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Biomedical subjects

B E Murphy

Publications and source records attributed to B E Murphy.

At least 73 records · Page 4Linked to original sources

In vitro metabolism of prednisolone, dexamethasone, betamethasone, and cortisol by the human placenta.

Many of the factors influencing the pharmacologic action of corticosteroids on the maternal-placental-fetal unit remains obscure. To clarify the effect of the placenta on corticoid transfer, tritiated steroids were incubated in saline for 2 hours with minces of midgestational or term placental tissue. The media were extracted and chromatographed on Sephadex-LH-20. Large peaks corresponding to the inactive 11-keto metabolites were observed for cortisol (67 per cent) and prednisolone (51 per cent) while conversion of dexamethasone (1.8 per cent) and betamethasone (7.1 per cent) was low or negligible.

Betamethasone↗

Serum oestrogens and progesterone in mother and infant at delivery.

Whereas maternal venous levels of progesterone and oestrogens have been studied intensively in relation to parturition, little attention has been directed to fetal levels. In this study progesterone, oestrone (E1), oestriol (E2) and oestriol (E3) were measured in umbilical artery (UA) and umbilical vein (UV) serum at vaginal delivery (after induced or spontaneous onset of labour) and at elective Caesarean section. At least 14 samples were included in each group. All UV serum steroid levels were consistently higher than UA serum steroid levels. Cord serum levels of progesterone and arterio-venous differences were higher at vaginal delivery than at Caesarean section although maternal levels changed little. E1 and E2 levels were similar after spontaneous labour and at Caesarean section but were higher (P less than 0-05) after induced labour although E3 levels did not alter. E1 and E2 were higher and progesterone lower in primiparae than in multiparae. Fetal sex made no differences. These results suggest that induction of labour with oxytocin results in altered fetal hormone levels, that maternal hormone levels provide a poor reflection of fetal changes,and that current views about the mechanism of the onset of labour in animals may not be appropriate for man.

Delivery, Obstetric↗

Conversion of cortisol to cortisone by the human uterus and its reversal in pregnancy.

Inter-conversion of cortisol (F) and cortisone (E) was investigated by incubating minced tissue with tritiated cortisol or cortisone and then separating the products by Sephadex LH-20 column chromatography. In non-pregnant subjects conversion of F to E predominated (43.4+/-3.4% vs 0.1+/-0.4% for E to F). In early pregnancy F leads to E decreased and E leads to F rose while at term E leads to F (46.3+/-9.1%) exceeded F leads to E (15.1+/-6.8%). These results were in accord with those obtained by assaying the endogenous concentrations. In non-pregnant subjects the F/E ratio (1.1+/-0.6) was lower than that found in serum (6.3+/-2.2) while at term the uterine F/E (9.0+/-1.8) was similar to that of serum (8.8+/-2.0). These changes resulted in an 8-fold increase in uterine F compared with a 3-fold increase in serum F, while uterine E fell to 1/2 and serum E doubled. Thus, during pregnancy there is a dramatic reversal of the reaction in the uterus in favour of the active hormone. It seems possible that the increase in cortisol thus brought about may play an anti-immune role in uterine wall, the single tissue apart from blood in direct contact with fetal tissue.

Cortisone↗

Cortisol levels in maternal venous and umbilical cord arterial and venous serum at vaginal delivery.

To provide evidence that the high levels of cortisol found in mixed cord serum at spontaneous delivery are derived from the fetus rather than the mother, arterial and venous cord samples were collected separately along with simultaneous maternal venous samples at term. In the group with spontaneous labor, the difference between umbilical arterial levels of cortisol (78.6 +/- 4.1 ng. per milliliter) exceeded venous levels (61.9 +/- 4.1 ng. per milliliter) (P less than 0.0001). In the group with induced labor, the arterial level (58.4 +/- 6.9 ng. per milliliter) did not differ significantly from the venous level (50.6 +/- 5.9 ng. per milliliter) (P greater than 0.05). In four cases where spontaneous rupture of the membranes occurred prior to induction, values were similar to those of the group with spontaneous labor. The arterial levels of the group with spontaneous labor exceeded those of the group with induced labor (P less than 0.02). These differences cannot be related to duration of labor, gestational age, or maternal cortisol concentration, none of which differed between the group with electively induced and spontaneous labor. The present data provide further evidence that a rise in fetal cortisol production independent of the mother precedes and is involved in the mechanism initiating the spontaneous onset of human labor.

Delivery, Obstetric↗

Inhibition of a parathyroid hormone-stimulated renal adenylate cyclase by cyclic AMP.

Plasma membranes were isolated from bovine renal cortex. This particulate, adenylate cyclase-containing fraction was stimulated to produce cyclic AMP by parathyroid hormone and fluoride. When the time-course of adenylate cyclase activity was investigated, it was found that while PTH-stimulated cyclic AMP production comes to a halt in about 15 minutes after the initiation of the reaction, fluoride-stimulated activity continues unabated for at least an hour. Experiments to determine the cause of this showed that the cyclase enzyme is not degraded under our experimental conditions, but is inhibited by a soluble, unbound product of the reaction which requires ATP for its synthesis. In our experiments degradation of parathyroid hormone was relatively slow and could not account for the rapid inhibition of PTH-stimulated cyclase activity. Of the various agents tested, cyclic AMP was found capable of inhibiting PTH-stimulated cyclic AMP production by our purified membrane preparation. Half-maximal inhibition was observed at around 10(-6) M concentrations of the nucleotide. Pyrophosphate, adenosine, 5'-AMP and ADP had no effects. The significance of these results in relation to the regulation of adenylate cyclase activity is discussed.

Adenylyl Cyclases↗

Non-chromatographic radiotransinassay for cortisol: application to human adult serum, umbilical cord serum, and amniotic fluid.

Rapid (1-2 hour) non-chromatographic radiotransinassay using horse transcortin can be used to measure cortisol in umbilical cord serum (after hexane-carbon tetrachloride prewash and methylene chloride extraction), in amniotic fluid (after methylene chloride extraction only), and in adult serum (after dilution and boiling without extraction). Since horse transcortin has high affinity (2.4 x 10(9) l/mol) for cortisol, only a few microlitres of sample is required. The assay appears to be highly specific for cortisol clinically except in congenital adrenal hyperplasia.

Amniotic Fluid↗

Interaction of gelatin with stereospecific binding proteins and its enhancement of competitive binding assays.

The effect of gelatin (0.5 g/l) on binding curves at high dilution of three classes of stereo-specific binding proteins was studied. These included two antibodies (to oestradiol and aldosterone), six transins (horse and dog transcortins, human thyroxine-binding globulin, human sex steroid-binding globulin, and guinea pig transprogestin), and one receptor (bovine adrenal protein kinase). Gelatin increased the apparent binding of all these proteins, particularly at the highest dilutions and sometimes in a striking manner. While much of this action can be attributed to its decreasing the adhesion of the dilute binding protein to glass, gelatin also increased the apparent uptake of some tracers by certain adsorbents. Similar findings were obtained using human gamma globulin (2 g/l). These effects resulted in increased sensitivity and improved reproducibility in the assays employing them.

Aldosterone↗