The active investigation of these factors and the applied psychological assessment protocol are useful to identify MEN2 patients requiring psychological assistance.

  12. Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634

    Directory of Open Access Journals (Sweden)

    Ješić Maja D.

    2014-01-01

    Full Text Available Introduction. The multiple endocrine neoplasia type 2A (MEN 2A syndrome, comprising medullary thyroid carcinoma (MTC, pheochromocytoma and primary hyperparathyroidism (PHPT is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy’s father and grandmother and paternal aunt in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml, has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

  13. The Endocrine Machinery.

    Science.gov (United States)

    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)

  14. Endocrine diseases in ferrets

    NARCIS (Netherlands)

    Schoemaker, N.J.; van Zeeland, Y.R.A.

    2013-01-01

    SUMMARY Endocrine diseases are among the most commonly seen conditions in ferrets. Tumours of the islet cells in the pancreas, referred to as insulinomas, and tumours of the adrenal glands, referred to as hyperadrenocorticism, are more commonly described in this species than in any other species.

  15. [Vitamin D and endocrine diseases].

    Science.gov (United States)

    Schuch, Natielen Jacques; Garcia, Vivian Cristina; Martini, Ligia Araújo

    2009-07-01

    Vitamin D insufficiency/deficiency has been worldwide reported in all age groups in recent years. It has been considered a Public Health matter since decreased levels of vitamin D has been related to several chronic diseases, as type 2 diabetes mellitus (T2DM), obesity and hypertension. Glucose intolerance and insulin secretion has been observed during vitamin D deficiency, both in animals and humans resulting in T2DM. The supposed mechanism underlying these findings is presence of vitamin D receptor in several tissues and cells, including pancreatic beta-cells, adipocyte and muscle cells. In obese individuals, the impaired vitamin D endocrine system, characterized by high levels of PTH and 1,25(OH)(2)D(3) could induce a negative feedback for the hepatic synthesis of 25(OH)D and also contribute to a higher intracellular calcium, which in turn secrete less insulin and deteriorate insulin sensitivity. In hypertension, vitamin D could act on renin-angiotensin system and also in vascular function. Administration of 1,25(OH)(2)D(3) could decreases renin gene expression and inhibit vascular smooth muscle cell proliferation. However, prospective and intervention human studies that clearly demonstrates the benefits of vitamin D status adequacy in the prevention and treatment of endocrine metabolic diseases are lacking. Further research still necessary to assure the maximum benefit of vitamin D in such situations.

  16. Detection of estrogen receptor endocrine disruptor potency of commonly used organochlorine pesticides using the LUMI-CELL ER bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J D; Chu, A C; Clark, G C [Xenobiotic Detection Systems, Inc., Durham, NC (United States); Chu, M D [Alta Analytical Perspectives, Wilmington, NC (United States); Denison, M S [Dept. of Environmental Toxicology, Univ. of California, Davis, CA (United States)

    2004-09-15

    In order to detect the endocrine disrupting potency of organochlorine pesticides and other compounds, BG-1 (human ovarian carcinoma) cells containing a stably transfected estrogenresponsive luciferase reporter gene plasmid (BG1Luc4E2), was used. This cell line, termed the LUMI-CELL trademark ER estrogenic cell bioassay system, responds in a time-, dose dependent- and chemical-specific manner with the induction of luciferase gene expression in response to exposure to estrogen (but not other steroid hormones) and estrogenic chemicals in a high-throughput screening (HTPS) format6. Here we describe studies in which the LUMI-CELL trademark ER estrogenic cell bioassay system was used for high throughput screening (HTPS) analysis of the estrogenic disrupting potency of several commonly used pesticides and organochlorines: p,p'DDT; p,p'-DDE; DDD; {alpha}a-chlordane; {psi}-chlordane; Kepone; Methoxychlor; Vinclozolin; Fenarimol; 2,4,5-Trichlorophenoxyacetic Acid; and Dieldrin. Our results demonstrate the utility of XDS's LUMI-CELL trademark ER bioassay HTPS system for screening chemicals for estrogenic activity.

  17. Detection of estrogen receptor endocrine disruptor potency of commonly used organochlorine pesticides using the LUMI-CELL ER bioassay

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J.D.; Chu, A.C.; Clark, G.C. [Xenobiotic Detection Systems, Inc., Durham, NC (United States); Chu, M.D. [Alta Analytical Perspectives, Wilmington, NC (United States); Denison, M.S. [Dept. of Environmental Toxicology, Univ. of California, Davis, CA (United States)

    2004-09-15

    In order to detect the endocrine disrupting potency of organochlorine pesticides and other compounds, BG-1 (human ovarian carcinoma) cells containing a stably transfected estrogenresponsive luciferase reporter gene plasmid (BG1Luc4E2), was used. This cell line, termed the LUMI-CELL trademark ER estrogenic cell bioassay system, responds in a time-, dose dependent- and chemical-specific manner with the induction of luciferase gene expression in response to exposure to estrogen (but not other steroid hormones) and estrogenic chemicals in a high-throughput screening (HTPS) format6. Here we describe studies in which the LUMI-CELL trademark ER estrogenic cell bioassay system was used for high throughput screening (HTPS) analysis of the estrogenic disrupting potency of several commonly used pesticides and organochlorines: p,p'DDT; p,p'-DDE; DDD; {alpha}a-chlordane; {psi}-chlordane; Kepone; Methoxychlor; Vinclozolin; Fenarimol; 2,4,5-Trichlorophenoxyacetic Acid; and Dieldrin. Our results demonstrate the utility of XDS's LUMI-CELL trademark ER bioassay HTPS system for screening chemicals for estrogenic activity.

  18. Endoplasmic Reticulum (ER Stress and Endocrine Disorders

    Directory of Open Access Journals (Sweden)

    Daisuke Ariyasu

    2017-02-01

    Full Text Available The endoplasmic reticulum (ER is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR, which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI, Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2 are discussed in this article.

  19. Endoplasmic Reticulum (ER) Stress and Endocrine Disorders

    Science.gov (United States)

    Ariyasu, Daisuke; Yoshida, Hiderou; Hasegawa, Yukihiro

    2017-01-01

    The endoplasmic reticulum (ER) is the organelle where secretory and membrane proteins are synthesized and folded. Unfolded proteins that are retained within the ER can cause ER stress. Eukaryotic cells have a defense system called the “unfolded protein response” (UPR), which protects cells from ER stress. Cells undergo apoptosis when ER stress exceeds the capacity of the UPR, which has been revealed to cause human diseases. Although neurodegenerative diseases are well-known ER stress-related diseases, it has been discovered that endocrine diseases are also related to ER stress. In this review, we focus on ER stress-related human endocrine disorders. In addition to diabetes mellitus, which is well characterized, several relatively rare genetic disorders such as familial neurohypophyseal diabetes insipidus (FNDI), Wolfram syndrome, and isolated growth hormone deficiency type II (IGHD2) are discussed in this article. PMID:28208663

  20. Circulating miRNAs as biomarkers for endocrine disorders.

    Science.gov (United States)

    Butz, H; Kinga, N; Racz, K; Patocs, A

    2016-01-01

    Specific, sensitive and non-invasive biomarkers are always needed in endocrine disorders. miRNAs are short, non-coding RNA molecules with well-known role in gene expression regulation. They are frequently dysregulated in metabolic and endocrine diseases. Recently it has been shown that they are secreted into biofluids by nearly all kind of cell types. As they can be taken up by other cells they may have a role in a new kind of paracrine, cell-to-cell communication. Circulating miRNAs are protected by RNA-binding proteins or microvesicles hence they can be attractive candidates as diagnostic or prognostic biomarkers. In this review, we summarize the characteristics of extracellular miRNA's and our knowledge about their origin and potential roles in endocrine and metabolic diseases. Discussions about the technical challenges occurring during identification and measurement of extracellular miRNAs and future perspectives about their roles are also highlighted.

  1. Epigenetic regulation of non-lymphoid cells by Bisphenol-A, a model endocrine disrupter: Potential Implications for Immunoregulation

    Directory of Open Access Journals (Sweden)

    Deena eKhan

    2015-06-01

    Full Text Available Endocrine disrupting chemicals (EDC abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical and consumer product industries. Many of the EDCs such as Bisphenol A (BPA have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system.

  2. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  3. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    International Nuclear Information System (INIS)

    Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

    2013-01-01

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors

  4. The Roles of Three Types of Knowledge and Perceived Uncertainty in Explaining Risk Perception, Acceptability, and Self-Protective Response—A Case Study on Endocrine Disrupting Surfactants

    Directory of Open Access Journals (Sweden)

    Hien Ho

    2018-02-01

    Full Text Available The ubiquitous surfactants nonylphenol (NP and its ethoxylates (NPEOs, which are known as endocrine disrupters, have appeared in the lists of restricted chemical substances, monitoring programs, and environmental quality standards of many countries due to their adverse effects. Recent studies have reported alarming levels of NP, as the final metabolite of NPEOs, in Vietnamese urban waters, whilst response to this issue is negligible. With the aim of addressing how the public perceives and expects to avoid the risk of endocrine disrupting surfactants (EDSs, the study tested the hypothesized roles of specific knowledge, general knowledge, and perceived uncertainty using structural equation modelling. The findings revealed that different types of knowledge played certain roles in explaining risk perception, risk acceptability, and self-protective response, which are distinguished by experience amongst the public. Evidence of the mediating role that perceived uncertainty may play in the decrease of risk perception and the increase of risk unacceptance has been provided. The insights gained from the study may help answer why the public are in favor of taking non-diet-related self-protective measures rather than changing their dietary habits, which illustrates a comparison with the basis of health belief model. The needs for building cognitive capacity amongst the public, particularly pregnant women and young mothers, and risk communication concerning endocrine disrupting contamination linked to reproductive health are highlighted.

  5. Endocrine effects of contaminated sediments on the freshwater snail Potamopyrgus antipodarum in vivo and in the cell bioassays in vitro.

    Science.gov (United States)

    Mazurová, E; Hilscherová, K; Jálová, V; Köhler, H-R; Triebskorn, R; Giesy, J P; Bláha, L

    2008-09-17

    Lake Pilnok located in the black coal-mining region Ostrava-Karvina, Czech Republic, contains sediments highly contaminated with powdered waste coal. Moreover, population of the endangered species of narrow-clawed crayfish Pontastacus leptodactylus with high proportion of intersex individuals (18%) was observed at this site. These findings motivated our work that aimed to evaluate contamination, endocrine disruptive potency using in vitro assays and in vivo effects of contaminated sediments on reproduction of sediment-dwelling invertebrates. Chemical analyses revealed low concentrations of persistent chlorinated compounds and heavy metals but concentrations of polycyclic aromatic hydrocarbons (PAH) were high (sum of 16 PAHs 10 microg/g dw). Organic extracts from sediments caused significant in vitro AhR-mediated activity in the bioassay with H4IIE-luc cells, estrogenicity in MVLN cells and anti-androgenicity in recombinant yeast assay, and these effects could be attributed to non-persistent compounds derived from the waste coal. We have also observed significant in vivo effects of the sediments in laboratory experiments with the Prosobranchian euryhaline mud snail Potamopyrgus antipodarum. Sediments from Lake Pilnok as well as organic extracts of the sediments (externally added to the control sediment) significantly affected fecundity during 8 weeks of exposure. The effects were stimulations of fecundity at lower concentrations at the beginning of the experiment followed by inhibitions of fecundity and general toxicity. Our study indicates presence of chemicals that affected endocrine balance in invertebrates, and emphasizes the need for integrated approaches combining in vitro and in vivo bioassays with identification of chemicals to elucidate ecotoxicogical impacts of contaminated sediment samples.

  6. Genetic Analysis of Multiple Endocrine Neoplasia Type 1 ( Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1

    Directory of Open Access Journals (Sweden)

    Dong Min Lee

    2014-06-01

    Full Text Available BackgroundMultiple endocrine neoplasia type 1 (MEN1 is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands. MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above.MethodsA 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1.ResultsGenomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion.ConclusionThere is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma

  7. Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients.

    Science.gov (United States)

    Faggiano, Antongiulio; Tavares, Lidice Brandao; Tauchmanova, Libuse; Milone, Francesco; Mansueto, Gelsomina; Ramundo, Valeria; De Caro, Maria Laura Del Basso; Lombardi, Gaetano; De Rosa, Gaetano; Colao, Annamaria

    2008-11-01

    In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

  8. In vitro and in vivo studies with [18F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor

    International Nuclear Information System (INIS)

    Nejjari, Mimoun; Kryza, David; Poncet, Gilles; Roche, Colette; Perek, Nathalie; Chayvialle, Jean-Alain; Le Bars, Didier; Scoazec, Jean-Yves; Janier, Marc; Borson-Chazot, Francoise

    2008-01-01

    Purpose: The aim of this study was to investigate (a) in vitro the relationship between [ 18 F]fluorocholine ([ 18 F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [ 18 F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [ 18 F]FCH and that of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) were measured before and after cytotoxic therapy. [ 18 F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [ 18 F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC 50 values calculated with the [ 18 F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [ 18 F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [ 18 F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [ 18 F]FCH in liver metastases but there was a significant uptake of [ 18 F]FDG. Conclusions: In vitro studies suggested that the incorporation of [ 18 F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [ 18 F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [ 18 F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded

  9. [Disperse endocrine system and APUD concept].

    Science.gov (United States)

    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.

  10. The role of monocytes and monocyte-derived dendritic cells in type 1 diabetes mellitus and autoimmune thyroid disease

    NARCIS (Netherlands)

    W.K. Lam-Tse

    2003-01-01

    textabstractType 1 diabetes mellitus (DM1) and autoimmune thyroid disease (AITD) are organ specific autoimmune diseases in which the immune system is directed against the ß cells and the thyrocytes respectively. The etio-pathogenesis of organ-specific or endocrine autoimmune diseases is complex,

  11. Immunohistochemical localization of glucagon and pancreatic polypeptide on rat endocrine pancreas: coexistence in rat islet cells

    Directory of Open Access Journals (Sweden)

    YH Huang

    2009-08-01

    Full Text Available We used immunofluorescence double staining method to investigate the cellular localization of glucagon and pancreatic polypeptide (PP in rat pancreatic islets. The results showed that both A-cells (glucagon-secreting cells and PP-cells (PPsecreting cells were located in the periphery of the islets. However, A-cells and PP-cells had a different regional distribution. Most of A-cells were located in the splenic lobe but a few of them were in the duodenal lobe of the pancreas. In contrast, the majority of PP-cells were found in the duodenal lobe and a few of them were in the splenic lobe of the pancreas. Furthermore, we found that 67.74% A-cells had PP immunoreactivity, 70.92% PP-cells contained glucagon immunoreactivity with immunofluorescence double staining. Our data support the concept of a common precursor stem cell for pancreatic hormone-producing cells.

  12. Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors.

    Science.gov (United States)

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J; Jensen, Robert T

    2013-05-01

    Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking.To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%-14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature

  13. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    International Nuclear Information System (INIS)

    Bedia, Carmen; Dalmau, Núria; Jaumot, Joaquim; Tauler, Romà

    2015-01-01

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  14. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es; Tauler, Romà, E-mail: roma.tauler@idaea.csic.es

    2015-07-15

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  15. Coexistence of GH-Producing Pituitary Macroadenoma and Meningioma in a Patient with Multiple Endocrine Neoplasia Type 1 with Hyperglycemia and Ketosis as First Clinical Sign

    Directory of Open Access Journals (Sweden)

    A. Herrero-Ruiz

    2017-01-01

    Full Text Available We present the clinical case of a patient who was admitted with an onset of diabetes mellitus (DM with associated ketosis and whose clinical, hormonal, and radiological evolution revealed the presence of primary hyperparathyroidism, pancreatic neuroendocrine tumor, and GH-producing pituitary macroadenoma in the context of multiple endocrine neoplasia type 1 (MEN1. DM is relatively common in cases of acromegaly, but it is not generally associated with ketosis. Simultaneously, the patient presented a meningioma, which is associated with pituitary macroadenoma only in extremely rare cases.

  16. A simple assay for the detection of antibodies to endocrine islet cell surface antigens

    International Nuclear Information System (INIS)

    Contreas, G.; Madsen, O.D.; Vissing, H.; Lernmark, Aa.

    1986-01-01

    A simple and sensitive immunoradiometric assay for the detection of islet cell surface antibodies (CIRMA) has been developed. Live, transformed islet cells derived from a liver metastasis of a transplantable islet cell tumor were grown in removable microtiter wells and incubated with antibody. Cell-bound antibodies were quantitated using 125 I-labelled second antibodies. The assay was used to detect islet cell antibodies present in sera from non-diabetic and diabetic BB rats and proved to be particularly effective for screening hybridoma supernatants in order to identify monoclonal antibodies recognizing islet cell surface antigens. (Auth.)

  17. Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion

    Directory of Open Access Journals (Sweden)

    Hall MJ

    2015-02-01

    Full Text Available Michael J Hall,1 Julie Innocent,2 Christina Rybak,1 Colleen Veloski,3 Walter J Scott,4 Hong Wu,5 John A Ridge,4 John P Hoffman,4 Hossein Borghaei,2 Aruna Turaka,6 Mary B Daly1 1Department of Clinical Genetics, 2Department of Medical Oncology, 3Department of Internal Medicine, 4Department of Surgical Oncology, 5Department of Pathology, 6Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA Introduction: Multiple endocrine neoplasia 1 (MEN1 is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report: A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A. Discussion: Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A in a male proband meeting the criteria

  18. The enteroinsular axis and endocrine pancreatic function in chronic alcohol consumers: evidence for early beta-cell hypofunction.

    Science.gov (United States)

    Patto, R J; Russo, E K; Borges, D R; Neves, M M

    1993-09-01

    Chronic alcohol consumers may have, as judged by functional criteria, exocrine as well as endocrine pancreatic dysfunction, the latter represented by a decreased insulin response to an oral glucose load. To investigate whether this decreased insulin response was due to an ethanol-induced beta-cell dysfunction or to an ethanol-induced dysfunction of the enteroinsular axis, we determined glucose, insulin, and C-peptide plasma concentrations following an oral and an intravenous glucose load in 16 healthy volunteer nonalcohol consumers and in 10 chronic alcohol consumers. In each group, total integrated response for glucose did not significantly change whether glucose was given orally or intravenously, indicating isoglycemic glucose loads. The total integrated response values for insulin in the alcoholic group following both glucose loads as well as C-peptide plasma concentrations were significantly lower than in the control group. Moreover, in both groups the insulin TIR values following the oral glucose load were significantly greater than the values obtained following the intravenous glucose load, indicating an incretin effect. These results indicate that the decreased insulin response observed in alcoholics was not caused by a dysfunction of the enteroinsular axis because it also occurred following an intravenous glucose load, but by an ethanol-induced beta-cell dysfunction because C-peptide and insulin were proportionally decreased in this group.

  19. Trauma and the endocrine system.

    Science.gov (United States)

    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. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

  20. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Melissa A. Davis

    2015-01-01

    Full Text Available Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR. This study evaluated the effect of fetal adrenal demedullation (AD on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA, a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.

  1. Fetal Adrenal Demedullation Lowers Circulating Norepinephrine and Attenuates Growth Restriction but not Reduction of Endocrine Cell Mass in an Ovine Model of Intrauterine Growth Restriction

    Science.gov (United States)

    Davis, Melissa A.; Macko, Antoni R.; Steyn, Leah V.; Anderson, Miranda J.; Limesand, Sean W.

    2015-01-01

    Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses. PMID:25584967

  2. Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

    DEFF Research Database (Denmark)

    Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul

    2000-01-01

    Fetal antigen 1 (FA1) is a circulating EGF multidomain glycoprotein. FA1 and its membrane-associated precursor is defined by the mRNAs referred to as delta-like (dlk), preadipocyte factor 1 (pref-1) or zona glomerulosa-specific factor (ZOG). Using a polyclonal antibody recognising both forms......, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present...... in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive...

  3. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

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

    Science.gov (United States)

    Palmieri, C; Shivaprasad, H L

    2014-12-01

    The cytoarchitecture of the endocrine pancreas of 10 raptors (golden eagles, peregrine falcons, Saker falcon, turkey vultures, red-tailed hawk and unspecified falcon) was examined by immunohistochemistry. Three islet types were identified: type A mixed islets composed mainly by glucagon (A)-secreting cells, type B mixed islets with predominantly insulin (B)-secreting cell component and type M mixed islets (type M) consisting of variable number of glucagon-, insulin- and somatostatin (D)-secreting cells. The latter were further characterized into Type I, II or III according to the cell distribution of the three cell types. A and D cells were also randomly scattered within the exocrine pancreas. The results of this study suggest that the classical concept in birds of a segregation of A and B cells in well-defined and distinct islets is not applicable in raptors, reflecting an evolutionary adaptation to different dietary habits and variation in developmental mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Endocrine aspects of cancer gene therapy.

    Science.gov (United States)

    Barzon, Luisa; Boscaro, Marco; Palù, Giorgio

    2004-02-01

    The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene targeting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, including the possibility to exploit hormone and hormone receptor functions for regulating therapeutic gene expression, the use of endocrine-specific genes as new therapeutic tools, the effects of viral vector delivery and transgene expression on the endocrine system, and the endocrine response to viral vector delivery. Present ethical concerns of gene therapy and the risk of germ cell transduction are also discussed, along with potential lines of innovation to improve cell and gene targeting.

  6. Effects of micro-encapsulation on morphology and endocrine function of cryopreserved neonatal porcine islet-like cell clusters.

    Science.gov (United States)

    Murakami, M; Satou, H; Kimura, T; Kobayashi, T; Yamaguchi, A; Nakagawara, G; Iwata, H

    2000-10-27

    For the success of clinical islets transplantation, the development of a long-term storage method is necessary. However, the structure of digested islets is scanty for culture and cryopreservation. In this study, the effect of micro-encapsulation to cryopreserved porcine islet-like cell clusters (ICCs) was investigated. The ICCs prepared from neonatal pigs by collagenase digestion and culture technique were cryopreserved and micro-encapsulated in 5% agarose membranes. After cryopreservation, ICC cultured without encapsulation (group A) and cultured with encapsulation (group B) were assessed by comparison with no cryopreserved ICC (control) both in vitro by static incubation test and in vivo in a xenotransplantation study. Micro-encapsulation was able to maintain the fine morphology and the number of ICCs of group B after 7 days of culture. There were not significant differences in insulin secretion of group B and control on day 1 and 7 of culture (1 day:11+/-0.99, 7 days: 5.30+/-1.08 microU/ICC/hr NS versus control). On day 7 of culture, the retrieval rate of group B (105.2+/-9.8%) is obviously higher compared with group A (63.0+/-6.3%). In the xenotransplatation model, the ICCs of group B showed long survival time (7.9+/-0.4 weeks) and good transplantation effect. Our study suggests that micro-encapsulation is one of the useful method for cryopreserved ICC to maintain the fine morphology and effectively recover the endocrine function.

  7. Loss of MutL Disrupts CHK2-Dependent Cell-Cycle Control through CDK4/6 to Promote Intrinsic Endocrine Therapy Resistance in Primary Breast Cancer.

    Science.gov (United States)

    Haricharan, Svasti; Punturi, Nindo; Singh, Purba; Holloway, Kimberly R; Anurag, Meenakshi; Schmelz, Jacob; Schmidt, Cheryl; Lei, Jonathan T; Suman, Vera; Hunt, Kelly; Olson, John A; Hoog, Jeremy; Li, Shunqiang; Huang, Shixia; Edwards, Dean P; Kavuri, Shyam M; Bainbridge, Matthew N; Ma, Cynthia X; Ellis, Matthew J

    2017-10-01

    Significant endocrine therapy-resistant tumor proliferation is present in ≥20% of estrogen receptor-positive (ER + ) primary breast cancers and is associated with disease recurrence and death. Here, we uncover a link between intrinsic endocrine therapy resistance and dysregulation of the MutL mismatch repair (MMR) complex ( MLH1/3 , PMS1/2 ), and demonstrate a direct role for MutL complex loss in resistance to all classes of endocrine therapy. We find that MutL deficiency in ER + breast cancer abrogates CHK2-mediated inhibition of CDK4, a prerequisite for endocrine therapy responsiveness. Consequently, CDK4/6 inhibitors (CDK4/6i) remain effective in MutL-defective ER + breast cancer cells. These observations are supported by data from a clinical trial where a CDK4/6i was found to strongly inhibit aromatase inhibitor-resistant proliferation of MutL-defective tumors. These data suggest that diagnostic markers of MutL deficiency could be used to direct adjuvant CDK4/6i to a population of patients with breast cancer who exhibit marked resistance to the current standard of care. Significance: MutL deficiency in a subset of ER + primary tumors explains why CDK4/6 inhibition is effective against some de novo endocrine therapy-resistant tumors. Therefore, markers of MutL dysregulation could guide CDK4/6 inhibitor use in the adjuvant setting, where the risk benefit ratio for untargeted therapeutic intervention is narrow. Cancer Discov; 7(10); 1168-83. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047 . ©2017 American Association for Cancer Research.

  8. Endocrine and paracrine regulation of zebrafish spermatogenesis : The Sertoli cell perspective

    NARCIS (Netherlands)

    Schulz, R. W.; Nóbrega, R. H.; Vidal de Souza Morais, Roberto Daltro; De Waal, P. P.; França, L. R.; Bogerd, J.

    2015-01-01

    Spermatogonial stem cells (SSCs) either self-renew or differentiate into spermatogonia that further develop into spermatozoa. Self-renewal occurs when residing in a specific micro-environment (niche) while displacement from the niche would tip the signalling balance towards differentiation.

  9. The early effects of ionizing radiation on pancreatic endocrine cells in mouse: an immunocytochemistry study

    International Nuclear Information System (INIS)

    Kosanlavit, Rachian; McCullough, Stephen

    2003-06-01

    Prodromal radiation sickness can occur within 30 minutes following irradiation. The early sign is a fatigue, accompanied by other symptoms including diarrhoea, intestinal cramps, nausea and vomiting. This event is often very significant. The contribution of pancreatic damage towards these post-irradiation symptoms is not clear. This study is to assess the volume density, by using the point counting method, of insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-containing cells of mouse pancreas following X-irradiation with doses of 5 and 10 Gy. It uses an in vitro system sampled at 30 minutes, 1 and 3 hours. A radiation dose of 10 Gy significantly decreased the volume density of glucagon-containing cells at 1 hour incubation time and radiation doses of 5 and 10 Gy slightly decreased the volume density of somatostatin-containing cells at all time points. These changes may result in disturbances in metabolism of nutrients, which possibly lead to several symptoms (e.g. fatigue and weight loss) associated with prodromal radiation sickness

  10. Spectrum of Endocrine Disorders in Central Ghana

    Directory of Open Access Journals (Sweden)

    Osei Sarfo-Kantanka

    2017-01-01

    Full Text Available Background. Although an increasing burden of endocrine disorders is recorded worldwide, the greatest increase is occurring in developing countries. However, the spectrum of these disorders is not well described in most developing countries. Objective. The objective of this study was to profile the frequency of endocrine disorders and their basic demographic characteristics in an endocrine outpatient clinic in Kumasi, central Ghana. Methods. A retrospective review was conducted on endocrine disorders seen over a five-year period between January 2011 and December 2015 at the outpatient endocrine clinic of Komfo Anokye Teaching Hospital. All medical records of patients seen at the endocrine clinic were reviewed by endocrinologists and all endocrinological diagnoses were classified according to ICD-10. Results. 3070 adults enrolled for care in the endocrine outpatient service between 2011 and 2015. This comprised 2056 females and 1014 males (female : male ratio of 2.0 : 1.0 with an overall median age of 54 (IQR, 41–64 years. The commonest primary endocrine disorders seen were diabetes, thyroid, and adrenal disorders at frequencies of 79.1%, 13.1%, and 2.2%, respectively. Conclusions. Type 2 diabetes and thyroid disorders represent by far the two commonest disorders seen at the endocrine clinic. The increased frequency and wide spectrum of endocrine disorders suggest the need for well-trained endocrinologists to improve the health of the population.

  11. Relationship of visfatin level to pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index in overweight women who performed hydraulic resistance exercise.

    Science.gov (United States)

    Ha, Chang Ho; Swearingin, Brenda; Jeon, Yong Kyun

    2015-09-01

    [Purpose] This study aimed to examine the correlation of visfatin level to pancreatic endocrine hormone level, homeostasis model assessment of insulin resistance (HOMA-IR) index, and HOMA β-cell index in hydraulic resistance exercise. Furthermore, it investigated the relationship between visfatin level and other variables affected by exercise in overweight women. [Subjects and Methods] The exercise group trained for 12 weeks, 70 minutes/day, 5 days/week. Visfatin level, pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index were measured before and after the intervention. Based on the blood insulin and glucose concentrations, HOMA-IR index, the indicator of insulin resistance, and HOMA β-cell index, the indicator of insulin secretion level, were assessed. [Results] Interaction effects on visfatin level, insulin level, HOMA-IR index, and HOMA β-cell index were observed. Interaction effects on glucagon and glucose levels were not observed between the intervention groups. The correlations of visfatin level to insulin, glucagon, and glucose levels, and HOMA-IR and HOMA β-cell indexes were not significant for any of the subjects. [Conclusion] Therefore, the 12-week resistance exercise affected body composition, visfatin level, insulin level, HOMA-IR index, and HOMA β-cell index. Finally, visfatin was not related to insulin, glucagon, and glucose levels, and HOMA-IR and HOMA β-cell indexes.

  12. The effect of electroacupuncture at the MA-IC 3 endocrine ear acupoint on fasting blood glucose levels in type 2 diabetes mellitus patients

    Science.gov (United States)

    Simadibrata, C.; Budihardjo, F. A.; Srilestari, A.

    2017-08-01

    The management of diabetes mellitus (DM) involves education, nutritional intervention, and physical exercise, in addition to pharmacological interventions, with the long-term goal of preventing complications through the control of blood glucose levels. Several studies have shown that acupuncture, both conventional acupuncture and electroacupuncture, is useful for lowering blood glucose levels in patients with DM. This study aimed to determine the additional effect of electroacupuncture at the MA-IC 3 Endocrine ear acupoint on fasting blood glucose levels in patients with Type 2 DM who were receiving oral hypoglycemic agents at Banjar General Hospital. In this randomized controlled study, fifty-four study participants who were being treated with oral antidiabetics were allocated into two groups, receiving either electroacupuncture (EA) at the MA-IC 3 ear acupoint with dense disperse wave for 30 minutes or acupuncture at the same point and for the same duration but without EA (No EA). Fasting blood glucose levels were measured before and after the intervention. In Group A (EA), the mean fasting blood glucose (FBG) level decreased from 157.26±24.485 to 142.59±26.771 (p < 0.05), whereas in Group B (No EA), the mean FBG decreased from 149.67±21.485 to 148.74±21.326 (p < 0.05). The difference in the amount of FBG decrease between Group A (EA) and Group B (No EA) was statistically significant (p < 0.05). EA at the MA-IC 3 Endocrine lowers FBG levels to a greater degree than acupuncture with no EA in patients with type 2 DM.

  13. Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals

    International Nuclear Information System (INIS)

    Wens, B.; De Boever, P.; Verbeke, M.; Hollanders, K.; Schoeters, G.

    2013-01-01

    Endocrine disrupting chemicals (EDCs) have the potential to interfere with the hormonal system and may negatively influence human health. Microarray analysis was used in this study to investigate differential gene expression in human peripheral blood cells (PBMCs) after in vitro exposure to EDCs. PBMCs, isolated from blood samples of four male and four female healthy individuals, were exposed in vitro for 18 h to either a dioxin-like polychlorinated biphenyl (PCB126, 1 μM), a non-dioxin-like polychlorinated biphenyl (PCB153, 10 μM), a brominated flame retardant (BDE47, 10 μM), a perfluorinated alkyl acid (PFOA, 10 μM) or bisphenol (BPA, 10 μM). ANOVA analysis revealed a significant change in the expression of 862 genes as a result of EDC exposure. The gender of the donors did not affect gene expression. Hierarchical cluster analysis created three groups and clustered: (1) PCB126-exposed samples, (2) PCB153 and BDE47, (3) PFOA and BPA. The number of differentially expressed genes varied per compound and ranged from 60 to 192 when using fold change and multiplicity corrected p-value as filtering criteria. Exposure to PCB126 induced the AhR signaling pathway. BDE47 and PCB153 are known to disrupt thyroid metabolism and exposure influenced the expression of the nuclear receptors PPARγ and ESR2, respectively. BPA and PFOA did not induce significant changes in the expression of known nuclear receptors. Overall, each compound produced a unique gene expression signature affecting pathways and GO processes linked to metabolism and inflammation. Twenty-nine genes were significantly altered in expression under all experimental conditions. Six of these genes (HSD11B2, MMP11, ADIPOQ, CEL, DUSP9 and TUB) could be associated with obesity and metabolic syndrome. In conclusion, microarray analysis identified that PBMCs altered their gene expression response in vitro when challenged with EDCs. Our screening approach has identified a number of gene candidates that warrant

  14. Nanotoxicity: a growing need for study in the endocrine system.

    Science.gov (United States)

    Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

    2013-05-27

    Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Designing Endocrine Disruption Out of the Next Generation of Chemicals.

    Science.gov (United States)

    Schug, T T; Abagyan, R; Blumberg, B; Collins, T J; Crews, D; DeFur, P L; Dickerson, S M; Edwards, T M; Gore, A C; Guillette, L J; Hayes, T; Heindel, J J; Moores, A; Patisaul, H B; Tal, T L; Thayer, K A; Vandenberg, L N; Warner, J; Watson, C S; Saal, F S Vom; Zoeller, R T; O'Brien, K P; Myers, J P

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via

  16. SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

    Directory of Open Access Journals (Sweden)

    M. Yu. Yukina

    2016-01-01

    Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

  17. Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

    Science.gov (United States)

    Endocrine disrupting chemicals (EDCs) are exogenous substances that alter endocrine system function(s) and consequently cause adverse health effects in intact organisms or its progeny. The endocrine system is important for a wide range of biological processes, from normal cell si...

  18. Redox regulation of stress signals: possible roles of dendritic stellate TRX producer cells (DST cell types).

    Science.gov (United States)

    Yodoi, Junji; Nakamura, Hajime; Masutani, Hiroshi

    2002-01-01

    Thioredoxin (TRX) is a 12 kDa protein with redox-active dithiol (Cys-Gly-Pro-Cys) in the active site. TRX is induced by a variety of stresses including viral infection and inflammation. The promoter sequences of the TRX gene contain a series of stress-responsive elements including ORE, ARE, XRE, CRE and SP-1. TRX promotes DNA binding of transcription factors such as NF-kappaB, AP-1 and p53. TRX interacts with target proteins modulating the activity of those proteins. We have identified TRX binding protein-2 (TBP-2), which was identical to vitamin D3 up-regulated protein 1 (VDUP1). Potential action of TBP-2/VDUP1 as a redox-sensitive tumor suppressor will be discussed. There is accumulating evidence for the involvement of TRX in the protection against infectious and inflammatory disorders. We will discuss the role of TRX-dependent redox regulation of the host defense mechanism, in particular its relation to the emerging concept of constitutive and/or inducible TRX on special cell types with dendritic and stellate morphology in the immune, endocrine and nervous systems, which we provisionally designate as dendritic stellate TRX producer cells (DST cell types).

  19. Endocrine Disruptors

    Science.gov (United States)

    ... Smoke Cockroaches Dust Mites Pets & Animals Pollen Aloe Vera Arsenic Bisphenol A (BPA) Cell Phones Climate Change ... effects from Safety Data Sheets for this chemical. E.hormone: Hormones and the Environment - A gateway to ...

  20. Immunologic Endocrine Disorders

    Science.gov (United States)

    Michels, Aaron W.; Eisenbarth, George S.

    2010-01-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

  1. Industrial n-type solar cells with >20% cell efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Romijn, I.G.; Anker, J.; Burgers, A.R.; Gutjahr, A.; Koppes, M.; Kossen, E.J.; Lamers, M.W.P.E.; Heurtault, Benoit; Saynova-Oosterling, D.S.; Tool, C.J.J. [ECN Solar Energy, Petten (Netherlands)

    2013-03-15

    To realize high efficiencies at low costs, ECN has developed the n-Pasha solar cell concept. The n-Pasha cell concept is a bifacial solar cell concept on n-Cz base material, with which average efficiencies of above 20% have been demonstrated. In this paper recent developments at ECN to improve the cost of ownership (lower Euro/Wp) of the n-Pasha cell concept are discussed. Two main drivers for the manufacturing costs of n-type solar cells are addressed: the n-type Cz silicon material and the silver consumption. We show that a large resistivity range between 2 and 8 cm can be tolerated for high cell efficiency, and that the costs due to the silver metallization can be significantly reduced while increasing the solar cell efficiency. Combining the improved efficiency and cost reduction makes the n-Pasha cell concept a very cost effective solution to manufacture high efficient solar cells and modules.

  2. [Methuosis: a novel type of cell death].

    Science.gov (United States)

    Cai, Hongbing; Liu, Jinkun; Fan, Qin; Li, Xin

    2013-12-01

    Cell death is a major physiological or pathological phenomenon in life activities. The classic forms of cell death include apoptosis, necrosis, and autophagy. Recently, a novel type of cell death has been observed and termed as methuosis, in which excessive stimuli can induce cytoplasmic uptake and accumulation of small bubbles that gradually merge into giant vacuoles, eventually leading to decreased cellular metabolic activity, cell membrane rupture and cell death. In this article, we describe the nomenclature, morphological characteristics and underlying mechanisms of methuosis, compare methuosis with autophagy, oncosis and paraptosis, and review the related researches.

  3. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

    DEFF Research Database (Denmark)

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H

    2016-01-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies...... and for the worry of being diagnosed with a cancer susceptibility syndrome....

  4. The molecular classification of hereditary endocrine diseases.

    Science.gov (United States)

    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. Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome.

    Science.gov (United States)

    Naik, Chinna; Basu, Sandip

    2017-01-01

    Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177 Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region ( n = 1), duodenum ( n = 1), and pancreas ( n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25-75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [ 99m Tc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/ 68 Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177 Lu-DOTA-octreotate (DOTATATE) PRRT was

  6. Bariatric surgery, gut morphology and enteroendocrine cells

    DEFF Research Database (Denmark)

    Hansen, Carl Frederik

    40 hormones. In this PhD study, gut morphology and the population of endocrine cells have been examined in three rodent animal models using stereological techniques. First, in a rodent model of type-2 diabetes (T2DM), the Zucker diabetic fatty rat (ZDF), the population of endocrine L-cells...... to contribute to the positive effects of bariatic surgery but the mechanisms remain largely unknown. The endocrine cells of the gastrointestinal tract that produce and secrete hormones are difficult to examine as they are distributed as single cells. Several types of endocrine cells together produce more than...... and the gut morphology were quantified. The number of Lcells was 4.8 million in the normal rat and the L-cells were found to double in number in the diabetic ZDF rat model. Second, the L-cell population, gut morphology and endocrine cell gene expression were examined in a rodent model of Roux-en-Y gastric...

  7. The Relation between Anxiety, Depression and Sexual Dysfunction and the Level of Blood Glucose Control in Patients with Type 2 Diabetes Attending Endocrine Clinic of Taleghani Hospital

    Directory of Open Access Journals (Sweden)

    Afarin Ahmadian

    2018-02-01

    Full Text Available Diabetes, as a common disease, is one of the major health problems in countries all over the world. There has been evidence of an increase in the prevalence rate of psychological disorders such as anxiety and depression and sexual dysfunction in people with diabetes compared to other people. The study aimed to investigate the relation between blood glucose control and anxiety, depression and sexual dysfunction. For this purpose, 141 patients with type 2 diabetes attending to Endocrine clinic of Taleghani Hospital in Tehran were randomly selected. In order to assess the prevalence rate of anxiety and depression, the HADS questionnaire was applied, and ARIZONA questionnaire was used to assess prevalence rate of sexual dysfunction. The status of blood glucose control was assessed based on the HbA1c scale as well. According to the results of the present research, 93.9% of the subjects in the uncontrolled blood glucose group suffered from either anxiety or depression, or both of them, and 6.1% in the control blood glucose group. 77.2% of patients in uncontrolled blood glucose group had severe sexual disorder; while, 22.8% of patients in controlled blood glucose group had this problem. Based on the obtained results of data analysis, there is a significant relationship between the status of blood glucose control based on the HbA1c scale and the prevalence rate of anxiety, depression and sexual dysfunction.

  8. Removal of an endocrine disrupting chemical (17 alpha-ethinyloestradiol) from wastewater effluent by activated carbon adsorption: Effects of activated carbon type and competitive adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Ifelebuegu, A.O.; Lester, J.N.; Churchley, J.; Cartmell, E. [Cranfield University, Cranfield (United Kingdom). School of Water Science

    2006-12-15

    Granular activated carbon has been extensively used for the adsorption of organic micropollutants for potable water production. In this study the removal of an endocrine disrupting chemical from wastewater final effluent by three types of granular activated carbon (wood, coconut and coal based) has been investigated in batch adsorption experiments and correlated with the removal of chemical oxygen demand (COD), total organic carbon (TOC) and ultraviolet absorbance (UV). The results obtained demonstrated 17 alpha-ethinyloestradiol (EE2) removals of 98.6%, 99.3%, and 96.4% were achieved by the coal based (ACo), coconut based (ACn) and wood based (AWd) carbons respectively at the lowest dose of carbon (0.1 gl{sup -1}). The other adsorbates investigated all exhibited good removal. At an equilibrium concentration of 7 mgl{sup -1} the COD adsorption capacities were 3.16 mg g{sup -1}, 4.8 mg g{sup -1} and 7.1 mg g{sup -1} for the wood, coconut and coal based carbons respectively. Overall, the order of removal efficiency of EE2 and the other adsorbates for the three activated carbons was ACn {gt} ACo {gt} AWd. The adsorption capacities of the carbons were found to be reduced by the effects of other competing adsorbates in the wastewater effluent.

  9. Endocrine pathology: past, present and future.

    Science.gov (United States)

    Asa, Sylvia L; Mete, Ozgur

    2018-01-01

    Endocrine pathology is the subspecialty of diagnostic pathology which deals with the diagnosis and characterisation of neoplastic and non-neoplastic diseases of the endocrine system. This relatively young subspecialty was initially focused mainly on thyroid and parathyroid pathology, with some participants also involved in studies of the pituitary, the endocrine pancreas, and the adrenal glands. However, the endocrine system involves much more than these traditional endocrine organs and the discipline has grown to encompass lesions of the dispersed neuroendocrine cells, including neuroendocrine tumours (NETs) of the lungs, gastrointestinal tract, thymus, breast and prostate, as well as paraganglia throughout the body, not just in the adrenals. Indeed, the production of hormones is the hallmark of the endocrine system, and some aspects of gynecological/testicular, bone and liver pathology also fall into the realm of this specialty. Many of the lesions that are the focus of this discipline are increasing in incidence and their pathology is becoming more complex with increased understanding of molecular pathology and a high incidence of familial disease. The future of endocrine pathology will demand a depth of understanding of structure, function, prognosis and prediction as pathologists play a key role in the multidisciplinary care team of patients with endocrine diseases. It is anticipated that new technologies will allow increased subspecialisation in pathology and growth of this important area of expertise. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  10. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    Science.gov (United States)

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. [Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

    Science.gov (United States)

    Iaglov, V V; Iaglova, N V

    2011-01-01

    The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

  12. Endocrine Actions of Osteocalcin

    Directory of Open Access Journals (Sweden)

    Aurora Patti

    2013-01-01

    Full Text Available Osteocalcin is the most abundant noncollagenous protein of bone matrix. Once transcribed, this protein undergoes posttranslational modifications within osteoblastic cells before its secretion, including the carboxylation of three glutamic residues in glutamic acid, which is essential for hydroxyapatite binding and deposition in the extracellular matrix of bone. Recent provocative data from experimental observations in mice showed that the circulating undercarboxylated fraction of osteocalcin increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral fat in both genders, while it enhances testosterone production by the testes in males. Moreover, both total and undercarboxylated osteocalcins increase following physical activity with potential positive effects on glucose tolerance. Despite that these evidences have been only in part confirmed in humans, further prospective investigations are needed to definitively establish the endocrine role of osteocalcin both in the general population and cohorts of patients with diabetes or other metabolic disorders.

  13. Effects of young coconut juice on the numbers of argyrophil endocrine cells in the gastrointestinal tract of male rats: Novel preliminary findings

    Directory of Open Access Journals (Sweden)

    Nisaudah Radenahmad

    2014-12-01

    Full Text Available Apart from calcium itself, there are many factors including vitamin D and estrogen, that play important roles in bone formation. Hormones, especially estrogen, used for replacement therapy is highly effective at reducing the rate of bone loss and can also replace lost bone in postmenopausal women. Estrogen replacement therapy has been proposed to prevent bone loss in males as well as in females. Estrogen, however, has been considered to be one of the hormonal risk factors of benign prostatic hyperplasia and prostate cancer and also other side effects. With this background, in the present study, young coconut juice (YCJ, that is known to contain the phytoestrogen, -sitosterol, was investigated for its possible beneficial effects on delaying osteoporosis using a male orchidectomized rat model, and as a replacement for estrogen replacement therapy. In the present study we used the Grimelius stain which is a broad endocrine cell marker, especially in the gastrointestinal (GI tract to quantify the argyrophil endocrine cells and if possible to relate this to reflex GI functions, e.g. calcium absorption, GI motility etc. that might have an influence on osteoporosis. There were five groups of rats (6 per group included in this study. The first group consisted of sham-operated rats, the second group consisted of orchidectomized (orx rats, and the third group consisted of orx rats injected intraperitoneally with exogenous estrogen (2.5 g/kgBW of estradiol benzoate, EB five days a week for two weeks. The fourth group consisted of orx rats that received YCJ (100 mL/ kgBW/day and the fifth group was sham-operated rats receiving YCJ (100 mL/kgBW/day for two weeks. After sacrifice, the GI tract including stomach, small and large intestines were removed, fixed and paraffin embedded for routine H&E and Grimelius silver staining. Most of the argyrophil cells were dispersed in the mucosa, particularly in the basal mucosa and were generally round or spindle

  14. Hypothesis: Musculin is a hormone secreted by skeletal muscle, the body's largest endocrine organ. Evidence for actions on the endocrine pancreas to restrain the beta-cell mass and to inhibit insulin secretion and on the hypothalamus to co-ordinate the neuroendocrine and appetite responses to exercise.

    Science.gov (United States)

    Engler, Dennis

    2007-01-01

    Recent studies indicate that skeletal muscle may act as an endocrine organ by secreting interleukin-6 (IL-6) into the systemic circulation. From an analysis of the actions of IL-6 and of additional literature, we postulate that skeletal muscle also secretes an unidentified hormone, which we have named Musculin (Latin: musculus = muscle), which acts on the pancreatic beta-cell to restrain the size of the (beta-cell mass and to tonically inhibit insulin secretion and biosynthesis. It is suggested that the amount of Musculin secreted is determined by, and is positively correlated with, the prevailing insulin sensitivity of skeletal muscle, thereby accounting for the hyperinsulinemia that occurs in insulin resistant disorders such as type 2 diabetes mellitus, obesity, and the polycystic ovary syndrome. In addition, it is postulated that Musculin acts on the hypothalamus (arcuate nucleus, dorsomedial hypothalamic nucleus) to co-ordinate the neuroendocrine and appetite responses to exercise. However, the possibilities that Musculin may act on additional central nervous system sites and that an additional hormone(s) may be responsible for these actions are not excluded. It is suggested that a search be made for Musculin, since analogues of such a substance may be of therapeutic benefit in the treatment of the current global diabetes and obesity epidemic.

  15. Establishment and culture optimization of a new type of pituitary immortalized cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kokubu, Yuko [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Asashima, Makoto [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577 (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan)

    2015-08-07

    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  16. NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Endocrine Challenges--Thyroid Dysfunction, Growth Impairment, Bone Health, & Reproductive Risks

    Science.gov (United States)

    Dvorak, Christopher C.; Gracia, Clarisa R.; Sanders, Jean E.; Cheng, Edward Y.; Baker, K. Scott; Pulsipher, Michael A.; Petryk, Anna

    2011-01-01

    The endocrine system is highly susceptible to damage by high-dose chemotherapy and/or irradiation prior to hematopoietic cell transplantation (HCT) during childhood. The specific endocrine organs most affected by HCT include the thyroid gland, the pituitary, and the gonads. In addition, hormones that support development and stability of the skeletal system are also affected. Insufficiency of thyroid hormone is one of the most common late sequelae of HCT, and occurs more often in young children. Deficiency in the pituitary’s production of growth hormone is a problem of unique concern to the pediatric population. The reproductive risks of HCT depend on the patient’s gender and pubertal status at the time of HCT. Pubertal or gonadal failure frequently occurs, especially in females. Infertility risks for both genders remain high, while methods of fertility preservation are limited in all but post-pubertal males. Bone health post-HCT can be compromised by low bone mineral density as well as avascular necrosis, but the data on both problems in the pediatric HCT population are limited. In this paper, the current state of knowledge, gaps in that knowledge, and recommendations for future research are addressed in detail for each of these systems. PMID:22005649

  17. Clinical course of a cohort with type 2 diabetes mellitus after endocrine assessment. A 26-week study.

    Science.gov (United States)

    Herranz-Antolín, Sandra; Álvarez-de Frutos, Visitación; Torralba, Miguel

    2018-04-01

    To assess the degree of metabolic control and hypoglycemic treatments in a cohort of patients with type 2 diabetes mellitus (T2DM) after evaluation in an endocrinology clinic. A prospective cohort study on 465 patients with T2DM who were not being monitored at an endocrinology clinic. Blood glucose control data and treatments received were recorded at an initial visit and after 26 weeks of follow-up. Baseline glycosylated hemoglobin (HbA1c) level was 8.3±1.8%, as compared to 6.6±0.9% after 26 weeks of follow-up (P1). The proportion of patients with HbA1c levels 1% to 71.3% (P1). In 59.9% of patients, a decrease ≥0.8% in HbA1c was seen. In the multivariate analysis, variables predicting for an improvement in the degree of metabolic control were older age (OR 1.038; 95%CI 1-1.07; P=.041), higher baseline HbA1c values (OR 5.51; 95%CI 3.4-9; P1), T2DM duration 1.6-13.3; P=.005), and change in hypoglycemic treatment (OR 2.77, 95%CI 1.1-6.9; P=.03). Hypoglycemic therapy was changed in 75.1% of study patients with T2DM. After 26 weeks of follow-up, decreases were seen in both the proportion of patients who receiveding no treatment (from 7% to 0.3%, P1) and the proportions of patients on oral antidiabetic therapy (60.9% vs 55.5%, P=.003) and insulin (10.5% vs 6.2%, P=.021). However, the proportion of patients receiving insulin combined with oral antidiabetic drugs increased from 21.1% to 38% (P1). An improved metabolic control was seen in this cohort of patients with T2DM after their evaluation in an endocrinology clinic. However, HbA1c levels 17 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Conserved genetic pathways controlling the development of the diffuse endocrine system in vertebrates and Drosophila.

    Science.gov (United States)

    Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina L

    2010-05-01

    The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. Copyright 2009. Published by Elsevier Inc.

  19. Stem Cell Treatment for Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-03-01

    Full Text Available Type 1 diabetes mellitus (T1DM is a common chronic disease in children, characterized by a loss of  cells, which results in defects in insulin secretion and hyperglycemia. Chronic hyperglycemia causes diabetic complications, including diabetic nephropathy, neuropathy and retinopathy. Curative therapies mainly include diet and insulin administration. Although hyperglycemia can be improved by insulin administration, exogenous insulin injection cannot successfully mimic the insulin secretion from normal  cells, which keeps blood glucose levels within the normal range all the time. Islet and pancreas transplantation achieves better glucose control, but there is a lack of organ donors. Cell based therapies have also been attempted to treat T1DM. Stem cells such as embryonic stem cells, induced pluripotent stem cells and tissue stem cells (TSCs such as bone marrow-, adipose tissue- and cord blood-derived stem cells, have been shown to generate insulin-producing cells. In this review, we summarize the most-recently available information about T1DM and the use of TSCs to treat T1DM.

  20. Neurocutaneous spectrum of multiple endocrine neoplasia-1

    Directory of Open Access Journals (Sweden)

    Shireen Furtado

    2012-01-01

    Full Text Available Multiple endocrine neoplasia type I or Wermer syndrome is characterized by primary hyperparathyroidism, enteropancreatic endocrine tumor, and a pituitary pathology. A 35-year-old male presented with visual field defects, hyperprolactinemia, and hypogonadism. He also had multiple infraumbilical skin-colored nodules. A syndromal association of Wermer syndrome was derived using the dermal, pituitary, parathyroid, and gastrointestinal hormonal manifestations of the tumor. The radiological and histological findings of lesion which underwent biopsy are discussed. The presence of collagenomas, lipomas, and hypopigmented macules in a patient with neuroendocrine symptoms should raise the suspicion of an underlying multiple endocrine neoplasia.

  1. Non-invasive prenatal diagnosis of multiple endocrine neoplasia type 2A using COLD-PCR combined with HRM genotyping analysis from maternal serum.

    Science.gov (United States)

    Macher, Hada C; Martinez-Broca, Maria A; Rubio-Calvo, Amalia; Leon-Garcia, Cristina; Conde-Sanchez, Manuel; Costa, Alzenira; Navarro, Elena; Guerrero, Juan M

    2012-01-01

    The multiple endocrine neoplasia type 2A (MEN2A) is a monogenic disorder characterized by an autosomal dominant pattern of inheritance which is characterized by high risk of medullary thyroid carcinoma in all mutation carriers. Although this disorder is classified as a rare disease, the patients affected have a low life quality and a very expensive and continuous treatment. At present, MEN2A is diagnosed by gene sequencing after birth, thus trying to start an early treatment and by reduction of morbidity and mortality. We first evaluated the presence of MEN2A mutation (C634Y) in serum of 25 patients, previously diagnosed by sequencing in peripheral blood leucocytes, using HRM genotyping analysis. In a second step, we used a COLD-PCR approach followed by HRM genotyping analysis for non-invasive prenatal diagnosis of a pregnant woman carrying a fetus with a C634Y mutation. HRM analysis revealed differences in melting curve shapes that correlated with patients diagnosed for MEN2A by gene sequencing analysis with 100% accuracy. Moreover, the pregnant woman carrying the fetus with the C634Y mutation revealed a melting curve shape in agreement with the positive controls in the COLD-PCR study. The mutation was confirmed by sequencing of the COLD-PCR amplification product. In conclusion, we have established a HRM analysis in serum samples as a new primary diagnosis method suitable for the detection of C634Y mutations in MEN2A patients. Simultaneously, we have applied the increase of sensitivity of COLD-PCR assay approach combined with HRM analysis for the non-invasive prenatal diagnosis of C634Y fetal mutations using pregnant women serum.

  2. A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A.

    Science.gov (United States)

    Bethanis, Sotirios; Koutsodontis, George; Palouka, Theodosia; Avgoustis, Christos; Yannoukakos, Drakoulis; Bei, Thalia; Papadopoulos, Savas; Linos, Dimitrios; Tsagarakis, Stylianos

    2007-01-01

    Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.

  3. Non-invasive prenatal diagnosis of multiple endocrine neoplasia type 2A using COLD-PCR combined with HRM genotyping analysis from maternal serum.

    Directory of Open Access Journals (Sweden)

    Hada C Macher

    Full Text Available The multiple endocrine neoplasia type 2A (MEN2A is a monogenic disorder characterized by an autosomal dominant pattern of inheritance which is characterized by high risk of medullary thyroid carcinoma in all mutation carriers. Although this disorder is classified as a rare disease, the patients affected have a low life quality and a very expensive and continuous treatment. At present, MEN2A is diagnosed by gene sequencing after birth, thus trying to start an early treatment and by reduction of morbidity and mortality. We first evaluated the presence of MEN2A mutation (C634Y in serum of 25 patients, previously diagnosed by sequencing in peripheral blood leucocytes, using HRM genotyping analysis. In a second step, we used a COLD-PCR approach followed by HRM genotyping analysis for non-invasive prenatal diagnosis of a pregnant woman carrying a fetus with a C634Y mutation. HRM analysis revealed differences in melting curve shapes that correlated with patients diagnosed for MEN2A by gene sequencing analysis with 100% accuracy. Moreover, the pregnant woman carrying the fetus with the C634Y mutation revealed a melting curve shape in agreement with the positive controls in the COLD-PCR study. The mutation was confirmed by sequencing of the COLD-PCR amplification product. In conclusion, we have established a HRM analysis in serum samples as a new primary diagnosis method suitable for the detection of C634Y mutations in MEN2A patients. Simultaneously, we have applied the increase of sensitivity of COLD-PCR assay approach combined with HRM analysis for the non-invasive prenatal diagnosis of C634Y fetal mutations using pregnant women serum.

  4. Primary hyperparathyroidism as the first clinical manifestation of multiple endocrine neoplasia type 2A in a 5-year-old child.

    Science.gov (United States)

    Magalhães, Patrícia Künzle Ribeiro; Antonini, Sonir Roberto Rauber; de Paula, Francisco José Albuquerque; de Freitas, Luiz Carlos Conti; Maciel, Léa Maria Zanini

    2011-05-01

    Primary hyperparathyroidism occurs in only 10%-30% of patients with multiple endocrine neoplasia type 2A (MEN2A), rarely as the sole clinical manifestation, and is usually diagnosed after the third decade of life. A 5-year-old girl was referred for prophylactic thyroidectomy as she carried the p.C634R RET mutation. She was clinically asymptomatic, with a normally palpable thyroid and with the cervical region free of lymphadenopathy or other nodules. Preoperative tests revealed hypercalcemia associated with elevation of parathyroid hormone (PTH) (calcium = 11.2 mg/dL, calcium ion = 1.48 mmol/L, phosphorus = 4.0 mg/dL, alkaline phosphatase = 625 U/L, parathyroid hormone (PTH) PTH = 998 pg/mL). A thyroid ultrasound was normal and parathyroid scintigraphy with (99m)Tc-Sestamibi revealed an area of radioconcentration in the upper half of the left thyroid lobe suggesting hyperfunctioning parathyroid tissue. She underwent total thyroidectomy and parathyroidectomy and developed hypocalcemia. The anatomopathological examination showed no histopathological changes in the thyroid tissue and an adenoma of the parathyroid gland, confirming the diagnosis of hyperparathyroidism. Primary hyperparathyroidism can be a precocious manifestation of MEN2A. This case report highlights that asymptomatic hypercalcemia should be scrutinized in children related to patients with MEN2A who carry a mutation in the RET proto-oncogene, especially mutations in the codon 634, before the currently recommended age of 8 years.

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

    DEFF Research Database (Denmark)

    Martin, David; Kim, Yung-Hae; Sever, Dror

    2015-01-01

    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...

  6. Central control of glucose homeostasis: the brain--endocrine pancreas axis.

    Science.gov (United States)

    Thorens, B

    2010-10-01

    A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  7. Multiple Endocrine Neoplasia Type I

    Science.gov (United States)

    ... other experts. The NIDDK would like to thank: Stephen J. Marx, M.D., NIDDK Contact Us The ... La información de la salud en español Health Statistics Healthy Moments Radio Broadcast Clinical Trials For Health ...

  8. Endocrine manifestations of celiac disease

    Directory of Open Access Journals (Sweden)

    R Philip

    2012-01-01

    Full Text Available Background: Celiac disease can have extra gastrointestinal tract (GIT presentations, most of which are endocrine. The aim of this study was to present patients diagnosed to have celiac disease from an endocrine department and to study the prevalence of endocrinopathies in celiac disease. Materials and Methods: A total of 36 patients from the endocrinology department (LLRM Medical College, Meerut between January 2011 and July 2012 and who were diagnosed to have celiac disease were included in the study. Results: Short stature was the commonest presentation (25%, other presentations included short stature and delayed puberty (20%, delayed puberty (11%, screening for celiac disease in type-1 DM patients (17%, rickets (6%, anemia not responding to oral therapy (6%, type-1 DM with recurrent hypoglycaemia (6%, and osteomalacia (3%. The endocrine manifestations include (after complete evaluation short stature (58%, delayed puberty (31%, elevated alkaline phospahatase (67%, low calcium (22%, X-rays suggestive of osteomalacia or rickets (8%, capopedal spasm (6%, and night blindness (6%. Anti-TPO antibody positivity was found in 53%, hypothyroidism in 28%, subclinical hypothyroidism in 17%, and type-1 DM in 25% of the patients. A total of 14% patients had no GI symptoms. Conclusion: Celiac disease is an endocrine disrupter as well as the great masquerader having varied presentations including short stature, delayed puberty, and rickets. Some patients who have celiac disease may not have any GI symptoms, making the diagnosis all the more difficult. Also, there is significant incidence of celiac disease with hypothyroidism and type-1 DM, making screening for it important in these diseases.

  9. Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.

    Science.gov (United States)

    Sansone, Pasquale; Ceccarelli, Claudio; Berishaj, Marjan; Chang, Qing; Rajasekhar, Vinagolu K; Perna, Fabiana; Bowman, Robert L; Vidone, Michele; Daly, Laura; Nnoli, Jennifer; Santini, Donatella; Taffurelli, Mario; Shih, Natalie N C; Feldman, Michael; Mao, Jun J; Colameco, Christopher; Chen, Jinbo; DeMichele, Angela; Fabbri, Nicola; Healey, John H; Cricca, Monica; Gasparre, Giuseppe; Lyden, David; Bonafé, Massimiliano; Bromberg, Jacqueline

    2016-02-09

    The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy.

  10. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas.

    Science.gov (United States)

    Saisho, Yoshifumi

    2016-01-01

    The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better.

  11. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

    Science.gov (United States)

    Saisho, Yoshifumi

    2016-01-01

    The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better. PMID:28012279

  12. Standardizing Clinically Meaningful Outcome Measures Beyond HbA1c for Type 1 Diabetes: A Consensus Report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange.

    Science.gov (United States)

    Agiostratidou, Gina; Anhalt, Henry; Ball, Dana; Blonde, Lawrence; Gourgari, Evgenia; Harriman, Karen N; Kowalski, Aaron J; Madden, Paul; McAuliffe-Fogarty, Alicia H; McElwee-Malloy, Molly; Peters, Anne; Raman, Sripriya; Reifschneider, Kent; Rubin, Karen; Weinzimer, Stuart A

    2017-12-01

    To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A 1c (HbA 1c ) based upon a review of the evidence, consensus from clinical experts, and input from researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work. A Steering Committee-comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange-was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees. The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome's short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes-specific development is needed. The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA 1c in the research, development, and evaluation of type 1 diabetes

  13. A possible new syndrome with double endocrine tumors in association with an unprecedented type of familial heart-hand syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yamagishi Masakazu

    2010-10-01

    Full Text Available Abstract Introduction The combination of a pituitary prolactinoma and an aldosterone-producing adrenal adenoma is extremely rare. To the best of our knowledge, double endocrine tumors in association with heart-hand syndrome have not previously been reported. Case presentation A 21-year-old Japanese woman presented with galactorrhea and decreased visual acuity. A large pituitary adenoma with an increased level of serum prolactin was apparent by computed tomography. She additionally showed mild hypertension (136/90 mmHg accompanied by hypokalemia. The plasma aldosterone concentration was increased. Computed tomography showed a mass in the right adrenal gland. No other tumors were found despite extensive imaging studies. Physical and radiographic examinations showed skeletal malformations of the hands and feet, including hypoplasia of the first digit in all four limbs. An atrial septal defect was demonstrated by echocardiography. Similar digital and cardiac abnormalities were detected in our patient's father, and a clinical diagnosis of hereditary heart-hand syndrome was made. Conclusion No established heart-hand syndrome was wholly compatible with the family's phenotype. Her father had no obvious endocrine tumors, implying that the parent of transmission determined variable phenotypic expression of the disease: heart-hand syndrome with multiple endocrine tumors from the paternal transmission or no endocrine tumor from the maternal transmission. This suggests that the gene or genes responsible for the disease may be under tissue-specific imprinting control.

  14. The clandestine organs of the endocrine system.

    Science.gov (United States)

    Garcia-Reyero, Natàlia

    2018-02-01

    This review analyzes what could be regarded as the "clandestine organs" of the endocrine system: the gut microbiome, the immune system, and the stress system. The immune system is very closely related to the endocrine system, with many intertwined processes and signals. Many researchers now consider the microbiome as an 'organ' that affects the organism at many different levels. While stress is certainly not an organ, it affects so many processes, including endocrine-related processes, that the stress response system deserved a special section in this review. Understanding the connections, effects, and feedback mechanisms between the different "clandestine organs" and the endocrine system will provide us with a better understanding of how an organism functions, as well as reinforce the idea that there are no independent organs or systems, but a complex, interacting network of molecules, cells, tissues, signaling pathways, and mechanisms that constitute an individual. Published by Elsevier Inc.

  15. Endocrine manifestations in celiac disease.

    Science.gov (United States)

    Freeman, Hugh James

    2016-10-14

    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.

  16. Loss of heterozygosity on chromosome 11q13 in two families with acromegaly/gigantism is independent of mutations of the multiple endocrine neoplasia type I gene.

    Science.gov (United States)

    Gadelha, M R; Prezant, T R; Une, K N; Glick, R P; Moskal, S F; Vaisman, M; Melmed, S; Kineman, R D; Frohman, L A

    1999-01-01

    Familial acromegaly/gigantism occurring in the absence of multiple endocrine neoplasia type I (MEN-1) or the Carney complex has been reported in 18 families since the biochemical diagnosis of GH excess became available, and the genetic defect is unknown. In the present study we examined 2 unrelated families with isolated acromegaly/gigantism. In family A, 3 of 4 siblings were affected, with ages at diagnosis of 19, 21, and 23 yr. In family B, 5 of 13 siblings exhibited the phenotype and were diagnosed at 13, 15, 17, 17, and 24 yr of age. All 8 affected patients had elevated basal GH levels associated with high insulin-like growth factor I levels and/or nonsuppressible serum GH levels during an oral glucose tolerance test. GHRH levels were normal in affected members of family A. An invasive macroadenoma was found in 6 subjects, and a microadenoma was found in 1 subject from family B. The sequence of the GHRH receptor complementary DNA in 1 tumor from family A was normal. There was no history of consanguinity in either family, and the past medical history and laboratory results excluded MEN-1 and the Carney complex in all affected and unaffected screened subjects. Five of 8 subjects have undergone pituitary surgery to date, and paraffin-embedded pituitary blocks were available for analysis. Loss of heterozygosity on chromosome 11q13 was studied by comparing microsatellite polymorphisms of leukocyte and tumor DNA using PYGM (centromeric) and D11S527 (telomeric), markers closely linked to the MEN-1 tumor suppressor gene. All tumors exhibited a loss of heterozygosity at both markers. Sequencing of the MEN-1 gene revealed no germline mutations in either family, nor was a somatic mutation found in tumor DNA from one subject in family A. The integrity of the MEN-1 gene in this subject was further supported by demonstration of the presence of MEN-1 messenger ribonucleic acid, as assessed by RT-PCR. These data indicate that loss of heterozygosity in these affected family

  17. α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Marcela Brissova

    2018-03-01

    Full Text Available Many patients with type 1 diabetes (T1D have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia.

  18. Physiology of the endocrine pancreas.

    Science.gov (United States)

    Engelking, L R

    1997-11-01

    The endocrine pancreas is composed of nests of cells called the islets of Langerhans, which comprise only about 20% of pancreatic cell mass and secrete insulin, glucagon, somatostatin, and pancreatic polypeptide. Insulin is anabolic, increasing storage of glucose, fatty acids and amino acids, while glucagon namely stimulates hepatic glycogenolysis, gluconeogenesis, and ketogenesis. Somatostatin acts as a paracrine agent to inhibit both insulin and glucagon release, and, therefore, to modulate their output. This article explores factors controlling release of these hormones, as well as the way in which they affect fuel metabolism in the whole animal.

  19. Comparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine

    Science.gov (United States)

    Jocsak, Gergely; Kiss, David Sandor; Toth, Istvan; Goszleth, Greta; Bartha, Tibor; Frenyo, Laszlo V.; Horvath, Tamas L.; Zsarnovszky, Attila

    2016-01-01

    Background: Humans and animals are continuously exposed to a number of environmental substances that act as endocrine disruptors (EDs). While a growing body of evidence is available to prove their adverse health effects, very little is known about the consequences of simultaneous exposure to a combination of such chemicals; Methods: Here, we used an in vitro model to demonstrate how exposure to bisphenol A, zearalenone, arsenic, and 4-methylbenzylidene camphor, alone or in combination, affect estrogen receptor β (ERβ) mRNA expression in primary cerebellar cell cultures. Additionally, we also show the modulatory role of intrinsic biological factors, such as estradiol (E2), triiodo-thyronine (T3), and glial cells, as potential effect modulators; Results: Results show a wide diversity in ED effects on ERβ mRNA expression, and that the magnitude of these ED effects highly depends on the presence or absence of E2, T3, and glial cells; Conclusion: The observed potency of the EDs to influence ERβ mRNA expression, and the modulatory role of E2, T3, and the glia suggests that environmental ED effects may be masked as long as the hormonal milieu is physiological, but may tend to turn additive or superadditive in case of hormone deficiency. PMID:27338438

  20. Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy

    Directory of Open Access Journals (Sweden)

    A.L. Márquez-Aguirre

    2015-01-01

    Full Text Available Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis, and converting non-β cells within the pancreas to β cells (transdifferentiation are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

  1. Types and distribution of mucous cells of the abalone Haliotis ...

    African Journals Online (AJOL)

    user

    2012-05-08

    May 8, 2012 ... Key words: Haliotis diversicolor; mucous cells, types, distribution. .... Figure 2. The shape of the mucous cells. O (oval or circle-like); c (cup- like); s ... (J) mucous cells at base of gill filaments, small cells, type II and type III; (K) a ...

  2. A Germanium Back Contact Type Thermophotovoltaic Cell

    International Nuclear Information System (INIS)

    Nagashima, Tomonori; Okumura, Kenichi; Yamaguchi, Masafumi

    2007-01-01

    A Ge back contact type photovoltaic cell has been proposed to reduce resistance loss for high current densities in thermophotovoltaic systems. The back contact structure requires less surface recombination velocities than conventional structures with front grid contacts. A SiO2/SiNx double anti-reflection coating including a high refractive index SiNx layer was studied. The SiNx layer has an enough passivation effect to obtain high efficiency. The quantum efficiency of the Ge cell was around 0.8 in the 800-1600 nm wavelength range. The conversion efficiency for infrared lights was estimated at 18% for a blackbody surface and 25% for a selective emitter by using the quantum efficiency and a simulation analysis

  3. Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Zhongmin Alex Ma

    2012-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic islet β-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to β-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS produced by β-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead to β-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reduced β-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochrome c release into cytosol and apoptosis. Group VIA phospholipase A2 (iPLA2β appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increases β-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects on β-cell mitochondrial phospholipids might prevent or retard development of T2DM.

  4. Increased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance

    OpenAIRE

    Mazzawi, Tarek; Gundersen, Doris Irene; Hausken, Trygve; El-Salhy, Magdy

    2015-01-01

    The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA i...

  5. Endocrine system: part 2.

    Science.gov (United States)

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

    2014-06-03

    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.

  6. SLEEP APNEA IN ENDOCRINE DISORDERS

    Directory of Open Access Journals (Sweden)

    I. V. Misnikova

    2016-01-01

    Full Text Available In the recent years, an association between sleep apnea and a  number of endocrine diseases has been established. The secretion of many hormones after falling asleep is considerably changed, compared to the period of wakefulness. In patients with endocrine disorders, abnormal hormonal secretion and its pathological consequences may contribute to sleep apnea. Sleep fragmentation and intermittent hypoxia arising in sleep apnea result in a decrease in insulin sensitivity, which contributes to the development of type 2 diabetes mellitus. The prevalence of sleep apnea increases in acromegaly, which may affect the risk of cardio-pulmonary complications. There is an association between sleep apnea and testosterone treatment in men, as well as in postmenopausal women. Sleep apnea in hypothyroidism is most frequently related to the development of hypothyroidism per se and can therefore be reversed with thyroid hormone replacement therapy. Timely detection and treatment of sleep apnea in patients with endocrine disorders can improve their survival prognosis and quality of life.

  7. [Novel concepts in biology of diffuse endocrine system: results and future investigations].

    Science.gov (United States)

    Iaglov, V V; Iaglova, N V

    2012-01-01

    Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.

  8. CT and MR imaging findings of endocrine tumor of the pancreas according to WHO classification

    International Nuclear Information System (INIS)

    Rha, Sung Eun; Jung, Seung Eun; Lee, Kang Hoon; Ku, Young Mi; Byun, Jae Young; Lee, Jae Mun

    2007-01-01

    The pancreatic endocrine tumors are rare neuroendocrine tumors of the pancreas originating from totipotential stem cells or differentiated mature endocrine cells within the exocrine gland. Endocrine tumors are usually classified into functioning and non-functioning tumors and presents with a range of benignity or malignancy. In this article, we present the various CT and MR imaging findings of endocrine tumors of pancreas according to recent WHO classification

  9. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

    OpenAIRE

    Saisho, Yoshifumi

    2016-01-01

    The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the ...

  10. Genome-edited human stem cell-derived beta cells: a powerful tool for drilling down on type 2 diabetes GWAS biology.

    Science.gov (United States)

    Beer, Nicola L; Gloyn, Anna L

    2016-01-01

    Type 2 diabetes (T2D) is a disease of pandemic proportions, one defined by a complex aetiological mix of genetic, epigenetic, environmental, and lifestyle risk factors. Whilst the last decade of T2D genetic research has identified more than 100 loci showing strong statistical association with disease susceptibility, our inability to capitalise upon these signals reflects, in part, a lack of appropriate human cell models for study. This review discusses the impact of two complementary, state-of-the-art technologies on T2D genetic research: the generation of stem cell-derived, endocrine pancreas-lineage cells and the editing of their genomes. Such models facilitate investigation of diabetes-associated genomic perturbations in a physiologically representative cell context and allow the role of both developmental and adult islet dysfunction in T2D pathogenesis to be investigated. Accordingly, we interrogate the role that patient-derived induced pluripotent stem cell models are playing in understanding cellular dysfunction in monogenic diabetes, and how site-specific nucleases such as the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system are helping to confirm genes crucial to human endocrine pancreas development. We also highlight the novel biology gleaned in the absence of patient lines, including an ability to model the whole phenotypic spectrum of diabetes phenotypes occurring both in utero and in adult cells, interrogating the non-coding 'islet regulome' for disease-causing perturbations, and understanding the role of other islet cell types in aberrant glycaemia. This article aims to reinforce the importance of investigating T2D signals in cell models reflecting appropriate species, genomic context, developmental time point, and tissue type.

  11. Types and distribution of mucous cells of the abalone Haliotis ...

    African Journals Online (AJOL)

    The types and distribution of mucous cells of Haliotis diversicolorwere observed and analyzed using the alcian blue and periodic acid schiffs (AB-PAS) reaction and histological procedures. According to the color of the mucous cells, they were divided into four types: Type I, pure red; type II, pure blue; type III, purple reddish; ...

  12. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

    DEFF Research Database (Denmark)

    Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae

    2015-01-01

    that line the ducts during development, and in the ducts after birth, but not in differentiated endocrine or acinar cells. Genetic inactivation of Bicc1 leads to ductal cell over-proliferation and cyst formation. Transcriptome comparison between WT and Bicc1 KO pancreata, before the phenotype onset, reveals......(+) endocrine progenitor production. Its deletion leads to a late but sustained endocrine progenitor decrease, resulting in a 50% reduction of endocrine cells. We show that BICC1 functions downstream of ONECUT1 in the pathway controlling both NEUROG3(+) endocrine cell production and ductal morphogenesis...

  13. The endolymphatic sac, a potential endocrine gland?

    DEFF Research Database (Denmark)

    Qvortrup, K; Rostgaard, J; Holstein-Rathlou, N H

    1999-01-01

    A previous investigation indicated that the chief cells of the endolymphatic sac produce an endogenous inhibitor of sodium re-absorption in the kidneys, which has tentatively been named "saccin". In this study, the ultrastructure of the endolymphatic sac and in particular the chief cells...... is described, demonstrating that this organ fulfils the morphological criteria of a potential endocrine gland. Accordingly, the chief cells are shown to exhibit all the organelles and characteristics of cells that simultaneously synthesize, secrete, absorb and digest proteins....

  14. Recombinant cell bioassays for the detection of (gluco) corticosteroids and endocrine-disrupting potencies of several enviromental PCB contaminants

    NARCIS (Netherlands)

    Bovee, T.F.H.; Helsdingen, J.R.; Hamers, A.R.M.; Brouwer, B.A.; Nielen, M.W.F.

    2011-01-01

    Sensitive and robust bioassays for glucocorticoids are very useful for the pharmaceutical industry, environmental scientists and veterinary control. Here, a recombinant yeast cell was constructed that expresses the human glucocorticoid receptor alpha and a green fluorescent reporter protein in

  15. The role of phytoplankton composition, biomass and cell volume in accumulation and transfer of endocrine disrupting compounds in the Southern Baltic Sea (The Gulf of Gdansk).

    Science.gov (United States)

    Staniszewska, Marta; Nehring, Iga; Zgrundo, Aleksandra

    2015-12-01

    Endocrine disrupting compounds (EDCs) like bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP) are introduced to the trophic webs through among others phytoplankton. This paper describes BPA, OP and NP concentrations in phytoplankton in the Gulf of Gdansk (Southern Baltic Sea) in the years 2011-2012. The assays of BPA, OP and NP in samples were performed using HPLC with fluorescence detection. The concentrations of BPA, the most commonly used of the three compounds, were over ten times higher than OP and NP concentrations. The concentrations of the studied EDCs in phytoplankton from the Gulf of Gdansk depended on anthropogenic factors and on phytoplankton properties (species composition, biomass, volume). An increase in phytoplankton biomass did not always result in an increase of BPA, OP and NP concentrations. However, the load of the studied EDCs accumulated in phytoplankton biomass increase with a rise of biomass. An increase in BPA, OP and NP concentrations was effected by biomass growth and the proportions ofciliates, dinoflagellates, diatoms and green algae. A strong positive correlation between OP and NP concentrations and negative correlation between BPA concentrations and biomass of organisms with cells measuring <1000 μm(3) in volume results from the differing properties of these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Endocrine neoplasms in familial syndromes of hyperparathyroidism.

    Science.gov (United States)

    Li, Yulong; Simonds, William F

    2016-06-01

    Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. © 2016 Society for Endocrinology.

  17. The preventive role of type 2 NKT cells in the development of type 1 diabetes.

    Science.gov (United States)

    Sørensen, Jakob Ørskov; Buschard, Karsten; Brogren, Carl-Henrik

    2014-03-01

    In the last two decades, natural killer T (NKT) cells have emerged as an important factor in preventing type 1 diabetes (T1D) when investigated in the experimental non-obese diabetic (NOD) mouse model. So far, investigations have largely focused on type 1 NKT cells with invariant T-cell receptors, whereas the role of type 2 NKT cells with diverse T-cell receptors is less well understood. However, there have been several findings which indicate that in fact type 2 NKT cells may regulate the progression of type 1 diabetes in NOD mice, including a fraction of these cells which recognize β-cell-enriched sulfatide. Therefore, the focus for this review is to present the current evidence of the effect of type 2 NKT cells on the development of T1D. In general, there is still uncertainty surrounding the mechanism of activation and function of NKT cells. Here, we present two models of the effector mechanisms, respectively, Th1/Th2 polarization and the induction of tolerogenic dendritic cells (DC). In conclusion, this review points to the importance of immunoregulation by type 2 NKT cells in preventing the development of T1D and highlights the induction of tolerogenic DC as a likely mechanism. The possible therapeutic role of type 1 and type 2 NKT cells are evaluated and future experiments concerning type 2 NKT cells and T1D are proposed. © 2013 APMIS. Published by John Wiley & Sons Ltd.

  18. Maternal microchimerism: increased in the insulin positive compartment of type 1 diabetes pancreas but not in infiltrating immune cells or replicating islet cells.

    Directory of Open Access Journals (Sweden)

    Jody Ye

    Full Text Available Maternal microchimeric cells (MMc transfer across the placenta during pregnancy. Increased levels of MMc have been observed in several autoimmune diseases including type 1 diabetes but their role is unknown. It has been suggested that MMc are 1 effector cells of the immune response, 2 targets of the autoimmune response or 3 play a role in tissue repair. The aim of this study was to define the cellular phenotype of MMc in control (n = 14 and type 1 diabetes pancreas (n = 8.Using sex chromosome-based fluorescence in-situ hybridization, MMc were identified in male pancreas and their phenotype determined by concomitant immunofluorescence.In normal pancreas, MMc positive for endocrine, exocrine, duct and acinar markers were identified suggesting that these cells are derived from maternal progenitors. Increased frequencies of MMc were observed in type 1 diabetes pancreas (p = 0.03 with particular enrichment in the insulin positive fraction (p = 0.01. MMc did not contribute to infiltrating immune cells or Ki67+ islet cell populations in type 1 diabetes.These studies provide support for the hypothesis that MMc in human pancreas are derived from pancreatic precursors. Increased frequencies of MMc beta cells may contribute to the initiation of autoimmunity or to tissue repair but do not infiltrate islets in type 1 diabetes.

  19. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  20. Spreeta-based biosensor for endocrine disruptors

    NARCIS (Netherlands)

    Marchesini, G.R.; Koopal, K.; Meulenberg, E.; Haasnoot, W.; Irth, H.

    2007-01-01

    The construction and performance of an automated low-cost Spreeta¿-based prototype biosensor system for the detection of endocrine disrupting chemicals (EDCs) is described. The system consists primarily of a Spreeta miniature liquid sensor incorporated into an aluminum flow cell holder, dedicated to

  1. What Is Men's Endocrine Health?

    Science.gov (United States)

    ... Search form Search What is Men's Endocrine Health? Men's endocrine health incorporates physical activity and sound nutrition to maintain a strong body; however, a major emphasis includes male sexuality ...

  2. Factors influencing the mechanical stability of alginate beads applicable for immunoisolation of mammalian cells

    NARCIS (Netherlands)

    Bhujbal, Swapnil V.; Paredes, Genaro A.; Niclou, Simone P.; de Vos, Paul

    Transplantation of microencapsulated cells has been proposed as a cure for many types of endocrine disorders. Alginate-based microcapsules have been used in many of the feasibility studied addressing cure of the endocrine disorders, and different cancer types. Despite years of intensive research it

  3. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  4. Endocrine pancreatic function changes after acute pancreatitis.

    Science.gov (United States)

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  5. Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling

    DEFF Research Database (Denmark)

    Sørensen, Amalie Møller; Hansen, Cecilie Hurup; Bonomo, Silvia

    2016-01-01

    ) and its two enantiomers on the human steroidogenesis using the H295R cell line. Differences in production of 16 steroid hormones were analyzed using LC-MS/MS. Additionally, to evaluate the differences in binding modes of these enantiomers, docking and molecular dynamics (MD) simulations of S-omeprazole (S......-OME) and R-omeprazole (R-OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17α-hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed...

  6. A Web-Server of Cell Type Discrimination System

    Directory of Open Access Journals (Sweden)

    Anyou Wang

    2014-01-01

    Full Text Available Discriminating cell types is a daily request for stem cell biologists. However, there is not a user-friendly system available to date for public users to discriminate the common cell types, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and somatic cells (SCs. Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top layer application of our recent publication regarding cell type discriminations, which employs DNA-methylation as biomarkers and machine learning models to discriminate cell types. Implemented by Django, Python, R, and Linux shell programming, run under Linux-Apache web server, and communicated through MySQL, WCTDS provides a friendly framework to efficiently receive the user input and to run mathematical models for analyzing data and then to present results to users. This framework is flexible and easy to be expended for other applications. Therefore, WCTDS works as a user-friendly framework to discriminate cell types and subtypes and it can also be expended to detect other cell types like cancer cells.

  7. Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt-Christensen, Anja; Hansen, Lisbeth; Ilegems, Erwin

    2013-01-01

    the endocrine pancreas during initiation and progression of insulitis in the NOD mouse. Individual, ACE-transplanted islets of Langerhans were longitudinally and repetitively imaged by stereomicroscopy and two-photon microscopy to follow fluorescently labelled leucocyte subsets. Results We demonstrate that......, in spite of the immune privileged status of the eye, the ACE-transplanted islets develop infiltration and beta cell destruction, recapitulating the autoimmune insulitis of the pancreas, and exemplify this by analysing reporter cell populations expressing green fluorescent protein under the Cd11c or Foxp3......Aims/hypothesis The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes. Methods We adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltrating...

  8. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Sleep and the endocrine system.

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. CD4+ CD25+ cells in type 1 diabetic patients with other autoimmune manifestations

    Directory of Open Access Journals (Sweden)

    Dalia S. Abd Elaziz

    2014-11-01

    Full Text Available The existence of multiple autoimmune disorders in diabetics may indicate underlying primary defects of immune regulation. The study aims at estimation of defects of CD4+ CD25+high cells among diabetic children with multiple autoimmune manifestations, and identification of disease characteristics in those children. Twenty-two cases with type 1 diabetes associated with other autoimmune diseases were recruited from the Diabetic Endocrine and Metabolic Pediatric Unit (DEMPU, Cairo University along with twenty-one normal subjects matched for age and sex as a control group. Their anthropometric measurements, diabetic profiles and glycemic control were recorded. Laboratory investigations included complete blood picture, glycosylated hemoglobin, antithyroid antibodies, celiac antibody panel and inflammatory bowel disease markers when indicated. Flow cytometric analysis of T-cell subpopulation was performed using anti-CD3, anti-CD4, anti-CD8, anti-CD25 monoclonal antibodies. Three cases revealed a proportion of CD4+ CD25+high below 0.1% and one case had zero counts. However, this observation did not mount to a significant statistical difference between the case and control groups neither in percentage nor absolute numbers. Significant statistical differences were observed between the case and the control groups regarding their height, weight centiles, as well as hemoglobin percentage, white cell counts and the absolute lymphocytic counts. We concluded that, derangements of CD4+ CD25+high cells may exist among diabetic children with multiple autoimmune manifestations indicating defects of immune controllers.

  11. Imaging of endocrine system

    International Nuclear Information System (INIS)

    Das, B.K.; Noreen Norfaraheen Lee Abdullah

    2012-01-01

    In recent years, the role of nuclear medicine in the study of morphology and pathophysiology of various endocrine organs has greatly expanded. Newly developed radiopharmaceuticals, new instrumentation, innovative study designs and dual isotope techniques have contributed significantly to the evaluation of parathyroid and adrenal diseases. In selected cases, patients with metabolic bone disorders and infertility have greatly been benefited. (author)

  12. Endocrine System (For Parents)

    Science.gov (United States)

    ... Problems With the Endocrine System Print en español Sistema endócrino Although we rarely think about them, the ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  13. Pediatric endocrine surgery development

    Directory of Open Access Journals (Sweden)

    Ivan I. Dedov

    2017-12-01

    Full Text Available Department of pediatric surgery at the Endocrinology Research Centre has been around for nearly two years. During operation, surgical treatment has received more than 500 patients with various endocrine disorders. The article discusses modern diagnostic approaches and surgical options for diseases included in the new direction of pediatric surgery – endocrine surgery in children. There are discussions about options for radical treatment of Graves disease in children, positive and negative aspects of surgical and radioactive iodine treatment. Is own stats of postoperative hyperparathyroidism. Is proposed to optimize the algorithm of actions in identifying thyroid nodules in children. In primary hyperparathyroidism, the emphasis is on the complexity of the postoperative management of patients related to the feature of children’s age in determining the severity of the reactions on the water-electrolyte disorders. Separately reviewed the literature of the adrenal glands diseases in children, demonstrating their own clinical cases which required surgical intervention. The authors describe the possibilities of modern neurosurgical equipment in the Endocrinology Research Centre in operations on the pituitary gland in children. Patients of different age groups performed transnasal transsphenoidal removal of tumors of the chiasm-sellar region using endoscopic assistance. The article also cited research data of pancreas diseases and their surgical treatment. Much attention is paid to the gender section of endocrine surgery in children. Discusses the tactics in disorders of sex development, gonadal tumors in children, diseases of the breast. In conclusion outlines the prospects for the development of endocrine surgery in children.

  14. Nigerian Endocrine Practice: Submissions

    African Journals Online (AJOL)

    Original Articles should be restricted to clinical or basic studies, particularly translational research, which add new information to the etiology, treatment, and outcomes of endocrine disorders that have not been published previously. These manuscripts should be restricted to 3,500 words, no more than 40 references, and no ...

  15. Nigerian Endocrine Practice

    African Journals Online (AJOL)

    The journal accepts original contributions related to the practice and science of clinical endocrinology, articles updating the clinical endocrinologist on current areas of interest in the diagnosis and treatment of endocrine disorders, articles discussing dilemma facing endocrinologists in the clinical, social, and ethical arena of ...

  16. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...

  17. Repopulation of denuded tracheal grafts with alveolar type II cells

    International Nuclear Information System (INIS)

    Johnson, N.F.

    1988-01-01

    Repopulation of denuded heterotopic tracheal grafts with populations of specific epithelial cell types is one approach to study the differentiation potential of various cell types. This technique has been adopted to delineate the differentiation pathways of alveolar type II cells isolated from rat lungs. Under the conditions of this experiment, the reestablished epithelial lining was alveolar-like, however, ultrastructural analysis of the cells showed them to be like Clara cells. These preliminary results suggest that the secretary cells of the lung parenchyma and terminal airways may share a common ancestry. (author)

  18. The role of phytoplankton composition, biomass and cell volume in accumulation and transfer of endocrine disrupting compounds in the Southern Baltic Sea (The Gulf of Gdansk)

    International Nuclear Information System (INIS)

    Staniszewska, Marta; Nehring, Iga; Zgrundo, Aleksandra

    2015-01-01

    Endocrine disrupting compounds (EDCs) like bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP) are introduced to the trophic webs through among others phytoplankton. This paper describes BPA, OP and NP concentrations in phytoplankton in the Gulf of Gdansk (Southern Baltic Sea) in the years 2011–2012. The assays of BPA, OP and NP in samples were performed using HPLC with fluorescence detection. The concentrations of BPA, the most commonly used of the three compounds, were over ten times higher than OP and NP concentrations. The concentrations of the studied EDCs in phytoplankton from the Gulf of Gdansk depended on anthropogenic factors and on phytoplankton properties (species composition, biomass, volume). An increase in phytoplankton biomass did not always result in an increase of BPA, OP and NP concentrations. However, the load of the studied EDCs accumulated in phytoplankton biomass increase with a rise of biomass. An increase in BPA, OP and NP concentrations was effected by biomass growth and the proportions ofciliates, dinoflagellates, diatoms and green algae. A strong positive correlation between OP and NP concentrations and negative correlation between BPA concentrations and biomass of organisms with cells measuring <1000 μm"3 in volume results from the differing properties of these compounds. - Highlights: • The concentration of BPA was higher than OP, NP in phytoplankton. • The concentration of BPA, OP, NP depended on phytoplankton properties. • The load of BPA, OP, NP accumulated with phytoplankton increase with a rise of the biomass. • Ciliates, dinoflagellates, diatoms, green algae accumulated the most BPA, OP, NP. • Higher biomass of smaller volume organisms more accumulated OP, NP and less BPA. - The study has shown that factors affecting concentration of BPA, NP and OP were: species composition, biomass, volume and location of sampling station.

  19. Current advanced therapy cell-based medicinal products for type-1-diabetes treatment.

    Science.gov (United States)

    Cañibano-Hernández, Alberto; Del Burgo, Laura Sáenz; Espona-Noguera, Albert; Ciriza, Jesús; Pedraz, Jose Luis

    2018-03-27

    In the XXI century diabetes mellitus has become one of the main threats to human health with higher incidence in regions such as Europe and North America. Type 1 diabetes mellitus (T1DM) occurs as a consequence of the immune-mediated destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. The administration of exogenous insulin through daily injections is the most prominent treatment for T1DM but its administration is frequently associated to failure in glucose metabolism control, finally leading to hyperglycemia episodes. Other approaches have been developed in the past decades, such as whole pancreas and islet allotransplantation, but they are restricted to patients who exhibit frequent episodes of hypoglycemia or renal failure because the lack of donors and islet survival. Moreover, patients transplanted with either whole pancreas or islets require of immune suppression to avoid the rejection of the transplant. Currently, advanced therapy medicinal products (ATMP), such as implantable devices, have been developed in order to reduce immune rejection response while increasing cell survival. To overcome these issues, ATMPs must promote vascularization, guaranteeing the nutritional contribution, while providing O 2 until vasculature can surround the device. Moreover, it should help in the immune-protection to avoid acute and chronic rejection. The transplanted cells or islets should be embedded within biomaterials with tunable properties like injectability, stiffness and porosity mimicking natural ECM structural characteristics. And finally, an infinitive cell source that solves the donor scarcity should be found such as insulin producing cells derived from mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Several companies have registered their ATMPs and future studies envision new prototypes. In this review, we will discuss the mechanisms and etiology of

  20. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

    Science.gov (United States)

    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

  1. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through

  2. Dual Paraneoplastic Endocrine Syndromes Heralding Onset of Extrapulmonary Small Cell Carcinoma: A Case Report and Narrative Review

    Directory of Open Access Journals (Sweden)

    Jill B. Feffer

    2018-04-01

    Full Text Available ObjectiveExtrapulmonary small cell carcinoma (EPSCC is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance.MethodsClinical, laboratory, imaging, and pathology data are presented.ResultsA 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube. Laboratory results included calcium 13.8 mg/dL (8.5–10.5 mg/dL, albumin 3.6 g/dL (3.5–5 mg/dL, and potassium 2.8 mmol/L (3.5–5.2 mmol/L. Hypercalcemia investigation revealed intact PTH 19 pg/mL (16–87 pg/mL, 25-OH vitamin D 15.7 ng/mL (>30 ng/mL, and PTH-related peptide (PTHrP 63.4 pmol/L (<2.3 pmol/L. Workup for hypokalemia yielded aldosterone 5.3 ng/dL (<31 ng/dL, renin 0.6 ng/mL/h (0.5–4 ng/mL/h, and 6:00 a.m. cortisol 82 µg/dL (6.7–22.6 µg/dL with ACTH 147 pg/mL (no ref. range. High-dose Dexamethasone suppression testing suggested ACTH-dependent ectopic hypercortisolism. Contrast-enhanced CT findings included masses in the liver and right renal pelvis, a heterogeneous enlarged mass in the region of the prostate invading the bladder, bilateral adrenal thickening, and lytic lesions in the pelvis and spine. Liver biopsy identified epithelioid malignancy with Ki proliferation index 98% and immunohistochemical staining positive for synaptophysin and neuron-specific enolase, compatible with high-grade small cell carcinoma. Staining for ACTH was negative; no stain for CRH was available. Two weeks after chemotherapy, 6:00 a.m. cortisol normalized and CT scans showed universal improvement.ConclusionExtensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes.

  3. Diabetic and endocrine emergencies

    OpenAIRE

    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, hyperca...

  4. Endocrine disorders in pregnancy

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Mathiesen, Elisabeth R

    2011-01-01

    The endocrinology of pregnancy involves endocrine and metabolic changes as a consequence of physiological alterations at the foetoplacental boundary between mother and foetus. The vast changes in maternal hormones and their binding proteins complicate assessment of the normal level of most hormones...... during gestation. The neuroendocrine events and their timing in the placental, foetal and maternal compartments are critical for initiation and maintenance of pregnancy, for foetal growth and development, and for parturition. As pregnancy advances, the relative number of trophoblasts increase...

  5. Radiotherapy of endocrine orbitopathy

    International Nuclear Information System (INIS)

    Weischedel, U.; Wieland, C.

    1985-01-01

    After a review of the history and a discussion of recent theories about pathogenesis of endocrine ophthalmopathy the authros give a report on their radiotherapeutical treatment results with cobalt-60-γ-rays in 50 patients. Amelioration was achieved in 50% of the cases, in the other 50% no progression was seen. Radiotherapy is of antiphlogistic and functional effectivity and should be integrated in the treatment regime in early stages. (orig.) [de

  6. Improved fuel-cell-type hydrogen sensor

    Science.gov (United States)

    Rudek, F. P.; Rutkowski, M. D.

    1968-01-01

    Modified hydrogen sensor replaces oxygen cathode with a cathode consisting of a sealed paste of gold hydroxide and a pure gold current collector. The net reaction which occurs during cell operation is the reduction of the gold hydroxide to gold and water, with a half-cell potential of 1.4 volts.

  7. Tissue-type plasminogen activator in somatostatin cells of rat pancreas and hypothalamus

    DEFF Research Database (Denmark)

    Kristensen, P; Larsson, L I; Danø, K

    1987-01-01

    -PA, and immunoblotting analysis demonstrated one band with a similar electrophoretic mobility. No urokinase-type PA immunoreactivity was found in the rat endocrine pancreas. A granular t-PA immunoreactivity resembling that found in adjacent sections with somatostatin antiserum was found in the median eminence...

  8. [Endocrine function in obesity].

    Science.gov (United States)

    Álvarez-Castro, Paula; Sangiao-Alvarellos, Susana; Brandón-Sandá, Iria; Cordido, Fernando

    2011-10-01

    Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels. Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.

  9. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.

    1995-12-01

    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  10. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    Science.gov (United States)

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

  11. Disruption of type 2 iodothyronine deiodinase activity in cultured human glial cells by polybrominated diphenyl ethers.

    Science.gov (United States)

    Roberts, Simon C; Bianco, Antonio C; Stapleton, Heather M

    2015-06-15

    Polybrominated diphenyl ether (PBDE) flame retardants are endocrine disruptors and suspected neurodevelopmental toxicants. While the direct mechanisms of neurodevelopmental toxicity have not been fully elucidated, it is conceivable that alterations in thyroid hormone levels in the developing brain may contribute to these effects. Cells within the brain locally convert thyroxine (T4) to the biologically active triiodothyronine (T3) through the action of the selenodeiodinase type 2 iodothyronine deiodinase (DIO2). Previous studies have demonstrated that PBDEs can alter hepatic deiodinase activity both in vitro and in vivo; however, the effects of PBDEs on the deiodinase isoforms expressed in the brain are not well understood. Here, we studied the effects of several individual PBDEs and hydroxylated metabolites (OH-BDEs) on DIO2 activity in astrocytes, a specialized glial cell responsible for production of more than 50% of the T3 required by the brain. Primary human astrocytes and H4 glioma cells were exposed to individual PBDEs or OH-BDEs at concentrations up to 5 μM. BDE-99 decreased DIO2 activity by 50% in primary astrocyte cells and by up to 80% in the H4 cells at doses of ≥500 nM. 3-OH-BDE-47, 6-OH-BDE-47, and 5'-OH-BDE-99 also decreased DIO2 activity in cultured H4 glioma cells by 45-80% at doses of approximately 1-5 μM. Multiple mechanisms appear to contribute to the decreased DIO2 activity, including weakened expression of DIO2 mRNA, competitive inhibition of DIO2, and enhanced post-translational degradation of DIO2. We conclude that decreases in DIO2 activity caused by exposure to PBDEs may play a role in the neurodevelopmental deficits caused by these toxicants.

  12. Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.

    Science.gov (United States)

    Anway, Matthew D; Memon, Mushtaq A; Uzumcu, Mehmet; Skinner, Michael K

    2006-01-01

    The current study was designed to examine the actions of a model endocrine disruptor on embryonic testis development and male fertility. Pregnant rats (F0) that received a transient embryonic exposure to an environmental endocrine disruptor, vinclozolin, had male offspring (F1) with reduced spermatogenic capacity. The reduced spermatogenetic capacity observed in the F1 male offspring was transmitted to the subsequent generations (F2-F4). The administration of vinclozolin, an androgen receptor antagonist, at 100 mg/kg/day from embryonic day 8-14 (E8-E14) of pregnancy to only the F0 dam resulted in a transgenerational phenotype in the subsequent male offspring in the F1-F4 generations. The litter size and male/female sex ratios were similar in controls and the vinclozolin generations. The average testes/body weight index of the postnatal day 60 (P60) males was not significantly different in the vinclozolin-treated generations compared to the controls. However, the testicular spermatid number, as well as the epididymal sperm number and motility, were significantly reduced in the vinclozolin generations compared to the control animals. Postnatal day 20 (P20) testis from the vinclozolin F2 generation had no morphological abnormalities, but did have an increase in spermatogenic cell apoptosis. Although the P60 testis morphology was predominantly normal, the germ cell apoptosis was significantly increased in the testes cross sections of animals from the vinclozolin generations. The increase in apoptosis was stage-specific in the testis, with tubules at stages IX-XIV having the highest increase in apoptotic germ cells. The tubules at stages I-V also had an increase in apoptotic germ cells compared to the control samples, but tubules at stages VI-VIII had no increase in apoptotic germ cells. An outcross of a vinclozolin generation male with a wild-type female demonstrated that the reduced spermatogenic cell phenotype was transmitted through the male germ line. An outcross

  13. Radiation effects on polyethylene foam of open cell type

    International Nuclear Information System (INIS)

    Tang Beilin; Kanako Kaji; Iwao Yoshizawa; Choji Kohara; Motoyoshi Hatada

    1991-01-01

    The effects of electron beam irradiation on polyethylene foam of open cell type have been studied. Experiments for determining of gel fraction and physical-mechanical properties of irradiated polyethylene foam of open cell type as a function of dose, respectively, were carried out. The dimensional stability of irradiated specimens at elevated temperatures was measured. It was found that tensile strength did not change and gel fraction increased when the specimen was irradiated in nitrogen atmosphere with increasing dose up to 300 kGy. The result shows that dimensional stability of polyethylene foam of open cell type after being kept in an oven at 70 deg C and 110 deg C for 22 h is improved by irradiation in nitrogen atmosphere. The similar results of irradiated EVA foam of open cell type irradiated foam of open cell type were obtained

  14. New-tools to assess the toxicological hazard of endocrine disruptor organoclorine contaminants in Mediterranean cetaceans

    Energy Technology Data Exchange (ETDEWEB)

    M. Cristina Fossi; Marsili, L.; Casini, S. [Dept. of Environmental Sciences, Univ. of Siena (Italy)

    2004-09-15

    The Mediterranean top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants (OCs), incurring high toxicological risk. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Four types of organochlorine endocrine disruptors are commonly found in Mediterranean cetaceans: (1) environmental estrogens, (2) environmental androgens, (3) anti-estrogens and (4) anti-androgens. Endocrine disruptors act by mimicking sex steroid hormones, both estrogens and androgens, by binding to hormone receptors or influencing cell pathways (environmental estrogens and androgens), or by blocking and altering hormone receptor binding (anti-estrogens, antiandrogens). Environmental estrogens are the most common and most widely studied EDCs. The relative estrogenic power of these chemicals, identified by in vitro and in vivo screening methods is rather weak (10{sup -3} or less) compared with the reference power of 17-estradiol or DES. However, the high levels of organochlorine compounds detected in marine mammals, particularly in pinnipeds and odontocetes, and consequently, the high levels of organochlorines with ED capacity, cannot be ignored. Here the hypothesis that some Mediterranean cetaceans (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus) are ''potentially at risk'' due to organochlorines with endocrine disrupting capacity is investigated using new non-lethal tools. As ''diagnostic'' tool we use benzo(a)pyrene monooxygenase (CYP1A1) activity in skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. As ''prognostic'' tool we propose the immunofluorescence technique in fibroblast cell cultures, for a qualitative and quantitative evaluation of the target

  15. Cell Type-Specific Contributions to the TSC Neuropathology

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0415 TITLE: Cell Type-Specific Contributions to the TSC Neuropathology PRINCIPAL INVESTIGATOR: Gabriella D’Arcangelo...AND SUBTITLE Cell Type-Specific Contributions to the TSC Neuropathology 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0415 5c. PROGRAM...how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells , in vivo

  16. Transcriptome atlas of eight liver cell types uncovers effects of ...

    Indian Academy of Sciences (India)

    ... types, and bioinformatic and systems biology approaches were employed to analyse the relationship between above genes and rat liver regeneration. The results showed that the urocanic acid (UA) was degraded from histidine in Kupffer cells, acts on Kupffer cells itself and dendritic cells to generate immune suppression ...

  17. Manipulation of the extracellular microenvironment by micro- and nanotechnology approaches to improve the generation of pancreatic endocrine cells from human embryonic stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Camilla Holzmann; Rønn Petersen, Dorthe

    ) alteration of substrate topography and elasticity (paper 2) and 3) initial seeding and cell distribution (paper 3). With the first strategy an array screen was performed to systematically identify ECM protein coatings, which induced or inhibited the differentiation of hES cells towards DE. Almost 500...... different ECM protein combinations were screened and several candidates were found. The majority of these candidates could be validated in microtitre well plates and further studies demonstrated that certain ECM proteins regulate the differentiation of hES cells towards DE. Netrin 1, collagen 1 and collagen...... characters. The study consisted of an investigation of the differentiation of hES cells towards DE and PE on nanopillars. The nanopillars with soft character were not favoured by hES cells with regards to attachment and growth. However, DE cells appeared earlier during the DE differentiation on the soft...

  18. Radiological imaging in endocrine hypertension

    Directory of Open Access Journals (Sweden)

    Chandan J Das

    2011-01-01

    Full Text Available While different generations of assays have played important role in elucidating causes of different endocrine disorders, radiological techniques are instrumental in localizing the pathology. This statement cannot be truer in any disease entity other than endocrine hypertension. This review makes an effort to highlight the role of different radiological modalities, especially ultrasonography, computed tomography and magnetic resonance imaging, in the evaluation of different causes of endocrine hypertension.

  19. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  20. Functional cell types in taste buds have distinct longevities.

    Directory of Open Access Journals (Sweden)

    Isabel Perea-Martinez

    Full Text Available Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

  1. Functional cell types in taste buds have distinct longevities.

    Science.gov (United States)

    Perea-Martinez, Isabel; Nagai, Takatoshi; Chaudhari, Nirupa

    2013-01-01

    Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU) to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor) taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic) taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

  2. Electrical Characterization of HIT type solar cells

    NARCIS (Netherlands)

    Rath, J.K.

    2012-01-01

    The silicon heterojunction solar cell (SHJ) has made rapid progress in reaching high efficiency and it is already developed as an industrially viable product. However, much of its progress has come through process development while there is scarce knowledge on the microscopic nature of the

  3. Characterization of HIT type solar cells

    NARCIS (Netherlands)

    Rath, J.K.

    2011-01-01

    The silicon heterojunction solar cell (SHJ) has made rapid progress in reaching high efficiency and it is already developed as an industrially viable product. However, much of its progress has come through process development while there is scarce knowledge on the microscopic nature of the

  4. Patient characteristics related to metabolic disorders and chronic complications in type 2 diabetes mellitus patients hospitalized at the Qingdao Endocrine and Diabetes Hospital from 2006 to 2012 in China.

    Science.gov (United States)

    Dong, Yanhu; Gao, Weiguo; Zhang, Lei; Wei, Jia; Hammar, Niklas; Cabrera, Claudia S; Wu, Xiaoli; Qiao, Qing

    2017-01-01

    To study the clinical characteristics related to metabolic disorders and complications in type 2 diabetes mellitus patients hospitalized in the Qingdao Endocrine and Diabetes Hospital from 2006 to 2012 in Qingdao, China. Data from 14,289 (51% males) type 2 diabetes mellitus patients hospitalized between 2006 and 2012 were collected and analysed. Information on patients' demographic, anthropometric, laboratory and disease histories were extracted from electronic medical records. The mean age of the patients was 60.5 years, with median diabetes duration of 9.0 years. Mean haemoglobin A1c was 8.4%, where 1.9% had hypertriglyceridaemia. Retinopathy was diagnosed in 51.1% of patients, nephropathy in 21.6%, neuropathy in 50.4%, hypertension in 77.4%, coronary heart disease in 27.6% and peripheral vascular disease in 58.6%. Once hospitalized, 71.1% of patients underwent insulin injection treatments, either mono-therapy or combined with other anti-diabetic drugs. Metformin was prescribed to 36.9% of patients, followed by acarbose 29.9%, thiazolidinediones 18.1%, meglitinides 14.8% and sulfonylureas 10.7%. Inadequate control of hyperglycaemia, poor metabolic profiles and diabetic complications were common challenges for long-term diabetes management in Chinese patients with type 2 diabetes mellitus. © The Author(s) 2016.

  5. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy

    2008-01-01

    The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Type...... II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells...

  6. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset.

    Science.gov (United States)

    Dasgupta, Suryasarathi; Kumar, Vipin

    2016-08-01

    Type II natural killer T cells (NKT) are a subset of the innate-like CD1d-restricted lymphocytes that are reactive to lipid antigens. Unlike the type I NKT cells, which express a semi-invariant TCR, type II NKT cells express a broader TCR repertoire. Additionally, other features, such as their predominance over type I cells in humans versus mice, the nature of their ligands, CD1d/lipid/TCR binding, and modulation of immune responses, distinguish type II NKT cells from type I NKT cells. Interestingly, it is the self-lipid-reactivity of type II NKT cells that has helped define their physiological role in health and in disease. The discovery of sulfatide as one of the major antigens for CD1d-restricted type II NKT cells in mice has been instrumental in the characterization of these cells, including the TCR repertoire, the crystal structure of the CD1d/lipid/TCR complex, and their function. Subsequently, several other glycolipids and phospholipids from both endogenous and microbial sources have been shown to activate type II NKT cells. The activation of a specific subset of type II NKT cells following administration with sulfatide or lysophosphatidylcholine (LPC) leads to engagement of a dominant immunoregulatory pathway associated with the inactivation of type I NKT cells, conventional dendritic cells, and inhibition of the proinflammatory Th1/Th17 cells. Thus, type II NKT cells have been shown to be immunosuppressive in autoimmune diseases, inflammatory liver diseases, and in cancer. Knowing their relatively higher prevalence in human than type I NKT cells, understanding their biology is imperative for health and disease.

  7. 3-D Imaging Reveals Participation of Donor Islet Schwann Cells and Pericytes in Islet Transplantation and Graft Neurovascular Regeneration

    OpenAIRE

    Juang, Jyuhn-Huarng; Kuo, Chien-Hung; Peng, Shih-Jung; Tang, Shiue-Cheng

    2015-01-01

    The primary cells that participate in islet transplantation are the endocrine cells. However, in the islet microenvironment, the endocrine cells are closely associated with the neurovascular tissues consisting of the Schwann cells and pericytes, which form sheaths/barriers at the islet exterior and interior borders. The two cell types have shown their plasticity in islet injury, but their roles in transplantation remain unclear. In this research, we applied 3-dimensional neurovascular histolo...

  8. Freedom of expression: cell-type-specific gene profiling.

    Science.gov (United States)

    Otsuki, Leo; Cheetham, Seth W; Brand, Andrea H

    2014-01-01

    Cell fate and behavior are results of differential gene regulation, making techniques to profile gene expression in specific cell types highly desirable. Many methods now enable investigation at the DNA, RNA and protein level. This review introduces the most recent and popular techniques, and discusses key issues influencing the choice between these such as ease, cost and applicability of information gained. Interdisciplinary collaborations will no doubt contribute further advances, including not just in single cell type but single-cell expression profiling. © 2014 Wiley Periodicals, Inc.

  9. X-Ray semiotics of cranial involvement in endocrine diseases

    International Nuclear Information System (INIS)

    Spuzyak, M.I.; Kramnoj, I.E.; Belaya, L.M.; Tyazhelova, O.V.; Litvinenko, V.M.

    1992-01-01

    The incidence and type of X-ray semeiotics of the skull involvement were studied in 703 patients with endocrine diseases. Craniorgam analysis involved study of the thickness and structure of the vault bones, shape and size of the skull, status of the sutures, internal plate relief, changes of the base of the skull, of the sella turcica first of all, and facial bone. The characteristic X-ray symprom complexes of the involvement of the skull in some endocrine diseases were distinguished

  10. Your Endocrine System (For Kids)

    Science.gov (United States)

    ... Kids / Your Endocrine System Print en español Tu sistema endocrino You might say endocrine (say: EN-doh- ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  11. Mitochondrial disease and endocrine dysfunction.

    Science.gov (United States)

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  12. Glutathione synthesis and homeostasis in isolated type II alveolar cells

    International Nuclear Information System (INIS)

    Saito, K.; Warshaw, J.B.; Prough, R.A.

    1986-01-01

    After isolation of Type II cells from neonatal rat lung, the glutathione (GSH) levels in these cells were greatly depressed. The total glutathione content could be increased 5-fold within 12-24 h by incubating the cells in media containing sulfur amino acids. Similarly, the activity of γ-glutamyltranspeptidase was low immediately after isolation, but was increased 2-fold during the first 24 h culture. Addition of either GSH or GSSG to the culture media increased the GSH content of Type II cells 2-2.5-fold. Buthionine sulfoximine and NaF prevented this replenishment of GSH during 24 h culture. When the rates of de novo synthesis of GSH and GSSG from 35 S-cysteine were measured, the amounts of newly formed GSH decreased to 80% in the presence of GSH or GSSG. This suggests that exogenous GSH/GSSG can be taken up by the Type II cells to replenish the intracellular pool of GSH. Methionine was not as effective as cysteine in the synthesis of GSH. These results suggest that GSH levels in the isolated Type II cell can be maintained by de novo synthesis or uptake of exogenous GSH. Most of the GSH synthesized from cysteine, however, was excreted into the media of the cultured cells indicative of a potential role for the type II cell in export of the non-protein thiol

  13. [Dementia due to Endocrine Diseases].

    Science.gov (United States)

    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.

  14. Endocrine disorders in mitochondrial disease.

    Science.gov (United States)

    Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

    2013-10-15

    Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease.

    Science.gov (United States)

    Weng, Xiufang; He, Ying; Visvabharathy, Lavanya; Liao, Chia-Min; Tan, Xiaosheng; Balakumar, Arjun; Wang, Chyung-Ru

    2017-10-01

    Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of type II NKT cells in the etiology of chronic liver inflammation. Transgenic mice with the Lck promoter directing CD1d overexpression on T cells in Jα18 wild-type (Lck-CD1dTgJα18 + ; type I NKT cell sufficient) and Jα18-deficient (Lck-CD1dTgJα18 o , type I NKT cell deficient) mice were analyzed for liver pathology and crosstalk between type II NKT cells and conventional T cells. CD1d expression on T cells in peripheral blood samples and liver sections from autoimmune hepatitis patients and healthy individuals were also examined. Lck-CD1dTgJα18 o and Lck-CD1dTgJα18 + mice developed similar degrees of liver pathology resembling chronic autoimmune hepatitis in humans. Increased CD1d expression on T cells promoted the activation of type II NKT cells and other T cells. This resulted in T h 1-skewing and impaired T h 2 cytokine production in type II NKT cells. Dysfunction of type II NKT cells was accompanied by conventional T cell activation and pro-inflammatory cytokine production, leading to a hepatic T/B lymphocyte infiltration, elevated autoantibodies and hepatic injury in Lck-CD1dTg mice. A similar mechanism could be extended to humans as CD1d expression is upregulated on activated human T cells and increased presence of CD1d-expressing T cells was observed in autoimmune hepatitis patients. Our data reveals enhanced crosstalk between type II NKT cells and conventional T cells, leading to a T h 1-skewed inflammatory milieu, and consequently, to the development of chronic autoimmune liver disease. Lay summary: CD1d overexpression on T cells enhances crosstalk between type II NKT cells and T cells, resulting in their aberrant activation and leading to the

  16. Retrofit designs for small bench-type blood cell counters.

    Science.gov (United States)

    Ferris, C D

    1991-01-01

    This paper describes several retrofit designs to correct operational problems associated with small bench-type blood cell counters. Replacement electronic circuits as well as modifications to the vacuum systems are discussed.

  17. Mid-infrared spectroscopy in skin cancer cell type identification

    Science.gov (United States)

    Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

    2017-07-01

    Mid infrared spectroscopy samples were developed for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin cancer diagnostics.

  18. Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

    LENUS (Irish Health Repository)

    Rahma, M B.

    2016-09-01

    A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

  19. Development of a dual luciferase activity and fluorescamine protein assay adapted to a 384 micro-well plate format: Reducing variability in human luciferase transactivation cell lines aimed at endocrine active substances

    Science.gov (United States)

    Brennan, Jennifer; Tillitt, Donald E.

    2018-01-01

    There is a need to adapt cell bioassays to 384-well and 1536-well formats instead of the traditional 96-well format as high-throughput screening (HTS) demands increase. However, the sensitivity and performance of the bioassay must be re-verified in these higher micro-well plates, and verification of cell health must also be HT (high-throughput). We have adapted two commonly used human breast luciferase transactivation cell bioassays, the recently re-named estrogen agonist/antagonist screening VM7Luc4E2 cell bioassay (previously designated BG1Luc4E2) and the androgen/glucocorticoid screening MDA-kb2 cell bioassay, to 384-well formats for HTS of endocrine-active substances (EASs). This cost-saving adaptation includes a fast, accurate, and easy measurement of protein amount in each well via the fluorescamine assay with which to normalize luciferase activity of cell lysates without requiring any transfer of the cell lysates. Here we demonstrate that by accounting for protein amount in the cell lysates, antagonistic agents can easily be distinguished from cytotoxic agents in the MDA-kb2 and VM7Luc4E2 cell bioassays. Additionally, we demonstrate via the fluorescamine assay improved interpretation of luciferase activity in wells along the edge of the plate (the so-called “edge effect”), thereby increasing usable wells to the entire plate, not just interior wells.

  20. β-Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells.

    Science.gov (United States)

    Sui, Lina; Danzl, Nichole; Campbell, Sean R; Viola, Ryan; Williams, Damian; Xing, Yuan; Wang, Yong; Phillips, Neil; Poffenberger, Greg; Johannesson, Bjarki; Oberholzer, Jose; Powers, Alvin C; Leibel, Rudolph L; Chen, Xiaojuan; Sykes, Megan; Egli, Dieter

    2018-01-01

    β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These β-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-β-cells maintain normal blood glucose levels after ablation of the mouse endogenous β-cells. Cystic structures, but no teratomas, were observed in NT-ES-β-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in β-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-β-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy. © 2017 by the American Diabetes Association.

  1. [Functional properties of taste bud cells. Mechanisms of afferent neurotransmission in Type II taste receptor cells].

    Science.gov (United States)

    Romanov, R A

    2013-01-01

    Taste Bud cells are heterogeneous in their morphology and functionality. These cells are responsible for sensing a wide variety of substances and for associating detected compounds with a different taste: bitter, sweet, salty, sour and umami. Today we know that each of the five basic tastes corresponds to distinct cell populations organized into three basic morpho-functional cell types. In addition, some receptor cells of the taste bud demonstrate glia-related functions. In this article we expand on some properties of these three morphological receptor cell types. Main focus is devoted to the Type II cells and unusual mechanism for afferent neurotransmission in these cells. Taste cells of the Type II consist of three populations detecting bitter, sweet and umami tastes, and, thus, evoke a serious scientific interest.

  2. Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth

    Directory of Open Access Journals (Sweden)

    Jan Krivanek

    2017-06-01

    Full Text Available Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix–producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

  3. Endocrine disrupting compounds

    DEFF Research Database (Denmark)

    Bøgh, I B; Christensen, P; Dantzer, V

    2001-01-01

    of alkylphenols, these are disseminated in the environment with sewage sludge, and domestic animals and humans are likely to be exposed via the food chain. Using the pig as an in vivo model, we studied the effect of intrauterine exposure to tertiary octylphenol (OP) on essential reproductive parameters over 3......With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...

  4. MANAGEMENT OF ENDOCRINE DISEASE: The effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

    Science.gov (United States)

    Krul-Poel, Yvonne H M; Ter Wee, Marieke M; Lips, Paul; Simsek, Suat

    2017-01-01

    Epidemiologic studies suggest that vitamin D status plays a role in glycaemic control in patients with type 2 diabetes. However, intervention studies yielded inconsistent results. The aim of this study is to systematically review the effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes. Systematic review and meta-analysis. We searched Medline, Embase and the Cochrane Library for RCTs examining the effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes. A random-effects model meta-analysis was performed to obtain a summarized outcome of vitamin D supplementation on HbA 1c , fasting glucose and homeostasis model assessment - insulin resistance (HOMA-IR). Twenty-three RCTs were included in this systematic review representing a total of 1797 patients with type 2 diabetes. Mean (± s.d.) change in serum 25-hydroxyvitamin D varied from 1.8 ± 10.2 nmol/L to 80.1 ± 54.0 nmol/L. Nineteen studies included HbA 1c as outcome variable. Combining these studies no significant effect in change of HbA 1c was seen after vitamin D intervention compared with placebo. A significant effect of vitamin D supplementation was seen on fasting glucose in a subgroup of studies (n = 4) with a mean baseline HbA 1c  ≥ 8% (64 mmol/mol) (standardized difference in means: 0.36; 95% CI: 0.12-0.61, P = 0.003). Current evidence of RCTs does not support short-term vitamin D supplementation in a heterogeneous population with type 2 diabetes. However, in patients with poorly controlled diabetes, a favourable effect of vitamin D is seen on fasting glucose. © 2017 European Society of Endocrinology.

  5. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies

  6. The endocrine disruption properties of an adipose contaminant mixture extracted from East Greenland polar bears studied in the H295R cell line

    DEFF Research Database (Denmark)

    Hjorth, R.; Letcher, R. J.; Blair, D.

    been well described and especially the polar bear (Ursus maritimus) is recognized as being one of the most contaminated species in the Arctic. The present study investigated the in vitro endocrine disruptive effects of the POP mixture found in adipose tissue from 10 East Greenland polar bears collected...... (dehydroepiandrosterone and androstenedione). These results demonstrated comprehensive in vitro effects of POPs extracted from polar bear adipose tissue on key elements in the steroidogenesis, and identifies disruption of CYP17 activity as a mode of action. A POP-induced interference with CYP17 can potentially explain...... previously observed hormone levels in polar bears and could pose a risk to their reproductive health....

  7. Monogenic autoimmune diseases of the endocrine system.

    Science.gov (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Endocrine potency of wastewater: Contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays

    DEFF Research Database (Denmark)

    Kusk, Kresten Ole; Krüger, Tanja; Long, Manhai

    2011-01-01

    chemical analysis and a battery of bioassays. Influent samples, collected at the first STP grate, and effluent samples, collected after the sewage treatment, were extracted using solid phase extraction. Extracts were analyzed for the content of a range of industrial chemicals with endocrine disrupting...... properties: phthalate metabolites, parabens, industrial phenols, ultraviolet screens, and natural and synthetic steroid estrogens. The endocrine disrupting bioactivity and toxicity of the extracts were analyzed in cell culture assay for the potency to affect the function of the estrogen, androgen, aryl......Industrial and municipal effluents are important sources of endocrine disrupting compounds (EDCs) discharged into the aquatic environment. This study investigated the endocrine potency of wastewater and the cleaning efficiency of two typical urban Danish sewage treatment plants (STPs), using...

  9. The development and plasticity of alveolar type 1 cells

    Science.gov (United States)

    Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  10. Purinergic receptors in the endocrine and exocrine pancreas

    DEFF Research Database (Denmark)

    Novak, I

    2008-01-01

    The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly......, there is also evidence for other P2 and adenosine receptors in beta cells (P2Y(2), P2Y(4), P2Y(6), P2X subtypes and A(1) receptors) and in glucagon-secreting alpha cells (P2X(7), A(2) receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors...

  11. Generation of multiple cell types in Bacillus subtilis.

    Science.gov (United States)

    Lopez, Daniel; Vlamakis, Hera; Kolter, Roberto

    2009-01-01

    Bacillus subtilis is a Gram-positive bacterium that is well known for its ability to differentiate into metabolically inactive spores that are highly resistant to environmental stresses. In fact, populations of genetically identical B. subtilis comprise numerous distinct cell types. In addition to spores, cells can become genetically competent, motile, produce extracellular matrix or degradative enzymes, or secrete toxins that allow them to cannibalize their neighbors. Many of the cell fates listed above appear to be mutually exclusive. In this review, we discuss how individual cells within a population control their gene expression to ensure that proper regulation of differentiation occurs. These different cell fates are regulated by an intricate network that relies primarily on the activity of three major transcriptional regulators: Spo0A, DegU, and ComK. While individual cells must choose distinct cell fates, the population as a whole exhibits a spectrum of phenotypes whose diversity may increase fitness.

  12. Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

    International Nuclear Information System (INIS)

    Kucka, Marek; Pogrmic-Majkic, Kristina; Fa, Svetlana; Stojilkovic, Stanko S.; Kovacevic, Radmila

    2012-01-01

    Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s. -- Highlights: ► Atrazine stimulates cAMP accumulation in pituitary and Leydig cells. ► Atrazine also stimulates PRL and androgens secretion. ► Stimulatory effects of atrazine were abolished in cells with IBMX-inhibited PDEs. ► Atrazine specificity toward c

  13. Cell type discovery using single-cell transcriptomics: implications for ontological representation.

    Science.gov (United States)

    Aevermann, Brian D; Novotny, Mark; Bakken, Trygve; Miller, Jeremy A; Diehl, Alexander D; Osumi-Sutherland, David; Lasken, Roger S; Lein, Ed S; Scheuermann, Richard H

    2018-05-01

    Cells are fundamental function units of multicellular organisms, with different cell types playing distinct physiological roles in the body. The recent advent of single-cell transcriptional profiling using RNA sequencing is producing 'big data', enabling the identification of novel human cell types at an unprecedented rate. In this review, we summarize recent work characterizing cell types in the human central nervous and immune systems using single-cell and single-nuclei RNA sequencing, and discuss the implications that these discoveries are having on the representation of cell types in the reference Cell Ontology (CL). We propose a method, based on random forest machine learning, for identifying sets of necessary and sufficient marker genes, which can be used to assemble consistent and reproducible cell type definitions for incorporation into the CL. The representation of defined cell type classes and their relationships in the CL using this strategy will make the cell type classes being identified by high-throughput/high-content technologies findable, accessible, interoperable and reusable (FAIR), allowing the CL to serve as a reference knowledgebase of information about the role that distinct cellular phenotypes play in human health and disease.

  14. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    Directory of Open Access Journals (Sweden)

    P. V. Novokhatny

    2014-02-01

    Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

  15. PPARgamma in immunity and inflammation: cell types and diseases.

    Science.gov (United States)

    Széles, Lajos; Töröcsik, Dániel; Nagy, László

    2007-08-01

    The lipid activated transcription factor, PPARgamma appears to have multiple functions in the immune system. There are several cell types expressing the receptor, most prominently antigen presenting cells, such as macrophages and dendritic cells. The receptor's activation leads to primary transcriptional activation of many, mostly lipid metabolism-related genes. However, gene regulation also occurs on immunity and inflammation-related genes. Key questions are: in what way lipid metabolism and immune regulation are connected and how activation and/or repression of gene expression may modulate inflammatory and anti-inflammatory responses and in what way can these be utilized in therapy. Here we provide a cell type and disease centric review on the role of this lipid activated transcription factor in the various cells of the immune system it is expressed in, and in some major inflammatory diseases such as atherosclerosis, inflammatory bowel disease and rheumatoid arthritis.

  16. Hyaluronan and Hyaluronan-Binding Proteins Accumulate in Both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate With Inflammatory Cells in Insulitis

    Science.gov (United States)

    Bogdani, Marika; Johnson, Pamela Y.; Potter-Perigo, Susan; Nagy, Nadine; Day, Anthony J.; Bollyky, Paul L.

    2014-01-01

    Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor–stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes. PMID:24677718

  17. Mash1-expressing cells could differentiate to type III cells in adult mouse taste buds.

    Science.gov (United States)

    Takagi, Hiroki; Seta, Yuji; Kataoka, Shinji; Nakatomi, Mitsushiro; Toyono, Takashi; Kawamoto, Tatsuo

    2018-03-10

    The gustatory cells in taste buds have been identified as paraneuronal; they possess characteristics of both neuronal and epithelial cells. Like neurons, they form synapses, store and release transmitters, and are capable of generating an action potential. Like epithelial cells, taste cells have a limited life span and are regularly replaced throughout life. However, little is known about the molecular mechanisms that regulate taste cell genesis and differentiation. In the present study, to begin to understand these mechanisms, we investigated the role of Mash1-positive cells in regulating adult taste bud cell differentiation through the loss of Mash1-positive cells using the Cre-loxP system. We found that the cells expressing type III cell markers-aromatic L-amino acid decarboxylase (AADC), carbonic anhydrase 4 (CA4), glutamate decarboxylase 67 (GAD67), neural cell adhesion molecule (NCAM), and synaptosomal-associated protein 25 (SNAP25)-were significantly reduced in the circumvallate taste buds after the administration of tamoxifen. However, gustducin and phospholipase C beta2 (PLC beta2)-markers of type II taste bud cells-were not significantly changed in the circumvallate taste buds after the administration of tamoxifen. These results suggest that Mash1-positive cells could be differentiated to type III cells, not type II cells in the taste buds.

  18. Generation of male differentiated germ cells from various types of stem cells.

    Science.gov (United States)

    Hou, Jingmei; Yang, Shi; Yang, Hao; Liu, Yang; Liu, Yun; Hai, Yanan; Chen, Zheng; Guo, Ying; Gong, Yuehua; Gao, Wei-Qiang; Li, Zheng; He, Zuping

    2014-06-01

    Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients. © 2014 Society for Reproduction and Fertility.

  19. Parenting characteristics of female caregivers of children affected by chronic endocrine conditions: a comparison between disorders of sex development and type 1 diabetes mellitus.

    Science.gov (United States)

    Kirk, Katherine D; Fedele, David A; Wolfe-Christensen, Cortney; Phillips, Timothy M; Mazur, Tom; Mullins, Larry L; Chernausek, Steven D; Wisniewski, Amy B

    2011-12-01

    Rearing a child with a chronic illness is stressful and can potentially affect parenting style, which may result in poorer outcomes for children. The purpose of this study was to compare parenting characteristics of female caregivers rearing children with a disorder of sex development (DSD) to female caregivers rearing children with type 1 diabetes mellitus (T1DM). Caregivers of both groups were matched according to age and compared on measures of stress and parenting practices. Both groups demonstrated significant levels of stress and negative parenting practices. Children with T1DM and male children with non-life-threatening DSD were perceived as more vulnerable by their caregivers. Better understanding of parenting experiences of female caregivers rearing children with DSD, particularly male children, will facilitate the development of individualized interventions to ameliorate negative parenting practices and stress, with the long-term goal of improved health outcomes for their children. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. What Is Women's Endocrine Health?

    Science.gov (United States)

    ... harness the power to prevent endocrine disorders, the Power of Prevention. Childhood Childhood is a time of rapid growth and development to learn healthy living habits and priorities. It can, however, be a great ...

  1. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert

    2008-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  2. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert

    2007-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

  3. Endocrine Therapy of Breast Cancer

    National Research Council Canada - National Science Library

    Clarke, Robert S

    2005-01-01

    ...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40...

  4. Skin Manifestations of Endocrine Diseases.

    Science.gov (United States)

    Demirkesen, Cuyan

    2015-01-01

    Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

  5. Determination of bisphenol-type endocrine disrupting compounds in food-contact recycled-paper materials by focused ultrasonic solid-liquid extraction and ultra performance liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    Pérez-Palacios, David; Fernández-Recio, Miguel Ángel; Moreta, Cristina; Tena, María Teresa

    2012-09-15

    Focused ultrasonic solid-liquid extraction (FUSLE) and reverse-phase ultra performance liquid chromatography (UPLC) coupled to a quadrupole-time of flight mass spectrometer (Q-TOF-MS) was applied to the determination of bisphenol-type endocrine disrupting compounds (EDCs) in food-contact recycled-paper materials. Recycled paper is a potential source of EDCs. Bisphenol A (BPA), bisphenol F (BPF) and their derivatives bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE) are used for the production of epoxy resins employed in the formulation of printing inks. The FUSLE of bisphenol-type EDCs from packaging is reported for the first time. First, different extraction solvents were studied and methanol was selected. Then, the main FUSLE factors affecting the extraction efficiency (solvent volume, extraction time and ultrasonic irradiation power) were studied by means of a central composite design. The FUSLE conditions selected for further experiments were 20 ml of methanol at ultrasonic amplitude of 100% for 5s. Finally, the number of extraction cycles necessary for complete extraction was established in two. The analysis of the FUSLE extracts was carried out by UPLC-Q-TOF-MS with electrospray ionization and the determination of the four analytes took place in only 4 min. The FUSLE and UPLC-ESI-QTOF-MS method was validated and applied to the analysis of different food-contact recycled-paper-based materials and packaging. The proposed method provided recoveries from 72% to 97%, repeatability and intermediate precision under 9% and 14%, respectively, and detection limits of 0.33, 0.16, 0.65 and 0.40 μg/g for BPA, BPF, BADGE and BFDGE, respectively. The analysis of paper and cardboard samples confirmed the presence of EDCs in these packaging. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Cell-type specific four-component hydrogel.

    Directory of Open Access Journals (Sweden)

    Timo Aberle

    Full Text Available In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin to generate a blend (technical term: quattroGel, an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.

  7. Endocrine-disrupting chemicals: associated disorders and mechanisms of action.

    Science.gov (United States)

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

  8. Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Sam De Coster

    2012-01-01

    Full Text Available The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.

  9. Cytokine-induced killer cells are type II natural killer T cells

    Directory of Open Access Journals (Sweden)

    Schmidt-Wolf, Ingo G.H.

    2007-09-01

    Full Text Available Background: Until now, cytokine-induced killer (CIK cells were assumed to be part of the type I natural killer T (NKT cell population, but it was not yet investigated if this is correct. Methods: For analysis, CIK cells were generated by various culture conditions. Human type I NKT cells express a T cell receptor (TCR composed of an invariant Vα24-JαQ chain combined with one of several Vβ chains. The Vα24 is a reliable marker for the presence of these TCRs. Results: While comparing cultures stimulated with different substances, we observed the lack of any Vα24 on the surface of CIK culture cells. Conclusion: We conclude that CIK cells do not belong to the type I NKT cells.

  10. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.

    Science.gov (United States)

    Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm

    2015-01-01

    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential. Copyright© Ferrata Storti Foundation.

  11. Respiratory manifestations in endocrine diseases

    OpenAIRE

    LENCU, CODRU?A; ALEXESCU, TEODORA; PETRULEA, MIRELA; LENCU, MONICA

    2016-01-01

    The control mechanisms of respiration as a vital function are complex: voluntary ? cortical, and involuntary ? metabolic, neural, emotional and endocrine. Hormones and hypothalamic neuropeptides (that act as neurotrasmitters and neuromodulators in the central nervous system) play a role in the regulation of respiration and in bronchopulmonary morphology. This article presents respiratory manifestations in adult endocrine diseases that evolve with hormone deficit or hypersecretion. In hyperthy...

  12. Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    De Long, Nicole E.; Barry, Eric J. [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1 (Canada); Pinelli, Christopher; Wood, Geoffrey A. [Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1 (Canada); Hardy, Daniel B. [Department of Obstetrics and Gynecology, Physiology and Pharmacology, University of Western, London, ON N6A 3K6 (Canada); Morrison, Katherine M. [Department of Pediatrics, McMaster University, Hamilton, ON L8S 4K1 (Canada); Taylor, Valerie H. [Department of Psychiatry, University of Toronto, Toronto, ON M5S 1A1 (Canada); Gerstein, Hertzel C. [Department of Medicine, McMaster University, Hamilton, ON L8S 4K1 (Canada); Holloway, Alison C., E-mail: hollow@mcmaster.ca [Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4K1 (Canada)

    2015-05-15

    Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in

  13. Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

    International Nuclear Information System (INIS)

    De Long, Nicole E.; Barry, Eric J.; Pinelli, Christopher; Wood, Geoffrey A.; Hardy, Daniel B.; Morrison, Katherine M.; Taylor, Valerie H.; Gerstein, Hertzel C.; Holloway, Alison C.

    2015-01-01

    Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetine exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in

  14. Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death

    Directory of Open Access Journals (Sweden)

    Naira F. Z. Schneider

    2018-03-01

    Full Text Available Cardiac glycosides (CGs are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities.

  15. Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

    Science.gov (United States)

    Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco

    2017-09-11

    The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

  16. Endocrine myopathy: Case-based review

    Directory of Open Access Journals (Sweden)

    Babul Reddy Hanmayyagari

    2016-01-01

    Full Text Available Endocrine myopathy means muscle weakness in the presence of an abnormal endocrine state. Most of the endocrine disorders are associated with myopathy and it is usually reversible with correction of the underlying disturbance, though, there is an increasing knowledge of the metabolic effects of hormones, endocrine myopathy is a less recognized and often overlooked entity in clinical practice. Here, we describe this association in three of our patients, then, we discuss systematically about endocrine myopathy.

  17. Endocrine system on chip for a diabetes treatment model.

    Science.gov (United States)

    Nguyen, Dao Thi Thuy; van Noort, Danny; Jeong, In-Kyung; Park, Sungsu

    2017-02-21

    The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion. Thus, we constructed a co-culture of intestinal-pancreatic cells to measure the effect of glucose on the production of glucagon-like peptide-1 (GLP-1) from the L-cell line (GLUTag) and insulin from the pancreatic β-cell line (INS-1). After three days of culture, both cell lines formed aggregates, exhibited 3D cell morphology, and showed good viability (>95%). We separately measured the dynamic profile of GLP-1 and insulin release at glucose concentrations of 0.5 and 20 mM, as well as the combined effect of GLP-1 on insulin production at these glucose concentrations. In response to glucose stimuli, GLUTag and INS-1 cells produced higher amounts of GLP-1 and insulin, respectively, compared to a static 2D cell culture. INS-1 combined with GLUTag cells exhibited an even higher insulin production in response to glucose stimulation. At higher glucose concentrations, the diabetes model on chip showed faster saturation of the insulin level. Our results suggest that the endocrine system developed in this study is a useful tool for observing dynamical changes in endocrine hormones (GLP-1 and insulin) in a glucose-dependent environment. Moreover, it can potentially be used to screen GLP-1 analogues and natural insulin and GLP-1 stimulants for diabetes treatment.

  18. The repair of damage to DNA in different cell types

    International Nuclear Information System (INIS)

    Karran, P.

    1974-01-01

    DNA single strand breaks induced by either X-ray irradiation or by methyl methanesulphonate (MMS) were studied in different lymphoid cell populations directly taken from the animal and maintained in tissue culture merely for the duration of the experiment. The results obtained from these cell populations were compared with those obtained with L5178Y cells maintained in tissue culture. All cell types studied were found to possess at least one class of enzymes required for repair of DNA damage, namely those enzymes involved in the rejoining of X-ray induced by MMS is different in each cell type. Repair replication was at much reduced levels and the endonucleolytic degradation was at much reduced levels and the endonucleolytic degradation was initiated at lower MMS concentration in the lymphoid cells as compared to L5178Y cells. It is suggested that the overall ''repair capacity'' of a population may be related to the number of cells in a cycle which, moreover, might be the only ones to have the ability to repair damage to DNA induced by MMS (G.G.)

  19. [TNF-α, diabetes type 1 and regulatory T cells].

    Science.gov (United States)

    Ryba, Monika; Myśliwska, Jolanta

    2010-01-01

    Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

  20. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    International Nuclear Information System (INIS)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi

    2015-01-01

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells

  1. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: ikejimat@vip.sina.com [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)

    2015-02-20

    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  2. Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.).

    Science.gov (United States)

    Bado-Nilles, A; Techer, R; Porcher, J M; Geffard, A; Gagnaire, B; Betoulle, S; Sanchez, W

    2014-09-01

    Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Diffuse-type giant cell tumor of the subcutaneous thigh

    International Nuclear Information System (INIS)

    Sanghvi, D.A.; Purandare, N.C.; Jambhekar, N.A.; Agarwal, A.; Agarwal, M.G.

    2007-01-01

    Diffuse-type giant cell tumor is an extra-articular form of pigmented villonodular synovitis. The localized form of this lesion (tenosynovial giant cell tumor) is frequent, representing the most common subset arising from the synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the fingers. The less frequent diffuse-type giant cell tumors are commonly located in the periarticular soft tissues, but on rare occasions these lesions can be purely intramuscular or subcutaneous We report the case of a 26-year-old female with diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint, bursa or tendon sheath. A review of the literature did not reveal any similar description of a diffuse-type giant cell tumor completely within the subcutaneous thigh, remote from a joint, bursa or tendon sheath. These lesions were initially regarded as inflammatory or reactive processes, but since the identification of clonal abnormalities in these patients, and in view of their capacity for autonomous growth, they are now widely considered to represent benign neoplasms. (orig.)

  4. Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition.

    Science.gov (United States)

    Gervin, Kristina; Page, Christian Magnus; Aass, Hans Christian D; Jansen, Michelle A; Fjeldstad, Heidi Elisabeth; Andreassen, Bettina Kulle; Duijts, Liesbeth; van Meurs, Joyce B; van Zelm, Menno C; Jaddoe, Vincent W; Nordeng, Hedvig; Knudsen, Gunn Peggy; Magnus, Per; Nystad, Wenche; Staff, Anne Cathrine; Felix, Janine F; Lyle, Robert

    2016-09-01

    Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood. The aim of this study was to generate a reference data set from cord blood to enable correct adjustment of the cell type composition in samples collected at birth. The purity of the isolated cell types was very high for all samples (>97.1%), and clustering analyses showed distinct grouping of the cell types according to hematopoietic lineage. We explored whether this cord blood and the adult peripheral blood reference data sets impact the estimation of cell type composition in cord blood samples from an independent birth cohort (MoBa, n = 1092). This revealed significant differences for all cell types. Importantly, comparison of the cell type estimates against matched cell counts both in the cord blood reference samples (n = 11) and in another independent birth cohort (Generation R, n = 195), demonstrated moderate to high correlation of the data. This is the first cord blood reference data set with a comprehensive examination of the downstream application of the data through validation of estimated cell types against matched cell counts.

  5. Islet β cell failure in type 2 diabetes

    Science.gov (United States)

    Prentki, Marc; Nolan, Christopher J.

    2006-01-01

    The major focus of this Review is on the mechanisms of islet β cell failure in the pathogenesis of obesity-associated type 2 diabetes (T2D). As this demise occurs within the context of β cell compensation for insulin resistance, consideration is also given to the mechanisms involved in the compensation process, including mechanisms for expansion of β cell mass and for enhanced β cell performance. The importance of genetic, intrauterine, and environmental factors in the determination of “susceptible” islets and overall risk for T2D is reviewed. The likely mechanisms of β cell failure are discussed within the two broad categories: those with initiation and those with progression roles. PMID:16823478

  6. Molecular cloning, genomic organization, and expression of a C-type (Manduca sexta-type) allatostatin preprohormone from Drosophila melanogaster

    DEFF Research Database (Denmark)

    Williamson, M; Lenz, C; Winther, A M

    2001-01-01

    neurons of the brain and abdominal ganglia and in endocrine cells of the midgut. This is the first publication on the structure of a C-type allatostatin from insects other than moths and the first report on the presence of all three types of allatostatins in a representative of the insect order Diptera...

  7. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  8. Single-cell LEP-type cavity on measurement stand

    CERN Multimedia

    CERN PhotoLab

    1982-01-01

    A single-cell cavity, made of copper, with tapered connectors for impedance measurements. It was used as a model of LEP-type superconducting cavities, to investigate impedance and higher-order modes and operated at around 600 MHz (the LEP acceleration frequency was 352.2 MHz). See 8202500.

  9. Receptosecretory nature of type III cells in the taste bud.

    Science.gov (United States)

    Yoshie, Sumio

    2009-01-01

    Type III cells in taste buds form chemical synapses with intragemmal afferent nerve fibers and are characterized by the presence of membrane-bound vesicles in the cytoplasm. Although the vesicles differ in shape and size among species, they are primarily categorized into small clear (40 nm in diameter) and large dense-cored (90-200 nm) types. As such vesicles tend to be closely juxtaposed to the synaptic membrane of the cells, it is reasonable to consider that the vesicles include transmitter(s) towards the gustatory nerve. In the guinea-pig taste bud, stimulation with various taste substances (sucrose, sodium chloride, quinine hydrochloride, or monosodium L-glutamate) causes ultrastructural alterations of the type III cells. At the synapse, the presynaptic plasma membrane often displays invaginations of 90 nm in a mean diameter towards the cytoplasm, which indicates the dense-cored vesicles opening into the synaptic cleft by means of exocytosis. The vesicles are also exocytosed at the non-synaptic region into the intercellular space. These findings strongly suggest that the transmitters presumably contained in the vesicles are released to conduct the excitement of the type III cells to the nerves and also to exert their paracrine effects upon the surroundings, such as the Ebner's salivary gland, acting as local hormones.

  10. Automated cell type discovery and classification through knowledge transfer

    Science.gov (United States)

    Lee, Hao-Chih; Kosoy, Roman; Becker, Christine E.

    2017-01-01

    Abstract Motivation: Recent advances in mass cytometry allow simultaneous measurements of up to 50 markers at single-cell resolution. However, the high dimensionality of mass cytometry data introduces computational challenges for automated data analysis and hinders translation of new biological understanding into clinical applications. Previous studies have applied machine learning to facilitate processing of mass cytometry data. However, manual inspection is still inevitable and becoming the barrier to reliable large-scale analysis. Results: We present a new algorithm called Automated Cell-type Discovery and Classification (ACDC) that fully automates the classification of canonical cell populations and highlights novel cell types in mass cytometry data. Evaluations on real-world data show ACDC provides accurate and reliable estimations compared to manual gating results. Additionally, ACDC automatically classifies previously ambiguous cell types to facilitate discovery. Our findings suggest that ACDC substantially improves both reliability and interpretability of results obtained from high-dimensional mass cytometry profiling data. Availability and Implementation: A Python package (Python 3) and analysis scripts for reproducing the results are availability on https://bitbucket.org/dudleylab/acdc. Contact: brian.kidd@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28158442

  11. White blood cell subtypes and risk of type 2 diabetes.

    Science.gov (United States)

    Zhang, Hongmei; Yang, Zhen; Zhang, Weiwei; Niu, Yixin; Li, Xiaoyong; Qin, Li; Su, Qing

    2017-01-01

    It is reported that total white blood cell is associated with risk of diabetes mellitus. The present study is to investigate the relationship of white blood cell subsets with incidence of type 2 diabetes at baseline and 3year follow-up. We chose individuals without diabetes history as our study population; 8991 individuals were included at baseline. All of the participants underwent a 75-g OGTT at baseline. White blood cell count including all the subsets were measured along with all the other laboratory indices. The participants who were not diagnosed with type 2 diabetes according to the WHO 1999 diagnostic criteria underwent another 75-g OGTT at 3year follow-up. The total WBC count, neutrophil count, and lymphocyte count were significantly increased in subjects newly diagnosed with diabetes mellitus compared to non-DM subjects at baseline (all ptype 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Type II NKT-TFH cells against Gaucher lipids regulate B-cell immunity and inflammation.

    Science.gov (United States)

    Nair, Shiny; Boddupalli, Chandra Sekhar; Verma, Rakesh; Liu, Jun; Yang, Ruhua; Pastores, Gregory M; Mistry, Pramod K; Dhodapkar, Madhav V

    2015-02-19

    Chronic inflammation including B-cell activation is commonly observed in both inherited (Gaucher disease [GD]) and acquired disorders of lipid metabolism. However, the cellular mechanisms underlying B-cell activation in these settings remain to be elucidated. Here, we report that β-glucosylceramide 22:0 (βGL1-22) and glucosylsphingosine (LGL1), 2 major sphingolipids accumulated in GD, can be recognized by a distinct subset of CD1d-restricted human and murine type II natural killer T (NKT) cells. Human βGL1-22- and LGL1-reactive CD1d tetramer-positive T cells have a distinct T-cell receptor usage and genomic and cytokine profiles compared with the classical type I NKT cells. In contrast to type I NKT cells, βGL1-22- and LGL1-specific NKT cells constitutively express T-follicular helper (TFH) phenotype. Injection of these lipids leads to an increase in respective lipid-specific type II NKT cells in vivo and downstream induction of germinal center B cells, hypergammaglobulinemia, and production of antilipid antibodies. Human βGL1-22- and LGL1-specific NKT cells can provide efficient cognate help to B cells in vitro. Frequency of LGL1-specific T cells in GD mouse models and patients correlates with disease activity and therapeutic response. Our studies identify a novel type II NKT-mediated pathway for glucosphingolipid-mediated dysregulation of humoral immunity and increased risk of B-cell malignancy observed in metabolic lipid disorders. © 2015 by The American Society of Hematology.

  13. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

    Science.gov (United States)

    Altieri, Barbara; Muscogiuri, Giovanna; Barrea, Luigi; Mathieu, Chantal; Vallone, Carla V; Mascitelli, Luca; Bizzaro, Giorgia; Altieri, Vincenzo M; Tirabassi, Giacomo; Balercia, Giancarlo; Savastano, Silvia; Bizzaro, Nicola; Ronchi, Cristina L; Colao, Annamaria; Pontecorvi, Alfredo; Della Casa, Silvia

    2017-09-01

    In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

  14. Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma.

    Science.gov (United States)

    Zhang, Guqin; Nie, Hanxiang; Yang, Jiong; Ding, Xuhong; Huang, Yi; Yu, Hongying; Li, Ruyou; Yuan, Zhuqing; Hu, Suping

    2011-12-01

    Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.

  15. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  16. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Endocrine and Neuroendocrine Neoplasias discusses inherited syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN1, MEN2, MEN4), familial pheochromocytoma and paraganglioma, Carney-Stratakis syndrome, and familial nonmedullary thyroid cancer. Learn more in this clinician summary.

  17. Tributyltin: Advancing the science on assessing endocrine disruption with an unconventional endocrine-disrupting compound

    Science.gov (United States)

    Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ronald C.; Guiney, Patrick; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P.

    2018-01-01

    Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated—interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

  18. Tributyltin: Advancing the Science on Assessing Endocrine Disruption with an Unconventional Endocrine-Disrupting Compound.

    Science.gov (United States)

    Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ron; Guiney, Patrick D; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P

    Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

  19. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  20. Endocrine alterations in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    Sujit Kumar Tripathy

    2015-01-01

    Full Text Available Aims and objectives: To study the frequency of thyroid, adrenal and gonadal dysfunction in newly diagnosed HIV-infected patients and to correlate them at different levels of CD4 cell counts. Materials and Methods: Forty-three HIV-positive cases were included in the study group. Cases were divided into three groups on the basis of CD4 cell count. Serum free T3, free T4, TSH, Cortisol, FSH, LH, testosterone and estradiol were estimated by the radioimmunoassay method. Hormone levels between cases were compared and their correlation with CD4 count was analyzed. Results: Prevalence of gonadal dysfunction (88.3% was the most common endocrine dysfunction followed by thyroid (60.4% and adrenal dysfunction (27.9%. Secondary hypogonadism (68.4% was more common than primary (31.6%. Low T3 syndrome, that is, isolated low free T3, was the most common (25.6% thyroid dysfunction followed by secondary hypothyroidism (16.2% and subclinical hypothyroidism (11.6%. Adrenal excess (16.3% was more common than adrenal insufficiency (11.6%. The difference in hormonal dysfunction between male and female was statistically insignificant (P > 0.05. 27.9% of patients had multiple hormone deficiency. There was negligible or no correlation between CD4 count and serum hormone level. Conclusion: In our study, endocrine dysfunction was quite common among HIV-infected patients but there was no correlation between hormone levels and CD4 count. Endocrine dysfunctions and role of hormone replacement therapy in HIV-infected patient needs to be substantiated by large longitudinal study, so that it will help to reduce morbidity, improve quality of life.

  1. Characterization of tissue plasminogen activator binding proteins isolated from endothelial cells and other cell types

    International Nuclear Information System (INIS)

    Beebe, D.P.; Wood, L.L.; Moos, M.

    1990-01-01

    Human tissue plasminogen activator (t-PA) was shown to bind specifically to human osteosarcoma cells (HOS), and human epidermoid carcinoma cells (A-431 cells). Crosslinking studies with DTSSP demonstrated high molecular weight complexes (130,000) between 125 I-t-PA and cell membrane protein on human umbilical vein endothelial cells (HUVEC), HOS, and A-431 cells. A 48-65,000 molecular weight complex was demonstrated after crosslinking t-PA peptide (res. 7-20) to cells. Ligand blotting of cell lysates which had been passed over a t-PA affinity column revealed binding of t-PA to 54,000 and 95,000 molecular weight proteins. Several t-PA binding proteins were identified in immunopurified cell lysates, including tubulin beta chain, plasminogen activator inhibitor type 1 and single chain urokinase

  2. Scintigraphic imaging of endocrine organs

    International Nuclear Information System (INIS)

    Gross, M.D.; Shapiro, B.; Thrall, J.H.; Freitas, J.E.; Beierwaltes, W.H.

    1984-01-01

    The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach

  3. Psychosocial approach to endocrine disease.

    Science.gov (United States)

    Sonino, Nicoletta; Tomba, Elena; Fava, Giovanni A

    2007-01-01

    In recent years, there has been growing interest in the psychosocial aspects of endocrine disease, such as the role of life stress in the pathogenesis of some conditions, their association with affective disorders, and the presence of residual symptoms after adequate treatment. In clinical endocrinology, exploration of psychosocial antecedents may elucidate the temporal relationships between life events and symptom onset, as it has been shown to be relevant for pituitary (Cushing's disease, hyperprolactinemia) or thyroid (Graves' disease) conditions, as well as the role of allostatic load, linked to chronic stress, in uncovering a person's vulnerability. After endocrine abnormalities are established, they are frequently associated with a wide range of psychological symptoms: at times, such symptoms reach the level of psychiatric illness (mainly mood and anxiety disorders); at other times, however, they can only be identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR). Indeed, in a population study, the majority of patients suffered from at least one of the three DCPR syndromes considered: irritable mood, demoralization, persistent somatization. In particular, irritable mood was found to occur in 46% of 146 patients successfully treated for endocrine conditions, a rate similar to that found in cardiology and higher than in oncology and gastroenterology. Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses. In patients who showed persistence or even worsening of psychological distress upon proper endocrine treatment, the value of appropriate psychiatric interventions was underscored. As it happened in other fields of clinical medicine, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary for improving

  4. Radioimmunoassay of type D oncovirus from continuous J-96 cells

    International Nuclear Information System (INIS)

    Vlasenkova, N.K.; Altshtejn, A.D.; Zhdanov, V.M.; Kitsak, V.Ya.

    1978-01-01

    The radioimmunoassay of the J-96 virus and an extract of J-96 cells in the homologous and heterologous systems aimed at detecting antigenic determinants of p25 of Mason-Pfizer virus and group-specific and interspecies antigenic determinants p30 of Rauscher leukaemia virus demonstrated that (1) J-96 virus contains a major internal protein immunologically identical with p25 protein of Mason-Pfizer virus based on the antigenic determinants detectable by the radioimmunoassay used; and (2) no interspecies antigenic determinants characteristic of the major internal protein of mammalian type C viruses were detectable in the J-96 virus or the J-96 cell extract. (author)

  5. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Endocrine ophthalmopathy and radioiodine therapy

    International Nuclear Information System (INIS)

    Karlsson, F. Anders

    2006-01-01

    Endocrine ophthalmopathy is to some degree present in most patients with Graves' disease. In few cases, a severe form of the condition develops and in the majority of these cases, the course of the eye problems has been influenced by the treatment for thyrotoxicosis. In this regard, radioiodine therapy has been increasingly recognized as carrying a special risk. Here, the current understanding of endocrine ophthalmopathy and the risks associated with the development of severe eye disease are discussed. The results of a retrospective investigation of patients with severe eye disease in our hospital, and the experience with corticosteroid administration following radioiodine in order to reduce the risk of ophthalmopathy, are also presented

  7. Delicate balance among three types of T cells in concurrent regulation of tumor immunity

    Science.gov (United States)

    Izhak, Liat; Ambrosino, Elena; Kato, Shingo; Parish, Stanley T.; O’Konek, Jessica J.; Weber, Hannah; Xia, Zheng; Venzon, David; Berzofsky, Jay A.; Terabe, Masaki

    2013-01-01

    The nature of the regulatory cell types that dominate in any given tumor is not understood at present. Here we addressed this question for Tregs and type II NKT cells in syngeneic models of colorectal and renal cancer. In mice with both type I and type II NKT cells, or in mice with neither type of NKT cell, Treg depletion was sufficient to protect against tumor outgrowth. Surprisingly, in mice lacking only type I NKT cells, Treg blockade was insufficient for protection. Thus, we hypothesized that type II NKT cells may be neutralized by type I NKT cells, leaving Treg cells as the primary suppressor, whereas in mice lacking type I NKT cells, unopposed type II NKT cells could suppress tumor immunity even when Tregs were blocked. We confirmed this hypothesis in three ways by reconstituting type I NKT cells as well as selectively blocking or activating type II NKT cells with antibody or the agonist sulfatide, respectively. In this manner, we demonstrated that blockade of both type II NKT cells and Tregs is necessary to abrogate suppression of tumor immunity, but a third cell, the type I NKT cell, determines the balance between these regulatory mechanisms. As cancer patients often have deficient type I NKT cell function, managing this delicate balance among three T cell subsets may be critical for the success of immunotherapy of human cancer. PMID:23319803

  8. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.

    Science.gov (United States)

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-03-25

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed.

  9. Cystic degeneration of neuro endocrine tumor of pancreas and ...

    African Journals Online (AJOL)

    Pancreatic endocrine tumors (PETs) or islet cell tumors are rare lesions, the incidence of which is estimated to be less than 1 per 100,000 person-years in the general population . PETs can be divided into functional (exhibit a distinct clinical syndrome due to hormone hypersecretion) and non-functional tumors. The majority ...

  10. Arterial and venous thrombosis in endocrine diseases

    NARCIS (Netherlands)

    van Zaane, Bregje; Stuijver, Danka J. F.; Squizzato, Alessandro; Gerdes, Victor E. A.

    2013-01-01

    Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency,

  11. Operating method of molten carbonate type fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Tsuneo

    1988-12-06

    Molten carbonate type fuel cell involves a problem of oxidation of anode while the unit is stopped. Although there is a method proposed wherein an inactive gas is supplied to anode during the stoppage, the market-available inactive gas contains a slight amount of oxygen which makes it difficult to prevent the deterioration of the anode. In this invention, at the start and the stop other than the normal operation, a protective gas mixture of an inactive gas with a small amount of hydrogen is supplied to the anode. The inactive gas is a commercial type nitrogen, argon or helium; hydrogen is mixed in amount 0.5 - 2.0% of the inactive gas. By this method, oxygen in air which comes in from the gas-sealed portion of the cell is reduced by hydrogen in the protective gas and is discharged in the form of water. 2 figs.

  12. Preimplantation HLA typing for stem cell transplantation treatment of hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Anver Kuliev

    2014-09-01

    Full Text Available Preimplantation genetic diagnosis (PGD for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.

  13. Study of homogeneous fuel cells type 10 x 10

    International Nuclear Information System (INIS)

    Montes, J.L.; Perusquia, R.; Ortiz, J.J.; Francois, J.L.; Marquez, C.M.

    2005-01-01

    At the moment in the National Institute of Nuclear Research (ININ) are carried out studies with the purpose of to establish a methodology that allows to carry out the neutron design of fuel cells of type 10 x 10. During the initial stage of the process of cells design, starting from the data that have to do with the planned energy demand it requires to be estimated the average value of the enrichment in U 235 w/o of the one assemble. The experience has shown that the accuracy that is achieved in this estimate it depends, among other factors, of the information (e.g. concentrations of U 235 and Gd 2 O 3 ) of the cells that its are disposed in that moment. For what we consider convenient to enlarge the available information by means of a series of calculations of cell physics; and to the one same time some aspects can be studied on the parameters that define the characteristics of a fuel cell. In this work the effect of the presence of different distributions of the concentrations of the fissile material is analyzed and of burnup poisons on the reactivity parameters of the cell as well as in the peak factor of local power (LPPF-Local Power Peaking Factor). (Author)

  14. Endocrine-disrupting chemicals and male reproductive health: a review

    Directory of Open Access Journals (Sweden)

    Damjan Balabanič

    2018-03-01

    Full Text Available Balanced functioning of the endocrine system is essential for preservation of human species by providing normal growth and development, reproduction, and normal functioning of all other organ systems. In the last decades, emerging area of interest is the impact of environmental exposures to human health. Important environmental pollutants are endocrine-disrupting che- micals (EDCs, which can have adverse e ects on the living organism due to their interference with the endocrine system. The group of known EDCs embraces ubiquitous synthetic substan- ces used as industrial lubricants and solvents, with their by-products, incomplete combustion remains, pharmaceuticals and personal care products, pesticides and plasticizers. Natural com- pounds such as genistein, a phytoestrogen, and heavy metals can also have endocrine e ects. Endocrine disruption is a serious public health problem. EDCs among other health problems ge- nerate reproductive disorders in males, such as decreases in sperm count and quality, increases in testicular germ cell numbers, prostate and breast cancers, cryptorchidism and hypospadias, impaired fertility, and infertility. This paper critically reviews the current knowledge of the impa- ct of EDCs on reproductive disorders in human males.

  15. Delicate balance among three types of T cells in concurrent regulation of tumor immunity.

    Science.gov (United States)

    Izhak, Liat; Ambrosino, Elena; Kato, Shingo; Parish, Stanley T; O'Konek, Jessica J; Weber, Hannah; Xia, Zheng; Venzon, David; Berzofsky, Jay A; Terabe, Masaki

    2013-03-01

    The nature of the regulatory cell types that dominate in any given tumor is not understood at present. Here, we addressed this question for regulatory T cells (Treg) and type II natural killer T (NKT) cells in syngeneic models of colorectal and renal cancer. In mice with both type I and II NKT cells, or in mice with neither type of NKT cell, Treg depletion was sufficient to protect against tumor outgrowth. Surprisingly, in mice lacking only type I NKT cells, Treg blockade was insufficient for protection. Thus, we hypothesized that type II NKT cells may be neutralized by type I NKT cells, leaving Tregs as the primary suppressor, whereas in mice lacking type I NKT cells, unopposed type II NKT cells could suppress tumor immunity even when Tregs were blocked. We confirmed this hypothesis in 3 ways by reconstituting type I NKT cells as well as selectively blocking or activating type II NKT cells with antibody or the agonist sulfatide, respectively. In this manner, we showed that blockade of both type II NKT cells and Tregs is necessary to abrogate suppression of tumor immunity, but a third cell, the type I NKT cell, determines the balance between these regulatory mechanisms. As patients with cancer often have deficient type I NKT cell function, managing this delicate balance among 3 T-cell subsets may be critical for the success of immunotherapy for human cancer. ©2012 AACR.

  16. Decreased α-cell mass and early structural alterations of the exocrine pancreas in patients with type 1 diabetes: An analysis based on the nPOD repository.

    Directory of Open Access Journals (Sweden)

    Fidéline Bonnet-Serrano

    Full Text Available Abnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D, but their respective anatomical substrata have seldom been investigated. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of α-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD.The ratio of β- and α-cell area to total tissue area were quantified in 75 patients with T1D (thereafter patients and 66 control subjects (thereafter controls, on 2 insulin-stained and 4 glucagon-stained slides from both the head and the tail of the pancreas. The β- and α-cell masses were calculated in the 66 patients and the 50 controls for which the pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non-acinar, non-insular tissue to total tissue area ratio was evaluated on both insulin- and glucagon-stained slides. Results were expressed as mean ±SD.An automated quantification method was set up using the R software and was validated by quantification of β-cell mass, a well characterized parameter. β-cell mass was 29.6±112 mg in patients and 628 ±717 mg in controls (p<0.0001. α-cell mass was 181±176 mg in patients and 349 ±241mg in controls (p<0.0001. Non-exocrine-non-endocrine area to total tissue area ratio was 39±9% in patients and 29± 10% in controls (p<0.0001 and increased with age in both groups, with no correlation with diabetes duration in patients.The absolute α-cell mass was lower in patients compared to controls, in proportion to the decrease in pancreas weight observed in patients. Non-exocrine-non-endocrine area to total tissue area ratio increased with age in both groups but was higher in patients at all ages.

  17. Trophic significance of solitary cells of the prymnesiophyte Phaeocystis globosa depends on cell type

    DEFF Research Database (Denmark)

    Dutz, Jörg; Koski, Marja

    2006-01-01

    With the use of five different isolates of Phaeocystis globosa solitary cells from the North Sea, we conducted experiments to reveal whether grazing and development of the nauplii of the calanoid copepod Temora longicornis varies in response to the cell type. Two P. globosa strains representing n...

  18. Endocrine emergencies in dogs and cats.

    Science.gov (United States)

    Koenig, Amie

    2013-07-01

    Success in treatment of endocrine emergencies is contingent on early recognition and treatment. Many endocrine diseases presenting emergently have nonspecific signs and symptoms. In addition, these endocrine crises are often precipitated by concurrent disease, further making early identification difficult. This article concentrates on recognition and emergency management of the most common endocrine crises in dogs and cats. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    International Nuclear Information System (INIS)

    Martinez, V. D.; Becker-Santos, D. D.; Vucic, E. A.; Lam, S.; Lam, W. L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epi genomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

  20. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  1. New type of cells with multiple chromosome rearrangements

    International Nuclear Information System (INIS)

    Aseeva, E.A.; Domracheva, E.V.; Neverova, A.L; Bogomazova, A.N.; Snigiryova, G.P.; Novitskaya, N.N.; Khazins, E.D.

    2008-01-01

    Full text: A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. MAC were found in most of the examined groups and they were absent in the control population. A highest MAC frequency was observed in people exposed to alpha radiation (Pu, Ra). This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the FISH method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods is discussed

  2. Ca(2+) currents and voltage responses in Type I and Type II hair cells of the chick embryo semicircular canal.

    Science.gov (United States)

    Masetto, Sergio; Zampini, Valeria; Zucca, Giampiero; Valli, Paolo

    2005-11-01

    Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed.

  3. The Functions of Type I and Type II Natural Killer T (NKT) Cells in Inflammatory Bowel Diseases

    Science.gov (United States)

    Liao, Chia-Min; Zimmer, Michael I.; Wang, Chyung-Ru

    2013-01-01

    CD1d-restricted natural killer T (NKT) cells are a distinct subset of T cells that rapidly produce an array of cytokines upon activation and play a critical role in regulating various immune responses. NKT cells are classified into two groups based on differences in T cell receptor (TCR) usage. Type I NKT cells have an invariant TCRα-chain and are readily detectable by α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. Type II NKT cells have a more diverse TCR repertoire and cannot be directly identified. Both types of NKT cells as well as multiple CD1d-expressing cell types are present in the intestine and their interactions are likely to be modulated by pathogenic and commensal microbes, which in turn contribute to the intestinal immune responses in health and disease. Indeed, in several animal models of inflammatory bowel disease (IBD), Type I NKT cells have been shown to make both protective and pathogenic contributions to disease. In contrast, in human patients suffering from ulcerative colitis (UC), and a mouse model in which both CD1d expression and the frequency of Type II NKT cells are increased, Type II NKT cells appear to promote intestinal inflammation. In this review, we summarize present knowledge on the antigen recognition, activation and function of NKT cells with a particular focus on their role in IBD, and discuss factors that may influence the functional outcome of NKT cell responses in intestinal inflammation. PMID:23518808

  4. Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition

    NARCIS (Netherlands)

    Gervin, K. (Kristina); Page, C.M. (Christian Magnus); H.C.D. Aass (Hans Christian Dalsbotten); M.A.E. Jansen (Michelle); Fjeldstad, H.E. (Heidi Elisabeth); B.K. Andreassen (Bettina Kulle); L. Duijts (Liesbeth); J.B.J. van Meurs (Joyce); M.C. van Zelm (Menno); V.W.V. Jaddoe (Vincent); Nordeng, H. (Hedvig); Knudsen, G.P. (Gunn Peggy); P. Magnus (Per); W. Nystad (Wenche); Staff, A.C. (Anne Cathrine); J.F. Felix (Janine); R. Lyle (Robert)

    2016-01-01

    textabstractEpigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused

  5. The Vitamin D Endocrine System.

    Science.gov (United States)

    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)

  6. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N

    1999-01-01

    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

  7. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  8. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    Science.gov (United States)

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Inhibition of type I NKT cells by retinoids or following sulfatide-mediated activation of type II NKT cells attenuates alcoholic liver disease

    Science.gov (United States)

    Maricic, Igor; Sheng, Huiming; Marrero, Idania; Seki, Ehikiro; Kisseleva, Tatiana; Chaturvedi, Som; Molle, Natasha; Mathews, K. Stephanie; Gao, Bin; Kumar, Vipin

    2015-01-01

    Innate immune mechanisms leading to liver injury following chronic alcohol ingestion are poorly understood. Natural killer T (NKT) cells, enriched in the liver and comprised of at least two distinct subsets, type I and type II, recognize different lipid antigens presented by CD1d molecules. We have investigated whether differential activation of NKT cell subsets orchestrates inflammatory events leading to alcoholic liver disease (ALD). We found that following chronic plus binge feeding of Lieber-DeCarli liquid diet in male C57BL/6 mice, type I but not type II NKT cells are activated leading to recruitment of inflammatory Gr-1highCD11b+ cells into liver. A central finding is that liver injury following alcohol feeding is dependent upon type I NKT cells. Thus liver injury is significantly inhibited in Jα18−/− mice deficient in type I NKT cells as well as following their inactivation by sulfatide-mediated activation of type II NKT cells. Furthermore we have identified a novel pathway involving all-trans retinoic acid (ATRA) and its receptor RARγ signaling that inhibits type I NKT cells and consequently ALD. A semi-quantitative PCR analysis of hepatic gene expression of some of the key proinflammatory molecules shared in human disease indicated that their upregulation in ALD is dependent upon type I NKT cells. Conclusion Type I but not type II NKT cells become activated following alcohol feeding. Type I NKT cells-induced inflammation and neutrophil recruitment results in liver tissue damage while type II NKT cells protect from injury in ALD. Inhibition of type I NKT cells by retinoids or by sulfatide prevents ALD. Since the CD1d pathway is highly conserved between mice and humans, NKT cell subsets might be targeted for potential therapeutic intervention in ALD. PMID:25477000

  10. Growth of the endocrine pancreas

    DEFF Research Database (Denmark)

    Gaarn, Louise Winkel

    Diabetes er karakteriseret ved en enten absolut eller relativ mangel paa insulin producerende ß-celler (henholdsvis type 1 og 2 diabetes). Den mest oplagte behandling ville vaere at genskabe den funktionelle ß-cellemasse ved enten regenerering eller celle terapi og dermed genindfoere normal gluco...

  11. Endocrine system: acromegaly

    International Nuclear Information System (INIS)

    Linfoot, J.A.

    1980-01-01

    Acromegaly and gigantism represent multisystem diseases resulting from either a primary pituitary tumor or an ill-defined hypothalamo-hypophyseal dysfunction causing somatotropic cell hyperplasia and tumor formation. Clinical manifestations of the disease result from three major processes: (1) excessive growth hormone (HGH) secretion, (2) deficiencies of other pituitary tropic hormones, and (3) local invasion of parasellar neural and vascular structures. The treatment of this disease, and side effects, are discussed

  12. ER Stress and β-Cell Pathogenesis of Type 1 and Type 2 Diabetes and Islet Transplantation

    OpenAIRE

    Kataoka, Hitomi Usui; Noguchi, Hirofumi

    2013-01-01

    Endoplasmic reticulum (ER) stress affects the pathogenesis of diabetes. ER stress plays important roles, both in type 1 and type 2 diabetes, because pancreatic β-cells possess highly developed ER for insulin secretion. This review summarizes the relationship between ER stress and the pathogenesis of type 1 and type 2 diabetes. In addition, the association between islet transplantation and ER stress is discussed.

  13. Endocrine therapy and urogenital outcomes among women with a breast cancer diagnosis

    Science.gov (United States)

    Doll, Kemi M.; Bensen, Jeannette T.; Hendrix, Laura; Anders, Carey K.; Wu, Jennifer M.; Nichols, Hazel B.

    2018-01-01

    Purpose Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers. Methods Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort. Tumor characteristics and endocrine therapy use were collected from medical and prescription records. We calculated multivariable prevalence ratios (PR) and 95 % confidence intervals (CI) for the association of endocrine therapy (versus no endocrine therapy) and urinary incontinence, overall and by therapy type (tamoxifen or aromatase inhibitors). PROMIS Sexual Function and Satisfaction domain scores were compared across endocrine therapy groups. Results Among the 548 women with a breast cancer diagnosis, 49 % received endocrine therapy. Overall, 18 % of women reported urinary incontinence symptoms. We observed no association between urinary incontinence and endocrine therapy use overall (PR = 0.97; 95 % CI 0.67, 1.43), tamoxifen (PR = 1.20; 95 % CI 0.74, 1.96), or aromatase inhibitors (PR = 0.89; 95 % CI 0.55, 1.42), compared to no use. Approximately 55 % of women were sexually active. Sexual function scores did not vary according to endocrine therapy use, although urinary incontinence was associated with lower satisfaction scores (p = 0.05). Conclusions Our findings demonstrate a high prevalence of urinary incontinence after breast cancer diagnosis similar to the overall prevalence in older U.S. women, and this did not vary strongly according to use of endocrine therapy. PMID:27680018

  14. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  15. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Cell-type-specific gene delivery into neuronal cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Parveen, Zahida; Mukhtar, Muhammad; Rafi, Mohammed; Wenger, David A.; Siddiqui, Khwaja M.; Siler, Catherine A.; Dietzschold, Bernhard; Pomerantz, Roger J.; Schnell, Matthias J.; Dornburg, Ralph

    2003-01-01

    The avian retroviruses reticuloendotheliosis virus strain A (REV-A) and spleen necrosis virus (SNV) are not naturally infectious in human cells. However, REV-A-derived viral vectors efficiently infect human cells when they are pseudotyped with envelope proteins displaying targeting ligands specific for human cell-surface receptors. Here we report that vectors containing the gag region of REV-A and pol of SNV can be pseudotyped with the envelope protein of vesicular stomatitis virus (VSV) and the glycoproteins of different rabies virus (RV) strains. Vectors pseudotyped with the envelope protein of the highly neurotropic RV strain CVS-N2c facilitated cell type-specific gene delivery into mouse and human neurons, but did not infect other human cell types. Moreover, when such vector particles were injected into the brain of newborn mice, only neuronal cells were infected in vivo. Cell-type-specific gene delivery into neurons may present quite specific gene therapy approaches for many degenerative diseases of the brain

  17. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

    2009-07-01

    Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  18. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  19. Endocrine disrupting chemicals (bisphenol A, 4-nonylphenol, 4-tert-octylphenol) modulate expression of two distinct cytochrome P450 aromatase genes differently in gender types of the hermaphroditic fish Rivulus marmoratus.

    Science.gov (United States)

    Lee, Young-Mi; Seo, Jung Soo; Kim, Il-Chan; Yoon, Yong-Dal; Lee, Jae-Seong

    2006-06-30

    To understand the effect of endocrine-disrupting chemicals (EDCs) on cytochrome P450 aromatase (rm-cyp19) gene expression between gender types in the hermaphroditic fish Rivulus marmoratus, we cloned two distinct rm-cyp19 genes using RT-PCR with degenerative primers, obtained full-length cDNAs using 5'- and 3'-RACE-PCR methods, and completely sequenced them. The brain aromatase (rm-cyp19b) cDNA consisted of 2,124 bp including the open reading frame (ORF), which encoded a putative protein of 505 amino acids. The ovarian aromatase (rm-cyp19a) cDNA consisted of 2,075 bp, including the ORF encoding a putative protein of 516 amino acids. Expression patterns of rm-cyp19b and rm-cyp19a mRNAs were investigated in embryos of different developmental stages and in seven different tissues of adult fish. The rm-cyp19b gene in hermaphrodite and secondary male R. marmoratus was predominantly expressed in the brain, while the rm-cyp19a gene was expressed gender-specifically in the gonad. The expression of rm-cyp19b mRNA increased from stage 1 (2 d post fertilization) to stage 4 (12 d post fertilization) in a developmental stage-dependent manner but steeply decreased in the hatching stage. Compared to the rm-cyp19b gene, the abundance of ovarian aromatase rm-cyp19a transcripts was very low, and its expression was first detected at stage 3 and then decreased gradually to the hatching stage. Alteration of rm-cyp19b and rm-cyp19a gene expression was further analyzed in the brain and gonad by real-time RT-PCR 96 h after EDC exposure in hermaphrodites and secondary males. The brain aromatase rm-cyp19b gene was up-regulated in the brain after 4-nonylphenol (4-NP)-exposure, while the ovarian aromatase rm-cyp19a gene was significantly down-regulated in the gonad. In 300 microg/L 4-tert octylphenol (4-tert-OP), or 600 microg/L bisphenol A-exposed brain and gonad, both rm-cyp19b and rm-cyp19a genes were up-regulated. In the case of secondary males, the rm-cyp19b gene was highly expressed in

  20. Dissecting engineered cell types and enhancing cell fate conversion via CellNet

    Science.gov (United States)

    Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

    2014-01-01

    SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792

  1. Basal Cell Carcinoma in Type 2 Segmental Dariers Disease

    International Nuclear Information System (INIS)

    Robertson, L.; Sauder, M. B.

    2012-01-01

    Dariers disease (DD), also known as Keratosis Follicularis or Dariers-White disease, is a rare disorder of keratinisation. DD can present as a generalized autosomal dominant condition as well as a localized or segmental post zygotic condition (Vasquez et al., 2002). Clinical features of DD include greasy, warty papules and plaques on seborrhoeic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Dariers disease with only 8 previous cases reported to date. In addition, non melanoma skin cancer (NMSC) arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  2. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Directory of Open Access Journals (Sweden)

    Lynne Robertson

    2012-01-01

    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  3. Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.

    Science.gov (United States)

    Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S; Bowden, Michaela; Rao, Prakash; Long, Henry W; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

    2017-05-30

    The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

  4. Enteroviruses and type 1 diabetes mellitus putative pathogenic pathways

    NARCIS (Netherlands)

    Vreugdenhil, Gienke Rolien

    2001-01-01

    Type I diabetes mellitus is a chronic autoimmune disease that results from the destruction of the insulin-producing beta-cells in the endocrine pancreas. There is strong evidence that besides genetic factors, environmental factors are involved in the pathogenesis of the disease. Increasing

  5. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

  6. Radiological imaging of endocrine diseases

    International Nuclear Information System (INIS)

    Bruneton, J.N.

    1999-01-01

    Imaging studies are playing an increasingly role in the evaluation of endocrine diseases; accordingly, familiarity with the specific indications for the various modalities, and with the characteristic findings, is essential. This multi-author work, which is intended for both radiologists and endocrinologists, considers the role of all the recent imaging techniques, including ultrasound (particular color Doppler), computed tomography, MRI, and scintigraphy. Following an extensive introduction on the pituitary, subsequent chapters discuss in detail the normal anatomy and pathology of the female and male reproductive systems. Remaining chapters provide state-of-the-art data on the thyroid, parathyroids, pancreatic endocrine tumors, adrenal glands, hormonal tumors (carcinoids and MEN), and imaging of the complications of hormone therapy. (orig.)

  7. Afferent Endocrine Control of Eating

    DEFF Research Database (Denmark)

    Langhans, Wolfgang; Holst, Jens Juul

    2016-01-01

    The afferent endocrine factors that control eating can be separated into different categories. One obvious categorization is by the time course of their effects, with long-term factors that signal adiposity and short-term factors that operate within the time frame of single meals. The second...... obvious categorization is by the origin of the endocrine signalling molecules. The level of knowledge concerning the physiological mechanisms and relevance of the hormones that are implicated in the control of eating is clearly different. With the accumulating knowledge about the hormones' actions......, various criteria have been developed for when the effect of a hormone can be considered 'physiologic'. This chapter treats the hormones separately and categorizes them by origin. It discusses ALL hormones that are implicated in eating control such as Gastrointestinal (GI) hormone and glucagon-like peptide...

  8. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum

    OpenAIRE

    Barkla, Bronwyn J.; Vera-Estrella, Rosario

    2015-01-01

    One of the remarkable adaptive features of the halophyte and facultative CAM plant Mesembryathemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC) which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and tr...

  9. ERE environment- and cell type-specific transcriptional effects of estrogen in normal endometrial cells.

    Science.gov (United States)

    Lascombe, I; Sallot, M; Vuillermoz, C; Weisz, A; Adessi, G L; Jouvenot, M

    1998-04-30

    Our previous results have suggested a repression of E2 (17beta-estradiol) effect on the c-fos gene of cultured guinea-pig endometrial cells. To investigate this repression, the expression of three human c-fos gene recombinants, pFC1-BL (-2250/+41), pFC2-BL (-1400/+41) and pFC2E (-1300/-1050 and -230/+41), known to be E2-responsive in Hela cells, was studied in stromal (SC) and glandular epithelial cells (GEC). In both cellular types, pFC1-BL was not induced by E2, even in the presence of growth factors or co-transfected estrogen receptor. The pattern of pFC2-BL and pFC2E expression was strikingly different and depended on the cellular type: pFC2-BL and pFC2E induction was restricted to the glandular epithelial cells and did not occur in the SCs. We argue for a repression of E2 action which is dependent on the estrogen-responsive cis-acting element (ERE) environment and also cell type-specific involving DNA/protein and/or protein/protein interactions with cellular type-specific factors.

  10. Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

    International Nuclear Information System (INIS)

    Medina, D.; Oborn, C.J.; Li, M.L.; Bissell, M.J.

    1987-01-01

    The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appeared to represent myoepithelial cells. The cell lines were examined for expression of β-casein mRNA in the presence or absence of prolactin. The inducibility of β-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types

  11. Revisit the Candidacy of Brain Cell Types as the Cell(s of Origin for Human High-Grade Glioma

    Directory of Open Access Journals (Sweden)

    Fangjie Shao

    2018-02-01

    Full Text Available High-grade glioma, particularly, glioblastoma, is the most aggressive cancer of the central nervous system (CNS in adults. Due to its heterogeneous nature, glioblastoma almost inevitably relapses after surgical resection and radio-/chemotherapy, and is thus highly lethal and associated with a dismal prognosis. Identifying the cell of origin has been considered an important aspect in understanding tumor heterogeneity, thereby holding great promise in designing novel therapeutic strategies for glioblastoma. Taking advantage of genetic lineage-tracing techniques, performed mainly on genetically engineered mouse models (GEMMs, multiple cell types in the CNS have been suggested as potential cells of origin for glioblastoma, among which adult neural stem cells (NSCs and oligodendrocyte precursor cells (OPCs are the major candidates. However, it remains highly debated whether these cell types are equally capable of transforming in patients, given that in the human brain, some cell types divide so slowly, therefore may never have a chance to transform. With the recent advances in studying adult NSCs and OPCs, particularly from the perspective of comparative biology, we now realize that notable differences exist among mammalian species. These differences have critical impacts on shaping our understanding of the cell of origin of glioma in humans. In this perspective, we update the current progress in this field and clarify some misconceptions with inputs from important findings about the biology of adult NSCs and OPCs. We propose to re-evaluate the cellular origin candidacy of these cells, with an emphasis on comparative studies between animal models and humans.

  12. Pituitary autoantibodies in endocrine disorders

    OpenAIRE

    Bensing, Sophie

    2005-01-01

    Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid...

  13. Induction of expression of two phenotypic markers of pulmonary type II cells in a cultured cell line

    International Nuclear Information System (INIS)

    Henderson, R.F.; Waide, J.J.; Scott, G.G.

    1994-01-01

    The functions of pulmonary type II cells, such as synthesis of pulmonary surfactant and metabolism of inhaled xenobiotics, can be studied in primary isolates of lung cells. However, isolated type II cells, when cultured, quickly lose the phenotypic expressions characteristics of type II cells, including surfactant lipid and protein synthesis and alkaline phosphatase (AP) activity. A cultured cell line that maintained expression of type II cell markers of differentiation would be advantageous for the study of such functions as surfactant synthesis and secretion. Such a cell line would allow generation of a large number of homogeneous cells for study. The purpose of the current study was to induce markers of differentiated type II cells in a cultured cell line to facilitate studies of factors that control surfactant synthesis and secretion

  14. Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction

    Directory of Open Access Journals (Sweden)

    Marcin Szczot

    2017-12-01

    Full Text Available Summary: Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception. Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Sensory neurons from both mice and humans express a large repertoire of Piezo2 variants, whereas non-neuronal tissues express predominantly a single isoform. Notably, even within sensory ganglia, we demonstrate the splicing of Piezo2 to be cell type specific. Biophysical characterization revealed substantial differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics among Piezo2 splice variants. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli. : Szczot et al. find that the mechanoreceptor Piezo2 is extensively alternatively spliced, generating multiple distinct isoforms. Their findings indicate that these splice products have specific tissue and cell type expression patterns and exhibit differences in receptor properties. Keywords: Piezo, touch, sensation, ion-channel, splicing

  15. Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish

    Directory of Open Access Journals (Sweden)

    Ellertsdottir Elin

    2011-10-01

    Full Text Available Abstract Background Insulin-producing beta cells emerge during pancreas development in two sequential waves. Recently described later-forming beta cells in zebrafish show high similarity to second wave mammalian beta cells in developmental capacity. Loss-of-function studies in mouse and zebrafish demonstrated that the homeobox transcription factors Pdx1 and Hb9 are both critical for pancreas and beta cell development and discrete stage-specific requirements for these genes have been uncovered. Previously, exocrine and endocrine cell recovery was shown to follow loss of pdx1 in zebrafish, but the progenitor cells and molecular mechanisms responsible have not been clearly defined. In addition, interactions of pdx1 and hb9 in beta cell formation have not been addressed. Results To learn more about endocrine progenitor specification, we examined beta cell formation following morpholino-mediated depletion of pdx1 and hb9. We find that after early beta cell reduction, recovery occurs following loss of either pdx1 or hb9 function. Unexpectedly, simultaneous knockdown of both hb9 and pdx1 leads to virtually complete and persistent beta cell deficiency. We used a NeuroD:EGFP transgenic line to examine endocrine cell behavior in vivo and developed a novel live-imaging technique to document emergence and migration of late-forming endocrine precursors in real time. Our data show that Notch-responsive progenitors for late-arising endocrine cells are predominantly post mitotic and depend on pdx1. By contrast, early-arising endocrine cells are specified and differentiate independent of pdx1. Conclusions The nearly complete beta cell deficiency after combined loss of hb9 and pdx1 suggests functional cooperation, which we clarify as distinct roles in early and late endocrine cell formation. A novel imaging approach permitted visualization of the emergence of late endocrine cells within developing embryos for the first time. We demonstrate a pdx1-dependent

  16. Endocrine autoimmune disease: genetics become complex.

    Science.gov (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  17. Membrane Targeting of P-type ATPases in Plant Cells

    International Nuclear Information System (INIS)

    Harper, Jeffrey F.

    2004-01-01

    How membrane proteins are targeted to specific subcellular locations is a very complex and poorly understood area of research. Our long-term goal is to use P-type ATPases (ion pumps), in a model plant system Arabidopsis, as a paradigm to understand how members of a family of closely related membrane proteins can be targeted to different subcellular locations. The research is divided into two specific aims. The first aim is focused on determining the targeting destination of all 10 ACA-type calcium pumps (Arabidopsis Calcium ATPase) in Arabidopsis. ACAs represent a plant specific-subfamily of plasma membrane-type calcium pumps. In contrast to animals, the plant homologs have been found in multiple membrane systems, including the ER (ACA2), tonoplast (ACA4) and plasma membrane (ACA8). Their high degree of similarity provides a unique opportunity to use a comparative approach to delineate the membrane specific targeting information for each pump. One hypothesis to be tested is that an endomembrane located ACA can be re-directed to the plasma membrane by including targeting information from a plasma membrane isoform, ACA8. Our approach is to engineer domain swaps between pumps and monitor the targeting of chimeric proteins in plant cells using a Green Fluorescence Protein (GFP) as a tag. The second aim is to test the hypothesis that heterologous transporters can be engineered into plants and targeted to the plasma membrane by fusing them to a plasma membrane proton pump. As a test case we are evaluating the targeting properties of fusions made between a yeast sodium/proton exchanger (Sod2) and a proton pump (AHA2). This fusion may potentially lead to a new strategy for engineering salt resistant plants. Together these aims are designed to provide fundamental insights into the biogenesis and function of plant cell membrane systems

  18. Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

    2017-01-01

    Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

  19. Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

    Science.gov (United States)

    Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

    2014-01-01

    Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

  20. A model for cell type localization in the migrating slug of ...

    Indian Academy of Sciences (India)

    PRAKASH

    . Localization of the three major cell types within the migrating slug stage is a dynamic process (Sternfeld 1992;. A model for cell type localization in the migrating slug of Dictyostelium discoideum based on differential chemotactic sensitivity to ...

  1. Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells.

    Science.gov (United States)

    Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun; Ma, Ning; Srinivasan, Rajini; Jahanbani, Fereshteh; Lee, Jaecheol; Zhang, Sophia L; Snyder, Michael P; Wu, Joseph C

    2017-11-10

    Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31 + CD144 + ), cardiac progenitor cells (Sca-1 + ), fibroblasts (DDR2 + ), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering

  2. Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.

    Science.gov (United States)

    Casas, Jessica; Friedman, David F; Jackson, Tannoa; Vege, Sunitha; Westhoff, Connie M; Chou, Stella T

    2015-06-01

    Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported. This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles. Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fy(b) expression. DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution. © 2015 AABB.

  3. The Macrophage Galactose-Type C-Type Lectin (MGL Modulates Regulatory T Cell Functions.

    Directory of Open Access Journals (Sweden)

    Ilaria Grazia Zizzari

    Full Text Available Regulatory T cells (Tregs are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the immunosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines.

  4. The Concerted Action of Type 2 and Type 3 Deiodinases Regulates the Cell Cycle and Survival of Basal Cell Carcinoma Cells.

    Science.gov (United States)

    Miro, Caterina; Ambrosio, Raffaele; De Stefano, Maria Angela; Di Girolamo, Daniela; Di Cicco, Emery; Cicatiello, Annunziata Gaetana; Mancino, Giuseppina; Porcelli, Tommaso; Raia, Maddalena; Del Vecchio, Luigi; Salvatore, Domenico; Dentice, Monica

    2017-04-01

    Thyroid hormones (THs) mediate pleiotropic cellular processes involved in metabolism, cellular proliferation, and differentiation. The intracellular hormonal environment can be tailored by the type 1 and 2 deiodinase enzymes D2 and D3, which catalyze TH activation and inactivation respectively. In many cellular systems, THs exert well-documented stimulatory or inhibitory effects on cell proliferation; however, the molecular mechanisms by which they control rates of cell cycle progression have not yet been entirely clarified. We previously showed that D3 depletion or TH treatment influences the proliferation and survival of basal cell carcinoma (BCC) cells. Surprisingly, we also found that BCC cells express not only sustained levels of D3 but also robust levels of D2. The aim of the present study was to dissect the contribution of D2 to TH metabolism in the BCC context, and to identify the molecular changes associated with cell proliferation and survival induced by TH and mediated by D2 and D3. We used the CRISPR/Cas9 technology to genetically deplete D2 and D3 in BCC cells and studied the consequences of depletion on cell cycle progression and on cell death. Cell cycle progression was analyzed by fluorescence activated cell sorting analysis of synchronized cells, and the apoptosis rate by annexin V incorporation. Mechanistic investigations revealed that D2 inactivation accelerates cell cycle progression thereby enhancing the proportion of S-phase cells and cyclin D1 expression. Conversely, D3 mutagenesis drastically suppressed cell proliferation and enhanced apoptosis of BCC cells. Furthermore, the basal apoptotic rate was oppositely regulated in D2- and D3-depleted cells. Our results indicate that BCC cells constitute an example in which the TH signal is finely tuned by the concerted expression of opposite-acting deiodinases. The dual regulation of D2 and D3 expression plays a critical role in cell cycle progression and cell death by influencing cyclin D1-mediated

  5. Pulmonary complications of endocrine and metabolic disorders.

    Science.gov (United States)

    Milla, Carlos E; Zirbes, Jacquelyn

    2012-03-01

    There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. [Arterial hypertension secondary to endocrine disorders].

    Science.gov (United States)

    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.

  7. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

    Directory of Open Access Journals (Sweden)

    Sylvie Lachmann

    Full Text Available The mammalian protein kinase N (PKN family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

  8. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

    Science.gov (United States)

    Lachmann, Sylvie; Jevons, Amy; De Rycker, Manu; Casamassima, Adele; Radtke, Simone; Collazos, Alejandra; Parker, Peter J

    2011-01-01

    The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

  9. When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine.

    Science.gov (United States)

    Beers, Michael F; Moodley, Yuben

    2017-07-01

    Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers," which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

  10. Congenital CMV with LAD type 1 and NK cell deficiency.

    Science.gov (United States)

    Rai, Narendra; Thakur, Neha

    2013-08-01

    We report a rare case of congenital cytomegalovirus (CMV) in a patient who was subsequently diagnosed as leukocyte adhesion defect type 1 with natural killer cell deficiency. The clinical course was complicated by severe CMV pneumonitis during the newborn period. Thereafter the infant suffered from recurrent skin infections without pus formation, otitis media, and bronchopneumonia since 3 months of age. The patient had congenital CMV infection as urine and blood plasma was positive for CMV from day 12 onward. Neutrophil chemotaxis studies showed a decrease in directed chemotaxis. Neutrophils were dyspoetic and nonfunctional lacking HLA DR, CD11c, and CD18. Lymphocytes were polyclonal but lacked CD56, CD16, and surface membrane immunoglobulin.

  11. Update on endocrine disturbances in anorexia nervosa

    DEFF Research Database (Denmark)

    Støving, R K; Hangaard, J; Hagen, C

    2001-01-01

    The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes...... of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories....

  12. Radiotherapy for unresectable endocrine pancreatic carcinomas

    International Nuclear Information System (INIS)

    Tennvall, J.; Ljungberg, O.; Ahren, B.; Gustavsson, A.; Nillson, L.O.

    1992-01-01

    Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or α-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas. (author)

  13. Internalisation of engineered nanoparticles into mammalian cells in vitro: influence of cell type and particle properties

    International Nuclear Information System (INIS)

    Busch, Wibke; Bastian, Susanne; Trahorsch, Ulrike; Iwe, Maria; Kühnel, Dana; Meißner, Tobias; Springer, Armin; Gelinsky, Michael; Richter, Volkmar; Ikonomidou, Chrysanthy; Potthoff, Annegret; Lehmann, Irina; Schirmer, Kristin

    2011-01-01

    Cellular internalisation of industrial engineered nanoparticles is undesired and a reason for concern. Here we investigated and compared the ability of seven different mammalian cell cultures in vitro to incorporate six kinds of engineered nanoparticles, focussing on the role of cell type and particle properties in particle uptake. Uptake was examined using light and electron microscopy coupled with energy dispersive X-ray spectroscopy (EDX) for particle element identification. Flow cytometry was applied for semi-quantitative analyses of particle uptake and for exploring the influence on uptake by the phagocytosis inhibitor Cytochalasin D (CytoD). All particles studied were found to enter each kind of cultured cells. Yet, particles were never found within cell nuclei. The presence of the respective particles within the cells was confirmed by EDX. Live-cell imaging revealed the time-dependent process of internalisation of technical nanoparticles, which was exemplified by tungsten carbide particle uptake into the human skin cells, HaCaT. Particles were found to co-localise with lysosomal structures within the cells. The incorporated nanoparticles changed the cellular granularity, as measured by flow cytometry, already after 3 h of exposure in a particle specific manner. By correlating particle properties with flow cytometry data, only the primary particle size was found to be a weakly influential property for particle uptake. CytoD, an inhibitor of actin filaments and therewith of phagocytosis, significantly inhibited the internalisation of particle uptake in only two of the seven investigated cell cultures. Our study, therefore, supports the notion that nanoparticles can enter mammalian cells quickly and easily, irrespective of the phagocytic ability of the cells.

  14. Evidence for Differential Glycosylation of Trophoblast Cell Types*

    Science.gov (United States)

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E.; Longtine, Mark S.; Schust, Danny J.; Haslam, Stuart M.; Blois, Sandra M.; Dell, Anne; Clark, Gary F.

    2016-01-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3–4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2–3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2–3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. PMID:26929217

  15. Evidence for Differential Glycosylation of Trophoblast Cell Types.

    Science.gov (United States)

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E; Longtine, Mark S; Schust, Danny J; Haslam, Stuart M; Blois, Sandra M; Dell, Anne; Clark, Gary F

    2016-06-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3-4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2-3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2-3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. The impact of opioids on the endocrine system.

    Science.gov (United States)

    Katz, Nathaniel; Mazer, Norman A

    2009-02-01

    Opioids have been used for medicinal and analgesic purposes for centuries. However, their negative effects on the endocrine system, which have been known for some times, are barely discussed in modern medicine. Therefore, we conducted a systematic review of the impact of opioids on the endocrine system. A review of the English language literature on preclinical and clinical studies of any type on the influence of opioids on the endocrine system was conducted. Preliminary recommendations for monitoring and managing these problems were provided. Long-term opioid therapy for either addiction or chronic pain often induces hypogonadism owing to central suppression of hypothalamic secretion of gonadotropin-releasing hormone. Symptoms of opioid-induced hypogonadism include loss of libido, infertility, fatigue, depression, anxiety, loss of muscle strength and mass, osteoporosis, and compression fractures in both men and women; impotence in men; and menstrual irregularities and galactorrhea in women. In view of the increased use of opioids for chronic pain, it has become increasingly important to monitor patients taking opioids and manage endocrine complications. Therefore, patients on opioid therapy should be routinely screened for such symptoms and for laboratory abnormalities in sex hormones. Opioid-induced hypogonadism seems to be a common complication of therapeutic or illicit opioid use. Patients on long-term opioid therapy should be prospectively monitored, and in cases of opioid-induced hypogonadism, we recommend nonopioid pain management, opioid rotation, or sex hormone supplementation after careful consideration of the risks and benefits.

  17. Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

    Directory of Open Access Journals (Sweden)

    Oriana del Rocío Cruz Guzmán

    2012-01-01

    Full Text Available Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

  18. Cosmetics as endocrine disruptors: are they a health risk?

    Science.gov (United States)

    Nicolopoulou-Stamati, Polyxeni; Hens, Luc; Sasco, Annie J

    2015-12-01

    Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

  19. CCAR1 is required for Ngn3-mediated endocrine differentiation

    International Nuclear Information System (INIS)

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

    2012-01-01

    Highlights: ► We identify CCAR1 to directly interact with Ngn3. ► CCAR1 is co-localized with Ngn3 in the nucleus. ► CCAR1 cooperates with Ngn3 in activating NeuroD expression. ► 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.

  20. Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation

    International Nuclear Information System (INIS)

    Droms, K.; Sueoka, N.

    1987-01-01

    This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of three derivative cell types, RT4-B, RT4-D, or RT4-E, with a frequency of about 10(-5). The RT4-AC cells express some properties characteristic of both neuronal and glial cells. Of these neural properties expressed by RT4-AC cells, only the neuronal properties are expressed by the RT4-B and RT4-E cells, and only the glial properties are expressed by the RT4-D cells. This in vitro cell-type conversion of RT4-AC to three derivative cell types is a branch point for the coordinate regulation of several properties and seems to resemble determination in vivo. In our standard culture conditions, several other neuronal and glial properties are not expressed by these cell types. However, addition of dibutyryl-cAMP induces expression of additional properties, in a cell-type-specific manner: formation of long cellular processes in the RT4-B8 and RT4-E5 cell lines and expression of high-affinity uptake of gamma-aminobutyric acid, by a glial-cell-specific mechanism, in the RT4-D6-2 cell line. These new properties are maximally expressed 2-3 days after addition of dibutyryl-cAMP

  1. Carbonate Precipitates During Heat Evolution in FP-Type Cells

    International Nuclear Information System (INIS)

    Bruce L. Cain

    2000-01-01

    In previous work, we reported measurement of large amounts of heat generated during experiments using an FP-type open cell with concentrated LiOH/D 2 O electrolytes and thin-film Pd cathodes. During the heat evolution in several runs, which produced >100 W for more than 20 h, we consistently observed the concomitant evolution of gases from the electrolyte and the precipitation of large amounts of lithium carbonate. The carbonate production was clearly visible during production of heat, creating an opaque electrolyte even during long periods with no electrolysis current. These results indicated an unusual chemical reaction, either catalyzed by the heating process or possibly creating the heat itself. The total energy released during the earlier experiments was ∼7 MJ, while the heat of formation for the lithium carbonate in the cell was only 0.8 MJ. Hence, only ∼10% of the heat signatures from these experiments can be attributed to the precipitate formation, the balance of the heat presumably arising from nonchemical sources in the cells. The earlier experiments that produced heat also suffered from problems of reproducibility, with only 5 of 38 runs producing any heat at all. The unsuccessful runs also did not produce precipitates, and the only gas produced in these cells was due to the normal electrolysis of D 2 O to produce oxygen and deuterium in the electrodes. Recent work has focused on recreating the chemical precipitation reaction, in efforts to understand and/or trigger the heat production process. With findings from these experiments, new experiments were conducted using larger (1 L LiOH/D 2 O) cells with Pt anodes and Pd film cathodes immersed but left open-circuited. After the addition of H 2 O 2 , and subsequent heating and cooling, these cells visually reproduced the precipitation and gas evolution of the earlier heat-producing runs. However, these new runs only produced a few watts of power for several minutes, consistent with the normal exothermal

  2. ENDOCRINE OPHTHALMOPATHY: ETIOLOGY, PATHOGENESIS, CLINICAL PICTURE, DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    Nikonova L. V.

    2018-03-01

    Full Text Available The relevance of the study of endocrine ophthalmopathy is due to the high prevalence of this disease and a high risk of developing impaired vision that leads to disability of patients. This lecture presents the main genetic, immunological, clinical manifestations of endocrine ophthalmopathy in order to improve the diagnosis and treatment of this pathology. The clinical picture of endocrine ophthalmopathy is various, unique for every patient and depends on the activity and severity of the process, which requires combined etiopathogenetic therapy. The importance of timely diagnosis for endocrine ophthalmopathy with an assessment of the activity of the process for choosing the right tactics for managing patients is very high.

  3. Effect of Endocrine Disruptor Pesticides: A Review

    Directory of Open Access Journals (Sweden)

    Benoit Roig

    2011-06-01

    Full Text Available 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.

  4. Galvanic Cell Type Sensor for Soil Moisture Analysis.

    Science.gov (United States)

    Gaikwad, Pramod; Devendrachari, Mruthyunjayachari Chattanahalli; Thimmappa, Ravikumar; Paswan, Bhuneshwar; Raja Kottaichamy, Alagar; Makri Nimbegondi Kotresh, Harish; Thotiyl, Musthafa Ottakam

    2015-07-21

    Here we report the first potentiometric sensor for soil moisture analysis by bringing in the concept of Galvanic cells wherein the redox energies of Al and conducting polyaniline are exploited to design a battery type sensor. The sensor consists of only simple architectural components, and as such they are inexpensive and lightweight, making it suitable for on-site analysis. The sensing mechanism is proved to be identical to a battery type discharge reaction wherein polyaniline redox energy changes from the conducting to the nonconducting state with a resulting voltage shift in the presence of soil moisture. Unlike the state of the art soil moisture sensors, a signal derived from the proposed moisture sensor is probe size independent, as it is potentiometric in nature and, hence, can be fabricated in any shape or size and can provide a consistent output signal under the strong aberration conditions often encountered in soil moisture analysis. The sensor is regenerable by treating with 1 M HCl and can be used for multiple analysis with little read out hysteresis. Further, a portable sensor is fabricated which can provide warning signals to the end user when the moisture levels in the soil go below critically low levels, thereby functioning as a smart device. As the sensor is inexpensive, portable, and potentiometric, it opens up avenues for developing effective and energy efficient irrigation strategies, understanding the heat and water transfer at the atmosphere-land interface, understanding soil mechanics, forecasting the risk of natural calamities, and so on.

  5. Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells

    NARCIS (Netherlands)

    Lu, Z.F.; Zandieh Doulabi, B.; Wuisman, P.I.; Bank, R.A.; Helder, M.N.

    2008-01-01

    Tissue microenvironment plays a critical role in guiding local stem cell differentiation. Within the intervertebral disc, collagen type II and nucleus pulposus (NP) cells are two major components. This study aimed to investigate how collagen type II and NP cells affect adipose tissue-derived stem

  6. Early and late endocrine effects in pediatric central nervous system diseases.

    Science.gov (United States)

    Aslan, Ivy R; Cheung, Clement C

    2014-01-01

    Endocrinopathies are frequently linked to central nervous system disease, both as early effects prior to the disease diagnosis and/or late effects after the disease has been treated. In particular, tumors and infiltrative diseases of the brain and pituitary, such as craniopharyngioma, optic pathway and hypothalamic gliomas, intracranial germ cell tumor, and Langerhans cell histiocytosis, can present with abnormal endocrine manifestations that precede the development of neurological symptoms. Early endocrine effects include diabetes insipidus, growth failure, obesity, and precocious or delayed puberty. With improving prognosis and treatment of childhood brain tumors, many survivors experience late endocrine effects related to medical and surgical interventions. Chemotherapeutic agents and radiation therapy can affect the hypothalamic-pituitary axes governing growth, thyroid, gonadal, and adrenal function. In addition, obesity and metabolic alterations are frequent late manifestations. Diagnosing and treating both early and late endocrine manifestations can dramatically improve the growth, well-being, and quality of life of patients with childhood central nervous system diseases.

  7. Red cell distribution width in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Nada AM

    2015-10-01

    Full Text Available Aml Mohamed Nada Department of Internal Medicine, Unit of Endocrinology, Diabetes and Metabolism, Faculty of Medicine, Mansoura University, Mansoura, Egypt Objective: To study the indices of some elements of the complete blood count, in type 2 diabetic patients, in comparison with nondiabetic healthy controls; and to find out the effects of glycemic control and different medications on these indices. To the best of our knowledge, this study is novel in our environment and will serve as a foundation for other researchers in this field. Methods: This retrospective study included 260 type 2 diabetic patients on treatment and 44 healthy control subjects. Sex, age, weight, height, blood pressure, complete blood count, fasting plasma glucose, hemoglobin A1c (HbA1c, and lipid profile data, were available for all of the study population. For diabetic patients, data on duration of diabetes and all medications were also available. Results: Red cell distribution width (RDW was significantly higher in diabetic patients than in control subjects (P=0.008. It was also higher in patients with uncontrolled glycemia (HbA1c >7% than those with good control (HbA1c ≤7%; P=0.035. Mean platelet volume (MPV was comparable in both diabetic patients and healthy controls (P=0.238. RDW and MPV did not significantly correlate with fasting plasma glucose, HbA1c, or duration of diabetes. Both aspirin and clopidogrel did not show a significant effect on MPV. Both insulin and oral hypoglycemic agents did not show a significant effect on RDW, mean corpuscular volume, MPV, platelet count, or white blood cell count. Diabetic patients treated with indapamide or the combined thiazides and angiotensin receptor blockers showed no significant difference in RDW when compared with the control subjects. Conclusion: RDW, which is recently considered as an inflammatory marker with a significant predictive value of mortality in diseased and healthy populations, is significantly higher in

  8. CD4(+) type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes.

    Science.gov (United States)

    Kadri, Nadir; Korpos, Eva; Gupta, Shashank; Briet, Claire; Löfbom, Linda; Yagita, Hideo; Lehuen, Agnes; Boitard, Christian; Holmberg, Dan; Sorokin, Lydia; Cardell, Susanna L

    2012-04-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic β cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry diverse TCRs, prevented T1D in the NOD mouse model for the human disease. In this study, we show that CD4(+) 24αβ type II NKT cells, but not CD4/CD8 double-negative NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells in adoptive transfer experiments. CD4(+) 24αβ NKT cells exhibited a memory phenotype including high ICOS expression, increased cytokine production, and limited display of NK cell markers, compared with double-negative 24αβ NKT cells. Blocking of ICOS or the programmed death-1/programmed death ligand 1 pathway was shown to abolish the regulation that occurred in the pancreas draining lymph nodes. To our knowledge, these results provide for the first time cellular and molecular information on how type II CD1d-restricted NKT cells regulate T1D.

  9. Genetic basis of endocrine pathology

    Directory of Open Access Journals (Sweden)

    T.V. Sorokman

    2017-05-01

    Full Text Available The purpose of the review was analysis of literature data relating to the molecular genetic basis and diagnosis of endocrine pathology. We searched for published and unpublished researches using Pubmed as the search engine by the keywords: ‘genes’, ‘endocrine diseases’, ‘molecular diagnostics’, ‘prohormones’, ‘nuclear receptors and transcription factors’, taking into consideration studies conducted over the last 10 years, citation review of relevant primary and review articles, conference abstracts, personal files, and contact with expert informants. The criterion for the selection of articles for the study was based on their close relevance to the topic, thus out of 144 analyzed articles, the findings of the researchers covered in 32 articles were crucial. The described nosologies presented various heredi­tary forms of hypopituitarism, disturbances of steroid hormone biosynthesis, abnormal gender formation, monogenic forms of diabetes mellitus, endocrine tumors, etc. Pathology is identified that is associated with a mutation of genes encoding protein prohormones, receptors, steroid biosynthesis enzymes, intracellular signaling molecules, transport proteins, ion channels, and transcription factors. Among the endocrine diseases associated with defects in genes encoding protein prohormones, the defects of the GH1 gene are most common, the defects in the gene CYP21A2 (21-hydroxylase are among diseases associated with defects in genes encoding enzymes. More often mutations of genes encoding proteins belong to the class of G-protein coupled receptors. Most of the mutations associated with MEN-2A are concentrated in the rich cysteine region of the Ret receptor. More than 70 monogenic syndromes are known, in which there is a marked tolerance to glucose and some form of diabetes mellitus is diagnosed, diabetes mellitus caused by mutation of the mitochondrial gene (mutation tRNALeu, UUR is also detected. Of all the monogenic forms of

  10. Endocrine Disease in Aged Horses.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Reconstructing human pancreatic differentiation by mapping specific cell populations during development

    DEFF Research Database (Denmark)

    Ramond, Cyrille; Glaser, Nicolas; Berthault, Claire

    2017-01-01

    . Endocrine maturation progresses by up-regulating SUSD2 and lowering ECAD levels. Finally, in vitro differentiation of pancreatic endocrine cells derived from human pluripotent stem cells mimics key in vivo events. Our work paves the way to extend our understanding of the origin of mature human pancreatic......Information remains scarce on human development compared to animal models. Here, we reconstructed human fetal pancreatic differentiation using cell surface markers. We demonstrate that at 7weeks of development, the glycoprotein 2 (GP2) marks a multipotent cell population that will differentiate...... cell types and how such lineage decisions are regulated....

  12. An improved ontological representation of dendritic cells as a paradigm for all cell types

    Directory of Open Access Journals (Sweden)

    Mungall Chris

    2009-02-01

    Full Text Available Abstract Background Recent increases in the volume and diversity of life science data and information and an increasing emphasis on data sharing and interoperability have resulted in the creation of a large number of biological ontologies, including the Cell Ontology (CL, designed to provide a standardized representation of cell types for data annotation. Ontologies have been shown to have significant benefits for computational analyses of large data sets and for automated reasoning applications, leading to organized attempts to improve the structure and formal rigor of ontologies to better support computation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL's utility for computation and for cross-species data integration. Results To enhance the CL's utility for computational analyses, we developed a method for the ontological representation of cells and applied this method to develop a dendritic cell ontology (DC-CL. DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. We avoid multiple uses of is_a by linking DC-CL terms to terms in other ontologies via additional, formally defined relations such as has_function. Conclusion This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. Accordingly, we propose our method as a general strategy for the ontological representation of cells. DC-CL is available from http://www.obofoundry.org.

  13. Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type: Review of the literature

    Directory of Open Access Journals (Sweden)

    Burak Uz

    2016-01-01

    Full Text Available In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6 release from a tumor, and common genetic mutations. Further investigations are warranted.

  14. Lineage relationship of prostate cancer cell types based on gene expression

    Directory of Open Access Journals (Sweden)

    Ware Carol B

    2011-05-01

    Full Text Available Abstract Background Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells. Methods Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology and pattern 4 (aglandular sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype and LuCaP 49 (neuroendocrine/small cell carcinoma grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts. Results Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness. Conclusions Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

  15. CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides.

    Science.gov (United States)

    Nishioka, Yusuke; Masuda, Sakiko; Tomaru, Utano; Ishizu, Akihiro

    2018-01-01

    NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II. CD1d-restricted type I NKT cells express invariant T cell receptors (TCRs) and react with lipid antigens, including the marine sponge-derived glycolipid α-galactosylceramide. On the contrary, CD1d-restricted type II NKT cells recognize a wide variety of antigens, including glycolipids, phospholipids, and hydrophobic peptides, by their diverse TCRs. In this review, we focus particularly on CD1d-restricted type II NKT cells that recognize endogenous hydrophobic peptides presented by CD1d. Previous studies have demonstrated that CD1d-restricted type I NKT cells usually act as pro-inflammatory cells but sometimes behave as anti-inflammatory cells. It has been also demonstrated that CD1d-restricted type II NKT cells play opposite roles to CD1d-restricted type I NKT cells; thus, they function as anti-inflammatory or pro-inflammatory cells depending on the situation. In line with this, CD1d-restricted type II NKT cells that recognize type II collagen peptide have been demonstrated to act as anti-inflammatory cells in diverse inflammation-induction models in mice, whereas pro-inflammatory CD1d-restricted type II NKT cells reactive with sterol carrier protein 2 peptide have been demonstrated to be involved in the development of small vessel vasculitis in rats.

  16. Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models.

    Science.gov (United States)

    Caldwell, A S L; Middleton, L J; Jimenez, M; Desai, R; McMahon, A C; Allan, C M; Handelsman, D J; Walters, K A

    2014-08-01

    Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age, causing a range of reproductive, metabolic and endocrine defects including anovulation, infertility, hyperandrogenism, obesity, hyperinsulinism, and an increased risk of type 2 diabetes and cardiovascular disease. Hyperandrogenism is the most consistent feature of PCOS, but its etiology remains unknown, and ethical and logistic constraints limit definitive experimentation in humans to determine mechanisms involved. In this study, we provide the first comprehensive characterization of reproductive, endocrine, and metabolic PCOS traits in 4 distinct murine models of hyperandrogenism, comprising prenatal dihydrotestosterone (DHT, potent nonaromatizable androgen) treatment during days 16-18 of gestation, or long-term treatment (90 days from 21 days of age) with DHT, dehydroepiandrosterone (DHEA), or letrozole (aromatase inhibitor). Prenatal DHT-treated mature mice exhibited irregular estrous cycles, oligo-ovulation, reduced preantral follicle health, hepatic steatosis, and adipocyte hypertrophy, but lacked overall changes in body-fat composition. Long-term DHT treatment induced polycystic ovaries displaying unhealthy antral follicles (degenerate oocyte and/or > 10% pyknotic granulosa cells), as well as anovulation and acyclicity in mature (16-week-old) females. Long-term DHT also increased body and fat pad weights and induced adipocyte hypertrophy and hypercholesterolemia. Long-term letrozole-treated mice exhibited absent or irregular cycles, oligo-ovulation, polycystic ovaries containing hemorrhagic cysts atypical of PCOS, and displayed no metabolic features of PCOS. Long-term dehydroepiandrosterone treatment produced no PCOS features in mature mice. Our findings reveal that long-term DHT treatment replicated a breadth of ovarian, endocrine, and metabolic features of human PCOS and provides the best mouse model for experimental studies of PCOS pathogenesis.

  17. Amiloride-sensitive channels in type I fungiform taste cells in mouse

    Directory of Open Access Journals (Sweden)

    Clapp Tod R

    2008-01-01

    Full Text Available Abstract Background Taste buds are the sensory organs of taste perception. Three types of taste cells have been described. Type I cells have voltage-gated outward currents, but lack voltage-gated inward currents. These cells have been presumed to play only a support role in the taste bud. Type II cells have voltage-gated Na+ and K+ current, and the receptors and transduction machinery for bitter, sweet, and umami taste stimuli. Type III cells have voltage-gated Na+, K+, and Ca2+ currents, and make prominent synapses with afferent nerve fibers. Na+ salt transduction in part involves amiloride-sensitive epithelial sodium channels (ENaCs. In rodents, these channels are located in taste cells of fungiform papillae on the anterior part of the tongue innervated by the chorda tympani nerve. However, the taste cell type that expresses ENaCs is not known. This study used whole cell recordings of single fungiform taste cells of transgenic mice expressing GFP in Type II taste cells to identify the taste cells responding to amiloride. We also used immunocytochemistry to further define and compare cell types in fungiform and circumvallate taste buds of these mice. Results Taste cell types were identified by their response to depolarizing voltage steps and their presence or absence of GFP fluorescence. TRPM5-GFP taste cells expressed large voltage-gated Na+ and K+ currents, but lacked voltage-gated Ca2+ currents, as expected from previous studies. Approximately half of the unlabeled cells had similar membrane properties, suggesting they comprise a separate population of Type II cells. The other half expressed voltage-gated outward currents only, typical of Type I cells. A single taste cell had voltage-gated Ca2+ current characteristic of Type III cells. Responses to amiloride occurred only in cells that lacked voltage-gated inward currents. Immunocytochemistry showed that fungiform taste buds have significantly fewer Type II cells expressing PLC signalling

  18. Analysis of endocrine disruptor compounds in marine sediments by in cell clean up-pressurized liquid extraction-liquid chromatography tandem mass spectrometry determination.

    Science.gov (United States)

    Salgueiro-González, N; Turnes-Carou, I; Muniategui-Lorenzo, S; López-Mahía, P; Prada-Rodríguez, D

    2014-12-10

    A less time-, solvent- and sorbent-consuming analytical methodology for the determination of bisphenol A and alkylphenols (4-tert-octylphenol, 4-octylphenol, 4-n-nonylphenol, nonylphenol) in marine sediment was developed and validated. The method was based on selective pressurized liquid extraction (SPLE) with a simultaneous in cell clean up combined with liquid chromatography-electrospray ionization tandem mass spectrometry in negative mode (LC-ESI-MS/MS). The SPLE extraction conditions were optimized by a Plackett-Burman design followed by a central composite design. Quantitation was performed by standard addition curves in order to correct matrix effects. The analytical features of the method were satisfactory: relative recoveries varied between 94 and 100% and repeatability and intermediate precision were <6% for all compounds. Uncertainty assessment of measurement was estimated on the basis of an in-house validation according to EURACHEM/CITAC guide. Quantitation limits of the method (MQL) ranged between 0.17 (4-n-nonylphenol) and 4.01 ng g(-1) dry weight (nonylphenol). Sensitivity, selectivity, automaticity and fastness are the main advantages of this green methodology. As an application, marine sediment samples from Galicia coast (NW of Spain) were analysed. Nonylphenol and 4-tert-octylphenol were measured in all samples at concentrations between 20.1 and 1409 ng g(-1) dry weight, respectively. Sediment toxicity was estimated and no risk to aquatic biota was found. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Next-generation sequencing for endocrine cancers: Recent advances and challenges.

    Science.gov (United States)

    Suresh, Padmanaban S; Venkatesh, Thejaswini; Tsutsumi, Rie; Shetty, Abhishek

    2017-05-01

    Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.

  20. Regulated gene expression in cultured type II cells of adult human lung

    OpenAIRE

    Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

    2010-01-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

  1. Diagnosis and pathology of endocrine diseases

    International Nuclear Information System (INIS)

    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

  2. The application of PET in endocrine tumors

    International Nuclear Information System (INIS)

    Yuan Zhibin

    2003-01-01

    There are wide application of PET in endocrine tumors, including thyroid cancer, parathyroid adenoma, pheochromocytoma and neuroblastoma. Many papers concluded that in diagnosing endocrine tumors, PET does not show apparent advantages comparing with traditional radionuclide imaging methods. But as a useful complementary method, its clinical value has been recognized

  3. Diagnosis and pathology of endocrine diseases

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Intrinsic imperfections of endocrine replacement therapy

    NARCIS (Netherlands)

    Romijn, J. A.; Smit, J. W. A.; Lamberts, S. W. J.

    2003-01-01

    Hormonal substitution therapy has been extremely successful, with respect to morbidity and mortality, in the treatment of the major syndromes of endocrine insufficiency. However, many patients treated for endocrine insufficiencies still suffer from more or less vague complaints and a decreased

  5. Tailoring endocrine treatment for early breast cancer

    NARCIS (Netherlands)

    Fontein, Duveken Berthe Yvonne

    2014-01-01

    This thesis describes several important aspects of adjuvant endocrine therapy for postmenopausal women with endocrine-sensitive, early-stage breast cancer. In our ongoing efforts to tailor treatment so as to provide the best possible care to each of our patients, we studied the influence of various

  6. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

    Science.gov (United States)

    Rizzo, Benedetta; Zambonin, Laura; Leoncini, Emanuela; Vieceli Dalla Sega, Francesco; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

    2013-01-01

    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. PMID:24327825