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Page 1: CONTENTS OF VOLUME 101 - COnnecting REpositories200 Distribution of the VLA Family of Integrins in Normal and Pathological Human Liver Tissue R . VOLPES , J.J VA N DE OORD AND V.J
Page 2: CONTENTS OF VOLUME 101 - COnnecting REpositories200 Distribution of the VLA Family of Integrins in Normal and Pathological Human Liver Tissue R . VOLPES , J.J VA N DE OORD AND V.J

C O N T E N T S O F V O L U M E 101

NO. 1, JULY 1991

1 This Month in G A S T R O E N T E R O L O G Y

A L I M E N T A R Y T R A C T

3 Sensitivity of the Gastric Mucosa to Acid and Duodenal Contents in Patients With Nonulcer Dyspepsia A . A . GEORGE, M . TSUCHIYOSE, AND C P . DOOLEY

7 Phospholipid- and Neutral Lipid-Containing Organelles of Rat Gastroduodenal Mucous Cells Y . -C . J . K A O AND L . M . LICHTENBERGER

22 Acute Intestinal Injury Induced by Acetic Acid and Casein: Prevention by Intraluminal Misoprostol M . J . S . MILLER, X . - J . Z H A N G , X . Gu, A N D D . A . CLARK

31 T-Lymphocyte Modulation of Intestinal Muscle Function in the Tricliine/ia-Infected Rat D . L . VERMILLION, P . B . ERNST, AND S . M . COLLINS

39 Use of Azathioprine or 6-Mercaptopurine in the Treatment of Crohn's Disease J.J. O 'BRIEN, T . M . BAYLESS, AND J . A . BAYLESS

47 Localization of Endothelinlike Immunoreactivity and Endothelin Binding Sites in Human Colon H . INAGAKI, A . E . BISHOP, C . ESCRIG, J. W H A R T O N ,

T . G . ALLEN-MERSH, AND J . M . POLAK

55 The Mechanism of Action of Peppermint Oil on Gastrointestinal Smooth Muscle J . M . HILLS AND P . I . AARONSON

66 Gastric Acid Secretion and Parietal Cell Mass: Effect of Sex Hormones K . A . ADENIYI

70 Proliferation of Endocrine Cells in the Rat Stomach Caused by Drug-Induced Achlorhydria R. EISSELE, B . RoßKOPF, H . KOOP, G. ADLER, AND R. ARNOLD

77 A Novel Enzyme Immunoassay for Serodiagnosis of Helicobacter pylori Infection T . SUGIYAMA, K . I M A I , H . YOSHIDA, Y . T A K A Y A M A , T . Y A B A N A ,

K . YOKOTA, K . O G U M A , AND A . Y A C H I

84 The Effect of Elemental Diet on Intestinal Permeability and Inflammation in Crohn's Disease K. TEAHON, P. SMETHURST, M . PEARSON, A . J . LEVI ,

AND I . BjARNASON

90 Lamina Propria Lymphocytes Are Derived From Circulating Cells That Lack the Leu-8 Lymph Node Homing Receptor M . BERG, Y . M U R A K A W A , D. CAMERINI, AND S.P. JAMES

100 Effect of Enteric Pacing on Intestinal Motility and Hormone Secretion in Dogs With Short Bowel S . B . REISER, V . SCHUSDZIARRA, E . BOLLSCHWEILER,

A . H . HÖLSCHER, AND J.R. SlEWERT

107 Scintigraphic Measurement of Regional Gut Transit in Idiopathic Constipation T . STIVLAND, M . CAMILLERI, M . VASSALLO, M . PROANO, D. R A T H ,

M . BROWN, G. THOMFORDE, J. PEMBERTON, AND S. PHILLIPS

116 Lipase and Pepsin Activity in the Gastric Mucosa of Infants, Children, and Adults J. DiPALMA, C . KIRK, M . H A M O S H , A . R . COLON, S .B. BENJAMIN,

AND P. H A M O S H

122 Epidemiology of Inflammatory Bowel Disease Among U.S. Military Veterans A . SONNENBERG AND L H . WASSERMAN

131 Basophil-Bound and Serum Immunoglobulin E Directed Against Helicobacter pylori in Patients With Chronic Gastritis A . ACETI , D . CELESTINO, M . CAFERRO, V . CASALE, F . CITARDA,

E . M . CONTI , A . GRASSI, A . GRILLI, A . PENNICA, F . SCIARRETTA,

O . LERI, F . AMEGLIO, AND A . SEBASTIANI

138 Pharmacokinetics of Oral and Intravenous Omeprazole in Patients With the Zollinger-Ellison Syndrome R. VINAYEK, M . A M A N T E A , P . N . M A T O N , H . FRUCHT,

J . D . GARDNER, AND R . T . JENSEN

148 Long-Term Prognosis After Partial Gastrectomy for Benign Conditions A . C . TERSMETTE, G . J . A . OFFERHAUS, F . M . GIARDIELLO, R. BRAND,

K . W . F . TERSMETTE, G . N . J . TYTGAT, AND J.P. VANDENBROUCKE

154 Genetic Characterization of the A P C Locus Involved in Familial Adenomatous Polyposis S. OLSCHWANG, B . WEIFFENBACH, P . LAURENT-PUIG, T . M E L O T ,

A . VASSAL, K . FALLS, R.J. SALMON, R . PARC, L . STRONG,

Y . N A K A M U R A , L . HERRERA, AND G . THOMAS

161 Induction of Heat Shock Proteins and Their Implication in Protection Against Ethanol-Induced Damage in Cultured Guinea Pig Gastric Mucosal Cells K . N A K A M U R A , K . ROKUTAN, N . M A R U I , A . AOIKE, AND K . K A W A I

167 Positive Serum Antibody and Negative Tissue Staining for Helicobacter pylori in Subjects With Atrophic Body Gastritis W . E . KARNES, JR., I . M . SAMLOFF, M . SIURALA, M . KEKKI,

P. SIPPONEN, S . W . R . K I M , AND J . H . W A L S H

175 Reproducibility of Measurements of Trace Gas Concentrations in Expired Air A . STROCCHI, C . ELLIS, AND M . D . LEVITT

L I V E R , P A N C R E A S , A N D B I L I A R Y T R A C T

180 Increased Paracellular Permeability in Intrahepatic Cholestasis Induced by Carmustine (BCNU) in Rats H . KRELL, H . FROMM, AND R . E . LARSON

189 Cost-Effectiveness of Extracorporeal Shock-Wave Lithotripsy Versus Cholecystectomy for Symptomatic Gallstones E . B . BASS, E .P . STEINBERG, H . A . PITT, G . P . SABA, K . D . LILLEMOE,

D . R . KAFONEK, T . R . GADACZ, T . A . GORDON, AND G . F . ANDERSON

200 Distribution of the V L A Family of Integrins in Normal and Pathological Human Liver Tissue R. VOLPES, J.J. VAN DEN OORD, AND V . J . DESMET

207 The Bentiromide Test Using Plasma p-Aminobenzoic Acid for Diagnosing Pancreatic Insufficiency in Young Children D . LAUFER, G . CLEGHORN, G . FORSTNER, L . ELLIS, G . KOREN,

AND P . DURIE

214 Factors Affecting the Measurement of Cholesterol Nucleation in Human Gallbladder and Duodenal Bile J . W . MARKS, P. BROOMFIELD, G . G . BONORRIS,

AND L . J . SCHOENFIELD

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iv C O N T E N T S G A S T R O E N T E R O L O G Y V o l . 101, No. 6

220 Secretagogue Response of Azaserine-Induced Rat Pancreatic Acinar Tumors in Vivo K . - H . HERZIG, W . CREUTZFELDT, A N D U . R . FÖLSCH

228 Impaired Hepatic Handling and Processing of Lysophosphatidylcholine in Rats With Liver Cirrhosis M . ANGELICO, D . ALVARO, A . CANTAFORA, R. MASELLA,

E . GAUDIO, C . G A N D I N , S . G . CORRADINI, F . ARIOSTO, O . RIGGIO,

A N D L . CAPOCACCIA

C A S E R E P O R T S

238 Growth in Adulthood After Liver Transplantation for Glycogen Storage Disease Type I B . S . KIRSCHNER, A . L . BAKER, AND F . K . THORP

242 Development of Sustained Achlorhydria in a Patient With the Zollinger-Ellison Syndrome Treated With Omeprazole J .L . GRIFFITH, O . W . CUMMINGS, AND B . I . HIRSCHOWITZ

247 Cytomegalovirus Infection of the Appendix in a Patient With the Acquired Immunodeficiency Syndrome S. VALERDIZ-CASASOLA AND F J . P A R D O - M I N D A N

250 Ursodeoxycholic Acid for the Treatment of Home Parenteral Nutrition-Associated Cholestasis K . D . LlNDOR AND }. BURNES

C L I N I C A L C H A L L E N G E S

254 Exacerbation of Ulcerative Colitis D . J . HERMENS A N D P . B . MINER, JR.

S E L E C T E D S U M M A R I E S

263 Treatment of Bleeding Arteriovenous Malformations With Oral Contraceptives: Safe Sex?

264 How Enterocytes Stick and What They Stick To

266 Superficial Esophageal Carcinoma: Will Early Detection Help?

267 Evidence for a Direct Hepatoprotective Action of Ursodeoxycholic Acid in Primary Human Hepatocytes

268 Toward a Treatment for Anorexia and Cachexia in Patients With Cancer

271 B O O K R E V I E W S

C O R R E S P O N D E N C E

274 24-Hour Intragastric Acidity and Plasma Gastrin After Omeprazole Treatment and After Proximal Gastric Vagotomy in Duodenal Ulcer Patients

274 Persisting Benzodiazepine Metabolites Responsible for the Reaction to the Benzodiazepine Antagonist Flumazenil in Patients With Hepatic Encephalopathy

275 Treatment of Cholesterol Gallstone Patients With Ursodeoxycholic Acid

276 Abstract Creep' in G A S T R O E N T E R O L O G Y

276 Pancreatic Exocrine Secretion in Acute Experimental Pancreatitis

278 Efficacy of Dextran-70 As a Substitute for Albumin

280 Calcium Carbonate Solubility in Human Common Duct Bile: Calcium Carbonate Precipitation in Gallstones

281 Acute Necrotizing Esophagitis: Another Case

283 N O T I C E S

NO. 2, AUGUST 1991

285 This Month in G A S T R O E N T E R O L O G Y

A L I M E N T A R Y T R A C T

287 The Parietal Cell Autoantibodies Recognized in Neonatal Thymectomy-Induced Murine Gastritis Are the a and ß Subunits of the Gastric Proton Pump C M . JONES, J . M . CALLAGHAN, P . A . GLEESON, Y . M O R I ,

T . M A S U D A , A N D B . - H . T O H

295 Microvascular Permeability Increases Early in the Course of Acid-Induced Esophageal Injury F . G . ZIJLSTRA, T . T . HYNNA-LIEPERT, P . K . D I N D A , L T . BECK,

A N D W . G . PATERSON

303 Establishment and Characterization of a Human Carcinoid in Nude Mice and Effect of Various Agents on Tumor Growth B . M . EVERS, C M . TOWNSEND, JR., J.R. UPP, E. A L L E N ,

S .C . HURLBUT, S . W . K I M , S. RAJARAMAN, P. SINGH, J . C REUBI,

AND J .C. THOMPSON

312 Posttranslational Cleavage of Rat Intestinal Lactase Occurs at the Luminal Side of the Brush Border Membrane K . - Y . Y E H , M . Y E H , P . - C . P A N , A N D P . R . H O L T

319 Effects of Vibrio cholerae Recombinant Strains on Rabbit Ileum In Vivo C D . L I N D , R . H . DAVIS , R . L . GUERRANT, J.B. KAPER,

AND J.R. M A T H I A S

325 Effect of Neuropeptide Y on Jejunal Water and Ion Transport in Humans U . HOLZER-PETSCHE, W . PETRITSCH, T . HINTERLEITNER, A . EHERER.

G . SPERK, A N D G.J. KREJS

331 Mechanism of Short-Chain Fatty Acid Uptake by Apical Membrane Vesicles of Rat Distal Colon N . MASCOLO, V . M . RAJENDRAN, AND H . J . BINDER

339 Developmental Characteristics of the Kitten Antrum A . C . HlLLEMEIER, K . N . BlTAR, AND P . BlANCANI

344 Abnormal Esophageal Motility B . T . MASSEY, W . J . DODDS, W . J . H O G A N , J . C BRASSEUR,

AND J.F. H E L M

355 Regional Esophageal Distribution and Clearance of Refluxed Gastric Acid R. SHAKER, W . J . DODDS, J.F. H E L M , M . K . KERN, A N D W . J . HOGAN

360 Intestinal Absorption of Fructose in the Rat T . FUJISAWA, J. RlBY, AND N . KRETCHMER

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December 1991 C O N T E N T S v

368 Long-Term Survival Analysis in Hereditary Hemochromatosis P . C . A D A M S , M . SPEECHLEY, AND A . E . KERTESZ

373 Variation of Muscle Tone in the Human Colon C.J. S T E A D M A N , S .F . PHILLIPS, M . CAMILLERI, A . C . H A D D A D ,

AND R . B . H A N S O N

382 Premicellar Taurocholate Enhances Ferrous Iron Uptake From A l l Regions of Rat Small Intestine A . J . SANYAL, M . L . SHIFFMAN, J . I . HIRSCH, AND E . W . MOORE

390 T-Lymphocyte Dysfunctions Occurring Together With Apical Gut Epithelial Cell Autoantibodies J . M . M A R T I N - V I L L A , J.R. REGUEIRO, D . DE JUAN, P. PEREZ-ACIEGO,

M . PEREZ B L A S , J. MANZANARES, G . VARELA,

AND A . A R N A I Z - V I L L E N A

398 Ion Transport Abnormalities in Rectal Suction Biopsies From Children With Cystic Fibrosis H J . VEEZE, M . SINAASAPPEL, J. BIJMAN, J. BOUQUET,

AND H . R . DE JONGE

404 Aspirin Induces Morphological Transformation to the Secretory State in Isolated Rabbit Parietal Cells U . K . M U R T H Y A N D R . A . LEVINE

410 Circadian Rhythm of Cellular Proliferation in the Human Rectal Mucosa K . N . B U C H I , J . G . MOORE, W . J . M . HRUSHESKY, R . B . SOTHERN,

AND N . H . R U B I N

416 Sensory Neurons Signal for an Increase in Rat Gastric Mucosal Blood Flow in the Face of Pending Acid Injury P. HOLZER, E . H . LIVINGSTON, A N D P . H . G U T H

424 Presence of Atrial Natriuretic Factor Prohormone in Enterochromaffin Cells of the Human Large Intestine A . L . GERBES, W . N A T H R A T H , M . C A N T I N , AND H . DENECKE

430 Increased N a + - H + Exchange in Jejunal Brush Border Membrane Vesicles of Spontaneously Hypertensive Rats S. AcRA A N D F . K . GHISHAN

437 Helicobacter pylori Infection Induces Antibodies Cross-Reacting With Human Gastric Mucosa R. NEGRINI, L . LISATO, I . ZANELLA, L . C A V A Z Z I N I , S. GULLINI ,

V . VlLLANACCI, C . POIESI, A . ALBERT1NI, AND S. GHIELMI

L I V E R , P A N C R E A S , A N D B I L I A R Y T R A C T

446 Activation of Mast Cells by Bile Acids R . G . QUIST, H . - T . T O N - N U , J. LILLIENAU, A . F . H O F M A N N ,

AND K . E . BARRETT

457 Cell Type-Dependent Effect of Phospholipid and Cholesterol on Bile Salt Cytotoxicity A . L . M . VELARDI , A . K . GROEN, R . P . J . O . ELFERINK,

R. VAN DER MEER, G . PALASCIANO, AND G . N . J . TYTGAT

465 Pancreatic Lesions in the von Hippel-Lindau Syndrome H . P . H . N E U M A N N , E . DINKEL, H . BRAMBS, B . W I M M E R ,

H . FRIEDBURG, B . V O L K , G . SIGMUND, P. RIEGLER, K . H A A G ,

P. SCHOLLMEYER, AND O . D . WIESTLER

472 The Stomach in Liver Cirrhosis S. VIGNERI, R . TERMINI , A. PIRAINO , A. SCIALABBA, G . PISCIOTTA,

AND N . F O N T A N A

479 Bile Evacuation Induced by Hypothalamic Stimulation in Dogs N . FURUKAWA AND H . O K A D A

490 Comparative Evaluation of Chenodeoxycholic and Ursodeoxycholic Acids in Obese Patients G . M A Z Z E L L A , F . B A Z Z O L I , D . FESTI, M . RONCHI, R . A L D I N I ,

A. RODA, B . GRIGOLO, P. S I M O N I , N . VILLANOVA, A N D E. RODA

497 Comparison of 1 or 3 MU of Interferon Alfa-2b and Placebo in Patients With Chronic Non-A, Non-B Hepatitis X . CAUSSE, H . GODINOT, M . CHEVALLIER, P. CHOSSEGROS,

F . Z O U L I M , D . O U Z A N , J.-P. HEYRAUD, T. FONTANGES,

J. ALBRECHT, C . MESCHIEVITZ, AND C . TREPO

503 Role of Cholecystokinin in the Regulation of Gastric Emptying and Pancreatic Enzyme Secretion in Humans M . FRIED, U . ERLACHER, W . SCHWIZER, C . LÖCHNER, J. KOERFER,

C . BEGLINGER, J .B. JANSEN, C . B . LAMERS, F . HARDER,

A . BISCHOF-DELALOYE, G . A . STALDER, AND L . R O V A T I

512 Intraductal Mucin-Hypersecreting Neoplasms of the Pancreas F . RICKAERT, M . CREMER, J. DEVIERE, L . TAVARES,

J.P. LAMBILLIOTTE, S. SCHRÖDER, D . WURBS, AND G . KLÖPPEL

C A S E R E P O R T S

520 Intestinal and Hepatic Apolipoprotein B Gene Expression in Abetalipoproteinemia D . D . BLACK, R . V . H A Y , P . L . ROHWER-NUTTER, H . ELLINAS,

J .K . STEPHENS, H . SHERMAN, B . - B . TENG, P . F . W H I T I N G T O N ,

AND N . O . DAVIDSON

529 Rhabdomyolysis and Cutaneous Necrosis Following Intravenous Vasopressin Infusion D . MORENO-SÄNCHEZ, B . CASIS, A . M A R T I N , P. ORTIZ ,

G . CASTELLANO, M . T . M U N O Z , F . VANACLOCHA,

AND J . A . SOLIS-HERRUZO

533 Idiopathic Myointimal Hyperplasia of Mesenteric Veins R . M . GENTA AND R . C HAGGITT

B R I E F R E P O R T S

540 Metabolism of Trinitrobenzene Sulfonic Acid by the Rat Colon Produces Reactive Oxygen Species M . B . GRISHAM, C . VOLKMER, P. Tso, AND T. Y A M A D A

S P E C I A L R E P O R T S A N D R E V I E W S

548 Reports From the NIH DDDN F . A . H A M I L T O N AND J . H . HOOFNAGLE

S E L E C T E D S U M M A R I E S

550 Antibiotic Prophylaxis for Prevention of Spontaneous Bacterial Peritonitis?

552 Nitroglycerin in the Treatment of Portal Hypertension

553 Endoscopic Management of Gastric Outlet Obstruction

554 At Long Last—The Histamine H 2-Receptor Gene Is Cloned

555 NSAID-Induced Gastroduodenal Injury: What's the Score?

558 B O O K R E V I E W S

T R A I N I N G A N D E D U C A T I O N I N G A S T R O E N T E R O L O G Y

560 List of Available Training Programs

C O R R E S P O N D E N C E

589 Ethanol Stimulates Pepsinogen Release From Isolated Guinea Pig Chief Cells

590 Hemodynamic Events in a Prospective Randomized T r i a l of Propranolol Versus Placebo in the Prevention of a First Variceal Hemorrhage

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v i CONTENTS GASTROENTEROLOGY Vol . 101, No. 6

592 The Possible Role of Phospholipase in Gallstone Pathogenesis

593 Host Response to Mycobacterial Infection in the Alcoholic Rat

594 Tumor Necrosis Factor a in the Pathophysiology of Necrotizing Enterocolitis

594 Fasting and Postprandial Residual Gallbladder Volumes

595 C O R R E C T I O N

596 N O T I C E S

NO. 3, SEPTEMBER 1991

597 This Month in G A S T R O E N T E R O L O G Y

A L I M E N T A R Y T R A C T

599 The Cephalic and Gastric Phases of Gastric Secretion During H 2-Antagonist Treatment H . S . M E R K I , C . H . WILDER-SMITH, R . P . W A L T , AND F . HALTER

607 Effect of Intrathoracic Pressure on Plasma Arginine Vasopressin Levels J . A . SOLIS-HERRUZO, D . MORENO, A . GONZALEZ, L . LARRODERA,

G . CASTELLANO, J. GUTIERREZ, AND A . GOZALO

618 Expression of Sucrase-Isomaltase and Dipeptidylpeptidase IV in Human Small Intestine and Colon J .P. GORVEL, A . FERRERO, L . CHAMBRAUD, A . RIGAL, J. BONICEL,

A N D S. M A R O U X

626 Intestinal Obstruction During Shigellosis: Incidence, Cl inical Features, Risk Factors, and Outcome M . L . BENNISH, A . K . A Z A D , AND D . YOUSEFZADEH

635 Sulindac Causes Regression of Rectal Polyps in Familial Adenomatous Polyposis D . LABAYLE, D . FISCHER, P . VIELH, F . DROUHIN, A . PARIENTE,

C . BORIES, O . D U H A M E L , M . TROUSSET, AND P. A T T A L I

640 Radioautographic Localization of Epidermal Growth Factor Receptors in Human Fetal Gut D. M E N A R D A N D P. POTHIER

650 Observations on a Proposed Measure of Genotoxicity in Rat Gastric Mucosa S. H O L T , Z . Z H A O - H U A , AND R . E . POWERS

657 Hypertrophic Smooth Muscle in the Partially Obstructed Opossum Esophagus J .L . CONKLIN, C . Du, K. SCHULZE-DELRIEU, A N D S. SHIRAZI

664 Trichinella spiralis Infection Alters Small Bowel Motor Activity in the Fed State V . E . COWLES AND S . K . SARNA

670 Immunohistochemical Characterization, Distribution, and infrastructure of Lymphocytes Bearing T-Cell Receptor 7/8 in Inflammatory Bowel Disease K . FUKUSHIMA, T . M A S U D A , H . O H T A N I , I . SASAKI, Y . FUNAYAMA,

S. M A T S U N O , A N D H . NAGURA

679 Quality of Life After Proctocolectomy L . W . KÖHLER, J . H . PEMBERTON, A . R . ZINSMEISTER,

A N D K . A . KELLY

685 Acute Abdomen as the First Presentation of Pseudomembranous Colitis G . TRIADAFILOPOULOS AND A . E . HALLSTONE

692 Isolation, Characterization, and Attachment of Rabbit Distal Colon Epithelial Cells R . V . BENYA, L . N . SCHMIDT, J. S A H I , T . J . LAYDEN, AND M . C . RAO

703 Mechanism for the Gastrokinetic Action of Domperidone T . T A K A H A S H I , S. KUROSAWA, J . W . WILEY, AND C . O W Y A N G

711 Cancer Incidence Following Subtotal Gastrectomy G . N . STEMMERMANN , A . M . Y . N O M U R A , AND P . - H . CHYOU

716 Rat Enterocyte Injury by Oxygen-Dependent Processes S.S. B A K E R A N D C . L . CAMPBELL

721 Fecal Carriage of Streptococcus bovis and Colorectal Adenomas R. DUBROVV, S. EDBERG, E. WIKFORS, D . C A L L A N , F . TRONCALE,

R . VENDER, M . BRAND, AND R. YAPP

726 Antitumor Effect of Synthetic Derivatives of Lipid A in an Experimental Model of Colon Cancer in the Rat J.-F. JEANNIN, N . ONIER, P. LAGADEC, N . VON JENEY, P. STÜTZ,

AND E. LIEHL

734 Neural and Hormonal Mechanisms Mediate the Enterogastric Reflex: A Study in Intestinal Transplants in Rats S . L . ORLOFF, N . W . BUNNETT, H . W O N G , J . H . W A L S H ,

AND H . T . DEBAS

743 Classic and Vigorous Achalasia: A Comparison of Manometric, Radiographic, and Clinical Findings S.P. GOLDENBERG, M . BURRELL, G . G . FETTE, C . VOS,

AND M . TRAUBE

749 Apolipoprotein Synthesis in Normal and Abetalipoproteinemic Intestinal Mucosa R . M . GLICKMAN, J . N . GLICKMAN , A. M A G U N , AND M . BRIN

756 Nonsalicylate Nonsteroidal Antiinflammatory Drugs Augment Prestimulated Acid Secretion in Rabbit Parietal Cells R .A . LEVINE, J. N A N D I , AND R . L . K I N G

L I V E R , P A N C R E A S , A N D B I L I A R Y T R A C T

766 Detection and Partial Sequencing of Hepatitis C Virus RNA in the Liver K . HOSODA, O . YOKOSUKA, M . O M A T A , N . K A T O , AND M . O H T O

772 The Effects of Benzodiazepine-Receptor Antagonists and Partial Inverse Agonists on Acute Hepatic Encephalopathy in the Rat D . K . BOSMAN, C . A . C . G . VAN DEN BUIJS, J .G . DE H A A N ,

M . A . W . M A A S , AND R . A . F . M . CHAMULEAU

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December 1991 C O N T E N T S v i i

782 Elevation of Serum Interleukin-6 Concentration Precedes Acute-Phase Response and Reflects Severity in Acute Pancreatitis H . - G . LESER, V . GROSS, C . SCHEIBENBOGEN, A . HEINISCH, R . S A L M ,

M . LAUSEN, K . RÜCKAUER, R . ANDREESEN, E . H . FARTHMANN,

A N D J. SCHÖLMERICH

786 Acalculous Biliary Pain: Cholecystectomy Alleviates Symptoms in Patients With Abnormal Cholescintigraphy L . Y A P , A . G . WYCHERLEY, A . D . MORPHETT, A N D } . TOOULI

794 Noninvasive Measurement of Liver Regeneration With Positron Emission Tomography and [2- n C]Thymidine T . VANDER BORGHT, L . LAMBOTTE, S. PAUWELS, D . LABAR,

C . BECKERS, A N D C . DIVE

800 The Effects of Chronic Endoscopic Variceal Sclerotherapy on Portal Pressure in Cirrhotics J. KORULA AND P. RALLS

806 Chronic Dietary Iron Overload in Rats Results in Impaired Calcium Sequestration by Hepatic Mitochondria and Microsomes R . S . BRITTON, R. O ' N E I L L , B . R . BACON

812 Inhibition of Prostaglandin Synthesis Fails to Prevent Gallbladder Mucin Hypersecretion in the Cholesterol-Fed Prairie Dog D . P . O'LEARY, W . W . L A M O R T E , T . E . SCOTT, M . L . BOOKER,

A N D J. STEVENSON

821 Microanalysis of Bile Acid Composition in Intrahepatic Calculi and Its Etiological Significance J. SHODA, N . T A N A K A , Y . M A T S U Z A K I , A . H O N D A , T . OSUGA,

S. SHIGEMATSU, AND H . M I Y A Z A K I

C A S E R E P O R T S

831 Clonorchis-Associated Cholangiocarcinoma: A Report of Two Cases With Unusual Manifestations F . V . O N A AND J . N . T . DYTOC

B R I E F R E P O R T S

840 Interferon-Induced Chronic Active Hepatitis? M . O , SILVA, K . R . REDDY, L. J . JEFFERS, M . H I L L , AND E .R . SCHIFF

S P E C I A L R E P O R T S A N D R E V I E W S

843 A Reappraisal of the Magnitude and Implications of the Intestinal Unstirred Layer A . STROCCHI AND M . D . LEVITT

C L I N I C A L C H A L L E N G E S

848 Hypoproteinemia, Anemia, and Failure to Thrive in an Infant J.E. BINES A N D E.J. ISRAEL

E D I T O R I A L S

857 Lessons From Experimental Cholelithiasis: Gallbladder and Mucosa, Nonsteroidal Antiinflammatory Drugs, and Gallstones S.P. LEE

S E L E C T E D S U M M A R I E S

861 One More Reason for Weight Loss in Patients With A I D S

862 Hepatitis B and Human Immunodeficiency Virus: Double Trouble

863 Acute and Chronic Giant Cell Hepatitis: A Paramyxovirus Infection?

864 Peliosis Hepatis: Old Disease, New Cause

866 A Biopsychosocial Model for Functional Dyspepsia

869 B O O K R E V I E W S

C O R R E S P O N D E N C E

871 Vegetable Peroxidase Is Denatured by Gastric Acid

871 Estimation of Risk of Transmission of Non-A, Non-B Hepatitis by Needlestick Injury

872 Free Radical Scavengers and Inflammatory Bowel Disease

872 Role of Parenteral Nutrition in Crohn's Colitis

874 Treatment of Intestinal Cryptosporidiosis With Zidovudine and SMS 201-995, a Somatostatin Analog

874 Somatostatin and Acute Variceal Hemorrhage

875 Prevalence of Columnar-Lined (Barrett's) Esophagus

876 Asthmatics' Gastroesophageal Reflux With or Without Bronchodilator Therapy

878 N O T I C E S

NO. 4, OCTOBER 1991

879 This Month in G A S T R O E N T E R O L O G Y

A L I M E N T A R Y T R A C T

881 Comparison of Enteral Nutrition and Drug Treatment in Active Crohn's Disease H . LOCHS, H . J . STEINHARDT, B . K L A U S - W E N T Z , M . ZEITZ,

H . VOGELSANG, H . SOMMER, W . E . FLEIG, P . BAUER,

J. SCHIRRMEISTER, A N D H . M A L C H O W

889 The Effect of Histamine H 2-Receptor Blockade on Bismuth Absorption From Three Ulcer-Healing Compounds C . U . NWOKOLO, E.J. PREWETT, A . M . SAWYERR, M . H U D S O N ,

AND R . E . POUNDER

895 Electrolyte Transport in Piglets Infected With Transmissible Gastroenteritis Virus F . R. H O M A I D A N , A . TORRES, M . DONOWITZ, AND G . W . G . SHARP

902 Comparative Evaluation of Acid- and Bile-Induced Damage to Pedicled Jejunal or Colonic Segments in the Rat G . B . RATTO, P. ROMANO, AND D . ZACCHEO

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v i i i C O N T E N T S GASTROENTEROLOGY Vol . 101, No. 6

910 Mechanism of Inhibitory Action of Prostaglandins on the Growth of Human Gastric Carcinoma Cell Line K A T O III A . N A K A M U R A , T . Y A M A T A N I , T . FUJITA, AND T . CHIBA

919 Comparative Evaluation of Carcinoembryonic Antigen, Secretory Component, and Mucins in Index and Metachronous Adenomas of the Colorectum G . GRIFFIOEN, F . T . BOSMAN, H . W . VERSPAGET, K . F . M . SIER,

I . BlEMOND, AND C . B . H . W . LAMERS

927 Epidemiology of Colonic Symptoms and the Irritable Bowel Syndrome N . J . TALLEY, A . R . ZINSMEISTER, C . V A N DYKE,

A N D L . J . M E L T O N I I I

935 Action of Beer and Its Ingredients on Gastric Acid Secretion and Release of Gastrin in Humans M . V . SINGER, S. TEYSSEN, AND V . E . EYSSELEIN

943 Omeprazole Treatment Does Not Affect the Metabolism of Caffeine T . ANDERSSON, R. BERGSTRAND, C . CEDERBERG, S. ERIKSSON,

P . - O . LAGERSTRÖM, A N D I . SKÄNBERG

948 Tolerance During 5 Months of Dosing With Ranitidine, 150 mg Nightly: A Placebo-Controlled, Double-Blind Study C . U . NWOKOLO, E.J. PREWETT, A . M . SAVVYERR, M . HUDSON,

S. L I M , AND R . E . POUNDER

954 Role of Capsaicin-Sensitive Afferent Neurons in Alkaline Secretory Response to Luminal Acid in the Rat Duodenum K . TAKEUCHI, J. M A T S U M O T O , K . UESHIMA, AND S. OKABE

962 Reverse-Perfused Sleeve: A n Improved Device for Measurement of Sphincteric Function of the Crural Diaphragm B . SIVRI A N D R . K . M I T T A L

970 Opioids Inhibit Neuromuscular Transmission in Circular Muscle of Human and Baboon Jejunum A . J. BAUER, M . G . SARR, AND J . H . SZURSZEWSKI

977 Effect of Age on Gastric Acid Secretion and Serum Gastrin Concentrations in Healthy Men and Women M . GOLDSCHMIEDT, C . C . BARNETT, B . E . SCHWARZ, W . E . KARNES,

J.S. REDFERN, AND M . FELDMAN

991 Enterogastric Reflux After Various Types of Antiulcer Gastric Surgery: Quantitation by 9 9 m T c - H I D A Scintigraphy E . XYNOS, J .S . VASSILAKIS, A . FOUNTOS, G . PECHLIVANIDES,

A N D N . K A R K A V J T S A S

999 The Origin of Symptoms on the Brain-Gut Axis in Functional Dyspepsia F . M E A R I N , M . CUCALA, F . AZPIROZ, AND J.-R. MALAGELADA

1007 Electroencephalogram Patterns During Sleep Reflux in Infants J . M . SONDHEIMER AND E. HODDES

1012 In Vivo Evidence of Altered Chloride but Not Potassium Secretion in Cystic Fibrosis Rectal Mucosa J . L . GOLDSTEIN, A . B . SHAPIRO, M . C . R A O , AND T . J . LAYDEN

1020 Increased Activation of Isolated Intestinal Lamina Propria Mononuclear Cells in Inflammatory Bowel Disease S. SCHREIBER, R . P . MACDERMOTT, A . RAEDLER, R. PINNAU,

M . J . BERTOVICH, AND G . S . N A S H

1031 Effects of Diazepam and Ro 15-1788 on Duodenal Bicarbonate Secretion in the Rat B . S Ä F S T E N , G . JEDSTEDT, AND G . F L E M S T R Ö M

1039 Reversal of Protein-Bound Vitamin B 1 2 Malabsorption With Antibiotics in Atrophic Gastritis P . M . SUTER, B . B . GoLNER, B . R . GOLDIN, F . D . MORROW,

AND R . M . RUSSELL

1046 Short-Chain Glucose Polymer and Anthracene-9-carboxylic Acid Inhibit Water and Electrolyte Secretion Induced by Dibutyryl Cyclic AMP in the Small Intestine G . H . RABBANI, R . - B . L u , K. H O R V A T H , AND E. LEBENTHAL

L I V E R , P A N C R E A S , A N D B I L I A R Y T R A C T

1054 Light and Electron Microscopy of Neuropeptide Y -Containing Nerves in Human Liver, Gallbladder, and Pancreas W . - G . D I N G , M . FUJIMURA, A . M O R I , I . T O O Y A M A ,

AND H . KIMURA

1060 Ornipressin in the Treatment of Functional Renal Failure in Decompensated Liver Cirrhosis K . LENZ, H . HÖRTNAGL, W . DRUML, H . REITHER, R. SCHMID,

B . SCHNEEWEISS, A . LAGGNER, G . G R I M M , A N D A . L . GERBES

1068 Complications of Endoscopic Sphincterotomy S. SHERMAN, T . A . RUFFOLO, R . H . HAWES, A N D G . A . L E H M A N

1076 Defective Fc Receptor-Mediated Clearance in Patients With Primary Biliary Cirrhosis K. NILSSON EKDAHL, L. LÖÖF, A . NYBERG, U . R . NILSSON,

AND B . NILSSON

1083 Azathioprine Treatment Increases Hepatocyte Turnover N . ARBER, G . ZAJICEK, J. NORDENBERG, A N D Y . SIDI

1087 Prophylactic Sclerotherapy in High-Risk Cirrhotics Selected by Endoscopic Criteria R. DE FRANCHIS, M . PRIMIGNANI, P . G . ARCIDIACONO, P . M . R I Z Z I ,

P. VITAGLIANO, M . C . VAZZOLER, R. ARCIDIACONO, A . ROSSI,

A . ZAMBELLI , F . COSENTINO, G . CALETTI, S. BRUNATI ,

G . BATTAGLIA, AND G . GERUNDA

1094 An Na +-Dependent and an Na +-Independent System for Glutamine Transport in Rat Liver Basolateral Membrane Vesicles H . M . SAID, D . HOLLANDER, AND S. KHORCHID

1102 Glucocorticoids Stimulate Ornithine Decarboxylase Gene Expression in Pancreatic AR42J Cells S. ROSEWICZ A N D C . D . LOGSDON

1109 Aspirin Does Not Inhibit Cholesterol Cholelithiasis in Two Established Animal Models B . I . COHEN, E . H . MOSBACH, N . A Y Y A D , M . YOSHII ,

AND C . K . MCSHERRY

B R I E F R E P O R T S

1117 Hepatitis C Virus Antibodies in Acute Icteric and Chronic Non-A, Non-B Hepatitis J .G . M C H U T C H I S O N , G . K U O , M . HOUGHTON, Q . - L . CHOO,

AND A . G . REDEKER

C L I N I C A L C H A L L E N G E S

1120 Fecal Incontinence in a 39-Year-Old Man R.J. M A Y

E D I T O R I A L S

1127 Enteral Feeding Versus Drug Therapy in Crohn's Disease: A Continuing Story J . W . SINGLETON

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December 1991 C O N T E N T S ix

S E L E C T E D S U M M A R I E S

1129 Treatment of Severe Postgastrectomy Dumping With a Long-Acting Somatostatin Analog: Is Effective Management Finally Available?

1130 Sulfasalazine vs. Steroids in Crohn's Disease: David vs. Goliath?

1131 Recurrent Hepatitis B in Liver Transplant Recipients—No Easy Answers

1133 Sporadic vs. Posttransfusion Hepatitis C : Why the Differences?

1134 Bidirectional Communication Between Mast Cells and Nerves Controls Intestinal Secretion

1137 B O O K R E V I E W S

C O R R E S P O N D E N C E

1139 Concentration in Pancreatic Juice of Lithostathine

1140 Pathogenesis and Treatment of Rotavirus Diarrhea

1141 Prevalence of Spontaneous Hepatofugal Portal Flow in Liver Cirrhosis

1142 Enteric Neuronal Autoantibodies in Pseudoobstruction With Small-Cell Lung Carcinoma

1144 Hyperplastic Polyps and Risk of Adenomas

1146 N O T I C E S

NO. 5, NOVEMBER 1991

1147 This Month in G A S T R O E N T E R O L O G Y

A L I M E N T A R Y T R A C T

1149 A Critical Analysis, With Appropriate Controls, of Gastric Acid and Pepsin Secretion in Clinical Esophagitis B . I . HlRSCHOWITZ

1159 Primary B-CeII Gastric Lymphoma: A Clinicopathological Study of 145 Patients S .B . COGLIATTI, U . SCHMID, U . SCHUMACHER, F . ECKERT,

M . - L . H A N S M A N N , J. HEDDERICH, H . T A K A H A S H I , AND K . LENNERT

1171 Value of Transrectal Ultrasonography in Crohn's Disease M . J . V A N OUTRYVE, P . A . PELCKMANS, P .P . MICHIELSEN,

A N D Y . M . V A N MAERCKE

1178 -y-Aminobutyric Acid Localization and Function as Modulator of Cholinergic Neurotransmission in Rat Antral Mucosal/Submucosal Fragments R . F . HARTY, M . G . BOHARSKI, G . S . BOCHNA, T . A . CARR,

P . E . E A G A N , M . RINGS, D . C . LASSITER, M . P . POUR,

D . F . SCHAFER, A N D R . S . M A R K I N

1187 Histological Maturity of Healed Duodenal Ulcers and Ulcer Recurrence After Treatment With Colloidal Bismuth Subcitrate or Cimetidine S. P A N , C . - H . LTAO, G . - S . LIEN, AND S . - H . CHEN

1192 Portal Colopathy: Prospective Study of Colonoscopy in Patients With Portal Hypertension R . A . KOZAREK, V . A . B O T O M A N , J.E. BREDFELDT, J . M . ROACH,

D . J . PATTERSON, A N D T . J . B A L L

1198 Distribution of Aneuploid Cell Populations in Ulcerative Colitis With Dysplasia or Cancer D . S . LEVINE, P .S . RABINOVITCH, R . C . HAGGITT, P . L . BLOUNT,

P.J. D E A N , C . E . RUBIN, A N D B.J. REID

1211 Calcitonin Gene-Related Peptide and Substance P Decrease in the Rabbit Colon During Colitis V . E . EYSSELEIN, M . REINSHAGEN, F . COMINELLI, C . STERNINI,

W . DAVIS , A . PATEL, C . C . N A S T , D . BERNSTEIN, K . ANDERSON,

H . K H A N , AND W . J . SNAPE, JR.

1220 Mechanisms of Acid Injury to Rabbit Esophageal Epithelium N . A . TOBEY AND R . C . ORLANDO

1229 Prostaglandins and the Colonic Epithelium R . A . GOODLAD, N . M A N D I R , S . LEVIN, J .L . ALLEN,

AND N . A . W R I G H T

1235 Morphometry and Cell Proliferation in Endoscopic Biopsies: Evaluation of a Technique R . A . GOODLAD, S. LEVI , C . Y . LEE, N . M A N D I R , H . HODGSON,

AND N . A . WRIGHT

1242 The Role of Vasopressin in the Pathogenesis of Ethanol-Induced Gastric Hemorrhagic Erosions in Rats F. LÄSZLÖ, G . KARACSONY, E . SZABO, J. LÄNG, L . BALÄSPIRI,

AND F . A . LÄSZLÖ

1249 Central and Peripheral Control of Postprandial Pyloric Motility by Endogenous Opiates and Cholecystokinin in Dogs Y . LOPEZ, J. FIORAMONTI, AND L . BUENO

1256 Peptidergic Innervation of the Human Esophageal Smooth Muscle C . SlNGARAM, A . SENGUPTA, D . J . SUGARBAKER, A N D R . K . GOYAL

1264 Changes in the Structure and Regeneration Mode of the Rat Small Intestinal Mucosa Following Benzalkonium Chloride Treatment G . E. HOLLE

1274 Different Fibers Have Different Regional Effects on Luminal Contents of Rat Colon A . MCINTYRE, G . P . YOUNG, T . TARANTO, P .R. GIBSON,

AND P . B . W A R D

1282 Inversion of the Slow-Wave Frequency Gradient in Symptomatic Patients With Roux-en-Y Anastomoses G . VANTRAPPEN, G . COREMANS, J. JANSSENS, A . M A N T I D E S ,

AND F . VANDEN BORRE

1289 Colonic Motility and Transit in Health and Ulcerative Colitis S . N . REDDY, G . BAZZOCCHI, S. C H A N , K . A K A S H I ,

J. VILLANUEVA-MEYER, G . Y A N N I , I . M E N A , AND W . J . SNAPE, JR.

1298 Effect of Eating on Colonic Motility and Transit in Patients With Functional Diarrhea G . BAZZOCCHI, J. ELLIS, J. VILLANUEVA-MEYER, S . N . REDDY,

I . M E N A , AND W . J . SNAPE, JR.

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x C O N T E N T S GASTROENTEROLOGY Vol . 101, No. 6

1307 Quality of Life of Patients With Ulcerative Colitis Preoperatively and Postoperatively R . S . M C L E O D , D . N . CHURCHILL, A . M . LOCK, S. VANDERBURGH,

A N D Z . COHEN

1314 Perendoscopic Manometry of the Distal Ileum and Ileocecal Junction in Humans E . CORAZZIARI, F . BARBERANI, M . T O S O N I , S. BOSCHETTO,

A N D A . TORSOLI

1320 Delayed Gastrointestinal Transit Times in Anorexia Nervosa and Bulimia Nervosa N . K A M A L , T . C H A M I , A . ANDERSEN, F . A . ROSELL,

M . M . SCHUSTER, AND W . E . WHITEHEAD

L I V E R , P A N C R E A S , A N D B I L I A R Y T R A C T

1325 Ultrasonic Tissue Characterization of Chronic Liver Disease Using Cepstral Analysis K . SUZUKI , N . H A Y A S H I , Y . SASAKI , M . K O N O , Y . I M A I ,

H . FUSAMOTO, AND T . K A M A D A

1332 Treatment of Primary Biliary Cirrhosis With Low-Dose Weekly Methotrexate M . M . K A P L A N AND T . A . K N O X

1339 Effect of Phospholipase C on Cholesterol Solubilization in Model Bile N . R . PATTINSON AND K . E . W I L L I S

1345 Effectiveness of a Purified Human Hemoglobin as a Blood Substitute in the Perfused Rat Liver H . F . STARNES, JR., A . TEWARI , K . FLOKAS, J .C . KOSEK,

D . BROWN, A . L . VAN-KESSEL, A N D C . E . M O N D O N

1354 Abnormal Sympathetic and Renal Response to Sodium Restriction in Compensated Cirrhosis M . - A . S I M O N , J. DIEZ, AND J. PRIETO

1361 Lipase/Amylase Ratio V . V . GUMASTE, P . B . DAVE, D . W E I S S M A N , A N D J. MESSER

1367 H L A DRw8 and Complement C4 Deficiency as Risk Factors in Primary Biliary Cirrhosis M . P . M A N N S , A . BREMM, P . M . SCHNEIDER, A . N O T G H I ,

G . GERKEN, M . PRAGER-EBERLE, B . STRADMANN-BELLINGHAUSEN,

K . - H . MEYER Z U M BÜSCHENFELDE, A N D C . RITTNER

1374 Risk Factors for Septicemia Following Endoscopic Biliary Stenting S. M O T T E , J. DEVIERE, J . - M . D U M O N C E A U , E . SERRUYS,

J.-P. T H Y S , A N D M . CREMER

1382 A Shift in Balance Between Profibrinolytic and Antifibrinolytic Factors Causes Enhanced Fibrinolysis in Cirrhosis F . W . G . LEEBEEK, C . KLUFT, E . A . R . K N O T , M . P . M . D E M A A T ,

A N D J . H . P . W I L S O N

1391 Lithotripsy of Gallstones by Means of a Quality-Switched Giant-Pulse NeodymiumiYttrium-Aluminum-Garnet Laser J. HOCHBERGER, E. GRUBER, P . W I R T Z , U . DÜRR, A . K O L B ,

U . ZANGER, E . G . H A H N , AND C . E L L

1399 Portal and Biliary Phases of Enterohepatic Circulation of Corrinoids in Humans S. E L KHOLTY, J . -L. GUEANT, L . BRESSLER, M . DJALALI,

P . BOISSEL, P. GERARD, AND J.-P. NICOLAS

1409 Significance of Computed Tomography for Shock-Wave Therapy of Radiolucent Gallbladder Stones C . ELL, H . T . SCHNEIDER, J. BENNINGER, S. THEOBALDY,

N . FRIEDEL, W . RÖDL, P. WlRTZ, A N D E . G . H A H N

C A S E R E P O R T S

1417 Postinfantile Giant Cell Hepatitis in Association With Hypereosinophilia A . K U M A R AND G . Y . M I N U K

1420 Idiopathic Neonatal Iron-Storage Disease J . A . BARNARD I I I AND E. M A N C I

B R I E F R E P O R T S

1428 Cholecystokinin-Mediated Ileal Electrolyte Transport in the Guinea Pig J .F. KACHUR, S . - X . W A N G , G . W . GULLIKSON,

AND T . S . GAGINELLA

C L I N I C A L C H A L L E N G E S

1432 Recurrent Gastrointestinal Bleeding Associated With Myelofibrosis and Diffuse Intestinal Telangiectasias S . D . FREEDMAN, R . E . DREWS, D. J . GLOTZER, D . K I M ,

H . GARDNER, AND S.J. GALLI

E D I T O R I A L S

1440 Methotrexate Therapy of Primary Biliary Cirrhosis: Promising but Worrisome J . H . HOOFNAGLE AND N . V . BERGASA

S E L E C T E D S U M M A R I E S

1443 Pregnancy in Liver Transplant Patients—And Vice Versa

1444 The p53 Gene and Hepatocellular Carcinoma

1445 Transforming Growth Factors in Human Chronic Hepatitis and Cirrhosis: Correlations With Fibrogenesis and Hepatic Regeneration

1446 Somatostatin Therapy for AIDS Diarrhea: Muddy Waters

1448 H 2 Antagonists by Continuous Infusion: IV or IG?

1450 B O O K R E V I E W S

C O R R E S P O N D E N C E

1452 Functional Bowel Disease: The Role of Fructose and Sorbitol

1453 Role of Fructose-Sorbitol Malabsorption in the Irritable Bowel Syndrome

1454 Fructose Malabsorption and the Irritable Bowel Syndrome

1454 Helicobacter pylori Infection and Inflammation of the Gastric Corpus

1455 Postparacentesis Plasma Expansion Prevents Asymptomatic Laboratory Abnormalities, but Does It Have Any Impact on Morbidity or Mortality?

1457 Cancer Risk in Left-Sided Colitis

1458 Stress Ulcer Prophylaxis

1459 The Use of 6-Mercaptopurine in Adolescents With Crohn's Disease

1460 C O R R E C T I O N S

1461 N O T I C E S

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December 1991 C O N T E N T S x i

NO. 6, DECEMBER 1991

1463 This Month in G A S T R O E N T E R O L O G Y

A M E R I C A N G A S T R O E N T E R O L O G I C A L A S S O C I A T I O N

1465 Presidential Address D . H . ALPERS

1468 Presentation of the Julius Friedenwald Medal to Cyrus E . Rubin, M.D. W . M . WEINSTEIN

A L I M E N T A R Y T R A C T

1471 Galanin Inhibition of Vasoactive Intestinal Polypeptide Release and Circular Muscle Motility in the Isolated Perfused Canine Ileum J . - A . E . T . FOX-THRELKELD, T . J . M C D O N A L D , S. CIPRIS,

Z . WOSKOWSKA, AND E .E . DANIEL

1477 The Minor Components of the Rat Asialoglycoprotein Receptor Are Apically Located in Neonatal Enterocytes C . Hu, E .Y . LEE, J .E. HEWITT, J . U . BAENZIGER, J . - Z . M U ,

K . DESCHRYVER-KECSKEMETI, AND D . H . ALPERS

1488 Gastrointestinal Motor Effects of Erythromycin in Humans S . K . SARNA, K . H . SOERGEL, T . R . K O C H , J.E. STONE, C M . W O O D ,

R . P . R Y A N , R . C . ARNDORFER, J .H. C A V A N A U G H , H . N . NELLANS,

AND M . B . LEE

1497 Colonic Fermentation to Short-Chain Fatty Acids Is Decreased in Antibiotic-Associated Diarrhea M . R . CLAUSEN, H. BONNEN, M . TVEDE, AND P . B . MORTENS EN

1505 Differential Effect on Neuropeptide Release of Different Concentrations of Hydrogen Ions on Afferent and Intrinsic Neurons of the Rat Stomach P. GEPPETTI, M . T R A M O N T A N A , S. EVANGELISTA, D . RENZI,

C A . M A G G I , B . M . FUSCO, AND E . D E L BIANCO

1512 High Incidence of Esophageal Motor Disorders in Consecutive Patients With Globus Sensation G . MOSER, G . V . VACARIU-GRANSER, C SCHNEIDER, T . - A . A B A T Z I ,

P. POKIESER, G . STACHER-JANOTTA, G . G A U P M A N N , U . WEBER,

T . WENZEL, M . RODEN, A N D G . STACHER

1522 Imbalance of Plasminogen Activators and Their Inhibitors in Human Colorectal Neoplasia C . F . M . SIER, H.W. VERSPAGET, G . GRIFFIOEN, J.H. VERHEIJEN,

P . H . A . Q U A X , G . DOOIJEWAARD, P . A . F . DE BRUIN,

AND C.B .H.W. LAMERS

1529 Activation and Signaling Status of Human Lamina Propria T Lymphocytes L . Q I A O , G . SCHÜRMANN, M . BETZLER, AND S . C MEUER

1537 Colonic Motor Response to a Meal in Acute Colitis A . K . SETHI AND S . K . SARNA

1547 Antral Gastrin Cell Hyperfunction in Children B . ANNIBALE, M . BONAMICO, G . R I N D I , L . V I L L A N I , E . FERRANTE,

A . V A N I A , E . SOLCIA, AND G . DELLE FAVE

1552 Regulation of Rat Antral Gastrin and Somatostatin Gene Expression During Starvation and After Refeeding V . Wu, K . S U M I I , A . T A R I , M . S U M I I , AND J.H. W A L S H

1559 Radial and Longitudinal Asymmetry of Human Pharyngeal Pressures During Swallowing V . W . SEARS, JR., J . A . CASTELL, A N D D . O . CASTELL

1564 Cisapride in Children With Chronic Intestinal Pseudoobstruction C . Di LORENZO, S . N . REDDY, J. VILLANUEVA-MEYER, I . M E N A ,

S. M A R T I N , A N D P . E . H Y M A N

1571 Colonic Motility in Innervated and Extrinsically Denervated Loops in Dogs C S HIB AT A, I . SASAKI , S. M A T S U N O , A . M I Z U M O T O , AND Z . I T O H

1579 Dual Effect of Trimebutine on Contractility of the Guinea Pig Ileum via the Opioid Receptors K . T A M Y A M A, I . S A N O , S. N A K A Y A M A , S. M A T S U Y A M A ,

K . TAKEDA, C . YOSHIHARA, A N D C . T A N A K A

1588 Flow-Cytometric D N A Content Analysis of Esophageal Squamous Cell Carcinomas M . ROBASZKIEWICZ, B.J . REID, A . V O L A N T , J . M . C A U V I N ,

P . S . RABINOVITCH, A N D H . GOUEROU

1594 Loss of Interleukin-2-Producing Intestinal C D 4 + T Cells in Inflammatory Bowel Disease K . K U S U G A M I , T . M A T S U U R A , G . A . WEST, K . R . Y O U N G M A N ,

D . RACHMILEWITZ, A N D C . FIOCCHI

1606 Sensorial and Intestinointestinal Reflex Pathways in the Human Jejunum J . - M . ROUILLON, F . AZPIROZ, A N D J.-R. MALAGELADA

1613 Modification of the Effects of Blood on Amino Acid Metabolism by Intravenous Isoleucine N . E . P . D E U T Z , P . L . M . REIJVEN, M . C F . BOST, C L . H . VAN BERLO,

A N D P . B . SOETERS

1621 Enhanced Perception of Physiological Intestinal Motility in the Irritable Bowel Syndrome J .E. KELLOW, G . M . ECKERSLEY, AND M . P . JONES

L I V E R , P A N C R E A S , A N D B I L I A R Y T R A C T

1628 Gas in Gallstones: Quantitative Determinations and Possible Effects on Fragmentation by Shock Waves N . V A K I L A N D E . C EVERBACH

1635 The Antiinflammatory Effect of Dopamine in Alcoholic Hemorrhagic Pancreatitis in Cats N . D . KARANJIA, A . L . W I D D I S O N , F.J. LUTRIN, Y . - B . C H A N G ,

A N D H . A . REBER

1642 A Prospective Controlled Study of the Risk of Bacteremia in Emergency Sclerotherapy of Esophageal Varices H . H O , M . J . ZUCKERMAN, A N D C . WASSEM

1649 Patterns of Hepatitis Delta Virus Reinfection and Disease in Liver Transplantation A . OTTOBRELLI, A . M A R Z A N O , A . SMEDILE, S. RECCHIA,

M . S A L I Z Z O N I , C . C O R N U , M . E . L A M Y , J .B. OTTE,

B . DE HEMPTINNE, A . GEUBEL, M . GRENDELE, M . COLLEDAN,

D. G A L M A R I N I , G . M A R I N U C C I , C . D I GIACOMO, S. AGNES,

F . BONINO, A N D M . RIZZETTO

1656 Spontaneous Bacterial Peritonitis in Patients With Hepatitis B-Related Cirrhosis and Hepatocellular Carcinoma S.-S. W A N G , Y . - T . T S A I , S . -D. LEE, H . - T . CHEN, C . - W . L U ,

F . - Y . LEE, J.-S. JENG, Y . - C . L I U , AND K. - J . L O

1663 Regional Orientation of Actin Filaments in the Pericanalicular Cytoplasm of Rat Hepatocytes M . I S H I I , H . W A S H I O K A , A . TONOSAKI, AND T . T O Y O T A

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x i i CONTENTS GASTROENTEROLOGY Vol . 101. No. 6

1673 Acute Infusions of Bile Salts Increase Biliary Excretion of Iron in Iron-Loaded Rats P. L E W , M . D U M O N T , P . BRISSOT, A. LETREUT, A. FAVIER,

Y. DEUGNIER, AND S. ERLINGER

1680 Differential Inhibition of Individual Human Liver Cytochromes P-450 by Cimetidine R.G. KNODELL, D . G . BROWNE, G . P . GWOZDZ, W . R . B R I A N ,

A N D F . P . GUENGERICH

1692 Experimental Evaluation of an Endoscopic Balloon for Manometry of Esophageal Varices P. GERTSCH, A . M . WHEATLEY, R. M A I B A C H , G.J. M A D D E R N ,

A N D J . -N. VAUTHEY

1701 Occult Microlithiasis in Idiopathic ' Acute Pancreatitis: Prevention of Relapses by Cholecystectomy or Ursodeoxycholic Acid Therapy E . Ros, S. NAVARRO, C . B R U , A. GARCIA-PUGES,

A N D R. VALDERRAMA

1710 Glucagon Hinders the Effects of Somatostatin on Portal Hypertension M . P . PIZCUETA, J.C. G A R C I A - P A G A N , M . FERNANDEZ,

R. CASAMITJANA, J. BOSCH, A N D J. RODES

1716 Intraacinar Profiles of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Activities in Human Liver L P . M A L Y AND D . SASSE

1724 Antibodies to Hepatitis C Virus in Low-Risk Blood Donors: Implications for Counseling Positive Donors H . H . Hsu, M . GONZALEZ, S . K . H . FOUNG, S . M . FEINSTONE,

A N D H . B . GREENBERG

C A S E R E P O R T S

1728 Successful Orthotopic Liver Transplantation in a Patient With Refractory Biliary Candidiasis K . B . NOACK, D.R. O S M O N , K . P . BATTS , M . W I L H E L M ,

R .A .F . K R O M , A N D K . D . LINDOR

1731 Acute Biliary-Vascular Fistula Following Needle Aspiration of the Liver M . S . VERHILLE A N D S J . M U N O Z

1734 Severe Monochlorobenzene-Induced Liver Cell Necrosis G . BAB ANY, J. BERNUAU, A. CAILLEUX, J.-F. CADRANEL,

C . DEGOTT, S. ERLINGER, AND J.-P. B E N H A M O U

1737 Severe Cholestatic Jaundice Associated With Piroxicam K . S . HEPPS, G . M . M A L I H A , R. ESTRADA, AND R . W . GOODGAME

E D I T O R L A L S

1741 Liver Transplantation: A Model for the Transmission of Hepatitis Delta Virus W . S . M A S O N AND J . M . TAYLOR

S E L E C T E D S U M M A R I E S

1744 Laparoscopic Treatment of Duodenal Ulcer: A Plea for Clinical Trials

1745 Alcohol Abuse and Liver Disease: True, True, but Not Necessarily Related

1747 Sphincter of Oddi Manometry in Patients With Possible Sphincter of Oddi Dysfunction

1748 Palliation of Advanced Esophageal Cancer: A (Laser) Light at the End of the Tunnel

1750 Is Exercise Good for Gastrointestinal Function?

1752 B O O K R E V I E W S

C O R R E S P O N D E N C E

1754 Extracorporeal Shock-Wave Lithotripsy for the Management of Bile Duct Stones: Is It Always a Safe Procedure?

1755 Microvillus Inclusion Disease

1756 Hyperplastic Polyps Do Not Predict Adenomatous Polyps

1757 A Role for NMR in Alcoholism?

1758 Whither Biliary Sludge—Do You Exist?

1759 Helicobacter pylori in Autoimmune Gastritis

1759 Propranolol for Prophylactic Treatment of a First Variceal Hemorrhage

1761 Intestinal Lymphangiectasia: Lack of Efficacy of Antiplasmin Therapy?

1761 C O R R E C T I O N S

1762 N O T I C E S

1763 S P E C I A L N O T I C E

1768 A U T H O R I N D E X T O V O L U M E 101

1781 S U B J E C T I N D E X T O V O L U M E 101

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G A S T R O E N T E R O L O G Y 1991;101:424-429

Presence of Atrial Natriuretic Factor Prohormone in Enterochromaffin Cells of the Human Large Intestine

ALEXANDER L. GERBES, W A L T E R NATHRATH, MARC CANTIN, and HEIKO DENECKE Departments of Pathology and Surgery, Medizinische K l i n i k I I , K l i n i k u m Großhadern, University of M u n i c h , M u n i c h , Germany; and Clinical Research Institute, Montreal , Quebec, Canada

Atrial natriuretic factor is a hormone intimately involved in water and salt homeostasis. The heart constitutes the major but not exclusive site of synthe­sis of this hormone. Among other functions, the gastrointestinal tract has endocrine functions, plays an important role in volume regulation of the body, and seems to be a target organ for atrial natriuretic factor. Therefore, the presence of atrial natriuretic factor was investigated in the human gut. Immuno-reactive atrial natriuretic factor was found in intra-operatively obtained samples of normal human co­lon. Acidic extracts of human large intestine contained about 0.4 pmol/g wet wt of atrial natri­uretic factor. Analysis of atrial natriuretic factor immunoreactivity by gel-filtration and reverse-phase high-performance liquid chromatography showed that about 65% of the immunoreactivity corresponded to the atrial natriuretic factor prohor­mone and about 35% corresponded to the C-termi-nal ANF 9 9. 1 2 6. Immunohistochemistry showed atrial natriuretic factor prohormone location in entero-chromaffin cells of the colon mucosa. Altogether, these findings show the presence of atrial natriuretic factor prohormone in enterochromaffin cells of the human large intestine and may suggest this organ as a site of atrial natriuretic factor synthesis in hu­mans.

Atrial natriuretic factor (ANF) is involved in salt j L j L a n d water homeostasis. It was first discovered in mammalian atrial myocytes, where it is synthesized and stored as a 126-amino-acid prohormone (1,2). Upon appropriate stimulation, the prohormone is cleaved and released into the circulation where the C-terminal 28-amino-acid peptide ANF 9 9 _ 1 2 6 has been identified as a biologically active hormone (3,4).

Subsequently, the presence of ANF has been deter­mined in several tissues other than the heart (5-9), and recently it has been discovered in guinea pig and rat intestine (10,11). The gastrointestinal tract plays an important role in volume regulation. Moreover, it seems to be a target organ for ANF with specific ANF binding sites (12-17). These findings, together with the endocrine properties of the gut (18-21), a major organ under endocrine control, might suggest a role of ANF in the intestine. Therefore, the aim of this study was to investigate the presence of ANF in the intes­tines of human subjects.

Materials and Methods

Tissues

Large i n t e s t i n a l t i ssue w a s o b t a i n e d f r o m 1 4 h u m a n subjects d u r i n g s u r g e r y for t h e r e s e c t i o n o f t u m o r s o f the c o l o n . Segments o f n o n t u m o r o u s t i ssue ( 1 - 2 g) w e r e w a s h e d w i t h 4 ° C sa l ine i m m e d i a t e l y af ter r e s e c t i o n a n d w e r e a d d e d to 4 m L o f 0 . 1 N H C l for e x t r a c t i o n or w e r e f i x e d i n B o u i n ' s f l u i d f o r i m m u n o h i s t o c h e m i s t r y .

Extraction Procedure

T i s s u e sect ions w e r e b o i l e d i n 0 . 1 N H C l i n a m i c r o ­w a v e o v e n f o r 5 m i n u t e s a n d w e r e s u b s e q u e n t l y h o m o g e ­n i z e d w i t h a p o l y t r o n for 3 0 seconds. T h e r e s u l t i n g h o m o g e -nate w a s b o i l e d for a n o t h e r 5 m i n u t e s a n d c e n t r i f u g e d s u b s e q u e n t l y f o r 3 0 m i n u t e s at 4°C ( 2 0 , 0 0 0 x g). T h e s u p e r n a t a n t w a s a p p l i e d to s m a l l c o l u m n s f i l l e d w i t h

Abbreviations used in this paper: A N F , atrial natriuretic factor; proANF, atrial natriuretic factor prohormone; T F A , triflu-oroacetic acid.

© 1991 by the American Gastroenterological Association 0016-5085/91/$3.00

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August 1991 ANF PROHORMONE I N H U M A N INTESTINE 425

a m b e r l i t e X A D - 2 adsorbent r e s i n (Serva, H e i d e l b e r g , Ger­m a n y ) . T h e c o l u m n s w e r e w a s h e d w i t h 0 . 1 % t r i f l u o r o a c e t i c a c i d ( T F A ) a n d e l u t e d w i t h 4 m L o f 8 0 % a c e t o n i t r i l e i n 0 . 1 % T F A . T h e e luates w e r e l y o p h i l i z e d f o r f u r t h e r a n a l y s i s .

Radioimmunoassay and Recovery

Determination

T h e r a d i o i m m u n o a s s a y ( R I A ) w a s p e r f o r m e d as d e s c r i b e d p r e v i o u s l y (22,23) ; a n t i b o d y T o n i I I I (g i f t o f R. A r e n d t ) d i r e c t e d against t h e c a r b o x y t e r m i n u s o f A N F r e c o g n i z e s A N F 9 9 . 1 2 ß as w e l l as t h e A N F p r o h o r m o n e ( p r o A N F ) . R e c o v e r y of i m m u n o r e a c t i v e A N F w a s e v a l u a t e d b y a d d i n g 250 o r 500 f m o l o f A N F 9 9 . 1 2 6 or p r o A N F 2 1 2 6 (g i f ts o f D r s . S c h ö n e , P r e i b i s c h , a n d Se ipke , H ö c h s t A G , F r a n k f u r t , G e r m a n y ) to t h e a c i d i c t i ssue h o m o g e n a t e a n d p e r f o r m i n g e x t r a c t i o n a n d s e p a r a t i o n p r o c e d u r e s .

Chromatographic Analysis of Atrial Natriuretic

Factor Immunoreactivity

Gel filtration. The lyophilized extract of colonic tissue was dissolved in 250 \xL of 0.1% T F A and loaded on a Sephadex G 50 column (860 x 16 mm; Pharmacia, Uppsala, Sweden). The dynamic phase was 0.1N acetic acid, the flow rate was 10 mL/h, and the fraction size was 2.5 mL. Calibration was performed with albumin (VJ, vitamin B 1 2

(V t), proANF2_12f„ and ANF 9 0 . 1 2 6 . Reverse-phase high-performance liquid chromatogra­

phy. An aliquot of the pooled lyophilized fractions ob­tained by gel filtration was taken up in 50 uJL 0.5% T F A and loaded on a high-performance liquid chromatography (HPLC) C H column (5 u.m, 750 x 4.6 mm; Beckman Instru­ments, San Ramon, CA). Elution was performed with a linear gradient of acetonitrile (20%-55%, 55 minutes) in 0.1% T F A (flow rate, 0.5 mL/min). Calibration of the column was carried out with A N F 9 9 . 1 2 6 and proANF 2 . 1 2 6 .

Immunohistochemistry

C o l o n i c t issue s p e c i m e n s f i x e d i n B o u i n ' s f l u i d w e r e d e h y d r a t e d i n a l c o h o l s a n d e m b e d d e d i n p a r a f f i n . A n i n d i r e c t i m m u n o p e r o x i d a s e m e t h o d w a s c a r r i e d o u t as p r e v i o u s l y d e s c r i b e d (25) . I n br ie f , 5 - jxm sect ions o f the B o u i n - f i x e d , p a r a f f i n - e m b e d d e d t issues w e r e d e w a x e d i n x y l e n e a n d r e h y d r a t e d t h r o u g h g r a d e d a l c o h o l s . E n d o g e ­n o u s p e r o x i d a s e a c t i v i t y w a s q u e n c h e d b y s e q u e n t i a l treat­m e n t w i t h 7 .5% h y d r o g e n p e r o x i d a s e , 2 . 2 8 % p e r i o d i c a c i d , a n d 0 . 0 2 % s o d i u m b o r o h y d r i d e . A f t e r o v e r l a y i n g the t issue i n 2 % n o r m a l goat s e r u m , the s p e c i f i c a n t i b o d i e s w e r e a p p l i e d as f o l l o w s : a n t i b o d y T o n i I I I , r e a c t i n g w i t h b o t h p r o A N F a n d A N F 9 9 . 1 2 6 , w a s d i l u t e d i n p h o s p h a t e - b u f f e r e d s a l i n e (PBS) at a r a t i o o f 1:400; a n t i b o d y G T - 2 3 (24) , ra i sed aga ins t the N - t e r m i n a l f r a g m e n t o f p r o A N F a n d r e a c t i n g w i t h the p r o h o r m o n e b u t n o t w i t h A N F 9 9 . 1 2 6 , w a s u s e d i n a 1:100 d i l u t i o n ; a n d the m o u s e m o n o c l o n a l a n t i b o d y ra i sed against h u m a n c h r o m o g r a n i n [ L K 2 H 10; (26)] w a s d i l u t e d

1:200. Incubation time was 2 hours at 37°C for each antibody. After washing in PBS, peroxidase-conjugated goat anti-rabbit immunoglobulin (Ig) G or goat anti-mouse IgG, diluted 1:250 and 1:1800, respectively, was applied for 5 minutes at 22°C. Peroxidase reaction was visualized with aminoethylcarbazole, and hematoxylin was used to counter-stain the nuclei. Controls included substitution of first and/or second antibody by PBS, normal mouse serum, or normal rabbit serum.

Materials

H u m a n A N F g 9 . , 2 6 was p u r c h a s e d f r o m N o v a B i o -c h e m , L ä u f e l f m g e n , S w i t z e r l a n d ; r a t p r o A N F 2 . 1 2 6 w a s a g i f t f r o m D r s . S c h ö n e , P r e i b i s c h , a n d Se ipke , H ö c h s t A G , F r a n k f u r t , G e r m a n y . , 2 5 I - i o d i n a t e d A N F 9 9 . l 2 6 w a s o b t a i n e d f r o m B i o t r e n d , C o l o g n e , G e r m a n y (sp act, 2000 C i / m m o l ) . A n t i b o d y T o n i I I I w a s a g i f t f r o m R. A r e n d t , M e d i z i n i s c h e K l i n i k I , K l i n i k u m G r o ß h a d e r n , U n i v e r s i t y o f M u n i c h , M u n i c h , G e r m a n y ; a n t i b o d y G T - 2 3 w a s p r o v i d e d b y D r s . M . C a n t i n a n d G. T h i b a u l t , C l i n i c a l Research I n s t i t u t e , M o n t ­r e a l , Q u e b e c , C a n a d a . A m b e r l i t e X A D r e s i n a n d s o d i u m b o r o h y d r i d e w e r e o b t a i n e d f r o m Serva, H e i d e l b e r g , Ger­m a n y . N o r m a l goat , r a b b i t , a n d m o u s e sera a n d p e r o x i d a s e goat a n t i - m o u s e I g G w e r e o b t a i n e d f r o m N o r d i c B i o g e n z i a , B o c h u m , G e r m a n y . H y d r o g e n p e r o x i d e a n d p e r i o d i c a c i d w e r e o b t a i n e d f r o m M e r c k , D a r m s t a d t , G e r m a n y . P e r o x i ­dase goat a n t i - r a b b i t IgG, a m i n o e t h y l c a r b a z o l e , a n d a l l o t h e r c h e m i c a l s w e r e o b t a i n e d f r o m S i g m a , T a u f k i r c h e n , G e r m a n y .

Results Large intestine tissue samples preextracted by

XAD resin and purified by Sephadex G 50 gel filtra­

tion contained 0.4 pmol/g wet wt ANF immunoreactiv­

ity. Recovery rates of A N F 9 9 . 1 2 6 and proANF 2 . 1 2 6 were

27% and 21%, respectively. After Sephadex G 50 gel

filtration of the tissue extracts, the majority of ANF

immunoreactivity coeluted with the prohormone (Fig­

ure 1A). When the ANF fractions obtained by gel

filtration were subjected to reverse-phase HPLC, about

65% of the immunoreactivity coeluted with the prohor­

mone and 35% with A N F 9 9 . 1 2 6 (Figure IB).

The localization of ANF immunoreactivity was

analyzed by immunohistochemistry. The antibody

Toni III, directed against both the prohormone and

the A N F 9 9 . 1 2 6 segment, showed specific intracytoplas-

mic staining of single epithelial cells within the colon

mucosa (Figure 2A). On parallel sections, virtually

identical staining patterns were achieved using anti­

body GT-23 (Figure 2B) and antibody against chromo­

granin (Figure 2C). No immunostaining was seen at

other locations, particularly not in stromal or plasma

cells. Controls were always negative.

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426 GERBES ET A L . GASTROENTEROLOGY Vol . 101, No. 2

A N F 9 9 - 1 2 6 A N F 2 - 1 2 6

Figure 1. Characterization of A N F immunoreactivity.

A Separation of A N F immunoreact iv i ty i n extracted colonic tissue samples by Sephadex G 50 gel filtration. Calibration was performed w i t h a lbumin (VJ , v i tamin B 1 2 (V,), p r o A N F 2 . 1 2 6 > and A N F 9 9 . 1 2 6 . The majority of A N F immunoreact ivi ty elutes i n the range of p r o A N F 2 1 2 6 .

B. Characterization of the A N F immunoreac t iv i ty obtained by reverse-phase HPLC. About 65% of the immunoreact ivi ty coelutes w i t h p r o A N F 2 . 1 2 6 , whereas about 35% coelutes w i t h the C-terminal A N F 9 9 . 1 2 6 .

Discussion Initially the cardiac atria were considered to be

the major source of ANF synthesis. However, subse­quent reports found evidence for release of ANF in organs other than the heart (5,6), and recently the presence of ANF has been shown in the intestine of the guinea pig and the rat (10,11). Because the intestinal tract plays an important role in fluid regula­tion of the body, this finding, together with the demonstration of ANF binding sites in the gut (12,14,17), suggested a possible role of this hormone in mammalian intestinal fluid absorption. Indeed, in various species, ANF has been shown to influence intestinal fluid and electrolyte handling (13,15,16,27), whereas in others there was no effect (28,29).

In the present study we found evidence for the presence of ANF prohormone in enterochromaffin cells of the human large intestine. This assumption is based on the following findings:

1. Atrial natriuretic factor immunoreactivity could be determined in extracted and purified colonic tis­sue samples of human subjects.

2. High-performance liquid chromatography analysis showed elution of the majority of the ANF immu­noreactivity with the A N F prohormone. About one third of the immunoreactivity coeluting with

A N F 9 9 . 1 2 6 might be due to degradation of the prohor­mone, which occurs rapidly in the gut (10).

3. Immunohistochemical staining with two different antibodies showed the presence of ANF prohor­mone in cells of the large intestine. The same cell type was stained with the antibody against chro-mogranin, highly suggesting that ANF immunore­activity and most likely ANF synthesis is localized in enterochromaffin cells.

Enterochromaffin cells contribute to the endocrine regulation of the gut by containing and releasing various hormones (30,31), and the biosynthesis and secretion of ANF has been shown in chromaffin cells of the adrenal glands (32).

In the present study we examined colonic tissue, but we have also found ANF immunoreactivity in tissue extracts of the jejunum and the ileum (data not shown). Recently, immunohistochemical evidence for ANF was found in biopsy samples of various parts of the gastrointestinal tract, but characterization of the ANF immunoreactivity or the ANF-containing cells was not performed (33). Thus, the regional distribu­tion, cellular localization, and characterization of ANF immunoreactivity in other parts of the human intestine remains to be elucidated.

Altogether, our results for the first time suggest that

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August 1991 A N F PROHORMONE IM H U M A N INTESTINE 427

Figure 2. Immunohistochemistry in a sigmoid colonic tissue sample. A l l three figures show 5-fim parallel paraffin sections of a Bouin-fixed sigmoid colon tissue block with indirect immu-noperoxidase reactions stained with aminoethyl-carbazole and with nuclear hematoxylin coun-terstaining (original magnification X 5 6 0 ) .

A Ant ibody T o n i I I I , w h i c h recognizes both proANF and A N F 9 9 1 2 6 , shows strong specific i m -munostaining of cytoplasm of single cells w i t h i n the mucosa epi the l ium.

B. Ant ibody GT-23, w h i c h reacts w i t h proANF but not w i t h A N F 9 9 . 1 2 6 > shows the same pattern and distr ibut ion of specific immunosta ining as shown i n A

C. The antibody against chromogranin shows the specifically stained enterochromaffin cells w i t h a vir tual ly identical staining and dis t r ibut ion pat­tern as shown i n A and B, suggesting that proANF is present i n enterochromaffin cells of the human colon.

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428 GERBES ET A L . GASTROENTEROLOGY Vol . 101, No. 2

the large intestine is a site of ANF synthesis in humans. The physiological and pathophysiological implications of this finding could be of considerable interest.

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Received August 20, 1990. Accepted December 23, 1990. Address requests for reprints to: Alexander L. Gerbes, M . D . ,

Medizinische K l i n i k I I , K l i n i k u m Großhadern, Univers i ty of M u ­n i c h , Marchioninistraße 15, D 8000 München 70, Germany.

Supported by the Deutsche Forschungsgemeinschaft (GE 576) and by the Deutsche Gesellschaft für Verdauungs- u n d Stoff­wechselkrankheiten (Asche S t i p e n d i u m to A.L.G.) .

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August 1991 A N F PROHORMONE I N H U M A N INTESTINE 429

This study was presented at the 91st A n n u a l Meet ing of the American Gastroenterological Association, May 1990, San A n t o ­nio, Texas, and was published i n abstract f o r m (Gastroenterology 1990;98:A495).

The authors thank Dr. R. M . A r e n d t for his support , i n part icular for providing the antibody T o n i I I I . The technical assistance of M .

Bauch and M . Koch is greatly appreciated. They are grateful for the help of the colleagues of the Department of Surgery, i n particular Dr. Pratschke, for their cooperation i n obtaining the tissue samples. The authors also thank E. Greiner for the i l lustrat ions, S. Sperl for the photographs, and M . Raab for the preparation of the manu­script.