True Interindividual Variability Exists in Postprandial Appetite Responses in Healthy Men But Is Not Moderated by the FTO Genotype

Background: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. Objectives: The aim of this study was to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. Methods: Using a replicated crossover design, 18 healthy men (mean ± SD age: 28.5 ± 9.8 y; BMI: 27.0 ± 5.0 kg/m2) recruited according to FTO genotype (9 AA, 9 TT) completed 2 identical control and 2 identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin, and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson’s product-moment correlations between the first and second replicates of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition and genotype-by-condition interactions. Results: The meal suppressed acylated ghrelin and appetite perceptions [standardized effect size (ES): 0.18–4.26] and elevated total PYY, insulin, and glucose (ES: 1.96–21.60). For all variables, SD of change scores was greater in the meal than in the control conditions. Moderate-to-large positive correlations were observed between the 2 replicates of controladjusted meal responses for all variables (r = 0.44–0.86, P ≤ 0.070). Participant-by-condition interactions were present for all variables (P ≤ 0.056). FTO genotype-by-condition interactions were nonsignificant (P ≥ 0.19) and treatment effect differences between genotype groups were small (ES ≤ 0.27) for all appetite parameters. Conclusions: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but we detected no moderation by the FTO genotype. These findings highlight the importance of exploring individual differences in appetite for the prevention and treatment of obesit

Analysis of expression profiles of MAGE-A antigens in oral squamous cell carcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>The immunological response to solid tumours is insufficient. Therefore, tumour specific antigens have been explored to facilitate the activation of the immune system. The cancer/testis antigen class of MAGE-A antigens is a possible target for vaccination. Their differential expression profiles also modulate the course of the cancer disease and its response to antineoplastic drugs.</p> <p>Methods</p> <p>The expression profiles of MAGE-A2, -A3, -A4, -A6 and -A10 in five own oral squamous cell carcinoma cell lines were characterised by rt-PCR, qrt-PCR and immunocytochemistry with a global MAGE-A antibody (57B) and compared with those of an adult keratinocyte cell line (NHEK).</p> <p>Results</p> <p>All tumour cell lines expressed MAGE-A antigens. The antigens were expressed in groups with different preferences. The predominant antigens expressed were MAGE-A2, -A3 and -A6. MAGE-A10 was not expressed in the cell lines tested. The MAGE-A gene products detected in the adult keratinocyte cell line NHEK were used as a reference.</p> <p>Conclusion</p> <p>MAGE-A antigens are expressed in oral squamous cell carcinomas. The expression profiles measured facilitate distinct examinations in forthcoming studies on responses to antineoplastic drugs or radiation therapy. MAGE-A antigens are still an interesting aim for immunotherapy.</p

Genetic analysis of common variants of MMPs and their involvement in Rheumatoid Arthritis in the East Midlands, UK

Introduction: Rheumatoid arthritis (RA) affects around 1% of population and causes irreversible synovial joint damage and bone erosion. Matrix metalloproteinases (MMPs) play a role in pathologic processes; however their involvement in RA is not clear. This study investigated the association of MMP2, MMP7 and MMP9 with RA. Methods: DNA samples from European (103 controls, 125 patients) and South Asian (91 controls, 115 patients) populations were genotyped for MMP7 (rs11568818), MMP9 (rs17576) and MMP2 (rs2241145). Diplotype and triplotypes analyses were performed. Results: An individual is twice as likely to develop RA if they have an AG genotype at both the MMP9 and MMP7 loci in European (OR 2.2, CI 1.03-4.70) or South Asian population (OR 2.28, CI 1.00-5.20). A CG genotype at the MMP2 locus and AG at MMP9- 836 gives protection within a European population (OR 0.34, CI 0.17-0.70). Heterozygous genotype combination on all three loci in South Asians increases risk of RA by three times (OR 3.27, CI 1.04-10.20). South Asians showed a significant doubling of RA risk with a total genetic risk score of three or more. Conclusion: Our results show that polymorphisms at these three MMP loci impact RA susceptibility and have a synergetic effect