SYMPHONY consortium:Orchestrating personalized treatment for patients with bleeding disorders

Background Treatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an integrated interdisciplinary national research program. Objectives The SYMPHONY consortium strives to orchestrate personalized treatment in patients with an inborn bleeding disorder, by unraveling the mechanisms behind interindividual variations of bleeding phenotype. Patients The SYMPHONY consortium will investigate patients with an inborn bleeding disorder, both diagnosed and not yet diagnosed. Results Research questions are categorized under the themes: (1) diagnosis, (2) treatment, and (3) fundamental research, and consist of work packages addressing specific domains. Importantly, collaborations between patients and talented researchers from different areas of expertise promise to augment the impact of the SYMPHONY consortium, leading to unique interactions and intellectual property. Conclusions SYMPHONY will perform research on all aspects of care, treatment individualization in patients with inborn bleeding disorders, as well as diagnostic innovations and results of molecular genetics and cellular model technology with regard to the hemostatic process. We believe that these research investments will lead to health-care innovations with long-term clinical and societal impact. This consortium has been made possible by a governmental, competitive grant from the Netherlands Organization for Scientific Research (NWO) within the framework of the NWA-ORC Call grant agreement NWA.1160.18.038

Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?

<p>Abstract</p> <p>Background</p> <p>To investigate the etiology of <it>MLH1 </it>promoter methylation in mismatch repair (MMR) mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer.</p> <p>Methods</p> <p>We studied a set of 46 MSI-H colon tumors cases with <it>MLH1 </it>promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13). Tumors were tested for CIMP marker methylation and mutations linked to methylation: <it>BRAF, KRAS</it>, <it>GADD45A </it>and the <it>MLH1 </it>-93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for <it>GADD45A </it>mutations and germline <it>MLH1 </it>methylation. SNP array analysis was performed on a subset of tumors.</p> <p>Results</p> <p>We identified two cases (33 and 60 years) with <it>MLH1 </it>germline promoter methylation. <it>BRAF </it>mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044). CIMP-high was infrequent and related to <it>BRAF </it>mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. <it>GADD45A </it>sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity.</p> <p>Conclusion</p> <p>Somatic or germline <it>GADD45A </it>mutations did not explain sporadic MSI-H colon cancer. Although germline <it>MLH1 </it>methylation was found in two individuals, locus-specific somatic <it>MLH1 </it>hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through somatic mutation of <it>BRAF</it>.</p

Processing of facial and nonsocial information is differentially associated with severity of symptoms in patients with multiepisode schizophrenia

Patients with schizophrenia show impairments in social cognitive abilities, such as recognizing facial emotions. However, the relation to symptoms remains unclear. The goal of this study was to explore whether facial emotion recognition and face identity recognition are associated with severity of symptoms and to which extent associations with symptoms differ for processing of social versus nonsocial information. Facial emotion recognition, face recognition, and abstract pattern recognition were evaluated in 98 patients with multiepisode schizophrenia. Severity of symptoms was measured using a five-factor model of the Positive and Negative Syndrome Scale. Results show that facial emotion recognition and, to a lesser extent, face recognition were predominantly associated with severity of disorganization symptoms. In contrast, recognition of nonsocial patterns was associated with negative symptoms, excitement, and emotional distress. Reaction time rather than accuracy of social cognition explained variance in symptomatology. These results lead to the conclusion that facial emotion processing in schizophrenia appears to be associated with severity of symptoms, especially disorganizatio

A preliminary map of epitopes on envelope glycoprotein E1 of HCV strain Brescia

Monoclonal antibodies (MAbs) directed against envelope glycoprotein E1 (gp51-54) of hog cholera virus (HCV) strain Brescia have been shown to recognized four different antigenic domains A, B, C and D. Epitopes of within domain A have mainly been found conserved among HCV strains, whereas epitopes within domains B, C and D are not conserved. We used transiently expressed hybrid E1 genes of HCV strains Brescia and "C" to map the non-conserved epitopes on E1. Epitopes in domains B and C are located within the ultimate N-terminal 104 amino acids. The non-conserved subdomain A3 is most probably located between domains B/C and a hydrophobic region, which is highly conserved between HCV strains Brescia and "C". The conserved subdomains A1 and A2 are probably located in the vicinity and C-terminally of this conserved, hydrophobic region, which is near the centre of the E1 amino acid sequence.</p

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data-3

<p><b>Copyright information:</b></p><p>Taken from "Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data"</p><p>BMC Bioinformatics 2006;7():183-183.</p><p>Published online 3 Apr 2006</p><p>PMCID:PMC1450310.</p><p>Copyright © 2006 Vinciotti et al; licensee BioMed Central Ltd.</p>her order polynomials), as determined by microarray and qPCR assays, are plotted. The left panel shows the log-ratios with respect to time point 1 estimated from the microarray data; the middle panel shows the fitted second order polynomials; the right panel shows the log-ratios determined by quantitative PCR, as an independent confirmation method for the microarray data. X-axis represents time points. Solid lines represent WT mice; dashed lines MDX mice; dotted lines BSG mice; dashed line interrupted with dots GSG mice

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data-1

<p><b>Copyright information:</b></p><p>Taken from "Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data"</p><p>BMC Bioinformatics 2006;7():183-183.</p><p>Published online 3 Apr 2006</p><p>PMCID:PMC1450310.</p><p>Copyright © 2006 Vinciotti et al; licensee BioMed Central Ltd.</p> test only for genes significant at the 5% confidence level according to the non-temporal test (shaded in grey)