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Biomedical subjects

C D Ward

Publications and source records attributed to C D Ward.

At least 55 records · Page 3Linked to original sources

Ribosomes from a relC mutant strain of Escherichia coli show altered activity with bacterial release factor-1.

Ribosomes from a relC mutant of Escherichia coli, JF505, are altered in the large subunit protein L11. This protein has abnormal mobility on gel electrophoresis. The ribosomes have a lowered specific activity for release factor-1 which is intermediate between that found for ribosomes containing normal L11 and that for L11 lacking ribosomes. JF505 ribosomes are as sensitive to inactivation of in vitro termination by thiostrepton as normal ribosomes when the antibiotic is added in dimethylsulphoxide but less sensitive when it is added in ethanol.

Escherichia coli↗

The ribosomal binding domain for the bacterial release factors RF-1, RF-2 and RF-3.

The Escherichia coli ribosomal proteins, L7/L12, are dominant over L11 in modulating the binding of RF-1 and RF-2 to ribosomes. The elevated activity of RF-2 on L11-lacking ribosomes over those containing L11 is abolished by IgG against L7/L12 or by removing the L7/L12 proteins. Adding back L7/L12 restores the original phenotype. The stimulatory factor, RF-3, is active on ribosomes depleted of L7/L12 but on those which lack L11 the stimulatory effects are less pronounced or often not seen. RF-3 cannot restore activity with RF-1 or RF-2 to ribosomes lacking both these sets of proteins. The stimulatory effects of an absence of either L11 or RF-3 on the activity of RF-2 are not additive or synergistic.

Binding Sites↗

Cloning of the Escherichia coli release factor 2 gene.

The protein release factor 2 (RF2) participates in Escherichia coli polypeptide chain termination with codon specificity (UAA or UGA). A colicin E1 recombinant identified in the Carbon and Clarke E. coli bank contains the protein release factor 2 gene. A 1.7-kilobase E. coli fragment has been subcloned into the plasmid pUC9 vector. Bacterial cells, containing the plasmid recombinant, produce elevated levels of protein release factor 2 as detected by an immune precipitation assay and in vitro measurement of UGA-directed peptide chain termination and [3H]UGA codon recognition.

Bacteriocin Plasmids↗

L-dopa decarboxylation in chronically treated patients.

We measured decarboxylation of oral L-dopa in patients chronically treated with L-dopa, and in untreated controls. Chronic L-dopa and carbidopa administration did not affect the extent of whole-body decarboxylation, and it is therefore unlikely that on-off fluctuations are related to chronic changes in the activity of L-aromatic amino acid decarboxylase. The observed duration of action and dose-response properties of carbidopa suggested that current empirically based dose schedules are optimal and supported the concept that decarboxylase inhibitors enhance the clinical effect of L-dopa largely by reducing the extent of first-pass metabolism rather than through an action on the decarboxylase enzyme in cerebral capillaries.

Adult↗

Parkinson's disease in 65 pairs of twins and in a set of quadruplets.

Among 43 monozygotic (MZ) and 19 dizygotic (DZ) pairs in which an index case had definite Parkinson's disease (PD), only one MZ pair was definitely concordant for PD. When pairs with questionable clinical features were included, 4 of 48 MZ and 1 of 19 DZ pairs were concordant. The frequency of PD in MZ cotwins of index cases with PD was similar to that expected in an unrelated control group matched for age and sex. Although we were unable to identify a single environmental agent, we conclude that the major factors in the etiology of PD are nongenetic.

Female↗

Olfactory impairment in Parkinson's disease.

In comparison with closely matched controls, patients with Parkinson's disease had reduced scores in tests of odor detection and qualitative discrimination. Olfactory impairment was not related to age, duration of symptoms, treatment, intellectual function, or genetic factors and seemed to be a nonmotor manifestation of the disease.

Adult↗

Comparison of pergolide and bromocriptine therapy in parkinsonism.

Twenty-four parkinsonian patients compared pergolide and bromocriptine therapy in a randomized double-blind, two-period crossover study. Both drugs were adjusted to an optimal balance between benefits and side effects. The mean daily dose and dose range for pergolide and bromocriptine were 3.3 mg (0.7 to 7.2) and 42.7 mg (5.8 to 87.5), respectively. Adjunctive medications, which for most patients included levodopa (plus carbidopa), were not altered during the study. A similar spectrum of clinical effects was found with both drugs and with lisuride, which was used to treat 13 of the patients in a previous study. Despite neurochemical differences in the antiparkinsonian ergots, their clinical utility is quite similar. We draw attention to hepatotoxicity and pleural reactions that may occur rarely with these drugs.

Aged↗

The Shine and Dalgarno hypothesis for termination: the 3' terminus of the 16S rRNA of the Escherichia coli ribosome can be modified or base-paired with a complementary oligonucleotide without affecting termination in vitro.

The occurrence of the nucleotides "...CCUUAOH" at the 3' terminus of the 16S rRNA of the small subunit of the Escherichia coli ribosome led to the suggestion that they may have a direct base pairing with the termination codon in the termination event of protein biosynthesis (Shine and Dalgarno 1974). We have examined this concept with two approaches, firstly using a 30S subunit whose 16S rRNA has been modified with a fluorescein moiety on the terminal adenosine together with the antibody against the moiety, and secondly with an oligonucleotide, UAAGG, complementary to the terminal pentanucleotide sequence of the rRNA. Collectively the data suggest that the nucleotides at the 3' terminus of 16S rRNA are not critically involved in base pairing during termination codon recognition.

Base Composition↗

Methods for evaluating treatment in Parkinson's disease.

Objective measurements of movement time, reaction time, and gait were compared with a clinical rating performed at the same times on several occasions in 10 patients with Parkinson's disease (PD). Positive correlations between objective measures and clinical evaluation were demonstrated. Movement time was the single most useful index of motor deficit, but no objective tests were more sensitive than clinical evaluations in the detection of motor disorder. It is concluded that there is at present no effective substitute for clinical procedures, although the convenience and future potential of objective measurement justify the further development of such systems for use in the experimental study of PD.

Adult↗

Lisuride versus bromocriptine treatment in Parkinson disease: a double-blind study.

Twenty-eight parkinsonian patients were studied in a double-blind, crossover comparison of lisuride and bromocriptine. All but two patients completed the study, with each drug adjusted to an optimal dose (mean daily intake of 4.5 mg for lisuride and 56.5 mg for bromocriptine). Treatment with each drug was given for 7 to 10 weeks; three assessments were made at biweekly intervals with optimal dose levels. Conventional antiparkinsonian medications, including levodopa, were not changed. Efficacy and adverse effects were assessed by objective and subjective techniques. The only significant difference was slightly better control of akinesia with bromocriptine. There was considerable variability in the optimal dose of each drug, though the clinical profile of lisuride was quite similar to that of bromocriptine.

Adult↗

Lisuride in parkinsonism.

We studied the actions of lisuride, a dopaminergic ergot derivative, in 20 parkinsonian patients. When the dose was increased gradually, most patients tolerated up to 5 mg daily. Clinical assessment and objective, computer-assisted evaluation revealed improvement in akinesia, rigidity and tremor. Adverse reactions were similar to those seen with levodopa and bromocriptine, but somnolence tended to occur more often with lisuride.

Adult↗

Long-term effects of repeated plasma exchange in myasthenia gravis.

Plasma exchange produces a short-term clinical improvement in myasthenia gravis (M.G.) which may be attributable to removal of acetylcholine receptor (AChR) antibody. The possibility that repeated plasma exchanges might confer cumulative long-term benefits was investigated. Serum-AChR-antibody and clinical response were followed for 4--12 months (mean 8 months) in six M.G. patients receiving 4--25 plasma exchanges of 2--4 1 together with immunosuppressive drugs (azathioprine [2.5 mg/kg] with or without alternate-day prednisone therapy), and in seven M.G. patients on immunosuppressive drugs alone. Percentage decrease in AChR antibody was not significantly different in the two treatment groups. Decline in antibody titre was associated with clinical improvement. Eight patients with previous thymoma showed significantly greater decline in antibody than the remaining five patients, irrespective of plasma exchange. Since repeated plasma exchange had no cumulative long-term benefit, the value of this treatment as used here lies only in short-term control of severe M.G. symptoms.

Acetylcholine↗

Treatment of myoclonus with pheneturide.

Twenty-one patients with various forms of myoclonus are presented. Phenacemide was given to five patients with considerable benefit to three, but with serious toxic effects in two. Another acetylurea derivative, pheneturide, was given to 19 patients and was well tolerated. Myoclonus was completely or substantially controlled in 12 patients.

Adolescent↗