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.     

Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan

Background Helicobacter pylori CagA protein is considered to be one of the virulence factors associated with gastric cancer. CagA is injected into gastric epithelial cells, undergoes tyrosine phosphorylation, and binds to Src homology 2 domain-containing protein-tyrosine phosphatase (SHP-2). Two major subtypes of CagA have been observed in the SHP-2-binding site, the Western and East Asian types. The East Asian-type CagA binds to SHP-2 more strongly than the Western-type CagA. The diversity of CagA, which collectively determines the binding affinity of CagA to SHP-2, may be an important variable in determining the clinical outcome of infection by different H. pylori strains. Methods We investigated the relationship between the diversity of CagA and clinical outcome in Okinawa, Japan. A total 24 strains, 13 gastric cancer strains and 11 duodenal ulcer strains, were studied. We sequenced full-length cagA genes and analyzed the phylogenetic relationships between Okinawa isolates and previously characterized Western H. pylori strains. Results All isolates examined were cagA positive. The prevalence of East Asian CagA-positive strains was significantly higher in patients with gastric cancer (84.6%) than in patients with duodenal ulcer (27.3%) (χ-squared = 8.06, P = 0.011). The phylogenetic analysis showed that all gastric cancer strains with East Asian-type CagA were in the East Asian cluster, and that most duodenal ulcer strains were in the Western cluster. Conclusions The origins of H. pylori isolates are different between gastric cancer strains and duodenal ulcer strains, and East Asian CagA-positive H. pylori infection is associated with gastric cancer. The strain diversity observed in Okinawa may affect the difference in the prevalence of disease associated with H. pylori infection in Japan.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> CagA protein variation associated with gastric cancer in Asia

Recent molecular analysis has provided the pathological actions of CagA on gastric epithelial cells. CagA is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes; the East Asian and the Western type. The East Asian CagA protein possesses stronger SHP-2 binding activity than the Western CagA. The grades of inflammation, activity of gastritis, and atrophy are significantly higher in gastritis patients infected with the East Asian CagA-positive strain than in gastritis patients infected with the cagA-negative or Western CagA-positive strains. The prevalence of the East Asian CagA-positive strain is associated with the mortality rate of gastric cancer in Asia. Endemic circulation of H. pylori populations carrying biologically more active CagA proteins in East Asian countries, where the mortality rate of gastric cancer is among the highest in the world, may be involved in increasing the risk of gastric cancer in these populations.     

Infection by CagA-Positive Helicobacter pylori Strains in Patients with Ischemic Heart Disease: Prevalence and Association with Exercise-Induced Electrocardiographic Abnormalities

The role of H. pylori infection in increasing the risk of ischemic heart diseases (IHD) is still debated. We determined serologically the prevalence of overall H. pylori and CagA-positive H. pylori infection in 63 consecutive patients with IHD and 189 gender- and age-matched controls. We also determined in patients the influence of the infection and the CagA serological status on the results of an exercise ECG test and other parameters considered possible variables that may enhance the risk of IHD. The prevalence of H. pylori infection in patients and controls was 79.3% and 73.0%, respectively (P = 0.403) and that of CagA-positive H. pylori infection was 69.8% and 42.3%, respectively (P = 0.0002). The scores of the ECG S-T segment and T-wave abnormalities in the course of an exercise ECG in uninfected patients and in patients infected by CagA-negative and CagA-positive H. pylori strains were (mean ± sd): 1.59 ± 0.67, 1.92 ± 0.64, and 2.19 ± 0.70, respectively; (P = 0.011, 95% confidence limits of difference 0.15–1.07, CagA-positive infected vs uninfected patients). There was no intergroup difference in the levels of peripheral whiteblood cells, glucose, cholesterol, triglycerides, creatinine, and systolic and diastolic pressure. In conclusion, genetic heterogeneity of H. pylori could possibly explain some conflicting results concerning the association of H. pylori infection with IHD. Coronary vessels of IHD patients infected by CagA-positive H. pylori strains may be damaged more severely than those of uninfected patients.     

Prevalence of Helicobacter pylori Infection in Male Patients with Osteoporosis and Controls

Cytokines that regulate bone turnover (tumor necrosis factor-, interleukin-6, etc.) may influence the pathogenesis of skeleton disorders, such as osteoporosis. Since Helicobacter pylori infection increases the systemic levels of inflammatory cytokines, we investigated the possibility that this infection increases the risk of developing osteoporosis and affects the bone metabolism in a group of male patients with osteoporosis. We examined 80 osteoporotic male patients and 160 controls for serum antibodies to H. pylori and the CagA protein and determined, in patients alone, the most important biochemical and instrumental parameters of the disease. Fifty-one patients (63.7%) and 107 controls (66.8%) were seropositive for H. pylori infection (nonsignificant); 30 infected patients (58.8%) and 43 infected controls (40.1%) were positive for anti-CagA antibodies (P = 0.028; OR = 2.13). Levels of estradiol in infected CagA-positive patients were significantly lower than in infected CagA-negative patients (28.5 [SD = 10.18] vs. 39.5 [SD = 14.50] pg/ml; P = 0.002) and uninfected patients (35.2 [SD = 12.7] pg/ml; P = 0.028). Levels of urinary cross-laps(a marker of bone resorption) were increased in patients infected by CagA-positive strains compared to patients infected by CagA-negative strains (282.9 [SD = 103.8] vs. 210.5 [SD = 150.1] g/mmol; P = 0.048) and uninfected patients (204.3 [SD = 130.1] g/mmol; P = 0.016). Differences among uninfected and infected patients, independent of CagA status, were observed for other markers of bone turnover, but they did not reach statistical significance. Infection by CagA-positive H. pylori strains is more prevalent in men with osteoporosis, who show reduced systemic levels of estrogens and increased bone turnover. H. pylori infection by strains expressing CagA may therefore be considered a risk factor for osteoporisis in men.     

Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: an immunohistochemical study of East-Asian-type CagA

Background and Aims: Recently, we successfully produced an anti‐East‐Asian‐type CagA‐specific antibody called α‐EAS Ab, which is specifically immunoreactive only with East‐Asian‐type CagA but not Western‐type CagA. In this study, the correlations between Helicobacter pylori CagA protein diversity and gastric mucosal condition was investigated using immunohistochemical staining with α‐EAS Ab in Japan. Methods: There were 254 H. pylori‐positive patients enrolled in this study. α‐EAS Ab was used to determine the CagA phenotype instead of cagA sequencing, and, moreover, the histological findings and endoscopic gastric mucosal condition were evaluated according to the updated Sydney System and the Kimura–Takemoto classification system, respectively. Results: A total of 224 (88.2%) of the patients were immunoreactive for α‐EAS Ab. The remaining 30 (11.8%) were negative for α‐EAS Ab, suggesting that they were infected with either Western‐type CagA or CagA‐negative strains (i.e. non‐East‐Asian‐type CagA strains). The grades of activity of gastritis, mucosal atrophy and intestinal metaplasia according to the updated Sydney System were significantly higher in patients infected with East‐Asian‐type CagA strains than those infected with non‐East‐Asian‐type CagA strains. The grade of endoscopic gastric mucosal atrophy evaluated using the Kimura–Takemoto classification system was similar. All 28 strains isolated from patients with gastric cancer possessed the East‐Asian‐type CagA. Conclusions: Infection with East‐Asian‐type CagA H. pylori was more closely associated with gastric mucosal atrophy and gastric cancer than infection with non‐East‐Asian‐type CagA H. pylori. The efficiency of immunohistochemical analysis for CagA should be equivalent to that of cagA sequencing.     

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

Background: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. Methods: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. Results:H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR)?=?1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P?=?0.008). Current smoking (OR?=?2.65; 95% CI, 1.14-6.15; P?=?0.02), CagA status (OR?=?2.28; 95% CI, 1.24-4.19; P?=?0.008), dyspepsia (OR?=?6.89; 95% CI, 1.84-25.76; P?=?0.004) and past history of peptic ulcer disease (OR?=?3.15; 95% CI, 1.43-6.92; P?=?0.004) were associated significantly with increased risk of bleeding peptic ulcer. Conclusions: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.     

Infection by CagA-Positive <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Strains may Contribute to Alter the Sperm Quality of Men with Fertility Disorders and Increase the Systemic Levels of TNF-α

This study was aimed to address the possibility that Helicobacter pylori infection may play a detrimental role in semen quality of men with idiopathic infertility. Infection by H. pylori and by strains expressing CagA was determined in 80 male infertile patients by Western blotting and ELISA. Semen analysis was performed by light microscopy and transmission electron microscopy quantitatively elaborated (fertility index, immaturity, necrosis, and apoptosis percentages). Systemic levels of IL-6 and TNF-α were evaluated. Infertile patients infected with H. pylori showed a low sperm quality respective to uninfected patients. Particularly, in CagA-positive patients we observed a significant reduction in sperm motility and in the fertility index, while apoptosis and necrosis were increased. In these patients, the means of systemic TNF-α levels were higher than those of uninfected patients. The negative influence of CagA-positive H. pylori infection on sperm quality may help to understand the role of chronic infections in reproductive disorders.     

Clinical Relevance of CagA-specific Antibodies Related to CagA Status of Heliobacter pylori Isolates Using Immunofluorescence Test and PCR

Background: The cagA (cytotoxin-associated gene A) protein is found in about 50% of Helicobacter pylori strains; its clinical relevance in gastroduodenal disease is uncertain. Patients and Methods: The frequency of IgG antibodies to cagA was studied by using a commercial Western blot assay in sera of 189 patients with endoscopically and histologically confirmed gastroduodenal disease. In addition, 38 H. pylori strains isolated from biopsies were analyzed by immunofluorescence test (IFT) and PCR for detection of cagA protein and cagA gene sequences, respectively. Results: 54.3–60.0% of all patients with gastrointestinal diseases (chronic gastritis, gastric or duodenal ulcer and chronic duodenitis) and 28.6% with a normal mucosa were found to be positive for anti-cagA IgG antibodies. There was no significant difference in anti-cagA IgG seroprevalence between the different clinical entities. CagA-positive (cagA⁺) H. pylori strains were detected in 44.7% and 50% of the 38 isolates by PCR and IFT, respectively. 22 of 23 patients infected with cagA⁺ strains had anti-cagA antibodies. Using PCR as a gold standard, the sensitivity and specificity of the cagA IgG Western blot were 100.0% and 35.0%, respectively; the sensitivity and specificity of the cagA IFT were 76.5% and 71.4%, respectively. The incidence of the cagA⁺ H. pylori strains detected either by PCR or IFT was significantly higher (p < 0.05 and p < 0.01, respectively) in patients with chronic duodenitis, gastric or duodenal ulcer compared to patients with chronic gastritis (66.7%, 80% and 30.4%, respectively). Conclusion: In this study the cagA-specific serological status in H. pylori infections as diagnosed by IgG Western blot was of no predictive value for severity of disease. In contrast, the cagA status of H. pylori isolates, diagnosed by IFT or PCR, was a predictive marker for severe disease and, therefore, also of clinical relevance in the assessment of the virulence of the infecting strain. Received: July 21, 2000 · Revision accepted: March 2, 2001     

Association between diversity in the Src homology 2 domain--containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer

We investigated the relationship between the diversity of Helicobacter pylori CagA protein and clinical outcome. The cagA gene was sequenced in 115 clinical isolates. The binding affinity of CagA to Src homology 2 domain-containing tyrosine phosphatase (SHP-2) was examined by in vitro infection. Two major CagA subtypes were observed--the East Asian and the Western type. The grades of inflammation, activity of gastritis, and atrophy were significantly higher in patients with gastritis infected with the East Asian CagA-positive strain than in patients with gastritis infected with cagA-negative or Western CagA-positive strains. All strains isolated from patients with gastric cancer were East Asian CagA positive. East Asian CagA exhibited stronger SHP-2-binding activity than did Western CagA. These findings suggest that infection with East Asian CagA-positive H. pylori is associated with atrophic gastritis and gastric cancer and that persistent active inflammation induced by the East Asian CagA-positive strain may play a role in the pathogenesis of disease.     

αPix interacts with Helicobacter pylori CagA to induce IL-8 expression in gastric epithelial cells

Objective.Helicobacter pylori CagA, translocated into gastric epithelial cells, induces IL-8 expression through the signalling pathways, including extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB). We previously demonstrated that CagA interacts with host αPix. The present study was purposed to determine the role of the interaction of αPix with CagA on the signalling pathways for IL-8 expression in H. pylori-infected gastric epithelial cells. Material and methods.H. pylori HP99 strain (CagA+, VacA + ) was infected to gastric epithelial AGS cells transfected with non-targeting (NT) or αPix- targeting siRNA. Activation of signalling molecules including p21-activated kinase (PAK), ERK and NF-κB, and expression of IL-8 in the cells were assessed. Results:H. pylori CagA was delivered into AGS cells and then interacted with αPix at 4 h following H. pylori infection. PAK1, ERK and NF-κB were activated in the cells containing NT and αPix siRNA at 1–2 h following H. pylori infection. However, after 4 h, the time when CagA was delivered into the cells, the activations of PAK1, ERK and NF-κB were inhibited by down-regulation of αPix using siRNA but not by NT siRNA. The results indicate that αPix is required for H. pylori-mediated signalling of PAK1, ERK and NF-κB. Additionally, αPix siRNA suppressed IL-8 induction after translocation of CagA into the cells, indicating that interaction of CagA with αPix is critical for CagA-mediating signalling for IL-8 expression. Conclusions. The interaction of αPix with CagA activates PAK1, ERK and NF-κB, which induces IL-8 expression in H. pylori-infected gastric epithelial cells.     

Pathogenetic role of the tyrosine-phosphorylated CagA EPIYA sequence of Helicobacter pylori in histological gastritis in Japanese patients

Background   Helicobacter pylori (H. pylori) CagA protein plays an important role in the clinical outcome of gastritis treatment. Tyrosine phosphorylated Glu-Pro-Ile-Tyr-Ala motif in CagA (CagA-P) plays a critical role in the morphological transformation of cells. Aim  We examine the relationship between serum titer of anti-CagA-P antibody and gastric inflammation as well as the status of the CagA-P expression in gastric mucosa. Methods  Fasting sera from 127 dyspeptic patients were collected, and anti-CagA-P antibody was evaluated. Gastric biopsy specimens were collected and histological gastritis was evaluated. We investigate the expression of CagA-P in human gastric mucosa by Western blotting and immunohistochemistry. Results  The titers of anti-CagA-P antibodies in the sera of H. pylori (+) patients were significantly higher than those of H. pylori (–) patients (P < 0.001). In 107 H. pylori (+) patients, anti-CagA-P titer was statistically higher in patients with high gastritis scores in the corpus than in those with low scores (P < 0.05). CagA-P expression was detected in the foveolar epithelium of the H. pylori infected gastric mucosa. Conclusion  CagA-P is an antigen-peptide against the host, and serum titer of anti-CagA-P antibody may be a new marker for gastritis in the corpus. Grant support: Tsuchiya Medical Foundation.     

Anti‐CagA and anti‐VacA antibodies in Helicobacter pylori‐infected patients with and without peptic ulcer disease in Serbia and Montenegro

Background: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori‐positive dyspeptic patients in Serbia and Montenegro. Methods: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49?±?15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti‐IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non‐ulcer dyspepsia (NUD) in the remaining 142 patients. Results: 129 (74.6%) patients were H. pylori‐positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P?P?Conclusions: In Serbia and Montenegro there is high seroprevalence of CagA‐positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA‐positive strains are more closely related to peptic ulcer disease.     

Association of the CagA status of Helicobacter pylori and serum levels of interleukin (IL)‐17 and IL‐23 in duodenal ulcer patients

OBJECTIVE: It has been reported that the cytotoxin‐associated gene A (cagA+) H. pylori strains induce severe gastric mucosal inflammation. The aim of this study was to investigate the association of the virulence factor CagA with IL‐17 and IL‐23 serum levels in duodenal ulcer (DU) patients and H. pylori‐infected asymptomatic (AS) carriers. METHODS: In total, 45 H. pylori‐infected DU patients were enrolled to study: 23 tested positive for the anti‐CagA antibody (anti‐CagA+) and 22 tested negative for the anti‐CagA antibody (anti‐CagA‐), 30 were AS carriers (15 were anti‐CagA+ and 15 were anti‐CagA‐) and 15 were healthy uninfected participants (as a control group). The IL‐17 and IL‐23 serum levels of participants were measured by enzyme‐linked immunosorbent assay method. RESULTS: The mean IL‐17 levels in DU patients were significantly higher than those in AS and control groups (P < 0.001 and P < 0.0001 respectively). In the DU group, the mean IL‐17 levels in participants testing positive for anti‐CagA (10.84 ± 5.79 pg/mL) were significantly higher than those observed in participants testing negative for anti‐CagA (7.65 ± 4.74 pg/mL; P < 0.05). The mean IL‐23 levels in the DU and AS groups were significantly higher than in the control group (P < 0.02 and P < 0.03 respectively) but were not significantly different in participants testing positive and negative for anti‐CagA. CONCLUSION: These results showed higher IL‐17 and IL‐23 serum levels in H. pylori‐infected participants than in the control group. In the DU group the expression of IL‐17 was influenced by the CagA factor.     

Functional Dyspepsia is Associated with cagA-positive Helicobacter pylori Strains

Background: The antigen CagA can be used as a marker for virulence of Helicobacter pylori. It is tempting to assume that H. pylori strains positive for cytotoxin-associated gene A (cagA) could be responsible for functional dyspepsia. A cross-sectional study was performed in patients presenting with functional dyspepsia to correlate the clinical presentation with the presence of cagA-positive and -negative H. pylori strains. Methods: Consecutive patients referred for endoscopy were studied. An inclusion criterion was the absence of any endoscopic abnormality. Biopsy specimens were obtained from the gastric antrum for HE and immunoperoxidase stain, rapid urease test, and culture. A serum sample was taken for detection of IgG antibodies against H. pylori as well as CagA. A validated questionnaire of 14 questions regarding the upper gastrointestinal tract was used for assessment of the clinical presentation. Nine questions were scored on a 5-point Likert scale. Results: 422 patients were included, 222 were H. pylori-positive, the remaining 200 were H. pylori-negative. Mean symptom score in patients with cagA-positive strains was significantly higher than in patients with cagA-negative strains. No difference was present if cagA-negative patients were compared with H. pylori-negative dyspeptics. Four different complaints were more prevalent in the cagA-positive patients compared with cagA-negatives. When cagA-positive patients were compared with H. pylori-negative dyspeptics, seven complaints were significantly more prevalent in cagA-positives; when cagA-negatives were compared this number was only two. Conclusions: Functional dyspeptics with cagA-positive H. pylori strains have more dyspeptic symptoms and higher symptom scores than patients with cagA-negative H. pylori strains as well as H. pylori-negative functional dyspeptics.     

Augmented levels of gastric mucosal leucocyte activation by infection with cagA gene-positive Helicobacter pylori

The possession of the cytotoxin-associated gene (cagA) of Helicobacter pylori is thought to be highly associated with peptic ulcer disease. However, the pathogenic role of cagA is still unknown. We have emphasized the importance of the interrelationship between H. pylori-derived ammonia and oxygen radicals from in?ltrated leucocytes. The aim of the present study was to explore the relationship between oxygen radical production and H. pylori strain diversity based on cagA possession. An endoscopic examination and gastric mucosal biopsy were performed in 30 H. pylori-infected patients with gastric ulcer. Myeloperoxidase (MPO) content and the luminol-dependent chemiluminescence value in the biopsied gastric specimens were measured as an index for leucocyte in?ltration and oxygen radical production. From the precipitates of cultured bacterial isolates of biopsied specimens, bacterial DNA was puri?ed and analysed by polymerase chain reaction to characterize the possession of cagA. While all patients had ureC-positive strains, 22 had cagA-positive and eight had cagA-negative strains. In patients with cagA-positive strains, MPO contents as well as chemiluminescence values in the gastric corpus were signi?cantly higher than those in patients with cagA-negative strains. Gastric mucosal leucocyte recruitment and activation are suggested to be enhanced by cagA gene-positive H. pylori infection.     

Discovery of unique African Helicobacter pylori CagA-multimerization motif in the Dominican Republic

BACKGROUND Helicobacter pylori (H. pylori) colonizes the human stomach and is a major cause of peptic ulcer disease and gastric cancer. However, although the prevalence of H. pylori is high in Africa, the incidence of gastric cancer is low, and this phenomenon is called to be African enigma. The CagA protein produced by H. pylori is the most studied virulence factor. The carcinogenic potential of CagA is associated with the Glu-Pro-Ile-Tyr-Ala (EPIYA) patterns and CagA-multimerization (CM) motifs.AIMTo better understand the EPIYA patterns and CM motifs of the cagA gene.METHODSGastric mucosal biopsy specimens were obtained from 258 patients with dyspepsia living in the Dominican Republic, from which 120 H. pylori strains were cultured. After the bacterial DNA extraction, the EPIYA pattern and CM motif genotypes were determined using a polymerase chain reaction-based sequencing. The population structure of the Dominican Republic strains was analyzed using multilocus sequence typing (MLST). Peptic ulcer disease and gastric cancer were identified via endoscopy, and gastric cancer was confirmed by histopathology. Histological scores of the gastric mucosa were evaluated using the updated Sydney system.RESULTSAll CagA-positive strains carried the Western-type CagA according to the identified EPIYA patterns. Twenty-seven kinds of CM motifs were observed. Although the typical Western CM motif (FPLKRHDKVDDLSKVG) was observed most frequently, the typical East Asian CM motif (FPLRRSAAVNDLSKVG) was not observed. However, “FPLRRSAKVEDLSKVG”, similar to the typical East Asian CM motif, was found in 21 strains. Since this type was significantly more frequent in strains classified as hpAfrica1 using MLST analysis (P = 0.034), we termed it Africa1-CM (Af1-CM). A few hpEurope strains carried the Af1-CM motif, but they had a significantly higher ancestral Africa1 component than that of those without the Af1-CM motif (P = 0.030). In 30 cagA-positive strains, the "GKDKGPE" motif was observed immediately upstream of the EPIYA motif in the EPIYA-A segment, and there was a significant association between strains with the hpAfrica1 population and those containing the “GKDKGPE” motif (P = 0.018). In contrast, there was no significant association between the CM motif patterns and histological scores and clinical outcomes.CONCLUSIONWe found the unique African CM motif in Western-type CagA and termed it Africa1-CM. The less toxicity of this motif could be one reason to explain the African enigma.     

Clinical relevance of Helicobacter pylori vacA and cagA genotypes in gastric carcinoma

Helicobacter pylori infection is the major etiological factor of gastric carcinoma. This disease is the result of a long, multistep, and multifactorial process, which occurs only in a small proportion of patients infected with H. pylori. Gastric carcinoma development is influenced by host genetic susceptibility factors, environmental factors, and H. pylori virulence. H. pylori is genetically highly variable, and variability that affects H. pylori virulence factors may be useful to identify strains with different degrees of pathogenicity. This review will focus on VacA and CagA that have polymorphic regions that impact their functional properties. The characterization of H. pylori vacA and cagA-associated could be useful for identifying patients at highest risk of disease, who could be offered H. pylori eradication therapy and who could be included in programs of more intensive surveillance in an attempt to reduce gastric carcinoma incidence.     

Delay in gastric emptying in patients with chronic renal failure

Background: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). Delayed gastric emptying might be a possible pathophysiological mechanism. The aims of this study were to evaluate gastric emptying in patients with CRF and to correlate the findings with GI symptoms and evaluate the impact of Helicobacter pylori infection in CRF patients on gastric emptying. Methods: Thirty‐nine patients with CRF (17 F, 22 M) were compared with 131 healthy subjects (74 F, 57 M). A standardized breakfast was given with 20 spherical, radiopaque markers (ROMs). The emptying was followed by fluoroscopy after 4, 5 and 6?h. Gastric emptying was assessed by calculating the individual mean percentual gastric retention of markers, 4 to 6?h after the meal. The perceived severity of GI symptoms was assessed with a validated questionnaire. Because of gender differences in gastric emptying, men and women were compared separately and a percentile of 95 was chosen as the upper reference value. H. pylori infection was assessed using a serological method. Results: Delayed gastric emptying was found in 14 out of 39 (36%) of the CRF patients. There was no relationship between delayed gastric emptying and age, GI symptoms, H. pylori infection or underlying renal disease. However, a higher proportion of patients in peritoneal dialysis demonstrated delayed gastric emptying compared with predialytic patients (6 of 9 versus 2 of 13, P?=?0.026). Men with CRF had a higher gastric retention compared with healthy men (16.6 (0–63.3)% versus 0 (0–2.1)%, P?P?P?=?0.93), but 4 women with CRF had delayed gastric emptying (P?=?0.02). Eighteen of the CRF patients had GI symptoms (6 F, 12 M) and 21 were asymptomatic (11 F, 10 M). There was no difference in mean gastric retention in patients with CRF with and without GI symptoms (M: 13.3 (0–55.0)% versus 47.5 (5.0–65.0)%, P?=?0.51, F: 16.6 (0–63.3)% versus 13.3 (0–59.2)%, P?=?0.96). Gastric emptying in CRF patients with and without H. pylori infection showed no difference. Conclusions: Delayed gastric emptying is common in patients with chronic renal failure, particularly in men. The delay was not associated with the presence of GI symptoms, underlying renal disease or H. pylori infection. However, the dialytic status might have an impact on gastric emptying in patients with CRF.     

Helicobacter pylori‐eradication therapy decreases the level of neutrophil‐derived oxidants in the ulcerous mucosa of the human stomach: Relationship between ulcer stage and mucosal oxidant level

Background: The purpose of the present study was to determine the effect of Helicobacter pylori eradication on the intensity of inflammation in the ulcerous mucosa by measuring the level of neutrophil‐associated oxidants and to understand the role of mucosal inflammation in ulcer relapse from the viewpoints of the scarring stage and the H. pylori‐infection status. The level of inflammation in the gastric mucosa after the eradication of H. pylori was examined using biopsy samples obtained from patients with gastric ulcers. Methods: Gastric mucosal specimens were endoscopically obtained before and after H. pylori‐eradication therapy from 39 patients with gastric ulcers and a positive H. pylori‐infection status. The level of neutrophil‐derived oxidants was then measured in each sample using a luminol‐dependent chemiluminescence (ChL) assay. Results: Chemiluminescence activity in the ulcer portion and the background gastric mucosa (antrum and corpus) was significantly reduced 3 months after successful therapy (n = 32). The ChL activity was further decreased 9 months after successful therapy, but the activity in the ulcer portion remained unchanged. In patients who did not respond to the H. pylori‐eradication therapy (n = 7), the ChL activities were not altered in any mucosal portion after the therapy. Before the H. pylori‐eradication therapy, a higher ChL activity was observed in open ulcer tissue than in scarred tissue. The ChL activity in the scarred tissue was reduced 3 months after the successful eradication of H. pylori; however, the ChL activity in the red scars was significantly higher than that in the white scars. The ChL level in the white scars was almost equivalent to that in the background mucosa 9 months after the completion of the H. pylori‐eradication therapy. Conclusion: The eradication of H. pylori may reduce the level of oxidant production in gastric ulcers, promoting the prevention of ulcer recurrence. Furthermore, the presence of a red scar may indicate unstable healing, even after the successful eradication of H. pylori.