Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.3.4.6 (urease)
7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori can be considered a very successful organism effectively colonizing the majority of the world's population. Although various disease states associated with this infection have been described, the mechanisms of pathogenicity remain unknown. The easiest virulence factors to identify are those enabling the organism to colonize the hazardous microenvironment of the gastric epithelium, survive at this site, and multiply sufficiently for transmission to a new host. The factors identified to date include the bacterial enzymes urease and catalase, flagella, and lectin-like adhesins. In addition, it is proposed that the organism has evolved mechanisms to avoid the local antibody responses of the host. Several putative virulence factors that could directly cause gastroduodenal damage have also been identified. These include the direct tissue damage by cytotoxins or the products of urease activity and the indirect tissue damage due to disruption of mucin integrity. Such mechanisms may contribute to peptic ulcer formation; however, the chronic superficial gastritis most frequently associated with this infection is probably caused by immunopathologic events mediated by the host in response to the continued antigen load on the gastric mucosa.
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PMID:Virulence factors of Helicobacter pylori. 177 22

A plaque growth chamber was developed for long-term growth of five separate plaques from the same plaque or saliva sample under identical conditions of temperature and gas phase. Reagent addition and growth conditions for each plaque could be independently controlled, and each was accessible for sequential sampling and electrode insertion. Plaques were cultured for over six weeks on pellicle-coated Lux (TM) 25-mm diameter cover-slips at 35 degrees C under 5% CO2 in N2, and supplied with a medium containing 0.25% mucin (BMM) at 3.6 mL/h, and with periodic 5% sucrose. Electron microscopy and flora analysis of microcosm plaques showed that they had close similarities to reported characteristics of natural dental plaques. Diverse motile bacteria were present. Sucrose-induced Stephan pH curves and urea-induced pH rises were also similar to those reported for natural plaques. Changes in plaque urease, calcium, phosphate concentrations, and the flora were followed over five weeks in a plaque supplied with BMM containing additional 2.5 mmol/L calcium and 7.5 mmol/L phosphate. Despite this high environmental calcium phosphate concentration, there was no continuing increase in calcium levels, although plaque phosphate doubled. Urease levels fluctuated. Changes in the cultivable flora were minor. A urea-containing calcium phosphate/mono-fluorophosphate pH 5 solution, applied for six min every two h for seven days, increased plaque calcium, phosphate, and fluoride to high levels. Thus, plaques grown over several weeks in the multi-station artificial mouth exhibited metabolic and pH behavior typical of natural plaques, could be analyzed during development, and the system allowed manipulation of environmental variables important in plaque pH control and calcification.
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PMID:A multi-station dental plaque microcosm (artificial mouth) for the study of plaque growth, metabolism, pH, and mineralization. 196 Feb 50

The prevalence of Helicobacter pylori (HP) in the gastric mucosa of patients with chronic atrophic gastritis has been reported to be significantly higher than in normal mucosa. To clarify the role of HP in the etiology of chronic atrophic gastritis, we assessed the effect of ammonia on the gastric mucosal structure in rats, since HP has a strong urease activity and produces abundant amounts of ammonia. Ammonia administered orally at 0.01% and 0.1% as drinking water for two to four weeks decreased the mucosal thickness and the parietal cell number and oxyntic gland number in a dose- and time-dependent manner. The decrease of mucosal thickness was significantly greater in the antral mucosa than in the body mucosa. The border between the antral and body mucosa shifted toward the cardia, reflecting the decrease in oxyntic gland numbers. Furthermore, intracellular mucin was also decreased in a dose- and time-dependent manner, especially in the antral mucosa. Thus, ammonia chronically administered orally in rats led to changes in gastric mucosal structures and functions. The results suggest that the ammonia produced by HP partly plays an etiologic role in chronic atrophic gastritis.
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PMID:Chronic effect of intragastric ammonia on gastric mucosal structures in rats. 198 2

The association between colonization of the antrum mucosa by Campylobacter pylori and antrum gastritis as well as peptic ulcers has been documented in a number of studies. The ability of these bacteria to produce a cytotoxin and a protease that hydrolyzes the mucosa-protecting mucin assigns pathogenetic properties to this species that suggest an etiological role for C. pylori in the pathogenesis of peptic ulcers and gastritis. This concept is supported by some preliminary results of therapeutic trials which have shown that successful eradication of the organism leads to histologic improvement of the gastritis and markedly reduced relapse rates regarding peptic lesions. Best results were achieved using combinations of a bismuth salt with an antibiotic such as amoxicillin. Diagnosis of C. pylori infection is based on culturing the organism from antral biopsies. Detecting the urease activity directly in the biopsy has also been shown to be an effective and reliable method. As a noninvasive method serologic testing for C. pylori may also be employed. An IgG-ELISA used by us showed a good correlation with cultural and histological results.
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PMID:[Campylobacter pylori: significance, diagnosis and treatment]. 329 1

The pathogenic role of Helicobacter pylori virulence factors has been studied with a mouse model of gastric disease. BALB/c mice were treated orally with different amounts of sonic extracts of cytotoxic H. pylori strains (NCTC 11637, 60190, 84-183, and 87A300 [CagA+/Tox+]). The pathological effects on histological sections of gastric mucosae were assessed and were compared with the effects of treatments with extracts from noncytotoxic strains (G21 and G50 [CagA-/Tox-]) and from strains that express either CagA alone (D931 [CagA+/Tox-]) or the cytotoxin alone (G104 [CagA-/Tox+]). The treatment with extracts from cytotoxic strains induced various epithelial lesions (vacuolation, erosions, and ulcerations), recruitment of inflammatory cells in the lamina propria, and a marked reduction of the mucin layer. Extracts of noncytotoxic strains induced mucin depletion but no other significant pathology. Crude extracts of strain D931, expressing CagA alone, caused only mild infiltration of inflammatory cells, whereas extracts of strain G104, expressing cytotoxin alone, induced extensive epithelial damage but little inflammatory reaction. Loss of the mucin layer was not associated with a cytotoxic phenotype, since this loss was observed in mice treated with crude extracts of all strains. The pathogenic roles of CagA, cytotoxin, and urease were further assessed by using extracts of mutant strains of H. pylori defective in the expression of each of these virulence factors. The results obtained suggest that (i) urease activity does not play a significant role in inducing the observed gastric damage, (ii) cytotoxin has an important role in the induction of gastric epithelial cell lesions but not in eliciting inflammation, and (iii) other components present in strains which carry the cagA gene, but distinct from CagA itself, are involved in eliciting the inflammatory response.
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PMID:Role of the Helicobacter pylori virulence factors vacuolating cytotoxin, CagA, and urease in a mouse model of disease. 755 33

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole. Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A2 activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of gastrin release by somatostatin. This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of acid suppressant, gastroprotective and anti-H. pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H. pylori.
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PMID:Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data. 920 47

A continuous, adherent mucus gel layer with mucosal bicarbonate secretion is the initial protective barrier in the stomach and duodenum against erosion by the gastric juice. H. pylori resides within the adherent mucus gel layer close to the epithelial surface. The barrier function of the mucus layer in vivo depends on (i) its thickness, and (ii) its gel structure, a property which is linearly dependent on the polymeric mucin content. We have shown in vivo that H. pylori colonisation alone did not decrease the thickness of the adherent gastric mucus barrier, although there was a mean 20% decrease in mucus thickness in those H. pylori positive subjects with underlying gastric atrophy. There was, however, a significant mean 18% reduction in the gel-forming polymeric mucin content of mucus from H. pylori subjects, independent of underlying atrophy. Studies in vitro suggest this loss of gel structure might arise from a H. pylori mediated, high local pH generated by urease activity rather than by proteolysis. This study shows that H. pylori infection alone does not compromise the overall integrity of the mucus barrier in vivo. However, in the immediate environment of the organism there appears to be a localised loss of mucus gel structure. The mucus barrier is compromised if H. pylori associated gastric atrophy or peptic ulceration follows.
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PMID:Mucus and H. pylori. 937 12

A simple, reproducible and high yield method of Helicobacter pylori urease enzyme purification was developed using a heparinoid (Cellufine sulfate) affinity gel. The purification method involved two sequential steps using the same gel that takes advantage of the differential affinity of urease to the heparinoid at two levels of hydrogen ion concentration. SDS-polyacrylamide gel electrophoresis analysis of affinity-purified urease revealed two major protein bands with about 62- and 30-kDa molecular mass. When whole cell lysates of clinical and laboratory strains of H. pylori were probed by Western blot, anti-urease hyperimmune serum produced by affinity-purified urease in rabbit recognized only the two bands corresponding to the urease A and B subunits. To probe the molecular relevance of affinity gel adherence to mucin adherence, the purified urease was derivatized with N-hydroxysuccinimidobiotin and used in adherence assays. Competitive inhibition tests revealed commonality of urease receptors among gastric mucin, heparin, and heparinoid. Composite data on adherence kinetics modulated by pH, salt, incubation time, and concentration of urease or mucin were indicative of conformation-dependent ligand-receptor interaction.
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PMID:Affinity purification of Helicobacter pylori urease. Relevance to gastric mucin adherence by urease protein. 966 Jul 71

Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the secreted apomucins of the stomach. A gradient from the surface epithelium (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in the opposite direction was found for MUC6. Our goal was to determine the distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to the H. pylori status. Gastric corpus biopsy specimens from patients who underwent partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem repeats of both proteins. A scoring system (0-3) was used to assess staining intensity at four sites: the lumen, the foveola, the mucous neck cells, and the glands. Helicobacter pylori status was determined by histology and rapid urease test and was considered positive or negative when both tests were positive or negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori-negative patients. No significant change in MUC5AC or MUC6 synthesis and secretion was demonstrated between H. pylori-positive or -negative patients. A gradient similar to that shown for the intact stomach (from the surface epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein presentation from the mucous neck cell to the glands were demonstrated. The pattern of MUC5AC protein synthesis was not different between H. pylori-positive and -negative patients in the postoperative stomach. MUC6 expression was higher in the foveola in H. pylori-positive patients, whereas there was no difference in the other cell layers.
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PMID:Gastric corpus mucin expression after partial gastrectomy, in relation to colonization with Helicobacter pylori. 1124 47

The emergence of antibiotic-resistant Helicobacter pylori is of concern in the treatment of H. pylori-associated gastroduodenal diseases. As the organism was reported to bind gastric mucin, we used porcine gastric mucin as substrate to assess the antiadhesive property of polysaccharides derived from Spirulina (PS), a commercially available microalga, against the binding of H. pylori to gastric mucin. Results show that polysaccharides prevented H. pylori from binding to gastric mucin optimally at pH 2.0, without affecting the viability of either bacteria or gastric epithelial cells, thus favouring its antiadhesive action in a gastric environment. Using ligand overlay analysis, polysaccharide was demonstrated to bind H. pylori alkyl hydroperoxide reductase (AhpC) and urease, which have shown here to possess mucin-binding activity. An in vivo study demonstrated that bacteria load was reduced by >90% in BALB/c mice treated with either Spirulina or polysaccharides. It is thus suggested that polysaccharides may function as a potential antiadhesive agent against H. pylori colonization of gastric mucin.
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PMID:Antiadhesive property of microalgal polysaccharide extract on the binding of Helicobacter pylori to gastric mucin. 1752 57


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