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)

Dihydropyrimidine dehydrogenase (DHPDase), dihydropyrimidinase (DHPase) and beta-ureidopropionase (betaUPase) are the enzymes that catalyze the first, second, and third steps of the degradation of pyrimidines, respectively. beta-Ureidopropionate (betaUP) and beta-ureidoisobutyrate (betaUIB) are increased in the urine of patients with betaUPase deficiency. The original case in which betaUPase deficiency was discovered by NMR spectroscopy was an 11-month-old patient who presented with hypotonia and dystonic movement. We detected a second but asymptomatic case during a pilot study of neonatal screening with filter-paper urine, urease pretreatment and gas chromatography/mass spectrometry (GC/MS). The urease pretreatment of urine without fractionation resulted in a high recovery of these polar ureide compounds and allowed the highly sensitive GC/MS detection and diagnosis of betaUPase deficiency. betaUP and betaUIB were identified using GC/MS techniques. In the urine of the neonate with betaUPase deficiency, betaUP and betaUIB were persistently increased. Thymine, 5,6-dihydrothymine and 5,6-dihydrouracil were increased only moderately but significantly. It is known that thymine and uracil increase markedly in DHPDase deficiency, and 5,6-dihydrothymine and 5,6-dihydrouracil increase in DHPase deficiency. Therefore, betaUPase deficiency can be differentially diagnosed from the first and second enzyme deficiencies. Application of this specific and sensitive diagnostic procedure will lead to an understanding of the clinical heterogeneity of betaUPase deficiency. Furthermore, the identification of patients with defects in pyrimidine metabolism will enable doctors to avoid cancer chemotherapy with pyrimidine analogues such as 5-fluorouracil, which could be dangerous for these patients.
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PMID:Screening and diagnosis of beta-ureidopropionase deficiency by gas chromatographic/mass spectrometric analysis of urine. 1227 38

Since Marshall's discovery before 20 years, Helicobacter pylori (H. pylori) infection is reportedly to be associated with a variety of clinical outcomes including peptic ulcer disease and gastric cancer. The first step of the H. pylori colonization might be its adhesion to the surface epithelial cells, which evokes gastric inflammatory events initiated by neutrophil recruitment from the microcirculation. Mongolian gerbil is one of the suitable animal models for H. pylori infection, which exerts gastric ulcer and cancer with its bacterial infection. In H. pylori-colonized gerbils, extensive levels of microvascular leukocyte adhesion and migration into the parenchymal side and significant levels of inflammatory cell infiltration are encountered. Bacterial urease not only neutralizes gastric luminal acid, but also plays as an adhesion factor to the surface epithelium. Recently, such an adhesion to the epithelium is reported to be important for bacterial type IV secretory system, which intermediates Cag A injection into the epithelial cells. Then, multiple chemokine and cytokine networks are activated and mucosal inflammatory lesion formation would be completed. In the long-term colonization of H. pylori, gastric mucosal cell turnover would be modified due to persistent inflammation and then such deregulation of cell turnover might link to the precancerous lesion formation.
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PMID:Gastric mucosal response to Helicobacter pylori. 1252 36

Clinical scientists from eight European countries and China gathered in the ancient Chinese capital of Xi'an on April 26-28, 2001 to discuss collaboration on a modern approach to gastric cancer prevention. Participants at the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer presented their most up-to-date research results on topics ranging from epidemiology and immune mechanisms to Helicobacter pylori and vaccine development. Researchers then formed groups with their Chinese or European counterparts to plan future research endeavors which will benefit Chinese and European populations alike. After 3 years of organization between the Institute of Digestive Diseases of the Fourth Medical University in Xi'an, China and the Laboratory of Immunogenetics, VU University Medical Center in Amsterdam, the first workshop came into being under the joint sponsorship of the Commission of the European Union, National Natural Science Foundation of China and the Institute of Digestive Diseases, Xi'an, China. As gastric cancer is the most prevalent malignant tumor in China, the workshop was of special significance to the Chinese researchers and to the Chinese population in general. During the workshop, presentations on the epidemiology of gastric cancer showed that this disease is in fact common the world over: it is the second most common cancer next to lung cancer and about 1 million new cases were diagnosed in 2000. Three-quarters of the cases of gastric cancer occur in Asia, and approximately 80% of these cases are in China and Japan. Genetic factors and environmental factors such as diet and H. pylori infection play a role in gastric carcinogenesis. As a recognized cause of gastric cancer, H. pylori was the subject of various presentations ranging from immunological studies, molecular analysis of strains and pathogenesis to vaccine development. Specific areas of discussion included bacterial-epithelial interactions in H. pylori infection, epidemiology in China, global distribution of vacA and cagA genotypes, new evidence for host factors, nonsteroidal antiinflammatory drugs and H. pylori as independent risk factor for gastric cancer, new diagnostic techniques for H. pylori using serum levels of pepsinogen I, and autoimmune processes in corpus atrophy. Vaccine development using a variety of strategies against H. pylori was the subject of an entire session of talks. Oral immunization with urease with Escherichia coli heat labile enterotoxin was shown to be safe and immunogenic in humans as a mucosal adjuvant. Results of a study using attenuated Salmonella typhimurium as a vehicle for DNA-mediated immunization in mice were also presented. A final presentation discussed an ongoing trial comparing strain variability in the vacA and cagA gene sequences and disease expression between H. pylori infection in Europe and China. Researchers also discussed the role of IL1 gene family and TNF gene polymorphisms in gastric pathology and various immune mechanisms involved in gastric cancer, such as down-regulation of NF kappa B, IL-1 and IL-1RA, cyclooxygenase signalling, and identification of MGAg antibodies. An interactive discussion followed each presentation and ideas and suggestions were provided. According to specialty, the presenters were then assigned to groups of four or five to make plans for joint research projects. A number of international and Chinese observers were present, including representatives from the European Commission, the World Health Organization and the Chinese National Center for Biotechnology Development, and offered input on the financial feasibility of such projects.
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PMID:The immunogenetics and pathogenesis of gastric cancer. Highlights of the First Sino-European Workshop on the Immunogenetics and Pathogenesis of Gastric Cancer. 1253 77

The diagnostics of Helicobacter pylori infection is now one of the most important aspects of the diagnosis of various gastroduodenal diseases. New data have shown that Helicobacter pylori is a causative agent of peptic ulcer disease and an important factor in cancer development. Numerous diagnostic tests are now available. They can be divided into two groups: invasive and noninvasive tests. All invasive test methods are based on endoscopic examination during which biopsy specimens are obtained for direct (histological analysis, isolation) or indirect (urease test) diagnosis of Helicobacter pylori infection. Noninasive methods reveal the presence of Helicobacter pylori by measuring the activity of urease (urea breath test), then by confirming the presence of antibodies in the serum or saliva of the infected person or by confirming the presence of Helicobacter pylori antigens in the feces.
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PMID:[Diagnosis of Helicobacter pylori infection]. 1259 10

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving dilated atypical gastric gland situated "back-to-back". This glandular atypia failed to show lamina propria or submucosa infiltration corresponding to gastric intraepithelial neoplasia. The GBF in Hp-infected gerbils was significantly lower, and a 6-7 fold increase in plasma gastrin levels combined with a significant fall in gastric luminal somatostatin contents observed at all tested periods as compared to vehicle-controls and these effects were counteracted by anti-Hp triple therapy. We conclude that: 1). Hp-infection in Mongolian gerbils in early stages before adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal microcirculation and gastrin-somatostatin link, and 2). this deleterious influence of Hp on gastric morphology and gastric functions is greatly attenuated in gerbils treated with Hp-eradication therapy.
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PMID:Triple eradication therapy counteracts functional impairment associated with Helicobacter pylori infection in Mongolian gerbils. 1267 17

H. pylori colonisation of the stomach causes the recruitment of the inflammatory cells by the adherence of the bacteria with the epithelium and the release of factors of virulence either to the contact (oipA or other soluble factors) or in the cell by translocation (CagA). Such contact triggers interleukin 8 expression in the epithelial cell and attracts lymphocytes and monocytes into the chorion. Bacterial lipopolysaccharide and urease support the activation of these inflammatory cells. The lymphocytes produce pro-inflammatory cytokines, which direct the immune response towards the Th1 pathway. The variability of the inflammatory response depends on hereditary factors of the host such as the interleukin 1 genotypes, which determine the level of the pro-inflammatory cytokine expression, and of bacterial factors such as the cag pathogenicity island, the lipopolysaccharide and the vacuolating toxin, vacA. The mucosal inflammation provokes apoptosis and atrophy of the epithelial cells through the effect of pro-inflammatory cytokines and free radicals. Epithelial proliferation is a consequence of excessive apoptosis caused by the infection. It is stimulated by the expression of inducible cyclo-oxygenase and inducible nitric oxide synthase. The development of atrophic gastritis towards cancer is supported by nitric oxide which has a mutagenic effect on DNA and inhibits p53 protein and by the bacterium itself which decreases DNA mismatch repairing activity. The gastritis induced by Helicobacter pylori changes acid secretion according to the prevalent location of the gastritis in the antrum or in the gastric body. Prevalent gastritis in the gastric body causes hypochlorhydria by reducing the release of histamin from ECL cells and inhibiting the parietal cells through the effect of tumor necrosis factor and interleukin 1-beta. Hypochlorhydria is more marked among patients having a pro-inflammatory genotype for interleukin 1-beta and those infected by bacteria with virulence factors. In the event of antrum predominant gastritis, the pro-inflammatory cytokines cause a reduction of somatostatin and gastrin releases from the D and the G cells, respectively. The result of all is increased maximal acid output and the meal-stimulated acid secretion.
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PMID:[What are the gastric modifications induced by acute and chronic Helicobacter pylori infection?]. 1270 Apr 95

The longitudinal stability of the urea breath test (UBT), which measures urease as a biomarker for infection with Helicobacter pylori (a major risk factor for gastric cancer), was evaluated in the environs of Tsukuba, Japan. 13C-UBT measurements were monitored at four time points in 46 free-living, H. pylori-infected, asymptomatic volunteers over a period of 7 weeks. Subjects were asked to refrain from eating cruciferous vegetables, which might confound interpretation of results. Their compliance was monitored using both dietary records and direct biochemical testing of overnight urine. There was large between-subject UBT variation in this population (logUBT mean, 3.34; SD, 0.67). Within-subject (longitudinal) UBT values were remarkably stable in about one-quarter of the subjects (coefficients of variations for these individuals were <21%), whereas coefficients of variations in the highest quartile of variability ranged from 40% to 80%. About half of the sequential UBTs (63 of 138 such measurement pairs) changed >10 per thousand "delta over baseline" between measurements. This study provides the elements to optimize the design of a clinical trial in this population to examine the efficacy of a dietary intervention to reduce H. pylori infection. The number of subjects required to detect a 30% difference in average UBT value is highly dependent on the baseline stability of UBT measurements. For the least variable quartile, as few as 12 subjects would be needed; for the most variable quartile, at least 147 subjects would be required in each arm.
Cancer Epidemiol Biomarkers Prev 2004 Oct
PMID:Dietary amelioration of Helicobacter pylori infection: design criteria for a clinical trial. 1546 77

Several cytokine gene polymorphisms have been associated with increased risk of distal gastric cancer (GC) and its precursor histological markers in Caucasian, Asian and Portuguese populations although little is known about their role in other ethnic groups. Our study investigates the role of the IL-1B-31, IL-1RN and TNF-A-308 gene polymorphisms as risk factors for the development of GC in a Mexican population. We studied 278 patients who were enrolled at the Hospital Universitario Dr. Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon. The subjects were divided into 2 groups. Sixty-three patients with histologically confirmed distal GC (mean age = 58.8 years, range = 22-84, F:M = 0.56), and 215 patients with no evidence of distal or proximal GC (mean age = 56.1 years, range = 18-92, F:M = 1.17). The IL-1B-31 and the TNF-A-308 polymorphisms were determined by PCR-RFLP and pyrosequencing, respectively, in all cases and controls. The VNTR polymorphism in intron 2 of the 1L-1RN gene was typed by PCR in 25 cases and 201 controls. The H. pylori status was determined by histology, rapid urease test, culture and serology for non-cancer controls and by histology for the GC cases. The carriage of the proinflammatory IL-1B-31*C allele was associated with increased risk of distal GC (odds ratio [OR] = 7.63, 95% confidence interval [CI] = 1.73-46.94, p = 0.003). When cases and controls were matched by age and gender, the OR value was higher (OR = 8.05, 95% CI = 1.8-50.22, p = 0.001). When only H. pylori GC cases and controls were compared, the OR value was 7.8 (95% CI = 1.05-161.8, p = 0.04). No association was found between any of the other polymorphisms studied and distal GC. In this Mexican population, the IL-1B proinflammatory genotype increases the risk of distal GC. These findings are similar to previous reports in Caucasian populations and underscore the importance of cytokine gene polymorphisms in the development of distal GC.
Int J Cancer 2005 Mar 20
PMID:Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. 1554 Feb 24

Helicobacter pylori is a human pathogen that infects over 50% of the population worldwide. It is the most important etiologic agent of gastroduodenal ulcers and malignancies. Helicobacter pylori urease enzyme is considered the main factor for the organism's colonization in the gastroduodenal mucosa. Hens immunized with the purified urease produce a highly specific anti-H. pylori urease immunoglobulin (IgY-urease) in their egg yolks. Immunoglobulin Y-urease was stable at 60 to 65 degrees C for 30 min and at pH 4.0 for 7 h. Its activity was lost at 80 degrees C for 20 min and at pH 2 for 4 h. Specially designed functional drinking yogurt containing Lactobacillus acidophilus and Bifidobacterium spp. with 1% egg yolk IgY-urease was produced commercially. Immunoglobulin Y-urease activity showed stability in the product up to 7 d, and then decreased to 85% after 3 wk of storage. A clinical study was conducted to determine the effectiveness of IgY-urease yogurt to suppress infection in humans. Forty-two volunteers who tested positive for H. pylori using a 13C-urea breath test were recruited. A total of 450 mL of IgY-urease (test group) or IgY-urease-free yogurt (control group) was consumed in 150-mL portions 3 times daily for 4 wk. Volunteers were tested after 2 and 4 wk; urea breath test values significantly decreased in the test group compared with the control group. The results indicate that suppression of H. pylori infection in humans could be achieved by consumption of drinking yogurt fortified with IgY-urease.
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PMID:Suppressive effect of functional drinking yogurt containing specific egg yolk immunoglobulin on Helicobacter pylori in humans. 1554 68

Helicobacter pylori is prevalent worldwide, especially in developing countries, and is associated with several upper gastrointestinal diseases. Since it is present in over 90% of duodenal ulcer patients, empirical eradication in these patients is often recommended. In gastric ulcer patients, eradication is indicated only after the infection is confirmed. Testing for H. pylori infection should be carried out in patients with peptic ulcer hemorrhage, because eradication has been shown to reduce recurrent bleeding. Both H. pylori and NSAIDs are risk factors for peptic ulceration, and it is reasonable to screen for and eradicate H. pylori infection in peptic ulcer patients taking NSAIDs. H. pylori is a group I carcinogen for gastric adenocarcinoma, and should be eradicated for the primary prevention of this cancer. Eradication of this organism has been reported to result in regression of early low-grade mucosa-associated lymphoid tissue lymphoma. The role of H. pylori infection in the causation of gastroesophageal reflux and non-ulcer dyspepsia is not clearly established. Several tests are available for the diagnosis of H. pylori infection. These include invasive tests, such as histology, culture and urease test, and non-invasive tests, such as serology, urea breath test and stool antigen test. The choice of test is determined by clinical indication, pretest probability of infection, as well as the availability, cost, sensitivity and specificity of the test. H. pylori eradication therapy using proton pump inhibitor with clarithromycin and amoxycillin for 7 days has a success rate of 85-90%. Improved living standard and sanitation are vital in the control of H. pylori transmission and infection. Future development may include the use of vaccines against H. pylori, and therapies specifically targeting cagA strains of the bacteria.
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PMID:Eradication of Helicobacter pylori in clinical situations. 1559 83


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