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41.
Blood-perfused working isolated rat heart 总被引:5,自引:0,他引:5
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Xiangdan Wang Valerie Quarmby Carl Ng Anan Chuntharapai Theresa Shek Charles Eigenbrot Robert F. Kelley Steven Shia Krista M McCutcheon John Lowe Cecilia Leddy Kyle Coachman Gary Cain Felix Chu Isidro Hotzel Mauricio Maia Eric Wakshull Jihong Yang 《MABS-AUSTIN》2013,5(4):540-554
Pharmacokinetic (PK) and immunohistochemistry (IHC) assays are essential to the evaluation of the safety and efficacy of therapeutic monoclonal antibodies (mAb) during drug development. These methods require reagents with a high degree of specificity because low concentrations of therapeutic antibody need to be detected in samples containing high concentrations of endogenous human immunoglobulins. Current assay reagent generation practices are labor-intensive and time-consuming. Moreover, these practices are molecule-specific and so only support one assay for one program at a time. Here, we describe a strategy to generate a unique assay reagent, 10C4, that preferentially recognizes a panel of recombinant human mAbs over endogenous human immunoglobulins. This “panel-specific” feature enables the reagent to be used in PK and IHC assays for multiple structurally-related therapeutic mAbs. Characterization revealed that the 10C4 epitope is conformational, extensive and mainly composed of non-CDR residues. Most key contact residues were conserved among structurally-related therapeutic mAbs, but the combination of these residues exists at low prevalence in endogenous human immunoglobulins. Interestingly, an indirect contact residue on the heavy chain of the therapeutic appears to play a critical role in determining whether or not it can bind to 10C4, but has no affect on target binding. This may allow us to improve the binding of therapeutic mAbs to 10C4 for assay development in the future. Here, for the first time, we present a strategy to develop a panel-specific reagent that can expedite the development of multiple clinical assays for structurally-related therapeutic mAbs. 相似文献
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Robert W. Fogel Louis Cain Joseph Burton Brian Bettenhausen 《Economics & Human Biology》2013,11(3):269-280
Making use of those Union Army veterans for whom death certificates are available, we compare the conditions with which they were diagnosed by Civil War pension surgeons to the causes of death on the certificates. We divide the data between those veterans who entered the pension system early because of war injuries and those who entered the pension system after the 1890 reform that made it available to many more veterans. We examine the correlation between specific medical conditions rated by the surgeons and death causes to gauge support for the hypothesis that death is attributable to something specific. We also examine the correlation between the accumulation of rated conditions to the length of time until death to gauge support for the “insult hypothesis.” In general, we find support for both hypotheses. Examining the hazard ratios for dying of a specific condition, there is support for the idea that what ail’d ya’ is what kill’d ya’. 相似文献
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W. J. Lawson W. D.L. Ride A. J. Cain C. J. Uys G. J. Broekhuysen J. Martin 《Ostrich》2013,84(2):90-91