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Biomedical subjects

R A O'Brien

Publications and source records attributed to R A O'Brien.

52 records · Page 3Linked to original sources
PubMed1971

Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5-hydroxytryptamine.

1. We have studied the mechanism of quinidine uptake by normal human blood platelets.2. Platelets in plasma or Krebs solution took up quinidine extremely rapidly, the maximal drug concentration ratio of platelet to medium being 24 to 1 after 1 minute.3. The effects of metabolic inhibitors on uptake were equivocal. Ouabain had no effect but iodoacetate and dinitrophenol were effective. However, as accumulation was not inhibited by low temperature, it was probably not energy dependent.4. Interactions between quinidine and 5-HT were also investigated.5. Quinidine blocked 5-HT uptake, but conversely, neither 5-HT itself nor 5-HT uptake inhibitors, such as cocaine, dexamphetamine, and desipramine interfered with quinidine accumulation.6. Electronmicrographs of platelets incubated with 10(-5), 10(-4) or 2 x 10(-3)M quinidine in Krebs solution for 2 h showed no changes at the lower concentrations, but gross ultastructural damage, including disintegration of the plasma membrane, at 2 x 10(-3)M.7. Further evidence for intracellular penetration was obtained because quinidine released endogenous 5-HT and ATP, and also (14)C-5-HT from loaded cells.8. We conclude that quinidine is taken up by the platelet by a passive process, unrelated to the 5-HT transport mechanism. It is probably accumulated largely in the plasma membrane and outer protein layer, but intracellular penetration and ultrastructural damage may occur.9. Although the effects on 5-HT and ATP were not due to platelet damage, this may occur in vivo and be the cause of quinidine induced thrombocytopenic purpura.

Adenosine Triphosphate↗
PubMed1971

Abnormalities of 5-hydroxytryptamine uptake and binding by blood platelets from children with Down's syndrome.

1. Blood platelets from normal children and children with the trisomy 21 form of Down's syndrome (mongolism) were studied to determine the cause of the well established reduction in platelet 5-HT in the disease.2. Concentrations of endogenous 5-HT in the platelets from mongols were 25.3% of the concentrations found in normal children.3. The net accumulation of 5-HT in the mongol cells was decreased to 52.7% of normal. This reduction was probably due, in part, to a defect in 5-HT transport, because the initial rates of 5-HT uptake at plasma concentrations of 10(-6) and 10(-5)M were significantly slower.4. Experiments on the efflux of 5-HT from mongol platelets loaded with amine showed that the rate of loss was initially 2.6 and later 7.8 times faster than normal.5. Platelet ATP in mongol cells was 26% of normal, and the reduction of ATP and 5-HT was in the molar ratio of 3:1.6. It is considered that the low platelet 5-HT in Down's syndrome is due to a defective 5-HT transport mechanism and impaired 5-HT binding, resulting from a reduction in the essential binding substance, ATP.

Adenosine Triphosphate↗
PubMed1970

Accumulation of dopamine by blood platelets from normal subjects and parkinsonian patients under treatment with L-DOPA.

1. Human blood platelets have been shown to take up dopamine by an energy-dependent, saturable process that is inhibited by 5-hydroxytryptamine (5-HT), desipramine and other drugs.2. Platelets from parkinsonian subjects receiving oral L-DOPA also took up dopamine.3. When the responses of normal and parkinsonian platelets were compared, the parkinsonian cells showed the following differences: increased affinity for the dopamine transport process; decreased equilibrium concentrations of dopamine after incubation for 90 min, and greater efflux of dopamine from loaded platelets during a 10 min incubation.4. There were no differences in the uptake of 5-HT by parkinsonian platelets, but endogenous 5-HT was significantly reduced; ATP was normal.5. In two out of three samples of platelets from parkinsonian subjects, traces of a dopamine-like substance were detected, but this finding requires confirmation.6. If the platelet is a valid model for dopaminergic brain neurones, then the results described would suggest that dopamine uptake and storage may be abnormal in brain neurones in Parkinson's disease.

Adenosine Triphosphate↗
PubMed1970

Uptake of dopamine by platelets in vivo.

Circulating platelets of cats infused with (14)C-dopamine take up the amine against a concentration gradient, with maximal concentration occurring 10 min after infusion. 58%, of the platelet-bound radioactive dopamine was localized in a subcellular fraction rich in 5-hydroxytryptamine (5-HT) storage organelles. The results support earlier work with human platelets showing in vitro dopamine uptake by normal platelets, and in vivo accumulation in parkinsonian patients treated with L-dopa.

Animals↗
PubMed1969

The accumulation of guanethidine by human blood platelets.

1. When human blood platelets were incubated aerobically in plasma containing 2 x 10(-7) to 10(-3)M radioactive guanethidine for 10 min to 6 hr, the drug was accumulated against a concentration gradient until concentration ratios (platelet/plasma) of up to 80:1 were obtained.2. The decline in rate of uptake after 3 hr appeared to result from a decrease in platelet viability, because accumulation was reduced by prolonged incubation before addition of guanethidine.3. Uptake was energy-dependent because it was inhibited by cold and ouabain.4. Sodium ions were essential for guanethidine uptake and retention of 5-hydroxytryptamine (5-HT).5. Accumulation was inhibited by 5-HT, desipramine, cocaine, dexamphetamine, bretylium, tyramine and noradrenaline; bethanidine, p-chlorophenylalanine and (-)-alpha-methyldopa were inactive.6. Guanethidine was tightly bound to platelets, only 10% being lost from labelled cells during 60 min incubation in drug-free plasma; but efflux was increased by addition of amphetamine.7. The binding sites for guanethidine seemed to be different from those for 5-HT since guanethidine accumulation was independent of 5-HT levels, and neither guanethidine uptake or release were affected by reserpine.8. Guanethidine was not metabolized by platelets or plasma in vitro.9. We consider that, if our results regarding uptake, binding and release of guanethidine are confirmed in vivo, and also found to apply to other pharmacologically active agents, then the eventual loss of a platelet-bound substance may increase pharmacological action by raising plasma levels.

Autonomic Agents↗
PubMedDate not supplied

Isolation and identification of "diazepam-like" compounds from bovine urine.

Attempts to isolate the putative endogenous ligand for the benzodiazepine receptor from bovine urine resulted in the identification of three isoflavans: equol (1), 3',7-dihydroxyisoflavan (2), and 4'-hydroxy-7-methoxyisoflavan (9), as "diazepam-like" compounds. 3-Chloro-9H-carbazole (17) was found to enhance the binding of diazepam in the benzodiazepine receptor binding assay. Pinosylvine monomethyl ether (18), indigo (20), and indirubin (21) were isolated as inactive compounds.

Animals↗
PubMedDate not supplied

Catechol-O-methyltransferase activity in erythrocytes of children with autism.

1. The activity of the enzyme catechol-O-methyltransferase (COMT) was determined in the erythrocytes of normal and autistic children. 2. There was no difference in enzyme activity between the two groups, although in both the normal and autistic females the erythrocyte COMT activity showed considerable within-group variation. 3. When the erythrocyte homogenates were divided into particulate and soluble fractions, some differences were observed. The COMT activity in the soluble fraction was less in erythrocytes from autistic males than in those from control males, whereas that in autistic females was higher than in those from control females.

Autistic Disorder↗
PubMedDate not supplied

Relationship of parent-child communication to child's exploratory behavior and self-differentiation.

In a study that investigated the relationship between patterns of acknowledgment in parent--child communication and the child's exploratory behavior and self-differentiation, subjects included 77 healthy perschool children between the ages of 3 years, 3 months and 4 years, 9 months and their mothers. Data on parent--child communication were collected in the home setting during a 30-minute observation in which mothers and children were engaged in a series of semi-structured play activities. Maternal responses to their children's assertions were coded as nonevaluative recognition, positive recognition, negative recognition, direction, or nonrecognition. A score on parent--child communication was the ratio of parental nonevaluative recognition and positive recognition combined to parental negative recognition, direction, and nonrecognition combined. Testing of the children on exploratory behavior and self-differentiation was done on an individual basis in their respective nursery schools. A low positive correlation (r = .237, p less than .05) between parent--child communication and children's self-differentiation was observed. Contrary to expectation, a slight negative correlation (r = -.101, p greater than .05) between parent--child communication and children's exploratory behavior was observed. Auxiliary analyses of the data, taking into consideration the child's sex, revealed that the negative relationship between parent--child-communication and children's exploratory behavior was characteristic of the mother-daughter dyads only (r = -.325, p = .08). A correlation of .078 (p greater than .05 was obtained for mother--son communication with boys' exploratory behavior.

Child Behavior↗