John Newman | PubMed Health

PubMed2002

Quantitation of natural killer cell precursors in man.

A technique was developed to measure the frequency of natural killer cell precursors (NKpf) in human peripheral blood mononuclear cell (PBMC) samples. Functional maturity of NK cells was reflected in their ability to lyse target cells from the K562 cell line. During the development of the technique, venous blood was taken from one healthy adult and assayed at different times to avoid individual variation. The technique was based on the principle of limiting dilution analysis. The NKpf assay was set up with a range of cell dilutions from 40,000 to 625 per 100 microl/well in 96-well culture plates. At the end of the culture period, the K562 cell line labelled with europium (Eu-K562) was added and the Eu-release was measured in culture supernatants using time-resolved fluorometry. The NKpf value differed between individuals and was influenced by the length of time in culture, being maximal at day 5. Maturation of NKp required the continuous presence of recombinant interleukin 2 (rIL-2), or rIL-15, both being equally effective. In the absence of cytokines, the functional NK cells declined rapidly beyond 24 h in culture. Irradiated allogeneic cells appeared to substitute in part for cytokines, but the numbers of allo-activated NKpf were lower than those observed when allo-activated NKpf were cultured with rIL-2. This suggested selective activation by the allogeneic stimulus of subsets of NKp or rIL-2-rescue of NKp subsets destined for apoptotic cell death. Alternatively, the increased frequency could have been attributable to activation of precursors of natural killer-T cells (NK-Tp). This assay is suitable for estimating the total number of precursors of functional NK cells in the blood of patients.

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PubMed2002

Using performance standards to evaluate social programs with incomplete outcome data. General issues and application to a higher education block grant program.

The idea of program evaluation is both simple and appealing. Program outcomes are measured and compared to some minimum performance standard or threshold. In practice, however, evaluation is difficult. Two fundamental problems of outcome measurement must be addressed. The first, which we call the problem of auxiliary outcomes, is that we do not observe outcome of interest. The second, which we call the problem of counterfactual outcomes, is that we do not observe the threshold standard. This article examines how performance standard should be set and applied in the face of these problems in measuring outcomes. The central message is that the proper way to implement standards varies with the prior information an evaluator can credibly bring to bear to compensate for incomplete outcome data. By combining available data with credible assumptions on treatments and outcomes, the performance of a program may be deemed acceptable, unacceptable, or indeterminate.

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