Duodenal mucosal risk markers in patients with familial adenomatous polyposis: effects of celecoxib/ursodeoxycholic acid co-treatment and comparison with patient controls

Background

Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation.

Methods

Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor δ (PPARδ), caspase-3, cyclin D1, β-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n?=?37) were compared with levels in non-FAP patient controls (n?=?16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n?=?14) or celecoxib & placebo (n?=?13) were evaluated in patients with FAP.

Results

mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p?=?0.008) and caspase-3 (3.30% vs. 5.31%, p?=?0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA.

Conclusions

Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa.

Trial registration

http://ClinicalTrials.gov number NCT00808743

     

Prevalence of Salmonella serotypes in environmental waters and their relationships with indicator organisms

The incidence of serotypes of Salmonella in three types of environmental water (sea, river and fresh reservoirs) from north-east Spain was investigated. The study was performed at specific sampling locations during the summer for a period of five years (1992–1996). A total of 823 strains were isolated and 55 different serotypes were identified, 42 were recovered from sea water, 32 from river water and 12 from freshwater reservoirs. The most frequently isolated serotypes coincided with those involved in clinical cases in the area studied. Salmonella enteritidis was the most common (111 isolates), it was found in all types of water, although most predominantly in sea water (16.1% of the isolates). This serotype, together with S. hadar, significantly increased in frequency during the five year study period. The most frequent serotypes in river water and freshwater reservoirs were S. virchow (9.5%) and S. mikawasima (23.8%) respectively. Significant differences were assessed in the indicator organism densities between the samples with serotypes of clinical significance (S. enteritidis, S. infantis, S. typhimurium, S. virchow and S. paratyphi B) and those without clinical significance. Therefore their presence in all environmental waters may be of epidemiological significance.     

Complete type III secretion system of a mesophilic Aeromonas hydrophila strain

We have investigated the existence and genetic organization of a functional type III secretion system (TTSS) in a mesophilic Aeromonas strain by initially using the Aeromonas hydrophila strain AH-3. We report for the first time the complete TTSS DNA sequence of an Aeromonas strain that comprises 35 genes organized in a similar disposition as that in Pseudomonas aeruginosa. Using several gene probes, we also determined the presence of a TTSS in clinical or environmental strains of different Aeromonas species: A. hydrophila, A. veronii, and A. caviae. By using one of the TTSS genes (ascV), we were able to obtain a defined insertion mutant in strain AH-3 (AH-3AscV), which showed reduced toxicity and virulence in comparison with the wild-type strain. Complementation of the mutant strain with a plasmid vector carrying ascV was fully able to restore the wild-type toxicity and virulence.     

正常人左心室功能指标的参考值及其预计公式的初步研究报告*

目的: 当前评估左心室容量和功能仍常用正常值范围,个体化分析也仅使用体表面积进行校正。尚缺少个体化因素相关的大样本参考值和预计公式。方法: 本研究纳入美国加州洛杉矶县南湾地区1200名健康志愿者,其中男807女393,年龄20岁-94岁,心脏CT造影（CTA）,经过高精度三维成像技术处理,计算左心室容积在收缩和舒张过程中的连续动态变化,测定左心室（LV）容量和功能指标：舒张末期容积（EDV)、收缩末期容积(ESV)、每搏输出量(SV)、射血分数(EF)和心输出量(CO)。将以上指标与一般特征指标进行多因素相关分析,以探索正常人预计值计算公式。结果: 男性除LVEF小于女性外（P<0.001）,其余各指标均大于女性（P<0.001）。多元线性回归分析提示, 性别、年龄、身高和体质量均为EDV、ESV、SV的独立影响因子(P<0.001); 而CO仅受年龄、性别、体质量显著影响(P<0.001),但与身高无关(P>0.05)。CO的预测公式CO (L·min^-1)= 6.963+0.446(Male) -0.037×年龄(yr)+0.013×体质量(kg)。结论: 性别、年龄、身高、体质量均影响左心室容量和功能,建立预测值计算公式,对心血管疾病的无创评估和个体化精准医疗具有重要参考价值。     

Improved Detection of Magnetic Signals by a MEMS Sensor Using Stochastic Resonance

We introduce the behavior of the electrical output response of a magnetic field sensor based on microelectromechanical systems (MEMS) technology under different levels of controlled magnetic noise. We explored whether a particular level of magnetic noise applied on the vicinity of the MEMS sensor can improve the detection of subthreshold magnetic fields. We examined the increase in the signal-to-noise ratio (SNR) of such detected magnetic fields as a function of the magnetic noise intensity. The data disclosed an inverted U-like graph between the SNR and the applied magnetic noise. This finding shows that the application of an intermediate level of noise in the environment of a MEMS magnetic field sensor improves its detection capability of subthreshold signals via the stochastic resonance phenomenon.     

Phenotypic, genotypic, and phylogenetic discrepancies to differentiate Aeromonas salmonicida from Aeromonas bestiarum.

The taxonomy of the "Aeromonas hydrophila" complex (comprising the species A. hydrophila, A. bestiarum, A. salmonicida, and A. popoffii) has been controversial, particularly the relationship between the two relevant fish pathogens A. salmonicida and A. bestiarum. In fact, none of the biochemical tests evaluated in the present study were able to separate these two species. One hundred and sixteen strains belonging to the four species of this complex were identified by 16S rDNA restriction fragment length polymorphism (RFLP). Sequencing of the 16S rDNA and cluster analysis of the 16S-23S intergenic spacer region (ISR)-RFLP in selected strains of A. salmonicida and A. bestiarum indicated that the two species may share extremely conserved ribosomal operons and demonstrated that, due to an extremely high degree of sequence conservation, 16S rDNA cannot be used to differentiate these two closely related species. Moreover, DNA-DNA hybridization similarity between the type strains of A. salmonicida subsp. salmonicida and A. bestiarum was 75.6 %, suggesting that they may represent a single taxon. However, a clear phylogenetic divergence between A. salmonicida and A. bestiarum was ascertained from an analysis based on gyrB and rpoD gene sequences, which provided evidence of a lack of congruence of the results obtained from 16S rDNA, 16S-23S ISR-RFLP, DNA-DNA pairing, and biochemical profiles.     

First record of the rare species Aeromonas culicicola from a drinking water supply

We describe the recovery of the rare species Aeromonas culicicola, so far known only in mosquitoes in India, from a drinking water supply in Spain. Typing, using enterobacterial repetitive intergenic consensus-PCR, revealed that the 27 new isolates belonged to 3 very closely related strains. These strains were genetically identified by 16S rRNA gene sequencing. Spanish strains differed from the mosquito strains in three nucleotide positions. The AHCYTOEN gene was present in these water strains, which may have a public health significance.     

OXBench: A benchmark for evaluation of protein multiple sequence alignment accuracy

Background  

The alignment of two or more protein sequences provides a powerful guide in the prediction of the protein structure and in identifying key functional residues, however, the utility of any prediction is completely dependent on the accuracy of the alignment. In this paper we describe a suite of reference alignments derived from the comparison of protein three-dimensional structures together with evaluation measures and software that allow automatically generated alignments to be benchmarked. We test the OXBench benchmark suite on alignments generated by the AMPS multiple alignment method, then apply the suite to compare eight different multiple alignment algorithms. The benchmark shows the current state-of-the art for alignment accuracy and provides a baseline against which new alignment algorithms may be judged.