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排序方式: 共有10000条查询结果,搜索用时 367 毫秒
991.
M. Howard Tattum Samantha Jones Suvankar Pal Azedeh Khalili‐Shirazi John Collinge Graham S. Jackson 《Transfusion》2010,50(12):2619-2627
BACKGROUND: The causal association of variant Creutzfeldt‐Jakob disease (vCJD) with bovine spongiform encephalopathy has raised significant concerns for public health. Assays for vCJD infection are vital for the application of therapeutics, for the screening of organ donations, and to maintain a safe blood supply. Currently the best diagnostic tools for vCJD depend upon the detection of disease‐associated prion protein (PrPSc), which is distinguished from normal background PrP (PrPC) by proteinase K (PK) digestion, which can also degrade up to 90% of the target antigen. STUDY DESIGN AND METHODS: A sandwich enzyme‐linked immunosorbent assay method was developed using unique antibodies for the detection of disease‐associated PrP in the absence of PK treatment. In combination with immunoprecipitation the assay was optimized for the detection of pathogenic PrP in large volumes of whole blood. RESULTS: Optimization of the assay allowed detection of 2 × 104 LD50 units/mL spiked in whole blood. Application of the assay to clinically relevant volumes enabled the detection of 750 LD50 units/mL in 8 mL of whole blood. CONCLUSION: By combining the use of a unique antibody that selectively immunoprecipitates PrPSc with glycoform‐restrictive antibodies we have developed a rapid assay for vCJD infection that does not require any PK treatment to achieve high levels of specificity in whole human blood, the most challenging potential analyte. The sensitivity of detection of vCJD infection is greater than the equivalent of a more than 2.5 million‐fold dilution of infected brain, providing a highly sensitive immunoassay compatible with blood screening. 相似文献
992.
A method for determining the bidomain conductivity values is developed. The study was generated because the different sets
of measured conductivity values reported in the literature each produce significantly different bidomain simulation results.
The method involves mapping the propagation of the electrical activation of cardiac tissue, initiated by point stimulation,
via extracellular electrodes. A time-dependent bidomain model is used to simulate the electrical phenomena. The optimum set
of conductivity values is achieved by minimizing the difference between the bidomain model output and the measured extracellular
potential, by means of inverse techniques in parameter estimation least-squares and singular value decomposition. The method
is validated with synthetic data with added random noise. Other parameters in the model such as membrane capacitance and fiber
angle can also be estimated. The method takes a different approach to the conventional four-electrode technique, as it does
not require the small electrode separation needed to separate the extracellular current from the intracellular. 相似文献
993.
994.
Graham M. West Chandra L. Tucker Tao Xu Sung Kyu Park Xuemei Han John R. Yates III Michael C. Fitzgerald 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(20):9078-9082
Knowledge about the protein targets of therapeutic agents is critical for understanding drug mode of action. Described here is a mass spectrometry-based proteomics method for identifying the protein target(s) of drug molecules that is potentially applicable to any drug compound. The method, which involves making thermodynamic measurements of protein-folding reactions in complex biological mixtures to detect protein–drug interactions, is demonstrated in an experiment to identify yeast protein targets of the immunosuppressive drug, cyclosporin A (CsA). Two of the ten protein targets identified in this proof of principle work were cyclophilin A and UDP-glucose-4-epimerase, both of which are known to interact with CsA, the former through a direct binding event (Kd ∼ 70 nM) and the latter through an indirect binding event. These two previously known protein targets validate the methodology and its ability to detect both the on- and off-target effects of protein–drug interactions. The other eight protein targets discovered here, which include several proteins involved in glucose metabolism, create a new framework in which to investigate the molecular basis of CsA side effects in humans. 相似文献
995.
Bryony Sheaves Ray B Jones Graham R Williamson Rohan Chauhan 《BMC medical informatics and decision making》2011,11(1):20
Background
Use of the Internet for people with Long Term Conditions (LTCs) can have a positive effect on knowledge, social support, behavioural and clinical outcomes, yet there is concern that a 'digital divide' prevents some patients from benefitting. While some patients do not have access to the Internet, others that do may still lack expertise or the confidence to make full use of it. The aim of this pilot study was to develop an intervention and test methods for a definitive randomised controlled trial (RCT) of anonymous personal online email support for patients in this latter group. 相似文献996.
997.
David R Jones James W McBlane Graham McNaughton Nishanthan Rajakumaraswamy Kirsty Wydenbach 《British journal of clinical pharmacology》2013,76(2):203-209
The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible. Other factors are also taken into account during a review, such as regulatory requirements, and emerging non-clinical and clinical data from other trials on the same or similar products. This paper examines the regulatory review process of a Clinical Trial Authorization application from the perspectives of Quality, Non-Clinical and Clinical Regulatory Assessors at the Medicines and Healthcare products Regulatory Agency. It should be noted that each perspective has highlighted specific issues from their individual competence and that these can be different between the disciplines. 相似文献
998.
999.