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Factor CagA (factor + caga)

Distribution by Scientific Domains
Medical Sciences80%

Kinds of Factor CagA

  • virulence factor caga
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    Selected Abstracts

    Is the Association Between Helicobacter pylori and Gastric Cancer Confined to CagA-Positive Strains?

    HELICOBACTER, Issue 3 2004
    Maria Held
    ABSTRACT Background., Infection with Helicobacter pylori is associated with an increased risk of gastric cancer. Several studies have indicated that the association differs with strain type. We aimed to find out if infection with strains lacking the virulence factor CagA is linked to gastric cancer risk. Materials and methods., In a hospital-based case,control study, we collected sera from 100 case patients with a newly diagnosed gastric adenocarcinoma and 96 control patients with diseases unrelated to H. pylori status. Antibodies to H. pylori were analyzed by enzyme-linked immunosorbent assay (ELISA), and antibodies to CagA were detected by immunoblot. Logistic regression was used to obtain odds ratios (ORs) as estimates of relative risk, adjusted for potential confounding. Results., Among the case patients, 81% were ELISA positive and 86% had antibodies to CagA. The corresponding numbers among the controls were 58% and 55%, respectively. ELISA positivity was associated with an increased risk of gastric adenocarcinoma compared to ELISA negativity (OR for gastric cancer regardless of site 3.9, 95% CI 1.9,8.2). The OR was 7.4 (95% CI 3.3,16.6) for CagA-positive relative to CagA-negative subjects. Among ELISA-positive subjects the presence of CagA antibodies increased the risk 3.6 times (95% CI 1.2,11.1). ELISA-positive CagA-negative infections were associated with a fourfold increased risk (OR = 4.2, 95% CI 1.0,17.0) compared to no infection (ELISA-negative and CagA-negative). Conclusions., Although patients with antibodies to CagA have the greatest risk of developing gastric cancer, those with CagA-negative infections run a significantly greater risk than uninfected persons. [source]

    Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA -positive Helicobacter pylori pathogenicity

    CANCER SCIENCE, Issue 5 2004
    Megumi Higuchi
    RNA interference (RNAi) is a newly described biological phenomenon mediated by small interfering RNA (siRNA) that targets mRNA for degradation by cellular enzymes and has become a powerful method for studying gene functions in mammalian systems. The development of systems for inducing siRNA expression should enable examination of acute loss-of-function phenotypes in a cell of interest without the need to consider lethality or epigenetic adaptation of cells. We describe in this report an inducible siRNA expression system made by combined utilization of the RNA polymerase III-dependent promoter H1 and the bacterial lac repressor. Using this system, we established AGS gastric epithelial cells in which expression of SHP-2, a cellular tyrosine phosphatase known to specifically bind the Helicobacter pylori virulence factor CagA, is conditionally and reversibly silenced by the lactose analog isopropyl-1-thio-,-D-galactopyranoside (IPTG). Upon expression in AGS cells, CagA provoked a morphological transformation, termed the hummingbird phenotype, which is associated with CagA virulence. This morphogenetic activity of CagA was totally abolished when SHP-2 expression was silenced by inducible siRNA expression in AGS cells. Our results indicate that SHP-2 is a critical downstream effector of H. pylori CagA. The conditional gene silencing system described here should become a powerful tool for investigating the roles of cancer-related genes through a reversed genetic approach. [source]

    Helicobacter pylori Infection and Gastroesophageal Reflux in a Population-Based Study (The HUNT Study)

    HELICOBACTER, Issue 1 2007
    Helena Nordenstedt
    Abstract Background and Aim:, It has been suggested that Helicobacter pylori infection may prevent gastroesophageal reflux, possibly through gastric atrophy. Since, however, previous results are contradictory and no population-based studies are available, the relationship between H. pylori and reflux remains uncertain. The aim of this study was to investigate this relationship in a population-based, nested, case-control study. Methods:, From a cohort of 65,363 individuals, representing 71.2% of the adult population in the Norwegian county of Nord-Trondelag, we randomly selected 472 persons with recurrent reflux symptoms (cases) and 472 without such symptoms (controls). Occurrence of H. pylori and its virulence factor cagA was determined serologically, using an immunoblot assay. Gastric atrophy was assessed through serum levels of pepsinogen I. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for potential confounding factors, represented relative risks. Results:,H. pylori infection was not associated with a decreased risk of reflux symptoms (OR 1.1, 95% CI 0.8,1.6), irrespective of positive cagA status (OR 1.1, 95% CI 0.8,1.5). Gastric atrophy reduced the risk of reflux symptoms (OR 0.2, 95% CI 0.0,0.6). Infection with H. pylori entailed a ninefold increase in the risk of gastric atrophy compared to non-infection (OR 8.9, 95% CI 2.0,39.9). Conclusions:,H. pylori infection, irrespective of cagA status, did not affect the occurrence of reflux symptoms in this population-based setting. Infected individuals are at increased risk of gastric atrophy, which in turn reduces reflux symptoms, but due to the low frequency of gastric atrophy among infected individuals overall, there was no association with reflux symptoms on a population level. [source]

    Pathogenesis of Helicobacter pylori Infection

    HELICOBACTER, Issue 2008
    Javier Torres
    Abstract The clinical outcome of Helicobacter pylori infection is determined by a complex scenario of interactions between the bacterium and the host. The main bacterial factors associated with colonization and pathogenicity comprise outer membrane proteins including BabA, SabA, OipA, AlpA/B, as well as the virulence factors CagA in the cag pathogenicity island (cagPAI) and the vacuolating cytotoxin VacA. The multitude of these proteins and allelic variation makes it extremely difficult to test the contribution of each individual factor. Much effort has been put into identifying the mechanism associated with H. pylori -associated carcinogenesis. Interaction between bacterial factors such as CagA and host signal transduction pathways seems to be critical for mediating the induction of membrane dynamics, actin-cytoskeletal rearrangements and the disruption of cell-to-cell junctions as well as proliferative, pro-inflammatory and antiapoptotic nuclear responses. An animal model using the Mongolian gerbil is a useful system to study the gastric pathology of H. pylori infection. [source]

    Interleukin-1 receptor phosphorylation activates Rho kinase to disrupt human gastric tight junctional claudin-4 during Helicobacter pylori infection

    CELLULAR MICROBIOLOGY, Issue 5 2010
    Tamia K. Lapointe
    Summary Helicobacter pylori infects more than half of the human population worldwide. In the absence of treatment, this persistent infection leads to asymptomatic gastritis, which in some cases can progress into gastric ulcers and adenocarcinomas. The host,microbial interactions that govern the clinical outcome of infection remain incompletely understood. H. pylori is known to disrupt gastric epithelial tight junctions, which may represent a significant component of disease pathogenesis. The present study demonstrates that H. pylori disrupt epithelial tight junctional claudin-4 in a Rho kinase (ROCK)-dependent manner in human gastric epithelial (HGE-20) cell monolayers, independently of the virulence factors CagA and VacA, and without altering claudin-4 transcription. In the same epithelial cell model, interleukin (IL)-1,, mediated a similar ROCK-dependent pattern of tight junction disruption. Further experiments revealed that H. pylori infection induced IL-1 receptor type I (IL-1RI) phosphorylation, independently of epithelial secretion of its endogenous ligands IL-1,, IL-1, or IL-18. Finally, inhibition of IL-1RI activation prevented H. pylori -induced ROCK activation and claudin-4 disruption. Taken together, these findings identify a novel pathophysiological mechanism by which H. pylori disrupts gastric epithelial barrier structure via IL-1RI-dependent activation of ROCK, which in turn mediates tight junctional claudin-4 disruption. [source]