• Helicobacter pylori regulates the expression of inhibitors of DNA binding (Id) proteins by gastric epithelial cells.

      Manzo, Barbara Ada; Crabtree, Jean E; Fiona Campbell, M; Tweedle, David; Potten, Christopher S; Bajaj-Elliott, Mona; Sanderson, Ian R; Wilson, James W; Research Centre for Gastroenterology, Institute of Cell and Molecular Sciences, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, 4 Newark Street, London E1 2AT,UK. (2006-04)
      Id transcription factors control proliferation, differentiation and apoptosis by inhibiting the DNA binding of basic helix-loop-helix transcription factors. Increased expression of Id proteins promotes proliferation, inhibits differentiation, and is associated with intestinal tumorigenesis. We aimed to determine how Helicobacter pylori may alter the expression of Id proteins by gastric epithelial cells: it was hypothesised that H. pylori, a known carcinogen, would result in increased expression of one or more Id family members. In vitro and in vivo models of infection were employed, including treatment of AGS gastric epithelial cells with wild-type H. pylori strains, 60190 and SS1, and Mongolian gerbils infected with H. pylori SS1. A small cohort of human gastric mucosal biopsies was also examined. Treatment of AGS cells with H. pylori resulted in down-regulation of Id1 and Id3. Unexpectedly, expression of the main target of Id proteins, the basic helix-loop-helix transcription factor E2A, was also suppressed, with an associated decrease in E-box binding activity. In contrast, H. pylori induced the expression of the CDK inhibitor p21(WAF-1/cip1), and the homeobox transcription factor, Cdx2, an early marker of intestinal metaplasia of the stomach epithelium. Gastric epithelium from H. pylori-infected gerbils demonstrated similar changes, with decreased Id2, Id3 and E2A, and elevated p21(WAF-1/cip1) expression. In human gastric epithelium also, H. pylori infection was associated with reduced Id and E2A expression. In conclusion, H. pylori alters the expression of Id proteins, in vitro and in vivo; it is hypothesised that these changes contribute to H. pylori-associated pathologies.
    • Testing for Helicobacter pylori in primary care: trouble in store?

      Foy, R; Parry, J M; Murray, L; Woodman, Ciaran B J; Centre For Cancer Epidemiology, University of Manchester, Christie Hospital NHS Trust, Withington. (1998-05)
      STUDY OBJECTIVE: To assess the role of testing for Helicobacter pylori in the management of dyspeptic patients in primary care. DESIGN: Selective review of literature frequently quoted to support use of H pylori testing. MAIN RESULTS: Testing for H pylori and referral of only positive cases for endoscopy aims to reduce the number of "unnecessary" endoscopies. Patients with negative results may receive short-term reassurance and subsequently place fewer demands on health services. However, studies to date have only assessed this practice in secondary care settings. Given the relatively high prevalence of both dyspepsia and H pylori infection, the transfer of this practice to primary care may lead to a paradoxical increase in endoscopy referrals. Identification of H pylori and prescribing of eradication treatment also aims to reduce endoscopy referrals. No primary care trials have yet assessed this approach. Given that fewer than one in four of dyspeptic patients have peptic ulceration, a high proportion may fail to respond to eradication treatment and subsequently require referral for endoscopy. The longer term clinical and psychosocial sequelae of treating or labelling patients with an infection associated with gastric cancer remain unknown. CONCLUSIONS: Given uncertainty concerning the possible adverse effects of H pylori testing in primary care, we suggest a moratorium on its use in this setting until results from relevant clinical trials become available.