DOCSLIB.ORG

Cholecystokinin Expression in the Developing and Regenerating Pancreas and Intestine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cholecystokinin Expression in the Developing and Regenerating Pancreas and Intestine 233 Cholecystokinin expression in the developing and regenerating pancreas and intestine G Liu, S V Pakala, D Gu, T Krahl, L Mocnik and N Sarvetnick Department of Immunology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA (Requests for offprints should be addressed to N Sarvetnick; Email: [email protected]) Abstract In developmental terms, the endocrine system of neither NOD mice continued this pattern. By contrast, in IFN- the gut nor the pancreatic islets has been characterized transgenic mice, CCK expression was suppressed from fully. Little is known about the involvement of cholecysto- birth to 3 months of age in the pancreata but not intestines. kinin (CCK), a gut hormone, involved in regulating the However, by 5 months of age, CCK expression appeared secretion of pancreatic hormones, and pancreatic growth. in the regenerating pancreatic ductal region of IFN- Here, we tracked CCK-expressing cells in the intestines transgenic mice. In the intestine, CCK expression per- and pancreata of normal mice (BALB/c), Non Obese sisted from fetus to adulthood and was not influenced Diabetic (NOD) mice and interferon (IFN)- transgenic by IFN-. Intestinal cells expressing CCK did not mice, which exhibit pancreatic regeneration, during em- co-express glucagon, suggesting that these cells are bryonic development, the postnatal period and adulthood. phenotypically distinct from CCK-expressing cells in We also questioned whether IFN- influences the expres- the pancreatic islets, and the effect of IFN- on sion of CCK. The results from embryonic day 16 showed CCK varies depending upon the cytokine’s specific that all three strains had CCK in the acinar region of microenvironment. pancreata, and specifically in cells that also expressed Journal of Endocrinology (2001) 169, 233–240 glucagon. However, in adulthood only BALB/c and Introduction Previous studies showed that interferon (IFN)- not only contributed to the diabetic state by promoting Cholecystokinin (CCK) is a gut hormone and neuro- lymphocyte infiltration and islet cell destruction but also peptide whose important function is to stimulate gall- induced pancreatic islet cell regeneration and proliferation bladder contraction and regulate the digestive process. when expressed in the pancreatic islets of transgenic Two separate cell types produce CCK: endocrine cells of mice under the control of the human insulin promoter the proximal small intestine and pancreas, and neurons (Sarvetnick et al. 1988, Gu & Sarvetnick 1993, Gu et al. in the gastrointestinal tract and central nervous system 1994). This strain undergoes complex pathogenic changes (Liddle 1997). It was previously suggested that pancreatic that include proliferation of duct cells and islet regener- endocrine cells originate from neuroectoderm because a ation (Gu & Sarvetnick 1993, Gu et al. 1994, 1997, number of neuronal markers are expressed in these cells. Sarvetnick et al. 1990). To understand the hierarchy of However, current evidence suggests that endocrine cells in CCK-expressing endocrine cells in the normal and the pancreas originate from duct epithelial cells, which are regenerating pancreas, we examined the location of CCK- derived from two outpouchings from the primitive gut. expressing cells in the regenerating pancreas in IFN- These structures organize into islet clusters with centrally transgenic mice. The use of immunologically normal located cells surrounded by the other endocrine cell BALB/c mice, autoimmune Non Obese Diabetic (NOD) types. Recent reports indicated that CCK also has the mice and IFN- transgenic mice offered three situations capacity to stimulate and regulate insulin secretion and in which to analyze the developmental occurrence and glucose homeostasis (Ballinger et al. 1997, Liddle 1997, location of CCK-expressing cells. Our studies allowed Ahren et al. 2000). This implies that CCK is involved the identification of cellular sites of CCK expression in pancreatic function, yet little is known about the differ- during gastrointestinal and pancreatic development in entiation pathway of CCK-expressing cells during the these three strains of mice, and investigated the origin development of the pancreas and gastrointestinal tract in of CCK-expressing cells during embryonic and mature mice. life. Journal of Endocrinology (2001) 169, 233–240 Online version via http://www.endocrinology.org 0022–0795/01/0169–233 2001 Society for Endocrinology Printed in Great Britain Downloaded from Bioscientifica.com at 09/29/2021 10:00:35PM via free access 234 GLIUand others · Expression of CCK during intestine and pancreas development Materials and Methods anti-rabbit IgG (1:100 FL 1000, Vector, Burlingame, CA, USA). Guinea pig anti-glucagon primary polyclonal Female mice of the BALB/c, NOD and Ins-IFN- antibody (1:100, 1032, Linco, Charles, MO, USA) was transgenic strains back-crossed to the BALB/c background then applied and revealed by TRSC-labeled anti-guinea (Sarvetnick et al. 1990) were used in this study. The time pig IgG (1:100, 42289, Jackson Immunology Research of sacrifice and tissue excision ranged from embryonic (E) Lab, West Grove, PA, USA). For CCK and insulin or days 13 to 21 and postnatal days 1, 7, 14 and 21, to months glucagon and insulin double immunofluorescence, the 1, 2, 3, 4 and 5. Three to five mice were examined at each rabbit anti-CCK primary polyclonal antibody or rabbit time point. Fifteen to 20 sections per pancreas were anti-glucagon primary polyclonal antibody was applied detected and the sections were taken from different levels and revealed using FITC-labeled anti-rabbit IgG. Guinea through the pancreas. All animals were kept in a specific pig anti-insulin primary polyclonal antibody was then pathogen-free facility at The Scripps Research Institute in applied and revealed by TRSC-labeled anti-guinea pig accordance with the rules and regulations of the Institu- IgG. Sections were placed in mounting medium Slow tional Animal Care and Use Committee. Food and water Fade (S-746, Molecular Probes, Eugene, OR, USA) with were provided, and animals were housed under a con- a cover glass and were examined under a Zeiss laser trolled 12 h light : 12 h darkness cycle and allowed to feed scanning confocal microscope (MRC-1024, Bio Rad, ad libitum. Hercules, CA, USA). To rule out cross-reactivity in this staining system, the controls used were: first, single stain- ing with the alternative secondary antibody, and second, Histology and immunocytochemistry staining in the absence of primary antibody. In neither case was staining detectable. Gut and pancreatic tissues from the three murine strains were fixed in Bouin’s fixative and processed for embed- ding. The paraffin sections were deparaffinized in xylene, rehydrated in graded ethanol and distilled water. Excessive Results aldehydes in the fixed sections were quenched in 0·2M glycine for 30 min. The nonspecific binding sites were CCK expression during development of the gastrointestinal blocked in 10% normal goat serum for 30 min, and tract incubation followed with rabbit anti-CCK primary poly- To characterize the ontogeny of CCK-expressing cells clonal antibody (1:1000, AB1972, Chemicon, Temecula, during intestinal organogenesis, gut tissues from BALB/c, CA, USA) or the rabbit anti-glucagon primary polyclonal NOD mice and IFN- transgenic mice were examined by antibody (1:2500, A565, DAKO, Carpinteria, CA, USA) staining with anti-CCK antibody. The resulting cyto- or the guinea pig anti-insulin primary polyclonal antibody plasmic immunoreactivity appeared in scattered single (1:800, A0564, DAKO, Carpintera, CA, USA) at 4 C CCK-expressing cells located in the gut tube epithelium overnight. In these instances, biotinylated anti-rabbit IgG of BALB/c, NOD and IFN- transgenic mice beginning or biotinylated anti-guinea pig IgG was used as the at day E13 and extending into the postnatal period and secondary antibody. The sections were then treated with adulthood (Fig. 1). There was no significant difference in 1% hydrogen peroxide in methanol for 15 min to block the location, morphology, or number of CCK-positive endogenous peroxidase. Next, the sections were incubated cells in intestines from BALB/c, NOD or IFN- trans- in avidin–biotin–peroxidase complex (ABC kit, PK-4000, genic mice. Furthermore, no CCK-positive cells from gut Vector Labs, Burlingame, CA, USA), and the slides tube sections of these three strains co-expressed glucagon were developed in 0·07% hydrogen peroxide using during either fetal or adult life (not shown). diaminobenzidine (DAB) as chromogen. Sections were counter-stained in hematoxylin, dehydrated in graded ethanol, and mounted in Permount with a cover CCK expression during pancreatic development in BALB/c glass. and NOD mice To detect CCK expression in islets of normal and diabetes- prone mice, pancreatic sections from BALB/c and NOD Immunofluorescence mice respectively were tested from fetal through adult For indirect immunofluorescence assays, tissues were stages by using immunochemistry and immunofluores- stained as described above, except that fluorescein isothio- cence methods. CCK was first detected on day E16 and cyanate (FITC) or Texas Red (TRSC) was used in place was visible in cells located in the acinar region of the of peroxidase-labeled IgG. For CCK and glucagon double pancreas. During the postnatal period, CCK expression immunofluorescence, the rabbit anti-CCK primary poly- became strong in pancreatic islets and was very similar in clonal antibody was applied (1:1000 AB 1972, Chemicon, distribution (Fig. 2A and B) to glucagon expression. To Temecula, CA, USA) and revealed using FITC-labeled determine if the cells that express CCK also express the Journal of Endocrinology (2001) 169, 233–240 www.endocrinology.org Downloaded from Bioscientifica.com at 09/29/2021 10:00:35PM via free access Expression of CCK during intestine and pancreas development · GLIUand others 235 Figure 1 The positioning of the CCK-expressing cells showed scattered single cells located in the epithelium of intestine in mice by the immunohistochemistry method using DAB as a chromogen. (A) CCK expressed in the epithelium of gut tube in the E16 IFN- transgenic mouse.
Load more

Recommended publications
  • Endocrine Pancreatic Tumors: Ultrastructure
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 1 Copyright© 1980, Institute for Clinical Science, Inc. Endocrine Pancreatic Tumors: Ultrastructure MERY KOSTIANOVSKY, M.D. Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107 ABSTRACT Endocrine pancreatic tumors are frequently multicellular and produce several hormones and peptides. A review of the basic concepts of hormone secretion, pancreatic islet cell composition and ultrastructural make-up of tumors is presented. The importance of correlating ultrastructural, immuno- cytochemical and biochemical studies of these tumors is emphasized. Introduction Morphofunctional Aspects of Pancreatic Islets During the last few years a great amount of information was accumulated regarding At the present time four different types the mechanisms of synthesis, storage and of cells have been described in the pan­ release of hormones.14,28,31 The use of ex­ creatic islets,17,33 each having a specific perimental in vitro m odels21,25,26,28 was secretory product (table I). A variety of very helpful in clarifying the participation other cells possibly exists, although of different organelles in the biosynthesis, further identification is awaited. By light cellular “packaging” and emyocytosis of microscopy, it is not possible to distin­ the secretory products. In a review, Lacy31 guish one type of cell from the other. has proposed a working model for hor­ Histochemical procedures are of help, mone secretion, describing the sim­ however, and B cells are easily stained ilarities between different endocrine with aldehyde fuchsin. The dicferent pro­ glands. Some of this information was ob­ cedures and empiric nature oi the silver tained through the studies of endocrine stain22 added confusion in the nomen­ pancreatic tumors as in the case of the clature of the cells (as seen in table I) discovery of pro-insulin in a beta cell where the same cell has been described adenoma.62 The purpose of this paper is to by different names.
    [Show full text]
  • Reference ID: 4125998
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Determine the number of vials to be reconstituted based on the patient’s These highlights do not include all the information needed to use weight and prescribed dose (2.2) ® CHIRHOSTIM safely and effectively. See full prescribing information for • ChiRhoStim® must be reconstituted with 0.9% Sodium Chloride CHIRHOSTIM®. Injection prior to administration (2.2) • See full prescribing information for complete information on exocrine ® CHIRHOSTIM (human secretin) for injection, for intravenous use test methods (2.3) Initial U.S. Approval: 2004 -------------------------RECENT MAJOR CHANGES----------------------------­ ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ Dosage and Administration (2.1) 07/2017 For injection: 16 mcg or 40 mcg of human secretin as a lyophilized powder in Contraindications, removed (4) 07/2017 single-dose vial for reconstitution (3) Warnings and Precautions (5.1, 5.2) 07/2017 -------------------------------CONTRAINDICATIONS-----------------------------­ -------------------------INDICATIONS AND USAGE----------------------------- None (4) ChiRhoStim® is a secretin class hormone indicated for stimulation of: • pancreatic secretions, including bicarbonate, to aid in the diagnosis of -----------------------WARNINGS AND PRECAUTIONS-----------------------­ exocrine pancreas dysfunction (1) • Hyporesponse to Secretin Stimulation Testing in Patients with • gastrin secretion to aid in the diagnosis of gastrinoma (1) Vagotomy, Inflammatory Bowel Disease or Receiving
    [Show full text]
  • Digestive System Physiology of the Pancreas
    Digestive System Physiology of the pancreas Dr. Hana Alzamil Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin What are the types of glands? Anatomy of pancreas Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin Histology of the Pancreas Acini ◦ Exocrine ◦ 99% of gland Islets of Langerhans ◦ Endocrine ◦ 1% of gland Secretory function of pancreas Acinar and ductal cells in the exocrine pancreas form a close functional unit. Pancreatic acini secrete the pancreatic digestive enzymes. The ductal cells secrete large volumes of sodium bicarbonate solution The combined product of enzymes and sodium bicarbonate solution then flows through a long pancreatic duct Pancreatic duct joins the common hepatic duct to form hepatopancreatic ampulla The ampulla empties its content through papilla of vater which is surrounded by sphincter of oddi Objectives Pancreatic acini Pancreatic secretion Pancreatic enzymes Control of pancreatic secretion ◦ Neural ◦ Hormonal Secretin Cholecystokinin Composition of Pancreatic Juice Contains ◦ Water ◦ Sodium bicarbonate ◦ Digestive enzymes Pancreatic amylase pancreatic lipase Pancreatic nucleases Pancreatic proteases Functions of pancreatic secretion Fluid (pH from 7.6 to 9.0) ◦ acts as a vehicle to carry inactive proteolytic enzymes to the duodenal lumen ◦ Neutralizes acidic gastric secretion Enzymes ◦
    [Show full text]
  • Normal Pancreatic Function 1. What Are the Functions of the Pancreas?
    Normal Pancreatic Function Stephen J. Pandol Cedars-Sinai Medical Center and Department of Veterans Affairs Los Angeles, California USA [email protected] Version 1.0, June 13, 2015 [DOI: 10.3998/panc.2015.17] 1. What are the functions of the This chapter presents processes underlying the functions of the exocrine pancreas with pancreas? references to how specific abnormalities of the The pancreas has both exocrine and endocrine pancreas can lead to disease states. function. This chapter is devoted to the exocrine functions of the pancreas. The exocrine function 2. Where is the pancreas located? is devoted to secretion of digestive enzymes, ions and water into the intestine of the gastrointestinal The illustration in Figure 1 demonstrates the (GI) tract. The digestive enzymes are necessary anatomical relationships between the pancreas for converting a meal into molecules that can be and organs surrounding it in the abdomen. The absorbed across the surface lining of the GI tract regions of the pancreas are the head, body, tail into the body. Of note, there are digestive and uncinate process (Figure 2). The distal end enzymes secreted by our salivary glands, of the common bile duct passes through the head stomach and surface epithelium of the GI tract of the pancreas and joins the pancreatic duct as it that also contribute to digestion of a meal. enters the intestine (Figure 2). Because the bile However, the exocrine pancreas is necessary for duct passes through the pancreas before entering most of the digestion of a meal and without it the intestine, diseases of the pancreas such as a there is a substantial loss of digestion that results cancer at the head of the pancreas or swelling in malnutrition.
    [Show full text]
  • Physiology of the Pancreas
    Te xt . Only in Females’ slide . Only in Males’ slides . Important Lecture . Numbers No.4 . Doctor notes . Notes and explanation “Be The Best Version Of You” 1 We recommended you to study Histology & Anatomy of pancreas first. Physiology of the pancreas Objectives: 1-Functional Anatomy. 2-Major components of pancreatic juice and their physiologic roles. 3-Cellular mechanisms of bicarbonate secretion. 4-Cellular mechanisms of enzyme secretion. 5-Activation of pancreatic enzymes. 6-Hormonal & neural regulation of pancreatic secretion. 7-Potentiation of the secretory response. 8- Pancreatic acini. 2 Functional Anatomy & Histology of the Pancreas Today we are concern about the digestive role of pancreas not the endocrine role, the endocrine part represent 95% of its Extra function, the left 5% represent the digestive part. Functional Anatomy: The pancreas, which lies parallel to and beneath the stomach is a large compound gland with most of its internal structure similar to that of the salivary glands (Look like them so they have both acinar cells and tubal cells) Islet of langerhans in the pancreas: the pancreas, in addition to its digestive functions, secretes two important hormones: Insulin (beta cells, 60%). Islet of Langerhans have different type of cells (alpha, beta and delta) and If we go and get a cross section view of the every single one of them can release a certain hormone. pancreatic tissue. We can see many acinar Glucagon (alpha cells, ~25%). cells and in the middle we have a ductal That are crucial for normal regulation of glucose, lipid, and protein metabolism. Also somatostatin is lumen. secreted by delta cells (form ~10% of islets’s cells).
    [Show full text]
  • Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: an Etiopathogenetic Hypothesis
    JOP. J Pancreas (Online) 2005; 6(2):122-127. EDITORIAL Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: An Etiopathogenetic Hypothesis Giorgio Talamini Gastroenterology and Endoscopy Service, University of Verona. Verona, Italy Summary duodenum. Patients undergoing a Whipple procedure or side-to-side pancreaticojejuno- Chronic pancreatitis patients have an stomy are probably less critically affected increased risk of developing pancreatic because secretions transit, at least in part, via cancer. The cause of this increase has yet to the papilla. be fully explained but smoking and If the duodenal acidity hypothesis proves inflammation may play an important role. To correct, then, in addition to stopping smoking, these, we must now add a new potential risk reduction of duodenal acid load in patients factor, namely duodenal acidity. Patients with with pancreatic insufficiency may help chronic pancreatitis very often present decrease the risk of pancreatic cancer. pancreatic exocrine insufficiency combined with a persistently low duodenal pH in the postprandial period. The duodenal mucosa in Chronic pancreatitis (CP) patients have an chronic pancreas patients with pancreatic increased risk of developing pancreatic cancer insufficiency has a normal concentration of s- [1, 2]. The cause of this increase has yet to be cells and, therefore, the production of secretin fully explained and various hypotheses are is preserved. Pancreatic ductal cells are being explored [3, 4, 5, 6, 7]. Nevertheless, largely responsible for the amount of smoking unquestionably plays an important bicarbonate and water secretion in response to role [4, 8, 9] because the great majority of CP secretin stimulation.
    [Show full text]
  • Gastrointestinal Physiology 191
    98761_Ch06 5/7/10 6:27 PM Page 190 190 Board Review Series: Physiology Gastrointestinal chapter 6 Physiology I. STRUCTURE AND INNERVATION OF THE GASTROINTESTINAL TRACT A. Structure of the gastrointestinal (GI) tract (Figure 6-1) 1. Epithelial cells ■ are specialized in different parts of the GI tract for secretion or absorption. 2. Muscularis mucosa ■ Contraction causes a change in the surface area for secretion or absorption. 3. Circular muscle ■ Contraction causes a decrease in diameter of the lumen of the GI tract. 4. Longitudinal muscle ■ Contraction causes shortening of a segment of the GI tract. 5. Submucosal plexus (Meissner’s plexus) and myenteric plexus ■ comprise the enteric nervous system of the GI tract. ■ integrate and coordinate the motility, secretory, and endocrine functions of the GI tract. B. Innervation of the GI tract ■ The autonomic nervous system (ANS) of the GI tract comprises both extrinsic and intrin- sic nervous systems. 1. Extrinsic innervation (parasympathetic and sympathetic nervous systems) ■ Efferent fibers carry information from the brain stem and spinal cord to the GI tract. ■ Afferent fibers carry sensory information from chemoreceptors and mechanoreceptors in the GI tract to the brain stem and spinal cord. a. Parasympathetic nervous system ■ is usually excitatory on the functions of the GI tract. ■ is carried via the vagus and pelvic nerves. ■ Preganglionic parasympathetic fibers synapse in the myenteric and submucosal plexuses. ■ Cell bodies in the ganglia of the plexuses then send information to the smooth muscle, secretory cells, and endocrine cells of the GI tract. 190 98761_Ch06 5/7/10 6:27 PM Page 191 Chapter 6 Gastrointestinal Physiology 191 Epithelial cells, endocrine cells, and receptor cells Lamina propria Muscularis mucosae Submucosal plexus Circular muscle Myenteric plexus Longitudinal muscle Serosa FIGURE 6-1 Structure of the gastrointestinal tract.
    [Show full text]
  • Pancreas Anatomy, Physiology and Genetics
    GI Board Review 2014 Pancreas: A&P, Genetics PANCREAS ANATOMY, PHYSIOLOGY AND GENETICS David C Whitcomb MD PhD Professor of Medicine, Cell Biology & Physiology and Human Genetics Chief, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh Outline Overview Pancreatic Anatomy - Gross anatomy - Microanatomy Pancreatic Physiology - Acinar cell - Duct cell - Neurohormonal control - Meals and system integration Pancreatic Genetics - Mendelian disorders - Complex disorders - Genetic test in interpretation Questions References GI Board Review 2014 Pancreas: A&P, Genetics 1. Overview The pancreas is a vital organ that plays a central role in digestion and metabolism of nutrients. Major functions of the pancreas include: secretion of digestive enzymes into the duodenum for the breakdown of complex proteins, carbohydrates, lipids and nucleic acids, secretion of bicarbonate into the duodenum in order to neutralize the acidic chyme exiting the stomach, and secretion of islet cell hormones into the circulation to control systemic metabolism of nutrients after absorption. 2. Gross Anatomy A. Relationship of the Pancreas to other systems In the adult the pancreas lies behind the peritoneum of the posterior abdominal wall and is in an oblique orientation. The head of the pancreas is flanked by the duodenum on the right. The body is ventral to the 2nd-4th lumbar spine (making it susceptible to blunt trauma) and dorsal to the stomach. The blood supply to the pancreas can be quite variable, but comes, in general from branches of the gastroduodenal, superior mesenteric and splenic arteries. These form anterior and posterior arcades which supply the pancreatic head. The body and tail are supplied predominately by branches of the splenic artery.
    [Show full text]
  • Delta Cell Reprogramming During Mouse Pregnancy
    Aus dem Paul-Langerhans Institut Dresden Direktor: Prof. Dr. Michele Solimena Delta cell reprogramming during mouse pregnancy Dissertationsschrift zur Erlangung des akademischen Grades Doktor der Biomedizin Doctor rerum medicinalium (Dr. rer. medic.) vorgelegt der Medizinischen Fakultät Carl Gustav Carus der Technischen Universität Dresden von Julia Katharina Panzer geb. Stertmann aus Münster Dresden 2018 1. Gutachter: 2. Gutachter: Tag der mündlichen Prüfung: gez.:____________________________ Vorsitzender der Promotionskomission Success is the ability to go from one failure to another with no loss of enthusiasm. – Winston Churchill Table of contents 1 Introduction .............................................................................................. 1 1.1 The Pancreas ...................................................................................................... 1 1.1.1 Anatomy ............................................................................................................................... 1 1.1.2 Development ....................................................................................................................... 2 1.2 Islets of Langerhans ............................................................................................ 6 1.2.1 Islet architecture .................................................................................................................. 6 1.2.2 Islet cell function .................................................................................................................
    [Show full text]
  • EN GAST IND.Pdf
    EN_GAST_IND.QXD 08/31/2005 11:31 AM Page 825 Index The bold letter t or f following a page reference indicates that the information appears on that page only in a table or figure, respectively. abdomen: examination of, 41–8; regions, 43f acetylcholine, 145, 190t abdominal aortic reconstruction, 275t acetyl-CoA, 53 abdominal mass: about, 37–40; with colon N-acetylcysteine, 582 cancer, 365t; and constipation, 386; with achalasia, 118f; about, 121–2; Crohn’s disease, 314, 342t; with cystic cricopharyngeal, 117t, 118; esophageal, fibrosis, 456; GI tract, 307, 373, 375, 379; 6–8, 14, 96, 118f, 120f; and gas, 14; and with hepatocellular carcinoma, 647; in Hirschsprung’s disease, 388; vigorous, pancreas, 434, 445; with ulcerative colitis, 121–2 342t achlorhydria, 57t, 217, 245t, 451 abetalipoproteinemia, 194, 201t acid perfusion test, 98, 106t abscesses: amebic, 392; anorectal, 397, 399, acid suppressants, 145 406–7; appendiceal, 320t; colonic, 391; acidosis: children, 687t, 689, 698, 715, 727t, crypt, 285, 331, 332f; diverticuler, 253; 729; cirrhosis, 571, 591; ischemia, 253, and diverticulitis, 373; eosinophilic, 114; 266; liver transplantation, 641; pancreatitis, horseshoe, 406; liver, 474; lung, 113; 433t; ulcerative colitis, 335 pancreatic, 434; pararectal, 316t; perianal, acids (chemicals), 115 344t acinar cells, 56, 418–19, 422 absorption: of carbohydrates, 194–9, 227–8; acquired immunodeficiency syndrome. see in colon, 360, 362–4; of electrolytes, AIDS 185–92, 333; of fat, 192–4; of glucose, acrodermatitis enteropathica, 205t 194f; principles of, 178; of protein, actinomycosis, 149 199–202; of vitamins and minerals, acute abdomen, 24–7 178–83; of water, 183–5, 360 acute mesenteric ischemia, 252–4 acanthosis, glycogen, esophageal, 126t acyclovir, 294t, 301, 653 acanthosis nigricans, 126 acyclovir treatment, 114 ACE inhibitors.
    [Show full text]
  • The Physiology and Pathophysiology of Pancreatic Ductal Secretion the Background for Clinicians
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by SZTE Publicatio Repozitórium - SZTE - Repository of Publications REVIEW The Physiology and Pathophysiology of Pancreatic Ductal Secretion The Background for Clinicians Petra Pallagi, PhD,* Péter Hegyi, MD, PhD, DSc,*† and Zoltán Rakonczay, Jr, MD, PhD, DSc* and basolateral transporters involved in the secretory process. Abstract: The human exocrine pancreas consists of 2 main cell types: In all cases, the physiological function of this alkaline fluid is acinar and ductal cells. These exocrine cells interact closely to contribute to neutralize the acidic content secreted by acinar cells, to pro- to the secretion of pancreatic juice. The most important ion in terms of − vide an optimal pH for digestive enzymes, to flush down diges- the pancreatic ductal secretion is HCO3. In fact, duct cells produce an alka- − tive enzyme into the duodenum, and also to neutralize the line fluid that may contain up to 140 mM NaHCO3, which is essential for 7 − gastric acid entering the duodenum. Importantly, HCO3 has normal digestion. This article provides an overview of the basics of pancre- a crucial biochemical role in the physiological pH buffering atic ductal physiology and pathophysiology. In the first part of the article, system and is a chaotropic agent that prevents the denaturing we discuss the ductal electrolyte and fluid transporters and their regulation. of proteins such as digestive enzymes and mucins so it facili- The central role of cystic fibrosis transmembrane conductance regulator 4,8 − tates their solubilization in biological fluid. (CFTR) is highlighted, which is much more than just a Cl channel.
    [Show full text]
  • The Endodermal Origin of Digestive and Respiratory Tract APUD Cells Histopathologic Evidence and a Review of the Literature Gurdip S
    The Endodermal Origin of Digestive and Respiratory Tract APUD Cells Histopathologic Evidence and a Review of the Literature Gurdip S. Sidhu, MD Twenty-seven small cell carcinomas of the lung and three tumors of the large intestine with combined adenocarcinomatous and small cell and/or anaplastic carcinoid-type histologic features were studied by light and electron microscopy. It was shown that the small cells have morphologic characteristics of APUD cells. Also presented are the histologic features of a carcinoma of the lung with large cell undifferentiated carci- noma, adenocarcinoma, squamous cell carcinoma, and giant cell carcinoma areas in the primary site and in several metastatic foci. Two of the renal metastases showed small cell carcinoma. The combined tumors and the numerous other similar neoplasms described in the literature and reviewed here suggest an endodermal origin for diges- tive and respiratory tract APUD cells based on the hypothesis that cancer is a clonal proliferation, and mucous and squamous cell differentiation is an endodermal rather than neural crest characteristic. The ultrastructural features of tumors of cells of known neural crest origin, including a medullary carcinoma of the thyroid, three carotid body tumors, a pheochromocytoma, and two cutaneous melanomas were compared with those of other APUD cell tumors including small cell carcinomas of the lung, two bronchial carcinoids, a carcinoid of the appendix, and a carcinoid of the kidney. Cells of the latter group sometimes possessed cytoplasmic tonofibrils, round compact masses of cytoplasmic microfilaments, and ductal lumina. These features were lacking in the former group and may signify a different embryologic origin. The histologic, histo- pathologic, and embryologic evidence regarding the origin of digestive and respiratory tract APUD cells is reviewed, showing that the former are, and the latter probably are, of endodermal and not neuroectodermal origin.
    [Show full text]