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91.
PURPOSE OF REVIEW: The aim of this article is to discuss the potential value of biomarkers for atherosclerosis in the assessment of risk for cardiovascular disease, in the pathogenesis of atherosclerosis, and in the monitoring of pharmacological treatment. RECENT FINDINGS: In an attempt to improve global cardiovascular risk prediction, considerable effort has been made in the discovery and characterization of soluble biomarkers which can go beyond the measure of total and LDL cholesterol levels. In particular, circulating molecules related to chronic inflammation have emerged as potential biomarkers for atherosclerosis. Evidence, obtained from in-vitro and in-vivo experimental models, has also documented that the majority of biomarkers play a pathological role in atherogenesis. Multiple screening of different biomarkers may therefore improve the assessment of risk, diagnosis, and prognosis for cardiovascular disease. In addition, soluble biomarkers have been shown to be modulated by hypolipidemic drugs and to be potentially useful in determining the clinical benefits of pharmacological therapies that do not alter serum lipid levels. SUMMARY: Altered levels of soluble biomarkers are associated with cardiovascular disease, and profiling of multiple biomarkers for atherosclerosis will be a useful indicator for better risk assessment, diagnosis, and prognosis, as well as monitoring pharmacological treatments for atherosclerosis. 相似文献
92.
A simple model for evaluation of diffusion times of small molecule into protein crystals has been developed, which takes into account the physical and chemical properties both of protein crystal and the diffusing molecules. The model also includes consideration of binding and the binding affinity of a ligand to the protein. The model has been validated by simulation of experimental set-ups of several examples found in the literature. These experiments cover a wide range of situations: from small to relatively large diffusing molecules, crystals having low, medium, or high protein density, and different size. The reproduced experiments include ligand exchange in protein crystals by soaking techniques. Despite the simplifying assumptions of the model, theoretical and experimental data are in agreement with available data, with experimental diffusion times ranging from a few seconds to several hours. The method has been used successfully for planning intermediate cryotrapping experiments in maltodextrin phosphorylase crystals. 相似文献
93.
Piero Ruggenenti Paolo Cravedi Eliana Gotti Annarita Plati Maddalena Maras Silvio Sandrini Nicola Bossini Franco Citterio Enrico Minetti Domenico Montanaro Ettore Sabadini Regina Tardanico Davide Martinetti Flavio Gaspari Alessandro Villa Annalisa Perna Francesco Peraro Giuseppe Remuzzi 《PLoS medicine》2021,18(6)
BackgroundWe compared protection of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine (CsA) microemulsion maintenance immunosuppression.Methods and findingsATHENA, a pragmatic, prospective, multicenter trial conducted by 6 Italian transplant centers, compared the outcomes of 233 consenting recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to MMF (750 mg twice/day, n = 119) or AZA (75 to 125 mg/day, n = 114) added-on maintenance low-dose CsA microemulsion and 1-week steroid. In patients without acute clinical or subclinical rejections, CsA dose was progressively halved. Primary endpoint was biopsy-proven CAN. Analysis was by intention to treat.Participants were included between June 2007 and July 2012 and followed up to August 2016. Between-group donor and recipient characteristics, donor/recipient mismatches, and follow-up CsA blood levels were similar. During a median (interquartile range (IQR)) follow-up of 47.7 (44.2 to 48.9) months, 29 of 87 biopsied patients on MMF (33.3%) versus 31 of 88 on AZA (35.2%) developed CAN (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595). Twenty and 21 patients on MMF versus 34 and 14 on AZA had clinical [HR (95% CI): 0.58 (0.34 to 1.02); p = 0.057) or biopsy-proven subclinical [HR (95% CI): 1.49 (0.76 to 2.92); p = 0.249] ACR, respectively. Combined events [HR (95% CI): 0.85 (0.56 to 1.29); p = 0.438], patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate (GFR) [53.8 (40.6;65.7) versus 49.8 (36.8;62.5) mL/min/1.73 m2, p = 0.50], and adverse events (AEs) were not significantly different between groups.Chronicity scores other than CAN predict long-term graft outcome. Study limitations include small sample size and unblinded design.ConclusionsIn this study, we found that in deceased donor kidney transplant recipients on low-dose CsA and no steroids, MMF had no significant benefits over AZA. This finding suggests that AZA, due to its lower costs, could safely replace MMF in combination with minimized immunosuppression.Trial registrationClinicalTrials.gov ; NCT00494741EUDRACT 2006-005604-14.Piero Ruggenenti and co-workers study maintenance immunosuppression in deceased-donor kidney transplantation. 相似文献
94.
Mathematical Modelling of Mycobacterium tuberculosis VNTR Loci Estimates a Very Slow Mutation Rate for the Repeats 总被引:2,自引:0,他引:2
Minisatellites are highly variable tandem repeats used for over 20 years in humans for DNA fingerprinting. In prokaryotes fingerprinting techniques exploiting VNTR (variable number of tandem repeats) polymorphisms have become widely used recently in bacterial typing. However although many investigations into the mechanisms underlying minisatellite variation in humans have been performed, relatively little is known about the processes that mediate bacterial minisatellite polymorphism. An understanding of this is important since it will influence how the results from VNTR experiments are interpreted. The minisatellites of Mycobacterium tuberculosis are well characterized since they are some of the few polymorphic loci in what is otherwise a very homogeneous organism. Using VNTR results from a well-defined and characterized set of M. tuberculosis strains we show that the repeats at a locus are likely to evolve by stepwise contraction or expansion in the number of repeats. A stochastic continuous-time population mathematical model was developed to simulate the evolution of the repeats. This allowed estimation of the tendency of the repeats to increase or decrease and the rate at which they change. The majority of loci tend to lose rather than gain repeats. All of the loci mutate extremely slowly, with an average rate of 2.3 x 10(-8), which is 350 times slower than that of a set of VNTR repeats with similar diversity observed experimentally in Escherichia coli. This suggests that the VNTR profile of a strain of M. tuberculosis will be indicative of its clonal lineage and will be unlikely to vary in epidemiologically-related strains. 相似文献
95.
Lorusso A Decaro N Schellen P Rottier PJ Buonavoglia C Haijema BJ de Groot RJ 《Journal of virology》2008,82(20):10312-10317
Coronaviruses are positive-strand RNA viruses of extraordinary genetic complexity and diversity. In addition to a common set of genes for replicase and structural proteins, each coronavirus may carry multiple group-specific genes apparently acquired through relatively recent heterologous recombination events. Here we describe an accessory gene, ORF3, unique to canine coronavirus type I (CCoV-I) and characterize its product, glycoprotein gp3. Whereas ORF3 is conserved in CCoV-I, only remnants remain in CCoV-II and CCoV-II-derived porcine and feline coronaviruses. Our findings provide insight into the evolutionary history of coronavirus group 1a and into the dynamics of gain and loss of accessory genes. 相似文献
96.
Despite a reduction in exploitation of salmon stocks throughout the NE Atlantic, there continues to be a decline in many populations. The factors regulating these populations remain poorly understood, although there is evidence that environmental conditions experienced in freshwater can effect survival in the marine environment. The aim of this study was to investigate the impact of a brominated flame retardant (hexabromocyclododecane, HBCD) on the parr-smolt transformation in juvenile salmon. It is during this pre-adaptive period to marine life that olfactory imprinting to the natal river is considered to occur. Fish were exposed to low levels of HBCD for 30 days over the peak smoltification period in freshwater, and then transferred to clean seawater for 20 days. Fish were sampled weekly to assess changes in some of the physiological parameters associated with smoltification, and olfactory response to conspecific smolt urine was measured using an electro-olfactogram (EOG). Exposure to HBCD did not affect seawater adaptability, although there was some disruption of plasma thyroid hormone levels, as well as a reduction in olfactory function to conspecific smolt urine. The results are discussed in relation to the marine survival and successful homing of adult salmon. 相似文献
97.
98.
Marianna G. Terezow Nicola J. Nelson Timothy J. Markwell 《New Zealand journal of zoology.》2013,40(3):205-216
Abstract Knowledge of the circadian behaviour of young tuatara (Sphenodon spp.) is relatively scarce because tuatara are difficult to observe in the wild. We document diurnal, nocturnal and crepuscular emergence and movements (half‐body movement, walking and running) of three groups of captive juvenile tuatara (2‐ and 3‐year‐old Sphenodon guntheri, and 5‐year‐old S. punctatus). Juvenile tuatara emerge predominantly at night, but move around above ground, mainly during the day and around sunset. Differences in emergence andmove‐ment scores between the three study groups were evident, probably linked with age, species or housing conditions, which were inevitably coupled in our study. We found that 2‐year‐old tuatara in captive conditions emerged less frequently than, but once above ground, moved more than 3‐ and 5‐year‐olds in semi‐captive conditions. Activities in semi‐captive conditions were not correlated with temperature, light or humidity. We conclude that young tuatara may be primarily adapted to nocturnal activity, but thermal restrictions and possible hardwired adaptations to avoid predators and conspecifics may make day‐time movements safer. 相似文献
99.
100.
High expression level of a gene coding for a chloroplastic amino acid selective channel protein is correlated to cold acclimation in cereals 总被引:4,自引:0,他引:4
A cold-regulated gene (cor tmc-ap3) coding for a putative chloroplastic amino acid selective channel protein was isolated from cold-treated barley leaves combining the differential display and the 5-RACE techniques. Cor tmc-ap3 is expressed at low level under normal growing temperature, and its expression is strongly enhanced after cold treatment. A positive correlation between the expression of cor tmc-ap3 and frost tolerance was found both among barley cultivars and among cereal species. The COR TMC-AP3 protein was expressed in vitro, purified and used to raise a polyclonal antibody. Western analysis showed that the cor tmc-ap3 gene product is localized to the chloroplastic outer envelope fraction, supporting its putative function. The frost-resistant winter cultivar Onice accumulated COR TMC-AP3 more rapidly and at a higher level than the frost-susceptible spring cultivar Gitane. After 28 days of cold acclimation the winter cultivar had about 2-fold more protein than the spring genotype. All these results suggest that an increased amount of a chloroplastic amino acid selective channel protein could be required for cold acclimation in cereals. Hypotheses about the role of COR TMC-AP3 during the hardening process are discussed. 相似文献