ATP4A autoimmunity and Helicobacter pylori infection in children with type 1 diabetes.

Persistent presence of ATP4A autoantibodies (ATP4AA) directed towards parietal cells is typical for atrophic body gastritis (ABG), an autoimmune disease associated with type 1 diabetes. We assessed whether Helicobacter pylori (Hp) infection might be associated with positivity for ATP4AA in children with type 1 diabetes. Sera were collected from 70 (38♀) type 1 diabetes children [aged 13·2 ± 4·5 years, age at diagnosis 8·8 ± 4·3 years, diabetes duration 4·5 ± 3·8 years, mean HbA1c 7·8 ± 1·6% (62 ± 17·5 mmol/mol)] seen at the regional diabetes clinic in Katowice, Poland. Patients were tested concurrently for Hp infection by means of a 13C urea breath test. ATP4AA were measured using a novel radioimmunoprecipitation assay developed at the Barbara Davies Center for Childhood Diabetes, University of Colorado. ATP4AA were present in 21 [30%, 95% confidence interval (CI) = 19-41%] and Hp infection was detected in 23 (33%, 95% CI = 22-44%) children. There was no statistically significant association between ATP4AA presence and Hp status. ATP4AA presence was not associated with current age, age at type 1 diabetes diagnosis, diabetes duration or current HbA1c. ATP4AA were more prevalent in females [42% (26-58%)] than males [16% (3-28%)], P = 0·016. ATP4A are found in nearly one-third of children with type 1 diabetes and more common among females. In this cross-sectional analysis, Hp infection was not associated with autoimmunity against parietal cells.

Intragenic DNA methylation concomitant with repression of ATP4B and ATP4A gene expression in gastric cancer is a potential serum biomarker.

Based on our previous report on gastric cancer which documented ATP4A and ATP4B mRNA down- regulation in gastric tumors relative to normal gastric tissues, we hypothesized that epigenetic mechanisms could be responsible. ATP4A and ATP4B mRNA expression in gastric cancer cell lines AGS, SNU638 and NUGC-3 was examined using reverse transcriptase PCR (RT-PCR). AGS cells were treated with TSA or 5'-AzaDC and methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis were performed. MSP analysis was on DNA from paraffin embedded tissues sections and plasma. Expression analysis revealed downregulation of ATP4A and ATP4B genes in gastric cancer cell lines relative to normal gastric tissue, while treatment with 5'-AzaDC re-activated expression of both. Search for CpG islands in their putative promoter regions did not indicate CpG islands (CGI) but only further downstream in the bodies of the genes. Methylation specific PCR (MSP) in the exon1 of the ATP4B gene and exon7 in ATP4A indicated methylation in all the gastric cancer cell lines tested. MSP analysis in tumor tissue samples revealed methylation in the majority of tumor samples, 15/19, for ATP4B and 8/8 for ATP4A. There was concordance between ATP4B and ATP4A down-regulation and methylation status in the tumour samples tested. ATP4B methylation was detectable in cell free DNA from gastric cancer patient's plasma samples. Thus ATP4A and ATP4B down-regulation involves DNA methylation and methylated ATP4B DNA in plasma is a potential biomarker for gastric cancer.

Serum antibodies to H+,K+-ATPase, serum pepsinogen A and Helicobacter pylori in relation to gastric mucosa morphology in patients with low or low-normal concentrations of serum cobalamins.

OBJECTIVES: To compare the diagnostic performance of serum antibodies to H+,K+-ATPase (EC 3.6.1.36), serum pepsinogen A (EC 3.4.23.1) and the Schilling test in diagnosing chronic atrophic body gastritis; to study the interrelationships between H+,K+-ATPase antibodies, serology for Helicobacter pylori, and gastric morphology. DESIGN: Patients with suspected cobalamin deficiency and serum cobalamin < 200 micromol/l were investigated using upper gastrointestinal endoscopy, the Schilling test and serum tests for H+,K+-ATPase antibodies, pepsinogen A, and H. pylori. SETTING: The Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS: Ninety seven consecutively referred patients. MAIN OUTCOME MEASURES: Sensitivity and specificity of assays for serum H+,K+-ATPase antibodies, serum pepsinogen A, and the Schilling test. RESULTS: Assays of serum antibodies to H+,K+-ATPase and of serum pepsinogen A displayed equal diagnostic sensitivity for atrophic gastritis (around 0.90 for the severe forms) and higher than that for the Schilling test (0.65). The diagnostic specificity for pepsinogen A (1.0) was higher than for H+,K+-ATPase antibodies (about 0.80). The prevalence of antral gastritis and positivity for H. pylori antibodies declined with the transition of body gastritis into severe atrophy, while the prevalence of H+,K+-ATPase antibodies increased. CONCLUSION: Pepsinogen A is preferable to serum H+,K+-ATPase antibodies in the diagnosis of gastric body mucosal atrophy. The formation of H+,K+-ATPase antibodies does not seem to be a primary event in the development of gastric body muscosal atrophy.

Pharmacokinetics of lansoprazole in hemodialysis patients.

The pharmacokinetics of the new benzimidazole proton pump inhibitor lansoprazole and five of its metabolites were assessed after single oral dose administration to five hemodialysis patients. Patients were studied on dialysis and nondialysis days. Multiple blood and dialysate samples were collected after dosing and were assayed for lansoprazole and metabolite content via high-performance liquid chromatography. The degree of lansoprazole plasma protein binding was lower in hemodialysis patients than in subjects with normal renal function or patients with renal impairment not requiring dialytic therapy, although this tended to moderate when assessed immediately after dialysis. Examination of venous plasma concentration, paired arterial-venous concentration, and dialysate data revealed that lansoprazole and its metabolites were poorly dialyzable. No dosage adjustment of lansoprazole is necessary in hemodialysis patients nor is supplementation after hemodialysis sessions necessary.