HISTOLOGICAL TYPING of ENDOCRINE TUMOURS INTERNATIONAL HISTOLOGICAL CLASSIFICATION of TUMOURS No
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Expression Pattern of Delta-Like 1 Homolog in Developing Sympathetic Neurons and Chromaffin Cells
Published in "Gene Expression Patterns 30: 49–54, 2018" which should be cited to refer to this work. Expression pattern of delta-like 1 homolog in developing sympathetic neurons and chromaffin cells ∗ Tehani El Faitwria,b, Katrin Hubera,c, a Institute of Anatomy & Cell Biology, Albert-Ludwigs-University Freiburg, Albert-Str. 17, 79104, Freiburg, Germany b Department of Histology and Anatomy, Faculty of Medicine, Benghazi University, Benghazi, Libya c Department of Medicine, University of Fribourg, Route Albert-Gockel 1, 1700, Fribourg, Switzerland ABSTRACT Keywords: Delta-like 1 homolog (DLK1) is a member of the epidermal growth factor (EGF)-like family and an atypical notch Sympathetic neurons ligand that is widely expressed during early mammalian development with putative functions in the regulation Chromaffin cells of cell differentiation and proliferation. During later stages of development, DLK1 is downregulated and becomes DLK1 increasingly restricted to specific cell types, including several types of endocrine cells. DLK1 has been linked to Adrenal gland various tumors and associated with tumor stem cell features. Sympathoadrenal precursors are neural crest de- Organ of Zuckerkandl rived cells that give rise to either sympathetic neurons of the autonomic nervous system or the endocrine Development ffi Neural crest chroma n cells located in the adrenal medulla or extraadrenal positions. As these cells are the putative cellular Phox2B origin of neuroblastoma, one of the most common malignant tumors in early childhood, their molecular char- acterization is of high clinical importance. In this study we have examined the precise spatiotemporal expression of DLK1 in developing sympathoadrenal cells. We show that DLK1 mRNA is highly expressed in early sympa- thetic neuron progenitors and that its expression depends on the presence of Phox2B. -
Calcium-Sensing Receptor Is a Physiologic Multimodal Chemosensor Regulating Gastric G-Cell Growth and Gastrin Secretion
Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion Jianying Fenga, Clark D. Petersena, David H. Coyb, Jian-Kang Jiangc, Craig J. Thomasc, Martin R. Pollakd, and Stephen A. Wanka,1 aDigestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1804; bPeptide Research Laboratories, Department of Medicine, Tulane Health Sciences Center, New Orleans, LA 70112-2699; cNational Institutes of Health Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892; and dDivision of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA 02215 Edited* by Martha Vaughan, National Heart, Lung, and Blood Institute, Bethesda, MD, and approved September 1, 2010 (received for review June 25, 2010) The calcium-sensing receptor (CaR) is the major sensor and The sensing of extracellular Ca2+ and the regulation of Ca2+ regulator of extracellular Ca2+, whose activity is allosterically reg- homestasis has been largely attributed to the calcium-sensing ulated by amino acids and pH. Recently, CaR has been identified in receptor (CaR), a member of the C family of G protein-coupled the stomach and intestinal tract, where it has been proposed to receptors (GPCR). Consistent with this function, CaR is ex- 2+ function in a non-Ca2+ homeostatic capacity. Luminal nutrients, pressed on extracellular Ca -regulating cells such as para- such as Ca2+ and amino acids, have been recognized for decades thyroid, thyroid parafollicular, renal tubular, and bone cells (6). as potent stimulants for gastrin and acid secretion, although the The CaR has a large NH2 terminal extracellular domain molecular basis for their recognition remains unknown. -
Novel Autocrine Feedback Control of Catecholamine Release a Discrete Chromogranin a Fragment Is a Noncompetitive Nicotinic Cholinergic Antagonist Sushil K
Novel Autocrine Feedback Control of Catecholamine Release A Discrete Chromogranin A Fragment is a Noncompetitive Nicotinic Cholinergic Antagonist Sushil K. Mahata,* Daniel T. O’Connor,* Manjula Mahata,* Seung Hyun Yoo,‡ Laurent Taupenot,* Hongjiang Wu,* Bruce M. Gill,* and Robert J. Parmer* *Department of Medicine and Center for Molecular Genetics, University of California, San Diego, California 92093 and Department of Veterans Affairs Medical Center, San Diego, California 92161, and ‡National Institute of Deafness and Communicative Disorders, National Institutes of Health, Bethesda, Maryland 20892 Abstract completely established, recent evidence implicates chromogra- nin A as a precursor of several small biologically active secre- Catecholamine secretory vesicle core proteins (chromog- tion-inhibitory peptides that may play an autocrine regulatory ranins) contain an activity that inhibits catecholamine re- role in neuroendocrine secretion from a variety of cell types (3, lease, but the identity of the responsible peptide has been 7–10). The primary structure of chromogranin A reveals 8–10 elusive. Size-fractionated chromogranins antagonized nico- conserved pairs of basic amino acids that represent potential tinic cholinergic-stimulated catecholamine secretion; the in- proteolytic cleavage sites for the generation of such peptides hibitor was enriched in processed chromogranin fragments, (11–17), and chromogranin A is a substrate for the prohor- and was liberated from purified chromogranin A. Of 15 syn- mone convertases (18–20). of chromogranin A, one To date, several chromogranin A–derived peptides have %80 ف thetic peptides spanning (bovine chromogranin A344–364 [RSMRLSFRARGYGFRG- been identified that affect the secretory function of the parent PGLQL], or catestatin) was a potent, dose-dependent (IC50 cells. -
Overview of Gastrointestinal Function
Overview of Gastrointestinal Function George N. DeMartino, Ph.D. Department of Physiology University of Texas Southwestern Medical Center Dallas, TX 75390 The gastrointestinal system Functions of the gastrointestinal system • Digestion • Absorption • Secretion • Motility • Immune surveillance and tolerance GI-OP-13 Histology of the GI tract Blood or Lumenal Serosal Side or Mucosal Side Structure of a villus Villus Lamina propria Movement of substances across the epithelial layer Tight junctions X Lumen Blood Apical membrane Basolateral membrane X X transcellular X X paracellular GI-OP-19 Histology of the GI tract Blood or Lumenal Serosal Side or Mucosal Side Motility in the gastrointestinal system Propulsion net movement by peristalsis Mixing for digestion and absorption Separation sphincters Storage decreased pressure GI-OP-42 Intercellular signaling in the gastrointestinal system • Neural • Hormonal • Paracrine GI-OP-10 Neural control of the GI system • Extrinsic nervous system autonomic central nervous system • Intrinsic (enteric) nervous system entirely with the GI system GI-OP-14 The extrinsic nervous system The intrinsic nervous system forms complete functional circuits Sensory neurons Interneurons Motor neurons (excitatory and inhibitory) Parasympathetic nerves regulate functions of the intrinsic nervous system Y Reflex control of gastrointestinal functions Vago-vagal Afferent reflex Salivary Glands Composition of Saliva O Proteins α−amylase lactoferrin lipase RNase lysozyme et al mucus O Electrolyte solution water Na+ , K + - HCO3 -
Extra-Adrenal Chromaffin Cells of the Zuckerkandl´S Paraganglion: Morphological and Electrophysiological Study
275 Extra-adrenal chromaffin cells of the Zuckerkandl´s paraganglion: morphological and electrophysiological study. Beatriz Galán-Rodríguez, M. Pilar Ramírez-Ponce, Fadwa El Banoua, Juan A. Flores, Juan Bellido and Emilio Fernández-Espejo. Departamento de Fisiología Médica y Biofísica. Universidad de Sevilla. Spain. Correspondence: Dra. Beatriz Galán Rodríguez or Dr. Emilio Fernández-Espejo, Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, 41009. Sevilla. Spain. Phone: 34-954-556584; Fax: 34-954-551769; Email: [email protected] ; [email protected] Cell Biology of the Chromaffin Cell R. Borges & L. Gandía Eds. Instituto Teófilo Hernando, Spain, 2004 Cell Biology of the Chromaffin Cell 276 Parkinson´s disease is one of the most important neurodegenerative disorders that affects to one out of a hundred of the world population elder than 65. It has been observed in our laboratory, for the first time, that intrabrain transplantation of chromaffin cell aggregates from the Zuckerkandl´s organ, an extraadrenal paraganglion located adjacent to the lower abdominal aorta, induced gradual improvement of functional deficits in animal models of Parkinson´s disease1. This functional regeneration was likely caused by long-survival of grafted cells and chronic trophic action of dopaminotrophic factors, glial cell line-derived 2,3 4,5 factor (GDNF) and transforming growth factor beta1 (TGF-b1) , which are expressed and delivered by long-surviving grafted chromaffin cells. The objective of this study is to discern the morphological and cytological characteristics of extra-adrenal cells of the Zuckerkandl’s organ. On the other hand, long survival of extra-adrenal chromaffin cells could be related to resistance to hypoxia, since it is certainly know that hypoxia is a primary factor involved in cell death after intrabrain grafting. -
Cell Proliferation
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 1771-1775, March 1994 Neurobiology Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation MORTEN FRODIN* AND STEEN GAMMELTOFT*t Department of Clinical Chemistry, Bispebjerg Hospital, DK 2400 Copenhagen NV, Denmark Communicated by Viktor Mutt, November 29, 1993 (receivedfor review August 26, 1993) ABSTRACT We have investigated the effects of insulin- addition, NGF and bFGF stimulate transdifferentiation of like growth factors (IGFs), basic fibroblast growth factor cultured chromaffin cells into a sympathetic neuron-like (bFGF), and nerve growth factor (NGF) on DNA synthesis in phenotype and increase cell survival and catecholamine cultured chromaffin cells from fetal, neonatal, and adult rats synthesis (8, 9, 13-15). In adult rats, chromaffmi-cell replace- by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for ment decreases after denervation of the adrenal medulla, 24 or 48 h and immunocytochemical staining of cell nuclei. suggesting that neurogenic stimuli can regulate chromaffmi- After 6 days in culture in the absence ofgrowth factors, nuclear cell proliferation (16). BrdUrd incorporation was detected in 30% offetal chromafFin Insulin-like growth factor I and II (IGF-I and IGF-II, cells, 1.5% of neonatal cells, and 0.1% of adult cells. Addition respectively) act as neurotrophic factors in various parts of of 10 nM IGF-I or IGF-ll increased the fraction of BrdUrd- the developing and adult nervous system (17). IGF-II mRNA labeled nuclei to 50% offetal, 20% ofneonatal, and 2% ofadult and immunoreactivity have been demonstrated in adult hu- chromaffn cells. -
The Generation of Monoclonal Antibodies That Bind Preferentially to Adrenal Chromaffin Cells and the Cells of Embryonic Sympathetic Ganglia
The Journal of Neuroscience, November 1991, 7 7(11): 34933506 The Generation of Monoclonal Antibodies that Bind Preferentially to Adrenal Chromaffin Cells and the Cells of Embryonic Sympathetic Ganglia Josette F. Carnahaw and Paul l-i. Patterson Biology Division, California Institute of Technology, Pasadena, California 91125 Adrenal chromaffin ceils, sympathetic neurons, and small technical limitation in this effort is the lack of markers specific intensely fluorescent (SIF) cells are each derived from the for the various stagesof development within a particular lineage. neural crest, produce catecholamines, and share certain Without such markers, cells making key phenotypic decisions morphological features. These cell types are also partially cannot be identified. It has been especially difficult to find mo- interconvertible in cell culture (Doupe et al., 1985a,b; An- lecular labels for committed progenitor cells. Monoclonal an- derson and Axel, 1988). Thus, these cells are said to be tibodies can be used as highly specific markers, and the hybrid- members of the sympathoadrenal (SA) lineage and could oma method can be manipulated so asto enhancethe likelihood share a common progenitor. To investigate the origins of this of obtaining antibodies against rare antigens of interest (Mat- lineage further, we used the cyclophosphamide immuno- thew and Patterson, 1983; Barald and Wessels,1984; Agius and suppression method (Matthew and Patterson, 1983) to gen- Richman, 1986; Barclay and Smith, 1986; Golumbeski and Di- erate five monoclonal antibodies (SAl-5) that bind strongly mond, 1986; Hockfield, 1987; Mahana et al., 1987; Matthew to chromaffin cells, with little or no labeling of sympathetic and Sandrock, 1987; Norton and Benjamini, 1987; Huse et al., neurons or SIF cells in frozen sections from adult rats. -
Cellular Localization of Gastric Inhibitory Polypeptide in the Duodenum and Jejunum
Gut: first published as 10.1136/gut.14.4.284 on 1 April 1973. Downloaded from Gut, 1973, 14, 284-288 Cellular localization of gastric inhibitory polypeptide in the duodenum and jejunum JULIA M. POLAK, S. R. BLOOM', MARION KUZIO, J. C. BROWN, AND A. G. E. PEARSE From the Department ofHistochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, London, and the Department ofPhysiology, University ofBritish Columbia, Vancouver, Canada SUMMARY Indirect immunofluorescence studies using an antiserum to purified porcine gastric inhibitory polypeptide indicate, in the gastrointestinal tract of dog and man, that this polypeptide is present in cells situated predominantly in the mid-zone of the glands in the duodenum and, to a lesser extent, in the jejunum. Absolute correlation of the gastric inhibitory polypeptide cell with one or other of the known endocrine-like cells identified by electron microscopy awaits confirmation by electron immunocytochemistry. It is here identified as an endocrine polypeptide cell of the APUD series and, provisionally, as the D, cell. While the hormonal status of a given polypeptide depends ultimately on physiological experiments the present results strengthen the view that gastric inhibitory polypeptide is indeed a hormone. In 1969 Brown, Pederson, Jorpes, and Mutt described We report here the results of immunofluorescence an enterogastrone, extractable from porcine intestine, studies on the localization of GIP in human and http://gut.bmj.com/ which strongly inhibited gastric acid secretion. The canine intestine. purification of an apparently similar enterogastrone was reported in the same year by Lucien, Itoh, Sun, Material and Methods Meyer, Carlton, and Schally. The first of these poly- peptides, named gastric inhibitory polypeptide Operative samples of duodenal and jejunal mucosa (GIP) by Brown, Mutt, and Pederson (1970), was from seven human subjects were studied. -
Reciprocal Regulation of Antral Gastrin and Somatostatin Gene Expression by Omeprazole-Induced Achlorhydria
Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. S J Brand, D Stone J Clin Invest. 1988;82(3):1059-1066. https://doi.org/10.1172/JCI113662. Research Article Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells. Find the latest version: https://jci.me/113662/pdf Reciprocal Regulation of Antral Gastrin and Somatostatin Gene Expression by Omeprazole-induced Achlorhydria Stephen J. Brand and Deborah Stone Departments ofMedicine, Harvard Medical School and Massachusetts General Hospital, Gastrointestinal Unit, Boston, Massachusetts Abstract Substantial evidence supports the hypothesis that gastric acid inhibits gastrin secretion through somatostatin released Gastric acid exerts a feedback inhibition on the secretion of from antral D cells (9, 10). -
Stimulus-Secretion Coupling in Chromaffin Cells Isolated
Proc. Natl. Acad. Sci. USA Vol. 74, No. 11, pp. 5036-5040, November 1977 Cell Biology Stimulus-secretion coupling in chromaffin cells isolated from bovine adrenal medulla (catecholamine secretion/acetylcholine receptors/K+ depolarization/calcium requirement/microtubule disruption) ALLAN S. SCHNEIDER*, RUTH HERZ*, AND KURT ROSENHECKt * Sloan-Kettering Institute for Cancer Research, Cornell University Graduate School of Medical Sciences, New York, New York 10021; and tDepartment of Membrane Research, Weizmann Institute of Science, Rehovot, Israel Communicated by Francis 0. Schmitt, August 19,1977 ABSTRACT Bovine adrenal chromaffin cells were isolated membrane fusion and exocytosis, (iii) the possible role of cyclic by removal of the cortex and sequential collagenase digestion nucleotides coupled with ion translocation in mediating hor- of the medulla. The catecholamine secretory function of these cells was characterized with respect to acetylcholine stimula- mone and neurotransmitter synthesis and secretion, and (iv) tion, cation requirements, and cytoskeletal elements. The the role of microfilaments, microtubules, and/or a calcium- dose-response curve for stimulated release had its half-maxi- modulated contractile protein system in bringing secretory mum value at 10-5 M acetylcholine, and maximum secretion granules together with the plasma membrane to facilitate ex- was on the average 7 times that of control basal secretion. The ocytosis. Further advances may be possible on these and related differential release of epinephrine versus norepinephrine after questions through the use of isolated chromaffin cells. stimulation with 0.1 mM acetylcholine occurred in proportion to their distribution in the cell suspension. The cholinergic re- In the present work we provide a functional characterization ceptors were found to be predominantly nicotinic. -
Advances in Paraganglioma– Pheochromocytoma Cell Lines and Xenografts
27 12 Endocrine-Related J-P Bayley and P Devilee PPGL cell lines and xenografts 27:12 R433–R450 Cancer REVIEW Advances in paraganglioma– pheochromocytoma cell lines and xenografts Jean-Pierre Bayley 1 and Peter Devilee 1,2 1Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands 2Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands Correspondence should be addressed to J-P Bayley: [email protected] Abstract This review describes human and rodent-derived cell lines and xenografts developed over Key Words the last five decades that are suitable or potentially suitable models for paraganglioma– f paraganglioma pheochromocytoma research. We outline the strengths and weaknesses of various f pheochromocytoma models and emphasize the recurring theme that, despite the major challenges f succinate dehydrogenase involved, more effort is required in the search for valid human and animal cell models f models of paraganglioma–pheochromocytoma, particularly those relevant to cancers carrying f cell lines a mutation in one of the succinate dehydrogenase genes. Despite many setbacks, the f xenografts recent development of a potentially important new model, the RS0 cell line, gives reason f SV40 for optimism regarding the future of models in the paraganglioma–pheochromocytoma f MPC field. We also note that classic approaches to cell line derivation such as SV40-mediated f MTT immortalization and newer approaches such as organoid culture or iPSCs have been f imCC insufficiently explored. As many existing cell lines have been poorly characterized, we f hPheo1 provide recommendations for reporting of paraganglioma and pheochromocytoma f PC12 cell lines, including the strong recommendation that cell lines are made widely available via the ATCC or a similar cell repository. -
Chromaffin Cell Development in Mash1 Mutant Mice 4731
Development 129, 4729-4738 (2002) 4729 Printed in Great Britain © The Company of Biologists Limited 2002 DEV1866 Development of chromaffin cells depends on MASH1 function Katrin Huber1, Barbara Brühl1, François Guillemot2, Eric N. Olson3, Uwe Ernsberger1 and Klaus Unsicker1,* 1Neuroanatomy, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, INF 307, D-69120 Heidelberg, Germany 2IGBMC,CNRS/INSERM/Université Louis Pasteur, BP 163, 67404 Illkirch Cédex, Cu de Strasbourg, France 3Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75239-9148, USA *Author for correspondence (e-mail: [email protected]) Accepted 8 July 2002 SUMMARY The sympathoadrenal (SA) cell lineage is a derivative of population seen in Mash1+/+ mice is maintained in Mash1–/– the neural crest (NC), which gives rise to sympathetic mice at birth. Similar to Phox2b, cells expressing Phox2a neurons and neuroendocrine chromaffin cells. Signals that and Hand2 (dHand) clearly outnumber TH-positive cells. are important for specification of these two types of cells Most cells in the adrenal medulla of Mash1–/– mice do not are largely unknown. MASH1 plays an important role for contain chromaffin granules, display a very immature, neuronal as well as catecholaminergic differentiation. neuroblast-like phenotype, and, unlike wild-type adrenal Mash1 knockout mice display severe deficits in sympathetic chromaffin cells, show prolonged expression of ganglia, yet their adrenal medulla has been reported to be neurofilament and Ret comparable with that observed in largely normal suggesting that MASH1 is essential for wild-type sympathetic ganglia. However, few chromaffin neuronal but not for neuroendocrine differentiation. We cells in Mash1–/– mice become PNMT positive and show now that MASH1 function is necessary for the downregulate neurofilament and Ret expression.