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Biomedical subjects

L W Strijbosch

Publications and source records attributed to L W Strijbosch.

5 recordsLinked to original sources

Design methods for some dose-response models.

A recently described design method for one-parameter biomedical models such as limiting or serial dilution assays is generalized to two-parameter models for which the dose-response relationship can be expressed as a linear regression model with parameters alpha (intercept) and beta (slope). Design formulae are proposed for three different cases in which prior information about the unknown regression parameters alpha and beta is available (alpha known, beta known and neither known, respectively). A suitable transformation of the two-parameter model enables the direct application of the one-parameter design method to the first two cases, while the third needs more advanced considerations. Two experimental designs, taken from the literature, are reproduced as closely as possible using the methods described, thus showing under which circumstances these designs are suitable.

Animals

Computer aided design and evaluation of limiting and serial dilution experiments.

Two computer programs are presented which can be used for the determination of the design and the statistical evaluation of data in the context of limiting and serial dilution analysis. The first program (DESIGN) gives the experimenter the opportunity to set up different designs, to improve a design according to several suggestions, to make a picture of a design and to evaluate the results of artificial data, obtained from a random experiment corresponding with the chosen design, until (s)he is convinced of having a suitable design for a particular experiment. The second program (EVALUATE) evaluates the experimental data. The design method and the statistical methods used in the programs have been chosen on practical and theoretical grounds.

Colony Count, Microbial

Using jackknife methods for estimating the parameter in dilution series.

Dilution assays are quantal dose-response assays that detect a positive or negative response in each individual culture within groups of replicate cultures that vary in the dose of cells/organisms tested. We propose three jackknife versions of the maximum likelihood estimator of the unknown parameter, i.e., the frequency of a well-defined cell within the context of limiting dilution assays or the density of organisms within the context of serial dilution assays. The methods have been evaluated with artificial data from extensive Monte Carlo experiments. As a result of these experiments and theoretical considerations, the jackknife version based on deleting one individual culture at a time is proposed as the statistical procedure of choice. The next best method is the jackknife version based on leaving out the same replicate from each of the culture groups at a time.

Biometry

Limiting dilution assays. Experimental design and statistical analysis.

Two issues in limiting dilution analysis are considered. The first concerns the experimental design: a mathematical algorithm has been developed which calculates the number of replicate culture groups, and the (mean) number of cells per well to be used on the basis of the experimenter's a priori information about the unknown frequency. The procedure guarantees useful data if the a priori interval estimate of the frequency to be determined is correct and the cells are willing to grow. The second issue concerns the statistical method to be used for estimation of the unknown frequency. Several methods (minimum chi-square, maximum likelihood and the jackknife version of the maximum likelihood method) have been evaluated with artificial data from extensive Monte Carlo experiments. All three methods were useful in the statistical analysis of data. As a result of these experiments and theoretical considerations the jackknife version of the maximum likelihood estimation procedure is proposed as the statistical procedure of choice. The next best method is the maximum likelihood procedure.

Algorithms

Analysis of cytotoxic T lymphocyte response in rejecting allografted canine kidneys.

The involvement of cytotoxic T lymphocytes (CTL) in the rejection process of allografted canine kidneys was studied. The frequency of donor-specific (precursor) CTL was determined with a sensitive limiting dilution assay. Longitudinal sampling of peripheral blood and kidney aspiration biopsies were used to obtain information on the CTL response toward the graft. An accurate analysis of CTL kinetics in both kidney and peripheral blood of allografted dogs appeared to be technically possible. During the first days after transplantation precursor CTL (CTLp) frequencies decreased in both blood and kidney. A minimum CTLp frequency of 5-15% of the pretransplant value was reached in the peripheral blood at day 4 after transplantation. The cause of this decrease, which was observed in all 5 allografted dogs is discussed. CTLp frequencies increased after day 4 and showed an exponential rise in the kidney before serum creatinine increased due to loss of kidney function caused by rejection. The data obtained with the quantitative study of CTL show that rejection of a canine kidney allograft is accompanied by a rise in CTL numbers in the kidney. The methodology developed permits extensive functional analysis of cellular processes in allografted organs.

Animals