共查询到20条相似文献，搜索用时 15 毫秒
1.
Helle H. Nielsen Hans C. Beck Lars P. Kristensen Mark Burton Tunde Csepany Magdolna Simo Peter Dioszeghy Tobias Sejbaek Manuela Grebing Niels H. H. Heegaard Zsolt Illes 《PloS one》2015,10(10)
Objectives
Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO), NMO spectrum disorders (NMO-SD) and multiple sclerosis (MS). Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS.Methods
The proteins in urine samples from anti-aquaporin 4 (AQP4) seropositive NMO/NMO-SD patients (n = 32), patients with MS (n = 46) and healthy subjects (HS, n = 31) were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig) in the urine were validated by nephelometry in an independent cohort (n = 9–10 pr. groups).Results
The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002). Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD.Conclusion
The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS. 相似文献2.
Veronica Popescu Menno M. Schoonheim Adriaan Versteeg Nimisha Chaturvedi Marianne Jonker Renee Xavier de Menezes Francisca Gallindo Garre Bernard M. J. Uitdehaag Frederik Barkhof Hugo Vrenken 《PloS one》2016,11(1)
Background
Studies disagree on the location of grey matter (GM) atrophy in the multiple sclerosis (MS) brain.Aim
To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition).Materials and Methods
127 MS patients and 50 controls were included and cortical and deep grey matter (DGM) volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen’s d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM) and vertex-wise FreeSurfer were used for group-level comparisons.Results
The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.Conclusion
GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted. 相似文献3.
Objectives
This study aimed to compare the accuracy and performance of four genotyping methods for detecting single nucleotide polymorphisms (SNPs) in aldehyde dehydrogenase-2 (ALDH2), which is the principal enzyme involved in alcohol metabolism.Design and Methods
We genotyped rs671 of ALDH2 in 96 coronary heart disease (CHD) patients with four methods including high resolution melting analysis (HRM), TaqMan allelic discrimination assay (TaqMan), allele-specific PCR (AS-PCR) and pyrosequencing. Meanwhile, we compared the accuracy and performance of these methods.Results
All selected patients were successfully genotyped with referred methods. The results of these four assays showed 100% concordant results and had 100% accuracy as verified by Sanger sequencing.Conclusions
All of the referred methods can be used for genotyping ALDH2 rs671 with the same accuracy compared to Sanger sequencing. In small size of clinical samples, HRM and AS-PCR outperform over others due to their lower cost and less hands-on operation, which are suitable for clinical application. 相似文献4.
Gurmeet K. S. Singh Ben W. R. Balzer Patrick J. Kelly Karen Paxton Catherine I. Hawke David J. Handelsman Katharine S. Steinbeck 《PloS one》2015,10(11)
Background/Aims
The longitudinal relationships of within-individual hormone and anthropometric changes during puberty have not ever been fully described. The objectives of this study were to demonstrate that 3 monthly urine collection was feasible in young adolescents and to utilise liquid chromatography-tandem mass spectrometry assay methods for serum and urine testosterone (T), estradiol (E2) and luteinizing hormone (LH) in adolescents by relating temporal changes in urine and serum hormones over 12 months to standard measures of pubertal development.Methods
A community sample of 104 adolescents (57 female) was studied over 12 months with annual anthropometric assessment, blood sampling and self-rated Tanner staging and urine collected every 3 months. Serum and urine sex steroids (T, E2) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LH by immunoassay.Results
A high proportion (92%) of scheduled samples were obtained with low attrition rate of 6.7% over the 12 months. Urine hormone measurements correlated cross-sectionally and longitudinally with age, anthropometry and Tanner stage.Conclusion
We have developed a feasible and valid sampling methodology and measurements for puberty hormones in urine, which allows a sampling frequency by which individual pubertal progression in adolescents can be described in depth. 相似文献5.
Introduction
In intensive agriculture areas the use of pesticides can alter soil properties and microbial community structure with the risk of reducing soil quality.Materials and Methods
In this study the fatty acid methyl esters (FAMEs) evolution has been studied in a factorial lab experiment combining five substrates (a soil, two aged composts and their mixtures) treated with a co-application of three pesticides (azoxystrobin, chlorotoluron and epoxiconazole), with two extraction methods, and two incubation times (0 and 58 days). FAMEs extraction followed the microbial identification system (MIDI) and ester-linked method (EL).Results and Discussion
The pesticides showed high persistence, as revealed by half-life (t1/2) values ranging from 168 to 298 days, which confirms their recalcitrance to degradation. However, t1/2 values were affected by substrate and compost age down to 8 days for chlorotoluron in S and up to 453 days for epoxiconazole in 12M. Fifty-six FAMEs were detected. Analysis of variance (ANOVA) showed that the EL method detected a higher number of FAMEs and unique FAMEs than the MIDI one, whereas principal component analysis (PCA) highlighted that the monosaturated 18:1ω9c and cyclopropane 19:0ω10c/19ω6 were the most significant FAMEs grouping by extraction method. The cyclopropyl to monoenoic acids ratio evidenced higher stress conditions when pesticides were applied to compost and compost+soil than solely soil, as well as with final time.Conclusion
Overall, FAMEs profiles showed the importance of the extraction method for both substrate and incubation time, the t1/2 values highlighted the effectiveness of solely soil and the less mature compost in reducing the persistence of pesticides. 相似文献6.
Jair E. Garcia Madeline B. Girard Michael Kasumovic Phred Petersen Philip A. Wilksch Adrian G. Dyer 《PloS one》2015,10(5)
Background
The ability to discriminate between two similar or progressively dissimilar colours is important for many animals as it allows for accurately interpreting visual signals produced by key target stimuli or distractor information. Spectrophotometry objectively measures the spectral characteristics of these signals, but is often limited to point samples that could underestimate spectral variability within a single sample. Algorithms for RGB images and digital imaging devices with many more than three channels, hyperspectral cameras, have been recently developed to produce image spectrophotometers to recover reflectance spectra at individual pixel locations. We compare a linearised RGB and a hyperspectral camera in terms of their individual capacities to discriminate between colour targets of varying perceptual similarity for a human observer.Main Findings
(1) The colour discrimination power of the RGB device is dependent on colour similarity between the samples whilst the hyperspectral device enables the reconstruction of a unique spectrum for each sampled pixel location independently from their chromatic appearance. (2) Uncertainty associated with spectral reconstruction from RGB responses results from the joint effect of metamerism and spectral variability within a single sample.Conclusion
(1) RGB devices give a valuable insight into the limitations of colour discrimination with a low number of photoreceptors, as the principles involved in the interpretation of photoreceptor signals in trichromatic animals also apply to RGB camera responses. (2) The hyperspectral camera architecture provides means to explore other important aspects of colour vision like the perception of certain types of camouflage and colour constancy where multiple, narrow-band sensors increase resolution. 相似文献7.
Fiona Fouhy Jennifer Deane Mary C. Rea órla O’Sullivan R. Paul Ross Grace O’Callaghan Barry J. Plant Catherine Stanton 《PloS one》2015,10(3)
Background
High-throughput sequencing has enabled detailed insights into complex microbial environments, including the human gut microbiota. The accuracy of the sequencing data however, is reliant upon appropriate storage of the samples prior to DNA extraction. The aim of this study was to conduct the first MiSeq sequencing investigation into the effects of faecal storage on the microbiota, compared to fresh samples. Culture-based analysis was also completed.Methods
Seven faecal samples were collected from healthy adults. Samples were separated into fresh (DNA extracted immediately), snap frozen on dry ice and frozen for 7 days at -80°C prior to DNA extraction or samples frozen at -80°C for 7 days before DNA extraction. Sequencing was completed on the Illumina MiSeq platform. Culturing of total aerobes, anaerobes and bifidobacteria was also completed.Results
No significant differences at phylum or family levels between the treatment groups occurred. At genus level only Faecalibacterium and Leuconostoc were significantly different in the fresh samples compared to the snap frozen group (p = 0.0298; p = 0.0330 respectively). Diversity analysis indicated that samples clustered based on the individual donor, rather than by storage group. No significant differences occurred in the culture-based analysis between the fresh, snap or -80°C frozen samples.Conclusions
Using the MiSeq platform coupled with culture-based analysis, this study highlighted that limited significant changes in microbiota occur following rapid freezing of faecal samples prior to DNA extraction. Thus, rapid freezing of samples prior to DNA extraction and culturing, preserves the integrity of the microbiota. 相似文献8.
Jaime Moreno Melissa Hidalgo Carolina Duarte Olga Sanabria Jean Marc Gabastou Ana Belén Ibarz-Pavon 《PloS one》2015,10(8)
Background
Meningococcal carriage studies are important to improve our understanding of the epidemiology of meningococcal disease. The aim of this study was to determine the prevalence of meningococcal carriage and the phenotypic and genotypic characteristics of isolates collected from a sample of students in the city of Bogotá, Colombia.Materials and Methods
A total of 1459 oropharyngeal samples were collected from students aged 15–21 years attending secondary schools and universities. Swabs were plated on a Thayer Martin agar and N. meningitidis was identified by standard microbiology methods and PCR.Results
The overall carriage prevalence was 6.85%. Carriage was associated with cohabitation with smokers, and oral sex practices. Non-groupable and serogroup Y isolates were the most common capsule types found. Isolates presented a high genetic diversity, and circulation of the hypervirulent clonal complexes ST-23, ST-32 and ST-41/44 were detected.Conclusion
The meningococcal carriage rate was lower than those reported in Europe and Africa, but higher than in other Latin American countries. Our data also revealed antigenic and genetic diversity of the isolates and the circulation of strains belonging to clonal complexes commonly associated with meningococcal disease. 相似文献9.
Delphine Lamargue Hamel Mathilde Deloire Aurélie Ruet Julie Charré-Morin Aurore Saubusse Jean-Christophe Ouallet Bruno Brochet 《PloS one》2015,10(11)
Background
Depressive mood and other emotional symptoms are common in multiple sclerosis (MS). The patient-reported outcome version of the “Echelle d’Humeur Dépressive” (EHD-PRO) aims to differentiate between two dimensions of depressive mood in people living with MS (PwMS).Objectives
First, to compare EHD-PRO assessment and its two dimensions, lack of emotional control and emotional blunting, between a large sample of healthy controls (HCs) and two samples of PwMS, relapsing-remitting MS (RRMS) and primary progressive MS (PPMS); and second, to analyse the relationships between EHD-PRO scores with neurological disability, cognitive function, fatigue and health-related quality of life (HR-QOL).Results
Regardless of their phenotype, PwMS had significantly higher EHD-PRO scores than HCs. EHD-PRO scores did not differ between the two MS groups. EHD-PRO scores did not correlate with disability and fatigue scores, disease duration or cognitive z scores. In RRMS, the lack of emotional control was independently associated with a decrease in HR-QOL.Conclusion
The EHD-PRO is able to easily detect depressive mood and to differentiate between two clinical dimensions, emotional blunting and lack of emotional control. The scale is sensitive and seems robust to confounding factors. Lack of emotional control seems to contribute significantly to altered HR-QOL in RRMS. 相似文献10.
Morten Stilund Mikkel Carstensen Gjelstrup Thor Petersen Holger Jon M?ller Peter Vestergaard Rasmussen Tove Christensen 《PloS one》2015,10(4)
Background
Expression of soluble CD163 (sCD163), a macrophage/microglia biomarker, is increased in inflammatory conditions, and sCD163 levels in the cerebrospinal fluid (CSF) have recently been shown to be elevated in patients with multiple sclerosis (MS): the sCD163 CSF/serum ratio was elevated in patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and clinically isolated syndrome (CIS) compared with symptomatic controls.Objective
To investigate the contributions of the sCD163 CSF/serum ratio to a biomarker panel focusing on inflammation and axonal degeneration in newly diagnosed MS; thus optimising a diagnostic biomarker panel for MS.Methods
After a full MS diagnostic work-up, including collection of paired samples of CSF and serum, 125 patients were included in this study. Patients were divided into groups based on their diagnosis, and patients with normal clinical and paraclinical findings were defined as symptomatic controls. Serum and CSF levels, ratios, and indices of sCD163, CXCL13, osteopontin, neopterin, and CSF levels of neurofilament light polypeptide were determined by enzyme-linked immunosorbent assays (ELISAs). For sCD163 the results constitute a post-hoc analysis of already published data.Results
All tested biomarkers, notably the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the CSF level of NfL, the IgG index, and the serum level of OPN, were significantly correlated to RRMS, PPMS, and/or CIS. The individual biomarkers in single tests had a lower performance than the IgG index, however, their combined receiver operating characteristic (ROC) curve demonstrated excellent diagnostic discriminatory power.Conclusion
The biomarker panel showed distinct profiles for each patient group and could be a valuable tool for clinical differentiation of MS subgroups. The combined ROC analysis showed that sCD163 contributes positively as a diagnostic marker to a panel of established MS biomarkers. Patients with PPMS were demonstrated to have significantly elevated levels of both inflammatory and degenerative markers. 相似文献11.
12.
Background
Cases of hemorrhagic fever with renal syndrome (HFRS) are widely distributed in eastern Asia, especially in China, Russia, and Korea. It is proved to be a difficult task to eliminate HFRS completely because of the diverse animal reservoirs and effects of global warming. Reliable forecasting is useful for the prevention and control of HFRS.Methods
Two hybrid models, one composed of nonlinear autoregressive neural network (NARNN) and autoregressive integrated moving average (ARIMA) the other composed of generalized regression neural network (GRNN) and ARIMA were constructed to predict the incidence of HFRS in the future one year. Performances of the two hybrid models were compared with ARIMA model.Results
The ARIMA, ARIMA-NARNN ARIMA-GRNN model fitted and predicted the seasonal fluctuation well. Among the three models, the mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of ARIMA-NARNN hybrid model was the lowest both in modeling stage and forecasting stage. As for the ARIMA-GRNN hybrid model, the MSE, MAE and MAPE of modeling performance and the MSE and MAE of forecasting performance were less than the ARIMA model, but the MAPE of forecasting performance did not improve.Conclusion
Developing and applying the ARIMA-NARNN hybrid model is an effective method to make us better understand the epidemic characteristics of HFRS and could be helpful to the prevention and control of HFRS. 相似文献13.
James L. Sherwood Claire Corcoran Helen Brown Alan D. Sharpe Milena Musilova Alexander Kohlmann 《PloS one》2016,11(2)
Introduction
Non-invasive mutation testing using circulating tumour DNA (ctDNA) is an attractive premise. This could enable patients without available tumour sample to access more treatment options.Materials & Methods
Peripheral blood and matched tumours were analysed from 45 NSCLC patients. We investigated the impact of pre-analytical variables on DNA yield and/or KRAS mutation detection: sample collection tube type, incubation time, centrifugation steps, plasma input volume and DNA extraction kits.Results
2 hr incubation time and double plasma centrifugation (2000 x g) reduced overall DNA yield resulting in lowered levels of contaminating genomic DNA (gDNA). Reduced “contamination” and increased KRAS mutation detection was observed using cell-free DNA Blood Collection Tubes (cfDNA BCT) (Streck), after 72 hrs following blood draw compared to EDTA tubes. Plasma input volume and use of different DNA extraction kits impacted DNA yield.Conclusion
This study demonstrated that successful ctDNA recovery for mutation detection in NSCLC is dependent on pre-analytical steps. Development of standardised methods for the detection of KRAS mutations from ctDNA specimens is recommended to minimise the impact of pre-analytical steps on mutation detection rates. Where rapid sample processing is not possible the use of cfDNA BCT tubes would be advantageous. 相似文献14.
Ahmed Bassiouni Edward John Cleland Alkis James Psaltis Sarah Vreugde Peter-John Wormald 《PloS one》2015,10(4)
Background
The role of the sino-nasal microbiome in CRS remains unclear. We hypothesized that the bacteria within mucosal-associated biofilms may be different from the more superficial-lying, free-floating bacteria in the sinuses and that this may impact on the microbiome results obtained. This study investigates whether there is a significant difference in the microbiota of a sinonasal mucosal tissue sample versus a swab sample.Methods
Cross-sectional study with paired design. Mucosal biopsy and swab samples were obtained intra-operatively from the ethmoid sinuses of 6 patients with CRS. Extracted DNA was sequenced on a Roche-454 sequencer using 16S-rRNA gene targeted primers. Data were analyzed using QIIME 1.8 software package.Results
At a maximum subsampling depth of 1,100 reads, the mean observed species richness was 33.3 species (30.6 for swab, versus 36 for mucosa; p > 0.05). There was no significant difference in phylogenetic and non-phylogenetic alpha diversity metrics (Faith’s PD_Whole_Tree and Shannon’s index) between the two sampling methods (p > 0.05). The type of sample also had no significant effect on phylogenetic and non-phylogenetic beta diversity metrics (Unifrac and Bray-Curtis; p > 0.05).Conclusion
We observed no significant difference between the microbiota of mucosal tissue and swab samples. This suggests that less invasive swab samples are representative of the sinonasal mucosa microbiome and can be used for future sinonasal microbiome studies. 相似文献15.
Introduction
As bioaerosol research attracts increasing attention, there is a need for additional efforts that focus on method development to deal with different environmental samples. Bioaerosol environmental samples typically have very low biomass concentrations in the air, which often leaves researchers with limited options in choosing the downstream analysis steps, especially when culture-independent methods are intended.Objectives
This study investigates the impacts of three important factors that can influence the performance of culture-independent DNA-based analysis in dealing with bioaerosol environmental samples engaged in this study. The factors are: 1) enhanced high temperature sonication during DNA extraction; 2) effect of sampling duration on DNA recoverability; and 3) an alternative method for concentrating composite samples. In this study, DNA extracted from samples was analysed using the Qubit fluorometer (for direct total DNA measurement) and quantitative polymerase chain reaction (qPCR).Results and Findings
The findings suggest that additional lysis from high temperature sonication is crucial: DNA yields from both high and low biomass samples increased up to 600% when the protocol included 30-min sonication at 65°C. Long air sampling duration on a filter media was shown to have a negative impact on DNA recoverability with up to 98% of DNA lost over a 20-h sampling period. Pooling DNA from separate samples during extraction was proven to be feasible with margins of error below 30%. 相似文献16.
Background
Primary cutaneous amyloidosis (PCA) is a relatively rare and itchy skin disorder characterized by amyloid deposits in the superficial dermis. The cosmetic disfigurement and severe pruritus dramatically affects the patient’s quality of life. In spite of the prevalence of the disease in China, the quality of life (QoL) impact of the PCA has not been well defined and is the focus of this study.Objective
To examine the HRQoL of patients with PCA and to evaluate the association between HRQoL scores, disease, and socio-demographic determinants.Methods
A total of 104 PCA patients and 101 healthy participants completed the questionnaires. HRQoL was measured using dermatology life quality index (DLQI) and SF-36. The socio demographic and clinical data such as age, sex, duration of disease and distribution of lesion pattern were analyzed mainly by hierarchical multiple regression analyses.Results
Patients with PCA experienced significantly impaired health-related quality of life. The mean DLQI score was 9.05. Younger age, female gender, more pruritus and distribution pattern were independent predictor correlates of the high DLQI scores. The PCA group showed significantly decreasing average scores in several aspects of psychological symptoms, including SF, RE and MH.Conclusions
PCA disease has a negative impact on the HRQoL of patients, and the HRQoL is associated with various disease characteristics. In conjunction with medical interventions, psychological and sociocultural assessment and intervention should be an essential part of the management of these cases. 相似文献17.
Kai Mei Lei Du Min Yan Zhaohui Zhang Fengjiang Zhang Lina Gong Kai Sun Jie Zhang Yumin Tang Chunling Jiang Jin Liu 《PloS one》2015,10(6)
Background
Intraoperative blood salvage, an effective blood conservation strategy, has not been applied in onco-surgery, because of potential malignant cell contamination. In this study we tested effectiveness of a modified leukocyte depletion filter (M-LDF) for removal of tumor cells.Materials and Methods
The effects of M-LDF and regular LDF on removal of cells (HepG2 cell line) were compared. The safety of M-LDF was tested with blood (collected and washed during onco-surgery), the salvaged blood mixed with tumor cells from the solid tumor of the same patient, or mixed with HepG2 cells (n=30 in each protocol). Cancer cells were identified by flow cytometry, culture and bioassay with and without filtration.Results
M-LDF removed 5-log of HepG2 and nucleated cells, which was much higher than regular LDF, and cells were destroyed when they passed through M-LDF. Cytokeratin-positive cells in all samples were removed by M-LDF. Invasive growth adherent cells were found in most of unfiltered samples and 67% of the inoculated nude mice developed tumors in LDF-treated sample. Neither adherent cells nor nude mice developed tumors were found in M-LDF-treated samples.Discussion and Conclusion
Since M-LDF can effectively remove and destroy cancer cells in the salvaged blood, it has great potential for clinical application. 相似文献18.
Ivan Soldatovic Rade Vukovic Djordje Culafic Milan Gajic Vesna Dimitrijevic-Sreckovic 《PloS one》2016,11(1)
Objective
To evaluate siMS score and siMS risk score, novel continuous metabolic syndrome scores as methods for quantification of metabolic status and risk.Materials and Methods
Developed siMS score was calculated using formula: siMS score = 2*Waist/Height + Gly/5.6 + Tg/1.7 + TAsystolic/130—HDL/1.02 or 1.28 (for male or female subjects, respectively). siMS risk score was calculated using formula: siMS risk score = siMS score * age/45 or 50 (for male or female subjects, respectively) * family history of cardio/cerebro-vascular events (event = 1.2, no event = 1). A sample of 528 obese and non-obese participants was used to validate siMS score and siMS risk score. Scores calculated as sum of z-scores (each component of metabolic syndrome regressed with age and gender) and sum of scores derived from principal component analysis (PCA) were used for evaluation of siMS score. Variants were made by replacing glucose with HOMA in calculations. Framingham score was used for evaluation of siMS risk score.Results
Correlation between siMS score with sum of z-scores and weighted sum of factors of PCA was high (r = 0.866 and r = 0.822, respectively). Correlation between siMS risk score and log transformed Framingham score was medium to high for age groups 18+,30+ and 35+ (0.835, 0.707 and 0.667, respectively).Conclusions
siMS score and siMS risk score showed high correlation with more complex scores. Demonstrated accuracy together with superior simplicity and the ability to evaluate and follow-up individual patients makes siMS and siMS risk scores very convenient for use in clinical practice and research as well. 相似文献19.
Hideaki Nishihara Fumitaka Shimizu Yasuteru Sano Yukio Takeshita Toshihiko Maeda Masaaki Abe Michiaki Koga Takashi Kanda 《PloS one》2015,10(3)
Objective
Effect of fingolimod in multiple sclerosis (MS) is thought to involve the prevention of lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system across blood-brain barrier (BBB). However, brain microvascular endothelial cells (BMECs) represent a possible additional target for fingolimod in MS patients by directly repairing the function of BBB, as S1P receptors are also expressed by BMECs. In this study, we evaluated the effects of fingolimod on BMECs and clarified whether fingolimod-phosphate restores the BBB function after exposure to MS sera.Methods
Changes in tight junction proteins, adhesion molecules and transendothelial electrical resistance (TEER) in BMECs were evaluated following incubation in conditioned medium with or without fingolimod/fingolimod-phosphate. In addition, the effects of sera derived from MS patients, including those in the relapse phase of relapse-remitting (RR) MS, stable phase of RRMS and secondary progressive MS (SPMS), on the function of BBB in the presence of fingolimod-phosphate were assessed.Results
Incubation with fingolimod-phosphate increased the claudin-5 protein levels and TEER values in BMECs, although it did not change the amount of occludin, ICAM-1 or MelCAM proteins. Pretreatment with fingolimod-phosphate restored the changes in the claudin-5 and VCAM-1 protein/mRNA levels and TEER values in BMECs after exposure to MS sera.Conclusions
Pretreatment with fingolimod-phosphate prevents BBB disruption caused by both RRMS and SPMS sera via the upregulation of claudin-5 and downregulation of VCAM-1 in BMECs, suggesting that fingolimod-phosphate is capable of directly modifying the BBB. BMECs represent a possible therapeutic target for fingolimod in MS patients. 相似文献20.
Eduardo Samo Gudo Gabriela Pinto Sirkka Vene Arcildo Mandlaze Argentina Felisbela Muianga Julie Cliff Kerstin Falk 《PLoS neglected tropical diseases》2015,9(10)