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Biomedical subjects

S S Swart

Publications and source records attributed to S S Swart.

10 recordsLinked to original sources

Differential labeling of platelet alpha 2 adrenoceptors by 3H dihydroergocryptine and 3H yohimbine in patients with myeloproliferative disorders.

Platelet alpha adrenoceptor status was examined using the radioligands 3H-yohimbine (3H-YOH) and 3H-dihydroergocryptine (3H-DHE) in 14 patients with myeloproliferative disorder (MPD) and 10 normal controls. Platelets from normal controls and MPD patients sensitive to adrenaline induced aggregation exhibited approximately 50% more binding sites identified by 3H-DHE than 3H-YOH, whereas MPD platelets insensitive to adrenaline showed selective loss of these 'extra' 3H-DHE sites. In functional studies after 30 minutes preincubation with the unlabelled antagonists, DHE was more potent than YOH at inhibiting adrenaline induced aggregation in normal platelets. In addition, the affinity constant for DHE was virtually identical in binding and functional experiments, whereas for YOH the affinity constant for binding was approximately 10 fold more potent than that for aggregation. These results suggest that the alpha adrenoceptor binding site on human platelets labelled by 3H-DHE may be of more functional relevance than that labelled by 3H-YOH alone.

Blood Platelets↗

Alpha 2-adrenoceptor coupling to adenylate cyclase in adrenaline insensitive human platelets.

Coupling of the alpha 2-adrenoceptor to adenylate cyclase was assessed in platelets from 3 groups of subjects: normal controls and patients with myeloproliferative disorders whose platelets were either sensitive or specifically insensitive to the aggregatory effects of adrenaline. The ability of adrenaline to induce the formation of a complex between the alpha 2-adrenoceptor and the inhibitory guanine nucleotide binding protein was examined in all three groups by assessment of the effect of mono and divalent cations and Gpp(NH)p on the displacement of [3H]yohimbine binding to platelet membranes by adrenaline. Coupling to adenylate cyclase was also assessed in separate studies of the inhibition by adrenaline of PGE1 stimulated cyclic AMP accumulation in whole platelets. Both the formation of the ternary complex and the inhibition by adrenaline of cyclic AMP accumulation was not significantly different in platelets sensitive or insensitive to adrenaline. These results suggest that inhibition of cyclic AMP alone does not explain the mechanisms of adrenaline induced platelet aggregation.

Adenylyl Cyclases↗

Effects of adrenaline and alpha adrenergic antagonists on platelet aggregation in whole blood: evaluation of electrical impedance aggregometry.

The effects of adrenaline and alpha adrenergic antagonists on platelet aggregation in whole blood were assessed by electrical impedance. These effects were then compared to those found in platelet rich plasma assessed by both optical and impedance methods. Our data demonstrate a number of difficulties in attempting to measure platelet responsiveness by electrical impedance and re-emphasise the need for caution in interpretation of in vitro platelet aggregation studies in terms of their clinical relevance.

Adrenergic alpha-Antagonists↗

Human platelet alpha 2-adrenoceptors: relationship between radioligand binding studies and adrenaline-induced aggregation in normal individuals.

Using the alpha 2-adrenoceptor selective radioligand [3H]yohimbine maximum binding capacities (Bmax), dissociation constants (KD), and the affinity (KI) of adrenaline for the binding sites were measured in platelets obtained from a group of 42 normal individuals. These results were compared with the efficacy of adrenaline induced aggregation in platelet rich plasma in the same subjects. Wide interindividual variation was found in Bmax values as measured in whole platelets (sites/platelet) or platelet lysates (fmol/mg protein) and in KI values for adrenaline displacement of [3H]yohimbine binding. Adrenaline's ability to induce platelet aggregation measured as the concentration required to achieve half maximal aggregation assessed from dose-response curves showed similar interindividual variation. No correlation was found, however, between alpha 2-adrenoceptor status as assessed by radioligand binding studies and the functional studies. These results suggest that the present understanding of the relationship between alpha 2-adrenoceptor occupation and platelet aggregation may be incorrect.

Adult↗

Functional significance of the platelet alpha2-adrenoceptor: studies in patients with myeloproliferative disorders.

Platelet alpha-adrenoceptor status was examined in 35 patients with myeloproliferative disorders (MPD) and 35 normal controls by means of radioligand binding studies with 3H-yohimbine (3H-YOH) and in vitro platelet function tests. A group of 'adrenaline insensitive' MPD patients identified in the functional studies were found to be identical to normal controls and other MPD patients with respect to their alpha 2-adrenoceptor status as assessed by the binding studies. Possible explanations for the dissociation between radioligand binding studies and functional responses in the platelet are discussed.

Adenine Nucleotides↗

Pulmonary edema.

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Adult↗

Spinal cord ischaemia complicating meningococcal meningitis.

An extensive ischaemic cord syndrome developed in a patient with meningococcal meningitis complicated by 2 respiratory arrests but not by any period of prolonged hypotension or other signs of cardiovascular collapse. Excellent functional recovery occurred after intensive rehabilitation.

Adolescent↗