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Biomedical subjects

J I Davies

Publications and source records attributed to J I Davies.

At least 19 recordsLinked to original sources
PubMed2000

Detection of massive transplacental haemorrhage by flow cytometry.

Flow cytometry has been shown to be a more accurate and sensitive method than the Kleihauer-Betke test for the measurement of feto-maternal haemorrhage in Rh(D) incompatibility. This report describes the successful use of flow cytometry to detect and monitor the management of a massive transplacental haemorrhage (105 ml) of fetal Rh(D) positive cells in a Rh(D) negative woman. The report highlights the accuracy and reproducibility of the test and the stability of a blood sample when transferred 596 kilometres to a central testing facility.

Adolescent↗
PubMed1997

Automated reticulocyte counting: evaluation of the Coulter STKS Haematology Analyser reticulocyte counting function.

This study evaluated reticulocyte counting with the automated reticulocyte function of the Coulter STKS Haematology Analyser. This is an upgrade option for Coulter STKS and MAXIM haematology analysers. Reticulocyte counts obtained with the automated reticulocyte counting function were compared with those obtained by visual counting. Reticulocyte counting with both methods gave excellent comparability with a correlation coefficient of 0.98. Results were consistent with the well documented imprecision of the manual method with a coefficient of variation (CV) of 16-22%. In contrast, the automated reticulocyte counting function was more precise with a CV of 12.3%. In both cases, counts were stable after storage for 24 h at room temperature and 4 degrees C. Our results suggest that the use of this upgrade will be beneficial for many laboratories.

Autoanalysis↗
PubMed1996

Reduced susceptibility to oxidative damage of erythrocyte membranes from medicated schizophrenic patients.

Susceptibility to non-enzymatic peroxidation of erythrocyte membranes from medicated schizophrenic patients relative to healthy control subjects was investigated by measuring internalization into erythrocytes of ethylene glycol, cellobiotol or mannitol, with or without preincubation with cumene hydroperoxide or with chlorpromazine. The main finding was that erythrocytes from schizophrenic patients were less susceptible than those from control subjects to non-enzymatic oxidative damage from cumene hydroperoxide, as measured by internalization of cellobiotol and mannitol. At baseline before incubation, there was reduced internalization of cellobiotol and mannitol and this was reduced even further by preincubation with chlorpromazine. It is suggested that previous findings of fatty acid deficits in erythrocyte membranes from neuroleptic-treated schizophrenic patients are unlikely to have resulted from non-enzymatic oxidative damage of the membrane. Furthermore, it is suggested that depleted erythrocyte membrane essential fatty acids are more likely to be the result of the schizophrenic process rather than antipsychotic drug treatment, and that antipsychotic drugs may even offer protection against membrane lipid peroxidation.

Adolescent↗
PubMed1994

Zopiclone poisoning: tissue distribution and potential for postmortem diffusion.

Zopiclone is the first cyclopyrrolone hypnotic and is chemically unrelated to any existing drug. The authors studied the tissue distribution and postmortem redistribution of zopiclone in a fatal suicidal overdose. A 29-year-old female weighing 64 kg had cardiac blood ethanol 153 mg% and zopiclone blood concentrations in the range 0.9-2.0 microgram/ml in 10 distinct sampling sites. After 40 h at room temperature the range was 0.9-1.8 micrograms/ml in 15 samples. Portal venous blood and urine concentrations were 3.0 and 10.5 micrograms/ml, respectively. Tissue concentrations (microgram/g) were spleen 5.8, peri-renal fat 5.0, psoas muscle 3.3, brainstem 2.8, gastrocnemius muscle 1.9, myocardium 1.6, and kidney 1.7. Eight liver samples had concentrations in the range 0.5-4.9 micrograms/g, with highest concentrations in the left lobe and adjacent to the gallbladder, probably reflecting postmortem diffusion from gastric residue (700 ml, 55.1 micrograms/ml) and bile (14.1 micrograms/ml). Of six lung samples, paired upper and middle samples had concentrations in the range 2.1-2.3 micrograms/g, the right postero-basal 1.3 micrograms/g and the left postero-basal 3.4 micrograms/g. Drug concentration in putrefactive pleural fluid was also higher on the left (2.1 micrograms/ml) than the right (1.4 micrograms/ml), probably reflecting postmortem diffusion from gastric residue. The authors conclude that zopiclone showed little preferential concentration in solid organs and consequently has relatively stable postmortem blood concentrations, with little drug redistribution artefacts. Postmortem diffusion from gastric drug residue elevates drug levels in the left lobe of the liver and left lung lower lobe.

Adipose Tissue↗
PubMed1992

The sequestration of [3H]spiperone by lymphocytes in schizophrenics and their first-degree relatives: a limited vulnerability marker?

The sequestration of [3H]spiperone by lymphocytes was studied in preserved cells obtained from 22 schizophrenic subjects and 40 of their relatives, and the results were compared with those obtained from 25 healthy control subjects. Mean displaceable sequestration values, obtained from measurements made at a single radioligand concentration (1nM) which optimised the relative contribution of "high affinity" sequestration, were found to be similar for all groups of subjects. Furthermore, displaceable spiperone sequestration was abnormally high in only a small proportion of the schizophrenics (13.6%) and their relatives (5%). There was no evidence that either exposure to neuroleptic medication or duration of illness had an effect on sequestration values. The results suggest that, at least until the required experimental conditions are better established, [3H]spiperone sequestration by lymphocytes does not offer a useful vulnerability marker for schizophrenia.

Adolescent↗
PubMed1987

The interaction between the adenylate cyclase system and insulin-stimulated glucose transport. Evidence for the importance of both cyclic-AMP-dependent and -independent mechanisms.

UNLABELLED: The counter-regulatory effect of adenosine, isoprenaline and selected cyclic AMP analogues on insulin-stimulated 3-O-methylglucose transport and insulin binding were studied in rat fat-cells. Isoprenaline alone had no consistent effect on glucose transport in the presence of maximally effective insulin concentrations. However, it decreased insulin binding by approx. 20% and increased EC50 (concn. giving 50% of maximal stimulation) for insulin from 8 +/- 1 to 17 +/- 2 mu units/ml. Adenosine deaminase (ADA) alone only exerted a slight effect, whereas isoprenaline and ADA in combination consistently decreased the maximal effect of insulin on glucose transport, decreased insulin binding by approx. 30% and markedly decreased insulin-sensitivity (EC50 61 +/- 8 mu units/ml). In cells from pertussis-toxin-treated animals, isoprenaline alone decreased the insulin response by approx. 75%, decreased insulin binding by approx. 45% and caused a marked rightward shift in the dose-response curve for insulin (EC50 103 +/- 34 mu units/ml). The importance of cyclic AMP for these effects was evaluated with the analogue N6-monobutyryl cyclic AMP, which is resistant to hydrolysis by the phosphodiesterase. The importance of phosphodiesterase activation by insulin was studied with 8-bromo cyclic AMP, which is an excellent substrate for this enzyme. N6-Monobutyryl cyclic AMP, in contrast with 8-bromo cyclic AMP, markedly impaired insulin-sensitivity (EC50 approx. 100 mu units/ml). However, the maximal effect of insulin was only slightly attenuated. IN CONCLUSION: (1) beta-adrenergic stimulation and cyclic AMP markedly alter insulin-sensitivity, but not responsiveness, mainly through post-receptor perturbations; (2) when cyclic AMP is increased phosphodiesterase activation by insulin is a critical step to elicit insulin action; (3) adenosine modulates the insulin-antagonistic effect of beta-adrenergic stimulation via Ni (inhibitory nucleotide-binding protein) through both cyclic-AMP-dependent and -independent mechanisms.

3-O-Methylglucose↗
PubMed1985

Bacitracin enhances intracellular accumulation of insulin in rat adipocytes.

Bacitracin (1 mg/ml) markedly increased (approx. 75%) the cell-associated specifically bound 125I-labelled insulin without altering the affinity of the binding sites. Bacitracin also exerted a modest inhibitory effect on the degradation of insulin in the incubation medium determined as radioactivity not precipitated by trichloroacetic acid (from 9.6 to 4.8%). The effect on insulin binding was about 5-times as sensitive as the effect on degradation. The increased binding was due to intracellular accumulation of radioactivity which could not be removed by treating the cells with trypsin. This increase was not seen when the internalization process was reduced by ATP-depletion or low temperature. Since the trypsin-sensitive fraction of cell-associated radioactivity was apparently not altered, it is suggested that bacitracin, in addition to its well-known inhibition of extracellular degradation, also inhibits the intracellular degradation of insulin.

3-O-Methylglucose↗
PubMed1982

Catecholamines and the kinetics of lipolysis in isolated rat adipocytes. Statistical analysis and handling of day-to-day variability in dose-response curves: a general procedure for assessing and manipulating dose-response data.

(1) As a first step in studying the kinetics of the lipolytic system of rat adipocytes, the day-to-day variation between dose-response curves has been analysed. (2) Methods are described for the evaluation of large quantities of data relating noradrenaline to lipolysis. (3) A 'clustering' technique is presented which can be used both to estimate and minimise differences between curves along the response axis. Criteria are outlined to determine whether clustering is appropriate. (4) Our findings indicate that the basic form of the relationship between lipolysis and noradrenaline concentration is relatively stable and consequently that the data can be utilized to study the relationship in greater detail. (5) The techniques described should be applicable to all hormone-mediated responses and may therefore provide the first step towards a meaningful analysis of the relationship between hormone concentrations and response in many systems.

Adipose Tissue↗
PubMed1982

A kinetic analysis of the actions of L-noradrenaline and its related agonists and antagonists on in vitro lipolysis in rat adipose tissue.

(1) Iterative non-linearising optimisation techniques have been used to fit three alternative models to relationships between beta-adrenergic effector concentrations and the lipolytic response which they elicit in dispersed adipocytes derived from rat epididymal fat pads. (2) The models, which consist of a simple hyperbolic relationship, a Hill-type functions and a rational quadratic formulation, were fitted to data obtained with agonists, "partial" agonists and antagonists both alone and in combination. (3) Whereas the hyperbolic relationship was inadequate in all circumstances, the hill-type function accommodated dose-response curves which exhibit no "auto-inhibitory" hook or bell-shaped feature. However, the rational quadratic function could be satisfactorily fitted to the data whether or not the auto-inhibitory phase was apparent. (4) The mechanisms that govern the steepness of the dose-response relationships and their bell-shaped feature are discussed. Evidence is presented that the latter originates at the level of adenylate cyclase.

Adipose Tissue↗
PubMed1982

Analysis of apparent co-operativity in the catecholamine-stimulated lipolysis of rat adipose tissue.

(1) The methods available for assessment of the regulatory features of dose-response relationships that do not conform to the Hill equation are considered, and the sensitisation index Si introduced (2) The value of determining Si is assessed using lipolytic dose-response relationships yielded by beta-adrenergic agonists both alone and in the presence of their specific antagonists [D. M. F. Cooper and J. I Davies, Biochem. Pharmac. 31, 721 (1982)]. (3) It is shown that where the Hill equation is fitted to relationships between L-noradrenaline concentration and lipolysis, the high value obtained for the Hill coefficient (1.69) is artefactual (4) By fitting a rational quadratic model and evaluating Si, a solution is obtained (Si(max), 1.02) which is free of this artefact. (5) The relationship between the results obtained by analysis of dose-response curves and direct binding of catecholamine analogues to membrane receptors is discussed.

Adipose Tissue↗
PubMed1979

Seasonal variation in the effect of dietary RNA on criteria of energy homoeostasis in the rat.

1. RNA was administered to rats as part of a meal while standardizing food intake and minimizing the effects of psychological stress and diurnal metabolic rhythms. It was demonstrated that circulating levels of glucose and free fatty acids (FFA) in the animals, which were deprived of food for 48 h, were responsive to orally administered caffeine. 2. Inclusion of RNA in the diet slightly but consistently reduced the normal postprandial hyperglycaemia. Its effect on plasma FFA was variable although statistically significant in some experiments. The differences between RNA-and control-fed animals were not attributable to differences in the rate of passage of digesta along the gastrointestinal tract. 3. Evidence was obtained that the variability in the FFA response was related to a seasonally-dependent change in the state of animals. The synchronizer ('Zeitgeber') responsible for this change was not identified and no satisfactory way of suppressing its effect was found. 4. The present findings, taken in conjunction with those of previous workers, suggest that there is a seasonal influence on the sympathetic nervous system manifesting itself as a variable susceptibility to arousal or excitation.

Animals↗