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Biomedical subjects

L Engstrand

Publications and source records attributed to L Engstrand.

At least 37 records · Page 2Linked to original sources
PubMed2000

Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement.

Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.

Adult↗
PubMed2000

Are genetic influences on peptic ulcer dependent or independent of genetic influences for Helicobacter pylori infection?

BACKGROUND: Genetic factors play a role or roles in the etiology of peptic ulcer disease and the acquisition of Helicobacter pylori infection. OBJECTIVE: To evaluate the relative importance of genetic and environmental influences as well as the importance of H. pylori on peptic ulcer disease. DESIGN: Cross-sectional study on monozygotic (MZ) and dizygotic (DZ) twins, reared apart or together. PARTICIPANTS: Twins of the subregistry of the Swedish Twin Registry included in the Swedish Adoption/Twin Study of Aging. MEASUREMENTS: Peptic ulcer disease and H. pylori status were assessed in MZ and DZ twin pairs reared apart or together. A total of 258 twin pairs had information regarding H. pylori status and history of peptic ulcer. Helicobacter pylori status was assessed as the presence of anti-H. pylori IgG. RESULTS: The intraclass correlations for peptic ulcer disease for MZ twins reared apart and together and DZ twins reared apart and together were 0.67, 0.65, 0.22, and 0.35, respectively, which indicates that genetic effects are important for liability to peptic ulcer. The correlation coefficient for MZ twins reared apart (0.67) provides the best single estimate of the relative importance of genetic effects (heritability) for variation in liability to peptic ulcer disease, and structural model fitting analyses confirmed this result (heritability, 62%). The cross-twin cross-trait correlations for MZ and DZ twins were examined to determine whether genetic effects for peptic ulcer were shared with or independent of genetic influences for H. pylori. The cross-correlations for MZ and DZ twins were almost identical (0.25 and 0.29, respectively), suggesting that familial environmental rather than genetic influences mediate the association between peptic ulcer disease and H. pylori infection. CONCLUSIONS: Genetic influences are of moderate importance for liability to peptic ulcer disease. Genetic influences for peptic ulcer are independent of genetic influences important for acquiring H. pylori infection.

Adult↗
PubMed2000

Helicobacter pylori entry into human gastric epithelial cells: A potential determinant of virulence, persistence, and treatment failures.

BACKGROUND AND OBJECTIVES: Intracellular location of Helicobacter pylori in human gastric epithelial cells has been observed in biopsies. Whether this reflects an ability to invade host cells and establish an intracellular niche remains to be determined. METHODS: The interactions between a clinical isolate of H. pylori and primary cell cultures from human gastric epithelium or the human epithelial cell line HEp-2 were monitored using time-lapse photography. This technique allows studies of the dynamics of host-microbial interactions. RESULTS: H. pylori cells readily approached and established close contacts with epithelial cells followed by uptake of the bacteria into the cellular cytoplasm. Entry into epithelial cells was achieved through an active process of bacterial motility and penetration of the cell membranes. In conventional invasion assays using HEp-2 cells, an increased internalization in a strain producing the vacuolating cytotoxin was observed, compared to the isogenic VacA knockout mutant. CONCLUSION: Invasion of gastric epithelium represents a hitherto unappreciated trait of H. pylori that could contribute to the bacterium's ability to establish persistent infection that evades the mucosal immune defense and sometimes also antimicrobial therapy. A small number of bacterial cells with a transient intracellular habitat could serve as a seeder population, providing a backup for a constantly challenged and fluctuating luminal population.

Antigens, Bacterial↗
PubMed2000

Bacterial translocation in experimental shock is dependent on the strains in the intestinal flora.

BACKGROUND: Enteric microorganisms are responsible for a significant proportion of post-surgical infections. Intestinal mucosal injury may permit translocation of bacteria and endotoxin. This study investigates translocation in peritonitis and ischemia/reperfusion by inoculating different bacterial species into the small intestine. METHODS: Twenty-five pigs were monitored hemodynamically and divided into three groups: controls (C), ischemia/reperfusion (I/R), and peritonitis (P). Intramucosal pH (pHi) was calculated tonometrically. A perfusion tube was positioned in the ileum for inoculation of the bacterial strains. In a first study period a non-pathogenic bacterium was used, whereas Escherichia coli strains with known ability to translocate were used in a second. Blood and mesenteric lymph nodes (MLNs) were obtained for bacterial culture and endotoxin analyses. RESULTS: Mesenteric arterial blood flow and pHi decreased in groups I/R and P. Endotoxin levels increased in these groups in period 1, whereas in period 2 an increase over time was only observed in group P. No bacterial translocation to blood or MLNs occurred in period 1. In period 2 bacteria translocated to MLNs in all animals, including controls. Translocation to central and/or mesenteric venous blood was found in all groups, but mainly in I/R and P. The incidence of mucosal injury was similar in the two periods. CONCLUSIONS: Since positive blood and MLN samples were only found in period 2, we conclude that translocation of bacteria seems to be more dependent on the presence of translocating strains in the intestinal bacterial flora than on the mucosal insult.

Analysis of Variance↗
PubMed2000

Clustering of clinical strains of Helicobacter pylori analyzed by two-dimensional gel electrophoresis.

Strain variations of Helicobacter pylori have been tested by numerous methods and compared among different patient groups. The aim of this study was to investigate whether H. pylori expresses disease-specific proteins that can be detected by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). H. pylori strains isolated from duodenal ulcer, gastric cancer, and gastritis patients were analyzed. Extensive variation in spot patterns was observed between the strains, but a dendrogram analysis revealed that some strains within each disease group clustered together. Eight proteins were sequenced and found in the H. pylori genome sequence. 2-D PAGE is a useful method for studies of protein expression and for highlighting the extensive strain variation that H. pylori exhibits.

Adenocarcinoma↗
PubMed2000

Differences in genotypes of Helicobacter pylori from different human populations.

DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.

Amino Acid Isomerases↗
PubMed2000

Brachyspira aalborgi infection diagnosed by culture and 16S ribosomal DNA sequencing using human colonic biopsy specimens.

In this study we report on the isolation and characterization of the intestinal spirochete Brachyspira aalborgi using human mucosal biopsy specimens taken from the colon of a young adult male with intestinal spirochetosis. A selective medium, containing 400 microg of spectinomycin/ml and 5 microg of polymyxin/ml was used for the isolation procedure. A high degree of similarity, in terms of phenotypic properties and 16S ribosomal DNA sequence, was observed between the isolated strain, named W1, and the type strain, 513A, of B. aalborgi. A similarity of 99.7% in the nucleotide sequence was found between W1 and 513A(T), based on the almost-complete gene. A short segment of the 16S rRNA gene was amplified by PCR using genetic material enriched from paraffin-embedded biopsy specimens, which were taken from the patient on two occasions. The products showed 16S rRNA gene sequences virtually identical to that of strain 513A(T) in the actual region. Immunohistochemistry was performed on the colonic biopsy specimens with a polyclonal antibody raised against an intestinal spirochete isolated in a previous case of human intestinal spirochetosis. The antibody reacted strongly with the spirochete on the luminal epithelium. No immune reaction was seen within or below the surface epithelium. Routine histology did not reveal signs of colitis. Electron microscopy showed spirochetes attached end-on to the colonic mucosal surface. The isolate grew poorly on a commonly used selective medium for intestinal spirochetes, which may explain previous failures to isolate B. aalborgi.

Adult↗
PubMed2000

40- to 100-kD protein(s) of Helicobacter pylori stimulate DNA synthesis in epithelial cell lines without affecting apoptosis.

BACKGROUND: Previous in vitro studies have demonstrated that water extracts and sonicates of Helicobacter pylori increase DNA synthesis in a small intestinal epithelial cell line. The aim of this study was to identify mitogenic factor(s) in a water extract of a H. pylori strain and to examine their effects on DNA synthesis and apoptosis in vitro. METHODS: IEC-6 and FHs 74 cells were incubated for 24 h with different dilutions of a water extract of H. pylori (cytotoxic strain 88-23) or with 6 protein fractions obtained by gel filtration. Cells were labeled with tritiated thymidine and processed for autoradiography. DNA synthesis was evaluated by the labeling index (LI%). The proportion of IEC-6 cells undergoing apoptosis and/or necrosis was evaluated by flow cytometry using fluorescein isothiocyanate (FITC)-labeled annexin-V and propidium iodide. In vitro caspase activity was also determined as an alternative method for detection of apoptosis. RESULTS: The water extract of H. pylori 88-23 markedly increased DNA synthesis in both epithelial cell lines (p < 0.01). A marked stimulation of DNA synthesis was also observed in IEC-6 cells incubated with fraction II- containing proteins of a molecular weight ranging between 40 and 100 kD (p < 0.01). A lesser stimulation of DNA synthesis was observed in cells incubated with higher concentrations of the other protein fractions (p < 0.01). Neither the water extract of H. pylori 88-23 nor the protein fraction II (40-100 kD) induced apoptosis in IEC-6 cells. CONCLUSION: A water extract of H. pylori 88-23 and a protein fraction containing proteins with molecular weights of 40-100 kD stimulate DNA synthesis in a rat and human small intestinal cell line. Apoptosis was unaffected by the water extract and by protein fraction II, which indicate that the H. pylori-derived mitogen(s) have the capacity to directly enhance epithelial cell proliferation in vitro.

Animals↗
PubMed2000

Helicobacter pylori strain types and risk of gastric cancer: a case-control study.

The aim of this novel endoscopy clinic-based case-control study was to explore the influence of different Helicobacter pylori strain types on the risk of gastric adenocarcinoma using isolated bacterial strains, tissue samples, and sera. We included 72 cases with gastric adenocarcinoma and 324 age- and sex-matched controls. Histological characterization, culture, molecular typing of H. pylori genes by PCR (cagA/vacA), conventional IgG ELISA, and immunoblotting (Western blot) for the CagA and VacA proteins were performed. With four tests combined, H. pylori infection was detected in 57 (79%) cases and 213 (66%) controls. A positive association between H. pylori infection and gastric cancer risk was found [odds ratio (OR), 2.1; 95% confidence interval, 1.1-3.9]. Type I (OR, 1.8), intermediate (OR, 2.0), and type H (OR, 0.2) strains of H. pylori presented different serum antibody levels and different levels of association with gastric cancer. Our case-control study, based on molecular characterization and serology, provides further evidence that infection by more virulent strains of H. pylori and the presence of antibodies toward the CagA protein can be used as markers for an increased risk of gastric adenocarcinoma and that the strain types of H. pylori could be used in the future to determine disease outcome.

Adenocarcinoma↗
PubMed1999

Epstein-Barr virus and cytomegalovirus in relation to testicular-cancer risk: a nested case-control study.

An infectious etiology of testicular cancer has been suggested. We have evaluated seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to testicular-cancer risk in a case-control study, nested within a cohort of prospectively collected serum specimens from 293,692 individuals. For each of 81 cases of testicular cancer identified, 3 controls were randomly selected from the cohort. Serum IgG antibody titers against CMV and EBV were determined using enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence methods. Odds ratios (OR) were obtained from conditional logistic-regression models. No association was found between CMV positivity and testicular cancer overall (OR = 1.08; 95% confidence interval 0.60-1.94); risk for testicular seminoma was increased among CMV seropositive [OR = 1.70 (0.80-3.59)], whereas seropositivity was associated with decreased risk for testicular non-seminoma [OR = 0.54 (0.19-1.56)] (p for heterogeneity, 0.09). For EBV, the risk for testicular cancer was increased among individuals seropositive for viral capsid antigen (VCA) [OR = 2.74 (0.62-12.12)]. The results lend some support to the hypothesis of an infectious etiology, and we propose that future studies should take into account age at infection.

Adult↗
PubMed1999

[Development of resistant Helicobacter pylori in Sweden. Tendency toward increasing resistance to clarithromycin].

This study was designed to investigate the development of antibiotic resistance in Swedish H pylori isolated 1990-96. A total of 415 isolates collected from 10 clinical microbiology laboratories were examined. Three different methods of susceptibility testing were compared: agar dilution, the E-test and disc diffusion. None of the isolates was resistant to ampicillin or tetracycline, but approximately 30 per cent were resistant to metronidazole. An increase in resistance to clarithromycin was noted during 1996 (9% resistant strains), though the significance of this finding needs further investigation. The comparison of susceptibility tests suggested disc diffusion to be of doubtful value, but the E-test to be appropriate for testing H pylori. However, the number of isolates resistant to metronidazole was higher with the E-test than with agar dilution. The value of testing susceptibility to metronidazole is discussed.

Anti-Bacterial Agents↗
PubMed1999

One stomach--one strain: does Helicobacter pylori strain variation influence disease outcome?

The aim of the study was to determine inter- and intrapatient variation of Helicobacter pylori strains based on genomic fingerprinting and cagA (cytotoxin-associated gene A) status. Ten bacterial colonies from each of 10 patients with gastric cancer (GC), 10 with duodenal ulcer (DU), and 10 with gastritis (GI) were used. The presence of the putative adhesin gene, the cagA gene, and the strain specific banding pattern obtained by arbitrary primed (AP-) PCR was analyzed. Genomic fingerprinting showed extensive interpatient variation, but the banding patterns obtained from colonies from the same patient were always identical (intrapatient variation). In five patients, the cagA status varied between the colonies despite identical banding patterns. Among patients in a developed country such as Sweden, the proportion with multiple-strain infection of H. pylori is low, but subclones with differing cagA status exist within the strain.

Adhesins, Bacterial↗
PubMed1999

In vitro aging of Helicobacter pylori: changes in morphology, intracellular composition and surface properties.

BACKGROUND: During the conversion from the bacillary into the coccoid form, Helicobacter pylori organisms are known to change extensively. The aim of this study was to determine some of the changes that occur regarding morphology, intracellular composition and surface properties during the aging of bacteria in vitro. MATERIALS AND METHODS: H. pylori from agar plate cultures of different ages was used in this study. The intracellular composition of the two morphological forms of the bacteria was tested by density centrifugation, DNA extraction and quantitative OD, mRNA and ATP measurements. Immunoblotting was used to observe changes in secreted/superficial protein patterns, and hydrophobicity measurements were used to observe changes in surface properties. RESULTS: All bacillary H. pylori organisms changed morphology gradually over 10 days of culture. Rods had a higher density than cocci; bacteria stored in PBS had the highest density and bacteria stored in water had the lowest. The quantitative DNA, RNA and ATP content were reduced in the aging bacteria. Fewer immunogenic proteins were expressed, and an increased surface hydrophobicity was observed in the older cultures. CONCLUSION: This study highlights several aspects of H. pylori aging in vitro and shows some of the differences that exist between bacillary and coccoid forms. This information is important for understanding the transmission and survival of H. pylori outside the human host, as the degradative changes in the intracellular composition and the surface properties shown here point to dead bacteria, and not to a viable but nonculturable form.

Adenosine Triphosphate↗
PubMed1999

Helicobacter pylori extracts reduce gastric mucosal blood flow by a nitric oxide-independent but mast cell- and platelet-activating factor receptor-dependent pathway in rats.

BACKGROUND: We have previously shown that water extracts from Helicobacter pylori reduce gastric mucosal blood flow by approximately 15%. It has also been suggested that H. pylori can inhibit endogenous nitric oxide (NO) biosynthesis. Our aim was to examine whether the reduction in blood flow induced by H. pylori is the direct consequence of an NO synthase inhibition and the possible involvement of mast cell degranulation. METHODS: A water extract was produced from wildtype strain 88-23. The extract was applied on the exteriorized gastric corporal mucosa in inactin-anesthetized rats, after removing as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured with laser-Doppler flowmetry. RESULTS: In rats pretreated with the NO synthase inhibitor N-nitro-L-arginine there was a 19% +/- 6% reduction in blood flow 40 min after application of the extract, and a 27% +/- 9% reduction after another 20 min with saline. The reduction was abolished by concomitant pretreatment with the mast cell stabilizer ketotifen or the platelet-activating factor (PAF) receptor antagonist WEB2086. CONCLUSION: The reduction in mucosal blood flow induced by the extract was probably mediated through an acute inflammatory response involving mast cell degranulation with consequent PAF secretion. The effect on blood flow was not the result of a decrease in vascular tone due to an inhibition of endogenous NO biosynthesis.

Animals↗
PubMed1999

Occurence of resistance mutation and clonal expansion in Helicobacter pylori multiple-strain infection: a potential risk in clarithromycin-based therapy.

In a previous study, a patient was shown by means of DNA fingerprinting to be infected with different Helicobacter pylori strains before and after clarithromycin treatment. The strain isolated before treatment was susceptible (ClaS), whereas the strain isolated after 3 months of treatment was resistant (ClaR). Eighty H. pylori colonies from primary isolates were analyzed by DNA fingerprinting and restriction enzyme digestion of the 23S rRNA product of polymerase chain reaction in order to distinguish between ClaS and ClaR strains. One of the 40 colonies from isolates recovered before treatment showed a DNA fingerprint similar to that of the 40 from after treatment. However, a notable difference was that this isolate was not ClaR before treatment. Two ClaS H. pylori strains were present in the patient before treatment. The underrepresented strain gained a resistance mutation in the 23S rRNA gene and underwent clonal expansion during treatment. Recrudescence of the H. pylori infection therefore was the result.

Anti-Bacterial Agents↗
PubMed1999

13C-urea breath test results in pigs challenged with Helicobacter pylori or other urease producing bacteria.

The gastric bacterial flora and its influence on the 13C-urea breath test (UBT) for detection of Helicobacter pylori infection was studied in a pig model. Seven SPF minipigs were used. H. pylori or a mix of other urease positive bacteria were administered orally. UBT, serum and biopsies for histology and culture were collected. Our results show that UBT is not specific for H. pylori in pigs as the gastric bacterial flora is responsible for the high UBT values observed. Furthermore, the Ellegaard Göttingen SPF minipigs are not useful in an animal model for H. pylori studies.

Animals↗