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)

Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to malignant degeneration is clinically important. Glutathione s-transferase (GST)-pi belongs to a class of protective enzymes whose activity has been shown to be much lower in Barrett's metaplasia than in the normal esophagus, where this form of GST is predominant. In the studies described here, using immunocytochemical analysis, we observed higher levels of cytoplasmic GST-pi protein in normal esophageal mucosa than in Barrett's metaplasia. Using northern blot analysis, we also observed lower GST-pi mRNA levels in Barrett's metaplasia than in normal esophagus or adenocarcinomas from the same patients. Using as model systems three Barrett's adenocarcinoma cell lines and short-term organ culture of freshly resected normal esophagus and Barrett's metaplasia, dose-dependent induction of GST-pi mRNA was observed by using butylated hydroxyanisole and dexamethasone. GST-pi mRNA in Barrett's metaplasia was induced up to 2.5-fold with 60 microM butylated hydroxyanisole and nearly fivefold with 320 nM dexamethasone after 24 h. These studies demonstrate the ability to induce protective GST-pi in Barrett's metaplasia and may suggest a mechanism for future chemoprevention studies in patients with this type of epithelium, which is at high risk for malignant degeneration.
Mol Carcinog 1999 Feb
PMID:Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines. 1007 40

Villin is an actin-binding cytoskeletal protein required for brush-border formation in the normal small intestinal and renal proximal tubule epithelium. Villin is a marker of cell differentiation in small intestinal and renal cell lineages, and recent studies have shown villin to be highly expressed in 100% of intestinal-type Barrett's metaplasias. This epithelium is the single greatest risk factor for developing esophageal adenocarcinoma and arises when the normal esophageal squamous epithelium is replaced by a small intestine-like columnar epithelium after damage by chronic gastroesophageal reflux. In intestinal-type Barrett's metaplasia, the villin protein exhibits a highly characteristic staining pattern in which strong apical, brush-border staining of columnar epithelial cells is observed. In this study, the ability to identify intestinal metaplastic cells by using this distinct villin staining pattern was examined in endoscopic esophageal brushings from patients with confirmed Barrett's metaplasia. Esophageal brushings from 81% (17 of 21) of patients with Barrett's metaplasia demonstrated individual columnar cells with the characteristic villin staining pattern, whereas all normal esophageal squamous cells, blood cells, and gastric columnar cells were negative for villin expression. Northern blot analysis demonstrated villin mRNA expression in Barrett's metaplasia but not in the normal squamous esophagus or gastric mucosa from the same patients. The combined use of villin immunohistochemical analysis and esophageal brush cytology may provide a simple and effective method of detecting intestinal-type Barrett's metaplasia in patients at higher risk for developing this epithelium, such as those experiencing chronic gastroesophageal reflux symptoms.
Mol Carcinog 1999 Feb
PMID:Identification of intestinal-type Barrett's metaplasia by using the intestine-specific protein villin and esophageal brush cytology. 1007 41

MIB-1, a proliferation marker may be useful in the assessment of esophageal biopsy specimens for gastroesophageal reflux disease (GERD). Forty-five hematoxylin and eosin-stained esophageal biopsy specimens were histologically assessed for basal zone height, papillary length, and inflammatory cell infiltrate and classified as 10 normal and 35 esophagitis. The percentage of MIB-1-positive area (MIB-1% area) was measured on immunostained sections using image analysis (CAS 200) in the basal half of well-oriented areas and adjacent to five cross-sectioned papillae (c-pap) in poorly oriented areas. The cell layer of the MIB-1-positive cell furthest from the basal layer of the c-pap was also noted. MIB-1% area was significantly greater in both well- and poorly oriented areas of esophagitis biopsy specimens compared with normal biopsy specimens. MIB-1 positivity in the basal half and c-pap were correlated (r = 0.43, p = 0.017). MIB-1 expression correlated with basal zone height and eosinophil infiltrate (r = 0.61, p < 0.001; r = 0.32, p = 0.03, respectively). The cell layer with positive cells furthest from c-pap in normal and esophagitis biopsy specimens was two and six layers, respectively. Using 31% as a threshold to detect abnormal findings, the MIB-1 sensitivity/specificity and positive predictive value in the basal half and c-pap were 86, 70, 91% and 80, 80, 94%, respectively. In summary, MIB-1 staining correlates with basal zone hyperplasia and eosinophil infiltrate seen in GERD. MIB-1 staining can be assessed both in well- and poorly oriented areas as MIB-1% areas. Alternatively simply finding MIB-1 positive cells more than three cell layers from the basal layer is abnormal and consistent with GERD.
Appl Immunohistochem Mol Morphol 2002 Jun
PMID:Use of MIB-1 in the assessment of esophageal biopsy specimens from patients with gastroesophageal reflux disease in well- and poorly oriented areas. 1205 30

Zenker's diverticulum (ZD) is a rare pathology, with a prevalence of between 0.01% and 0.11%. Definitive diagnosis of ZD can be accomplished by contrast radiographic examination (barium oesophagogram, BE); oesophageal manometry (ME) is recommended mainly for those patients suffering from dysphagia and/or gastro-oesophageal reflux. The aims of the present study were to assess whether oropharyngo-oesophageal scintigraphy (OPES) is able (a) to visualise ZD and (2) to demonstrate the corresponding alteration in the swallowing phases. We studied 16 patients (nine male, seven female, mean age 67.4 years), and 17 healthy volunteers (ten male, seven female, mean age 53 years) as a control group. All the patients underwent ME, BE and OPES. Nine patients underwent surgery and six of them were re-evaluated after 6 months. We administered 10 ml of water with 37 MBq of technetium-99m colloid through a straw, acquiring 480 sequential images (0.125 s/frame for a total of 60 s) with the patient standing in front of the gamma camera in the 80 degrees right anterior oblique position. Two static images were performed at the end of the dynamic phase, before and after ingestion of 100 ml of unlabelled water to evaluate the presence of inflammation (persistence of radioactivity in the diverticulum or oesophagus). Study of the sequential scintigraphic images and time-activity curves permitted both qualitative (diverticulum visualisation, multiple deglutitions, reflux, presence of inflammation) and quantitative analyses [oral, pharyngeal and oesophageal transit times and retention indexes, tracheal aspiration percentage] of swallowing disorders. OPES showed a good correlation with the results of other diagnostic techniques usually performed in patients with this pathology, and especially with ME in the evaluation of oropharyngeal phase disorders. Furthermore, OPES is a sensitive and simple technique that is well tolerated and entails a low irradiation dose for patients.
Eur J Nucl Med Mol Imaging 2003 Dec
PMID:Scintigraphic evaluation of Zenker's diverticulum. 1368 Jan 98

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.
Int J Mol Med 2005 Sep
PMID:Mucin expression and proliferating cell index of esophageal Barrett's adenocarcinoma. 1607 42

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease limited to the lungs and associated with the histologic appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. The estimated prevalence in the United States is between 35,000 and 55,000 cases,and evidence suggests that the prevalence is increasing for IPF. Risk factors associated with pulmonary fibrosis include smoking, environmental exposures, gastroesophageal reflux dis-ease, commonly prescribed drugs, diabetes mellitus, infectious agents, and genetic factors. The diagnosis requires a careful history and physical examination, characteristic physiological and radiological studies, and, in some cases, a surgical lung biopsy. The natural history of IPF is not known, but evidence supports the concept of a continuum of idiopathic interstitial pneumonias that may overlap in time. Most patients with IPF succumb to respiratory failure, cardiovascular disease, lung cancer, pulmonary embolism, infection, and other health problems. The median survival time for patients with IPF is less than 3 yr. Factors that predict poor outcome include older age, male gender, severe dyspnea, history of cigarette smoking, severe loss of lung function, appearance and severity of fibrosis on radiological studies, lack of response to therapy,and prominent fibroblastic foci on histopathologic evaluation. Conventional therapy (corticosteroids, azathioprine, cyclophosphamide) provides only marginal benefit. Lung transplantation should be considered for patients with IPF refractory to medical therapy. In light of the poor prognosis and lack of response to available anti-inflammatory therapy, alternative approaches to therapy are being pursued. Emerging strategies to treat patients with IPF include agents that inhibit epithelial injury or enhance repair, anti-cytokine approaches, agents that inhibit fibroblast proliferation or induce fibroblast apoptosis, and other novel approaches.
Methods Mol Med 2005
PMID:Pulmonary fibrosis. 1613 Feb 30

Lung transplantation has come of age with the development of a critical mass of experienced clinicians who are committed to pooling their knowledge to solve the clinical problems that continue to confound the benefits individual patients may enjoy from these life-saving procedures. Adequately powered clinical trials are in progress to assist decision making regarding the role of newer immunosuppressive agents. Therapeutic drug monitoring has become critical to minimizing preventable complications such as renal dysfunction with calcineurin inhibitors. Fibroproliferation inhibitors are used more widely to ameliorate the abnormal healing response to allodependent or alloindependent injury, the latter perhaps related to underrecognized gastroesophageal reflux disease for which fundoplication is now proposed as an effective preventative measure. Cumulative damage to the graft from low-grade rejection is now appreciated as a potential cause of graft loss perhaps via an insidious small vessel vasculitis causing bronchiolar ischemic injury. Clearly, despite some progress, substantive challenges remain.
Methods Mol Biol 2006
PMID:Current status of lung transplantation. 1679 Aug 48

It has been proposed recently that gastroesophageal reflux disease (GERD) patients may be categorized into three distinct groups exhibiting non-erosive reflux disease (NERD), erosive reflux disease (ERD), and Barrett's esophagus (BE). Measurement of relative gene expression levels was undertaken to identify distinct molecular subclasses in different variants of gastroesophageal disease. The measurements were made with Affymetrix U133A 2.0 GeneChips and RNA isolated from mucosal samples of normal squamous esophageal epithelium from 24, 28, and 26 patients with NERD, ERD and BE, respectively. Statistical testing of microarray data showed that gene expression profiles are discriminative for BE and NERD, but not for combinations of BE and ERD or NERD and ERD. In addition, women developing NERD exhibited transcriptional patterns that differed from those of men with BE. In clustering analyses, we did not observe correlations between sex and assignment of gene expression profile of ERD patients to either the NERD or the BE group. Although the biological significance of the identified genes remains uncertain, we hypothesize that GERD is a monophyletic disease that develops with the onset of gastroesophageal reflux and represents two main molecular classes, which may result in different progressions to inflammatory process within esophageal epithelium modulated by sexual dimorphism. While normal epithelium samples from NERD and BE patients are molecularly homogeneous, esophageal mucosa from ERD patients is molecularly similar to either NERD or BE. These findings may be useful for defining molecular markers which could predict potential progression to Barrett's metaplasia among patients with reflux disease.
J Mol Med (Berl) 2006 Oct
PMID:Three clinical variants of gastroesophageal reflux disease form two distinct gene expression signatures. 1692 68

Recent studies have shown that esophageal mucosal inflammatory response is involved in the pathophysiology of gastro-esophageal reflux disease. The aim of the present study was to identify specific gene expression profiles of the esophageal mucosa in a rat model of combined-type chronic reflux esophagitis. Esophagogastroduodenal anastomosis was carried out in male Wistar rats by anastomosing the jejunum to the gastroesophageal junction under diethyl-ether inhalation anesthesia. Esophageal epithelial cells were obtained from esophagi of rats by laser capture microdissection. Preparation of cRNA and target hybridization were performed according to the Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The gene expression profile was evaluated by the rat toxicology U34 GeneChip. Array data analysis was carried out using Affymetrix GeneChip operating software, ingenuity pathway analysis software, and Gene Springs software. A comparison between esophagitis and sham-operated rats 2 weeks after the operation revealed that 368 probes (36%) were significantly affected, i.e. 185 probes were up-regulated, and 183 probes were down-regulated, both at levels of at least 1.5-fold in the esophagitis rats. Ingenuity signal analysis of 207 affected probes revealed the interleukin-6 signaling pathway as the most significantly affected caronical pathway. In addition, the expression of many genes associated with cytokine and transcription factor was enhanced in the esophagitis rats. This transcriptome approach provided insight into genes and putative genetic pathways thought to be affected by stimulation with gastroduodenal refluxates.
Int J Mol Med 2006 Nov
PMID:Inflammatory response of esophageal epithelium in combined-type esophagitis in rats: a transcriptome analysis. 1701 11

Obesity and gastro-oesophageal reflux are the main predisposing factors for oesophageal adenocarcinoma. We have examined the effects of transient acid exposure and leptin on OE33 oesophageal adenocarcinoma cells. Leptin and acid individually stimulated proliferation and inhibited apoptosis and the combination was synergistic. Leptin receptor protein levels were unchanged by acid exposure. The COX-2 inhibitor NS 398 blocked the effects of acid and leptin but while both acid and leptin individually significantly increased PGE2 production and COX-2 mRNA levels, the combination was not more effective than either stimulant alone. Leptin synergistically enhanced acid-stimulated EGFR and ERK phosphorylation but did not further increase JNK or p38 MAP kinase phosphorylation. Specific EGFR and ERK inhibitors reduced the effects of leptin and acid alone and in combination. The combination of increased circulating leptin levels in obesity and transient reflux of gastric acid may promote oesophageal carcinogenesis by increasing proliferation and inhibiting apoptosis.
Mol Cell Endocrinol 2007 Aug 15
PMID:Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture. 1761 45


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