Gastric intestinal metaplasia: subtypes and natural history.

BACKGROUND: It has been suggested that the subtyping of intestinal metaplasia in the stomach is useful in stratifying patients with regard to risk of developing gastric cancer. AIM: To determine whether subtyping intestinal metaplasia provided useful information regarding the natural history of intestinal metaplasia. METHODS: The study used large cup gastric biopsy specimens from predetermined locations (gastric mapping). Follow up biopsies were obtained at one, two, and/or nine years. Biopsies with intestinal metaplasia were stained with high iron diamine/Alcian blue (HID/AB) to determine whether they expressed neutral mucins, sialomucins, or sulphomucins. RESULTS: Seventy nine patients with intestinal metaplasia were studied and characterised with regard to the most advanced subtype of intestinal metaplasia. The most severe type of intestinal metaplasia was type II in 33 patients and type III in 34 patients. Helicobacter pylori was cured in 67 patients. Follow up showed that changes in type of metaplasia (apparent regression or progression) occurred in both directions and were independent of H pylori status. For example, biopsy sites with "loss" of metaplasia at a follow up visit might have it "reappear" at a subsequent visit. During follow up, no patient developed gastric dysplasia or died from gastric cancer. CONCLUSION: HID subtyping did not provide useful information to the clinician or the pathologist. The data are consistent with the notion that the pattern, extent, and severity of atrophy with/without intestinal metaplasia is a far more important predictor of increased cancer risk than intestinal metaplasia subtype.

Helicobacter pylori infection in preschool and school-aged minority children: effect of socioeconomic indicators and breast-feeding practices.

Helicobacter pylori infection was examined among 356 asymptomatic white Hispanic and black children aged 2--16 years attending 13 licensed day care centers in Houston. Demographic information and socioeconomic factors were evaluated. H. pylori status was determined by (13)C-urea breath testing. The prevalence of active H. pylori infection was 24% and increased with age. Prevalence was almost identical among white Hispanic and black children. Children living in the most crowded conditions were at the greatest risk for H. pylori acquisition, and an inverse correlation was seen between the mother's education and H. pylori positivity in children. Breast-feeding played a protective role against the acquisition of H. pylori infection. Understanding the epidemiology of H. pylori infection in childhood requires better understanding of the interactions between environment, ethnic group, and socioeconomic conditions.

The gastric cardia in gastro-oesophageal disease.

BACKGROUND: There have been conflicting reports concerning the use of cardia biopsies in screening patients for gastro-oesophageal disease. AIM: To define the histopathological changes in the gastric cardia of patients with and without gastro-oesophageal disease. METHODS: Topographically mapped gastric biopsy specimens were obtained from patients with gastro-oesophageal disease and from controls. Biopsies were scored on a visual analogue scale of 0 to 5 for Helicobacter pylori, intestinal metaplasia, pancreatic metaplasia, foveolar hyperplasia, and active inflammation. The presence or absence of cardiac glands was recorded. RESULTS: Sixty-five patients with gastro-oesophageal disease and 71 controls were examined. Intestinal metaplasia was present in cardia biopsies of 10 patients with gastro-oesophageal disease and 11 controls. Only two patients with gastro-oesophageal disease and intestinal metaplasia in the cardia had no evidence of exposure to H pylori. Intestinal metaplasia was not found in the cardia of those with long segment Barrett's oesophagus. Carditis was strongly associated with active H pylori infection (p = 0.000) and resolved after treatment of the infection. A negative association was present between gastro-oesophageal disease and the presence of cardiac glands in cardiac biopsies (p = 0.003). Pancreatic metaplasia was found in 15 of 65 and foveolar hyperplasia in 19 of 65 cases but neither was related to gastro-oesophageal disease. CONCLUSION: Intestinal metaplasia in the cardia is uncommon in gastro-oesophageal disease in the absence of H pylori infection. With chronic H pylori infection the junction between the cardia and corpus expands in a cardia-corpal direction.

Helicobacter pylori infection in asymptomatic children: comparison of diagnostic tests.

BACKGROUND: Childhood is known to be a major risk period for acquiring Helicobacter pylori infection. Studies of the epidemiology of H. pylori infection depend on the validity of the diagnostic tools used to detect the infection in the pediatric setting. This study aims to conduct a combination of diagnostic tests on the same children, evaluate the sensitivity and the specificity of IgG antibody testing compared with the 13C-urea breath test, and examine the variability in the prevalence of H. pylori infection in asymptomatic children based on the use of different diagnostic tests. METHODS: 13C-urea breath test (13C-UBT), whole blood FlexSure (systemic antibodies), and OraSure (salivary antibodies) tests were conducted on 287 asymptomatic children (151 boys, 136 girls; ages 2-18 years). The three tests were conducted on each child during the same day. The prevalence was calculated using each test independently. RESULTS: H. pylori infection was detected in 32%, 22%, or 18% of the studied children, based on UBT, OraSure, or FlexSure, respectively. A total of 103 children tested positive for any one test (92 on UBT, 8 on FlexSure, 3 on OraSure), giving a prevalence of 35% based on the "parallel" method. Only 39 children tested positive in all three tests, giving a prevalence of 14% based on the "serial" method. Using the UBT as the gold standard, the sensitivity of FlexSure and OraSure were 48% and 65%, respectively, and the specificity of both tests was greater than 95%. When we applied the parallel method, the sensitivity and specificity of the combined antibody tests (FlexSure + OraSure) compared to the UBT were 71% and 95%, respectively. CONCLUSIONS: Among asymptomatic children, there is a wide variation in the prevalence of H. pylori infection based on the diagnostic test used. The study shows that antibody assays are less suitable than the UBT. However, under certain conditions, the IgG assays (combined systemic, salivary, or both) are less expensive alternative tools to the UBT for epidemiological studies in children.

The differential diagnosis of early gastric mucosa-associated lymphoma: polymerase chain reaction and paraffin section immunophenotyping.

The distinction between benign florid lymphoid hyperplasia and low-grade gastric mucosal-associated lymphoid tissue (MALT) lymphoma may be a challenge. The presence of monoclonal B cells in Helicobacter pylori-chronic active gastritis has suggested that polymerase chain reaction (PCR) data should be viewed with caution. We investigated the reliability of PCR versus immunophenotyping in diagnosing early gastric MALT lymphoma. We studied 1511 biopsies from eight patients with high-grade primary gastric lymphoma, 25 with low-grade MALT lymphoma, 32 with atypical lymphoid infiltrates, and 39 with Helicobacter pylori-chronic active gastritis. Paraffin sections from all cases were stained with antibodies to CD20, CD3, AE1/AE3, kappa and lambda. PCR was performed on paraffin sections using the primer set VH-FR3/J(H). Using histopathology as the gold standard in diagnosis, we confirmed monoclonality in 22 of 25 MALT lymphomas (88%); a clonal band was found in 38% (15 of 39) of patients with chronic active gastritis. An immunophenotype pattern with predominance of CD20-positive cells in lymphocytic infiltrates was associated with monoclonality in 92% of cases. The presence of an enlarged irregular mantle zone was found in both monoclonal and polyclonal areas. An equal prevalence of B and T cells in lymphocytic infiltrates was associated with a polyclonal pattern in 24 of 31 cases (77%). Immunostaining of sIg (kappa and lambda) was difficult in paraffin sections and convincing proof of monoclonality was not obtained. Lymphoepithelial lesions were infrequent in gastric biopsies and their presence was highlighted with keratin stains. Because monoclonal B cells are observed in Helicobacter pylori-associated gastritis, the correct interpretation of clonality by PCR remains unclear. Paraffin section IHC using CD20 and CD3 is especially useful to confirm the diagnosis of gastric MALT lymphoma.

A subset of SR proteins activates splicing of the cardiac troponin T alternative exon by direct interactions with an exonic enhancer.

The cardiac troponin T pre-mRNA contains an exonic splicing enhancer that is required for inclusion of the alternative exon 5. Here we show that enhancer activity is exquisitely sensitive to changes in the sequence of a 9-nucleotide motif (GAGGAAGAA) even when its purine content is preserved. A series of mutations that increased or decreased the level of exon inclusion in vivo were used to correlate enhancer strength with RNA-protein interactions in vitro. Analyses involving UV cross-linking and immunoprecipitation indicated that only four (SRp30a, SRp40, SRp55, and SRp75) of six essential splicing factors known as SR proteins bind to the active enhancer RNA. Moreover, purified SRp40 and SRp55 activate splicing of exon 5 when added to a splicing-deficient S100 extract. Purified SRp30b did not stimulate splicing in S100 extracts, which is consistent with its failure to bind the enhancer RNA. In vitro competition of SR protein splicing activity and UV cross-linking demonstrated that the sequence determinants for SR protein binding were precisely coincident with the sequence determinants of enhancer strength. Thus, a subset of SR proteins interacts directly with the exonic enhancer to promote inclusion of a poorly defined alternative exon. Independent regulation of the levels of SR proteins may, therefore, contribute to the developmental regulation of exon inclusion.

Regulation of tyrosine hydroxylase gene expression in IMR-32 neuroblastoma cells by basic fibroblast growth factor and ciliary neurotrophic factor.

The actions of basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) on tyrosine hydroxylase (TH) gene expression were studied using IMR-32 neuroblastoma cells. Treatment of these cells with bFGF for 3 days induced the expression of detectable levels of immunoreactive TH protein and TH mRNA. In contrast, CNTF did not affect TH expression unless bFGF was present. In the presence of saturating amounts of bFGF, CNTF increased TH protein and mRNA levels of TH two-to threefold over those found in bFGF-treated cultures. The effects of CNTF on TH expression diminished with increasing culture time, and after 6 days of incubation CNTF no longer enhanced TH levels. The requirement for bFGF as cofactor in the effects of CNTF on TH was specific, as CNTF did not affect TH when it was coadministered with 8-(4-chlorophenylthio)-cyclic AMP, another agent that stimulates TH development in this cell line, and bFGF was not required for CNTF to stimulate the development of choline acetyltransferase. Moreover, cotreatment with bFGF reduced the ability of CNTF to enhance choline acetyltransferase. These results demonstrate that bFGF and CNTF can enhance expression of TH and that bFGF can modify the effects of CNTF on neurotransmitter phenotype.