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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

Stringent and growth-rate-dependent control of the gua operon of Escherichia coli K-12.

The promoter of the gua operon has been located by transcript mapping using primer extension with reverse transcriptase. The surrounding nucleotide sequence has features characteristic of promoters under stringent and growth-rate-dependent regulation, namely a GC-rich discriminator next to the -10 hexamer, an upstream AT-rich sequence (the UP element) and potential FIS-binding sites. Transcriptional activity of the gua promoter was examined using transcriptional fusions to lacZ placed at a single chromosomal location. Expression from gua was reduced under stringent conditions in vivo, and varied with growth rate. Growth-rate control was independent of guanine-mediated repression. A fusion in which the GC-rich discriminator was mutated by insertion of an AT-rich oligonucleotide was used to demonstrate the importance of this region in control. Both stringent and growth-rate-dependent controls were abolished by the mutation. Other potential regulatory signals in the vicinity of the gua promoter are a pur operator (binding site for the PurR repressor), a gua operator, a DnaA-binding site and a CRP/FNR-binding sequence. The gua promoter lies back-to-back with the promoter for xseA (exonuclease VII), the two promoters being separated by only 20 bp.

Bacterial Proteins

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

The assessment of continuing medical education.

There is a close link between audit of clinical competence and audit of continuing medical education. Some of the earlier assumptions about the organisation of continuing medical education need to be reviewed. The increasing provision of resources for continuing medical education by the NHS means that added safeguards are necessary to ensure that professional standards are not subordinated to service exigencies. The introduction of higher educational methodology into continuing medical education should be critically examined with awareness of the limitations and controversies concerning many methods of teaching and assessing educational outcome. The methodology of higher education may need to be substantially modified to suit the uniqueness of the clinical process and the problems of altering the behaviour of experienced and practising doctors. Criticism of behaviourist educational methods should be based on an understanding and knowledge of these methods. A new functional clinical educational domain is proposed which links educational methods with the clinical application of new learning.

Clinical Competence

Calcium metabolism in bone disease: effects of treatment with microcrystalline calcium hydroxyapatite compound and dihydrotachysterol.

Microcrystalline calcium hydroxyapatite compound (MCHC) was given orally together with small doses of dihydrotachysterol (DHT) to a number of patients with osteogenesis imperfecta (OI). Serial calcium and phosphate balances in three patients representing wide variations in severity of OI are presented over periods from eight months to two years. The combination of MCHC and DHT resulted in an immediate positive calcium balance which was maintained throughout the period of assessment in 2 cases. However, no radiological improvement could be demonstrated. Substituting calcium gluconate for MCHC resulted in a reduction of positive balance. No adverse effects were noted. The reasons why MCHC with DHT should result in increased calcium retention are discussed. This combination of MCHC and DHT could be of benefit in many common situations of bone demineralization, such as osteoporosis.

Administration, Oral

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