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Biomedical subjects

B Davison

Publications and source records attributed to B Davison.

24 records · Page 2Linked to original sources

On the biopotency and site of action of drugs affecting endocrine tissues with special reference to the anti-steroidogenic effect of anaesthetic agents.

Dispersed guinea-pig adrenal cells or mouse Leydig cells were stimulated with a saturating dose of adrenocorticotrophin (ACTH, 50 ng/1) or luteinizing hormone (LH, 5IU/1), respectively. The incubations were performed in the presence of increasing concentrations (10(-9) - 5 X 10(-4)mol/l) of the anaesthetic agents propofol, thiopentone and etomidate. At the end of this stimulation period, cortisol (from the adrenal preparation) or testosterone (from the Leydig cell culture) were assayed by radioimmunoassay. Propofol, thiopentone and etomidate all inhibited ACTH-stimulated cortisol secretion in a dose-related fashion. Similar inhibition of LH-stimulated testosterone output was found with propofol and thiopentone whereas etomidate was without effect at any concentration employed, an observation in accordance with its known site of action, 11 beta-hydroxylase, an enzyme which is not involved in the biosynthesis of testosterone. The concentration (mumol/l) of anaesthetics which gave 50% inhibition (ED50) of ACTH-stimulated cortisol secretion was 0.1 +/- 0.002 (n = 7), 160 +/- 18 (n = 3) and 170 +/- 18 (n = 3) (mean +/- s.e.m.) for etomidate, thiopentone and propofol, respectively. The corresponding values for the LH stimulated testosterone output from the Leydig cell preparations were 186 (thiopentone) and 180 (propofol) mumol/l. In a separate series of experiments adrenal cells were stimulated with (a) the cortisol precursor steroids (all at 10(-5)mol/l) pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone and 11-deoxycortisol, (b) dibutyryl cAMP (10(-3)mol/l) or (c) ACTH (100 ng/l) in the presence and absence of either etomidate (5 X 10(-5)mol/l), propofol (2.5 X 10(-4)mol/l) or thiopentone (5 X 10(-4)mol/l). All the stimulators increased cortisol production by > 7-fold over that seen in their absence. Propofol depressed ACTH and dibutyryl cAMP induced cortisol output by > 60% (P < 0.05) but was without effect when the steroid precursors were used, suggestive of an inhibition between the sequence involving ACTH binding -> pregnenolone production. In contrast, etomidate and thiopentone reduced cortisol secretion by > 40% (P < 0.05) regardless of the stimulator used, indicating that at least one site of action was at the level of the final enzymic step of cortisol synthesis, i.e. 11beta-hydroxylase.

Adrenocorticotropic Hormone↗

Computerized continuous monitoring of cytochemical enzyme reaction product formation by the Vickers M85A microdensitometer.

An experimental set-up for the continuous monitoring of cytochemical enzyme reaction rates is described. The design consists of a 32K Commodore PET microcomputer, upgraded to Basic 4 and containing a graphics facility. The microcomputer is interfaced with a Vickers M85A microdensitometer, which has been modified and equipped with a Zeiss X63 water immersion objective. The software allows for the automatic transfer of density readings from the M85A to the microcomputer, and for the continuous monitoring of the enzyme reaction as its proceeds at short time intervals (i.e. down to 3.3 s). The relationship between the absorbance change of the enzyme final reaction product and time is printed both numerically and graphically. Initial velocity rates are calculated by regression analysis, and statistical evaluation of grouped data is possible.

20-Hydroxysteroid Dehydrogenases↗

Basal steroid production by the zona reticularis of the guinea-pig adrenal cortex.

The zonae glomerulosa and fasciculata (ZG/ZF) have been separated by microdissection from the zona reticularis (ZR) of the guinea-pig adrenal cortex. Using non-proliferative organ culture and specific radioimmunoassay the basal secretion of 12 steroids from each zone have been studied. The ZG/ZF secreted 9 times more cortisol (in pmol/mg dry weight 5 h culture) than the ZR. In contrast the androgens (androstenedione, 5-androstenediol, dehydroepiandrosterone, dehydroepiandrosterone-sulphate and testosterone) were preferentially produced (by a factor of 3) by the ZR which also secreted more of all the other steroids studied, with the exception of progesterone and 17-hydroxyprogesterone. The mean molar ratios of total androgen output to cortisol secretion were 1:1.7 and 1:45 for the ZR and ZF respectively. Using computerised image analysis the relative volumes of the ZG/ZF and ZR in the cortex were calculated to be 65 and 35% respectively. The medulla occupies 4.6% of the total gland. From the zonal composition of the cortex, the relationship between wet and dry weight for each zone and the basal secretion rate of each steroid/mg dry weight/5 h culture, we calculated that the ZR could be responsible for 7 and 66% of the cortisol and total androgen secretion respectively from the guinea-pig adrenal gland. It is concluded that the ZF and ZR are functionally as well as morphologically distinct.

Adrenal Cortex↗

Hip arthroplasty: patient satisfaction.

A total of 1074 patients, the survivors of a multicentre sample of 1085 who, 9-15 months earlier, had undergone total hip replacement, were asked to complete a questionnaire about their satisfaction with the outcome of surgery. Of 1027 (96%) who responded, 90% were satisfied, 5% were unsure and 3% were dissatisfied with the result--2% failed to answer the question about satisfaction. The highest satisfaction rate was found amongst patients who had undergone bilateral hip replacement (96%) and those with a diagnosis of rheumatoid arthritis (94%). Dissatisfaction was associated with previous surgery to the index hip and additional surgery following total hip replacement. In all but five of the 98 patients who did not express satisfaction an adequate reason could be found either in the case notes or from questionnaire responses.

Adolescent↗

Application of pattern recognition techniques to the analysis of protein crystal structure data. I. Characteristics of per-residue side chain contact frequency distributions.

A statistical study of amino acid side chain contact interactions was carried out using a data set based on 36 protein structures. For each type of amino acid, a distribution of per-residue inter-side-chain contacts was obtained, over the observed span of zero to 11 contacts per residue. Significant observations included the following: 1) The mean number of inter-side-chain contacts is proportional to side chain surface area with the exception of Lys and Arg. 2) The mean number of contacts was greater for amino acids in beta-sheet relative to alpha-helical regions. 3) The more polar or surface-loving amino acids exhibited non-normal distributions, whereas distributions for the non-polar or interior-loving amino acids fell within accepted limits of normality.

Amino Acids↗

Computer assisted transcutaneous oxygen monitoring.

A computerized system for acquisition of data from a transcutaneous PO2 (PtcO2) monitor is presented. A North Star Computer, Inc., "Horizon" microcomputer was used in this system. The PtcO2 monitor was a Radiometer TCM-1 equipped with an external printer interface. The system had a custom interface module to accept binary-coded decimal data from the PtcO2 monitor. In addition, a 16-channel, 12-bit A/D module, a real-time clock module with interrupt capability, and a high-resolution graphics module were incorporated.

Computers↗