Richard Peek

..Inactivation of PldD inhibited activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), indicating that H. pylori hemolytic phospholipases also harbor MAPK-activating properties...

..In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier...

..In this study, we analyzed the genome sequences of an H. pylori strain (98-10) isolated from a patient with gastric cancer and an H. pylori strain (B128) isolated from a patient with gastric ulcer disease...

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..pylori-host interactions will not only improve targeted diagnostic and therapeutic modalities, but may also provide insights into other diseases that arise within the context of pathogen-initiated inflammatory states...

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..These data implicate the cag island as a key mediator of pathogenic epithelial responses that may heighten the risk for gastric cancer...

..These findings indicate that a widely used and relatively safe class of drugs may represent a viable and effective anticancer strategy for a disease that causes over a half-million deaths per year...

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..Animal models have provided an invaluable resource with which to study H. pylori pathogenesis and carcinogenesis, and have permitted the development of a focused approach to selectively target human populations at high-risk of disease...

..pylori-infected individuals who can then be targeted for therapeutic intervention...

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..In addition to defining factors that mediate H. pylori-induced cancer, these results provide insight into mechanisms that may regulate the development of other malignancies arising within the context of inflammatory states...

..We previously determined that loss of amphiregulin (AR) promotes SPEM induced by acute oxyntic atrophy. We have now examined whether SPEM in the AR-/- mouse predisposes the stomach to gastric neoplasia...

..The effectiveness of eradication is dependent upon the timing of intervention, providing insights into mechanisms that may regulate the development of malignancies arising within the context of inflammatory states...

..Accumulating evidence suggests that both p73 and p63 play important roles in regulation of apoptosis, cell differentiation, and therapeutic drug sensitivity...

..These bacteria colonize a significant part of the world's population. We investigated the molecular mechanisms of p53 regulation in H pylori-infected cells...

..pylori-host interactions will not only improve targeted diagnostic and therapeutic modalities, but may also provide insights into other diseases that arise within the context of chronic pathogen infection...

..The combination of increased proliferation without a concordant increase in apoptosis may therefore contribute to the heightened retention of mutagenized cells, which over decades may increase the subsequent risk for gastric cancer...

..Collectively, these studies indicate that H. pylori-mediated induction of MMP-7 may serve to protect the gastric mucosa from pathophysiologic processes that promote carcinogenesis...

..cag- strains or uninfected persons. These results indicate that H. pylori-induced dysregulation of beta-catenin-dependent pathways may explain in part the augmentation in the risk of gastric cancer conferred by this pathogen...

..Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation...

..Since H. pylori inhibits the gastric epithelium of half of the world, it is crucial that we continue to gain understanding of host and microbial factors that increase the risk of developing more severe clinical outcomes...

..In vitro, hpyIM expression was higher during log-phase growth and was required for normal bacterial morphology, suggesting that hpyIM expression may be growth-phase regulated within the gastric niche...

..Gastric cancer incidence in African Americans is twice that of whites, and differing prevalence of Helicobacter pylori strain-specific isolates may help explain the disparity...

..Polymorphisms of interleukin-1B (IL1B) and its receptor antagonist (IL1RN) genes have been inconsistently associated with gastric cancer risk. We examined these associations by performing meta-analyses...

..pylori proteins to use in vaccine development and for screening persons infected with strains most likely to induce severe disease...

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..In contrast, in the high-risk area, eosinophils might promote a T helper 1-type response leading to progression of precancerous lesions...

..In contrast to many chronic inflammatory diseases in which IL-17RA signaling promotes an inflammatory response, IL-17RA signaling down-regulates the chronic mononuclear inflammation elicited by H. pylori infection...

..These results indicate that CagA variants are linked with premalignant lesions in distinct populations and that epithelial responses to these strains are selective based upon locale...

..These results indicate that selective and coordinated induction of mmp-7 expression by H. pylori cag(+) isolates may explain in part the augmentation in gastric cancer risk associated with these strains...

..Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response...

..Inactivation of HP0638 does not alter epithelial responses mediated by the cag island in vitro. Assessment of apoptosis in vitro identified a group of H. pylori isolates that induce more severe gastric inflammation and atrophy...

..Helicobacter pylori inhabits a highly restricted ecological niche in the human gastric mucosa. Microbial gene expression in the context of persistent infection remains largely uncharacterized...

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..pylori-infected persons may result from strain-dependent variations in VacA structure...

..pylori cag(+) strains induce up-regulation of a cognate cellular receptor in vitro and in vivo in a cag-dependent manner, representing the first evidence of regulation of an H. pylori host receptor by the cag pathogenicity island...

..The aim of the present study was to determine whether H. pylori could up-regulate the expression of the epidermal growth factor receptor (EGFR), a critical gene in the carcinogenic process...

..Because EGFR signaling regulates cell survival, we investigated whether activation of EGFR following H pylori infection promotes gastric epithelial survival...

..pylori-infected mice. These results indicate that DAF may regulate H. pylori-epithelial cell interactions relevant to pathogenesis...

..In this issue, Mimuro et al. shed light on mechanisms by which Helicobacter pylori attenuates apoptosis in the gastric epithelium to facilitate its persistence within the human stomach...

..To assess possible involvement of HP0222 in acid resistance, we constructed and assayed an H. pylori HP0222 null mutant. We propose that HP0222 is a novel transcriptional regulator in H. pylori...

..We determined whether MLCK was activated by H pylori and defined the mechanisms through which such activation dysregulates gastric epithelial barrier function...

..pylori-induced cell migration. These results indicate that PI3K-AKT signaling regulates pathophysiologic responses to H. pylori that may lower the threshold for carcinogenesis...

..It is speculated that inappropriate waning of the innate immune response during early stages of infection may be a factor that contributes to H. pylori persistence...

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..pylori proteome. Such subproteomes in the public domain will be effective instruments for identifying new virulence factors and antigens of potential diagnostic and/or curative value against infections with this important pathogen...

..In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer...

..A low G+C content of these two genes suggests they were acquired by horizontal transfer events...

..pylori-induced NF-kappaB activity, resulting in IL-8 production...

..Although a direct function for hrgA in virulence could not be demonstrated, our data indicate that hrgA is a strain-specific gene that might be associated with gastric cancer among H. pylori isolates from Asian patients...

..Differential induction of MMP-7 by H. pylori cag(+) isolates may explain in part the augmentation in gastric cancer risk associated with these strains...

..pylori infection. Cardia intestinal metaplasia is associated with H. pylori-related cardiac inflammation and intestinal metaplasia elsewhere in the stomach...

..It has also been linked, less strongly, to cardiovascular disease. The mechanisms by which certain strains of H pylori induce platelet aggregation through interactions with platelet glycoprotein Ib have been previously described...

..pylori flagellin plays no role in activating epithelial orchestration of inflammation. We conclude that H. pylori evades TLR5-mediated detection, which may contribute to its long-term persistence in individual hosts...

..These results provide more insight into how H. pylori and MAPK modulate AP-1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions...

..To determine the role of interleukin (IL)-17 in gastric ulcerogenesis...

..Stimulation of Reg1 by H. pylori required the virulence factor CagA. These data indicate that expression of the putative growth factor Reg1 is controlled through separate promoter elements by gastrin and Helicobacter...

..As a pathogen with a paucity of regulatory proteins, this dual regulation indicates that SabA expression is a tightly regulated process in H. pylori infection...

..These findings indicate that within an individual host, intragenomic recombination between H. pylori repetitive DNA produces strain variants differing in their signals to host cells...

..The INS-GAS model is effective for investigating discrete host-microbial interactions that culminate in gastric cancer within the context of biologic conditions induced by H. pylori...

..Apparent differences between African-American and Caucasian-American H. pylori gene pools may bear on our understanding of H. pylori transmission and disease outcome...

..To identify the bacterial flora in conditions such as Barrettos esophagus and reflux esophagitis to determine if they are similar to normal esophageal flora...

..pylori'-induced injury and carcinogenesis in vivo. This study will help to identify people who are at great risk for stomach cancer. This will greatly improve diagnosis and therapy of H. pylori infections. ..

..py/ori-induced B-catenin activation. 3. To define differences in epithelial molecular responses to carcinogenic H. pylori versus mutant strains using a transgenic murine model of gastric cancer. ..

..pylori'-induced injury and carcinogenesis in vivo. This study will help to identify people who are at great risk for stomach cancer. This will greatly improve diagnosis and therapy of H. pylori infections. ..

..PUBLIC HEALTH RELEVANCE: These studies will define bacterial and host factors that influence gastric cancer. Such findings may help to identify H. pylori-infected persons at high risk for gastric cancer, who thereby warrant therapy. ..

..We are encouraged by our ability to successfully train academic investigators. 6 of the 8 individuals currently in training are currently planning careers in academic medicine ..

..pylori-induced ?-catenin activation. 3. To define differences in epithelial molecular responses to carcinogenic H. pylori versus mutant strains using a transgenic murine model of gastric cancer. ..

..pylori-induced carcinogenesis and facilitate identification of potential therapeutic targets, but may also provide insights into other malignancies that arise within the context of inflammatory states. ..

..2)To identify and functionally characterize PPAR( target genes and microbially-induced NF-?B-regulated genes that are suppressed by PPAR(, activation using an in vitro model of intestinal epithelial cell inflammation. ..

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..pylori'-induced injury and carcinogenesis in vivo. This study will help to identify people who are at great risk for stomach cancer. This will greatly improve diagnosis and therapy of H. pylori infections. ..