Biomedical subjects

M D Simpson

Publications and source records attributed to M D Simpson.

28 records · Page 2Linked to original sources

PubMed1989

Reduced GABA uptake sites in the temporal lobe in schizophrenia.

The binding of [3H]nipecotic acid, a ligand for labelling GABA uptake sites in brain, was measured in left and right frontal cortex, polar temporal cortex, hippocampus and amygdala from control and schizophrenic postmortem brains. In schizophrenic brains, single concentration [3H]nipecotic acid binding was reduced bilaterally in amygdala and hippocampus and on the left side only in polar temporal cortex. These data suggest that GABA neurones are involved in the cerebral atrophy of schizophrenia and, in agreement with other studies, that this process is most pronounced in left temporal cortex.

Amygdala↗

PubMed1989

Reduced D-[3H]aspartate binding in Down's syndrome brains.

The binding of D-[3H]aspartate to glutamate uptake sites was measured in post-mortem brains from subjects with Down's syndrome (DS) and age-matched controls. DS brains had substantially reduced D-[3H]aspartate binding in the frontal and temporal cortex, hippocampus and caudate nucleus. There was no correlation between the numbers of Alzheimer-like plaques and tangles or clinically-assessed dementia and D-[3H]aspartate binding in DS brains. The binding of [3H]N-(1-[2-thienyl]cyclohexyl)piperidine ([3H]TCP) to postsynaptic N-methyl-D-aspartate sites was normal in DS brains. This study suggests that the reduction in glutamate uptake sites in DS is more substantial and widespread than in Alzheimer's disease.

Aged↗

PubMed1989

Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia.

Glutamatergic mechanisms have been investigated in postmortem brain samples from schizophrenics and controls. D-[3H]Aspartate binding to glutamate uptake sites was used as a marker for glutamatergic neurones, and [3H]kainate binding for a subclass of postsynaptic glutamate receptors. There were highly significant increases in the binding of both ligands to membranes from orbital frontal cortex on both the left and right sides of schizophrenic brains. The changes are unlikely to be due to antemortem neuroleptic drug treatment, because no similar changes were recorded in other areas. A predicted left-sided reduction in D-[3H]aspartate binding was refuted at 5% probability, but not at 10%. Previously reported high concentrations of dopamine in left amygdala were strongly associated with low concentrations of D-[3H]aspartate binding in left polar temporal cortex in the schizophrenics. The findings are compatible with an overabundant glutamatergic innervation of orbital frontal cortex in schizophrenia. The results also suggest that schizophrenia may involve left-sided abnormalities in the relationship between temporal glutamatergic and dopaminergic projections to amygdala.

Aspartic Acid↗

PubMed1988

Regional changes in [3H]D-aspartate and [3H]TCP binding sites in Alzheimer's disease brains.

The specific binding of [3H]D-aspartate, a marker for the presynaptic glutamate uptake site, and [3H]N-(1-[2-Thienyl]cyclohexyl)-piperidine [( 3H]TCP), a high affinity ligand for the N-methyl-D-aspartate (NMDA)-associated phencyclidine binding site, was measured in homogenates of brain from normal subjects and from subjects with neuropathologically confirmed Alzheimer's disease. Alzheimer's disease was associated with a reduction in [3H]D-aspartate binding density in temporal cortex and caudate nucleus. By contrast, a reduction in the receptor density for [3H]TCP binding was only recorded in the frontal cortex. Thus, glutamate-containing nerve terminals are severely reduced in Alzheimer's disease, whilst the postsynaptic NMDA-phencyclidine receptor complex is much less affected. These findings have implications for theories of glutamate neurotoxicity in Alzheimer's disease.

Aged↗

PubMed1988

Loss of cortical GABA uptake sites in Alzheimer's disease.

[3H]Nipecotic acid bound to membranes of human brain in a saturable, reversible manner which was totally dependent on the presence of sodium ions. The potencies of compounds in inhibiting the specific binding of [3H]nipecotic acid were closely correlated with their potencies in inhibiting the neuronal uptake of [3H]GABA. Compounds selective for GABA receptors were inactive. [3H]Nipecotic acid appears to label neuronal high affinity GABA uptake sites. The binding of [3H]nipecotic acid was substantially reduced in the temporal cortex of brains from subjects with Alzheimer-type dementia, but not in other brain regions. It is concluded that some loss of GABA terminals occurs in this disease.

Aged↗

PubMed1986

Hypophysectomy may non-selectively alter pharmacokinetic parameters to enhance the ability of haloperidol to increase striatal dopamine receptor density in the rat.

We have investigated the effect of a range of doses of haloperidol (0.625-5.0 mg/kg/day) or saline, administered for 14 days, followed by a 3 day drug washout period, to sham operated or hypophysectomized rats. Haloperidol increased the number of specific striatal 3H-spiperone binding sites (Bmax) in sham-operated animals at doses of 2.5 and 5.0 mg/kg/day, and in hypophysectomized animals at all doses used (0.625-5.0 mg/kg/day). The inhibition of locomotor activity produced by haloperidol was greater in hypophysectomized than sham-operated animals. Plasma and striatal haloperidol levels after equivalent doses were greater in hypophysectomized than in sham-operated animals. We conclude that hypophysectomy may enhance the ability of haloperidol to induce striatal dopamine receptor supersensitivity in the rat, and that this may be due to differences in the pharmacokinetic handling of haloperidol between sham-operated and hypophysectomized animals.

Animals↗

PubMed1986

Hyperprolactinaemia does not alter specific striatal 3H-spiperone binding in the rat.

We have investigated the effect of single injections (1 mg/animal i.v.) of prolactin or vehicle, and repeated depot (0.125-1.0 mg/animal/day) or bolus (1.0 mg/animal/day) administration of prolactin or vehicle for 6 days to adult male rats. The density (Bmax) and affinity (Kd) of specific striatal [3H]spiperone binding was not changed by any of the prolactin treatment schedules used. Allogeneic transplants of anterior pituitary glands resulted in an increased concentration of circulating prolactin but did not alter the density or affinity of specific striatal [3H]spiperone binding in male rats, measured 2 weeks following the operation. Prolactin did not displace specific striatal [3H]spiperone binding when incorporated in vitro. Any effect of prolactin on striatal dopamine receptor function appears to be exerted only by high, non-physiological concentrations, and such effects are difficult to reproduce.

Animals↗

PubMedDate not supplied

A two-process theory of schizophrenia: evidence from studies in post-mortem brain.

Glutamate and GABA are the principle neurotransmitters of the cerebral cortex and are known to modulate dopaminergic function. Evidence of structural abnormalities in the cortex raises the possibility that schizophrenia involves disturbances of cortical amino-acid neurotransmission. The psychotomimetic effects of phencyclidine, a glutamate antagonist, have been taken to suggest that schizophrenia involves reduced brain glutamate function. Direct evidence for diminished glutamate function in schizophrenia is lacking. However, in polar temporal cortex and hippocampus we reported evidence of an asymmetric loss of glutamate terminals, and of reduced GABA function, which may be secondary to the loss of glutamatergic input. Glutamate cell body markers are spared in temporal lobe; the neurones which degenerate may originate in frontal cortex. A number of studies have reported increases in markers of glutamatergic cell bodies and terminals in orbital frontal cortex in schizophrenia. These findings are consistent with the presence of an abnormally abundant glutamatergic innervation, which may be the result of an arrest in the normal process of cellular and synaptic elimination which occurs during development. There is evidence that frontal abnormalities in schizophrenia are genetically determined. We suggest that glutamatergic abnormalities in anterior temporal cortex in schizophrenia are the result of the degeneration of fronto-temporal projections. Orbital frontal projections to polar temporal cortex may be prone to degeneration because they arise from an unstable frontal cortical cytoarchitecture which has not completed the normal process of post-natal remodelling. The structural abnormality of the orbital frontal region may confer vulnerability to some intrinsic or extrinsic mechanism, which brings about a progressive degeneration of projections to polar temporal lobe.

Brain↗

PubMedDate not supplied

Dentin permeability: sealing the dentin in crown preparations.

Provisional restorations of full crown preparations may permit more microleakage of bacteria and their products than the final castings do. However, most investigations of the sealing qualities of cemented castings have reported that they too permit dye leakage. One approach to the problem is to seal the dentin with dentin bonding agents at the completion of the crown preparation. This study evaluated the ability of six different dentin bonding agents to seal the dentin of crown preparations of human teeth in vitro using two independent techniques. The first technique quantitated fluid filtration across dentin before and after treatment with dentin bonding agents at one hour, one day, one week, and one month and after thermocycling. The second method measured silver nitrate penetration of the thin veneers of dentin bonding agents into the dentin. Both methods correlated well with each other. The best seals were obtained with Prisma Universal Bond 2 or Superbond powder plus liquid. The worst seals were found using Gluma and Superbond liquid only. Clearfil PhotoBond, Amalgambond, and Scotchbond 2 gave intermediate results. Although the dentin bonding agents tend to accumulate on chamfers, thereby increasing their thickness to 200-300 microns, the method looks promising as a simple way to protect the pulp from the consequences of microleakage.

Analysis of Variance↗

PubMedDate not supplied

The effect of dentin depth on the permeability and ultrastructure of primary molars.

The purpose of this study was to measure the permeability of primary molar and permanent premolar dentin at various thicknesses from the pulp and to correlate permeability with the tubule density and diameter of dentin using SEM. The data were examined for statistically significant differences using two-way analysis of variance, multiple comparison Scheffe, and regression analysis. The permeability of all teeth increased with decreasing dentin thickness. The removal of the smear layer resulted in a significant increase in the permeability. However, the permeability of the dentin in premolars was significantly higher than that in the primary molars. The density and diameter of the dentinal tubular in primary molars were lower than the values reported for permanent teeth and may account for the lower permeability of the primary molars.

Adolescent↗