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- Adamsson, Jenni, 1977, et al.
(författare)
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Immune Responses Against Helicobacter pylori in Gastric Cancer Patients and in Risk Groups for Gastric Cancer.
- 2013
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Ingår i: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 18:1, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has previously been reported that weak serum IgG but elevated IgA antibody responses against H.pylori may be associated with risk of gastric cancer (GC) development. To search for potential immunologic markers for GC, we analyzed antibody responses against H.pylori in risk groups of cancer development. MATERIAL AND METHODS: Sera and stomach biopsies collected from H.pylori-infected GC patients as well as from patients with gastric ulcer (GU), atrophic gastritis, intestinal metaplasia (IM) and duodenal ulcer and from H.pylori-infected control subjects without atrophy or IM, and in addition from H.pylori-negative subjects were analyzed for IgG and IgA antibodies against three different H.pylori antigen preparations, that is, membrane protein (MP), urease, and CagA. RESULTS: We observed an increased serum IgA/IgG titer ratio against H.pylori anti-MP in GC and GU patients, and against CagA in Hp-infected GC patients and risk groups. Female patients with GC had a higher serum anti-MP IgA/IgG titer ratio and a higher proportion of poorly differentiated cancer compared with male patients. As earlier observed, the non-tumorous mucosa of H.pylori-infected GC patients contained considerably lower levels of total IgA and H.pylori-specific IgA compared with H.pylori-infected controls. Similarly, we observed decreased specific mucosal anti-MP IgA response in patients with IM. CONCLUSION: We observed several differences in local and systemic immunologic responses against H.pylori in H.pylori-infected GC patients and putative GC risk group patients compared with H.pylori-infected controls. These findings may be of importance in efforts to identify risk groups of GC or early stages of GC.
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- Andres, Sonke, et al.
(författare)
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Type I Restriction-Modification Loci Reveal High Allelic Diversity in Clinical Helicobacter pylori Isolates
- 2010
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 15:2, s. 114-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: A remarkable variety of restriction-modification (R-M) systems is found in Helicobacter pylori. Since they encompass a large portion of the strain-specific H. pylori genes and therefore contribute to genetic variability, they are suggested to have an impact on disease outcome. Type I R-M systems comprise three different subunits and are the most complex of the three types of R-M systems. Aims: We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori. Material and methods: Sixty-one H. pylori isolates from a Swedish hospital based case-control study and 6 H. pylori isolates of a Swedish population-based study were analyzed using polymerase chain reaction for the presence of the three R-M systems' subunits. Representative gene variants were sequenced. Results: Although the hsdM and hsdR genes appeared conserved in our clinical H. pylori isolates, the sequences of the hsdS loci were highly variable. Despite their sequence diversity, the genes per se were present at high frequencies. We identified a number of novel allelic hsdS variants, which are distinct from corresponding hsdS loci in the sequenced H. pylori strains 26695, J99 and HPAG1. In analyses of paired H. pylori isolates, obtained from the same individuals with a 4-year interval, we observed genetic modifications of hsdS genes in patients with atrophic gastric mucosa. Discussion: We propose that the genetic variability of hsdS genes in a bacterial population will give rise to new specificities of these enzymes, which might lead to adaptation to an ever-changing gastric environment.
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- Kalbina, Irina, et al.
(författare)
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Expression of Helicobacter pylori TonB Protein in Transgenic Arabidopsis thaliana : toward production of vaccine antigens in plants
- 2010
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Ingår i: Helicobacter. - : John Wiley & Sons. - 1083-4389 .- 1523-5378. ; 15:5, s. 430-437
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to produce a recombinant version of the highly antigenic Helicobacter pylori TonB (iron-dependent siderophore transporter protein HP1341) in transgenic plants as a candidate oral vaccine antigen. Materials and Methods: Using Agrobacterium-mediated gene transfer, we introduced three different constructs of the tonB gene into the genome of the model plant Arabidopsis thaliana. We investigated transgene insertion by PCR, produced TonB antibodies for analysis of the production of the recombinant protein in plants, verified the identity of the protein produced by mass spectrometry analysis, and analyzed the number of genetic inserts in the plants by Southern blotting. Results: Three different constructs of the expression cassette (full-length tonB, tonB truncated in the 5' end removing the codons for a transmembrane helix, and the latter construct with codons for the endoplasmic reticulum SEKDEL retention signal added to the 3' end) were used to find the most effective way to express the TonB antigen. Production of TonB protein was detected in plants transformed with each of the constructs, confirmed by both Western blotting and mass spectrometry analysis. No considerable differences in protein expression from the three different constructs were observed. The protein concentration in the plants was at least 0.05% of the total soluble proteins. Conclusions: The Helicobacter pylori TonB protein can be produced in Arabidopsis thaliana plants in a form that is recognizable by rabbit anti-TonB antiserum. These TonB-expressing plants are highly suitable for animal studies of oral adminstration as a route for immunization against Helicobacter infections.
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- Kivistö, Rauni, et al.
(författare)
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Characterization of multiple Helicobacter bizzozeronii isolates from a Finnish patient with severe dyspeptic symptoms and chronic active gastritis
- 2010
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 15:1, s. 58-66
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Helicobacter pylori is the primary cause of gastritis and peptic ulceration in humans. In a minority of patients with upper gastrointestinal symptoms, long tightly coiled spiral bacteria, provisionally named "Helicobacter heilmannii," are observed in gastric biopsies. These bacteria are extremely fastidious and only one previous study has succeeded in obtaining an isolate in vitro. MATERIALS AND METHODS: We used two different selective media to isolate "H. heilmannii" from the gastric mucosa of a Finnish patient presenting with severe dyspeptic symptoms. The isolates were characterized by testing for urease and catalase activity, by using light and electron microscopy, and by sequencing of the partial 16S rRNA and ureAB genes. Single-enzyme amplified fragment length polymorphism (sAFLP) was used to analyze the genetic diversity among the isolates. RESULTS: We obtained 15 isolates from different gastric biopsies prior and three after unsuccessful treatment of the patient. The isolates were identified as Helicobacter bizzozeronii. Eradication therapy was unsuccessful most probably due to high level of resistance to metronidazole. Persistent colonization by the same H. bizzozeronii clone was confirmed by sAFLP, however, small differences between the profiles suggested long-term colonization of the patient. CONCLUSIONS: Helicobacter bizzozeronii remains the only "H. heilmannii" species isolated from human gastric mucosa although it has been an infrequent observation among "H. heilmannii"-infected patients in PCR-based screening studies. The relevance of H. bizzozeronii and other potentially zoonotic gastric Helicobacter spp. in human disease remains to be determined.
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- Lindén, Sara K., 1974, et al.
(författare)
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Role of mucin Lewis status in resistance to Helicobacter pylori infection in pediatric patients.
- 2010
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Ingår i: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 15:4, s. 251-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Helicobacter pylori causes gastritis, peptic ulcer and is a risk factor for adenocarcinoma and lymphoma of the stomach. Gastric mucins, carrying highly diverse carbohydrate structures, present functional binding sites for H. pylori and may play a role in pathogenesis. However, little information is available regarding gastric mucin in children with and without stomach diseases. MATERIALS AND METHODS: Expression of mucins and glycosylation was studied by immunohistochemistry on gastric biopsies from 51 children with and without H. pylori infection and/or peptic ulcer disease. RESULTS: In all children, MUC5AC was present in the surface epithelium and MUC6 in the glands. No MUC6 in the surface epithelium or MUC2 was detected in any section. The Le(b) and Le(a) blood group antigens were present in the surface epithelium of 80% and 29% of children, respectively. H. pylori load was higher in Le(b) negative children than in Le(b) positive individuals (mean +/- SEM 17.8 +/- 3.5 vs 10.8 +/- 1.5; p < 0.05), but there was no correlation between Le(a) or Le(b) status and gastritis, nodularity, and gastric or duodenal ulcer (DU). Expression of sialyl-Le(x) was associated with H. pylori infection, and DU. CONCLUSIONS: Mucin expression and glycosylation is similar in children and adults. However, in contrast to adults, pediatric H. pylori infection is not accompanied by aberrant expression of MUC6 or MUC2. Furthermore, the lower H. pylori density in Le(b) positive children indicates that H. pylori is suppressed in the presence of gastric mucins decorated with Le(b), the binding site of the H. pylori BabA adhesin.
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