PubMed Health⌕ Search

Biomedical subjects

C D Ward

Publications and source records attributed to C D Ward.

At least 19 recordsLinked to original sources
PubMed1992

Molecular cloning of the NP and L genes of simian virus 5: identification of highly conserved domains in paramyxovirus NP and L proteins.

We have molecularly cloned and determined the nucleotide sequence of the 3' and 5' regions of the genomic RNA of the paramyxovirus simian virus 5 (SV5), including the 3' leader sequence, nucleocapsid protein (NP) gene, large (L) protein gene, and 5' anti-genomic leader (trailer) sequence. The vRNA 3' proximal leader sequence contains 55 nucleotides. The NP gene is 1725 nucleotides in length and encodes a negatively charged protein consisting of 509 residues (MW 56,534). A comparison of the amino acid sequences of 10 paramyxovirus NP proteins indicates a region of high sequence identity near the middle of the protein, and a C-terminal region which is enriched in negatively charged residues. Overall, the SV5 NP protein showed the highest degree of sequence identity with the NP proteins of parainfluenza type 2 virus (58%) and mumps virus (56%). The L gene extends 6804 nucleotides and encodes a positively charged protein consisting of 2255 residues (MW 255,923). The 5' proximal region of the vRNA consists of a 31 nucleotide trailer RNA. The SV5 L protein sequence showed 62% overall identity with the parainfluenza type 2 L protein. Although little overall sequence identity was found between the SV5 and other paramyxovirus L protein sequences, short stretches of extensive amino acid identity were found near the middle of each of the known paramyxovirus L protein sequences, and these common regions may represent sites important for enzymatic activity.

Amino Acid Sequence↗
PubMed1992

Determination of the poliovirus RNA polymerase error frequency at eight sites in the viral genome.

The poliovirus RNA polymerase error frequency was measured in vivo at eight sites in the poliovirus genome. The frequency at which specific G residues in poliovirion RNA changed to another base during one round of viral RNA replication was determined. Poliovirion RNA uniformly labeled with 32Pi was hybridized to a synthetic DNA oligonucleotide that was complementary to a sequence in the viral genome that contained a single internal G residue. The nonhybridized viral RNA was digested with RNase T1, and the protected RNA oligonucleotide was purified by gel electrophoresis. The base substitution frequency at the internal G residue was measured by finding the fraction of this RNA oligonucleotide that was resistant to RNase T1 digestion. A mean value of 2.0 x 10(-3) +/- 1.2 x 10(-3) was obtained at two sites. A modification of the above procedure involved the use of 5'-end-labeled RNA oligonucleotides. The mean value of the error frequency determined at eight sites in the viral genome by using this technique was 4.1 x 10(-3) +/- 0.6 x 10(-3). Sequencing two of the RNase T1-resistant RNA oligonucleotides confirmed that the internal G was changed to a C, A, or U residue in most of these oligonucleotides. Thus, our results indicated that the polymerase had a high error frequency in vivo and that there was no significant variation in the values determined at the specific sites examined in this study.

Base Sequence↗
PubMed1992

Medical education and the challenge of neurological disability.

The neuroscience curriculum should take account of the needs of patients and families and both undergraduate and postgraduate education should be guided by three criteria for quality of medical care--clinical competence, communication (and teamwork), and professional values. The assessment and management of neurological disability requires specific knowledge, skills and attitudes which can be supported by medical education. Suggestions are given on some of the elements which might be included in a curriculum relevant to neurological disability. The implementation of appropriate programmes is discussed.

Clinical Competence↗
PubMed1989

Retrieval from semantic and letter-initial categories in patients with Parkinson's disease.

We report the impaired performance by a group of 27 patients with Parkinson's disease (vs matched controls) on semantic and letter-initial verbal fluency tasks, carried out in both single and alternating category conditions. Individual differences in fluency were significantly correlated with confrontation picture naming scores in the patient group, but not in control subjects. However, the PD patients showed no significant correlation between verbal fluency scores, and rate of reciting days of the week as rapidly as possible. Both controls and patients produced more items when retrieving words from a single category than when alternately retrieving words from two categories. The magnitude of the decrement was nonetheless no greater in the patient than in the control population. This finding shows that "task switching" per se is not impaired in PD. We suggest that the verbal fluency deficit, while it may in part be attributed to motor-speech factors, primarily reflects an underlying cognitive disorder.

Cues↗
PubMed1989

Observations during transient global amnesia. A behavioural and neuropsychological study of five cases.

The clinical and behavioural features of 5 patients examined during transient global amnesia (TGA) are described. All underwent extensive neuropsychological testing during and sequentially after the attack. Our results show that in TGA there is a characteristic neuropsychological deficit which parallels that in the permanent amnesic syndrome. Personality, complex cognition and problem solving, semantic knowledge, language and visuospatial function remained intact. Immediate memory was preserved. Longer-term verbal and nonverbal memory was severely disrupted in all cases. In contrast, the extent of retrograde amnesia was highly variable. A famous faces test showed an extensive deficit in 3 cases, with improvement in all cases following the attack. Analysis of group data confirmed the presence of a reversible temporal gradient, in that more distant memories were relatively spared. On a famous events test, recognition was normal across all decades, but dating of events from the 1960s and 1970s was consistently impaired. The Crovitz test of remote personal episodic memory was given to 3 subjects; all showed impaired uncued autobiographical memory and in contrast to normal controls, had a virtual absence of recent memories. During recovery from TGA there was progressive shrinkage of retrograde amnesia but a permanent short retrograde gap of around 1 h remained in all cases. Although subjectively normal within 24 h, all cases demonstrated persisting impairment of new learning for at least a week post-TGA. The relevance of the neuropsychological data to theories concerning the amnesic syndrome is discussed. We postulate a temporary deficit in retrieval of remote memories which appears to be dissociable from the anterograde amnesia.

Aged↗
PubMed1988

Direct measurement of the poliovirus RNA polymerase error frequency in vitro.

The fidelity of RNA replication by the poliovirus-RNA-dependent RNA polymerase was examined by copying homopolymeric RNA templates in vitro. The poliovirus RNA polymerase was extensively purified and used to copy poly(A), poly(C), or poly(I) templates with equimolar concentrations of noncomplementary and complementary ribonucleotides. The error frequency was expressed as the amount of a noncomplementary nucleotide incorporated divided by the total amount of complementary and noncomplementary nucleotide incorporated. The polymerase error frequencies were very high and ranged from 7 x 10(-4) to 5.4 x 10(-3), depending on the specific reaction conditions. There were no significant differences among the error frequencies obtained with different noncomplementary nucleotide substrates on a given template or between the values determined on two different templates for a specific noncomplementary substrate. The activity of the polymerase on poly(U) and poly(G) was too low to measure error frequencies on these templates. A fivefold increase in the error frequency was observed when the reaction conditions were changed from 3.0 mM Mg2+ (pH 7.0) to 7.0 mM Mg2+ (pH 8.0). This increase in the error frequency correlates with an eightfold increase in the elongation rate that was observed under the same conditions in a previous study.

Nucleotidases↗
PubMed1988

Transient feelings of compulsion caused by hemispheric lesions: three cases.

There was strong evidence of a neurological explanation for transient feelings of compulsion reported by three patients. In at least two cases the mechanism was epileptic. The frontal lobe was implicated in all three. A feeling of compulsion, divorced from action, has rarely if ever been reported in epilepsy or other neurological disorders.

Adult↗
PubMed1987

Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus.

A radioimmunoassay has been developed for the measurement in urine of retinol-binding protein (alpha 2-microglobulin) and used as an index of renal tubular function in adult Type 1 (insulin-dependent) diabetics and to define reference ranges in non-diabetic controls. There was a significantly greater excretion (P less than 0.001) of retinol-binding protein in the diabetic group compared to the controls in both overnight and daytime samples. There was a weak positive correlation with albumin excretion (r = 0.33; P less than 0.01) but no correlation with HbA1, duration of diabetes or arterial blood pressure. The results indicate that retinol-binding protein excretion may be increased in diabetic subjects without increased albumin excretion. The possibility therefore exists that renal tubular damage may occur early in diabetic nephropathy without apparent glomerular dysfunction.

Adolescent↗
PubMed1986

The ribosomal binding domain of the Escherichia coli release factors. Modification of tyrosine in the N-terminal domain of ribosomal protein L11 affects release factors 1 and 2 differentially.

Ribosomal protein L11 is one of only two ribosomal proteins significantly iodinated when Escherichia coli 50 S subunits are modified by immobilized lactoperoxidase, and the major target has been shown previously to be tyrosine at position 7 in the N-terminal domain. This modification reduces in vitro termination activity with release factor (RF)-1 by 70-90%, but RF-2 activity is less affected (30-50%). The loss of activity parallels incorporation of iodine into the subunit. The 50 S subunits from L11-lacking strains of bacteria have highly elevated activity with RF-2 and low activity with RF-1. The iodination does not affect RF-2 activity but reduces the RF-1 activity further. Ribosomal proteins, L2, L6, and L25, are significantly labeled in L11-lacking ribosomes in contrast to the control 50 S subunits. L11 has been modified in isolation and incorporated back efficiently into L11-lacking ribosomes. This L11, iodinated also predominantly at Tyr 7, is unable to restore RF-1 activity to L11-lacking ribosomes in contrast to mock-iodinated protein. These results suggest the involvement of the N terminus of L11 in the binding domain of the bacterial release factors and indicate that there are subtle differences in how the two factors interact with the ribosome.

Binding Sites↗
PubMed1986

Decision-making in refractory epilepsy: an analysis based on computer simulation.

A program developed to simulate management of patients with recurrent seizures was tested in 24 subjects, including 13 experienced neurologists. Identifiable errors included excessive reliance on plasma anticonvulsant levels, misinterpretation of random effects, inefficiency in selection of follow-up intervals, and undue reference to arbitrary data, such as the initial dose, in the selection of "optimum" drug dosage.

Carbamazepine↗
PubMed1986

A double-blind, cross-over, study of oral N-acetylcysteine in Sjögren's syndrome.

Twenty-six patients with primary or secondary Sjögren's syndrome were treated in a double-blind, cross-over trial for a four week period with oral N-Acetylcysteine and placebo. Before treatment there were significantly elevated salivary lactoferrin levels in the patients when compared to 51 healthy controls (p = 0.0005), and significantly decreased levels of tear lysozyme when compared to 24 controls (p = 0.0003). Salivary sodium, potassium, inorganic phosphate, amylase and immunoglobulin G, A or M levels were not significantly different from control values. After treatment with N-Acetylcysteine, Sjögren's syndrome patients reported improvements in ocular soreness (p = 0.004), ocular irritability (p = 0.006), halitosis (p = 0.033) and daytime thirst (p = 0.033). N-Acetylcysteine, but not placebo improved the van Bijsterveld score (p = 0.026), but neither agent improved the Schirmer test, the tear break up time or any of the laboratory tests. These results suggest that N-Acetylcysteine may have a true therapeutic effect on the ocular symptoms of Sjögren's syndrome and be worthy of a longer study.

Acetylcysteine↗