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Biomedical subjects

F Owen

Publications and source records attributed to F Owen.

At least 55 records · Page 3Linked to original sources

Uptake of 77Br-spiperone in the striata of schizophrenic patients and controls.

Twelve patients with a diagnosis of schizophrenia and thirteen control subjects were injected with 77Br-bromospiperone and scanned using single photon emission tomography after 16 h. Although a statistically significant increase in patients by comparison with controls could be demonstrated, wide variations in specific activity of the ligand preclude a firm conclusion. In two patients but no controls an asymmetry in striatal uptake was noted, the uptake on the left being less than that on the right.

Adult↗

Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients.

Cholecystokinin (CCK) binding sites were assessed in post-mortem brain membrane preparations from controls and schizophrenic patients. 125I-BH CCK33 specific binding was reduced by 40% (p less than 0.02) in the hippocampus and by 20% (p less than 0.01) in the frontal cortex of schizophrenic patients compared with controls. There were no differences in 125I-BH CCK33 binding between the two groups in the amygdala, temporal cortex or caudate nucleus.

Adult↗

Chemical and structural changes in the brain in patients with movement disorder.

Neurochemical indices of dopaminergic function were assessed in basal ganglia of post-mortem brains of control subjects and schizophrenic patients who had been rated in life for the presence of movement disorder and neuroleptic intake. In schizophrenics who had been treated chronically with doses of neuroleptics, concentrations of dopamine D2 receptors were significantly increased above controls, whereas dopamine D1 receptors and dopamine metabolism were unchanged. Increased D2 receptors were also observed in basal ganglia of drug-free patients. Concentrations of dopamine D1 and D2 receptors in schizophrenics with movement disorder. Moreover, no relationship was found between dopamine receptor levels and the severity of movement disorder. Concentrations of the dopamine metabolite homovanillic acid were increased in the putamen and nucleus accumbens in a small number of patients with movement disorder compared with controls or patients without movement disorder. No changes were observed in markers of cholinergic and GABA-containing neurones. The present findings are not consistent with a "dopamine receptor hypersensitivity" concept of movement disorder in schizophrenia.

3,4-Dihydroxyphenylacetic Acid↗

Tritiated etorphine and naloxone binding to opioid receptors in caudate nucleus in schizophrenia.

Opioid receptor binding sites were assessed in membrane preparations of caudate nucleus from post-mortem brains of controls and of patients with schizophrenia. There was no difference between the two groups in the total specific binding of 3H-etorphine or in its 'mu' and ('delta + kappa') components. Similarly, the binding of 3H-naloxone did not differ between patients and controls. It is concluded that a previous report of reduced opioid receptors in caudate of schizophrenics is unlikely to prove a consistent finding and that the results of the present study offer no support to the claim that there is a general disturbance in opiate mechanisms in schizophrenia.

Aged↗

Dopamine D2 receptors in substantia nigra in schizophrenia.

Dopamine D2 receptors were assessed in samples of substantia nigra from controls and schizophrenics. Specific [3H]spiperone binding was significantly increased in both neuroleptic-free and neuroleptic-treated schizophrenics. This supports our previous suggestion that the increase in D2 receptors observed in striatum of schizophrenics is not wholly due to neuroleptic medication.

Aged↗

Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides.

In patients with Alzheimer-type dementia, in addition to the well-known losses of cholinergic neurones, there is evidence of degeneration of the noradrenergic and serotonergic innervation of the cerebral cortex. While noradrenergic and cholinergic receptors are preserved there is a loss of serotonin S1 and S2 receptors, particularly in the temporal lobe. The loss of serotonin S2 receptors may occur at an early stage of the disease and, in temporal and frontal cortex, is correlated with the loss of somatostatin immunoreactivity. In patients dying in hospital with depression, and in individuals committing suicide, there are no consistent changes in monoamine metabolites. Noradrenergic, serotonergic, and other neurotransmitter receptors were found to be unchanged, although there was a moderate decrease in imipramine binding in a small group (n = 6) of subjects with a history of depression, who had committed suicide.

Aged↗

Characterisation and distribution of vasoactive intestinal polypeptide binding sites in human brain.

The binding of 125I-vasoactive intestinal polypeptide (VIP) to human brain membranes has been studied. The binding was saturable with a dissociation constant (KD) of 4.4 +/- 2.0 nM and maximum binding value (Bmax) of 8.6 +/- 6.2 fmoles/mg tissue (mean +/- SD, n = 4), and was displaced by unlabelled VIP with an IC50 of 4 nM; secretin was much less potent with an IC50 of approximately 8 microM. The regional distribution of 125I-VIP binding in human brain revealed highest binding values to be in frontal and temporal cortices with intermediate values in amygdala, caudate and cerebellum, with lowest values in hippocampus, substantia nigra and hypothalamus.

Binding Sites↗

[3H]R05-4864 and [3H]flunitrazepam binding in kainate-lesioned rat striatum and in temporal cortex of brains from patients with senile dementia of the Alzheimer type.

In agreement with other workers we report increased [3H]R05-4864 binding in kainate-lesioned rat striatum. [3H]R05-4864 binding, a possible glial marker, was also increased in temporal cortex obtained post-mortem from patients with Alzheimer's disease. [3H]Flunitrazepam binding was decreased in these brain samples, possibly indicative of neuronal cell loss. It is suggested that the poor binding characteristics of [3H]R05-4864 in human brain samples may limit its usefulness in assessing gliosis.

Aged↗

The effects of cholecystokinin on dopaminergic mechanisms in rat striatum.

Intraventricular administration of cholecystokinin-octapeptide in unanesthetized rats results in a significant reduction in the number of [3H]spiperone binding sites. Striatal levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly reduced, whereas there was no significant reduction in the levels of the serotonin metabolite 5-hydroxyindoleacetic acid.

Animals↗

77Br-p-bromospiperone: a ligand for in vivo labelling of dopamine receptors.

A high striatum: cerebellum ratio of 77Br-p-bromospiperone (77Br-BrSp) was observed in rat brain following tail vein injection of the drug. Striatal 77Br-BrSp was stereospecifically displaced by the isomers of flupenthixol. After chronic haloperidol administration striatal dopamine receptor supersensitivity was demonstrated both by increased 3H-spiperone binding to striatal membranes in vitro and by increased striatal 77Br-BrSp content. These results confirm and extend previous findings and enhance interest in the use of 77Br-BrSp for the in vivo assessment of central dopamine receptors in man.

Animals↗

[3H]etorphine binding in rat striatum following lesions of the raphe nuclei.

Following 5,7-dihydroxytryptamine lesions of the rat raphe nuclei a significant reduction in striatal serotonin concentrations was observed. However, with [3H]etorphine as ligand no change in opiate receptor binding was observed in striatal membranes. Moreover, when [3H]etorphine binding was resolved into its mu- and delta + kappa-components no change in either component was observed compared with controls. It is concluded that opiate receptors are not on striatal serotonergic nerve terminals whose cell bodies are located in the raphe nuclei.

5,7-Dihydroxytryptamine↗

Preferential inhibition of ligand binding to calf striatal dopamine D1 receptors by SCH 23390.

The phenylbenzazepine derivative, SCH 23390 was found to be a potent inhibitor of 3H-piflutixol binding to calf striatal dopamine D1 receptors. In contrast SCH 23390 was only a weak inhibitor of 3H-spiperone binding to dopamine D2 receptors. Although possessing some activity at serotonin S2 and alpha 2 adrenergic receptors, SCH 23390 appears to be a potent and selective D1 receptor antagonist.

Animals↗

Hydroxy-indole-o-methyltransferase activity in human pineals: a comparison of controls and schizophrenics.

The activity of hydroxy-indole-o-methyltransferase (HIOMT) has been assayed in pineal glands from fifteen controls and twenty-three schizophrenics. There was no significant difference between the two groups in HIOMT activity and no significant effect of age, sex or neuroleptic treatment on the activity of the enzyme. A diurnal rhythm was not discernible in HIOMT activity and it is suggested that this may be the result of terminal illness. It is concluded that HIOMT activity in pineals of schizophrenics is unlikely to differ from controls.

Acetylserotonin O-Methyltransferase↗