PubMed Health⌕ Search

Biomedical subjects

J E Crabtree

Publications and source records attributed to J E Crabtree.

At least 19 recordsLinked to original sources
PubMed2006

Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected with Helicobacter pylori.

BACKGROUND: Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion. AIM: To study the association between the pattern of H pylori gastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease. METHODS AND MATERIALS: Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy and H pylori infection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO. RESULTS: Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R(2) = 0.62). CONCLUSION: Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected with H pylori.

Adolescent↗
PubMed2005

Protection against Helicobacter pylori infection in the Mongolian gerbil after prophylactic vaccination.

Vaccines against Helicobacter pylori could circumvent the problem of increasing antibiotic resistance. They would be particularly useful in developing countries, where re-infection rates are high following standard eradication regimes. The Mongolian gerbil is a good model for H. pylori infection, as the gastric pathology induced by infection is similar to that in humans. The H. pylori-induced inflammatory response in gerbils is considerably greater than in murine models. The aim of this study was to determine if gerbils could be vaccinated against H. pylori. Mongolian gerbils were vaccinated orally with an H. pylori whole cell sonicate preparation and cholera toxin adjuvant. Vaccinated gerbils and controls were challenged with the autologous H. pylori strain 42GX. All infection, and cholera toxin, control gerbils were H. pylori positive 6 weeks post-challenge. By contrast, a significant degree of protection was demonstrated in vaccinated gerbils. Only two of 10 of gerbils were H. pylori positive (P<0.001). Protection was associated with increased serum H. pylori IgG antibodies. Protected gerbils had histologically normal gastric mucosa and, in contrast to mice, no post-immunisation gastritis was evident. In the control groups, the degree of inflammation was variable, with some of the animals having corpus gastritis and corpus mucous metaplasia. The levels of gastric IL-12p40 and IFNgamma transcripts were significantly decreased in vaccinated animals compared to infection and cholera toxin controls (P<0.01). Gastric IL-10 and TGFbeta transcripts were found only at relatively low levels. These results demonstrate that Mongolian gerbils can be successfully vaccinated against H. pylori and protected from H. pylori-induced pathology.

Animals↗
PubMed2003

The effect of gender on Helicobacter felis-mediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model.

The murine Helicobacter felis model has been extensively used to investigate the importance of host factors in the development of chronic gastritis. The effect of gender in this murine model is unknown. Male and female C57BL/6J mice were infected with H felis for up to 1 year. At 4, 8, 19, 36, and 52 weeks post-infection, gastric histopathology, epithelial cell proliferation, and apoptosis were examined and compared with age- and gender-matched controls. In female mice, infection with H felis resulted in an earlier onset of chronic gastric inflammation, epithelial hyperplasia, and oxyntic cell loss than males. In females, there was a trend towards increased gastric pathology compared with males, with long-term-infected female mice having significantly greater (p < 0.05) chronic inflammation than male mice. The histopathological differences in male and female mice did not relate to the density of H felis infection. Female mice infected with H felis had significantly increased gastric epithelial cell proliferation in the cardia and corpus at both 8 and 52 weeks post-infection (p < 0.05). Epithelial cell apoptosis in the glandular mucosa of the corpus at 36 and 52 weeks post-infection was significantly increased (p < 0.05) in female mice compared with uninfected gender controls. In contrast, there was no significant increase in epithelial cell proliferation or apoptosis in any area of the stomach at any time point after H felis infection in male mice. These results demonstrate that there are gender differences in the gastric inflammatory and epithelial response to H felis in the murine model. The functional importance of gender should be considered in future murine studies on H felis- and H pylori-induced chronic gastritis.

Animals↗
PubMed2003

IgG subclass response to Helicobacter pylori and CagA antigens in children.

Specific serum IgG subclass antibodies against Helicobacter pylori antigens and recombinant CagA were analysed in 75 symptomatic children with histologically confirmed H. pylori infection. H. pylori stimulated an IgG1 predominant response, and IgG3 titres showed a positive association with peptic ulcer disease, chronicity of antral inflammation and density of H. pylori colonization. Two methods used for assessing serum IgG CagA antibody status, i.e. Western blotting and enzyme-linked immunosorbent assay (ELISA), were concordant. CagA stimulated an IgG1 and IgG3 predominant humoral response. Total CagA IgG titres were higher in children with active and more severe chronic antral inflammation. These findings suggest that in children the systemic humoral immune response to H. pylori infection may reflect gastroduodenal pathology.

Adolescent↗
PubMed2003

Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue.

BACKGROUND: Screening of cDNA arrays of the IMAGE library identified human zFOC1 as a differentially expressed cDNA that was upregulated in KATO III gastric cancer cells following stimulation with the gastric pathogen Helicobacter pylori. AIMS: To determine the expression of zFOC1 in gastric mucosa with and without H pylori infection and in patients with gastric cancer. RESULTS: zFOC1 is localised on chromosome 12q24.3 and encodes a zinc finger protein. Expression studies in human H pylori infected and uninfected gastric biopsies, gastric tumours, and gastric cancer cell lines revealed that zFOCI gene transcripts are significantly higher in gastric cancer than in non-cancerous gastric tissues. CONCLUSIONS: The zFOC1 gene appears to be a tumour marker associated with gastric cancer.

Amino Acid Sequence↗
PubMed2002

Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF.

Helicobacter pylori has a major aetiological role in human gastric carcinogenesis but the cellular and molecular pathways by which infection promotes transformation remain to be resolved. This study demonstrates that H. pylori exposure to MKN-1, ST42, and MKN-28 gastric epithelial tumour cells results in the activation of HB-EGF gene expression and EGFR tyrosine phosphorylation. These cell responses are induced by both cagPAI positive and cagPAI negative H. pylori strains and are dependent on cell surface expression of the HB-EGF precursor. The induction of HB-EGF gene transcription by H. pylori requires metalloprotease-, EGFR-, and Mek1-activities, indicating the involvement of the "triple membrane passing signal" (TMPS) for EGFR transactivation. Moreover, the release of the inflammatory cytokine IL-8 by cells exposed to H. pylori is significantly impaired by inhibitors of TMPS pathway elements. Our findings support a model in which H. pylori triggers constitutive EGFR signal activation, which enhances IL-8 production, and initiates neoplastic transformation of gastric epithelial cells.

Blotting, Northern↗
PubMed2002

Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.

Adult↗
PubMed2001

Expression of Interleukin-18, a Th1 cytokine, in human gastric mucosa is increased in Helicobacter pylori infection.

Interleukin-18 (IL-18), a cytokine that promotes Th1 responses, is processed to the active mature protein by caspase-1. The effects of Helicobacter pylori infection on gastric IL-18 and caspase-1 were examined. In antral mucosa, IL-18 mRNA expression was greater (P<.01) in H. pylori-positive (n=40) than in H. pylori-negative patients (n=29) with normal mucosa. Inactive precursor (24 kDa) and mature (18 kDa) IL-18 were present in antral biopsy specimens from uninfected and infected subjects. In corpus mucosa, mature IL-18 and a 16-kDa protein, corresponding to inactive IL-18, were present. Active caspase-1 p20 subunit was detected in antral and corpus mucosa of infected and uninfected subjects. These data show that, although H. pylori infection is associated with increased antral IL-18 mRNA expression, mature IL-18 protein and active caspase-1 p20 are present in mucosa of both H. pylori-infected and -uninfected subjects. IL-18 may have an important role in promoting gastric Th1 responses in H. pylori infection.

Adult↗
PubMed2001

cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes.

Helicobacter pylori strains containing the cag pathogenicity island (PAI) induce NF-kappaB activation and interleukin-8 secretion in gastric epithelial cells. The aim of this study was to investigate changes in epithelial gene expression induced by cag PAI-positive and -negative strains of H. pylori using high-density cDNA array hybridization technology. Radio-labeled cDNA prepared from H. pylori-infected Kato 3 gastric epithelial cells was hybridized to high-density cDNA arrays to identify changes in epithelial gene expression compared to noninfected controls. In vivo expression of selected, differentially expressed genes was examined by reverse transcription-PCR analysis of H. pylori-positive and -negative gastric mucosa. Screening of ca. 57,800 cDNAs identified 208 known genes and 48 novel genes and/or expressed sequence tags of unknown function to be differentially expressed in Kato 3 cells following H. pylori infection. Marked differences in gene expression profiles were observed following cag PAI-positive and cag PAI-negative infection with 15 novel cDNAs and 92 known genes being differentially expressed. H. pylori was found to change the expression of genes encoding growth factors and cytokine/chemokines and their receptors, apoptosis proteins, transcription factors and metalloprotease-disintegrin proteins (ADAMs), and tissue inhibitors of metalloproteinases. Gastric differential expression of selected known genes (amphiregulin and ADAM 10) and a novel gene (HPYR1) was confirmed in vivo in patients with H. pylori infection. Confirmation of the in vivo expression of selected genes demonstrates the usefulness of this approach for investigating pathogen-induced changes in host gene expression.

ADAM Proteins↗
PubMed2001

Influence of smoking and alcohol on gastric chemokine mRNA expression in patients with Helicobacter pylori infection.

AIM: Chemokines that play a primary role in active inflammation are increased in gastric mucosa infected with Helicobacter pylori. Cigarette smoking increases the risk of peptic ulcer disease and gastric cancer, whereas alcohol might exert an antibacterial role. The aim of this study was to examine the association between smoking or alcohol consumption and mucosal chemokine mRNA expression in H pylori associated gastritis. METHODS: Gastric biopsy specimens were obtained from 46 patients with dyspepsia who were infected with H pylori, and total RNA was extracted. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the mRNA expression of three C-X-C chemokines (interleukin 8 (IL-8), growth related oncogene alpha (GRO alpha), epithelial neutrophil activating protein 78 (ENA-78)) and two C-C chemokines (regulated on activation normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1)). RESULTS: GRO alpha and ENA-78 mRNA expression was significantly increased (p < 0.05) in 22 smokers compared with 24 non-smokers; however, no difference was seen in the expression of IL-8, RANTES, and MCP-1 mRNA. No differences were observed in chemokine mRNA expression in relation to alcohol consumption. CONCLUSIONS: The increased C-X-C chemokine mRNA expression seen in smokers might play a role in inducing enhanced inflammatory activity in gastritis and the consequent severe diseases associated with H pylori infection.

Alcohol Drinking↗
PubMed2000

Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study.

BACKGROUND AND AIMS: Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS: Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS: The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS: Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer.

Adult↗
PubMed2000

The effect of ammonia on omeprazole-induced reduction of gastric acidity in subjects with Helicobacter pylori infection.

OBJECTIVE: Omeprazole produces a higher intragastric pH during Helicobacter pylori (H. pylori) infection than after cure. We tested the hypothesis that this difference is due to the production of ammonia by H. pylori. METHODS: Gastric acidity and acid output (AO) were measured overnight in 12 subjects, with and without omeprazole, before and 1 and 6 months after cure of H. pylori infection. Gastric ammonia ([NH3]), total bile acid ([TBA]) and protein concentrations and plasma omeprazole levels were measured. RESULTS: During omeprazole, median AO were 0.0 mmol/h before, 0.86 mmol/h (p = 0.003 vs before cure) at 1 month, and 0.34 mmol/h (p = 0.02) at 6 months after cure; median NH3 output was 0.17 mmol/h before, 0.03 mmol/h (p = 0.002) at 1 month, and 0.02 mmol/h (p = 0.005) at 6 months after cure. AO and NH3 output were similar 1 and 6 months after cure. When corrected for [NH3], AO and gastric pH curves were similar before and after cure. Omeprazole plasma levels increased after cure and gastric [TBA] were unchanged. CONCLUSIONS: The higher pH observed before cure of H. pylori during omeprazole administration is attributable, in large part, to ammonia production. Other acid-neutralizing substances and changes in acid secretion may also be important, but duodenogastric reflux and omeprazole pharmacokinetics are not involved.

Adult↗
PubMed2000

Dyspepsia is associated with CagA-positive Helicobacter pylori.

OBJECTIVE: The role of Helicobacter pylori in nonulcer dyspepsia is controversial. Speculation has arisen that only strains of H. pylori carrying the CagA virulence factor are important in the development of dyspepsia. The objective of this study was to determine whether nonulcer dyspepsia correlated with CagA-positive H. pylori infection. METHODS: A total of 435 healthy blood donors and 102 general medicine clinic respondents completed the Bowel Disease Questionnaire and the PRIME-MD survey, a validated screen for common psychiatric disorders. Subjects were classified as cases of nonulcer dyspepsia if they reported pain in the upper abdomen more than six times in the previous year and denied a past or current history of peptic ulcer disease. Study participants were tested for IgG antibodies to H. pylori and the CagA protein. RESULTS: Clinic respondents were more likely than healthy blood donors to meet the case definition for nonulcer dyspepsia (34% vs 13%, p < 0.001), to be seropositive for H. pylori (54% vs 18%, p < 0.001), and to be CagA seropositive (41% vs 10%, p = 0.01). Logistic regression identified CagA seropositivity (p = 0.03), race (p = 0.001), and positive screens for depression (p = 0.007) or somatization (p < 0.001) as variables independently associated with nonulcer dyspepsia. CONCLUSION: Infection with a CagA-positive strain of H. pylori is associated with a clinical diagnosis of nonulcer dyspepsia. However, nonulcer dyspepsia was also strongly and independently associated with positive screens for depression or somatization disorder as well as with ethnicity. These potential sources of variance should be considered in the design of future studies evaluating nonulcer dyspepsia.

Adult↗
PubMed2000

Co-expression in Helicobacter pylori of cagA and non-opsonic neutrophil activation enhances the association with peptic ulcer disease.

AIMS: To investigate the association of cagA positivity and non-opsonic neutrophil activation capacity in wild-type Helicobacter pylori strains with peptic ulcer disease or chronic gastritis only. METHODS: Helicobacter pylori were isolated from antral biopsies of 53 consecutive patients with chronic antral gastritis, of whom 24 had peptic ulcer disease endoscopically. The presence of cagA, a marker for the cag pathogenicity island, was determined by polymerase chain reaction with specific oligonucleotide primers, and non-opsonic neutrophil activation capacity by luminol enhanced chemiluminescence. RESULTS: The cagA gene was present in 39 of 53 (73.6%) strains, 20 of which (83.3%) were from the 24 patients with peptic ulcer disease and 19 (65.5%) from the 29 patients with chronic gastritis only. Non-opsonic neutrophil activation was found in 29 (54.7%) strains, 16 of which (66.7%) were from patients with peptic ulcer disease, and 13 (44.8%) from those with chronic gastritis. Non-opsonic neutrophil activation was found more frequently in cagA+ than cagA- strains (59% v 42.9%). Whereas four of the 14 cagA- strains and eight of the 24 non-opsonic neutrophil activation negative strains were from patients with peptic ulcer disease, only two of 24 (8.3%) peptic ulcer disease strains expressed neither cagA nor non-opsonic neutrophil activation. The cagA gene and non-opsonic neutrophil activation capacity were co-expressed in 14 of 24 (58.3%) strains from patients with peptic ulcer disease, and in nine of 29 (31%) strains from individuals with chronic gastritis. CONCLUSIONS: Positivity for cagA and non-opsonic neutrophil activation occur independently in wild-type H pylori strains. However, co-expression of the two markers enhanced the prediction of peptic ulcer disease.

Antigens, Bacterial↗
PubMed1999

Gastric cancer, cytotoxin-associated gene A-positive Helicobacter pylori, and serum pepsinogens: an international study. The Eurogst Study Group.

BACKGROUND & AIMS: CagA-positive Helicobacter pylori infection has been more closely associated with gastric disease than CagA-negative infection. This study evaluated whether geographic variation in the prevalence of CagA could explain variation in gastric cancer rates. METHODS: The Eurogast study was conducted in 17 centers in 13 countries. Gastric cancer rates were calculated for each center, and serum samples from approximately 2850 subjects were assayed for immunoglobulin G antibodies to H. pylori and CagA and for pepsinogens A and C. RESULTS: The proportion of CagA-positive H. pylori infections varied across the centers, but this variation did not explain any more of the variation in gastric cancer rates than H. pylori alone. Subjects with CagA-positive infection had, however, significantly higher pepsinogen levels and a lower pepsinogen A/C ratio than subjects with CagA-negative infection; this pattern was observed consistently across the study centers. CONCLUSIONS: Variation in the seroprevalence of CagA did not explain geographic variation in gastric cancer rates any better than H. pylori alone. However, the consistent variation in pepsinogen levels with CagA status across the study centers supports the importance of the role of CagA in the development of gastric disease.

Adult↗
PubMed1999

Exaggerated systemic antibody response to mucosal Helicobacter pylori infection in IgA nephropathy.

Numerous studies in the literature report aberrant immune responsiveness in immunoglobulin A (IgA) nephropathy. However, all these studies investigate immune responses invoked by an artificially engineered antigen challenge. For the first time in IgA nephropathy, we report the systemic humoral responses generated as part of an active mucosal immune response against a common environmental pathogen, Helicobacter pylori (Hp). We studied 22 patients with IgA nephropathy and 9 controls without renal disease who were shown to be infected with Hp, using a 13C-urea breath test. Hp antigen-specific enzyme-linked immunosorbent assays were established to measure the anti-Hp IgA, IgG, and IgA and IgG subclass antibody levels. In addition, anti-Hp responses in the monomeric and polymeric (pIgA) fractions of serum IgA were measured after separation by gel filtration high-performance liquid chromatography. IgA nephropathy was associated with both a greater rate of IgA anti-Hp seropositivity (P < 0.05) and a more pronounced IgA anti-Hp antibody response (P < 0.01). In almost all cases, IgA anti-Hp was IgA1, and more than 90% was polymeric. There was no difference in the frequency of IgG anti-Hp seropositivity, but patients produced a much greater IgG anti-Hp response (P < 0.01). In addition, the IgG subclass responses were markedly different, with IgG1 predominant in controls and IgG2 and IgG3 the major subclasses produced in IgA nephropathy. We have shown an exaggerated systemic antibody response to mucosal infection caused by Hp in patients with IgA nephropathy, predominantly consisting of pIgA1, IgG2, and IgG3. This suggests that in IgA nephropathy, not only is pIgA1 production poorly controlled, but regulation of IgG isotype switching in response to mucosal pathogens is also deranged.

Adolescent↗
PubMed1999

Non-steroidal anti-inflammatory drugs inhibit Helicobacter pylori-induced human neutrophil reactive oxygen metabolite production in vitro.

BACKGROUND: Helicobacter pylori infection is associated with increased production of gastric mucosal reactive oxygen metabolites which have been implicated in mucosal damage and carcinogenesis. In vitro, neutrophils produce reactive oxygen metabolites following activation by H. pylori. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil activation by several factors, e.g. N-formyl-methionyl-leucyl-phenyalanine (f-MLP). AIM: To examine the effect of NSAIDs on H. pylori-induced reactive oxygen metabolite production by human peripheral blood neutrophils. METHODS: Neutrophils were stimulated by H. pylori (NCTC 11637) water extract or f-MLP in the presence or absence of NSAIDs. Reactive oxygen metabolite activity was measured by luminol-enhanced chemiluminescence. RESULTS: H. pylori water extract stimulated a sevenfold increase in chemiluminescence which was inhibited dose-dependently by diclofenac. All six NSAIDs studied (at 10-4 M) significantly inhibited H. pylori-and f-MLP-stimulated neutrophil reactive oxygen metabolite production. Meclofenamic acid and diclofenac had the greatest inhibitory effects on both H. pylori and f-MLP-stimulated neutrophil reactive oxygen metabolite production. The inhibitory effects of other NSAIDs varied with the activation stimulus. NSAIDs did not quench reactive oxygen metabolites generated in a cell-free xanthine:xanthine oxidase assay. CONCLUSION: Several NSAIDs attenuate H. pylori-induced neutrophil reactive oxygen metabolites production in vitro. This may be relevant to a potential chemopreventative role in gastric cancer and to a possible lack of synergy between H. pylori and NSAID use regarding peptic ulceration.

Adult↗