| 1. |
- Simán, Henrik, et al.
(författare)
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Association between Helicobacter pylori and gastric carcinoma in the city of Malmo, Sweden. A prospective study
- 1997
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 32:12, s. 1215-1221
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We have investigated the association between Helicobacter pylori and gastric carcinoma through a nested case-control study in a single city. METHODS: From a cohort of 32,906 residents recruited from 1974 through 1992, 56 cases of gastric adenocarcinoma and 224 matched controls were selected. The mean interval between serum collection and diagnosis was 5.7 years. Frozen serum or plasma samples were analysed for IgG antibodies against H. pylori with an enzyme-linked immunosorbent assay. RESULTS: The overall seropositivity prevalence in gastric cancer cases was 82%, compared with 49% in controls, giving an odds ratio (OR) of 5.0 (95% confidence interval (CI), 2.2-11.5). Partial gastrectomy because of peptic ulcer 5 to 36 year before diagnosis of gastric cancer could be a confounding factor. With exclusion of 10 such cases, H. pylori seropositivity among cases was 78%, as compared with 50% in matched controls (OR, 3.9; 95% CI, 1.7-9.2). Tumours of the cardia were not associated with H. pylori (OR, 0.92; 95% CI, 0.23-3.7), which is in contrast to tumours of the fundus, corpus, and antrum, which were significantly associated (OR, 11.1; 95% CI, 2.4-71.8). This difference in location was significant (P < 0.01). CONCLUSION: There is a significant association between prior infection with H. pylori and later development of gastric carcinoma, and the association is related to noncardia gastric cancer.
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| 2. |
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| 3. |
- Simán, Henrik, et al.
(författare)
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Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma.
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 42:8, s. 933-940
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Helicobacter pylori infection is an established risk factor for non-cardia gastric adenocarcinoma. Infection with H. pylori strains harbouring the cagA pathology island may augment this association. H. pylori infection may at the same time reduce the risk for oesophageal carcinoma. However, prospective data on the association between CagA seropositivity and gastric or oesophageal carcinomas are limited. The purpose of this study was to investigate whether CagA seropositivity among H. pylori seropositive subjects is associated with gastric or oesophageal carcinomas. Material and methods. A nested case-control study was performed in the Malmo Preventive Medicine cohort consisting of 32,906 middle-aged subjects. Tumour cases were identified by the Swedish National Cancer Registry. The Western blot method Helicoblot 2.1 was used to detect H. pylori and CagA seropositivity. Results. Non-cardia gastric adenocarcinoma was associated with H. pylori seropositivity, odds ratio 17.8 (95% CI: 4.2 - 74.8; 67 cases). The odds ratio for CagA seropositivity among H. pylori seropositive subjects was 9.7 ( 95% CI: 1.5 - infinity). No significant associations were found between cardia gastric adenocarcinoma and H. pylori or CagA seropositivity among H. pylori seropositive subjects; odds ratios were 1.5 ( 95% CI: 0.51 - 4.8) and 2.7 ( 95% CI: 0.38 - infinity), respectively ( 24 cases). Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma were not significantly associated with H. pylori seropositivity or with CagA seropositivity among H. pylori seropositive subjects; the odds ratios associated with oesophageal adenocarcinoma were 0.46 ( 95% CI: 0.07 - 2.6) and 0.38 ( 95% CI: 0.02 - 24), respectively. Corresponding odds ratios for oesophageal squamous cell carcinoma were 0.44 ( 95% CI: 0.15 - 1.2; 37 cases) and 2.0 ( 95% CI: 0.24 - infinity), respectively. Conclusions. CagA seropositivity among H. pylori seropositive subjects is a risk factor for non-cardia gastric adenocarcinoma.
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| 4. |
- Simán, Henrik, et al.
(författare)
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Helicobacter pylori infection is associated with a decreased risk of developing oesophageal neoplasms
- 2001
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 6:4, s. 310-316
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Tidskriftsartikel (refereegranskat)abstract
- Background. The role of Helicobacter pylori infection in the development of oesophageal malignancies was investigated through a multivariate conditional logistic regression analysis in a nested case-control study. Methods. Blood samples and a questionnaire on smoking and alcohol habits were collected from a cohort of 32,906 city residents during a health-screening programme between 1974 and 1992. Forty-four cases of oesophageal cancer and 149 matched controls were selected. The mean interval between screening and cancer diagnosis was 11.9 years. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG. Occupation was included in the statistical analysis as an indicator of socio-economic status. Results. Helicobacter pylori seropositivity was present in 10 of the cases (22.7%) and 67 of the controls (45.0%). In a multivariate model, vith adjustment for occupation, tobacco and alcohol consumption, the odds ratio for developing in oesophageal malignancy when infected with H. pylori was 0.29 (95% confidence interval (CI): 0.12-0.67). Current smokers had an odds ratio of 17.3 (95% Cl: 3.0-99.4) and the odds ratio for ex-smokers was 5.9 (95% CI: 1.15-29.9). High alcohol consumption was no longer significantly, associated with oesophageal neoplasms after tobacco smoking was included into the model, odds ratio 1.22 (95% CI: 0.46-3.2). The protective effect of H. pylori was more pronounced for oesophageal adenocarcinoma (seven cases, odds ratio 0.16, 95% Cl: 0.00-1.06) than for squamous-cell carcinoma (29 cases, odds ratio 0.41, 95% Cl: 0.14-1.2). Conclusions. Helicobacter pylori infection is associated with a decreased risk of developing an oesophageal malignancy. Current smokers and ex-smokers have instead a definite increased risk of oesophageal neoplasms.
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| 5. |
- Simán, Henrik, et al.
(författare)
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Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter pylori-infected individuals
- 2001
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Ingår i: Scandinavian Journal of Gastroenterology. - 1502-7708. ; 36:2, s. 208-213
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The importance of tobacco smoking and Helicobacter pylori infection as risk factors in the development of gastric carcinoma was investigated through multivariate conditional logistic regression analysis in a nested case-control study. METHODS: Blood samples and a questionnaire on smoking habits were collected from a cohort of 32,906 city residents during a health screening programme from 1974 to 1992. Fifty-six cases of gastric cancer and 224 matched controls were selected. The mean interval between screening and cancer diagnosis was 5.7 years. H. pylori infection was determined by IgG-serology. Occupation categorized into blue-collar workers, white-collar workers, self-employed and unknown occupation was included in the statistical analysis as an indicator of socio-economic status. RESULTS: The proportion of current smokers was 61% among gastric cancer cases, versus 41% among controls. H. pylori seropositivity was present in 82% of the cases and 49% of the controls. In a multivariate model current smokers had an odds ratio (OR) of 2.2 (95% confidence interval (CI): 1.2-4.2). With different levels of tobacco consumption, smoking less than 20 g tobacco each day gave the OR of 2.1 (95% CI: 0.98-4.4), and the OR when smoking more than 20 g tobacco per day was 2.5 (95% CI: 1.1-5.6). The OR of H. pylori infection was 5.0 (95% CI: 2.2-11.2). Among H. pylori-seropositive citizens, current smoking was associated with an increased risk of 2.3 (95% CI: 1.1-4.7) compared with non-smoking H. pylori-positive persons. CONCLUSIONS: Tobacco smoking and H. pylori are both risk factors in the development of gastric cancer, and tobacco smoking is still a risk factor among H. pylori-infected individuals. The risk of gastric cancer among H. pylori-infected current smokers is 11 times that of non-infected individuals not currently smoking.
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| 6. |
- Chen, Qi, et al.
(författare)
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Lipoprotein receptor mediated metabolism of 14C arachidonic acid labelled chylomicron remnants by Hep G2 cells
- 1992
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Ingår i: Lipids. - 0024-4201. ; 27:9, s. 664-668
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Tidskriftsartikel (refereegranskat)abstract
- During lipolysis of chylomicron triacylglycerol by lipoprotein lipase, arachidonic acid (AA) esters are hydrolyzed at a slower rate than the predominant 16-18 carbon fatty acid esters. The further metabolism of the AA that is hereby enriched in the chylomicron remnant acylglycerols has not been investigated. In the present study, we examined the low density lipoprotein (LDL) dependent and independent metabolism of [14C]AA present in chylomicron remnants in the human hepatoma cell line Hep G2. Mesenteric duct cannulated rats were fed [14C]AA and [3H]cholesterol in corn oil, and the chyle obtained was injected intravenously into hepatectomized rats to form chylomicron remnants labeled with [14C]AA in the triacylglycerol (TG) and with 3H in the cholesteryl ester portion. The remnants were then incubated with Hep G2 cells. The uptake of [14C]AA within 2-4 h was similar to that of [3H]cholesteryl ester. After uptake into the cells, [14C]AA was preferentially incorporated into phospholipids, a high proportion being found in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol. [14C]AA and [3H]cholesteryl ester uptake were influenced to similar extents by factors unknown to regulate the LDL receptor and by an anti-LDL receptor antibody. Addition of compactin thus increased the uptake of [14C]AA by 50% in 4 h and mevalonolactone decreased the uptake by 86%. Using an anti-LDL receptor antibody, 25.0% of [3H]cholesterol/cholesteryl ester and 37.7% of [14C]AA binding to the cells at 4 degrees C were blocked. There was no lipolysis of [14C]TG or [14C]diacylglycerol by lipase secreted into the medium during incubations.
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| 7. |
- Ekström, Ulf, et al.
(författare)
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An individual with a healthy phenotype in spite of a pathogenic LDL receptor mutation (C240F)
- 1999
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 55:5, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Familial hypercholesterolemia (FH) is caused by a defect in the function of the low density lipoprotein (LDL) receptor and inherited in an autosomal, codominant way. In this study we present a 13-year-old girl, compound heterozygote for the LDL receptor mutations C240F and Y167X. Fibroblasts from the patient showed very low cholesterol esterification rate, LDL uptake, and degradation compared to normal fibroblasts (< 2%, 8%, and < 2%, respectively). The C240F mutant was expressed in LDL receptor deficient CHOMldlA7 cells. Analysis of cell extracts by immunoblotting demonstrated delayed processing of the mutated LDL receptor, which was accumulated as a precursor protein of normal size. A high molecular weight form of the receptor was also detectable in these cells, which probably reflects cross-linking through the unpaired cysteine residue in the binding domain. Cells expressing the C240F mutant protein were unable to mediate uptake and degradation of LDL. The two siblings of the index case also carried the C240F mutation, but surprisingly one of them (a 17-year-old brother) showed no signs of hypercholesterolemia. This observation is consistent with the view that there may be cholesterol lowering mechanisms that can be activated, perhaps by mutations in known or hitherto unknown genes.
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| 8. |
- Ekström, Ulf, et al.
(författare)
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Mutations in the low-density lipoprotein receptor gene in Swedish familial hypercholesterolaemia patients: clinical expression and treatment response
- 1998
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972. ; 28:9, s. 740-747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
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| 9. |
- Elzuki, A, et al.
(författare)
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Alpha1-antitrypsin deficiency (PiZ) may be a risk factor for duodenal ulcer in patients with Helicobacter pylori infection
- 2000
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Ingår i: Scandinavian Journal of Gastroenterology. - 0036-5521. ; 35:1, s. 32-35
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Tidskriftsartikel (refereegranskat)abstract
- Abstract BACKGROUND: Most individuals with Helicobacter pylori infection in Western countries have no evidence of peptic ulcer disease (PUD). We therefore assessed the PiZ deficiency variant of the major plasma protease inhibitor alpha1-antitrypsin (alpha1AT) as a risk factor for PUD in H. pylori-infected individuals. METHODS: The cohort comprised 100 patients with endoscopically or surgically proven PUD (30 patients with duodenal ulcer (DU) and 70 patients with gastric ulcer (GU)) and 162 age- and sex-matched controls with PUD-negative endoscopic findings and no history of PUD. Plasma samples were screened for alpha1AT deficiency (PiZ) with an enzyme-linked immunosorbent assay (ELISA) and phenotyped by isoelectric focusing. H. pylori infection was evaluated with an IgG ELISA technique. RESULTS: Among the 262 patients 17 (6.5%) were positive for the PiZ alpha1AT deficiency, a frequency of the same magnitude as in the Swedish general population (4.7%). Of the PiZ carriers 76% (13 of 17) had H. pylori antibodies compared with 61% (151 of 245) of the non-PiZ carriers (NS). The prevalence of DU tended to be higher in H. pylori-positive PiZ carriers than in non-PiZ carriers (15.4%, 4 of 26 versus 0 of 4). Furthermore, among patients with DU a high PiZ allele frequency (13.3%, 4 of 30) was found compared with the general population (4.7%) (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.09-8.94; P = 0.02). All DU patients carrying the PiZ allele were positive for H. pylori. In addition, four of five PiZ carriers with H. pylori infection and PUD had DU. CONCLUSIONS: The PiZ allele may be a contributing factor in the development of DU in H. pylori-positive individuals.
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| 10. |
- Florén, Claes-Henrik, et al.
(författare)
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Binding, interiorization and degradation of cholesteryl ester labelled chylomicron remnant particles by rat hepatocyte monolayers
- 1977
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Ingår i: The Biochemical journal. - : Portland Press Ltd.. - 0264-6021. ; 168:3, s. 483-494
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Tidskriftsartikel (refereegranskat)abstract
- 1. The cholesteryl ester of isolated chylomicron-remnant particles was efficiently degraded by hepatocyte monolayers. The degradation was sensitive to metabolic inhibitors. 2. With increasing amounts of remnant cholesteryl ester the rate of uptake approached saturation and conformed to a linear double-reciprocal plot. The V(max.) was determined as 80ng of cholesteryl ester/h per mg of protein and the apparent K(m) as 1.4mug of cholesteryl ester per mg of protein. The time course for the uptake and hydrolysis suggested that binding of particles to the cell surface preceded the degradation. 3. Cholesteryl esters of native chylomicrons were degraded to a much smaller extent and their presence had only a small inhibitory effect on the degradation of chylomicron remnants. Intestinal very-low-density lipoproteins were degraded somewhat faster than chylomicrons, and caused more inhibition of remnant degradation. Rat high-density lipoproteins inhibited the hydrolysis of remnant cholesteryl ester by up to 50%, but had less influence on the amount of cholesteryl ester that was bound to the cells. Serum decreased both the uptake and hydrolysis, whereas d=1.21 infranatant had no effect. 4. The cholesteryl ester hydrolysis after the uptake by the cells was inhibited by chloroquine and by colchicine. Only 28-36% of the unhydrolysed cholesteryl ester could be released from these cells by trypsin treatment, indicating that the major portion was truly intracellular. The particles that could be released from the cell surface by trypsin and those remaining in the medium had the same triacylglycerol/cholesteryl ester ratio as the added remnant particles. Significant amounts of denser particles were thus not formed during contact with the cell surface. 5. The presence of heparin, as well as preincubation of the cells with heparin, increased the uptake of chylomicron remnants. This effect was most marked in the presence of serum. A much smaller proportion of the other serum lipoproteins was taken up, and this proportion was not increased by heparin.
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