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S N Freeman

Publications and source records attributed to S N Freeman.

6 recordsLinked to original sources
PubMed1992

A modelling strategy for recovery data from birds ringed as nestlings.

In this paper we propose a strategy for analysing recovery data from birds ringed as nestlings. The approach advocated starts with a global model, involving calendar year dependence of both reporting and first-year survival rates, and age-dependence of survival rates for older birds. Likelihood ratio tests are then used to choose between a range of submodels. The strategy is illustrated through application to three data sets, on mallards, herring gulls, and blue-winged teal. The effect of age-dependence operating also on reporting rates is examined through matched simulations, since a model with age-dependent reporting rates cannot be fitted directly. This reveals an underestimation of the first-year survival rates, when the probability of recovery for first-year birds is greater than that for older birds. It is argued that this bias may not be serious and indeed may be allowed for in practice. For mallards and teal, comparisons are drawn with the results from other models that additionally analyse recoveries of birds ringed as adults; the same general conclusions are reached.

Animals↗
PubMed1990

Urokinase- and tissue-type plasminogen activators are suppressed by cortisol in the involuting prostate of castrated rats.

The effects of cortisol on the inhibition of cell-death processes and suppression of plasminogen-activator (PA) activity during involution of the rat ventral prostate gland were investigated to determine the principal type of PA activated by castration and inhibited by this hormone and whether the mechanism responsible for decreased PA activity involved reductions in enzyme synthesis or increased activity of a PA inhibitor. By using the technique of fibrin-agarose zymography, three bands of PA activity were detected at 4 and 7 days after castration: a major band with a molecular mass of approx. 30 kDa and two minor bands of 48 kDa and 64 kDa. Both the 30 kDa and 48 kDa activities were inhibited with anti-[urokinase-type PA (u-PA)] IgG. The 64 kDa activity was inhibited by anti-[tissue-type PA (t-PA)] IgG. In addition to retarding prostatic involution, daily administration of cortisol to the castrated animals suppressed all three bands of PA activity. A comparison of the pattern of total PA activity and of e.l.i.s.a. estimates of u-PA concentration during the castration-induced rise and after cortisol inhibition indicated a near perfect correlation between the two parameters. Northern-blot analysis using prostatic polyadenylated RNA revealed that the level of u-PA mRNA was highest at 4 and 7 days after castration and that cortisol treatment repressed u-PA mRNA to a level similar to that in non-castrated controls. Neither Northern hybridizations nor reverse zymography detected RNA transcripts or activity corresponding to the PA inhibitor PAI-1 in any of the prostate samples. Western-blot analysis revealed that, although the amount of arginine esterase A, another prostatic proteinase, also increased after castration, the rise in concentration of this protein was not blocked by glucocorticoid administration. Together our findings indicate the following: (1) the predominant form of PA activity induced in the prostate after castration and inhibited by cortisol is a 30 kDa form of u-PA. Although less prominent, t-PA and a 48 kDa form of u-PA follow a similar pattern of induction and inhibition; (2) changes in u-PA activity in response to castration and cortisol treatment are due to alterations in the level of u-PA mRNA and protein rather than in the activity of PAI-1; (3) not all castration-induced proteinases in the prostate are inhibited by cortisol.

Animals↗
PubMed1989

A possible explanation for the peripheral selectivity of a novel non-steroidal pure antiandrogen, Casodex (ICI 176,334).

The in vivo antiandrogenicity of Casodex has been confirmed and characterised. Androgen receptor (AR) binding assays of rat ventral prostate gland cytosols revealed a relative binding affinity (RBA) for the AR of 0.267 and a k1 of 1.25 x 10(-7) M for Casodex. In addition, the peripheral selectivity of Casodex relative to other non-steroidal antiandrogens was confirmed in that daily treatment of non-castrated rats with Casodex (25 mg kg-1) did not elicit any changes in serum LH and testosterone concentrations relative to vehicle-treated controls, whereas elevated serum LH and testosterone were observed in rats treated with flutamide (25 mg kg-1). The peripheral selectivity of Casodex in the intact male rat was related to the distribution of radiolabelled antiandrogen following intravenous injection. All tissues with the exception of the hypothalamus and cerebral cortex (CC) sequestered radioactivity such that the tissue:serum ratio (TSR) for the drug was greater than unity. In the testis, the TSR was less than unity 1 h after injection but approached unity 5 h after injection and was greater than unity 10 h after injection. This may be explained by the presence of a blood-testis barrier for the drug, resulting in delayed equilibration between the blood and testis tissue. By comparison, an order of magnitude lower amounts of radioactivity in the hypothalamus and CC were maintained for the 10 h period after injection. These data, together with known physicochemical properties of Casodex suggest that a blood-brain barrier exists for the drug which results in exclusion of this antiandrogen from central sites of androgen negative feedback and that this accounts for its peripherally selective antihormonal profile.

Androgen Antagonists↗
PubMed1989

Cortisol alters gene expression during involution of the rat ventral prostate.

The ability of high doses of cortisol to retard the involution process in the rat ventral prostate was related to alterations in the pattern of gene expression. Poly(A)+ RNA preparations from the prostates of noncastrated, castrated, and castrated rats injected daily for 7 days with cortisol were compared by Northern blot hybridizations for the relative expression of genes associated with cell differentiation and maintenance (the C1 prostatic steroid binding protein gene and alpha-tubulin), with cell death (TRPM-2, hsp 70, and c-fos), and with hormone regulation (the androgen and glucocorticoid receptors). As anticipated, the concentration of C1 mRNA in the prostate fell to less than 4% of that in the noncastrated controls within 4 days after castration and was nearly undetectable after 7 days. This decline was retarded by cortisol treatment of 7-day castrated animals which sustained the level of C1 transcripts at approximately 50% of control. While the pattern of expression of alpha-tubulin indicated some minor fluctuations, with the highest level occurring 7 days after castration, the prostates of the cortisol-treated group had essentially the same concentration of this mRNA as the noncastrates. Cortisol also modified the expression of genes associated with prostatic cell death. The large increase in prostatic TRPM-2 mRNA, seen 7 days after castration, was reduced by over 80% after treatment with the glucocorticoid. Although not as abundantly expressed as TRPM-2, the castration-induced levels of transcripts for both hsp 70 and the protooncogene c-fos were substantially reduced by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗