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Biomedical subjects

G Triadafilopoulos

Publications and source records attributed to G Triadafilopoulos.

98 records · Page 6Linked to original sources
PubMed1988

Clostridium difficile toxin A stimulates intracellular calcium release and chemotactic response in human granulocytes.

Clostridium difficile, a common enteric pathogen, mediates tissue damage and intestinal fluid secretion by release of two protein exotoxins: toxin A, an enterotoxin, and toxin B, a cytotoxin. Because toxin A elicits an intense inflammatory reaction in vivo, we studied the effects of highly purified C. difficile toxins on activation of human granulocytes. Toxin A at concentrations of 10(-7) to 10(-6) M, but not toxin B, elicited a significant chemotactic and chemokinetic response by granulocytes that was comparable with that induced by the chemotactic factor N-FMLP (10(-7) M). Neither toxin stimulated release of superoxide anion from granulocytes. Toxin A produced a rapid, transient rise in cytosolic [Ca2+]i, as measured by quin 2 fluorescence. Pertussis toxin and depletion of intra- and extracellular calcium blocked the toxin A effect on cytosolic [Ca2+]i. These findings suggest that the inflammatory effects of C. difficile toxin A in the intestine may be related to its ability to mobilize intracellular Ca2+ and elicit a chemotactic response by granulocytes.

Bacterial Toxins↗
PubMed1987

Differential effects of Clostridium difficile toxins A and B on rabbit ileum.

The pathogenesis of Clostridium difficile enterocolitis appears to involve colonization of the bowel followed by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. The purpose of this study was to determine the effect of purified toxins A and B on intestinal secretion, epithelial permeability, and morphology in perfused rabbit ileal loops. Intestinal permeability after toxin exposure was assessed by blood-to-lumen clearance of [3H]mannitol. Toxin A at doses of 5-100 micrograms/10 cm ileal loop caused a threefold to fivefold increase in [3H]mannitol permeability (p less than 0.001) vs. equal concentrations of toxin B or buffer control. In addition, perfusate from toxin A-exposed loops contained significantly more neutrophils (p less than 0.001) than toxin B or control loops. Toxin A caused severe epithelial cell necrosis with destruction of villi and polymorphonuclear infiltration. Electron microscopy of mucosa subjected to a low dose of toxin revealed widespread nonspecific dilatation of endoplasmic reticulum and mitochondrial swelling. In contrast to these effects of toxin A in ileal loops, in vitro experiments with ileal explants in short-term organ culture revealed that toxin A had no effect on epithelial cell permeability, protein synthesis, release of alkaline phosphatase, or morphology. Our results show that purified toxin A but not toxin B causes severe inflammatory enteritis in rabbit ileal loops, but has no discernable effect on rabbit ileum in vitro. We speculate that toxin A may contribute significantly to intestinal damage in C. difficile-associated colitis and diarrhea.

Animals↗
PubMed1986

Clostridium difficile cytotoxin inhibits protein synthesis in fibroblasts and intestinal mucosa.

The pathophysiology of Clostridium difficile colitis is thought to be mediated by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. We compared the differential effects of toxin B on protein synthesis in IMR-90 fibroblasts and in hamster esophagus, stomach, gallbladder, small intestine, and cecum in organ culture. Toxin B in low concentrations stimulated (p less than 0.001) incorporation of [3H]leucine into fibroblast proteins, whereas at higher dosages it inhibited incorporation (p less than 0.001). This biphasic effect was independent of cell rounding and was not caused by a change in uptake of precursor. Purified toxin B had no effect on protein synthesis in a cell-free rabbit reticulocyte translation system, indicating that inhibition of protein synthesis in intact fibroblast monolayers and intestinal explants is a consequence of toxin B effect on some other cellular target. Toxin B significantly inhibited protein synthesis in hamster cecal explants in a dose-dependent fashion. Again, this inhibition was not mediated by altered precursor uptake. Toxin B significantly inhibited in vitro protein synthesis in hamster terminal ileum, cecum, and sigmoid colon, but not in esophagus, gallbladder, stomach, or duodenum. These results suggest that toxin B-mediated inhibition of protein synthesis may be a generalized toxic effect in tissue culture cells and intestinal epithelium. Inhibition of protein synthesis in the distal intestinal epithelium may contribute to the pathophysiology of colitis caused by this organism.

Cecum↗
PubMedDate not supplied

Esophageal wall thickening: a CT finding in diffuse esophageal spasm.

We report three patients with esophageal wall thickening, incidentally found at CT, in whom further evaluation led to the diagnosis of diffuse esophageal spasm (DES). All cases showed smooth, symmetric, circumferential wall thickening of the distal two-thirds of the esophagus with normal periesophageal fat. No lung parenchymal abnormalities suggestive of aspiration were seen. DES, although uncommon, is another benign condition that should be included in the differential diagnosis of esophageal wall thickening detected by CT.

Aged↗
PubMedDate not supplied

Recent developments in the molecular characterization of Barrett's esophagus.

Barrett's esophagus, or specialized intestinal metaplasia, is a common condition associated with gastroesophageal reflux and an increased risk for adenocarcinoma of the esophagus and gastric cardia. Currently, clinical surveillance for early detection of adenocarcinoma relies on the histopathological assessment of dysplasia. In this review we present data from the published literature, and combine this with results from our own research, to address what is currently known about the environmental factors and the molecular changes thought to be important in the pathogenesis of Barrett's esophagus. The most important and well-characterized molecular changes, preceding the development of dysplasia, are alterations in the p53 and erbB-2 genes and aneuploidy. These molecular changes, as well as environmental influences, such as the quality and quantity of gastroduodenal refluxate, may result in abnormal cell proliferation which in turn promotes further genetic abnormalities and deregulation of cell growth. The identification of molecular changes, in the context of predisposing environmental factors, will enhance our understanding of the malignant progression of Barrett's esophagus leading to more effective surveillance and treatment.

Adenocarcinoma↗
PubMedDate not supplied

Clostridium difficile toxin A stimulates enzyme secretion from isolated rat pancreatic acini.

Although Cl difficile bacteremia and the presence of antibodies to toxin A (TxA) have been reported, little information is available at present on TxA effect on the functional properties of various visceral organs. We have, therefore, examined the in vitro effects of TxA on amylase and trypsin secretion from rat isolated pancreatic acini. Dispersed rat pancreatic acini were exposed for 60 min to different concentrations of highly purified TxA and the rate of amylase, trypsin and LDH release were monitored. Free cytosolic calcium release in pancreatic acini after toxin A (10(-10)M to 10(-8)M) treatment was measured with Fura-2/AM, Ca-indicator dye. TxA (10(-10) to 10(-8)M) increased significantly the rate of both the amylase and trypsin secretion without any membrane damage, with toxin A exerting its action via calcium dependent pathway as suggested by intracellular calcium release measured with Fura-2/AM.

Amylases↗