Predicting cis-acting elements of Lactobacillus plantarum by comparative genomics with different taxonomic subgroups

Cis-acting elements in Lactobacillus plantarum were predicted by comparative analysis of the upstream regions of conserved genes and predicted transcriptional units (TUs) in different bacterial genomes. TUs were predicted for two species sets, with different evolutionary distances to L.plantarum. TUs were designated ‘cluster of orthologous transcriptional units’ (COT) when >50% of the genes were orthologous in different species. Conserved DNA sequences were detected in the upstream regions of different COTs. Subsequently, conserved motifs were used to scan upstream regions of all TUs. This method revealed 18 regulatory motifs only present in lactic acid bacteria (LAB). The 18 LAB-specific candidate regulatory motifs included 13 that were not described previously. These LAB-specific different motifs were found in front of genes encoding functions varying from cold shock proteins to RNA and DNA polymerases, and many unknown functions. The best-described LAB-specific motif found was the CopR-binding site, regulating expression of copper transport ATPases. Finally, all detected motifs were used to predict co-regulated TUs (regulons) for L.plantarum, and transcriptome profiling data were analyzed to provide regulon prediction validation. It is demonstrated that phylogenetic footprinting using different species sets can identify and distinguish between general regulatory motifs and LAB-specific regulatory motifs

Effect of a specific cyclooxygenase-gene polymorphism (A-842G/C50T) on the occurrence of peptic ulcer hemorrhage

Cyclooxygenases (COX) catalyze the conversion of arachidonic acid to prostaglandins (PGs). COX-inhibiting drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), increase the risk for peptic ulcer disease. As a corollary, COX gene polymorphisms could be important in the pathogenesis of peptic ulcer disease because these affect prostaglandin formation and impair its protective effect at the level of the gastric mucosa. This study was designed to investigate the association between the functional single-nucleotide polymorphism, A-842G/C50T, in the COX-1 gene and peptic ulcer bleeding. We obtained DNA samples from 106 patients who underwent upper gastrointestinal endoscopy because of bleeding peptic ulcer disease and from 88 healthy control subjects. Genetic polymorphism in A-842G/C50T was determined by PCR followed by restriction-fragment-length-polymorphism analysis. Adjusted logistic regression analysis was performed to evaluate the associations. Risk factors associated with peptic ulcer bleeding were male gender (odds ratio, 4.78; 95% confidence interval, 2.6-8.8) and NSAID/aspirin-use (odds ratio, 38.39; 95% confidence interval, 14.2-103.6). The A-842G/C50T heterozygote was less frequent in peptic ulcer bleeding (n = 7) compared with healthy control subjects (n = 11). The adjusted risk for peptic ulcer bleeding among individuals who were heterozygote for the A-842G/C50T polymorphism was 0.75 (range, 0.19-3.01) compared with wild type. The COX-1 A-842G/C50T SNP does not influence the risk for developing peptic ulcer bleedin

Gastrointestinal Symptoms are Still Prevalent and Negatively Impact Health-Related Quality of Life: A Large Cross-Sectional Population Based Study in The Netherlands

Contains fulltext : 119280.pdf (publisher's version ) (Open Access)BACKGROUND: Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms. RESULTS: A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43-1.77), asthma/COPD (aOR 1.47, 95% CI 1.21-1.79), use of paracetamol (aOR 1.33, 95% CI 1.20-1.47), antidepressants (aOR 1.56, 95% CI 1.22-2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65-0.87), and use of statins (aOR 0.75, 95% CI 0.61-0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SD = 0.21) compared to 0.92 (SD = 0.14) for persons without gastrointestinal symptoms (P<0.01). CONCLUSIONS: Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life

Pegfilgrastim to support CHOP-14 in elderly patients with non-Hodgkin's lymphoma

This study investigated whether pegfilgrastim support would enable on-schedule delivery of dose-dense cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP-14) to elderly patients with non-Hodgkin's lymphoma (NHL). Thirty patients 60 years of age and older with aggressive NHL were evaluated after receiving up to six cycles of CHOP-14 supported with pegfilgrastim. The median age was 68 years (range 61-74). Forty-seven per cent of patients received full dose chemotherapy on schedule for all cycles (range 65-93). Chemotherapy was delayed in 10 patients and dose reduced in 15 patients. Hematological toxicity was the most common reason for delays and dose reduction. Six of nine patients (67%) achieved a peripheral blood CD34(+) count of at least 20 cells x 10(6) L-1 on day 12 of cycle one. The delivery on schedule of dose-dense CHOP-14 to elderly patients with previously untreated aggressive NHL is safe and efficacious with once per cycle pegfilgrastim support

Open-access upper gastrointestinal endoscopy a decade after the introduction of proton pump inhibitors and helicobacter pylori eradication: a shift in endoscopic findings.

Contains fulltext : 51695.pdf (publisher's version ) (Closed access)BACKGROUND/AIM: Over the past 15 years, there were considerable changes in factors associated with the development and treatment of upper gastrointestinal symptoms, of which the introduction of proton pump inhibitors and Helicobacter pylori eradication in guidelines for treatment of patients with dyspepsia are the most prominent: findings at open-access upper gastrointestinal endoscopy have not been evaluated properly ever since. This study aims to compare the current prevalence of upper gastrointestinal endoscopic findings to the prevalence 15 years ago. METHODS: Data about endoscopic findings of consecutive patients for the first time referred for open-access upper gastrointestinal endoscopy between January 2002 and December 2004 was collected from medical files. The prevalence of each specific finding was compared with data described in three historical populations about 15 years ago. RESULTS: The current and historical study population consisted of 1,286 and 3,062 subjects, respectively. The prevalence of peptic ulcer disease and duodenitis significantly decreased by 12.6% (95% CI: 14.5-10.7) and 2.9% (95% CI: 4.5-1.3), respectively. On the other hand, the prevalence of reflux esophagitis and Barrett's esophagus both significantly increased by 6.9% (95% CI: 4.2-9.6) and 2.1% (95% CI: 0.8-4.4), respectively. CONCLUSIONS: Compared to 15 years ago, the prevalence of specific findings at open-access upper gastrointestinal endoscopy has changed considerably