Biomedical subjects
Publications and source records attributed to C H Clarke.
In a phage T7-resistand and galactose-sensitive derivative of E. coli B/r trp- it has been possible to show that MFD for UV-induced mutations is specific for Trp+ reversions (mainly of an ochre suppressor-containing type) but is without effect on galactose-resistant or D-fucose-resistant (ara Cc) forward mutations.
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1 Effect of four antihistamines, chlorpheniramine (4 mg), clemastine (1 mg), promethazine (10 mg) and terfenadine (60 mg), on visuo-motor coordination and on subjective assessments of performance and well-being were compared with placebo in six healthy females from 0.5--7.0 h after morning ingestion of each drug. The study was double-blind, and the doses used were believed to be equally potent in their antihistaminic activity. 2 There was impaired performance 1.5 h (P less than 0.01) after chlorpheniramine, 3.0 h (P less than 0.05) and 5.0 h (P less than 0.01) after clemastine, and 3.0 h (P less than 0.01) and 5.0 h (P less than 0.001) after promethazine. It was not possible to establish effects on performance after ingestion of terfenadine. Subjective assessments of performance were not altered. 3 The subjects as a group reported improved alertness (P less than 0.05) and improved wakefulness (P less than 0.05) 0.5 h and 3.5 h respectively after ingestion of terfenadine, and were less energetic (P less than 0.05) 7.0 h after ingestion of chlorpheniramine. There were not other consistent changes in assessments of well-being.
In E. coli strain 91P containing the mutator gene mutT-, caffeine, spermine and quinacrine, but not guanosine, act as antimutagens, reducing the frequencies of mutation from ara- leads to Ara.
1 The effect of the 1,5-benzodiazepines, clobazam (10 and 20 mg) and triflubazam (20 and 40 mg), on sleep was studied in six healthy males using electroencephalography for sleep measures and analogue scales for subjective assessments of well being and sleep quality. The effect of clobazam was limited to the night of ingestion. There was some evidence from subjective assessments that the effect of triflubazam may have persisted beyond the night of ingestion. 2 No effect of clobazam or triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep. With clobazam sleep onset latency was shortened (P less than 0.05), but this effect was not seen with triflubazam. The latency to stage 3 was shortened by both drugs. There was evidence of reduced duration of awake (stage 0) activity and drowsy (stage 1) sleep with both drugs. 3 The percentage stage 1 sleep was reduced by clobazam (10 and 20 mg) and by triflubazam (20 mg) (P less than 0.05), though the effect was not significant with triflubazam (40 mg). Clobazam (20 mg) increased the percentage stage 2 sleep (P less than 0.05), but reduced the percentage stage 3 (P less than 0.01) and stages 3 + 4 (P less than 0.05) sleep. There were no other effects on percentage of total sleep time occupied by various sleep stages or in duration (min) of sleep stages, except that the duration (min) of sleep stages, except that the duration (min) of stage 2 sleep in the second 2 h interval of sleep was increased with clobazam (20 mg) (P less than 0.01). 4 Subjects reported impaired sleep with triflubazam (40 mg) (P less than 0.05), and a sense of less wakefulness the morning after ingestion of clobazam (10 and 20 mg) (P less than 0.01) and triflubazam (40 mg) (P less than 0.05).
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In this review we outline the various factors which may contribute to the non-randomness of intragenic mutational spectra and the occurrence of hot spots. These factors include sample size limitation, particularly for sites of low mutability, and possible regions of low recombination potential. In addition, the nature of the gene product places great restraint on the detectability of either frameshift and premature chain-terminating mutations on one hand, or of the majority of missense mutations on the other. The nature of the Genetic Code itself also limits the mutational spectrum in so far as specific base pair substitutions lead only to a limited number of detectable amino acid replacements. Mutational hot spots may be a special example of the influence of neighbouring base pairs in the mutability of any given base pair. This is apparently true for frameshift mutations which tend to occur in runs of repeated base pairs or base pair doublets. Neighbouring base effects could operate not only at the level of initial reactivity with a mutagen, but also subsequently at the levels of DNA repair, recombination or replication. In some cases rare or modified bases may be responsible for neighbour effects. We suggest specific experimental approaches which seem likely to aid in the elucidation of these problems.
UV irradiation of the aerial spores of Streptomyces coelicolor pro arg hom cys strain A677 causes the induction of Arg+ and Cys+ revertants. Both phenotypic classes of revertants are induced according to approximately dose-squared kinetics. Some 30% of the induced Cys+ revertants were shown by direct genetic tests to be due to suppressor mutations. Indirect evidence, based on the fact that a high proportion of the UV-induced Arg+ revertants were also simultaneously Hom+, indicates that suppressors are probably also responsible for the Arg+ phenotype of many revertants.
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1 The effect of N-desmethyldiazepam (nordiazepam, 5 and 10 mg) and potassium clorazepate (15 mg, a precursor of nordiazepam) on sleep was studied in six healthy adult males. Electroencephalography (EEG) was used for sleep measures, and analogue scales were used for subjective assessments of well-being and sleep quality. 2 Effects on total sleep time were limited to the night of ingestion. There were increases with nordiazepam (5 and 10 mg) (P = 0.05) and 0.001 respectively), and with clorazepate (15 mg) (P = 0.01). Sleep onset latencies were shortened, particularly with nordiazepam, and awakening to stage 0 activity was reduced, by both drugs. The latency to stage 3 was reduced by nordiazepam (5 and 10 mg) (P = 0.05). 3 There were no effects of nordiazepam (5 mg) on the duration (min) of sleep stages. Nordiazepam (10 mg) and clorazepate (15 mg) reduced the duration of stage 0 and stage 1, and there were increases in stage 2. Reduced stage 1 and increased stage 2 sleep were observed during the recovery night. No effects were observed with stage 3, but there was evidence that stage 4 activity was depressed on the recovery night only. No effects were observed on REM sleep, except that the appearnace of the first REM period was delayed with clorazepate (15 mg) P = 0.01). The effect of nordiazepam (10 mg) and clorazepate (15 mg) were comparable, and each modified sleep for about 28-30 h after ingestion. 4 With nordiazepam (10 mg) and clorazepate (15 mg) the subjects, as a group, reported improved sleep, but subjective assessments of well-being were not altered. Correlations were calculated for sleep measures and subjective assessments.
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