Barrett's esophagus (BE), or specialized intestinal metaplasia, is a premalignant heterogeneous epithelium associated with reflux and an increased risk for adenocarcinoma. Since acid is a major component of refluxate, we investigated its effects ex vivo on cell differentiation as determined by villin expression; and on cell proliferation, as determined by tritiated thymidine incorporation and proliferating cell nuclear antigen expression. To mimic known physiological conditions, endoscopic biopsies of normal esophagus, BE, and duodenum were exposed, in organ culture, to acidified media (pH 3-5) either continuously, or as a 1-h pulse and compared with exposure to pH 7.4 for up to 24 h. Before culture, villin expression was noted in 25% of BE samples, and increased after 6 or 24 h of continuous acid to 50% or 83% of BE samples, respectively. Increased villin expression correlated with ultrastructural maturation of the brush border. In contrast, an acid-pulse followed by culture at pH 7.4, did not alter villin expression in BE. Moreover, continuous acid exposure blocked cell proliferation in BE, whereas, an acid-pulse enhanced cell proliferation, as compared to pH 7.4. Based on our ex vivo findings, we propose a model in which the diverse patterns of acid exposure in vivo may contribute to the observed heterogeneity and unpredictable progression to neoplasia of BE.
R C Fitzgerald, M B Omary, G Triadafilopoulos
Usage data is cumulative from September 2020 through September 2021.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.