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Biomedical subjects

I J Davies

Publications and source records attributed to I J Davies.

At least 19 recordsLinked to original sources

Perceptual studies on ultrasonic B-scan textures.

A pilot study of the perceptual characteristics of ultrasonic textured images is described. Scans of four models performed on four real-time machines optimised for display of a normal liver were used. A trial with 22 observers indicated that the model that gave images closest to the liver image varied between machines. A second, paired similarity test with five observers using all the model images was performed, with a cluster analysis of a multidimensional scaling procedure. This suggested that the prominent features of the textural images are often more closely related to the machines than to the models. Considerable further work is needed to confirm these pilot results and to identify the visual cues that are most significant in textured images.

Biophysical Phenomena

Progesterone receptor in the hypothalamic cytosol of female rats.

A progesterone (P)-binding component with a sedimentation coefficient of 8S has been demonstrated in hypothalamic cytosol from ovariectomized, estrogen-primed rats using both [H]P-containing sucrose-glycerol gradient analysis and dextran-coated charcoal adsorption of the preisolated 8S component. The association rate constant (K+1) was determined to be 1.90 +/- 0.38 (SD) X 10(6) M-1 min-1 at 0-2 C. The dissociation rate constant (K-1) was 1.86 x 10(-2) min-1, as calculated from the half-dissociation time [37.0 +/- 7.3 (SD) min]. The apparent dissociation constant (Kd) at 0-2 C was determined to be 6-10 nM by Scatchard plot analysis of data obtained from either direct [3HA]P binding or competition of the [3H]P binding by nonradioactive P and by calculating from K-1/K+1. The 8S binding component was protein in nature, and the concentration of binding sites was 12 fmol/mg cytosol protein. On a per U cytosol protein basis, the relative capacities of the specific 8S binding components were: uterus greater than pituitary greater than hypothalamus greater than hippocampus/amygdala greater than cerebral cortex. Competition studies showed a high specificity for P and 5 alpha-dihydroprogesterone. Corticosterone (C), although competing for the binding, had an affinity 8-fold less than P. Implantation of C in adrenalectomized, ovariectomized, estrogen-implanted rats suppressed the 8S binding of [3H]C without affecting the [3H]P binding. The binding of [3H]P to the cytoplasmic 8S component of hypothalamus was greater than that of combined hippocampus and amygdala, while the reverse was observed for the binding of [3H]dexamethasone. These results demonstrate in rat hypothalamic cytosol a tissue and hormone-specific, high affinity, 8S progesterone-binding protein which has many of the properties expected of a hormone receptor.

Animals

Pituitary gonadotropin responsiveness with danazol.

Danazol (17alpha-pregn-4-en-20-yno-[2,3-d]isoxazol-17-ol) was administered daily for 4 days to castrated female rats. As previously demonstrated, danazol lowered serum levels of luteinizing hormone (LH) in an apparent dose-dependent fashion. Animals which received danazol in a dose sufficient to lower serum LH responded to administered LH-releasing hormone (LHRH) with increases in serum LH levels which were not diminished as compared with those of control animals. Although these experiments do not preclude an effect of danazol directly on the pituitary, the results indicate that this agent probably lowers serum LH primarily by inhibition of hypothalamic LHRH secretion.

Animals

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

Thyrotropin-releasing hormone (TRH)-degrading activity was investigated in human cord, maternal, and euthyroid adult sera by measuring (a) the rate of disappearance of TRH and (b) the rate of formation of degradation products. The rate of TRH degradation in cord and maternal sera was 25-33% of that in euthyroid adult serum. Concomitantly, in cord and maternal sera, the rate of formation of proline, a major TRH degradation product in serum, was one-quarter to one-third that in euthyroid adult sera. The differences were highly significant (P less than 0.001). The decreased levels of TRH-degrading activity in cord and maternal sera cannot be explained by (a) the presence of a dialyzable inhibitor, (b) the absence of an activator of TRH degradation, or (c) a reversal of the degradation process. There was no difference in the types of radioactive degradation products formed by cord, maternal, and euthyroid adult sera. The low level of TRH-degrading activity and its possible relationship to high thyrotropin-stimulating hormone levels in cord serum suggest that TRH-degrading activity may be a factor to consider in investigations of the perinatal pituitary-thyroid axis, but further studies are needed to determine the role of serum degradation of TRH in regulating physiological levels of TRH.

Adult

Longitudinal studies showing alterations in the levels and functional response of T and B lymphocytes in human pregnancy.

Altered blood levels of T and B lymphocytes were found in the first half of human pregnancy. A total of twenty-two women were tested, using direct or indirect rosetting assays or the fluorescence-activated cell sorter, to determine the levels of peripheral blood T and B cells. In all cases, an inversion of T- and B-cell levels was observed, i.e. T-cell levels were decreased and B-cell levels (as measured by the presence of surface immunoglobulin or the presence of B-cell surface antigens) were increased. This inversion was exhibited as early as 1 week post-implantation. Lymphocytes from two fo the women were also examined for stimulation with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) at intervals during gestation, and the amount of [3H]thymidine uptake was compared to that of two non-pregnant women tested at each interval. The values obtained for the pregnant women with PHA were markedly lower, and with pokeweed mitogen slightly lower, than those of non-pregnant controls. However, the PHA and PWM values in the pregnant women returned to levels similar to those of the nonpregnant women shortly after the T- and B-cell levels returned to normal. Thus the decrease in the response of the lymphocytes to mitogens during early pregnancy appears to parallel the numerical deficiency of T cells.

B-Lymphocytes

Danazol inhibits steroidogenesis.

Danazol was found to inhibit multiple enzymes of steroidogenesis directly in the pregnant mare serum (PMS)-treated hamster ovary and the rat testis and adrenal in vitro. In the PMS-treated hamster ovary, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase. In the rat testis, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, 3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid dehydrogenase. In the rat adrenal, danazol inhibited 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11beta-hydroxylase. Two hours after a subcutaneous injection of 5 mg/kg of danazol to adult male rats, serum luteinizing hormone levels were significantly increased and serum testosterone levels were significantly suppressed. These findings suggest that in the rodent one of danazol's major pharmacologic effects is the direct inhibition of steroidogenesis.

Adrenal Glands

Catechol estrogen formation by the human fetal brain and pituitary.

Homogenates of central neuroendocrine tissues from 2 male and 1 female midtrimester fetuses were incubated with (23H) estradiol-17beta. Metabolism at the C-2 position was monitored by measuring the tritium incorporated into water in the incubate. Liberation of tritium from the substrate by hypothalamus, limbic tissues, parietal cortex and pituitary occurred to the extent of 5.1-12.7%, 1.6-8.5%, 4.7-10.8%, and 0.9-4.1% of starting radioactivity, respectively. The nature of the product was confirmed by the isolation of 14C labelled 2-hydroxyestrone derivative from separate incubations with 14C-estrone as the substrate. With or without correction for weight of tissue incubated, catechol estrogen formation under these conditions occurs at levels similar to those seen in rat brain homogenates except that in contrast to the rat, the human cortex is also highly active.

Brain

The effects of dexamethasone on the peripheral plasma concentrations of androstenedione, testosterone and cortisol in the pregnant rhesus monkey.

The concentrations of androstenedione, testosterone and cortisol have been measured in the maternal peripheral plasma of normal pregnant rhesus monkeys (Macaca mulatta), and in rhesus monkeys treated daily with dexamethasone during late pregnancy. During the last 30 days of pregnancy, the mean plasma concentrations of androstenedione, testosterone and cortisol were about 1400-2000 pg/m1375-425pg/ml and 300-400 ng/ml, respectively. None of these steroids increased significantly before parturition. As there was no rise in maternal androgens in late pregnancy when plasma estrogens increase sharply, it suggested that his elevation of plasma estrogens is related to an increase of fetal precursors Dexamethasone treatment resulted in 90% suppression of plasma cortisol and 40%-60% suppression of androstendione and testosterone. As the suppression of maternal androgens was of lesser magnitude than the decline of plasma estrogens, and as the androgens did not continue to fall with continuing dexamethasone treatment as did the estrogens, these findings also suggest that the decline in plasma estrogens is related in large part to suppression and atrophy of the fetal adrenals.

Androstenedione