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D R Robinson

Publications and source records attributed to D R Robinson.

114 records · Page 7Linked to original sources
PubMedDate not supplied

An analysis of in vivo hprt mutant frequency in circulating T-lymphocytes in the normal human population: a comparison of four datasets.

In this paper, we have compared mutant frequency data at the hprt locus in circulating T-lymphocytes from four large datasets obtained in the UK (Sussex), the USA (Vermont), France (Paris) and The Netherlands (Leiden). In total, data from > 500 non-exposed individuals ranging in age from newborns (cord blood samples) to > 80 years old have been included in the analysis. Based on raw data provided by the four laboratories, a model is presented for the analysis of mutant frequency estimations for population monitoring. For three of the laboratories, a considerable body of data was provided on replicate estimates of mutant frequency from single blood samples, as well as estimates from repeat blood samples obtained over a period of time from many of the individual subjects. This enabled us to analyse the sources of variation in the estimation of mutant frequency. Although some variation was apparent in the results from the four laboratories, overall the data were in general agreement. Thus, in all laboratories, cellular cloning efficiency of T-cells was generally high (> 30%), although in each laboratory considerable variation between experiments and subjects was seen. Mutant frequency per clonable T-cell was in general found to be inversely related to cloning efficiency. With the exception of a few outliers (which are to be expected), mutant frequencies at this locus were in the same range in each dataset; no effect of subject gender was found, but an overall clear age effect was apparent. When log mutant frequency was analysed vs log (age + 0.5) a consistent trend from birth to old age was seen. In contrast, the effect of the smoking habit did differ between the laboratories, there being an association of smoking with a significant increase in mutant frequency in the Sussex and Leiden datasets, but not in those from the Vermont or Paris datasets. Possible reasons for this are discussed. One of the objectives of population monitoring is an ability to detect the effect of accidental or environmental exposure to mutagens and carcinogens among exposed persons. The large body of data from non-exposed subjects we have analysed in this paper has enabled us to estimate the size of an effect that could be detected, and the number of individuals required to detect a significant effect, taking known sources of variation into account.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMedDate not supplied

Eicosanoids, inflammation, and anti-inflammatory drugs.

Many mediators of inflammation are derived from arachidonic acid including prostaglandins, leukotrienes, and other oxygenated derivatives. In addition, platelet activating factor is an acetylated ether-linked phospholipid formed by cleaving arachidonic acid from phospholipid precursors. Several of these mediators produce vasodilation and increased vascular permeability either alone or acting synergistically with other mediators. The E prostaglandins also stimulate bone resorption and activate adenylate cyclase, and leukotriene B4 is chemotactic and activates leukocytes. Both B and T cell functions are inhibited by PGE2 and some lipoxygenase products alter T cell function as well. Prostaglandin and leukotriene synthesis are closely regulated; they are stimulated by a number of activators, hormones, cytokines, and growth factors. The major therapeutic as well as toxic effects of NSAIDs are accounted for by inhibition of cyclooxygenase activity and, therefore, prostaglandin synthesis. The NSAIDs do not inhibit leukotriene synthesis, and under some conditions these drugs may augment the production of leukotrienes. Synthesis of both prostaglandins and leukotrienes are inhibited by glucocorticoids through lipomodulin-mediated inhibition of arachidonic acid release. Nutritional regulation of prostaglandin and leukotriene production may occur by substitution of alternative dietary polyunsaturated fatty acids such as the n-3 fatty acids present in marine lipids. New drugs which inhibit the synthesis of leukotrienes and platelet activating factor may be useful therapeutic agents.

Animals↗