Plasma protein profiling in a stage defined pancreatic cancer cohort - Implications for early diagnosis.

Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. Patients with stage I/II PDAC could be discriminated from NC with high accuracy based on a plasma protein signature, indicating a possibility for early diagnosis and increased detection rate of surgically resectable tumors.

Technical Advances of the Recombinant Antibody Microarray Technology Platform for Clinical Immunoproteomics.

In the quest for deciphering disease-associated biomarkers, high-performing tools for multiplexed protein expression profiling of crude clinical samples will be crucial. Affinity proteomics, mainly represented by antibody-based microarrays, have during recent years been established as a proteomic tool providing unique opportunities for parallelized protein expression profiling. But despite the progress, several main technical features and assay procedures remains to be (fully) resolved. Among these issues, the handling of protein microarray data, i.e. the biostatistics parts, is one of the key features to solve. In this study, we have therefore further optimized, validated, and standardized our in-house designed recombinant antibody microarray technology platform. To this end, we addressed the main remaining technical issues (e.g. antibody quality, array production, sample labelling, and selected assay conditions) and most importantly key biostatistics subjects (e.g. array data pre-processing and biomarker panel condensation). This represents one of the first antibody array studies in which these key biostatistics subjects have been studied in detail. Here, we thus present the next generation of the recombinant antibody microarray technology platform designed for clinical immunoproteomics.

Identification of plasma protein profiles associated with risk groups of prostate cancer patients.

PURPOSE: Early detection of prostate cancer (PC) using prostate-specific antigen (PSA) in blood reduces PC-death among unscreened men. However, due to modest specificity of PSA at commonly used cut-offs, there are urgent needs for additional biomarkers contributing enhanced risk classification among men with modestly elevated PSA. EXPERIMENTAL DESIGN: Recombinant antibody microarrays were applied for protein expression profiling of 80 plasma samples from routine PSA-measurements, a priori divided into four risk groups, based on levels of total and %free PSA. RESULTS: The results demonstrated that plasma protein profiles could be identified that pin-pointed PC (a malignant biomarker signature) and most importantly that showed moderate to high correlation with biochemically defined PC risk groups. Notably, the data also implied that the risk group with midrange PSA and low %free PSA, a priori known to be heterogeneous, could be further stratified into two subgroups, more resembling the lowest and highest risk groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In this pilot study, we have shown that plasma protein biomarker signatures, associated with risk groups of PC, could be identified from crude plasma samples using affinity proteomics. This approach could in the longer perspective provide novel opportunities for improved risk classification of PC patients.

Evaluation of aspects of binocular vision in children with dyslexia.

BACKGROUND: Prevalence of dyslexia is 5%-10% of the population. Opinions differ on how binocular function affects dyslexia. The aim of the present study was to evaluate the binocular function in dyslexic children and compare it with a group of age-matched control children. METHODS: The study was performed at Ängkärrskolan and at Kungsholmen elementary schools in Stockholm, Sweden. Sixty-three children with dyslexia and 60 control children between fourth and ninth grade participated. Monocular and binocular visual acuity, refractive error, best corrected visual acuity at distance and near, near point of convergence, amplitude of accommodation, stereopsis, phorias, and fusional reserves were evaluated in all of the children. RESULTS: The results show that there was no difference in the visual functions tested except for the amplitude of accommodation, which was found to be reduced both monocularly and binocularly in the dyslexic children. CONCLUSION: This study showed that only the amplitude of accommodation seems to differ in children with dyslexia as compared with the control children; however, the ability to accommodate was still good and is unlikely to hamper reading and learning ability. The results therefore support that the recent findings of binocular deficits in dyslexic children are a result of the phonological deficit of dyslexia and not an underlying cause of dyslexia.

Effect of four probiotic strains and Escherichia coli O157:H7 on tight junction integrity and cyclo-oxygenase expression.

Controversy exists as to whether contact between a probiotic bacterial cell and an epithelial cell in the gut is needed to confer beneficial effects of probiotics, or whether metabolites from probiotics are sufficient to cause this effect. To address this question, Caco-2 cells were treated with cell-free supernatants of four probiotics, Bifidobacterium lactis 420, Bifidobacterium lactis HN019, Lactobacillus acidophilus NCFM, Lactobacillus salivarius Ls-33, and by a cell-free supernatant of a pathogenic bacteria, Escherichia coli O157:H7 (EHEC). Tight junction integrity as well as expression of cyclo-oxygenases, which are prostaglandin-producing enzymes, were measured. Probiotic-specific as well as EHEC-specific effects on tight junction integrity and cyclo-oxygenase expression were evident, indicating that live bacterial cells were not necessary for the manifestation of the effects. B. lactis 420 cell-free supernatant increased tight junction integrity, while EHEC cell-free supernatant induced damage on tight junctions. In general, EHEC and probiotics had opposite effects upon cyclo-oxygenase expression. Furthermore, B. lactis 420 cell-free supernatant protected the tight junctions from EHEC-induced damage when administered prior to the cell-free supernatant of EHEC. These results indicate that probiotics produce bioactive metabolites, suggesting that consumption of specific probiotic bacteria might be beneficial in protecting intestinal epithelial cells from the deleterious effects of pathogenic bacteria.