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排序方式: 共有293条查询结果,搜索用时 15 毫秒
91.
Abdelilah el Barzouhi Carmen L. A. M. Vleggeert-Lankamp Geert J. Lycklama à Nijeholt Bas F. Van der Kallen Wilbert B. van den Hout Annemieke J. H. Verwoerd Bart W. Koes Wilco C. Peul for the Leiden–The Hague Spine Intervention Prognostic Study Group 《PloS one》2013,8(7)
Background
Magnetic Resonance Imaging (MRI) is considered the mainstay imaging investigation in patients suspected of lumbar disc herniations. Both imaging and clinical findings determine the final decision of surgery. The objective of this study was to assess MRI observer variation in patients with sciatica who are potential candidates for lumbar disc surgery.Methods
Patients for this study were potential candidates (n = 395) for lumbar disc surgery who underwent MRI to assess eligibility for a randomized trial. Two neuroradiologists and one neurosurgeon independently evaluated all MRIs. A four point scale was used for both probability of disc herniation and root compression, ranging from definitely present to definitely absent. Multiple characteristics of the degenerated disc herniation were scored. For inter-agreement analysis absolute agreements and kappa coefficients were used. Kappa coefficients were categorized as poor (<0.00), slight (0.00–0.20), fair (0.21–0.40), moderate (0.41–0.60), substantial (0.61–0.80) and excellent (0.81–1.00) agreement.Results
Excellent agreement was found on the affected disc level (kappa range 0.81–0.86) and the nerve root that most likely caused the sciatic symptoms (kappa range 0.86–0.89). Interobserver agreement was moderate to substantial for the probability of disc herniation (kappa range 0.57–0.77) and the probability of nerve root compression (kappa range 0.42–0.69). Absolute pairwise agreement among the readers ranged from 90–94% regarding the question whether the probability of disc herniation on MRI was above or below 50%. Generally, moderate agreement was observed regarding the characteristics of the symptomatic disc level and of the herniated disc.Conclusion
The observer variation of MRI interpretation in potential candidates for lumbar disc surgery is satisfactory regarding characteristics most important in decision for surgery. However, there is considerable variation between observers in specific characteristics of the symptomatic disc level and herniated disc. 相似文献92.
Daniel Warner Luis M. M. Ferreira Michel J. H. Breuer Jan Dijkstra Wilbert F. Pellikaan 《PloS one》2013,8(10)
We describe the use of carbon stable isotope (13C) labeled n-alkanes as a potential internal tracer to assess passage kinetics of ingested nutrients in ruminants. Plant cuticular n-alkanes originating from intrinsically 13C labeled ryegrass plants were pulse dosed intraruminally in four rumen-cannulated lactating dairy cows receiving four contrasting ryegrass silage treatments that differed in nitrogen fertilization level (45 or 90 kg nitrogen ha−1) and maturity (early or late). Passage kinetics through the gastrointestinal tract were derived from the δ13C (i.e. the ratio 13C:12C) in apparently undigested fecal material. Isotopic enrichment was observed in a wide range of long-chain n-alkanes (C27–C36) and passage kinetics were determined for the most abundant C29, C31 and C33
n-alkanes, for which a sufficiently high response signal was detected by combustion isotope ratio mass spectrometry. Basal diet treatment and carbon chain length of n-alkanes did not affect fractional passage rates from the rumen (K
1) among individual n-alkanes (3.71–3.95%/h). Peak concentration time and transit time showed a quantitatively small, significant (p≤0.002) increase with carbon chain length. K
1 estimates were comparable to those of the 13C labeled digestible dry matter fraction (3.38%/h; r = 0.61 to 0.71; p≤0.012). A literature review has shown that n-alkanes are not fermented by microorganisms in the rumen and affirms no preferential depletion of 13C versus 12C. Our results suggest that 13C labeled n-alkanes can be used as nutrient passage tracers and support the reliability of the δ13C signature of digestible feed nutrients as a tool to measure nutrient-specific passage kinetics. 相似文献
93.
94.
van Dooren SH Raijmakers R Pluk H Lokate AM Koemans TS Spanjers RE Heck AJ Boelens WC van Venrooij WJ Pruijn GJ 《Biochimie et biologie cellulaire》2011,89(6):545-553
The aminoacyl-tRNA synthetases are ubiquitously expressed enzymes that catalyze the esterification of amino acids to their cognate tRNAs. Autoantibodies against several aminoacyl-tRNA synthetases are found in autoimmune polymyositis and dermatomyositis patients. Because necrosis is often found in skeletal muscle biopsies of these patients, we hypothesized that cell-death-induced protein modifications may help in breaking immunological tolerance. Since cell death is associated with oxidative stress, the effect of oxidative stress on the main myositis-specific autoantibody target Jo-1 (histidyl-tRNA synthetase; HisRS) was studied in detail. The exposure of Jurkat cells to hydrogen peroxide resulted in the detection of several oxidized methionines and one oxidized tryptophan residue in the HisRS protein, as demonstrated by mass spectrometry. Unexpectedly, the tRNA aminoacylation activity of HisRS appeared to be increased upon oxidative modification. The analysis of myositis patient sera did not lead to the detection of autoantibodies that are specifically reactive with the modified HisRS protein. The results of this study demonstrate that the Jo-1/HisRS autoantigen is modified under oxidative stress conditions. The consequences of these modifications for the function of HisRS and its autoantigenicity are discussed. 相似文献
95.
This study formulates a model to maximize the profit of a lignocellulosic biofuel supply chain ranging from feedstock suppliers to biofuel customers. The model deals with a time-staged, multi-commodity, production/distribution system, prescribing facility locations and capacities, technologies, and material flows. A case study based on a region in Central Texas demonstrates application of the proposed model to design the most profitable biofuel supply chain under each of several scenarios. A sensitivity analysis identifies that ethanol (ETOH) price is the most significant factor in the economic viability of a lignocellulosic biofuel supply chain. 相似文献
96.
97.
Cecilia M?nsson Paolo Arosio Rasha Hussein Harm H. Kampinga Reem M. Hashem Wilbert C. Boelens Christopher M. Dobson Tuomas P. J. Knowles Sara Linse Cecilia Emanuelsson 《The Journal of biological chemistry》2014,289(45):31066-31076
The human molecular chaperone protein DNAJB6 was recently found to inhibit the formation of amyloid fibrils from polyglutamine peptides associated with neurodegenerative disorders such as Huntington disease. We show in the present study that DNAJB6 also inhibits amyloid formation by an even more aggregation-prone peptide (the amyloid-beta peptide, Aβ42, implicated in Alzheimer disease) in a highly efficient manner. By monitoring fibril formation using Thioflavin T fluorescence and far-UV CD spectroscopy, we have found that the aggregation of Aβ42 is retarded by DNAJB6 in a concentration-dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide. Quantitative kinetic analysis and immunochemistry studies suggest that the high inhibitory efficiency is due to the interactions of the chaperone with aggregated forms of Aβ42 rather than the monomeric form of the peptide. This interaction prevents the growth of such species to longer fibrils and inhibits the formation of new amyloid fibrils through both primary and secondary nucleation. A low dissociation rate of DNAJB6 from Aβ42 aggregates leads to its incorporation into growing fibrils and hence to its gradual depletion from solution with time. When DNAJB6 is eventually depleted, fibril proliferation takes place, but the inhibitory activity can be prolonged by introducing DNAJB6 at regular intervals during the aggregation reaction. These results reveal the highly efficacious mode of action of this molecular chaperone against protein aggregation, and demonstrate that the role of molecular chaperones can involve interactions with multiple aggregated species leading to the inhibition of both principal nucleation pathways through which aggregates are able to form. 相似文献
98.
Aniek D. van der Woude Esther J. M. Stoop Michael Stiess Sen Wang Roy Ummels Gunny van Stempvoort Sander R. Piersma Alessandro Cascioferro Connie R. Jiménez Edith N. G. Houben Joen Luirink Jean Pieters Astrid M. van der Sar Wilbert Bitter 《Cellular microbiology》2014,16(2):280-295
The pathogenicity of mycobacteria is closely associated with their ability to export virulence factors. For this purpose, mycobacteria possess different protein secretion systems, including the accessory Sec translocation pathway, SecA2. Although this pathway is associated with intracellular survival and virulence, the SecA2‐dependent effector proteins remain largely undefined. In this work, we studied a Mycobacterium marinum secA2 mutant with an impaired capacity to initiate granuloma formation in zebrafish embryos. By comparing the proteomic profile of cell envelope fractions from the secA2 mutant with wild type M. marinum, we identified putative SecA2‐dependent substrates. Immunoblotting procedures confirmed SecA2‐dependent membrane localization for several of these proteins, including the virulence factor protein kinase G (PknG). Interestingly, phenotypical defects of the secA2 mutant are similar to those described for ΔpknG, including phagosomal maturation. Overexpression of PknG in the secA2 mutant restored its localization to the cell envelope. Importantly, PknG‐overexpression also partially restored the virulence of the secA2 mutant, as indicated by enhanced infectivity in zebrafish embryos and restored inhibition of phagosomal maturation. These results suggest that SecA2‐dependent membrane localization of PknG is an important determinant for M. marinum virulence. 相似文献
99.
A star with stripes: zebrafish as an infection model 总被引:11,自引:0,他引:11
van der Sar AM Appelmelk BJ Vandenbroucke-Grauls CM Bitter W 《Trends in microbiology》2004,12(10):451-457
100.
Roxane Simeone Alexandre Bobard Juliane Lippmann Wilbert Bitter Laleh Majlessi Roland Brosch Jost Enninga 《PLoS pathogens》2012,8(2)
Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective. 相似文献