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R C Roberts

Publications and source records attributed to R C Roberts.

At least 37 records · Page 2Linked to original sources
PubMed1997

Benzodiazepine receptors in the post-mortem brain of suicide victims and schizophrenic subjects.

To examine the role of benzodiazepine (BZ) receptors in suicide and schizophrenia, we determined BZ receptors in post-mortem brain (Brodmann's area 10) obtained from suicide victims, schizophrenic patients, and control subjects using [3H]RO15-1788 as the radioligand. The maximum number of binding sites (Bmax) of BZ receptors in the cortex of suicide victims was significantly higher compared with controls, but this increase was mainly due to those suicide victims who died by violent means and whose Bmax was significantly higher than of those who died by non-violent means or control subjects. In schizophrenic patients, Bmax was not significantly different from that of control subjects. When the schizophrenic subjects were separated into two groups, those on neuroleptics and those off neuroleptics for at least 12 months, however, the mean Bmax of BZ receptors in the prefrontal cortex in post-mortem brain obtained from schizophrenic patients on neuroleptics was significantly lower than Bmax in drug-free schizophrenic patients or normal controls. There were no significant differences among groups in values of the apparent dissociation constant (KD) of [3H]RO15-1788 binding. These results suggest that BZ receptors are up-regulated in the cortex of suicide victims, specifically those who used violent means, and that neuroleptic treatment may result in decreased central BZ receptor binding in the cortex of schizophrenic patients. Thus, the method of suicide and previous exposure to neuroleptics should be considered in the interpretation of data on BZ receptors.

Adult↗
PubMed1997

Protein kinase C in the postmortem brain of teenage suicide victims.

Increased serotonin2A (5-HT2A) receptors have been reported in the postmortem brain of suicide victims. To examine if this increase is associated with the dysregulation of postreceptor sites in the signaling cascade, we determined [3H]phorbol dibutyrate (PDBU) binding to protein kinase C (PKC) in postmortem brain samples (Brodmann's areas 8 and 9) obtained from teenage suicide victims and control subjects. [3H]PDBU binding to PKC was determined in membranal and cytosolic fractions. We observed that Bmax of [3H]PDBU binding sites was significantly decreased in both membranal and cytosolic fractions in brain samples from Brodmann's areas 8-9 compared to matched controls. These results thus suggest that PKC may play a role in the pathophysiology of suicidal behavior.

Adolescent↗
PubMed1997

The effect of chronic haloperidol treatment on dendritic spines in the rat striatum.

Previous studies have shown that schizophrenics, in comparison to controls, have reduced cortical spine density and smaller striatal spines. The current study in the rat was conducted to determine whether such differences could result from chronic neuroleptic treatment and whether they are correlated with neuroleptic-induced oral dyskinesias. Rats administered 1.5 mg/kg/day of haloperidol (HA) (n = 28) or water (n = 10) were tested for vacuous chewing movements (VCMs). After 6 months, rats were divided into low and high VCM groups; all but seven high VCM rats were sacrificed. These rats (withdrawn group) were withdrawn from HA for 4 weeks. Random electron micrographs of the striatum were analyzed for spine changes. Spine size was not significantly affected by HA (0.193 vs 0.174 microm2, HA and control, respectively) nor correlated with oral dyskinesias (0.191 vs 0.196 microm2, low and high VCM groups, respectively). These results suggest that smaller spines in schizophrenic striatum may be correlated with the disease rather than caused by neuroleptic treatment. Spine density decreased in the HA-treated group (32.7 +/- 9.5) in comparison to controls (53.7 +/- 7.3, P < 0.001) and remained low in the withdrawn group (35.0 +/- 4.2, P < 0.01). Spine density also decreased in both the low (37.3 +/- 9.9, P < 0.01) and the high (28.0 +/- 7.0, P < 0.000) VCM groups in comparison to controls. However, there was no significant difference between high and low VCM groups, suggesting that decreased spine density is independent of oral dyskinesias. These results suggest that the decreased spine density observed in schizophrenic cortex may be a result of neuroleptic treatment.

Animals↗
PubMed1997

ERP repetition effects in indirect and direct tasks: effects of age and interitem lag.

Event-related potentials (ERPs) were recorded for visually presented words in young and older participants while they performed two tasks. In the indirect task, participants responded to occasional target words. Some of the nontarget words were repeated after a single intervening trial, and others were repeated after a mean of 10 trials. In the direct task participants responded to every item, discriminating between words presented for the first and the second times. Compared with ERPs to unrepeated words, those to words repeated in the indirect task after either lag were more positive in both participant groups. For the short lag, this effect was larger among the older participants. In the direct task, words repeated after either lag elicited a positive shift in the ERPs of the young participants. In the older participants, short lag repeats elicited a repetition effect, but smaller than the equivalent effect among the young participants. Long lag repeats failed to elicit a repetition effect in the direct task in the older participants. The findings show that word repetition in these tasks reflects the modulation of two ERP components, which differ in their sensitivity to age-related changes in memory function.

Adult↗
PubMed1997

Transcription of genes encoding DNA replication proteins is coincident with cell cycle control of DNA replication in Caulobacter crescentus.

DNA replication in the dimorphic bacterium Caulobacter crescentus is tightly linked to its developmental cell cycle. The initiation of chromosomal replication occurs concomitantly with the transition of the motile swarmer cell to the sessile stalked cell. To identify the signals responsible for the cell cycle control of DNA replication initiation, we have characterized a region of the C. crescentus chromosome containing genes that are all involved in DNA replication or recombination, including dnaN, recF, and gyrB. The essential dnaN gene encodes a homolog of the Escherichia coli beta subunit of DNA polymerase III. It is transcribed from three promoters; one is heat inducible, and the other two are induced at the transition from swarmer to stalked cell, coincident with the initiation of DNA replication. The single gyrB promoter is induced at the same time point in the cell cycle. These promoters, as well as those for several other genes encoding DNA replication proteins that are induced at the same time in the cell cycle, share two sequence motifs, suggesting that they represent a family whose transcription is coordinately regulated.

Amino Acid Sequence↗
PubMed1996

Synaptic organization of the human striatum: a postmortem ultrastructural study.

The goal of this study was to characterize the synaptic organization of the normal human adult striatum for comparison with other species and with the diseased human striatum. Samples of striatal tissue from the Maryland Brain Collection obtained at autopsy with postmortem intervals of less than 4 hours were prepared for electron microscopic analysis according to standard techniques. The caudate nucleus and the putamen were similar in terms of the proportions of synaptic subtypes, the lengths of synaptic subtypes, and the area of most types of axon terminals. The proportions of major striatal synaptic subdivisions, such as axospinous synapses (83.5%) and asymmetric synapses (77.5%), were similar to that of the monkey (82% and 77%, respectively) but slightly lower than found in the rat (90% and 89%, respectively). Interestingly, the proportion of synapses with perforated postsynaptic densities (23%), a type of synapse thought to represent synaptic plasticity, was much higher in humans than in rats (5-8%). The lengths of asymmetric synapses (0.697 micron) were significantly longer than that of symmetric synapses (0.423 microns), a relationship found in other mammals. Also, the areas of terminals forming asymmetric synapses (0.707 micron2) were larger than those forming symmetric synapses (0.401 micron2), also consistent with data from other species. The length of axospinous synapses (0.656 micron) and the area of the terminals forming them (0.611 micron2) were not significantly different from the length of axodendritic synapses (0.523 micron) or the area of terminals forming them (0.602 micron2). This study is the first quantitative study on synaptic organization in human postmortem striatum. The results indicate that the synaptic organization of the human striatum is similar, but not identical, to that of other mammalian species.

Adult↗
PubMed1996

D2-type dopamine receptors in postmortem human brain sections from normal and schizophrenic subjects.

The density of the presumed dopamine D4 receptor ([3H]YM-09151-2 minus [3H]raclopride), as well as the densities of the two ligands themselves were compared in various areas of cerebral tissue from normal versus schizophrenic subjects off or on antipsychotic drugs at the time of death. Using autoradiographic techniques, and analyzing various brain areas, no differences were found in the density of the D4 receptor, nor were differences found between the groups, in any brain region, in the amount of bound [3H]YM-09151-2 or [3H]raclopride. There were, therefore, no differences in the density of the D3-type receptors, including the D4 receptor, in normal and schizophrenic subjects off or on antipsychotic drugs at the time of death.

Adult↗
PubMed1996

Reduced striatal spine size in schizophrenia: a postmortem ultrastructural study.

Numerous studies using in vivo imaging or light microscopic analysis of autopsy specimens have found abnormalities in the striatum of schizophrenics. Striatal tissue from the Maryland Brain Collection with short postmortem intervals was used in the present study. Electron micrographs of striatal neuropil were digitized to determine the area of dendritic spines. Spines were similar in size in both the caudate and the putamen in normal individuals. The spines in tissue from schizophrenics were also similar in size between these two regions. However, striatal spines in schizophrenics were approximately 30% smaller than in controls (p < 0.05). Since the majority of synapses in the striatum are formed with spines, this change in the schizophrenic brain may represent aberrant synaptic conductance and/or efficacy.

Autopsy↗
PubMed1996

Identification of a Caulobacter crescentus operon encoding hrcA, involved in negatively regulating heat-inducible transcription, and the chaperone gene grpE.

In response to elevated temperature, both prokaryotic and eukaryotic cells increase expression of a small family of chaperones. The regulatory network that functions to control the transcription of the heat shock genes in bacteria includes unique structural motifs in the promoter region of these genes and the expression of alternate sigma factors. One of the conserved structural motifs, the inverted repeat CIRCE element, is found in the 5' region of many heat shock operons, including the Caulobacter crescentus groESL operon. We report the identification of another C. crescentus heat shock operon containing two genes, hrcA (hrc for heat shock regulation at CIRCE elements) and a grpE homolog. Disruption of the hrcA gene, homologs of which are also found upstream of grpE in other bacteria, increased transcription of the groESL operon, and this effect was dependent on the presence of an intact CIRCE element. This suggests a role for HrcA in negative regulation of heat shock gene expression. We identified a major promoter transcribing both hrcA and grpE and a minor promoter located within the hrcA coding sequence just upstream of grpE. Both promoters were heat shock inducible, with maximal expression 10 to 20 min after heat shock. Both promoters were also expressed constitutively throughout the cell cycle under physiological conditions. C. crescentus GrpE, shown to be essential for viability at low and high temperatures, complemented an Escherichia coli delta grpE strain in spite of significant differences in the N- and C-terminal regions of these two proteins, demonstrating functional conservation of this important stress protein.

Amino Acid Sequence↗
PubMed1995

D2-family receptor distribution in human postmortem tissue: an autoradiographic study.

The distribution throughout the normal human brain of the dopamine D2-family of receptors were investigated autoradiographically. Three ligands were used, [3H]-YM-09151-2 to define the D2, D3, D4 receptors; [3H]raclopride the D2 D3 receptors; and [3H](+)-7-OH-DPAT, in the presence of GTP, demonstrates D3 distribution. [3H]-YM-09151-2 and [3H]raclopride binding were highest in caudate (121 vs 130 fmol mg(-1)), putamen (96 vs 136 fmol mg(-1)), and nucleus accumbens (113 vs 120 fmol mg(-1)). [3H]-YM-09151-2 also displayed significant binding in several cortical areas (56-39 fmol mg(-1)) and hippocampus (27 fmol mg-1). [3H](+)-7-OH-DPAT was highest in the nucleus accumbens. Based upon the ligands properties it is inferred that D2 distribution is highest in putamen, caudate and nucleus accumbens; D3 in the nucleus accumbens; D4 receptor in cortical areas and hippocampus.

Adult↗
PubMed1995

Effects of suicide transport lesions of the striatopallidal or striatonigral pathways on striatal ultrastructure.

In the basal ganglia, centrally active suicide transport agents produce selective lesions of the striatopallidal and striatonigral pathways based on receptor binding and neuropeptide mRNA studies. Anatomical analyses indicate a selective, albeit modest, loss of projection neurons. In the present study, we sought to determine the ultrastructural sequelae in the striatum of suicide transport injections of the globus pallidus (GP) or substantia nigra (SN). Neostriata of adult rats were examined 10 days after lesions of the striatopallidal or striatonigral pathways with OX7-saporin or volkensin. Controls consisted of normal unoperated rats and animals injected into either target with ricin, a toxic lectin that is not transported in the central nervous system. Injections with OX7-saporin or volkensin into the GP or SN produced a decrease in striatal synaptic density of approximately 20%, relative to the contralateral side. Dark degenerating profiles, though very rare in the contralateral striata, were present throughout the neuropil in the ipsilateral striata. In animals with striatopallidal lesions, axospinous synapses of both the asymmetric and symmetric type were decreased in density, while the number of synapses formed with dendritic shafts was unaffected. In addition, the number of striatal mitochondrial profiles was decreased ipsilateral to the lesions. In animals with striatonigral lesions, the number of axospinous and axodendritic synapses of the asymmetric type was decreased ipsilateral to the lesions. Synaptic density and ultrastructural integrity remained unaffected in the striata of animals receiving ricin injections and in the contralateral striata of animals receiving OX7-saporin or volkensin injections. Our results, taken together with previous studies showing marked loss of receptors, uptake sites and mRNA, suggest that while most synapses are present and intact, the efficacy of synaptic transmission may be altered.

Animals↗
PubMed1995

Human platelet phenolsulfotransferases: cDNA cloning, stable expression in V79 cells and identification of a novel allelic variant of the phenol-sulfating form.

We have isolated cDNA clones encoding phenol- and monoamine-sulfating phenolsulfotransferases, using the reverse transcription-polymerase chain reaction method with human platelet mRNA as template. These cDNAs were stably expressed in the Chinese hamster fibroblast cell line V79 and their substrate specificities towards known sulfotransferase isoenzyme-selective compounds determined. The nucleotide and derived amino acid sequences of the monoamine-sulfating form were identical to those previously identified in human liver and brain, but the cDNA for the human platelet phenol-sulfating form we isolated contained 5 and 2 amino acid changes from the two previously published sequences from human liver and brain, suggesting that we have identified a new allelic variant of human phenol-sulfating phenolsulfotransferase.

Alleles↗
PubMed1995

Ultrastructural correlates of haloperidol-induced oral dyskinesias in rat striatum.

Neuroleptics given chronically to rats induce behavioral sequelae which mimic tardive dyskinesia in some respects. The intent of this study was to investigate the ultrastructural correlates of oral dyskinesias (vacuous chewing movements [VCMs]), induced by chronic haloperidol treatment. After 6 months of treatment, rats were divided into low or high VCM groups. Rats in the high VCM group were either sacrificed on drug or were withdrawn from drug for 4 weeks. Ultrastructural analyses of the striatum indicated that synaptic density: 1) was significantly decreased in both the low and high VCM groups compared to normal controls; 2) was more profoundly decreased in the high VCM group as compared to the low VCM group; and 3) recovered to normal following drug withdrawal. Compared to controls, the density of asymmetric synapses was reduced by a similar magnitude in both the low and high VCM groups, suggesting that this change is a result of haloperidol treatment and independent of VCMs. Conversely, the density of symmetric synapses was reduced compared to normal, only in the high VCM group, suggesting that this change is specifically related to the expression of VCMs. In addition, mitochondrial profiles were hypertrophied and less frequent in the high VCM group in comparison to controls; size, but not number, recovered following drug withdrawal. These results identify distinct ultrastructural correlates of chronic haloperidol treatment that are unique to rats that develop VCMs and suggest that these ultrastructural features may play a role in the pathophysiology of oral dyskinesias in rats.

Animals↗
PubMed1995

An investigation of hemispatial neglect using the Landmark Task.

The "Landmark Task" is designed to tease apart two major factors in determining line bisection errors in spatial neglect: one whose general nature is perceptual, the other whose nature is motor. On critical test trials, the subject is required to point to whichever end of a mid-transected line is judged as nearer to the transection. Seven out of eight neglect patients pointed consistently to the left end of such lines. Thus their misjudgments were made in the direction opposite to any putative "directional hypokinesia." One patient, however, pointed predominantly rightward on these test trials. Normal controls and unilateral stroke patients were also tested on the Landmark Task. Cueing of one end of a line led to a relative perceptual overestimation of that half of the line in all of these groups.

Aged↗
PubMed1995

Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine.

OBJECTIVE: The sulphation of the neurotransmitters dopamine and 5-hydroxytryptamine, and of the prototypical xenobiotic 4-nitrophenol, by phenolsulphotransferases was measured in platelet homogenates prepared from a group of migraine sufferers and a group of control subjects. RESULTS: The activity of the M form of phenolsulphotransferase, responsible for the sulphation of dopamine and 5-hydroxytryptamine was significantly reduced in the migraine population, by 28% with dopamine as substrate and by 20% with 5-hydroxytryptamine. The activity of the P form of the enzyme towards 4-nitrophenol was the same in both groups. We also report that the selective inhibition of P form phenolsulphotransferase by red wine is much more potent than previously thought, with a 2000-fold dilution of dealcoholised red wine having the ability to inhibit sulphation by this enzyme by 50%. CONCLUSION: Our findings suggest that a reduced capacity for sulphation and inactivation of biogenic amines and catecholamines may be related to susceptibility to migraine.

Adult↗