Pylori cagA-positive Strains Research Articles

Epstein-barr virus/Helicobacter pylori coinfection and gastric cancer: the possible role of viral gene expression and shp1 methylation.

Among the various factors involved in the development of gastric cancer (GC), infectious agents are one of the most important causative inducers. This study aimed to investigate the possible role of EBV gene expression on SHP1 methylation in co-infection with Helicobacter pylori in patients with GC. Formalin-fixed paraffin-embedded samples were obtained from 150 patients with gastrointestinal disorders. The presence of the H. pylori and EBV genome were examined by PCR. The expression level of viral gene transcripts and methylation status of the SHP1 cellular gene was assessed by quantitative real-time PCR and methyl-specific PCR. EBV and H. pylori coinfection were reported in 5.6% of patients. The mean DNA viral load was significant in patients coinfected with cagA-positive H. pylori (P= 0.02). The expression of BZLF1 and EBER was associated with GC. Also, the expression level of BZLF1in GC tissues was significantly higher in coinfection (P = 0.01). SHP1 methylation frequency was higher in the GC group than in the control group (P = 0.04). The correlation between the methylation rate and the H. pylori infection was highly significant (P<0.0001). The strongest positive correlation was observed in GC specimens between SHP1 methylation and H. pylori cagA-positive strains (p= 0.003). Our results suggested that cagA might involve in the elevation of EBV lytic gene expression and SHP1 methylation, and the development of gastric cancer. Understanding the mechanism of EBV H. pylori - cagA + coinfection, as well as host epigenetic changes, can play an important role in diagnosing and preventing gastric cancer.

Helicobacter pylori cytotoxin-associated gene A virulence and its association with the epithelial-mesenchymal transition in gastric cancer

Gastric cancer is currently one of the most prevalent malignancies worldwide with a high mortality rate. Helicobacter pylori (H. pylori) infection significantly contributes to the onset and progression of gastric cancer mainly due to the induction of chronic inflammatory responses. The pathogenicity of H. pylori is associated with a vast number of virulence factors among which cytotoxin-associated gene A (CagA) plays a crucial role. We conducted a literature review of PubMed, Web of Science, and Scopus on September 1st, 2021. There were no limits regarding the year and the language of publication. Articles included in this review concerned human and animal studies. The following search string was applied during the search: (gastric cancer) AND (epithelial-mesenchymal transition) AND (Helicobacter pylori) AND (cytotoxin-associated gene A). The final analysis included 135 articles independently reviewed by the authors. H. pylori CagA-positive strains seem to be more virulent compared to the CagA-negative strains. CagA pathogenicity includes the increased secretion of pro-inflammatory cytokines, induction of cancer stem cell-like properties, apoptosis prevention, or overactivation of particular oncogenic pathways. H. pylori might induce epithelial-mesenchymal transition (EMT) via numerous pathways, among which CagA-related pathogenicity is considered to be of high significance. Mechanisms associated with CagA action are involved in the maintenance of chronic H. pylori infection, subsequent EMT induction, and further onset and progression of gastric cancer. Because of a huge number of H. pylori strains with different virulence mechanisms, the clinical outcome of patients is also associated with the particular type of strain that infected a patient.

Epidemiology of Helicobacter pylori and CagA-Positive Infections and Global Variations in Gastric Cancer.

Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95–4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58–3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46–0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies.

CagA-positive Helicobacter pylori strain containing three EPIYA C phosphorylation sites produces increase of G cell and decrease of D cell in experimentally infected gerbils (Meriones unguiculatus)

PurposeHuman infection by Helicobacter pylori is associated with an increase in the number of gastrin-producing G cells and a concomitant decrease of somatostatin-producing D cells. However, to our knowledge, changes in G and D cell numbers in response to infection with H. pylori CagA-positive strains containing different number of EPIYA-C phosphorylation sites have not been analyzed to date. Therefore, the aim of this study was to perform a quantitative analysis of the number of G and D cells in Mongolian gerbils challenged with H. pylori strains with different numbers of EPIYA-C motifs. Materials and methodsMongolian gerbils were inoculated with isogenic H. pylori strains containing one to three phosphorylation sites. Mucosal fragments were evaluated by morphometry and immunohistochemistry using primary polyclonal rabbit anti-gastrin and anti-somatostatin antibodies. Positive cells were counted using an image analyzer. ResultsForty-five days after infection, there was a decrease in the number of D cells and an increase in the G/D cell ratio in the group with three EPIYA-C. Six months after infection, there was a progressive and significant increase in the number of G cells and in the G/D cell ratio, with a concomitant decrease in the number of D cells, especially in the three EPIYA-C group. ConclusionsCagA-positive H. pylori strains containing a large number of EPIYA-C phosphorylation sites induce a decrease in D cell number and an increase in G cell number and G/D ratio, which were correlated with the number of inflammatory cells of the lamina propria.

CagA EPIYA polymorphisms in Colombian Helicobacter pylori strains and their influence on disease-associated cellular responses.

To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori) strains from Colombia on the host cell biology. Eighty-four H. pylori-cagA positive strains with different Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs patterns, isolated from patients with gastritis (n = 17), atrophic gastritis (n = 17), duodenal ulcer (n = 16), intestinal metaplasia (n = 16) and gastric cancer (n = 18), were included. To determine the integrity of the cag pathogenicity island (cagPAI) we evaluated the presence of cagA, cagT, cagE, and cag10 genes by polymerase chain reaction. AGS gastric epithelial cells were infected with each strain and assayed for translocation and tyrosine phosphorylation of CagA by western blot, secretion of interleukin-8 (IL-8) by enzyme-linked immuno sorbent assay after taking supernatants from cocultures and cell elongation induction. For cell elongation quantification, coculture photographs were taken and the proportion of "hummingbird" cells (> 15 μm) was determined. Overall 72% (60/84) of the strains were found to harbor a functional cagPAI. Levels of phosphorylated CagA were significantly higher for isolates from duodenal ulcer than the ones in strains from gastritis, atrophic gastritis, intestinal metaplasia and gastric cancer (49.1% ± 23.1% vs 21.1% ± 19.5%, P < 0.02; 49.1% ± 23.1% vs 26.2% ± 14.8%, P < 0.045; 49.1% ± 23.1% vs 21.5% ± 19.5%, P < 0.043 and 49.1% ± 23.1% vs 29.5% ± 27.1%, P < 0.047 respectively). We observed variable IL-8 expression levels ranging from 0 to 810 pg/mL and from 8.8 to 1442 pg/mL at 6 h and 30 h post-infection, respectively. cagPAI-defective strains did not induce detectable levels of IL-8 at 6 h post-infection. At 30 h post-infection all strains induced IL-8 expression in AGS cells, although cagPAI-defective strains induced significantly lower levels of IL-8 than strains with a functional cagPAI (57.1 ± 56.6 pg/mL vs 513.6 ± 338.6 pg/mL, P < 0.0001). We did not observe differences in the extent of cell elongation induction between strains with a functional or a defective cagPAI in 6 h cocultures. At 24 h post infection strains with functional cagPAI showed high diversity in the extent of hummingbird phenotype induction ranging from 7% to 34%. cagPAI defective strains induced significantly lower levels of elongation than strains with functional cagPAI with one or more than one EPIYA-C motif (15.1% ± 5.2% vs 18.9% ± 4.7%, P < 0.03; and 15.1% ± 5.2% vs 20.0% ± 5.1%, P < 0.003 respectively). No differences were observed in cellular elongation induction or IL-8 expression among H. pylori strains bearing one and more than one EPIYA-C motifs, neither at 6 h nor at 24 h of coculture. There were no associations between the levels of induction of cell elongation or IL-8 expression and number of EPIYA motifs or pathology. The present work describes a lack of association between H. pylori CagA protein EPIYA motifs variations from Colombian isolates and disease-associated cellular responses.

EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains.

It is known that polymorphisms in C-terminal region of CagA influence gastric disease development on Helicobacter pylori infection. Additionally, the geographic distribution of these polymorphisms has been associated with the appearance of more severe gastroduodenal pathologies. Objective. To determine the CagA phosphorylation motifs pattern (EPIYA pattern) in Cuban H. pylori isolates, and to study its association with patient´s pathologies. DNAs from 95 H. pylori cagA-positive strains were used to amplify the 3´ variable region of cagA gene by PCR using two different strategies. Additionally, new primers were designed to identify either Western or Eastern CagAEPIYA motiftype by PCR. To confirm the PCR results, PCR products from 14 representative isolates were purified and sequenced. The distribution of the EPIYA motif found was: 2 AB (2.1 %), 1 AC (1.1 %), 1 BC (1.1 %), 70 ABC (73.6 %), 19 ABCC (20 %), and 2 ABCCC (2.1 %). Sequencing analysis confirmed the PCR classification in the 14 studied strains and showed three strains with unusual nucleotide sequences, not reported before. Distribution of the EPIYA-ABC pattern was equivalent in all pathologies (78.9 % in gastric ulcer, 72.5 % in duodenal ulcer and 72.2 % in non-ulcer dyspepsia). The PCR results using the new primers confirmed that all studied strains carried the Western CagA type. No specific EPIYA motif was associated with peptic ulcer. This is the first report that shows EPIYA motif distribution in H. pylori isolates from the Caribbean region.

EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains

Introduction. It is known that polymorphisms in C-terminal region of CagA influence gastric disease development on Helicobacter pylori infection. Additionally, the geographic distribution of these polymorphisms has been associated with the appearance of more severe gastroduodenal pathologies.Objective. To determine the CagA phosphorylation motifs pattern (EPIYA pattern) in Cuban H. pylori isolates, and to study its association with patient’s pathologies. Materials and methods. DNAs from 95 H. pylori cagA-positive strains were used to amplify the 3’ variable region of cagA gene by PCR using two different strategies. Additionally, new primers were designed to identify either Western or Eastern CagA EPIYA motif type by PCR. To confirm the PCR results, PCR products from 14 representative isolates were purified and sequencedResults. The distribution of the EPIYA motif found was: 2 AB (2.1 %), 1 AC (1.1 %), 1 BC (1.1 %), 70 ABC (73.6 %), 19 ABCC (20 %), and 2 ABCCC (2.1 %). Sequencing analysis confirmed the PCR classification in the 14 studied strains and showed three strains with unusual nucleotide sequences, not reported before. Distribution of the EPIYA-ABC pattern was equivalent in all pathologies (78.9 % in gastric ulcer, 72.5 % in duodenal ulcer and 72.2 % in non-ulcer dyspepsia).Conclusion. The PCR results using the new primers confirmed that all studied strains carried the Western CagA type. No specific EPIYA motif was associated with peptic ulcer. This is the first report that shows EPIYA motif distribution in H. pylori isolates from the Caribbean region.

Nuclear translocation of β-catenin correlates with CD44 upregulation in Helicobacter pylori-infected gastric carcinoma

Infection with Helicobacter pylori CagA-positive strains is associated with gastric adenocarcinoma. CagA H. pylori activates the β-catenin signal by translocation into nucleus which promotes carcinogenesis. Deregulated accumulation of nuclear β-catenin enhances transcription of β-catenin target genes including CD44 and promotes malignant transformation. The aim of this study was to investigate whether nuclear translocation of β-catenin correlates with CD44 expression in CagA H. pylori-infected gastric carcinoma. To address these issues, we examined 140 gastric biopsy specimens by using immunohistochemical and immunofluorescence staining, Western blot, and mutational analysis of the exon 3 β-catenin gene. The nuclear localization of β-catenin was significantly (χ(2) = 21.175; P < 0.001) increased in advanced gastric carcinoma and also correlated (χ(2) = 22.857; P < 0.001) with the CagA H. pylori positive specimens. We also observed that tyrosine-phosphorylated β-catenin was significantly (χ(2) = 14.207; P < 0.001) increased in samples showing nuclear localization of β-catenin and also it correlated (χ(2) = 43.69; P < 0.03) with the CagA H. pylori positive specimens. Exon 3 β-catenin gene mutation was not detected in H. pylori-infected gastric carcinoma. CD44 up regulation was significantly associated with tyrosine-phosphorylated β-catenin (χ(2) = 22.5; P < 0.001), and this change was closely associated with nuclear translocation of β-catenin (χ(2) = 13.393; P < 0.001) in CagA H. pylori-infected gastric carcinoma. In conclusion, our data suggest that CagA H. pylori infection is responsible for the tyrosine phosphorylation of β-catenin and its nuclear translocation, which upregulates β-catenin target gene CD44 in gastric carcinoma.

CpG Methylation and Reduced Expression of O6-Methylguanine DNA Methyltransferase Is Associated With Helicobacter pylori Infection

The gastric epithelium genome undergoes extensive epigenetic alterations during Helicobacter pylori-induced gastritis. Expression of the gene encoding the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) might be reduced via hypermethylation of its promoter in patients with H pylori gastritis. We characterized expression of MGMT and its epigenetic regulation via CpG methylation in gastric tissue from patients with H pylori gastritis and investigated the effects of H pylori infection eradication on MGMT expression. Gastric biopsy samples were collected from patients with H pylori gastritis before and after eradication and from H pylori-negative control subjects. AGS cells were cocultured with H pylori to study the effects of H pylori infection on MGMT RNA, protein expression, and CpG methylation. CpG methylation of MGMT was more frequent in the gastric mucosa of patients with H pylori gastritis (69.7%) than in those without (28.6%, P = .022). MGMT methylation was significantly reduced after H pylori eradication (from 70% to 48% of cases, P = .039), and mean levels of CpG methylation decreased from 12.6% to 5.7% (P = .025), increasing MGMT expression. MGMT methylation was significantly associated with CagA-positive H pylori (P = .035). H pylori reduced MGMT protein and RNA levels and induced MGMT CpG methylation in gastric AGS cells. H pylori gastritis, particularly in patients infected with H pylori CagA-positive strains, is associated with hypermethylation of MGMT and reduced levels of MGMT in the gastric epithelium. MGMT promoter methylation is partially reversible after eradication of H pylori infection. These data indicate that DNA repair is disrupted during H pylori gastritis, increasing mutagenesis in H pylori-infected gastric mucosa.

Role ofHelicobacter pyloriCagA Molecular Variations in Induction of Host Phenotypes with Carcinogenic Potential

Helicobacter pylori cagA-positive strains exert population-specific risks for gastric cancer. We determined whether variations in CagA phosphorylation motifs were associated with carcinogenic or proinflammatory epithelial phenotypes induced by strains from regions with divergent cancer risks (Colombia and Nashville, TN). Motif number was significantly related to levels of CagA phosphorylation and cytoskeletal abnormalities. Precancerous isolates possessed a higher number of motifs, and precancerous strains from Nashville induced higher levels of IL-8 than Colombian strains. These results indicate that CagA variants are linked with premalignant lesions in distinct populations and that epithelial responses to these strains are selective based upon locale.

Relationship Between Helicobacter pylori Infection and Esophageal Neoplasia: A Meta-analysis

Helicobacter pylori is an important causative factor in gastric carcinogenesis. However, its role in extragastric gastrointestinal malignancies, such as esophageal cancer, is controversial. The aim of this study was to explore the relationship of H. pylori infection and H. pylori cagA-positive strain with this malignancy by performing meta-analysis of all relevant studies. Extensive MEDLINE English language medical literature searches for human studies were performed through February 2007 with suitable keywords. Pooled estimates were obtained by using fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test. In adenocarcinoma patients there were inverse significant relationships with both the H. pylori prevalence (pooled odds ratio [OR], 0.52; 95% confidence interval [CI], 0.37-0.73; P < .001) and the prevalence of H. pylori cagA-positive strain (pooled OR, 0.51; 95% CI, 0.31-0.82; P = .006). Similarly in patients with Barrett's esophagus there were inverse significant relationships (pooled OR, 0.64; 95% CI, 0.43-0.94; P = .025 and pooled OR, 0.39; 95% CI, 0.21-0.76; P = .005, respectively). In patients with squamous cell carcinoma there were no significant relationships with both H. pylori prevalence (pooled OR, 0.85; 95% CI, 0.55-1.33; P = .48) and the prevalence of H. pylori cagA-positive strains (pooled OR, 1.22; 95% CI, 0.7-2.13; P = .48). The results showed an inverse statistically significant relationship of H. pylori infection with both esophageal adenocarcinoma and Barrett's esophagus, which might suggest a protective role of the infection in these entities. On the contrary, no statistically significant relationship with squamous cell carcinoma was found.

CagA gene variants in Malaysian Helicobacter pylori strains isolated from patients of different ethnic groups

Helicobacter pylori infection of a distinct subtype of cagA may lead to different pathological manifestation. The aim of this study is to determine the presence of cagA gene and its variants in H. pylori infection among different ethnic groups and its effect on gastroduodenal diseases. Overall detection of cagA among the 205 clinical isolates of H. pylori was 94%. Variations in size of the 3′ region of cagA gene were examined among 192 Malaysian H. pylori cagA-positive strains. Results showed that three cagA variants differing in fragment length of PCR products were detected and designated as type A (621–651 bp), type B (732–735 bp) and type C (525 bp). Although there was no association between any of the cagA subtypes with peptic ulcer disease ( p > 0.05), an association between cagA subtypes with a specific ethnic group was observed. Specific- cagA subtype A strains were predominantly isolated from Chinese compared to Malays and Indians ( p < 0.0005), and cagA subtype B strains were predominantly isolated from Malays and Indians compared to Chinese ( p < 0.05). The cagA type A strains of H. pylori is commonly found in the Chinese patients who have a higher risk of peptic ulcer disease, thus indicating that it could be used as an important clinical biomarker for a more severe infection.

Differential Effects of Helicobacter pylori Eradication on Oxidative DNA Damage at the Gastroesophageal Junction and at the Gastric Antrum

Abstract Background and Aim: Helicobacter pylori–associated gastritis causes accumulation of reactive oxygen species in the mucosal compartment. This prospective study evaluates DNA oxidative damage in biopsy samples obtained from both the antrum and the gastroesophageal junction (GEJ) before and after H. pylori eradication. Patients and Methods: Thirty-two consecutive H. pylori–positive patients underwent endoscopy with multiple biopsy sampling (i.e., antrum, incisura angularis, fundus, and cardia at the GEJ). After H. pylori eradication, 32 patients underwent a checkup endoscopy (mean interval, 5.7 months); in a subgroup of 13 subjects, a third endoscopy procedure was also performed (mean interval, 18 months). Additional biopsy samples (two from the antrum and two from the GEJ) were used to assess 8-hydroxydeoxyguanosine (8OHdG) levels using both high-pressure liquid chromatography with electrochemical detector and ELISA. Results: In the antral compartment, no significant modifications of 8OHdG levels were assessed after H. pylori eradication. Conversely, following eradication, 8OHdG levels significantly increased (high-pressure liquid chromatography with electrochemical detector, P = 0.04; ELISA method, P = 0.05) in biopsy samples taken from the GEJ, and a further increase was documented in the subgroup of patients who underwent a third endoscopy (P = 0.01). The increasing trend was more relevant in patients in whom H. pylori-cagA–positive strains were eradicated and in those affected by hiatal hernia. Conclusions: The levels of DNA adducts in the antral mucosa are not modified by H. pylori eradication; conversely, H. pylori eradication significantly increases the oxidative adducts at the GEJ. The clinical and biological importance of this situation and whether and how it relates to a higher risk of precancerous lesions is open to debate.

Helicobacter pylori density and cagA status in cirrhotic patients: a case-control study.

Despite a similar Helicobacter pylori prevalence, peptic ulcer is more frequent in cirrhotic patients than in controls. We evaluated whether cirrhotic patients had an increased bacterial density and/or a higher prevalence of H. pylori cagA-positive strains than controls. A total of 36 dyspeptic cirrhotic patients with H. pylori infection and 72 matched controls were enrolled. H. pylori infection was detected at histology on Giemsa staining, bacterial density was assessed using difference over baseline (DOB) values at 13C urea breath test, and cagA status was established at serology. Overall, both DOB values and prevalence of cagA did not significantly differ between cirrhotic patients and controls. However, peptic ulcer controls showed significantly higher DOB value (27.9 +/- 17.4 vs 19.4 +/- 9.3, respectively; P = 0.009) and cagA positive rate (85%vs 48%; P = 0.01) than non-ulcer dyspepsia patients. Although not statistically significant, a similar trend was observed in cirrhotic patients with peptic ulcer for DOB values (26.5 +/- 16.3 vs 18.3/1000 +/- 9.2, respectively; P = 0.07), whereas the cagA-positive rate was similar between peptic ulcer and non-ulcer dyspepsia patients (60%vs 50%; P = 0.30). The present data showed that both bacterial density and cagA prevalence did not differ between cirrhotic patients and controls.

The role of cagA Helicobacter pylori strains in gastro-oesophageal reflux disease.

The role of Helicobacter pylori infection in gastro-oesophageal reflux disease is controversial. The aim of this study was to evaluate the prevalence of colonization by cagA-positive and cagA-negative H. pylori strains in the spectrum of gastro-oesophageal reflux disease. A total of 108 patients (50 male/58 female; mean age, 50.3 years) with dyspepsia and peptic ulcer or erosive gastritis/duodenitis were categorized into patients without reflux and patients with reflux oesophagitis graded from I to IV. All patients underwent upper endoscopy with biopsies of the antrum. H. pylori was detected by histology, urease test and polymerase chain reaction. The cagA status was diagnosed in the gastric biopsy by polymerase chain reaction. The overall prevalence of H. pylori colonization in patients with reflux was 68.6% and was 70.2% in those without oesophageal disease (P = 0.862). Colonization by cagA-positive strains was also not statistically different between the two groups (31.4% versus 40.4%, P = 0.332). However, patients with grades II-IV reflux oesophagitis were less colonized by the bacterium (36.4%) than patients with grade I oesophagitis (77.5%) (P = 0.009). H. pylori cagA-positive strains were also less likely to colonize the stomach of patients with grades II-IV oesophagitis (0%), than grade I reflux oesophagitis (40%) patients and controls (40.4%). Infection of the stomach by H. pylori and especially by H. pylori cagA strains may play a protective role against the development of the most severe forms of gastro-oesophageal reflux disease.

Duodenal colonization by H. pylori is strongly associated with subsequent development of duodenal ulcer in patients with nonulcer dyspepsia

Background. The final step of the currently accepted mechanism of duodenal ulcer formation requires the colonization of the duodenum by H. pylori and the subsequent formation of the ulcer crater induced by the organism. On this basis, it would seem logical to hypothesize that patients with nonnlcer dyspepsia carrying the organism in the duodenum be at higher task of developing duodenal ulcer than those who do not. No data are available on this subject. Patiems and Methods. 363 consecutive, dyspeptic patients with an endoscopic diagnosis of nonulcer dyspepsia were characterized for H. pylori infection status at the level of the stomach (3 biopsies from the gastric antrum and 3 from the gastric corpus) and of the duodenum (3 biopsies from the duodenal bulb). At each site, infection was diagnosed if colture was positive and/or if the organism was concomitantly detected at histology (Giemsa staining) and urease testing. H. p2(lori cagPAI status was determined by PCR cagA amplification on isolated strains. All H. pylori positive patients were required to perform follow-up endoscopy one year later, or in the case of worsening clinical symptoms. Results. At basehne, infection was diagnosed in 189 patients (52%) in the stomach and in 50 patients (14%) in the duodenum. 87 patients (46%) were infected with cagA positive (cagA +) H. pylori strains in the stomach and 35 (70%) in the duodenum, a statistically significant difference ( P< 0.005, Chi-sqare test). 167 (79 cagA+, 47 with duodenal colonization) out of 189 H. pylori positive patients (85%) performed follow-up endoscopy after 1 year: a duodenal ulcer was diagnosed in 14; of these, 10 (71%) were cagA positive in the stomach at baseline, whereas 12 (86%) had H. pylori infection in the duodenum (10 cagA+) . This finding implies that stomach colonization by H. pylori cagA positive strains has a sensitivity of 69%, a specificity of 55%, a positive predictive value of 13%, and a negative predictive value of 96% for the development of duodenal ulcer one year after the diagnosis of nonulcer dyspepsia ; by contrast, the sensitivity, specificity, positive predictive value, and negative predictive value of duodenal colonization are 86%, 77%, 26%, and 98%, respectively. Conclusions. Assessment of duodenal colonization by H. pylori in patients with nonulcer dyspepsia is a better predictor for the development of duodenal ulcer than the assessmem of cagA status in the stomach.

Helicobacter pylori CagA-positive Strains Affect Oxygen Free Radicals Generation by Gastric Mucosa

Background:Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. Methods: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and 13C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. Results: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. Conclusions: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.

Association between Helicobacter pylori cytotoxic type I CagA-positive strains and migraine with aura.

Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the 'aura' phenomenon.

Helicobacter pylori in gastric biopsies of Taiwanese patients with gastroduodenal diseases.

This study was designed to study the in vivo prevalence and the heterogeneity of H. pylori in patients with gastroduodenal diseases in central Taiwan. H. pylori infection was detected in 74.1% (575/776) of the symptomatic population studied. The prevalence of H. pylori infection increased from 11.1% in those between the ages of one to 20, to 82.9% in those between the ages of 41 and 50, and to 84% in those between the ages of 51 and 60. There was no significant difference in the prevalence of H. pylori infection between men and women. Among different blood types, the prevalence and relative risk of H. pylori infection was significantly higher in blood group O patients (90.3%) than in blood group A (41%), blood group B (27.4%), or blood group AB (62%) patients. Metronidazole resistance was found in 6.7% of the primary isolates. The prevalence of metronidazole-resistant H. pylori strains was higher in women (7.69%) than in men (6.25%), but this difference was not significant. A total of 88% of H. pylori strains were cagA-positive. CagA gene-positive strains were present in 90.1% of duodenal ulcers, 90% of duodenal ulcers combined with gastric ulcer, 85.8% of gastric ulcers, and 69.2% of gastritis patients, and was significantly higher in peptic ulcer disease groups than in the gastritis group. In conclusion, there was a low incidence (6.7%) of metronidazole-resistant H. pylori strains and a high prevalence (88%) of H. pylori cagA-positive strains in central Taiwan. This study also demonstrated a significant in vivo correlation between active H. pylori infection and blood group O-positive patients, and showed a significant association between cagA gene-positive H. pylori strains and the development of peptic ulcers.