Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori, a gram-negative spiral bacterium, is the cause of chronic superficial (type B) gastritis and peptic ulcer disease. The urease enzyme of H. pylori was expressed as an inactive recombinant protein in Escherichia coli, purified as particulate structures of 550-600 kDa molecular mass with a diameter of approximately 12 nm. Given orally, 5 micrograms of urease with an appropriate mucosal adjuvant, such as the labile toxin of E. coli, protected 60%-100% of mice against challenge with virulent Helicobacter felis. Protection correlated with the level of secretory IgA antibodies against urease. Oral administration of antigen was as effective or better than intragastric administration. Parenteral injection of antigen or intragastric administration of high-dose antigen without adjuvant elicited serum IgG but no IgA antibodies and did not confer protection. Recombinant urease as an oral vaccine candidate deserves further investigation as an approach to the prevention of Helicobacter-induced chronic gastroduodenal diseases in humans.
 ...
PMID:Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis. 779 6

Recently many reports have shown a strong association between Helicobacter pylori infection in the stomach and recurrent peptic ulcer. Moreover, prospective cohort serological studies showed that H. pylori infected individuals have significantly increased rate of gastric cancer in the USA. H. pylori is a gram-negative spiral organism which has urease activity and produces ammonia and CO2 from urea, and nestles in the gastric pits and overlaying mucus gel layer. Many diagnostic methods of H. pylori infection are available; ie bacterial culture, 13C-urea breath test, histology, serum IgG antibody against H. pylori. We developed a new method, ie tissue IgA antibody against H. pylori and detection of H. pylori DNA in the gastric juice by PCR method. Triple therapies with metronidazole, bismuth compounds, and amoxicillin or tetracyclin are difficult to use in Japan because of their sever side effects. Thus, new methods with proton pump inhibitor (PPI) and amoxicillin have been introduced. We treated 14 patients of whom were H. pylori positive-active peptic ulcer with 30 mg/day of lansoprazole, a new PPI, plus 1,500 mg/day of amoxicillin for 2 weeks and 8 (57%) patients were eradicated. Gastric carcinogenesis are multi-steps and multifactorials process. Hypothetical sequence of intestinal type of gastric cancer is that superficial gastritis-->atrophic gastritis-->intestinal metaplasia-->dysplasia-->gastric cancer and H. pylori infection may play a role in the early stage of the sequence. We examined mucosal IgA antibody against H. pylori in chronic gastritis and intestinal metaplasia detected by the Tes-Tape method in 25 resected specimens after gastrectomy for gastric cancer. Positivity rates of tissue H. pylori IgA antibody were lower in the mucosa of intestinal metaplasia than in non-metaplastic gastric mucosa and were negative in carcinoma. Causal relationship between H. pylori infection and gastric cancer is not proven and factors other than H. pylori infection are also important in the gastric carcinogenesis. Finally we introduce 2 reports: (1) NIH Consensus Conference: Helicobacter pylori in peptic ulcer disease (JAMA. 1994; 272: 65-69). The consensus panel concluded that 1. ulcer patients with H. pylori infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; 2. the value of treating nonulcerative dyspepsia patients with H. pylori infection remains to be determined; and 3. the interesting relationship between H. pylori infection and gastric cancer requires further exploration. (2) World Health Organization: Working Group Meeting (Reported in World Congress of Gastroenterology, Los Angeles, 1994). H. pylori plays a causal role in the chain of events leading to cancer of the stomach. Group I: definite carcinogen.
 ...
PMID:[Helicobacter pylori in peptic ulcer and gastric cancer]. 785 88

The ability of oral immunization to interfere with the establishment of infection with Helicobacter felis was examined. Groups of Swiss Webster mice were immunized orally with 250 micrograms of Helicobacter pylori recombinant urease (rUrease) and 10 micrograms of cholera toxin (CT) adjuvant, 1 mg of H. felis sonicate antigens and CT, or phosphate-buffered saline (PBS) and CT. Oral immunization with rUrease resulted in markedly elevated serum immunoglobulin G (IgG), serum IgA, and intestinal IgA antibody responses. Challenge with live H. felis further stimulated the urease-specific intestinal IgA and serum IgG and IgA antibody levels in mice previously immunized with rUrease but activated primarily the serum IgG compartment of PBS-treated and H. felis-immunized mice. Intestinal IgA and serum IgG and IgA anti-urease antibody responses were highest in rUrease-immunized mice at the termination of the experiment. Mice immunized with rUrease were significantly protected (P < or = 0.0476) against infection when challenged with H. felis 2 or 6 weeks post-oral immunization in comparison with PBS-treated mice. Whereas H. felis-infected mice displayed multifocal gastric mucosal lymphoid follicles consisting of CD45R+ B cells surrounded by clusters of Thy1.2+ T cells, gastric tissue from rUrease-immunized mice contained few CD45R+ B cells and infrequent mucosal follicles. These observations show that oral immunization with rUrease confers protection against H. felis infection and suggest that gastric tissue may function as an effector organ of the mucosal immune system which reflects the extent of local antigenic stimulation.
 ...
PMID:Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis. 789 Mar 80

Experiments were performed to determine the antigenic specificity of a monoclonal antibody (immunoglobulin A [IgA] 71) previously demonstrated to neutralize the ability of Helicobacter felis to colonize mice. Immunoprecipitation of radiolabeled H. felis outer membrane proteins with IgA 71 revealed specificity for a 62-kDa protein. Another of our monoclonal antibodies, IgG 40, precipitated a protein of similar molecular weight. IgA 71 but not IgG 40 also precipitated purified recombinant H. pylori urease. The antigenic specificity of both antibodies was confirmed to be urease by the ability of each to select Escherichia coli clones expressing the H. felis urease genes. The two antibodies were shown to bind nonoverlapping epitopes in a competition enzyme-linked immunosorbent assay. Both IgA 71 and IgG 40 could effectively neutralize H. felis infectivity by incubating the bacteria with the antibodies prior to oral administration to naive mice. The mechanism of protection does not appear to be inhibition of urease activity, as IgA 71 does not inhibit the conversion of urea to ammonia by H. pylori urease in vitro. These results support a protective role for the secretory humoral immune response in Helicobacter immunity and provide further evidence that the urease enzyme can serve as a protective antigen.
 ...
PMID:Urease-specific monoclonal antibodies prevent Helicobacter felis infection in mice. 789 Apr 1

A number of direct (histology, specific culture) and indirect (serology, urease test, breath test) diagnostic tests for Helicobacter pylori (H. pylori) are available. The gold standard for H. pylori presence or absence is still histology (tissue stained by Giemsa) without or in combination with specific culture. For routine practice a combination of histology (two antral and two body biopsies) and the urease test (one antral and one body biopsy specimen) is recommended in patients undergoing upper GI endoscopy. The reaction velocity of the urease test can be semi-quantitatively graded and, thus, allows a rough estimate of the grade and the activity of gastritis. The simplest and least expensive non-invasive method is serologic testing for IgG and/or IgA antibodies. Latex-agglutination methods are "quick tests", useful for screening purposes. ELISA based tests accurately quantitate the amount of antibody (titer) present and are a promising tool for assessing the efficacy of H. pylori eradication treatment. 13 C/14 C-urea breath tests are reliable non-invasive methods for the diagnosis of ongoing H. pylori infection.
 ...
PMID:[Diagnosis of Helicobacter pylori infection]. 797 72

In a prospective study we examined 20 Helicobacter pylori (HP)-positive duodenal ulcer patients (5 female, 15 male; age 26-70 [mean 43] years), 20 HP-positive patients with non-ulcer dyspepsia (10 female, 10 male; age 26-79 [mean 48] years) and 10 HP-negative patients with non-ulcer dyspepsia (5 female, 5 male; age 21-76 [mean 45] years) during upper GI-endoscopy. HP was detected by histology (H&E, Giemsa), rapid urease test (CLO) and serology (Cobas Core Anti-H. pylori EIA). IgA anti-HP in gastric juice was determined by ELISA. HP-positivity included positivity in all methods, and HP-negativity failure to detect HP-infection by all methods used. Of the 20 duodenal ulcer patients, 10 patients (2 female, 8 male; age 26-70 [mean 42] years) had an endoscopically documented duodenal ulcer at an earlier endoscopy with no current ulcer, 10 patients had florid duodenal ulcer disease at the time of examination. Duodenal ulcer patients compared with non-ulcer dyspepsia patients were tended to have higher serum IgG anti-HP (551 +/- 240 vs. 338 +/- 159 U/ml) and significantly higher gastric juice IgA anti-HP (50.0 +/- 7.3 vs. 26.5 +/- 4.3 relative units). Concentrations of both serum IgG anti-HP and gastric juice IgA anti-HP tended to be higher in patients with positive ulcer history but no present ulcer compared with patients with florid ulcer disease (934 +/- 456 vs. 170 +/- 63 U/ml and 60.0 +/- 8.6 vs. 40.8 +/- 10.4 relative units).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Duodenal ulcer disease: a defect in the secretory immune response to Helicobacter pylori?]. 819 Dec 63

54 patients (22 females, 32 males, age 21-79, mean 45 years) referred for upper gastrointestinal endoscopy were investigated. Helicobacter pylori (HP) infection was determined using histology (H&E and Giemsa stain), rapid urease test (CLO) and serology (Cobas Core Anti-H. pylori EIA). Density of HP colonization was determined in gastric antral (3 biopsy specimens) and body mucosa (2 biopsy specimens) and semiquantitatively graded on a scale of 0 to 3. Gastric colonization was obtained by addition of the two scores. IgA anti-HP concentration was determined by ELISA using the same FPLC purified HP-antigen mixture as for serology. Gastric juice IgA anti-HP concentration in HP-positive patients (n = 40) was significantly higher than in HP-negative (n = 14) patients (38.3 +/- 4.6 vs. 5.4 +/- 1.2 relative units, p < 0.001). Comparison of HP-colonization density of gastric mucosa with gastric juice IgA anti-HP concentration of the 54 patients by binominal regression analysis yielded a correlation coefficient of 0.65 (p < 0.01). The biphasic course of the curve suggests a mutual relationship of HP-colonization density and IgA immune response. Increasing colonization densities seemed to induce increasing secretory immune responses. Half-maximal and higher immune responses, however, seemed to suppress further HP colonization in vivo without eradicating the infection.
 ...
PMID:[Suppression of Helicobacter pylori by local secretory immune response?]. 819 Dec 64

The systemic IgG response to Helicobacter pylori was examined in 70 patients with gastric cancer. H pylori IgG antibodies were assayed by enzyme linked immunosorbent assay (ELISA), and serological recognition of H pylori antigens was characterised by western blotting. A percentage of 78.5 were seropositive by ELISA. Two of five patients under age 50 were seronegative. Positivity was unrelated to age, sex, tumour type, or site. Ninety one per cent of ELISA positive cancer patients recognised the H pylori cytotoxin associated 120 kilodalton (kD) protein, significantly more than a control group of 47 ELISA positive patients with non-ulcer dyspepsia (72%). Four of 15 ELISA negative cancer patients also showed recognition of this protein in western blots. Mucosal IgA responses to H pylori were examined by immunoblotting supernatants of in vitro cultured resected antral mucosa in an overlapping group of 19 gastric cancer patients. Eighteen had a positive response, including 10 of 11 negative for H pylori by biopsy urease testing. The systemic and local immunoblotting results show that the high seroprevalence of H pylori antibodies detected by ELISA is nevertheless an underestimate of past infection. Dyspepsia screening policies based solely on H pylori ELISA would miss some young patients with gastric cancer. Further study of the relation of the H pylori cytotoxin to gastric precancerous lesions is warranted.
 ...
PMID:Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer. 824 98

IgA anti-HP concentrations in both gastric juice and saliva samples of 40 HP+ patients (15 f, 25 m) randomly referred for upper GI-endoscopy were measured. The presence of HP was investigated using histology (H&E and Giemsa stain), rapid urease test (CLO) and serology (Cobas Core Anti-H. pylori EIA, F. Hoffmann-La Roche). IgA anti-HP in gastric juice and saliva was determined by ELISA; the same HP antigen was used as for serology (FPLC-purified native cell surface antigens including urease, free of cross-reacting flagellar proteins). The 40 HP+ patients were positive for HP by all three methods (except 4x CLO false neg, 1x serology false neg). A control group consisted of 12 patients (6 f, 6 m) with no HP detectable by each of the three methods used. No correlation was discernible between IgA anti-HP concentration in saliva and gastric juice of HP-positive patients (R = 0.05). In contrast, the correlation coefficient in HP-negative patients was R = 0.69 (p < 0.02). Great interindividual differences in specific IgA concentrations of both secretions were found. Surprisingly, in saliva and gastric juice IgA anti-HP was also detectable in some subjects negative for HP by all three tests applied. This finding remains to be elucidated but could represent ongoing local immune response in the absence of HP gastritis. In conclusion, saliva was found to contain IgA binding to HP-antigen. In HP-negative subjects contamination of gastric juice by saliva seems to be responsible when small concentrations of IgA anti-HP antibodies were detectable in gastric juice.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[IgA-antibodies against Helicobacter pylori in gastric secretions: gastric secretory immune response or salivary contamination?]. 851 43

We evaluated the performance of three enzyme-linked immunosorbent assays (ELISAs) in detecting serum immunoglobulin G (IgG) and IgA antibodies to Helicobacter pylori; two were new ones from Pyloriset (Pyloriset EIA-G update and Pyloriset EIA-A update; Orion Diagnostica, Espoo, Finland), and the third was the Malakit EIA-G (Biolab, Limal, Belgium). Serum samples from 154 dyspeptic patients were collected. As a reference method, multiple biopsy specimens from different anatomical areas of the stomach were obtained by endoscopy and were analyzed by culture and/or histology and direct urease testing. Accordingly, 126 patients (82%) were found to be H. pylori positive and 28 patients (18%) were found to be H. pylori negative. To validate serology as a predictor of H. pylori infection, sensitivity, specificity, positive and negative predictive values, and accuracy of the assays were calculated against the H. pylori status as determined by the reference method. The corresponding data for the different ELISAs were 100%, 79%, 95%, 100%, and 96% for the Pyloriset ELA-G update, 81%, 89%, 97%, 52%, and 82% for the Pyloriset EIA-A update, and 87%, 86%, 96%, 60%, and 87% for the Malakit EIA-G, respectively. We conclude that the Pyloriset EIA-G update is a reliable and accurate test and that because of its 100% sensitivity, conjunctional IgA testing is not necessary. Its 100% negative predictive value makes it a very useful screening test. For purposes of excluding infection with H. pylori, the performance of the Malakit EIA-G is moderate but can be improved by conjunctional IgA testing. The Pyloriset EIA-A update can be useful as such a conjunctional test.
 ...
PMID:Comparison of three commercially available enzyme-linked immunosorbent assays and biopsy-dependent diagnosis for detecting Helicobacter pylori infection. 874 81


<< Previous 1 2 3 4 5 6 7 8 Next >>