Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis

To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5–7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa. © 2000 Cancer Research Campaig

Three-dimensional photographic analysis of the face in European adults from southern Spain with normal occlusion: reference anthropometric measurements

Background: Recent non-invasive 3D photography method has been applied to facial analysis, offering numerous advantages in orthodontic. The purpose of this study was to analyze the faces of a sample of healthy European adults from southern Spain with normal occlusion in order to establish reference facial soft tissue anthropometric parameters in this specific geographic-ethnic population, as well as to analyze sexual dimorphism. Methods: A sample of 100 healthy adult volunteers consisting of 50 women (mean age, 22.92 ± 1.56 years) and 50 men (mean age, 22.37 ± 2.12 years) were enrolled in this study. All participants had normal occlusion, skeletal Class I, mesofacial pattern, and healthy body mass index. Three-dimensional photographs of the faces were captured noninvasively using Planmeca ProMax 3D ProFace®. Thirty landmarks related to the face, eyes, nose, and orolabial and chin areas were identified. Results: Male displayed higher values in all vertical and transversal dimensions, with the exception of the lower lip height. Larger differences between sexes were observed in face, mandible, and nose. Male also had higher values in the angular measurements which referred to the nose. No sex differences were found in transverse upper lip prominence or transverse mandibular prominence. No differences were found in the ratio measurements, with the exception of intercantal width/nasal width, which was higher in women than in men. Conclusions: Reference anthropometric measurements of facial soft tissues have been established in European adults from southern Spain with normal occlusion. Significant sexual dimorphism was found, with remarkable differences in size between sexe

Identification of a Phytase Gene in Barley (Hordeum vulgare L.)

Background: Endogenous phytase plays a crucial role in phytate degradation and is thus closely related to nutrient efficiency in barley products. The understanding of genetic information of phytase in barley can provide a useful tool for breeding new barley varieties with high phytase activity. Methodology/Principal Findings: Quantitative trait loci (QTL) analysis for phytase activity was conducted using a doubled haploid population. Phytase protein was purified and identified by the LC-ESI MS/MS Shotgun method. Purple acid phosphatase (PAP) gene was sequenced and the position was compared with the QTL controlling phytase activity. A major QTL for phytase activity was mapped to chromosome 5 H in barley. The gene controlling phytase activity in the region was named as mqPhy. The gene HvPAP a was mapped to the same position as mqPhy, supporting the colinearity between HvPAP a and mqPhy. Conclusions/Significance: It is the first report on QTLs for phytase activity and the results showed that HvPAP a, which shares a same position with the QTL, is a major phytase gene in barley grains

Desipramine Inhibits Histamine H1 Receptor-Induced Ca2+ Signaling in Rat Hypothalamic Cells

The hypothalamus in the brain is the main center for appetite control and integrates signals from adipose tissue and the gastrointestinal tract. Antidepressants are known to modulate the activities of hypothalamic neurons and affect food intake, but the cellular and molecular mechanisms by which antidepressants modulate hypothalamic function remain unclear. Here we have investigated how hypothalamic neurons respond to treatment with antidepressants, including desipramine and sibutramine. In primary cultured rat hypothalamic cells, desipramine markedly suppressed the elevation of intracellular Ca2+ evoked by histamine H1 receptor activation. Desipramine also inhibited the histamine-induced Ca2+ increase and the expression of corticotrophin-releasing hormone in hypothalamic GT1-1 cells. The effect of desipramine was not affected by pretreatment with prazosin or propranolol, excluding catecholamine reuptake activity of desipramine as an underlying mechanism. Sibutramine which is also an antidepressant but decreases food intake, had little effect on the histamine-induced Ca2+ increase or AMP-activated protein kinase activity. Our results reveal that desipramine and sibutramine have different effects on histamine H1 receptor signaling in hypothalamic cells and suggest that distinct regulation of hypothalamic histamine signaling might underlie the differential regulation of food intake between antidepressants

Gene Expression Profiling in Gastric Mucosa from Helicobacter pylori-Infected and Uninfected Patients Undergoing Chronic Superficial Gastritis

Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray using in vitro culture cells and in vivo gastric biopsies from patients of the Chronic Abdominal Complaint. To further explore the effects of H. pylori infection on host gene expression, we have collected the gastric antral mucosa samples from 6 untreated patients with gastroscopic and pathologic confirmation of chronic superficial gastritis. Among them three patients were infected by H. pylori and the other three patients were not. These samples were analyzed by a microarray chip which contains 14,112 cloned cDNAs, and microarray data were analyzed via BRB ArrayTools software and Ingenuity Pathways Analysis (IPA) website. The results showed 34 genes of 38 differentially expressed genes regulated by H. pylori infection had been annotated. The annotated genes were involved in protein metabolism, inflammatory and immunological reaction, signal transduction, gene transcription, trace element metabolism, and so on. The 82% of these genes (28/34) were categorized in three molecular interaction networks involved in gene expression, cancer progress, antigen presentation and inflammatory response. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Taken together, these data indicated that H. pylori infection could alter cellular gene expression processes, escape host defense mechanism, increase inflammatory and immune responses, activate NF-κB and Wnt/β-catenin signaling pathway, disturb metal ion homeostasis, and induce carcinogenesis. All of these might help to explain H. pylori pathogenic mechanism and the gastroduodenal pathogenesis induced by H. pylori infection

Protein Glycosylation in Helicobacter pylori: Beyond the Flagellins?

Glycosylation of flagellins by pseudaminic acid is required for virulence in Helicobacter pylori. We demonstrate that, in H. pylori, glycosylation extends to proteins other than flagellins and to sugars other than pseudaminic acid. Several candidate glycoproteins distinct from the flagellins were detected via ProQ-emerald staining and DIG- or biotin- hydrazide labeling of the soluble and outer membrane fractions of wild-type H. pylori, suggesting that protein glycosylation is not limited to the flagellins. DIG-hydrazide labeling of proteins from pseudaminic acid biosynthesis pathway mutants showed that the glycosylation of some glycoproteins is not dependent on the pseudaminic acid glycosylation pathway, indicating the existence of a novel glycosylation pathway. Fractions enriched in glycoprotein candidates by ion exchange chromatography were used to extract the sugars by acid hydrolysis. High performance anion exchange chromatography with pulsed amperometric detection revealed characteristic monosaccharide peaks in these extracts. The monosaccharides were then identified by LC-ESI-MS/MS. The spectra are consistent with sugars such as 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Ac7Ac) previously described on flagellins, 5-acetamidino-7-acetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Am7Ac), bacillosamine derivatives and a potential legionaminic acid derivative (Leg5AmNMe7Ac) which were not previously identified in H. pylori. These data open the way to the study of the mechanism and role of protein glycosylation on protein function and virulence in H. pylori

Nature meets nurture: molecular genetics of gastric cancer

The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (including IL1B) is discussed