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Biomedical subjects

R C Roberts

Publications and source records attributed to R C Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differential effects of line length on bisection judgements in hemispatial neglect.

Recent studies have shown that certain symptoms of spatial neglect are co-determined by two major factors: one whose general nature is perceptual, the other whose nature is directional and/or motor. In the present study, patients whose neglect was classified as predominantly 'perceptual' or 'directional' through use of the Landmark task (Milner, Brechmann and Pagliarini, 1992) were asked to bisect lines ranging in length from 20 to only 2.5 cm. It was found that the one patient with predominantly directional neglect showed large rightward errors at all line lengths. In contrast, those with perceptual neglect made very small (usually leftward) errors on short lines. It is argued that it is essential to separate these different subtypes of neglect patient if we are to understand the causation of their behaviour in tasks such as line bisection.

Aged↗
PubMed1995

Different relative importances of the par operons and the effect of conjugal transfer on the maintenance of intact promiscuous plasmid RK2.

The par region of the broad-host-range, IncP alpha plasmid RK2 has been implicated as a stability determinant by its ability to enhance the maintenance of mini-RK2 plasmids or heterologous replicons in a growing population of host cells. The region consists of two operons: parCBA, which encodes a multimer resolution system, and parDE, which specifies a postsegregational response mechanism that is toxic to plasmidless segregants. To assess the importance of this region to the stable maintenance of the complete RK2 plasmid in different hosts, we used the vector-mediated excision (VEX) deletion system to specifically remove the entire par region or each operon separately from an otherwise intact RK2 plasmid carrying a lacZ marker. The par region was found to be important to stable maintenance of RK2lac (pRK2526) in Escherichia coli and five other gram-negative hosts (Agrobacterium tumefaciens, Azotobacter vinelandii, Acinetobacter calcoaceticus, Caulobacter crescentus, and Pseudomonas aeruginosa). However, the relative importance of the parCBA and parDE operons varied from host to host. Deletion of parDE had no effect on the maintenance of pRK2526 in A. calcoaceticus, but it severely reduced pRK2526 maintenance in A. vinelandii and resulted in significant instability in the other hosts. Deletion of parCBA did not alter pRK2526 stability in E. coli, A. tumefaciens, or A. vinelandii but severely reduced plasmid maintenance in A. calcoaceticus and P. aeruginosa. In the latter two hosts and C. crescentus, the delta parCBA mutant caused a notable reduction in growth rate in the absence of selection for the plasmid, indicating that instability resulting from the absence of parCBA may trigger the postsegregational response mediated by parDE. We also examined the effect of the conjugal transfer system on RK2 maintenance in E. coli. Transfer-defective traJ and traG mutants of pRK2526 were stably maintained in rapidly growing broth cultures. On solid medium, which should be optimal for IncP-mediated conjugation, colonies from cells containing the pRK2526 tra mutants displayed significant numbers of white (Lac-) sectors on X-Gal (5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside) plates, whereas sectors appeared rarely in colonies from tra+ plasmid-containing cells. Both the traJ and traG mutations further reduced the maintenance of the already unstable deltapar derivative. Thus, these experiments with defined mutations in an intact RK2 plasmid have revealed (i) that the par region allows RK2 to adapt to the different requirements for stable maintenance in various hosts and (ii) that conjugal transfer can contribute to the maintenance of RK2 in a growing population, particularly under conditions that are favorable to RK2 transfer.

Bacterial Proteins↗
PubMed1995

3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatum.

Glutamate, the major transmitter of the corticostriatal pathway, is present in abundance in the striatum. 3-Hydroxyanthranilic acid oxygenase (3HAO) is the biosynthetic enzyme for quinolinic acid, an endogenous agonist of the NMDA glutamate receptor subtype and a potent neurotoxin. In order to explore the anatomical basis of possible functional interactions between glutamate and quinolinic acid in the rat striatum, pre- and postembedding immunocytochemical methods were used to localize 3HAO immunoreactivity (-i) and glutamate-i at the electron microscopic level. In accordance with previous light microscopic and biochemical studies, 3HAO-i was detected exclusively in astrocytes throughout the striatum. Notably, 3HAO-i was present in fine-caliber glial processes that often surrounded or abutted synaptic profiles, both asymmetric and symmetric. Glutamate-i was heavily deposited (3-13-fold higher gold particle density than tissue average) in axon terminals forming asymmetric synapses with spines and, occasionally, dendrites. In contrast, terminals forming symmetric synapses, dendrites, neuronal somata, and glial cells contained significantly less labeling than terminals forming asymmetric synapses. In double-labeled material, 3HAO-i was observed in glial processes that partially surrounded or were adjacent to glutamate-labeled terminals forming asymmetric synapses. 3HAO-labeled glial processes were also adjacent to unlabeled terminals forming symmetric synapses. Since quinolinic acid is known to enter the extracellular compartment readily, these results suggest that astrocytic quinolinic acid may participate in the regulation of glutamatergic neurotransmission in the rat striatum.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1994

Immunocytochemical localization of the quinolinic acid synthesizing enzyme, 3-hydroxyanthranilic acid oxygenase, in the rat substantia nigra.

Quinolinic acid, an endogenous excitatory amino acid receptor agonist, may play a role in several brain diseases. In the present study, the immunocytochemical localization of 3-hydroxyanthranilic acid oxygenase (3HAO), the enzyme responsible for the synthesis of quinolinic acid, was examined in the adult rat substantia nigra at the light and electron microscopic levels. 3HAO-immunoreactivity was detected exclusively in astrocytes. Labeling was present in cell bodies and in fine glial processes, which frequently encircled capillaries and partially enveloped neuronal somata. Notably, 3HAO-labeled processes were in close contact with several types of synaptic profiles. Often, they partially engulfed asymmetric synapses, characteristic of excitatory neurotransmission. In addition, they were found in apposition to putative dopaminergic cell bodies. These data provide an anatomical basis for the idea that functional interactions may occur between glial processes which synthesize quinolinic acid, and synaptic profiles, many of which presumably utilize excitatory neurotransmitters.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1994

The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition associated with plasmid loss.

Recently, a 0.8 kb region of the broad-host-range plasmid RK2 has been shown to be sufficient to stabilize plasmids in a vector-independent, broad-host-range manner under some but not all growth conditions (Roberts, R. C. & Helinski, D. R. (1992). J. Bacteriol. 174, 8119-8132). This region encompasses the parDE operon, which encodes the small proteins ParD and ParE, both of which are required for the plasmid stabilization. This paper demonstrates that the 0.8 kb region encodes the capacity to inhibit cell growth of Escherichia coli, presumably of those bacteria that have lost plasmids carrying this stabilization region, and this inhibition appears to be associated with cell killing and bacterial cell filamentation. A good correlation was observed between the capacity of wild-type and mutated 0.8 kb regions to promote stable maintenance of a temperature-sensitive RK2 replicon plasmid and to inhibit bacterial cell division under specified medium conditions. The properties of the wild-type and mutant 0.8 kb regions further indicate that the ParE protein is responsible for the growth inhibition and the ParD protein neutralizes the toxic activity of the ParE protein. This is consistent with the finding that the presence of the parD gene in trans destabilizes a temperature-sensitive RK2 replicon carrying a copy of the functional 0.8 kb region. This destabilization appears to be the result of ParD protein-mediated suppression of growth inhibition, thus allowing survival of cells that have lost the temperature-sensitive plasmid. These observations indicate that the 0.8 kb sequence of RK2 encodes a growth inhibition function that is likely to play a role in the plasmid stabilization.

Bacterial Proteins↗
PubMed1994

Sulfation of endogenous compounds and xenobiotics--interactions and function in health and disease.

Sulfation is a major detoxication mechanism for endogenous compounds and xenobiotics performed by a family of sulfotransferase isoenzymes. Understanding the normal cellular functions of these different sulfotransferases and the way in which endogenous and exogenous factors are able to influence their activity and expression will provide us with the information necessary to develop novel therapeutic strategies for conditions where sulfation may be implicated. This concept is discussed and is illustrated by examples including adverse drug reactions, fetal development and cancer.

Amino Acid Sequence↗
PubMed1994

Word repetition effects on event-related potentials in healthy young and old subjects, and in patients with Alzheimer-type dementia.

Event-related potentials (ERPs) were recorded from 16 healthy young (mean age 21 years) and 16 healthy old subjects (mean age 64 years), and from 11 subjects with a diagnosis of Dementia of Alzheimer Type (DAT). The task requirement was to attend to a series of visually presented words so as to respond to occasional animal names. Non-animal names repeated after either a single or six intervening items. In the young subjects ERPs evoked by repeated words displayed a widespread, sustained positive-going shift relative to ERPs evoked by first presentations (the ERP repetition effect). This effect onset around 220 msec and did not differ as a function of inter-item lag. Other than for a delay in onset of approximately 80 msec, the ERP repetition effect in the healthy old group was in all respects equivalent to that of the young subjects. The ERP repetition effects in the DAT patients were statistically indistinguishable from those of an appropriately matched sub-set of the healthy old subjects. These results indicate that the ERP repetition effect remains robust in subjects in whom explicit memory has declined as a result of normal aging or DAT. Thus they suggest that the effect reflects processes independent of those underlying explicit memory, and that it may index a form of memory relatively unaffected by the pathology underlying DAT.

Adolescent↗
PubMed1994

Spatial bias in visually-guided reaching and bisection following right cerebral stroke.

Groups of patients with left or right unilateral cerebral stroke were tested for their ability to reach either toward a single visual target or midway between 2 targets. The tasks were performed both in free vision and in conditions preventing visual feedback from the hand. It was found that only the right CVA patients were inaccurate in reaching, and only when visual feedback was absent. This effect of right hemisphere lesions took the form of a rightward bias, present throughout the trajectory of the hand during the reach. It was present regardless of the hand used in reaching and whichever of the two tasks was performed, and was of a similar magnitude irrespective of target location. It is suggested that this rightward bias might reflect the 'premotor' effects that have been proposed to contribute to line-bisection errors in certain patients with visuospatial neglect.

Aged↗
PubMed1994

The cost of epilepsy in patients attending a specialist epilepsy service.

Epilepsy is a common disability, especially in young adults, and, as the costs to the community are likely to be high, estimates are required to plan health and community care. The neurological unit of Dundee Royal Infirmary provides an epilepsy clinic for the Tayside region (population 300,000) and in 1991 the records of over 303 patients were computerized using the Epicare system developed by Sanofi-Winthrop. It was calculated that the total state expenditure on care was 662,919 pounds (2188 pounds/head) in 1991. The direct health costs were obtained by reviewing database entries and medical records and were estimated to be 159,192 pounds (24%), including 77,171 pounds for drugs, 64,750 pounds for hospital care and 17,271 pounds for general practice consultations. The cost of welfare payments was 503,728 pounds/year (76%) (4419 pounds/recipient). The transfer payments to patients with epilepsy greatly exceed the costs of health care and any management strategy which improves the prospects for employment and independence of people with epilepsy is likely to produce significant fiscal benefits for both the individual and the state.

Adolescent↗
PubMed1994

Limb temperature and human tremors.

The changes in postural tremor of the hand produced by moderate cooling of the muscles of one forearm have been investigated in 16 normal subjects and in 16 patients with essential tremor. In both groups, cooling produced a profound long lasting decrease in tremor level of the ipsilateral hand. In normal subjects, although cooling reduced the tremor size, the EMG of the active muscle clearly increased. Warming the limb in normal subjects produced an increase in tremor level and decrease in EMG. Cooling or warming the limb did not, however, significantly change the peak frequency which was quite stable for each subject. The results of cooling were compared with a brief period of ischaemia, which also reduces tremor size. Local cooling may be a useful manoeuvre for patients with essential tremor, and for others who wish to reduce their tremor temporarily in order to improve dexterity.

Adult↗
PubMed1994

Correlations between dose, plasma concentrations, and antispastic action of tizanidine (Sirdalud).

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg's pendulum test. Blood samples, a clinical assessment of muscle tone by the Ashworth scale, and muscle strength by the British Medical Research Council scale were obtained concomitantly. Confirmatory analysis using the change in the relaxation index (R2 value) 1.5 hours after each treatment, showed a statistically significant (p = 0.0123) linear dose-response relation between single doses and antispastic action of tizanidine. Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0.014 and 0.004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually.

Adult↗
PubMed1994

Presynaptic inhibition of soleus Ia afferent terminals in Parkinson's disease.

The possible role of changes in presynaptic inhibition of muscle spindle primary afferent terminals in Parkinson's disease was investigated. The pathway from tibialis anterior Ia afferents to soleus Ia terminals was assessed in 20 patients with Parkinson's disease and in 17 age matched controls, both at rest and during maintenance of tonic plantar flexing torques about the ankle. At all torques less presynaptic inhibition was present in the patients with Parkinson's disease than in the controls. The difference was significant at rest (p < 0.03) and at 2 Nm (p < 0.05) but not at 5 Nm and 7 Nm torque. The amount of presynaptic inhibition did not change with torque in either group. The observed alteration in presynaptic inhibition in Parkinson's disease is likely to make only a small contribution to the rigidity and impaired movement control.

Afferent Pathways↗
PubMed1994

Pharmacokinetics and pharmacodynamics of tizanidine.

The relationship among tizanidine dose, plasma concentration, and antispastic action is linear in nature. Response to a given dose of this agent varies among patients, and determining the appropriate clinical dose requires individual titration.

Clonidine↗
PubMed1993

Characteristics and significance of DNA binding activity of plasmid stabilization protein ParD from the broad host-range plasmid RK2.

A region of the plasmid RK2 has been shown to stabilize plasmid replicons in a broad host-range manner. This region encodes two divergently transcribed operons: parCBA and parDE. The parCBA operon specifies a multimer resolution system, while the parDE operon alone is capable of stabilizing an RK2-derived minireplicon under defined growth conditions in several different Gram-negative bacteria. The observed autoregulation of the parDE operon is most likely the result of ParD protein binding within the PparDE region. The characteristics of ParD binding to this region and the role of such binding in plasmid stabilization were examined with purified ParD protein. The results indicate that the binding of a single dimer of ParD protein to the promoter region most likely blocks interaction of RNA polymerase holoenzyme with the promoter. DNase I protection experiments indicate that ParD binds to a discrete sequence of 48 base pairs in length. While the binding of ParD to PparDE is essential for proper regulation of expression of the ParD and ParE proteins in vivo, the analyses of binding properties of mutant ParD proteins suggest that binding to this region does not play a direct role in plasmid stabilization.

Amino Acid Sequence↗
PubMed1993

A selective lesion of striatonigral neurons decreases presynaptic binding of [3H]hemicholinium-3 to striatal interneurons.

We have used the suicide transport agent, volkensin, to produce selective lesions of striatal efferent neurons projecting to the substantia nigra in the rat. In order to evaluate potential trans-synaptic effects, we examined cholinergic interneurons intrinsic to the striatum following destruction of striatonigral projection neurons by nigral injection of volkensin. There was no change in the number of large interneurons identified either by Nissl stain or by immunocytochemistry for choline acetyltransferase, indicating that volkensin was not directly toxic to this group of neurons. However, [3H]hemicholinium-3 binding to the choline re-uptake site on the presynaptic cholinergic terminals decreased. No change in [3H]hemicholinium-3 binding was seen after destruction of dopaminergic afferents with 6-hydroxydopamine. Striatonigral afferents to the cholinergic interneurons contain substance P which has been shown to stimulate acetylcholine release. The decrease in [3H]hemicholinium-3 binding may reflect loss of this afferent input. However, striatonigral neurons are an efferent target of the cholinergic interneuron as well, and a presynaptic effect due to loss of target neurons also may contribute.

Animals↗
PubMed1993

The human phenolsulphotransferase polymorphism is determined by the level of expression of the enzyme protein.

We have examined the expression of platelet phenolsulphotransferase (PST) in 60 individuals. Using an antibody which recognizes both forms of PST present in man (P-PST and M-PST), we determined that the polymorphism of platelet P-PST activity is determined by the level of expression of the enzyme protein. The implications for susceptibility to adverse drug reactions and chemical carcinogenesis are discussed.

Arylsulfotransferase↗
PubMed1993

Common food additives are potent inhibitors of human liver 17 alpha-ethinyloestradiol and dopamine sulphotransferases.

Interactions between dietary xenobiotics, drugs and biologically active endogenous compounds are a potential source of idiosyncratic adverse pathology. We have examined the inhibition of the sulphation of a number of xenobiotics and endobiotics in human liver cytosol by 15 food additives and constituents. Sulphation of dehydroepiandrosterone was resistant to inhibition by all compounds tested; however, dopamine sulphotransferase (ST) activity was inhibited strongly by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine and vanillin. Sulphation of the xenobiotic steroid 17 alpha-ethinyloestradiol (EE2) was inhibited by vanillin, erythrosin B and octyl gallate. Of these compounds, only vanillin was found to be sulphated to a significant extent by both human liver and platelets, and vanillin was determined to be a substrate for the monoamine-sulphating isoenzyme of phenolsulphotransferase. Vanillin was found to inhibit 50% of liver EE2 ST activity (IC50) at a concentration of approximately 1.3 microM and the mode of inhibition was non-competitive. The implications of these results for the adverse side effects associated with food additives and oral contraceptives are discussed.

Arylsulfotransferase↗