8 research outputs found
Regeneration of T-cell helper function in zinc-deficient adult mice
Diets deficient in zinc cause rapid atrophy of the thymus and loss of T-cell helper function in the young adult A/J mouse. Because zinc deficiency, as well as other nutritional deficiences, causes extensive damage to the immune system, the question arose as to whether zinc-deficient mice could repair the thymus and fully regenerate T-cell helper function if returned to diets containing adequate amounts of zinc. Five-week-old A/J female mice were fed either a zinc-deficient (<1 μg of Zn per g) or a zinc-adequate (50 μg of Zn per g) diet for 31 days. Histological examination of thymuses from the zinc-deficient mice revealed that the cortex was preferentially involuted and the thymus was about one-third of normal size. The direct plaque-forming cells produced per mouse spleen in response to immunization with sheep erythrocytes was 34% of normal; indirect plaque-forming cells were 18% of normal (Jerne plaque assay). After the deficient mice had been fed a zinc-adequate diet for 1 week, their response was nearly normal, except that the indirect response was 68% of controls; in this same period, the thymuses of these mice had quadrupled in size and exhibited a greatly enlarged cortex repopulated with immature thymocytes. By 2 weeks, the thymuses of the previously zinc-deficient mice were normal in size and appearance; however, there was a slight increases in numbers of indirect plaque-forming cells. By 4 weeks, the thymus weights, direct and indirect plaque-forming cell counts, and secondary response of the previously deficient mice were normal. Mice that were nearly athymic after 45 days of dietary zinc deficiency were also able to fully reconstruct the thymus and regenerate T-cell helper function. The data show that the zinc-deficient young adult mouse has the capacity to fully restore the T-cell-dependent antibody-mediated responses upon nutritional repletion
Expression of the high-affinity immunoglobulin e receptor alpha-subunit in human blood eosinophilse
Confirmatory reanalysis of incurred bioanalytical samples
Bioanalytical methods used to support the drug development process are validated to ensure that they function in the manner in which they are intended. “Incurred” or study samples can vary in their composition when compared with the standards and quality control samples used to validate the method and analyze these samples. During the 3rd American Association of Pharmaceutical Scientists(AAPS)/Food and Drug Administration(FDA) Bioanalytical Workshop, it was suggested that the reproducibility in the analysis of incurred samples be evaluated in addition to the usual prestudy validation activities performed. This manuscript provides recommendations concerning the number and types of samples that should be analyzed in such an evaluation, as well as the manner in which the resultant data should be analyzed. Suggestions as to follow-up activities and data reporting are also discussed. This approach is at best a beginning and is offered as a platform for future discussion, comments, and revision