Biomedical subjects

Stephen E Wright

Publications and source records attributed to Stephen E Wright.

5 recordsLinked to original sources

PubMed2006

Optimal experimental design for a nonlinear response in environmental toxicology.

A start-stop experiment in environmental toxicology provides a backdrop for this design discussion. The basic problem is to decide when to sample a nonlinear response in order to minimize the generalized variance of the estimated parameters. An easily coded heuristic optimization strategy can be applied to this problem to obtain optimal or nearly optimal designs. The efficiency of the heuristic approach allows a straightforward exploration of the sensitivity of the suggested design with respect to such problem-specific concerns as variance heterogeneity, time-grid resolution, design criteria, and interval specification of planning values for parameters. A second illustration of design optimization is briefly presented in the context of concentration spacing for a reproductive toxicity study.

Animals↗

PubMed2006

A simulation study comparing different experimental designs for estimating uptake and elimination rates.

The design of ecotoxicological studies requires decisions about the number and spacing of exposure groups tested, the number of replications, the spacing of sampling times, the duration of the study, and other considerations. For example, geometric spacing of sampling times or toxicant concentrations is often used as a default design. Optimal design methods in statistics can suggest alternative spacing of sampling times that yield more precise estimates of regression coefficients. In this study, we use a computer simulation to explore the impact of the spacing of sampling times and other factors on the estimation of uptake and elimination rate constants in an experiment addressing the bioaccumulation of a contaminant. Careful selection of sampling times can result in smaller standard errors for the parameter estimates, thereby allowing the construction of smaller, more precise confidence intervals. Thus, the effort invested in constructing an optimal experimental design may result in more precise inference or in a reduction of replications in an experimental design.

Animals↗

PubMed2005

Prevalence of antibodies to Toxoplasmagondii and Neosporacaninum in red foxes (Vulpesvulpes) from around the UK.

The purpose of this study was to establish the prevalence of antibodies to Toxoplasma gondii and Neospora caninum in a random sample of red foxes from around the UK. Lung fluid from over 500 foxes was examined using an indirect fluorescent antibody test. Reciprocal titres of specific antibodies to T. gondii or N. caninum ranged from < 1:16 to 1:1024. A titre of 1:128 or greater was deemed indicative of exposure to the parasite. One hundred and eleven (20%) of the 549 foxes tested were seropositive to T. gondii, and only five (0.9%) were seropositive to N. caninum. No correlation could be made between positive samples and geographical distribution, as sample numbers varied greatly between regions. The results of this study indicate that red foxes of the UK have more exposure to T. gondii than to N. caninum in their environment.

Animals↗

PubMed2003

The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas.

To investigate the possible role of glycosylase action in causing tumor resistance, a full-length, histidine-tagged human alkyladenine glycosylase has been purified from the cloned human gene contained in a pTrc99A vector propagated in a tag alkA mutant Escherichia coli. This human enzyme releases both 3-methyladenine and 7-methylguanine from methylated DNA but in contrast to previous studies of the bacterial AlkA glycosylase, it does not release any adducts from [(3)H]chloroethylnitrosourea-modified DNA. This finding suggests that the alkyladenine DNA glycosylase-dependent resistance to the toxic effects of the chloroethylnitrosoureas reported previously in the literature may occur by a mechanism other than through direct glycosylase action.

Base Sequence↗

PubMed2002

Adoptive immunotherapy of mucin1 expressing adenocarcinomas with mucin1 stimulated human peripheral blood mononuclear cells.

Mucin1 stimulated hematopoietic mononuclear cells (M1SHMC) from patients with breast cancer, adoptively transferred to non-obese diabetic, severe combined immunodeficient (NOD SCID) mice, extended survival in a therapy model of gross adenocarcinoma and prevented tumor growth in a model of minimal disease. M1SHMC exhibited specific lysis of a human breast adenocarcinoma cell line expressing mucin1, MCF-7 and produced interferon gamma. M1SHMC were injected intraperitoneally (IP) in NOD SCID mice after gross, palpable tumors appeared after MCF-7 were injected subcutaneously (SC). Survival was increased as compared to no M1SHMC controls. However tumors eventually regrew in all mice. To determine whether minimal disease (MD) could be controlled, NOD SCID were injected with MCF-7 cells, and on the same day, injected IP with M1SHMC. The M1SHMC injected mice were protected from tumor growth. These results imply that M1SHMC can prolong survival, but not cure NOD SCID mice bearing gross palpable adenocarcinomas. However in a minimal disease model tumor growth was prevented.

Adenocarcinoma↗