53 research outputs found

    Polymorphisms in the CD28/CTLA4/ICOS genes: Role in malignant melanoma susceptibility and prognosis?

    Get PDF
    The appearance of vitiligo and spontaneous regression of the primary lesion in melanoma patients illustrate a relationship between tumor immunity and autoimmunity. T lymphocytes play a major role both in tumor immunity and autoimmunity. CD28, Cytotoxic T lymphocyte antigen 4 (CTLA4) and inducible costimulator (ICOS) molecules are important secondary signal molecules in the T lymphocyte activation. Single nucleotide polymorphisms (SNPs) in the CD28/CTLA4/ICOS gene region were reported to be associated with several autoimmune diseases including, type-1 diabetes, SLE, autoimmune thyroid diseases and celiac disease. In this study, we investigated the association of SNPs in the CD28, CTLA4 and ICOS genes with the risk of melanoma. We also assessed the prognostic effect of the different polymorphisms in melanoma patients. Twenty-four tagging SNPs across the three genes and four additional SNPs were genotyped in a cohort of 763 German melanoma patients and 734 healthy German controls. Influence on prognosis was determined in 587 melanoma cases belonging to stage I or II of the disease. In general, no differences in genotype or allele frequencies were detected between melanoma patients and controls. However, the variant alleles for two polymorphisms in the CD28 gene were differentially distributed in cases and controls. Similarly no association of any polymorphism with prognosis, except for the rs3181098 polymorphism in the CD28 gene, was observed. In addition, individuals with AA genotype for rs11571323 polymorphism in the ICOS gene showed reduced overall survival. However, keeping in view the correction for multiple hypothesis testing our results suggest that the polymorphisms in the CD28, CTLA4 and ICOS genes at least do not modulate risk of melanoma and nor do those influence the disease prognosis in the investigated population

    Variations in Suppressor Molecule CTLA-4 Gene Are Related to Susceptibility to Multiple Myeloma in a Polish Population

    Get PDF
    Various phenotype and functional T-cell abnormalities are observed in multiple myeloma (MM) patients. The aim of this study was to investigate the association between polymorphisms in the gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of the T-lymphocyte immune response and susceptibility to multiple myeloma in a Polish population. Two hundred MM patients and 380 healthy subjects were genotyped for the following polymorphisms: CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CT60 (CTLA-4g.*6230G>A), Jo31 (CTLA-4g.*10223G>T). Our study is the largest and most comprehensive evaluation to date of the association between genetic polymorphisms in the CTLA-4 molecule and multiple myeloma. It was found that CTLA-4c.49A>G[G], CT60[G], and Jo31[G] alleles were more frequently observed in MM patients than in controls (0.50 vs. 0.44, p = 0.03, 0.65 vs. 0.58, p = 0.04, and 0.63 vs. 0.57, p = 0.03, respectively). Moreover, the haplotype CTLA-4c.49A>G[G], CTLA-4g.319C>T[C], CTLA-4g.*642AT(8_33) [8], CT60[G], Jo31[G] including all susceptibility alleles increases the risk of MM about fourfold (OR: 3.79, 95%CI: 2.08–6.89, p = 0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies

    Association between the Cytotoxic T-Lymphocyte Antigen 4 +49G > A polymorphism and cancer risk: a meta-analysis

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>As a key gene in the immunosurveillance of cell malignancy, Cytotoxic T-lymphocyte antigen 4 (CTLA-4 is an important negative regulator of T cell activation and proliferation. The CTLA-4 +49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with cancer risks, but previous results have been conflicting.</p> <p>Methods</p> <p>We preformed a meta-analysis using 22 eligible case-control studies (including 32 datasets) with a total of 11,273 patients and 13,179 controls to summarize the existing data on the association between the <it>CTLA-4 </it>+49G > A polymorphism and cancer risk.</p> <p>Results</p> <p>Compared with the common <it>CTLA-4 </it>+49G > A GG genotype, the carriers of variant genotypes (<it>CTLA-4 </it>+49 GC/CC) had a 1.24-fold elevated risk of cancer (95% CI = 1.18-1.32, <it>P </it>< 0.05) under the dominant genetic model, as estimated using a fixed effect model. The effect of the <it>CTLA-4 </it>+49G > A polymorphism was further evaluated using stratification analysis. In four breast cancer studies, patients with the variant genotypes had a significantly increased risk of breast cancer (OR = 1.31, 95% CI = 1.17-1.48, <it>P </it>< 0.00001). A similar result was found in three skin cancer studies (OR = 1.30, 95% CI = 1.10-1.52, <it>P </it>= 0.001). In 26 solid tumor studies, subjects with the variant genotypes had a significantly higher risk of developing solid tumors (OR = 1.25, 95% CI = 1.18-1.33, <it>P </it>< 0.00001) compared with the 6 non-solid tumor studies (OR = 1.08, 95% CI = 0.79-1.48, <it>P </it>= 0.62). Patients with variant genotypes had significantly increased risk of non-epithelial tumors and epithelial tumors, with ORs of 1.23 (95% CI = 1.14-1.32, <it>P </it>< 0.00001) and 1.29 (95% CI = 1.17-1.41, <it>P </it>< 0.00001), respectively. It was also demonstrated that the increased risk of cancer associated with <it>CTLA-4 </it>+49G > A variant genotypes was more pronounced in Caucasians (OR = 1.29, 95% CI = 1.13-1.47, <it>P </it>= 0.0002), Asians (OR = 1.23, 95% CI = 1.16-1.32, <it>P </it>< 0.00001) and Chinese (OR = 1.23, 95% CI = 1.15-1.31, <it>P </it>< 0.00001).</p> <p>Conclusion</p> <p>Our meta-analysis suggests that the <it>CTLA-4 </it>+49G > A polymorphism genotypes (GA + AA) might be associated with an increased risk of cancer, especially in Caucasians and Chinese.</p

    Internet use by older adults with bipolar disorder: international survey results

    Get PDF
    Background: The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking. Methods: A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data. Results: Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values. Conclusions: Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder

    Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies

    Full text link

    Multicriteria mining company evaluation method

    No full text
    W artykule przedstawiono zbiór kryteriów do oceny przedsiębiorstwa górniczego zgodnie z zasadami zrównoważonego rozwoju. Dodatkowo zaprezentowano metody, za pomocą których można utworzyć liniowy ranking przedsiębiorstw. Pozwalają one również przeprowadzić analizę działalności przedsiębiorstwa w aspekcie zrównoważonego rozwoju.The paper presents a set of criteria for evaluating a mining enterprise according to the principles sustainable development. In addition, the method is presented with which you can create a linear ranking of companies. They also an analysis of activities of the company the context of sustainable development

    A Customizable Platform for High-availability Monitoring, Control and Data Distribution at CERN

    No full text
    In complex operational environments, monitoring and control systems are asked to satisfy ever more stringent requirements. In addition to reliability, the availability of the system has become crucial to accommodate for tight planning schedules and increased dependencies to other systems. In this context, adapting a monitoring system to changes in its environment and meeting requests for new functionalities are increasingly challenging. Combining maintainability and high-availability within a portable architecture is the focus of this work. To meet these increased requirements, we present a new modular system developed at CERN. Using the experience gained from previous implementations, the new platform uses a multiserver architecture to allow running patches and updates to the application without affecting its availability. The data acquisition can also be reconfigured without any downtime or potential data loss. The modular architecture builds on a core system that aims to be reusable for multiple monitoring scenarios, while keeping each instance as lightweight as possible. Both for cost and future maintenance concerns, open and customizable technologies have been preferred

    Demand planning support for polyurethane adhesive in coal mine

    No full text
    Praca przedstawia propozycję metody wspomagania planowania zapotrzebowania na klej poliuretanowy, która bazuje na metodach prognozowania szeregów czasowych oraz na podstawie modelu ekonometrycznego. Jako finalny model prognostyczny wspomagający planowanie wielkości zapotrzebowania zaproponowano kombinowany model agregujący prognozy postawione za pomocą wybranych modeli. Agregacja polega na zastosowaniu sumy ważonej, przy tym wagi ustalono na podstawie kryterium minimalnego błędu prognoz wygasłych.In this paper proposal of method for polyurethane adhesive demand planning support is presented. The method is based on models of time series forecasting and econometric model. The proposal is to combine the forecasts through application of weighted sum. The weight factors are determined by the minimal mean error of extinct forecasts criterion

    Multi-criteria model of largeness of material orders in carbon mine

    No full text
    W pracy przedstawiono wielokryterialny model wielkości Zamówienia, przy założeniu że wielkość zużycia materiału jest zmienną losową o znanym rozkładzie prawdopodobieństwa. W modelu przyjęto dwa kryteria: minimalizacji wielkości zamówienia oraz minimalizacji prawdopodobieństwa braku materiahi w procesie produkcyjnym. Rozważono dwa sposoby skalaryzacji i na przykładzie pokazano zastosowanie zbudowanych modeli dla wyznaczenia wielkości zamówienia kleju poliuretanowego, zużywanego do uszczelniania wyrobisk w kopalni.The paper presents multi-criteria model of largeness of order providing that need is random variable with continuous probability distribution, rn model two criteria are assumed, minimization of largeness of order and in minimization of probability of lack of material in productive process. Two scalarization methods and shown in example employment of models for assignment of largeness of order of polyurethane adhesive in carbon mine are considered
    • …
    corecore