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At least 19 recordsLinked to original sources

Increased phospholipase activity in Helicobacter pylori strains isolated from patients with gastric carcinoma.

PURPOSE: Phospholipase activity, one of Helicobacter pylori pathogenicity factors, has not been investigated enough, so far, although it may induce a remarkable damage to the gastric mucosa. In the present work, we have compared the whole phospholipase activity of H. pylori strains isolated from patients with gastric carcinoma with that of strains isolated from dyspeptic patients without gastric carcinoma. METHODS: We measured the phospholipase activity of one distinct H. pylori colony isolated from each of 10 patients with gastric carcinoma and 10 controls, dyspeptic patients without endoscopic and histological signs of gastric carcinoma. We also determined the phospholipase activity of 20 additional strains isolated from different areas of neoplastic and non-neoplastic tissue of two patients with gastric carcinoma, the cagA and vacA positive G27 and 328 wild strains and their respective vacA and cagA negative isogenic mutants. The whole phospholipase activity of strains was determined by measuring the release of (14)C-labeled palmitic acid from the radioactive l-3-phosphatidylcholine, 1,2-di[1-(14)C]palmiloyl substrate; results were expressed in pmol of palmitic acid per mg of protein. RESULTS: H. pylori strains isolated from patients with gastric carcinoma had levels of phospholipase activity significantly higher than those of strains isolated from controls (99.37 [S.D. 40.45] versus 34.46 [S.D. 16.46], P<0.001). In patients with gastric carcinoma, the mean phospholipase activity of strains isolated from neoplastic tissue was similar to that of strains isolated from non-neoplastic tissues (123.02 [S.D. 44.36] and 115.77 [S.D. 81.48], respectively. Interruption of cagA gene caused a ca. 20% reduction of phospholipase activity (36.38 versus 45.22 of the wild strain); that of vacA caused no reduction of phospholipase activity (26.53 and 25.37 of the wild strain). CONCLUSIONS: The infection by H. pylori strains that produce high levels of phospholipase may increase the risk of developing gastric carcinoma. We hypothesise that indirect products of phospholipase activity, such as prostaglandins, leukotrienes and lysophospholipids, may mediate carcinogenesis.

Antigens, Bacterial↗

Prevalence of Helicobacter pylori infection in male patients with osteoporosis and controls.

Cytokines that regulate bone turnover (tumor necrosis factor-alpha, 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]microg/mmol; P = 0.048) and uninfected patients (204.3 [SD = 130.1] microg/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.

Aged↗

[The diagnosis of helicobacter pylori infection: guidelines from the Maastricht 2-2000 Consensus Report].

The European Helicobacter pylori Study Group (EHPSG), during the Maastricht 2-2000 Workshop, revised and updated the original guidelines on the management of Helicobacter pylori (H. pylori) infection. The present review focuses on the diagnostic approach for patients referred to the primary care as well as to the specialist. Currently, two diagnostic methods can be used to detect H. pylori: invasive (urease test, histological detection, culture, polymerase chain reaction, smear examination, string test) or non-invasive (serology, urea breath test, antigen stool assay, ''doctor's tests'') tests. These methods vary in their sensitivity and specificity, and the choice depends on the situation, for example, whether the aim is to detect infection or the success of eradication treatment. Urea breath test (UBT) and antigen stool assay are recommended from EHPSG in patients without alarm symptoms or under 45 years of age, at low risk of malignancy in the ''test and treat strategy''. Confirmation of H. pylori eradication following treatment should be tested by UBT; a stool antigen assay is the alternative if the former is not available. Important added value can be gained from other tests: histology allows evaluation of the status of the mucosa while culture allows strain typing and tests for antibiotic susceptibility.

Adult↗

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 white blood 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.

Adult↗

Helicobacter pylori infection and infertility.

OBJECTIVE: To determine (1) the prevalence of Helicobacter pylori infection in male and female patients with reproductive disorders and controls; (2) the presence of anti-H. pylori antibodies in samples of follicular fluid, vaginal secretions and sperm; and (3) the existence of a structural homology between a major spermatozoa protein, tubulin, and H. pylori proteins. PATIENTS AND METHODS: Serum samples from 167 patients with infertility and 837 age- and gender-matched controls (blood donors) were examined by enzyme-linked immunosorbent assay (ELISA) and Western blotting to determine the seropositivity for H. pylori infection. The presence of anti-H. pylori antibodies in samples of follicular fluid, vaginal secretions and sperm was determined using the same techniques. The possible cross-reactivity with spermatozoa of anti-H. pylori hyperimmune sera and human antibodies was studied by immunofluorescence. The N-acid homology of human tubulin with the principal H. pylori proteins was assayed by the WU-blastp program available on the Internet. RESULTS: The prevalence of infection was significantly higher in patients than controls (49.1% v. 33.5%, P < 0.001). Follicular fluids from infected patients contained specific antibodies in all cases, sperm samples in about 50% of cases, and vaginal secretions in a minority of cases. Sera to H. pylori whole antigens and VacA reacted with the tails and the pericentriolar area of human spermatozoa (which are rich in tubulin); sera to urease and heat-shock protein (Hsp) did not. Follicular fluids with anti-H. pylori antibodies immune reacted with spermatozoa. A linear homology was found between beta-tubulin and three H. pylori proteins, flagellin, VacA and CagA. CONCLUSIONS: H. pylori infection may increase the risk of developing reproductive disorders or worsen the clinical expression of this syndrome.

Adolescent↗

Infection by Helicobacter pylori and acute myocardial infarction. Do cytotoxic strains make a difference?

The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the risk factors recently reported, several infectious agents appear to increase the risk of AMI. Helicobacter pylori (H. pylori) infection, a bacterium involved in duodenal and gastric ulcer, gastric cancer and MALT-lymphoma, seems to be strongly associated with AMI. More virulent (anti-CagA positive) strains of the bacterium are almost exclusively the causative agents of such diseases. To determine the prevalence of H. pylori infection and of virulent strains, a case-control study was conducted in a group of male patients with AMI. A group of patients consecutively admitted to the Emergency Care Unit served as controls. We studied 223 consecutive male patients, mean age 60.2 (range 40-79) years, admitted for AMI to the Coronary Care Units at Hospitals in two towns of Northern Italy, 223 age matched male patients (mean age 61.8, range 40-79 years) admitted to the Emergency Care Unit, served as control. H. pylori seroprevalence was assessed by presence of antibodies (IgG) against H. pylori and anti-CagA in circulation. Among the patients we investigated the presence of hypertension, levels of cholesterol and glucose in serum, fibrinogen in plasma and smoking habits. H. pylori infection was present in 189/223 (84.7%) of the patients and in 138/223 (61.8%) of the control population (p < 0.0001 OR 3.42 [IC 95% 2.12-5.54]). The anti-CagA antibodies were detected in 33.8% of infected patients with AMI (64/189) versus 26.8% in the control subjects (37/138) (p:0.17, OR 1.40 [IC 95% 0.84-2.33]). Classical risk factors for AMI did not differ among patients with and without H. pylori infection. Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of anti-H. pylori not restricted to virulent strains, when compared to a population of patients referred to the Emergency Care Unit. The classical risk factors for coronary disease were present in the patients with AMI irrespective of H. pylori status.

Adult↗

The African enigma: low prevalence of gastric atrophy, high prevalence of chronic inflammation in West African adults and children.

BACKGROUND: Helicobacter pylori infection is very common in Africa, yet peptic ulcer disease and gastric malignancy are rare. AIM: The aim of this study was to quantify mucosal responses to H. pylori in Gambian adults and children and to estimate the prevalence of antibodies to bacterial virulence factors (cagA and vacA) in a symptomatic population. PATIENTS AND METHODS: Adults (mean 36 SD 12 years) with dyspepsia and children (mean 1.4 years SD 0.4 years) with malnutrition underwent gastroscopy with biopsy. Blood was simultaneously drawn for cagA and vacA antibody status. Histopathological scoring used the modified Sydney classification. RESULTS: Both adults (n = 45) and children (n = 37) mainly demonstrated chronic mild antral inflammation. Only 2/83 cases of focal atrophy (GA) and 4/83 cases of intestinal metaplasia (IM) were observed. Adults tended to demonstrate more frequent acute (AI) and chronic inflammation (CI) (38% compared with 18% and 85% compared with 72%, respectively). Sixty-seven percent of children were cagA IgG+ and 21% vacA IgG+ and 93% of adults were IgG cagA+ and 86% vacA+. There were no differences in mucosal responses between those who were cagA or vacA positive compared with those who were negative. CONCLUSION: Gambian adults and children mount a CI response to H. pylori but GA, IM and AI are uncommon. cagA and vacA are commonly expressed in Gambian strains of H. pylori. Further studies are needed in order to confirm that GA and IM are not late findings in old age.

Adolescent↗

Risk factors for acquiring Helicobacter pylori infection in a group of Tuscan teenagers.

Risk factors for acquiring Helicobacter pylori infection include hygienic, social, and environmental conditions. Some of these conditions usually change over time. We therefore investigated the existence of risk factors in a group of teenagers living in a place with the same environmental characteristics, in which hygienic and crowding conditions have not changed significantly in the last 20 years. A group of 164 students, mostly borne in 1977, attending four different schools, were examined serologically for H. pylori infection and CagA status. The importance of the risk factors for the transmission of the infection were evaluated by the chi2 test. P values <0.05 were considered significant. Twenty-two students (13.4%) were H. pylori seropositive. Students attending teachers' college and high school of arts were infected significantly more often than those attending high school (P = 0.011 and P = 0.012, respectively). Students who smoked and students whose parents had a manual job had an increased risk of acquiring the infection (P = 0.002, and P = 0.036, respectively). Crowding conditions and the presence of domestic animals were close to being statistically significant. Other factors, such as gender, number of bathrooms and bedrooms, sharing the bed with adults as a child, presence of a sexual partner, and a family history of peptic ulcer and gastric cancer, did not increase the risk of infection. The prevalence of seropositivity for CagA was similar in the various risk groups. Manual job of parents and smoking were the most important factors for acquiring H. pylori infection.

Adolescent↗

Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries.

The predominant H. pylori strain circulating among geographic locations differs with regard to the genomic structure. This study determined whether structural subtypes of the cagA 3' repeat region could be used to identify the population of origin of H. pylori isolates. We examined 600 cagA-positive H. pylori (Colombia, 100; USA, 100; France, 100; Canada, 20; Italy, 20; Korea, 100; Japan, 100; Hong Kong, 20; Taiwan, 20; Vietnam, 20). The cagA 3' region was amplified by PCR using primers specific to Japanese and Western 3' cagA gene sequences. PCR using Japanese cagA primers resulted in PCR products in 99-6 % of strains from East Asia but no non-Asian strains. Conversely, PCR using Western cagA primers resulted in amplicons in 100% of non-Asian strains, and only one from East Asia. cagA genotyping is useful for molecular epidemiological studies as strains can be completely separated by differences in the cagA 3' region.

Adult↗

Helicobacter pylori seroconversion in asymptomatic blood donors: a five-year follow-up.

Several techniques have been developed to diagnose Helicobacter pylori infection and two noninvasive methods are available: carbon 13-urea breath test (UBT) and serology. Measurement of IgG serum antibodies by enzyme-linked immunosorbent assay (ELISA) is a reliable and inexpensive method for detection of infection. The aim of this study was to assess the seroconversion by different techniques after five to eight years. In 1990, 588 of 1,010 asymptomatic donors were found to be seronegative by ELISA, based on an H. pylori whole-cell suspension lysate (sensitivity and specificity: 92% and 97%). In 1995 serum samples from 418 of 588 seronegative donors were collected and retested using the same antigen. 411 of 418 samples were frankly negative, and 7 donors were found to be seroconverted. This group of seven sera represents the object of the study. They were retested by ELISA and western blotting using a different antigen (NCTC). To standardize our techniques, sera from 43 H. pylori positive and 47 H. pylori negative patients according to culture, histology, urease test, and UBT were used. The cutoff for ELISA-NCTC was 0.53 AI (absorbance index) (mean value + 2 SD), and for western blotting was negativity for CagA or <10 bands (sensitivity and specificity: 95% and 96%; 98% and 81% for ELISA and western blotting respectively). According to the results obtained in 1990 and 1995, seven donors were found to be seroconverted by ELISA using sonicated antigen; in five the seroconversion was confirmed by ELISA using NCTC antigen and in two there was concordance with WB. Four of the seven donors were contacted and asked to undergo UBT and a further serum sample was drawn to be reassessed in 1998. A seroconversion was found in all four donors by ELISA, while WB and UBT confirmed the seroconversion in only three of four donors. In conclusion the in-house ELISA used performed well compared to other theoretically better serologic assays and confirmed the low seroconversion rate for H. pylori infection in adult populations living in developed countries.

Adult↗

Anti-CagA reactivity in Helicobacter pylori-negative subjects: a comparison of three different methods.

Emerging evidence suggests that infection by CagA-positive Helicobacter pylori strains is related to the development of more serious gastroduodenal diseases, thus conferring to the determination of anti-CagA antibodies a relevant clinical significance in serological screenings. The detection of anti-CagA positivity in sera negative for anti-H. pylori antibodies raises the question of whether this apparently nonsense result is merely due to a false positive reaction. To address this issue, we compared three different methods for the detection of anti-CagA antibodies. In all, 272 selected sera from patients with precisely defined H. pylori status (positive or negative concordance of five tests, ie, histology by Giemsa in both antrum and corpus, rapid urease test, culture, [13C]urea breath test, IgG ELISA) were tested for anti-CagA reactivity by three different techniques (western immunoblotting, ELISA, and recombinant immunoblotting assay). In order to assess the sensibility and specificity of each tests, we considered as "true" anti-CagA positive sera those with two out of three positive results. Sera from 70% of H. pylori-positive patients and 10% from H. pylori-negative patients turned out to be "true" positives for anti-CagA antibodies. The three methods showed similar excellent results, in terms of both sensitivity and specificity, always over 93%. It is confirmed that a proportion of patients with a negative conventional serology against H. pylori possess anti-CagA antibodies in their sera. In this paper we demonstrate that it can happen even in patients without any biological signs of actual H. pylori infection. The possibility that this can be due to a false positive laboratory result is very likely ruled out by the accuracy of the three methods used. The clinical management of these patients needs further study on larger series.

Adult↗

Relationship between the cagA 3' repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH.

BACKGROUND & AIMS: The variation in size of Helicobacter pylori CagA is related to repeat sequences in the 3' region of the cagA gene. We investigated whether structural subtypes of the cagA 3' region are associated with presentation of the infection or to susceptibility to acid. METHODS: We examined 319 cagA-positive H. pylori isolates: 84 isolates from Bogota, Colombia; 83 from Houston, Texas; 24 from Siena, Italy; and 128 from Seoul, Korea. The cagA 3' region was amplified by polymerase chain reaction. Gastric histology and susceptibility to pH 3 were evaluated in relation to the number of cagA repeat regions. RESULTS: Strains with more than three repeat regions were associated with significantly higher scores for gastric mucosal atrophy and intestinal metaplasia than those with fewer repeat regions. H. pylori strains with three repeat regions were also significantly more susceptible to pH 3 than isolates with fewer repeat regions. CONCLUSIONS: H. pylori strains with more than three repeat regions in the 3' region of the cagA gene are associated with enhanced histological injury and with reduced survival in acidic conditions. It is hypothesized that these variants arise within the stomach.

Adult↗

Effect of Helicobacter pylori infection and its eradication on cell proliferation, DNA status, and oncogene expression in patients with chronic gastritis.

BACKGROUND: Helicobacter pylori, the main cause of chronic gastritis, is a class I gastric carcinogen. Chronic gastritis progresses to cancer through atrophy, metaplasia, and dysplasia. Precancerous phenotypic expression is generally associated with acquired genomic instability. AIM: To evaluate the effect of H pylori infection and its eradication on gastric histology, cell proliferation, DNA status, and oncogene expression. METHODS/SUBJECTS: Morphometric and immunohistochemical techniques were used to examine gastric mucosal biopsy specimens from eight controls, 10 patients with H pylori negative chronic gastritis, 53 with H pylori positive chronic gastritis, and 11 with gastric cancer. RESULTS: All patients with chronic gastritis were in a hyperproliferative state related to mucosal inflammation, regardless of H pylori infection. Atrophy was present in three of 10 patients with H pylori negative chronic gastritis and in 26 of 53 with H pylori positive chronic gastritis, associated in 18 with intestinal metaplasia. DNA content was abnormal in only 11 patients with atrophy and H pylori infection; eight of these also had c-Myc expression, associated in six cases with p53 expression. Fifty three patients with H pylori positive chronic gastritis were monitored for 12 months after antibiotic treatment: three dropped out; infection was eradicated in 45, in whom cell proliferation decreased in parallel with the reduction in gastritis activity; atrophy previously detected in 21/45 disappeared in five, regressed from moderate to mild in nine, and remained unchanged in seven; complete metaplasia disappeared in 4/14, and markers of genomic instability disappeared where previously present. In the five patients in whom H pylori persisted, atrophy, metaplasia, dysplasia, and markers of genomic instability remained unchanged. CONCLUSIONS: Chronic H pylori infection seems to be responsible for genomic instability in a subset of cases of H pylori positive chronic atrophic gastritis; eradication of H pylori infection can reverse inflammation and the related atrophy, metaplasia, and genomic instability.

Adult↗

Helicobacter pylori determinants of pathogenicity.

The bacterium Helicobacter pylori colonises the stomach of man and induces a strong inflammatory response. Differences in the possession of pathogenicity determinants by H. pylori isolates could account in part for the different clinical outcomes of infection. The main H. pylori pathogenic factors, i.e. urease, the cytotoxin VacA, and the genes involved in virulence contained in the pathogenicity island (PAI) cag, may promote tissue damage and ulceration, and could contribute to gastric cancer development. Strains with the mosaic vacA allelic type s1a/m1 and possessing the cag insertion are considered endowed with increased inflammatory potential, and are more likely to be isolated from patients with peptic ulcer and gastric cancer. The presence in H. pylori cag PAI of operons involved in the stimulation of gastric epithelial cells to secrete high levels of inflammatory cytokines, in mobilisation of DNA, and formation of secretory mechanisms and conjugation apparati, could contribute to increase the risk of gastric cancer development in patients infected by this microorganism.

Bacterial Outer Membrane Proteins↗

Food allergy and Helicobacter pylori infection.

BACKGROUND: Most antigens reach the immune system through mucosae. Gastrointestinal mucosa is a barrier for alimentary antigens. Inflammatory processes, such as Helicobacter pylori-associated gastritis, could alter the integrity of the gastric barrier, increase the mucosal permeability, and enhance crossing of food antigens which may stimulate allergic reactions. PURPOSE: The aim of this study was to establish whether patients with symptomatic food allergy and detectable immunoglobulin E (IgE) to alimentary antigens were infected by Helicobacter pylori more often than controls, and to determine the phenotype of the infecting Helicobacter pylori. PATIENTS AND METHODS: Thirty-eight consecutive patients with symptomatic food allergy and serum IgE to alimentary antigens, and 53 consecutive age-matched controls (subjects without food allergy and detectable levels of IgE anti-alimentary antigens) living in the same area and attending the same institution were investigated serologically to determine the prevalence of Helicobacter pylori infection, and an immune response to CagA, a marker of the most pathogenic strains. IgE to alimentary allergens were measured by a commercial kit. RESULTS: The prevalence of Helicobacter pylori infection in patients with food allergy and controls was similar (42.1% and 47.1%, respectively). Anti-CagA antibodies in Helicobacter pylori-infected persons were detected in 62.5% of patients with food allergy, and 28.0% of controls (p = 0.030, odds ratio = 4.29, RR = 2.23). The mean IgE level to the most common alimentary antigens was increased in CagA-positive, with respect to the CagA-negative, patients. CONCLUSIONS: The enhanced mucosal and inflammatory lesions commonly found in individuals infected by CagA-positive Helicobacter pylori strains could increase the epithelial permeability and render non-selective the passage of allergens which, in atopic persons, could directly stimulate an IgE response. Infection by CagA-positive Helicobacter pylori may increase the risk of food allergy.

Adolescent↗