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 (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.
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PMID:Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis. 151 5

The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.
Carcinogenesis 1995 Aug
PMID:Effect of Helicobacter mustelae infection on ferret gastric epithelial cell proliferation. 763 23

Although an association is suggested between gastric cancer and prior infection with Helicobacter pylori (HP), the role of HP in gastric carcinogenesis remains obscure. HP has potent urease activity and produces ammonia, a factor causing HP-related gastroduodenal mucosal lesions. In this study, rats were examined in an effort to determine effects of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After pretreatment with MNNG (83 mg/l) for 24 weeks, a solution of either 0.01% ammonia or plain tap water was administered to the animals as drinking water for an additional 24 weeks. The administration of the 0.01% ammonia solution significantly increased the incidence and number of cancers in the glandular stomach. The numbers of cases in which these cancers penetrated the muscle layer or deeper and of low-grade differentiated adenocarcinomas were significantly higher in rats receiving the ammonia solution. Continuing administration of ammonia accelerated cell proliferation in the gastric mucosa, but had no effect on the serum gastrin level. Therefore, gastric ammonia, which stimulates mucosal cell proliferation, appears to be an important promoter in carcinogenesis in rats and possibly in the HP-related gastric carcinogenesis in humans.
Carcinogenesis 1995 Mar
PMID:Mechanism for ammonia-induced promotion of gastric carcinogenesis in rats. 769 14

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.
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PMID:[Helicobacter pylori in peptic ulcer and gastric cancer]. 785 88

Gastric cancer is the world's overall second most common cancer, and carries a bad prognosis. In the Correa model of gastric carcinogenesis, environmental factors (salt, nitrate, a lack of vitamin C and beta-carotene, bile reflux, bacterial overgrowth in atrophic gastritis with nitrosamine formation) are related to the evolution from normal gastric tissue through superficial gastritis, multifocal atrophic gastritis, intestinal metaplasia and dysplasia to carcinoma. The incidence of H. pylori decreases with progressing preneoplastic lesions. In several studies, the prevalence of H. pylori was elevated in patients with gastric cancer, with a trend for a higher prevalence in intestinal type gastric cancer vs diffuse type. Family members of patients with gastric adenocarcinoma have a higher H. pylori prevalence than controls; patients infected with H. pylori have more family members with gastric cancer. Several epidemiological studies showed a higher H. pylori prevalence in regions or populations with high gastric cancer risk vs low-risk populations. Large-scale studies in China and Europe showed a correlation between H. pylori seroprevalence and gastric cancer incidence and mortality. Three prospective nested case-control studies showed that infection with H. pylori increased the risk of further development of gastric adenocarcinoma, showing that H. pylori infection precedes the development of gastric cancer. Several pathways can be identified explaining the association between H. pylori and gastric adenocarcinoma. We showed that gastric cell proliferation is increased in parallel with inflammation. The ascorbic acid concentrating mechanism is abolished in gastritis. Ammonia, generated by H. pylori's urease, gives rise to gastric mucosal atrophy. We showed that salt increases the gastric cell proliferation only in H. pylori-infected individuals. The organism's toxin may play a role in gastric cancer. Besides H. pylori, other environmental factors are important in determining the gastric cancer risk. For instance, we showed that in Belgium, Maghreb immigrants have a high prevalence of H. pylori infection but a low prevalence of intestinal metaplasia and gastric cancer. Gastric lymphoma is rare (about 5% of all gastric tumours), but its incidence is steadily increasing. It was shown that H. pylori also increases the risk for low-grade as well as high-grade gastric lymphoma. Eradication of H. pylori has been shown to cure several cases of unequivocally proven gastric low-grade lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Helicobacter pylori: the link with gastric cancer. 806 90

Helicobacter pylori infection has been associated with chronic atrophic gastritis, a precursor of gastric cancer. We conducted a prospective, case-controlled study to investigate whether H. pylori infection increases the risk of gastric cancer in Korean people with a high risk of gastric cancer. We enrolled 160 gastric cancer patients who were confirmed by endoscopic biopsy during 1994 and 160 age-matched control subjects with non-ulcer dyspepsia were compared to document the relationship between H. pylori infection and gastric cancer. The presence of H. pylori infection was determined by the rapid urease test and/or histology by Wright-Giemsa staining. The overall presence of H. pylori infection was 60% in gastric cancer patients and 51.9% in age-matched control subjects (odds ratio 1.39; 95% confidence interval 0.894-2.17; P = 0.143). Carcinomas of cardia, body and antrum were not associated with H. pylori infection (odds ratio 1.43, 1.69 and 1.29, respectively; 95% confidence interval, 0.271-7.52, 0.787-3.62 and 0.689-2.43, respectively; P = 0.178, 0.177 and 0.642, respectively) nor was the intestinal or diffuse type of cancer (odds ratio 1.39 and 1.40, respectively; 95% confidence interval 0.791-2.45 and 0.681-2.87, respectively; P = 0.250 and 0.835, respectively). Gender was not a risk for gastric cancer. In contrast to previous studies, these results do not provide evidence of H. pylori infection for gastric carcinogenesis in Korea.
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PMID:Helicobacter pylori infection and the risk of gastric cancer among the Korean population. 908 9

Colonization of Helicobacter pylori (Hp) to gastric mucosa plays an important role for the pathogenesis of gastric mucosal lesions. We previously reported the importance of monochloramine (NH2Cl), which was derived from the interaction between Hp-urease and infiltrated leukocytes, in the course of Hp-associated gastric mucosal injury. While the long-term infection of Hp in the gastric mucosa is known to be one of the virulent factors which closely link to the gastric carcinogenesis, the details of its pathogenetic mechanisms remain speculative. The present study is designed to examine whether a NH2Cl could damage the DNA of gastric cells. Rabbit gastric mucosal cells (RGMC) or KATO III cells were cultured and suspended. Cell suspensions were exposed to HOCl, NH3 or NH2Cl for 15 min to give a final concentration of 0.1 mM. The magnitude of a double strand break of DNA was quantified by measuring the remnant double strand stained by ethidium bromide (EB), and the fluorescence intensity of EB was analyzed by spectrophotometer. Separately, cell nuclei were stained by fluorescent dye (Hoechst No. 33258) in order to evaluate the levels of chromatin condensation evoked by DNA fragmentation. The number of cells with chromatin condensation was counted. During the entire experimental period, more than 85% of cells were persistently viable in all groups. NH2Cl significantly induced the DNA double strand break as well as chromatin condensation in RGMC and KATO III cells (P < 0.05). However, NH3 or HOCl did not induce the DNA double strand break as well as chromatin condensation in both cells. NH2Cl, but not its precursors (NH3 or HOCl), enhanced the levels of DNA injury, suggesting the possible involvement in the carcinogenesis of Hp-associated gastric mucosa.
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PMID:Extensive DNA damage induced by monochloramine in gastric cells. 914 31

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.
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PMID:Decreased gastric proliferation of foveolar epithelial cells after the eradication of Helicobacter pylori. 936

The role of Helicobacter pylori in gastric carcinogenesis is a subject of an increasing interest. In this report we describe a prospective study on the resected stomachs to establish the prevalence of H. pylori in different types of gastric carcinoma. The material consisted of 62 consecutive patients operated on stomach adenocarcinomas Fifty six percent of the patients were intestinal type, 34%--diffuse type and 10%--mixed type. The presence of H. pylori was studied in specimens from surgically removed stomachs. The conformation of the bacterial infection was done by means of rapid urease test, microbiological culture, Warthin-Starry and immunohistochemical staining. The overall prevalence of H. pylori infection was 69% (43/62). There was a statistically significant difference in the infection rates between the types of carcinoma--75% in the intestinal type and 62% in the diffuse type. The most sensitive was immunohistochemical staining. The bacterial colonies were cumulated far from the tumor tissue. In cardiac cancer the most intense of infection was an antrum and lower part of gastric body. In opposite; in antrum and pylorus cancer the scope of colonisation increased in fundus and subcardiac region with statistical signification. We could not detect H. pylori in the tumor tissue itself as in the normal mucosa of the stomach. In gastric antrum the most intense colonisation was detected on mucosal atrophy, but in the upper part of the stomach--on the mucosal metaplasia.
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PMID:Topography of Helicobacter pylori infection in gastric cancer patients. 944 64

A high-salt diet in humans and experimental animals is known to cause gastritis, has been associated with a high risk of atrophic gastritis, and is considered a gastric tumor promoter. In laboratory rodents, salt is known to cause gastritis, and when coadministered, it promotes the carcinogenic effects of known gastric carcinogens. Because Helicobacter pylori has been associated with a progression from gastritis to gastric cancer, we designed a study to determine whether excessive dietary NaCl would have an effect on colonization and gastritis in the mouse model of H. pylori infection. Seventy-two, 8-week-old female C57BL/6 mice were infected with H. pylori strain Sydney, and 36 control mice were dosed with vehicle only. One-half of the infected and control mice were fed a high-salt diet (7.5% versus 0.25%) for 2 weeks prior to dosing and throughout the entire experiment. Twelve infected and 6 control animals from the high-salt and normal diet groups were euthanized at 4, 8, and 16 weeks. At 8 and 16 weeks postinfection (WPI), the colony-forming units per gram of tissue were significantly higher (P < 0.05) in the corpus and antrum of animals in the high-salt diet group compared with those on the normal diet. Quantitative urease was significantly higher (P < 0.05) at 4 and 8 WPI in the corpus and antrum of animals on the high-salt diet when compared with controls. At 16 WPI, mice in both the normal and the high-salt diet groups developed moderate to marked atrophic gastritis of the corpus in response to H. pylori infection. However, the gastric pits of the corpus mucosa in mice on the high-salt diet were elongated and colonized by H. pylori more frequently than those in mice on the normal diet. The high-salt diet was also associated with a significant increase in proliferation in the proximal corpus and antrum and a multifocal reduction in parietal cell numbers in the proximal corpus, resulting in the elongation of gastric pits. We conclude that excessive NaCl intake enhances H. pylori colonization in mice and in humans and that chronic salt intake may exacerbate gastritis by increasing H. pylori colonization. Furthermore, elevated salt intake may potentiate H. pylori-associated carcinogenesis by inducing proliferation, pit cell hyperplasia, and glandular atrophy.
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PMID:High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. 1051 91


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