Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden

ABSTRACT: BACKGROUND: Chronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related toinfection with Helicobacter pylori (H. pylori). Two major virulence factors of H. pylori,CagA and VacA, have been associated with these sequelae of the infection. In this study, totalDNA was isolated from gastric biopsy specimens to assess the cagA and vacA genotypes. RESULTS: Variations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/dayregions were analysed in 155 H. pylori-positive gastric biopsies from 71 individuals usingPCR and sequencing. Analysis of a possible association between cagA and vacA genotypesand gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the samebiopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs wasassociated with atrophy in the gastric mucosa. No statistically significant relation betweenvacA genotypes and gastroduodenal pathogenesis was observed. CONCLUSIONS: The results of this study indicate that cagA genotypes may be important determinants in thedevelopment of gastroduodenal sequelae of H. pylori infection. In contrast to other studies,vacA genotypes were not related to disease progression or outcome. In order to fullyunderstand the relations between cagA, vacA and gastroduodenal pathogenesis, themechanisms by which CagA and VacA act and interact need to be further investigated.     

Recent Advances in the Treatment of Duodenal Ulcer Disease: A Surgical Perspective

Chronic peptic ulceration is a disease process in transition. During the past two decades, the disease has changed in its incidence, in its presentation and in its medical consequences. The pathogenesis of acid-peptic disease has been the major focus of numerous investigations, and major advances in understanding basic gastric physiology have led to specific and increasingly effective therapeutic approaches. With the introduction of H₂-receptor antagonists, the treatment of peptic ulceration has been radically altered, and many new therapies await clinical trial. Surgeons treating gastroduodenal ulceration will require greater knowledge of gastric physiology and an increasingly refined appreciation of both the power and limitations of various medical and surgical therapies.     

幽门螺杆菌致细胞空泡变性作用

This study was designed to observe vacuolation effect of Helicobacter pylori on gastric epithelial cells.The H.pylori isolates derived from patiens with peptic ulcer,chronic gastritis and gastric cancer were plated on common selective medium and their vacuolation effects on SGC\|7901 cells were compared. The percentage of H.pylori (Tox +) strain in clinical isolates from different gastroduodenal diseases had no significant difference.The toxicity of the H.pylori (Tox +) strain from peptic ulcer was si…     

幽门螺杆菌感染的治疗进展

幽门螺杆菌(helicobacter pylori,H.pylori,HP)感染是一个世界性问题。人类感染Hp可导致慢性胃炎、胃和十二指肠溃疡、消化性胃黏膜相关的淋巴样组织淋巴瘤和胃腺癌。根除幽门螺杆菌对胃肠疾病的转归和预防有着重要作用。但是由于抗茵药物的滥用,使得对幽门螺杆茵的治疗变得棘手。本文就Hp的致病机制、耐药性问题及治疗方法等的研究进展作一综述。     

Gastric control of duodenal electric activity--the function of the gastroduodenal junction.

An investigation was made into the links between electric activity of antral and of duodeno-jejunal musculature in different functional conditions. The function of the gastroduodenal junction in this linking mechanism was analysed. The following observations were made: (a) in the absence of gastric stimulation, the slow electric activities of stomach and duodenum appear to be completely independent; (b) the gastroduodenal junction evidences no electric activity of its own but is affected by that of the two adjacent structures; (c) chemical stimulation of the gastric mucosa causes activation of the electric and mechanical activity of the stomach and analogous activation of duodenal musculature; this effect is mediated by the gastroduodenal junction; (d) very probably, the transmission of gastric activation to the duodenum is myogenic for it ceases after surgical transection but not after cooling or after ligature. The possible functional role of the pyloric junction in the complex gastroduodenal mechanism is discussed.     

The status of the cagA gene does not predict Helicobacter pylori-associated peptic ulcer disease in Singapore

Discrepancies among reports from different geographical regions worldwide on the association between the presence of cagA and peptic ulcer disease prompted this study on the predictive value of the cagA gene in Helicobacter pylori-associated gastroduodenal diseases in the Singapore population. H. pylori strains were obtained from 169 patients with a peptic ulcer, 83 with non-ulcer dyspepsia, and nine with gastric cancer. The presence of the cagA gene was evaluated by polymerase chain reaction (PCR). The expected 400 bp PCR product coding for the cagA gene was present in 232/261 (89%) H. pylori isolates. Of these, 151/169 (89%) strains from patients with peptic ulcer, 73/83 (88%) strains from patients with non-ulcer dyspepsia and 8/9 (89%) strains from cancer patients were positive for the cagA gene. There was no statistically significant difference between the prevalence of cagA-positive strains from patients with distinct clinical outcomes (p > 0.05). The prevalence of cagA-positive strains in the Singapore population is high regardless of clinical disease status. The results suggest that the cagA gene is not a universal virulence marker of H. pylori.     

CagA and VacA: Virulence Factors of Helicobacter pylori in Thai patients with Gastroduodenal Diseases

Background. The aim of this study was to assess the seroprevalence of cytotoxin-associated gene A ( cag A) and vacuolating cytotoxin gene A ( vac A) of Helicobacter pylori in selected Thai populations with specific gastroduodenal diseases.
Materials and Methods. The immunoblot assay was used to detect serum antibodies against CagA and VacA obtained from the following patients: 87 cases of nonulcer dyspepsia (NUD), 61 cases of duodenal ulcer (DU), 49 cases of gastric ulcer (GU), and 10 cases of gastric cancer (GC).
Results. Serum antibodies to CagA were detected in 75.4% of all patients (70.1% of NUD, 78.7% of DU, 77.6% of GU, and 90% of GC). Although the prevalence of CagA seropositivity in GC patients was higher than in the other three groups, the difference was not statistically significant ( p > .05).
Conclusions. The high seroprevalence of the CagA-positive H. pylori strain in patients with peptic ulcer, GC, and NUD indicates that this strain is common in Thai patients with gastroduodenal diseases. Furthermore, phenotypic classification of H. pylori into type 1 (CagA-positive, VacA-positive) and type 2 (CagA-negative, VacA-negative) is not a useful marker for screening patients with severe forms of gastroduodenal diseases.     

Helicobacter pylori interacts with heparin and heparin-dependent growth factors

Abstract The pathogenic bacterium Helicobacter pylori , which causes active, chronic type B gastritis and peptic ulcer disease, and increases the risk for development of gastric cancer, could tentatively interfere with growth factors and growth factor receptors of importance for the gastroduodenal mucosa, e.g. heparin-binding FGFs (fibroblast growth factors). H. pylori binds FGF with an extremely strong affinity (3.8 × 10⁻¹² M), and also heparan sulfate and heparin with higher affinity ( K _d 9 × 10⁻⁹ M) than FGFs bind to heparin (10⁻⁸–10⁻⁹ M). FGF receptors are also dependent on heparin for their activation. Heparan sulfate binding proteins (HSBP) are exposed on and shed from the surface of H. pylori , which often are localised close to the epithelial stem cells in the gastroduodenal glands. H. pylori could thus efficiently interfere with growth factors and growth factor receptors, tentatively resulting in disturbance of the delicate balance that control the renewal, maintenance and repair of the gastroduodenal mucosa. This mode of action has previously not been considered, but may constitute part of its pathogenic mechanism. Such a dynamic mode of action of H. pylori may explain the reason for that infected victims may either suffer from gastrointestinal symptoms or lack clinical evidence of disease or discomfort.     

The Hsp60 protein of Helicobacter pylori: structure and immune response in patients with gastroduodenal diseases

Helicobacter pylori is a human pathogen that has been associated with gastritis, peptic ulcer and gastric carcinoma. The role of the direct action of H. pylori virulence factors and of the induction of autoreactive immunity in the development of chronic gastritis has not been clarified yet. Here we report the cloning and molecular characterization of a gene of H. pylori coding for a protein of 58kDa, recognized by sera of patients affected by H. pylori-induced gastroduodenal diseases. This antigen is present in all the H. pylori strains tested and it belongs to the Hsp60 family of heat-shock proteins, with high homology with other bacterial and eukaryotic proteins of the same family. This class of homologous proteins has been implicated in the induction of autoimmune disorders in different systems. The presence in infected patients of anti-H. pylori Hsp60 antibodies, potentially cross-reacting with the human homologue, and cross-reactivity between human Hsp60 and a rabbit antiserum against H. pylori Hsp60 suggest that a role of this protein in gastroduodenal diseases is possible.     

Lesions Associated with Gastroduodenal Haemorrhage,in Relation to Aspirin Intake

The incidence of aspirin ingestion during the week preceding overt gastroduodenal bleeding was recorded in 582 patients. A positive aspirin history was found in 80% of patients with acute gastric lesions, in 63% of those in whom no lesion was found, in 52% of those with a chronic duodenal ulcer, and in 49% of patients with a chronic gastric ulcer. In a control series of 542 consecutive patients without overt bleeding admitted to the same wards during part of the time of this investigation the aspirin incidence was 32%.The difference in aspirin habits between these two series confirms that aspirin is a factor in precipitating overt haemorrhage in acute and chronic peptic ulcers, and that it is an important cause of bleeding from the stomach or duodenum, or both, in the absence of a chronic peptic ulcer.     

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients

Objective. Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. Methods. This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori‐cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. Results. Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). Conclusions. Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.     

Helicobacter pylori, T cells and cytokines: the "dangerous liaisons"

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori-specific Th1 response, characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas-Fas ligand-mediated killing of B cells. In H. pylori-infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry.     

Echography of the stomach and duodenum in children in health and disease

The paper is concerned with the results of echography of the stomach and duodenum in 100 healthy children aged 1 month to 15 years and in 141 children with different types of gastritis, duodenitis and peptic ulcer. Echographic investigation of these hollow organs was made possible after their acoustic filling with 5% glucose solution. Echography permitted fast and reliable differentiation of the type and site of stomach and duodenal lesions, determining the presence of a gastroduodenal reflux and sizes of an ulcerative defect of the duodenal wall.     

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 (621-651bp), type B (732-735bp) 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.     

PULMONARY HYALINE MEMBRANE DISEASE—A Panel Discussion: Pediatrician's Point of View

Elevated serum amylase is a frequent concomitant of perforated gastroduodenal ulcer. To determine if there might be significant correlation between an increase in amylase and some of the other factors associated with ulcer perforation, a study was made of the clinical records of 1,000 patients with perforation of gastroduodenal ulcers. Sixteen per cent of the patients had amylase levels of 200 Somogyi units or more. This rise in serum amylase comes about in cases of perforated peptic ulcer as a result of peritoneal lymphatic absorption of fluid containing pancreatic enzyme which is spilled through the perforation. Among patients with perforated ulcers and elevated serum amylase levels, the higher the amylase level, the higher the mortality rate.The factors of amount of abdominal fluid spill, the duration of the perforation before surgical closure, the size of the perforation, shock and recent ingestion of food were also studied for possible relationship with elevated serum amylase. All appeared to be statistical if not etiological associates of abnormal serum amylase levels.Because high amylase values so often occur in perforated ulcer, there is no amylase level that can be considered diagnostic of acute pancreatitis.     

Analysis of possible causes of activation of gastric and the pancreatic excretory and incretory function after completion of space flight at the international space station

A comparative analysis of the excretory and incretory activity of the stomach and pancreas in astronauts soon after completion of space flights of various durations was performed. An increase in the fasting activity of gastric and pancreatic enzymes and hormones (insulin and C-peptide) in blood, reflecting the increased excretory and incretory activity of organs of the gastroduodenal region developing in microgravity, was demonstrated. The absence of subjects infected with Helicobacter pylori in the space flight crew excluded the involvement of this microorganism in the mechanism underlying the increase in the gastric secretory activity. The absence of correlation between the increase in the secretory activity of organs of the gastroduodenal region and the duration of the space flight allowed us to rule out the hypokinetic mechanism, which is associated with the duration of exposure to microgravity. It was concluded that the main mechanism underlying the changes in the functional state of the digestive system in space flight may be determined by the rearrangement of the venous hemodynamics of organs of the abdominal cavity, unrelated to the duration of exposure to microgravity. It was shown that, after completion of space flights and in ground-based experiments simulating the hemodynamic rearrangement occurring in microgravity, the increase in the basal excretory activity of gastroduodenal organs was not caused by gastrin secretion and occurred simultaneously with an increase in the secretion of insulin, which is considered as a putative hormonal component of the hemodynamic mechanism.     

Instructions for authors

Although Helicobacter pylori infects 50% of the total human population, only a small fraction of the infected people suffer from severe diseases like peptic ulcers and gastric adenocarcinoma. H. pylori strains, host genotypes and environmental factors play important role in deciding the extent and severity of the gastroduodenal diseases. The bacteria has developed a unique set of virulence factors to survive in the extreme ecological niche of human stomach. Together these virulence factors make H. pylori one of the most successful human pathogenic bacteria colonizing more than half of the human population. Understanding the mechanism of action of the major H. pylori virulence factors will shed light into the molecular basis of its pathogenicity.     

A Comprehensive Sequence and Disease Correlation Analyses for the C-Terminal Region of CagA Protein of Helicobacter pylori

Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B′, B′′) and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease.