Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.
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PMID:Experimental columnar metaplasia in the canine oesophagus. 334 94

Data on the frequency of regression of Barrett's esophagus after medical therapy or antireflux surgery in adult patients are conflicting; these data, with regard to pediatric age, where Barrett's esophagus is considered rare, are scarce and disappointing after antireflux surgery. We report a 4-month-old infant affected by severe reflux esophagitis who developed a junctional-type Barrett's epithelium. Histochemical procedures to detect mucin pattern were also carried out. The regression of Barrett's esophagus was observed 4 months after antireflux surgery whereas medical therapy had been unsuccessful. We suggest that esophageal biopsy should also be performed in the presence of severe esophagitis. Longer follow-up observations of other patients may clarify the role of antireflux surgery when Barrett's esophagus complicates gastroesophageal reflux (GER).
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PMID:Barrett's esophagus in an infant: a long standing history with final postsurgical regression. 339 49

Columnar epithelium-lined esophagus is an acquired phenomenon arising secondarily to chronic mucosal injury from gastroesophageal reflux. This report documents 11 children with complications of reflux and the histologic finding of gastric mucosa in the esophagus. Five children had strictures, one requiring esophageal replacement and four treated by antireflux surgery followed by sleeve-resection of a short fibrotic stricture. Specimens from two patients showed mild dysplasia and from six others slight nuclear atypia. Intestinal metaplasia was apparent in one case on routine histology and was revealed in six other cases by mucin histochemical strains. The significance of the histopathologic findings is discussed in the context of possible malignant potential.
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PMID:Barrett's esophagus in children: a histologic and histochemical study of 11 cases. 355 55

Aggressive factors operating within the esophageal lumen during gastroesophageal reflux are balanced by adequately mobilized protective mechanisms. Esophageal mucosal protection operates at three different although complementary dimensions: (1) preepithelial, (2) epithelial and (3) postepithelial. Since aggressive factors predominantly operate within the esophageal lumen, preepithelial defense is pivotal in mucosal protection. The preepithelial barrier is significantly enhanced by the quantity and the quality of salivary organic components such as salivary mucin, nonmucin protein, salivary epidermal growth factor (EGF) and salivary prostaglandin E2. The rate of secretion of salivary mucin, nonmucin protein and EGF under the impact of intraesophageal mechanical (bolus) and chemical (HCl/pepsin) stimulation, mimicking the natural gastroesophageal reflux scenario, is significantly impaired in patients with RE, whereas the rate of salivary PGE2 output remains essentially unchanged. Salivary secretory response to esophageal mechanical and chemical stimuli in terms of organic components, mediated by the esophagosalivary reflex pathway, exhibits a significant impairment in patients with reflux esophagitis.
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PMID:Do salivary organic components play a protective role in health and disease of the esophageal mucosa? 755 68

The integrity of the oesophageal mucosa depends upon an equilibrium between aggressive factors, predominantly acid and pepsin, and protective mechanisms. Protective mechanisms operate within the oesophageal mucosa as pre-epithelial, epithelial and post-epithelial defences. Only the protective components of the oesophageal pre-epithelial defence can be tested in vivo in humans. It has been recently demonstrated that human oesophageal submucosal glands elaborate mucous secretion rich in bicarbonate and non-bicarbonate buffers, mucin, prostaglandin E(2), epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha). This oesophageal secretion, accompanied by similarly protective factors within the swallowed saliva, defines the protective potential of the oesophageal pre-epithelial defence that exists in the form of a mucus-buffer layer covering the oesophageal mucosa and which retards the back-diffusion of hydrogen ions. It has also been demonstrated that patients with severe erosive reflux oesophagitis exhibit qualitative impairment in both the salivary and oesophageal components of the oesophageal pre-epithelial defence. Furthermore, patients with endoscopically negative gastro-oesophageal reflux disease have a significantly stronger oesophageal pre-epithelial defence than patients with erosive reflux oesophagitis. On the other hand, African-Americans, who are less likely to develop erosive reflux oesophagitis, have a stronger oesophageal pre-epithelial defence than do Caucasians. The salivary component of the oesophageal pre-epithelial defence can be enhanced by mastication and the administration of cisapride, whereas oesophageal secretion can only be significantly augmented by cisapride.
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PMID:Mechanisms of oesophageal mucosal defence. 1100 4

Barrett's esophagus is a complication of chronic gastroesophageal reflux disease and can be diagnosed when there is an endoscopic abnormality in which a biopsy shows evidence of specialized columnar epithelium, characterized by the presence of acid mucin-containing goblet cells. Much of the controversy in this body of literature relates to the complex anatomy of the esophagogastric junction and the difficulty in precisely identifying this landmark at endoscopy. By definition, in Barrett's esophagus, the squamocolumnar junction is proximal to the esophagogastric junction. Although fundic-type or cardiac-type (junctional) columnar epithelium may be present in Barrett's esophagus, it is only the presence of specialized columnar epithelium that is diagnostic of this condition. Patients with Barrett's esophagus are at risk of progressing to esophageal dysplasia and adenocarcinoma. There are several problems with using dysplasia as a marker for increased cancer risk in these patients, including problems with sampling error and intra- and interobserver variation in the recognition of dysplasia. It may be difficult to distinguish regenerative epithelial changes from dysplasia, low-grade from high-grade dysplasia, and high-grade dysplasia from intramucosal adenocarcinoma. Finally, there are relatively few prospective data evaluating the natural history of high-grade dysplasia. The management of patients with Barrett's-related dysplasia is controversial and varies from institution to institution. Future emphasis should be on cost-effective techniques for sampling as much of the esophageal mucosa as possible in patients who are at the highest risk of progressing to dysplasia and adenocarcinoma. Identification of biomarkers that identify such patients before the histologic recognition of dysplasia will be an area of intensive research.
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PMID:Barrett's esophagus and Barrett's-related dysplasia. 1269 97

Abnormal gastro-oesophageal reflux and bile acids have been linked to the presence of Barrett's oesophageal premalignant lesion associated with an increase in mucin-producing goblet cells and MUC4 mucin gene overexpression. However, the molecular mechanisms underlying the regulation of MUC4 by bile acids are unknown. Since total bile is a complex mixture, we undertook to identify which bile acids are responsible for MUC4 up-regulation by using a wide panel of bile acids and their conjugates. MUC4 apomucin expression was studied by immunohistochemistry both in patient biopsies and OE33 oesophageal cancer cell line. MUC4 mRNA levels and promoter regulation were studied by reverse transcriptase-PCR and transient transfection assays respectively. We show that among the bile acids tested, taurocholic, taurodeoxycholic, taurochenodeoxycholic and glycocholic acids and sodium glycocholate are strong activators of MUC4 expression and that this regulation occurs at the transcriptional level. By using specific pharmacological inhibitors of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, protein kinase A and protein kinase C, we demonstrate that bile acid-mediated up-regulation of MUC4 is promoter-specific and mainly involves activation of phosphatidylinositol 3-kinase. This new mechanism of regulation of MUC4 mucin gene points out an important role for bile acids as key molecules in targeting MUC4 overexpression in early stages of oesophageal carcinogenesis.
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PMID:Transcriptional regulation of human mucin MUC4 by bile acids in oesophageal cancer cells is promoter-dependent and involves activation of the phosphatidylinositol 3-kinase signalling pathway. 1458 90

Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.
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PMID:Stress and the gastrointestinal tract. 1574 Apr 74

Cervical inlet patch (CIP) is defined by the presence of gastric mucosa within the first few centimeters of the esophagus. Several endoscopic series have demonstrated a frequent association of CIP with Barrett's esophagus (BE) suggesting a pathogenetic link. A histochemical study reporting the presence of acid mucin in CIP, including sulfomucin, supports this hypothesis. We evaluated mucin core protein expression and cytokeratins 7 and 20 (CK7/CK20) pattern in biopsies of CIP, normal antrum, and BE to comment on a possible relationship of CIP with BE. We observed that both lesions have similar cytokeratin patterns with mixed CK7/CK20 reactivity on the surface and pits and lone CK7 positivity in the glands. MUC5AC was strongly expressed on the surface and pits but not in the glands of CIP and antral mucosa. Within BE, MUC5AC positivity was noted not only on the surface and pits but also in the glands. MUC6 similarly decorated the glands of CIP and BE. MUC2 was expressed rarely in CIP with goblet cells but conspicuously on the surface and pits of BE. MUC5B was seen in both CIP and BE and rarely in the antral mucosa. The similarities between CIP and BE but not with normal antral mucosa fits with the hypothesis that both lesions may originate from submucosal esophageal mucous glands. Two pathogenetic pathways can be entertained: focal upper esophageal mucosal misdevelopment in pediatric population and patchy metaplastic replacement of squamous mucosa in adults with gastroesophageal reflux disease.
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PMID:Cytokeratins 7 and 20 and mucin core protein expression in esophageal cervical inlet patch. 1576 95

Barrett's esophagus is a premalignant condition associated with gastroesophageal reflux disease, and consists of mucosa with a metaplastic columnar epithelium (specialized columnar epithelium). In this study, we examined the expression of mucin and the Ki-67 labeling index (LI) in 15 cases of esophageal Barrett's adenocarcinoma, and clarified the significance of incomplete intestinal metaplasia of Barrett's mucosa as a premalignant lesion. Gastric mucin (MUC5AC, HGM, and/or MUC6) was detected in 93.3% of the adenocarcinomas, while MUC2 and CD10 (markers of intestinal phenotypes) were detected in 73.3% and 46.2%, respectively. The Ki-67 LI was 34.1% in Barrett's adenocarcinoma. In all cases, gastric mucin was found in the non-neoplastic Barrett's mucosa around the adenocarcinoma. MUC2 was detected in 86.7% of proximal non-neoplastic mucosa and 100% of distal non-neoplastic mucosa, while CD10 was found in 20.0% of proximal non-neoplastic mucosa and 40.0% of distal non-neoplastic mucosa of Barrett's adenocarcinoma. In conclusion, Barrett's esophageal mucosa with intestinal metaplasia and a high Ki-67 LI is suggested to be more important as a premalignant lesion, and predominantly found in the proximal rather than distal region of Barrett's esophagus.
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PMID:Mucin expression and proliferating cell index of esophageal Barrett's adenocarcinoma. 1607 42


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