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71.
Flendrie M Vissers WH Creemers MC de Jong EM van de Kerkhof PC van Riel PL 《Arthritis research & therapy》2005,7(3):R666-R676
Various dermatological conditions have been reported during tumor necrosis factor (TNF)-α-blocking therapy, but until now
no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature
of clinically important dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis (RA).
RA patients starting on TNF-α-blocking therapy were prospectively followed up. The numbers and natures of dermatological events
giving rise to a dermatological consultation were recorded. The patients with a dermatological event were compared with a
group of prospectively followed up RA control patients, naive to TNF-α-blocking therapy and matched for follow-up period.
289 RA patients started TNF-α-blocking therapy. 128 dermatological events were recorded in 72 patients (25%) during 911 patient-years
of follow-up. TNF-α-blocking therapy was stopped in 19 (26%) of these 72 patients because of the dermatological event. More
of the RA patients given TNF-α-blocking therapy (25%) than of the anti-TNF-α-naive patients (13%) visited a dermatologist
during follow-up (P < 0.0005). Events were recorded more often during active treatment (0.16 events per patient-year) than during the period
of withdrawal of TNF-α-blocking therapy (0.09 events per patient-year, P < 0.0005). The events recorded most frequently were skin infections (n = 33), eczema (n = 20), and drug-related eruptions (n = 15). Other events with a possible relation to TNF-α-blocking therapy included vasculitis, psoriasis, drug-induced systemic
lupus erythematosus, dermatomyositis, and a lymphomatoid-papulosis-like eruption. This study is the first large prospective
study focusing on dermatological conditions during TNF-α-blocking therapy. It shows that dermatological conditions are a significant
and clinically important problem in RA patients receiving TNF-α-blocking therapy. 相似文献
72.
73.
We investigated the cytotoxic, neurotoxic, apoptotic and antiproliferative effects of extracts from Petalonia fascia, Jania longifurca and Halimeda tuna on the MCF-7 breast cancer cell line. J. longifurca extracts were more toxic than those of P. fascia and H. tuna. The algal extracts showed significant toxic effects at different dilutions. The toxic effects were due to increased oxidative stress and resulted in apoptosis. Algal toxicity may exert negative effects through the food chain or by direct interaction. Algal toxicity also has potential for cancer therapy. The toxic effects that we observed may be especially important for therapy for breast tumors. 相似文献
74.
Angela CM Luyf Barbera DC van Schaik Michel de Vries Frank Baas Antoine HC van Kampen Silvia D Olabarriaga 《BMC bioinformatics》2010,11(1):598
Background
Bioinformatics is confronted with a new data explosion due to the availability of high throughput DNA sequencers. Data storage and analysis becomes a problem on local servers, and therefore it is needed to switch to other IT infrastructures. Grid and workflow technology can help to handle the data more efficiently, as well as facilitate collaborations. However, interfaces to grids are often unfriendly to novice users. 相似文献75.
Joseph P McElroy Wuyan Zhang Kenneth J Koehler Susan J Lamont Jack CM Dekkers 《遗传、选种与进化》2006,38(6):637-655
Survival traits and selective genotyping datasets are typically not normally distributed, thus common models used to identify QTL may not be statistically appropriate for their analysis. The objective of the present study was to compare models for identification of QTL associated with survival traits, in particular when combined with selective genotyping. Data were simulated to model the survival distribution of a population of chickens challenged with Marek disease virus. Cox proportional hazards (CPH), linear regression (LR), and Weibull models were compared for their appropriateness to analyze the data, ability to identify associations of marker alleles with survival, and estimation of effects when all individuals were genotyped (full genotyping) and when selective genotyping was used. Little difference in power was found between the CPH and the LR model for low censoring cases for both full and selective genotyping. The simulated data were not transformed to follow a Weibull distribution and, as a result, the Weibull model generally resulted in less power than the other two models and overestimated effects. Effect estimates from LR and CPH were unbiased when all individuals were genotyped, but overestimated when selective genotyping was used. Thus, LR is preferred for analyzing survival data when the amount of censoring is low because of ease of implementation and interpretation. Including phenotypic data of non-genotyped individuals in selective genotyping analysis increased power, but resulted in LR having an inflated false positive rate, and therefore the CPH model is preferred for this scenario, although transformation of the data may also make the Weibull model appropriate for this case. The results from the research presented herein are directly applicable to interval mapping analyses. 相似文献
76.
Flavie Tortereau Hélène Gilbert Henri CM Heuven Jean-Pierre Bidanel Martien AM Groenen Juliette Riquet 《遗传、选种与进化》2010,42(1):42
Background
In pig, a number of experiments have been set up to identify QTL and a multitude of chromosomal regions harbouring genes influencing traits of interest have been identified. However, the mapping resolution remains limited in most cases and the detected QTL are rather inaccurately located. Mapping accuracy can be improved by increasing the number of phenotyped and genotyped individuals and/or the number of informative markers. An alternative approach to overcome the limited power of individual studies is to combine data from two or more independent designs.Methods
In the present study we report a combined analysis of two independent design (a French and a Dutch F2 experimental designs), with 2000 F2 individuals. The purpose was to further map QTL for growth and fatness on pig chromosomes 2, 4 and 6. Using QTL-map software, uni- and multiple-QTL detection analyses were applied separately on the two pedigrees and then on the combination of the two pedigrees.Results
Joint analyses of the combined pedigree provided (1) greater significance of shared QTL, (2) exclusion of false suggestive QTL and (3) greater mapping precision for shared QTL.Conclusions
Combining two Meishan x European breeds F2 pedigrees improved the mapping of QTL compared to analysing pedigrees separately. Our work was facilitated by the access to raw phenotypic data and DNA of animals from both pedigrees and the combination of the two designs with the addition of new markers allowed us to fine map QTL without phenotyping additional animals. 相似文献77.
Background
Information for mapping of quantitative trait loci (QTL) comes from two sources: linkage disequilibrium (non-random association of allele states) and cosegregation (non-random association of allele origin). Information from LD can be captured by modeling conditional means and variances at the QTL given marker information. Similarly, information from cosegregation can be captured by modeling conditional covariances. Here, we consider a Bayesian model based on gene frequency (BGF) where both conditional means and variances are modeled as a function of the conditional gene frequencies at the QTL. The parameters in this model include these gene frequencies, additive effect of the QTL, its location, and the residual variance. Bayesian methodology was used to estimate these parameters. The priors used were: logit-normal for gene frequencies, normal for the additive effect, uniform for location, and inverse chi-square for the residual variance. Computer simulation was used to compare the power to detect and accuracy to map QTL by this method with those from least squares analysis using a regression model (LSR).Results
To simplify the analysis, data from unrelated individuals in a purebred population were simulated, where only LD information contributes to map the QTL. LD was simulated in a chromosomal segment of 1 cM with one QTL by random mating in a population of size 500 for 1000 generations and in a population of size 100 for 50 generations. The comparison was studied under a range of conditions, which included SNP density of 0.1, 0.05 or 0.02 cM, sample size of 500 or 1000, and phenotypic variance explained by QTL of 2 or 5%. Both 1 and 2-SNP models were considered. Power to detect the QTL for the BGF, ranged from 0.4 to 0.99, and close or equal to the power of the regression using least squares (LSR). Precision to map QTL position of BGF, quantified by the mean absolute error, ranged from 0.11 to 0.21 cM for BGF, and was better than the precision of LSR, which ranged from 0.12 to 0.25 cM.Conclusions
In conclusion given a high SNP density, the gene frequency model can be used to map QTL with considerable accuracy even within a 1 cM region. 相似文献78.
Konstantinos Doris Sophia P Karabela Chrysoula A Kairi Davina CM Simoes Charis Roussos Spyros G Zakynthinos Ioannis Kalomenidis Timothy S Blackwell Georgios T Stathopoulos 《Respiratory research》2010,11(1):118
Background
Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.Methods
Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.Results
Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.Conclusions
Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer. 相似文献79.
Lucas A Smolders Bj?rn P Meij David Onis Frank M Riemers Niklas Bergknut Richard Wubbolts Guy CM Grinwis Martin Houweling Marian JA Groot Koerkamp Dik van Leenen Frank CP Holstege Herman AW Hazewinkel Laura B Creemers Louis C Penning Marianna A Tryfonidou 《Arthritis research & therapy》2013,15(1):R23
Introduction
Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration.Methods
Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age.Results
Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells.Conclusions
Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration. 相似文献80.
Sonja Melman Ellen NC Schoorel Carmen Dirksen Anneke Kwee Luc Smits Froukje de Boer Madelaine Jonkers Mallory D Woiski Ben Willem J Mol Johannes PR Doornbos Harry Visser Anjoke JM Huisjes Martina M Porath Friso MC Delemarre Simone MI Kuppens Robert Aardenburg Ivo MA Van Dooren Francis PJM Vrouenraets Frans TH Lim Gunilla Kleiverda Paulien CM van der Salm Karin de Boer Marko J Sikkema Jan G Nijhuis Rosella PMG Hermens Hubertina CJ Scheepers 《Implementation science : IS》2013,8(1):1-8