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Biomedical subjects

A J Cross

Publications and source records attributed to A J Cross.

At least 73 records · Page 4Linked to original sources
PubMed1989

The modulation by chlormethiazole of the GABAA-receptor complex in rat brain.

1. The interactions of chlormethiazole with gamma-aminobutyric acid (GABA) synthesis and release, and with ligand binding to sites associated with the GABAA-receptor complex and the GABAB-receptor have been studied in the rat. The GABAA-receptor was studied using [3H]-muscimol, [3H]-flunitrazepam was used to label the benzodiazepine modulatory site, and [35S]-butyl-bicyclophosphorothionate ([35S]-TBPS) to label the chloride channel. 2. Chlormethiazole had no effect on GABA synthesis in the cortex, hippocampus and striatum or on GABA release from cortical slices in vitro. Chlormethiazole did not displace [3H]-baclofen binding to the GABAB-receptor. 3. Chlormethiazole (IC50 = 140 microM) and pentobarbitone (IC50 = 95 microM) both inhibited [35S]-TBPS binding by increasing the rate of [35S]-TBPS dissociation. In addition, chlormethiazole caused an apparent decrease in the affinity of [35S]-TBPS binding. 4. Chlormethiazole enhanced the binding of [3H]-muscimol but had no effect on [3H]-flunitrazepam binding. In contrast, the sedative barbiturate pentobarbitone enhanced both [3H]-muscimol and [3H]-flunitrazepam binding. 5. It is concluded that the sedative and anticonvulsant effects of chlormethiazole are probably mediated through an action at the GABAA-receptor. However, chlormethiazole does not interact with the GABAA-receptor complex in an identical manner to the sedative barbiturate pentobarbitone.

Animals↗
PubMed1989

Autoradiographic visualization of kappa opioid receptors with labelled dynorphins in guinea pig brain.

The distribution of kappa opioid receptors in guinea pig brain was measured by in vitro receptor autoradiography using [3H]dynorphin A1-9, [3H]dynorphin A1-8 and [3H]bremazocine as ligands. The sites labelled by the two dynorphins had identical, heterogeneous distributions in brain sections. High levels of kappa receptors were seen in striatum, claustrum, nucleus accumbens and laminae V and VI of the cerebral cortex. The substantia nigra and superior colliculus also had high dynorphin binding levels. The [3H]dynorphin autoradiographs were closely similar to those obtained using [3H]bremazocine in the presence of mu and delta receptor displacers. It is concluded that tritiated dynorphin A fragments can be used for autoradiographic studies of kappa opioid receptors in brain.

Animals↗
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↗
PubMed1988

Autoradiographic localization of delta opiate receptors in rat and human brain.

In vitro quantitative receptor autoradiography was performed on frozen sections of rat and human brain to visualize delta opiate receptors using the specific ligand [3H][D-Pen2, D-Pen5]enkephalin. For comparison, rat brain sections were also labelled with [3H]D-Ala2, D-Leu5-enkephalin. Compounds which block mu and kappa binding were included to make the [3H]D-Ala2, D-Leu5-enkephalin binding more specific. The two ligands had similar, but not identical, distributions in rat forebrain sections. Sites labelled with [3H][D-Pen2,D-Pen5]enkephalin were distributed heterogeneously within the layers of the frontal and parietal cerebral cortex, with high densities in the superficial and deep cortical layers. The claustrum and striatum had the most delta sites, whereas the globus pallidus had no delta binding. The distribution of [3H]D-Ala2,D-Leu5-enkephalin binding sites was similar to that of [3H][D-Pen2,D-Pen5]enkephalin, except that there was less heterogeneity in the frontal cortex. In the human brain regions studied, the highest delta binding was in caudate, putamen, temporal cortex and amygdala. There was less heterogeneity in the binding of [D-Pen2,D-Pen5]enkephalin in the human cortex than in the rat. No delta binding was seen in the medial and lateral segments of the globus pallidus. In both species, a discrepancy between the high enkephalin content of the globus pallidus and the absence of delta binding was apparent.

Animals↗
PubMed1987

Subtraction autoradiography of opiate receptor subtypes in human brain.

Opiate binding sites in sections of human brain were labelled with [3H]etorphine. Many brain areas contained high levels of [3H]etorphine binding sites although the globus pallidus was an exception. Subtraction autoradiography was performed using selective displacement of [3H]etorphine with opioid agonists to visualise mu-, delta- and kappa-opiate receptor subtypes. mu-Receptors were most abundant in the thalamus, caudate nucleus, putamen and the superficial layers of the cerebral cortex. Kappa receptors were concentrated in the deep layers of the cortex, the claustrum and the caudate nucleus. Human brain contained very few delta-receptors. Some brain areas with high concentrations of endogenous opioid peptides have many receptors, but in other areas, for example the globus pallidus, there is a mismatch between peptide concentration and receptor density.

Autoradiography↗
PubMed1987

Sodium dependent D-[3H]aspartate binding in cerebral cortex in patients with Alzheimer's and Parkinson's diseases.

The sodium dependent binding of D-[3H]aspartate to the high-affinity glutamate uptake system was used as a marker of glutamate-releasing terminals in the cerebral cortex of brains from patients with Alzheimer-type dementia (ATD) and Parkinson's disease (PD). Sodium-dependent D-[3H]aspartate binding was reduced in the ATD patients but not in the PD patients. Within the PD patients no association was observed between sodium-dependent D-[3H]aspartate binding and the presence of dementia. In contrast choline acetyltransferase activity was reduced in both the ATD and the PD patients. The present results suggest that changes in the cortical cholinergic system can occur independently of the cortical glutamate system. The glutamatergic deficit in ATD may contribute to some of the clinical differences between the dementia of ATD and PD.

Aged↗
PubMed1987

Autoradiographic analysis of [3H]kainic acid binding in primate brain.

The distribution of [3H]kainic acid binding sites was studied in the primate brain using semiquantitative autoradiography. The highest levels of binding were observed in the hippocampal area CA3 and the dentate gyrus. The deep layers of pyriform, cingulate and insular cortex, the central nucleus of the amygdala and the caudate nucleus also displayed high levels of [3H]kainic acid binding. Although these areas receive putative excitatory amino acid-containing afferents, other regions containing a similar input displayed low levels of binding. Some similarities were apparent between the distribution of binding sites and pathological changes in human neurodegenerative disorders such as temporal lobe epilepsy.

Animals↗
PubMed1987

Cortical neuropathological and neurochemical substrates of Alzheimer's and Parkinson's diseases.

Whilst the neuropathological correlates of Alzheimer type dementia--cortical neurofibrillary tangles and senile plaques--are well defined, the prevalence of these cortical abnormalities in Parkinson's disease and their relation to dementia is unclear. In a series of 46 consecutive cases of clinically and pathologically established Parkinson's disease the prevalence of mild Alzheimer-type pathology (exceeding the normal but not as extensive as in Alzheimer's disease) was increased 2 to 3 fold compared with an age-matched control group, although there was no obvious relation to the presence or severity of dementia. In a subgroup of Parkinsonian cases (both demented and non-demented), examined neurochemically, there were both similarities (decreased choline acetyltransferase, nicotinic and serotonergic S 1 receptor activities) and distinctions (increased muscarinic receptor binding--particularly to the "L" subtype, and normal serotonergic S 2, somatostatin, and D-aspartate binding together with normal levels of an endogenous nicotine binding inhibitor) compared with a group of cases with Alzheimer's disease. Amongst the various pathological and chemical indices examined, only presynaptic cholinergic markers (including the number of Meynert neurons) and S 1 receptor binding were related to dementia in Parkinson's disease. It is suggested that whilst coincidental classical Alzheimer's disease is infrequent in Parkinson's disease (5% in the present series) Alzheimer's disease itself is distinguished from Parkinson's disease by the formation of numerous neocortical neurofibrillary tangles and a reduction in glutamate uptake, serotonergic S 2 receptors and possibly in endogenous nicotine binding inhibitor.

Adult↗
PubMed1986

Autoradiographic analysis of D-[3H]aspartate binding in human basal ganglia.

The binding of D-[3H]aspartate to sections of human basal ganglia was measured autoradiographically. Highest binding was observed in the cerebral cortex, nucleus accumbens, caudate nucleus and putamen. The level of binding in the globus pallidus was low. D-[3H]Aspartate binding had a similar distribution to the high-affinity [3H]glutamate uptake sites and may be a useful marker for glutamate-aspartate terminals in human brain.

Aged↗
PubMed1986

Reduced high-affinity glutamate uptake sites in the brains of patients with Huntington's disease.

The binding of D-[3H]aspartic acid to the high-affinity glutamate uptake system was studied in membrane preparations of postmortem brains from controls and Huntington's disease (HD) subjects. The groups were matched for age and postmortem delay. A large (60-72%) and significant reduction in D-[3H]aspartate binding was observed in both the caudate nucleus and putamen, but not in the frontal cortex of the HD brains. The loss of striatal D-[3H]aspartate binding may reflect a loss of the high-affinity glutamate uptake system contained on the terminals of corticostriatal afferents. In contrast, the binding of [3H]paroxetine to the serotonin uptake system was marginally increased in the caudate nucleus and unchanged in the putamen. It is suggested that the reduction of high-affinity glutamate uptake sites may contribute to the production of the striatal lesion in HD.

Aged↗
PubMed1986

The association of [3H]D-aspartate binding and high-affinity glutamate uptake in the human brain.

The binding of [3H]D-aspartate ([3H]D-Asp) to human cerebellum homogenate was compared with the uptake of [3H]glutamate ([3H]Glu) by homogenates prepared from rapidly frozen human cerebral cortex. There was a close correlation between the potencies of a range of drugs for inhibiting the binding of [3H]D-Asp and the uptake of [3H]L-Glu. Compounds selective for postsynaptic Glu receptors were inactive. The findings are consistent with the labelling of high-affinity Glu uptake sites by [3H]D-Asp, which may be a valuable ligand for studying excitatory amino acid terminals in human brain.

Aspartic Acid↗
PubMed1986

Neural mechanisms mediating 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced parkinsonism in the monkey: relative contributions of the striatopallidal and striatonigral pathways as suggested by 2-deoxyglucose uptake.

The neural mechanisms which mediate parkinsonian symptoms have been investigated in the monkey by application of the 2-deoxyglucose (2-DG) metabolic mapping technique to animals rendered parkinsonian by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results show that 2-DG uptake was dramatically increased in the globus pallidus, but not the substantia nigra pars reticulata, in parkinsonian monkeys compared to controls. This observation has been interpreted as indicating increased synaptic activity in the putaminopallidal, but not the caudatonigral, pathway which suggests a relatively greater involvement of the putaminopallidal pathway in relation to the motor manifestations of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Autoradiographic distribution of dynorphin1-9 binding sites in primate brain.

The autoradiographic distribution of kappa opioid binding sites was evaluated in sections of monkey brain using the selective ligand [3H]dynorphin1-9. Kappa receptors were highly concentrated in the deep layers of the cerebral cortex, the substantia nigra, the hippocampus and the dentate gyrus. Lower levels were seen in the outer cortical layers, the caudate nucleus, the claustrum, parts of the amygdala and the cerebellum. These data are discussed in relation to the distribution in brain of the endogenous kappa-ligand.

Animals↗
PubMed1986

A re-evaluation of the pour plate blood culture method for the detection of Candida and other septicaemias.

Over a 1-year period the use of a pour plate in detecting significant septicaemias due to bacteria and fungi was evaluated and compared with a conventional broth blood culture system. Of 207 significant bacterial blood culture isolates only 113 (56%) were detected by the pour plate. However, three out of four candidaemias were detected by the pour plate method alone. Despite its low positivity rate, the pour plate is cheap and allows for early detection of bacteraemia and candidaemia.

Bacteria, Aerobic↗
PubMed1986

Influence of inhibitor binding on the internal motions of lysozyme.

Time-resolved laser-induced fluorescence depolarization measurements of internal motions in lysozyme are presented. The fluorescent dye eosin binds in a one-to-one complex with the enzyme, and is used both to measure the overall tumbling time constants and to probe the motions of residues in the region of binding. The precision and accuracy of the present method for determining the overall tumbling time constants compare favorably with those from other methods used in the literature. The extent of the internal motions, as described by a model independent order parameter, S2, is temperature dependent, and changes when the inhibitor N,N',N"-triacetylchitotriose, (GlcNAc)3, is bound to the active site of the enzyme. The observed temperature dependence and changes in S2 upon binding of (GlcNAc)3 are interpreted in terms of a nonharmonic model of the effective potential that is consistent with the picture of concerted motions in the protein. The values of the parameters of the potential that reproduce the data with and without the bound inhibitor imply that (GlcNAc)3 binding causes an increase in the rigidity of the protein, which agree qualitatively with other results on the lysozyme-(GlcNAc)3 system.

Kinetics↗