February 1998

Volume 114Issue 2p233-425



Full length article

  • Heme oxygenase 2 is present in interstitial cell networks of the mouse small intestine

    • Steven M. Miller,
    • Gianrico Farrugia,
    • Philip F. Schmalz,
    • Leonid G. Ermilov,
    • Mahin D. Maines,
    • Joseph H. Szurszewski
    Published in issue: February 1998
    Background & Aims: The interstitial cell (IC) network may be of fundamental importance in regulating gastrointestinal motility. Intestinal smooth muscle cells are depolarized in the absence of ICs, and there are no spontaneous slow waves. The messenger molecules between IC network and smooth muscle are unknown. Exogenous administration of CO relaxes the opossum internal anal sphincter and the guinea pig ileum, and it modulates potassium current and membrane potential of circular smooth muscle cells of the human jejunum.
  • Infection of Helicobacter pylori in gastric adaptation to continued administration of aspirin in humans

    • Jan W. Konturek,
    • Artur Dembinski,
    • Stanislaw J. Konturek,
    • Jerzy Stachura,
    • Wolfram Domschke
    Published in issue: February 1998
    Background & Aims: Involvement of Helicobacter pylori in aspirin-induced gastropathy and adaptation to aspirin remains unclear. The aim of this study was to compare gastric damage and adaptation after repeated exposures to acetylsalicylic acid in the same subjects before and after eradication of H. pylori. Methods: Before and after H. pylori eradication, 8 volunteers were given aspirin, 2 g/day during 14 days. Mucosal damage was evaluated by endoscopy and histological analysis of biopsy samples.
  • A low rate of reinfection following effective therapy against Helicobacter pylori in a developing nation (China)

    • Hazel M. Mitchell,
    • Pinjin Hu,
    • Yi Chi,
    • Min Hu Chen,
    • Yu Yuan Li,
    • Stuart L. Hazell
    Published in issue: February 1998
    Background & Aims: In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. The aim of this study was to determine the rate of reinfection and ulcer recurrence in Chinese patients cured of H. pylori and duodenal ulcer disease. Methods: One hundred eighty-four patients with duodenal ulcer disease shown by endoscopic examination (1 month) and 14C-urea breath test (3 months) after termination of treatment to have cleared their H.
  • Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum

    • Geert R. D'Haens*,
    • Karel Geboes,
    • Mark Peeters*,
    • Filip Baert*,
    • Freddy Penninckx§,
    • Paul Rutgeerts*
    Published in issue: February 1998
    Background & Aims: Postoperative recurrence of Crohn's disease may be triggered by agents in the fecal stream. The aim of this study was to examine intestinal mucosal inflammation induced by contact with intestinal fluids in surgically excluded ileum. Methods: The effects of infusion of intestinal luminal contents into excluded ileum in 3 patients with Crohn's disease who had undergone a curative ileocolonic resection with ileocolonic anastomosis and temporary protective proximal loop ileostomy were studied by histopathology and electron microscopy.
  • Proapoptotic gene BAX is frequently mutated in hereditary nonpolyposis colorectal cancers but not in adenomas

    • Osmar Kenji Yagi*,
    • Yoshimitsu Akiyama,
    • Tadashi Nomizu§,
    • Takeo Iwama,
    • Mitsuo Endo*,
    • Yasuhito Yuasa
    Published in issue: February 1998
    Background & Aims: The p53 and BAX genes have been linked to apoptosis. p53 was not frequently found to be mutated in colorectal carcinomas with a microsatellite mutator phenotype, but frame-shift mutations in a tract of eight guanines within BAX were frequently found in these carcinomas. To understand the roles of these genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we examined whether BAX mutations occur in adenoma and carcinoma specimens from patients with HNPCC and also determined the frequencies of p53 mutations.
  • Apc1638N: A mouse model for familial adenomatous polyposis–associated desmoid tumors and cutaneous cysts

    • Ron Smits*,
    • Willemien van der Houven van Oordt,
    • Arne Luz§,
    • ...
    • Cor Breukel*,
    • P.Meera Khan*,
    • Riccardo Fodde*
    Published in issue: February 1998
    Background & Aims: Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to the formation of multiple colorectal adenomas. Moreover, patients with FAP are at high risk of developing several extracolonic manifestations, including desmoids, cutaneous cysts, and tumors of the upper gastrointestinal tract. Although by definition desmoids are nonmalignant, because of their aggressive invasion of local structures, they represent one of the major causes of morbidity and mortality among patients with FAP.
  • Gastric mucosal smooth muscles may explain oscillations in glandular pressure: Role of vasoactive intestinal peptide

    • Ingrid Synnerstad,
    • Eva Ekblad,
    • Frank Sundler,
    • Lena Holm
    Published in issue: February 1998
    Background & Aims: Oscillating (3–7 cycles/min) high pressures in gastric glands during acid secretion suggest the existence of rhythmically contracting mucosal muscles. The aim of this study was to study vasoactive intestinal peptide (VIP), an inhibitory neurotransmitter in the gastrointestinal tract, in relation to mucosal muscles, glandular pressure, and blood flow. Methods: Rat, dog, and human mucosae were examined immunocytochemically for smooth muscle actin and VIP. Glandular pressure was measured using microelectrodes, red blood cell velocity (VRBC) was measured using a cross-correlation technique, and blood flow was measured using laser Doppler flowmetry in exposed gastric mucosa of thiobutabarbital sodium–anesthetized rats.
  • Genetic analysis of long-term Barrett's esophagus epithelial cultures exhibiting cytogenetic and ploidy abnormalities

    • M.Corinna Palanca-Wessels,
    • Michael T. Barrett,
    • Patricia C. Galipeau,
    • Katherine L. Rohrer,
    • Brian J. Reid,
    • Peter S. Rabinovitch
    Published in issue: February 1998
    Background & Aims: Progression to cancer in Barrett's esophagus occurs through an accumulation of cell cycle and genetic abnormalities that have been documented in vivo. To better study neoplastic evolution in Barrett's esophagus, the aim of this study was to establish in vitro cultures from preneoplastic tissues. Methods: Mechanical and enzymatic dissociation methods were used to initiate Barrett's epithelial cultures from endoscopic biopsy specimens, and the cells were characterized using flow-cytometric, cytogenetic, and molecular genetic analyses.
  • Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: A new approach

    • Gary A. Abrams,
    • Navin C. Nanda,
    • Eva V. Dubovsky,
    • Michael J. Krowka,
    • Michael B. Fallon
    Published in issue: February 1998
    Background & Aims: We have reported that contrast echocardiography is a sensitive screening test for the hepatopulmonary syndrome (HPS). However, contrast echocardiography lacks specificity because many cirrhotic patients have positive study results with normal arterial blood gases and therefore do not fulfill criteria for HPS. The aim of this study was to assess the role of macroaggregated albumin lung perfusion scans (MAA scans) in the diagnosis of HPS. Methods: MAA scans were performed in 25 patients with HPS, 25 cirrhotic patients without HPS, and 15 hypoxemic subjects with intrinsic lung disease alone.
  • Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis

    • D.Keith George,
    • Stefano Goldwurm,
    • Graeme A. Macdonald,
    • ...
    • Patrick J. Ward,
    • Elizabeth C. Jazwinska,
    • Lawrie W. Powell
    Published in issue: February 1998
    Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients. Methods: Fifty-one patients with NASH were studied. The presence of the Cys282Tyr mutation was tested in all patients, and the data were analyzed with respect to the histological grade of steatosis, inflammation, Perls' staining, hepatic iron concentration (HIC), and serum iron indices.
  • Genotypic/phenotypic correlations in genetic hemochromatosis: Evolution of diagnostic criteria

    • Paul C. Adams*,
    • Subrata Chakrabarti
    Published in issue: February 1998
    Background & Aims: The identification of a candidate gene for hereditary hemochromatosis in 69%–100% of patients with hemochromatosis has resulted in a diagnostic genotypic test (C282Y). The aim of this study was to reassess the phenotypic diagnostic criteria for hemochromatosis in patients homozygous for the C282Y mutation of the HFE gene. Methods: Transferrin saturation, ferritin, hepatic iron index, and iron removed by venesection were studied in C282Y++ homozygotes and C282Y−− putative homozygotes.
  • Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1

    • Maria Grazia Clemente,
    • Antonella Meloni,
    • Petra Obermayer-Straub,
    • Fulvia Frau,
    • Michael Peter Manns,
    • Stefano de Virgiliis
    Published in issue: February 1998
    Background & Aims: Liver disease has been described in 10%–15% of patients with autoimmune polyglandular syndrome type 1 (APS-1). After the discovery of cytochrome P450 1A2 (CYP1A2) as a hepatocellular autoantigen in liver-kidney microsomal autoantibody (LKM)-positive patients with APS-1, the investigation of antiliver antibodies was extended to 11 Sardinian patients with APS-1. Methods: Indirect immunofluorescence and Western blotting analysis were performed to study the antiliver antibodies. Results: Immunofluorescence revealed LKM antibodies in 3 patients with APS-1, 1 of whom died of fulminant hepatitis.
  • Members of the glutathione S-transferase gene family are antigens in autoimmune hepatitis

    • Józefa Wȩsierska-Gądek,
    • Rudolf Grimm,
    • Eva Hitchman,
    • Edward Penner
    Published in issue: February 1998
    Background & Aims: Autoimmmune hepatitis (AIH), a chronic liver disorder, can be classified into two subtypes on the basis of the specificities of circulating autoantibodies. Type I AIH is defined by antibodies to nuclear and/or smooth muscle antigens (SMA), and type II is characterized by antibodies to cytochrome P450IID6. There is an additional type of AIH characterized by antibodies to a cytosolic soluble liver antigen (SLA), which can occur alone or in combination with antinuclear antibodies and SMA.
  • Increased adrenomedullin levels in cirrhosis: Relationship with hemodynamic abnormalities and vasoconstrictor systems

    • Mónica Guevara,
    • Pere Ginès,
    • Wladimiro Jiménez,
    • ...
    • Vicente Arroyo,
    • Francisca Rivera,
    • Juan Rodés
    Published in issue: February 1998
    Background & Aims: Arterial vasodilation in cirrhosis may be related to increased circulating levels of vasodilators. This study was designed to assess the circulating levels of adrenomedullin, a recently described vasodilator peptide, in cirrhosis. Methods: Plasma adrenomedullin levels were measured in 17 healthy subjects and 34 cirrhotic patients. Hemodynamic parameters, renal function, and levels of vasoactive substances were also assessed. Results: Patients with ascites had increased adrenomedullin levels (289 ± 47 pg/mL) compared with healthy subjects and patients without ascites (135 ± 17 and 142 ± 32 pg/mL, respectively; P < 0.05).
  • Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: Endothelial dysfunction in portal hypertension

    • Don C. Rockey,
    • John J. Chung
    Published in issue: February 1998
    Background & Aims: Intrahepatic vascular resistance is regulated in part by the vasoconstricting and relaxing effects of compounds such as endothelin and nitric oxide (NO). Although the hepatic endothelium is likely to be a prominent source of NO via production by endothelial cell NO synthase (ecNOS), this isoform has not been described in sinusoidal endothelial cells (SECs). The aim of this study was to determine whether ecNOS is produced by SECs, and, if so, to determine whether ecNOS- (mRNA/protein) or SEC-dependent production of NO varies after liver injury.
  • Isoforms and splice variant of transforming growth factor β–binding protein in rat hepatic stellate cells

    • Wenrong Gong,
    • Sylke Roth,
    • Kristin Michel,
    • Axel M. Gressner
    Published in issue: February 1998
    Background & Aims: Hepatic stellate cells (HSCs) are one important source for transforming growth factor β (TGF-β). They produce TGF-β in a latent form associated with latency-associated peptide and latent TGF-β–binding protein (LTBP). This study was designed to investigate, on RNA and protein levels, which isoforms of LTBP and TGF-β are expressed in HSCs and myofibroblasts. Methods: HSCs isolated from rat liver were analyzed for LTBP and TGF-β at various times of culture during transdifferentiation into myofibroblasts using immunocytochemical staining, metabolic labeling and immunoprecipitation, reverse-transcription polymerase chain reaction (RT-PCR), and sequencing.
  • Regulation by hypoxia of methionine adenosyltransferase activity and gene expression in rat hepatocytes

    • Matias A. Avila,
    • M.Victoria Carretero,
    • E.Nelson Rodriguez,
    • Jose M. Mato
    Published in issue: February 1998
    Background & Aims: Oxygen supply to the hepatic parenchyma is compromised by long- or short-term ethanol consumption and pathological conditions such as cirrhosis. Impairment in the production of S-adenosyl-L-methionine, the major methylating agent, occurs during hypoxia. In this study, the molecular mechanisms implicated in the regulation of S-adenosyl-L-methionine synthesis by oxygen levels were investigated. Methods: Rat hepatocytes were isolated and cultured under normoxic (21% O2) or hypoxic (3% O2) conditions for different periods.
  • Endogenous glucocorticoids decrease the acinar cell sensitivity to apoptosis during cerulein pancreatitis in rats

    • Kenji Kimura,
    • Tooru Shimosegawa,
    • Hironobu Sasano,
    • ...
    • Masaru Koizumi,
    • Hiroshi Nagura,
    • Takayoshi Toyota
    Published in issue: February 1998
    Background & Aims: We recently showed that activation of the hypothalamus-pituitary-adrenal axis may mitigate the progress of acute pancreatitis. To clarify the mechanism, the role of endogenous glucocorticoids in pancreatic acinar cell death was examined. Methods: The occurrence of apoptosis was studied in adrenalectomized or sham-operated rats with or without cerulein-induced pancreatitis. The effects of RU38486, a glucocorticoid-receptor antagonist, on the survival of cultured acinar cells (AR42J) were also examined.
  • Secretin and vasoactive intestinal peptide receptors: Members of a unique family of G protein–coupled receptors

    • Charles D. Ulrich II*,
    • Martin Holtmann,
    • Laurence J. Miller
    Published in issue: February 1998
    GASTROENTEROLOGY 1998;114:382-397

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