Stefan Schreiber

..We examined the impact of disease duration on clinical outcomes and safety in a post hoc analysis of a remission maintenance trial with adalimumab in patients with moderate to severe CD...

..The aim of this study was to analyse transcriptomal responses of reverse signalling induced by the TNFα binding agents infliximab (IFX) and CZP in myelomonocytic cells...

..The purpose of this study was to examine the differing perspectives and perceptual gaps relating to ulcerative colitis (UC) symptoms and their management between patients and healthcare professionals (HCPs)...

..Conclusions: This study provides striking evidence for association of chromosome 11q13.1 with sarcoidosis in Europeans, and thus identified a further genetic risk locus shared by sarcoidosis, Crohn disease and psoriasis...

..Microbial metabolites (short chain fatty acids, lactate, branched chain fatty acids, and ammonia) and the intestinal microbiota were analyzed...

..After each intervention biopsies were taken, whole genome expression microarrays were applied, and genes of interest were verified by realtime PCR...

..Intrigued by anecdotal evidence for functional non-AG 3' splice sites, we carried out a human genome-wide screen...

..Here, we focus on unusual donor sites with the motif GYNGYN (Y stands for C or T; N stands for A, C, G, or T)...

..NOD2 displays a tandem caspase recruitment domain (CARD) architecture, which is unique within the NLR family...

..A substantial proportion of the inter-individual variability in S CR level is explicable by genetic factors...

..tuberculosis. Based on the hypothesis that genes which regulate interferon gamma may influence tuberculosis susceptibility, we investigated polymorphisms in eight candidate genes...

..albicans. We used the esophageal cell line OE21 and analysed the role of paracrine signals from polymorphonuclear leukocytes (PMN) in an in vitro model of esophageal candidiasis...

..With the advent of next generation sequencing and its utilization for the analysis of the RNA sequence space, the level of detail on the global architecture of the transcriptome reached a new order of magnitude compared to microarrays...

..g. by the 1000 Genomes Project is confined by an affordable sequence depth. Combining target enrichment with NGS may represent a feasible approach...

..Here, we demonstrate that amplicon sequencing of pooled individual PCR products by the 454 technology allows in-depth determination of MSV haplotypes and estimation of DEFB CNs in parallel...

..Tissue specific constitutive and inducible expression patterns of NOD2 have been described that result from complex regulatory events for which the molecular mechanisms are not yet fully understood...

..Four published genomes revealed an identity of > 99 %. This remarkable finding raised questions about the existence of distinguishable genotypes in correlation with geographical and anatomical origin...

..oceanica has been attributed to a decrease in the photosynthetic components that are rich in iron. Genomic information on T. oceanica may shed light on the genetic basis of the physiological differences between the two species...

..However, comprehensive genetic information about the TPI1 locus is still lacking...

..Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models...

..This study aimed to define patterns of gallstone composition and identify demographic predictors of gallstone composition in a large sample of symptomatic gallstones from Northern Germany...

..The high level of automation and the large amount of data produced in a high-throughput laboratory require advanced software tools for quality control and workflow management...

..A computationally simple and intuitively appealing technique based on this observation is presented...

..An abscess has to be excluded. Due to the high risk of infection any symptoms which might be a sign of complications during therapy should result in a thorough diagnostic examination. Patients should be documented in registries...

..To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab' fragment of anti-tumor necrosis factor, CDP870) in Crohn's disease...

..It can be anticipated that genomic findings will profoundly influence the future therapy of inflammatory bowel disease...

..This study investigated the efficacy and safety of BIRB 796, a highly potent inhibitor of p38 MAPK, in chronic active CD...

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..Certolizumab pegol is a pegylated humanized Fab' fragment with a high binding affinity for tumor necrosis factor alpha that does not induce apoptosis of T cells or monocytes...

..These will probably target the molecular interaction on the mucosal surface between the products of the genome and the microbial metagenome of a patient...

..Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD)...

..The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD)...

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..We investigated the relation between production of TNF alpha and interleukin 1beta by mononuclear cells of the colonic lamina propria in patients with remitting Crohn's disease and the risk of relapse...

..Treatment options for fistulizing Crohn's disease (CD) are limited...

..The exploration of the genetic etiology of inflammatory bowel disease holds great future promises...

..Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003...

..We sought to analyze the efficacy (response and remission) and safety data from the PRECiSE 2 trial of certolizumab pegol according to duration of Crohn's disease since diagnosis at baseline...

..Thus, CARD8 represents a novel molecular switch involved in the endogenous regulation of NOD2-dependent inflammatory processes in epithelial cells...

..Given the survival advantage that is associated with the C allele of rs1776180, EXO1 can be considered a candidate for a novel longevity-enabling gene...

..Crohn's disease (CD) and sarcoidosis (SA) are chronic inflammatory barrier diseases that share several clinical and immunological features, including the occurrence of granulomas...

..6; P < 0.044]. H. pylori-induced upregulation of NOD1 and NOD2 in vivo may play a critical role in the recognition of this common pathogen. A missense mutation in the leucine-rich region of CARD15 is associated with gastric lymphoma...

..We investigated four functional promotor polymorphisms in the TNF-alpha gene for association with the development of primary gastric B-cell lymphoma...

..Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream), GRM8 (downstream), OR5V1 (downstream), PPP3R2 (downstream), NM_152575 (upstream) and HNF4G (intron)...

..This is suggestive of a complex pattern of gene-gene interaction between DLG5 and CARD15, reflecting the complex nature of polygenic diseases. Further functional studies will evaluate the biological significance of DLG5 variants...

..035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest...

..Thus, our mouse model will help investigate ADAM17 as a potential drug target...

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..The aim of this study was to investigate if genetic variants in MMPs involved in the inflammatory response to H. pylori could predispose patients with chronic H. pylori infection to develop gastric ulcer disease...

..While a reduced bacterial diversity has been reported in IBD, little is known about the fungal microbiota. The aim of this study was to carry out a systematic analysis of intestinal fungal microbiota in IBD...

..BMI tended to show lower values in His-allele carriers, (p = 0.067). In conclusion, risk-reducing effects of the minor His allele of the PTGES2 Arg298His polymorphism could be mediated partly by lowered BMI...

..We propose that the CD147-NOD2 interaction serves as a molecular guide to regulate NOD2 function at sites of pathogen invasion...

..Here, we compared the intestinal expression of drug transporters, metabolizing enzymes and putative regulatory genes between inflamed and noninflamed tissue and studied their modulation by disease activity...

..Our study gives further evidence that LINGO1 acts as a susceptibility gene for ET...

..003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD...

..Our findings favour the interpretation that postprandial adiponectin has the strongest and independent associations to postprandial TAG metabolism...

..This is the first genetic association study that investigated polymorphisms of MALT1 as genetic risk factors in the development of primary gastric lymphoma...

..Two attractive positional and functional candidate genes in apolipoprotein B mRNA-editing protein (APOBEC1) and peroxisome proliferator-activated receptor gamma (PPARG) are located in this interval...

..This approach, in conjunction with the examination of the mutational steps in a haplotype network, allows unambiguous identification of the potentially causative mutations...

..These data unveil another level of complexicity in the regulation of intracellular innate immunity and may have important implications for the molecular understanding of NOD/NALP protein-driven disease pathophysiology...

..However, little is known about a potential interaction between these risk factors. We investigated gene-environment interactions between CD-associated NOD2 alleles and cigarette smoking in a large sample of patients with CD...

..Addressing the potential role of gly96/iex-1 in the regulation of NF-kappaB in IBD, we used the dextran sodium sulfate (DSS) colitis model in mice in which the gly96/iex-1 gene had been deleted...

..81 x 10(-11) and P(rs5771069) = 4.21 x 10(-8), respectively)...

..The multiple unknown genes identified may stimulate new research in the fields of barrier mechanisms and cell signalling in the context of IBD, and ultimately new therapeutic approaches...

..41; P < 0.01). Our data indicate that FABP2 expression depends on (n-3) FA intake and FABP2 genotypes. FABP2 might be involved in regulating food intake and intestinal FA utilization...

..Dysregulated intestinal DMBT1 expression due to mutations in the NOD2/CARD15 gene may be part of the complex pathophysiology of barrier dysfunction in Crohn's disease...

..03). In conclusion, we identified a common splice site mutation (rs2291726) of the GIP gene which results in a truncated protein and provide preliminary evidence for an association of the heterozygous GIPR Glu354Gln genotype with CVD...

..We conclude that NLRC5 may represent a molecular switch of IFN-gamma activation sequence/IFN-specific response element signaling pathways contributing to antiviral defense mechanisms...

..g. as a promoter of inflammation at early stages of disease...

..Our results show the usefulness of joint analyses of clinically distinct immune-mediated diseases and enlarge the map of shared genetic risk loci...

..We suggest that the use of this software will facilitate the handling and interpretation of the currently emerging genome-wide association data...

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..On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E(2), the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes...

..We anticipate that this methodology may help in the functional annotation of SNPs in a more high-throughput fashion...

..Our results demonstrate a new role of ROS as effector molecules of protective cellular signalling in response to a defined danger signal carried out by a mammalian intracellular NLR system...

..The results highlight the need for a better understanding of the sequence characteristics of functional splice-sites to improve our ability to predict in silico the splicing relevance of empirically observed DNA sequence variants...

..v. can be used. If no response to treatment is seen, proctocolectomy should be considered. Biological agents such as beta-Interferon seem to be effective in mild to moderately ulcerative colitis, but further studies have to be performed...

..007). These results suggest that the rare allele of the MTP I128T polymorphism may be protective against impaired glucose tolerance, type 2 diabetes and other parameters of the metabolic syndrome...

..A recent GWAS in Dutch LLI independently confirmed the APOE-longevity association, thus strengthening the conclusion that this locus is a very, if not the most, important genetic factor influencing longevity...

..We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium...

..We nevertheless recommend either MACH or BEAGLE for practical use because these two programs are more user-friendly and generally require less memory than IMPUTE...

..Annexin A11 has complex and essential functions in several biological pathways, including apoptosis and proliferation...

..Lack of these regulatory events due to the L1007fsinsC variant may pivotally contribute to the induction and perpetuation of chronic inflammation...

..039). Together with the lack of association between rs2241880 and ulcerative colitis (P > 0.4), these data suggest that the underlying biological process may be specific to Crohn disease...

..To reveal susceptibility variants with low frequencies but strong effects, we performed a genome-wide linkage scan in a large sample of SA families...

..17 (1.01-1.34)). IL10 is an immunosuppressive cytokine that has long been proposed to influence IBD pathophysiology. Our findings strongly suggest that defective IL10 function is central to the pathogenesis of the UC subtype of IBD...

..Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection...

..pylori infection. Thus, we investigated the influence of functional genetic variants in the IL-1 gene cluster on the development of gastric ulcer disease...

..Crohn's disease is a heterogeneous disorder for which NOD2 (CARD 15) has been identified as a susceptibility gene. We investigate the relation between NOD2 genotype and phenotypic characteristics of patients with Crohn's disease...

..6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis...

..In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD...

..CONCLUSIONS: Mucosal inflammation in inflammatory bowel disease is associated with loss of normal anaerobic bacteria. This effect is independent of NOD2/CARD15 status of patients...

..The aim of this report was to describe the regulation and functional significance of NOD2 expression in intestinal epithelial cells...

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..The HLA-DP genes play an important role in antigen presentation and are located within the chromosome 6p linkage region...

..In a simulation, the SNP detection performance fell rapidly when the achieved coverage was below 40 x. Due to uneven representation of the target region when using LR-PCR, oversequencing of other regions is necessary...

..The gallstone trait is not allelic to progressive familial cholestasis at the ABCB11 locus. Systematic fine mapping of the Lith1 region is required to identify the causative genetic variants for gallstone in mice and humans...

..00027, IBD phenotype). On stratification based on NOD2 genotype, this significance increased to P = 0.0001. These results confirm the importance of NOD2 and provide evidence for a second IBD gene located on chromosome 16p...