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V Lloyd

Publications and source records attributed to V Lloyd.

7 recordsLinked to original sources

Not just pretty eyes: Drosophila eye-colour mutations and lysosomal delivery.

Analysis of Drosophila eye-colour mutations has made seminal contributions to the fields of genetics and biochemistry. Recent findings suggest that a subset of eye-colour genes is crucial for vesicular transport of proteins to pigment granules, specialized lysosomes of eye-pigment cells. Thus, classical work describing more than 85 eye-colour mutations and their genetic interactions offers a remarkable, untapped resource for the genetic analysis of protein delivery to lysosomes.

Animals

A Markov model for the assembly of heterochromatic regions in position effect variegation.

Here we give a mathematical model for the assembly of heterochromatic regions at the heterochromatin-euchromatin interface in position effect variegation. This probabilistic model predicts the proportions of cells in which a gene is active in cells with one and two variegating chromosomes. The association of heterochromatic proteins to form remodeled chromatin following DNA replication is mainly described by accumulation independent conditional probabilities. These probabilities are conditional on the boundary of the sites to which the proteins can bind; they give the relative attractiveness of the sites to a protein complex chosen at random from a pool of available complexes. The number of complexes available is assumed to be limited and rates of reaction are implicitly modeled by the conditional probabilities. In general, these conditional probabilities are not known, however, they can be experimentally determined. By comparing double variegation situations to single variegation, this model shows that there may be an effect on the expression of reporter genes located near the interfaces due to different sites competing for heterochromatic proteins. In addition, this model suggests that in some cases the attractiveness of sites may change in the presence of other chemical species. Consequently, the model distinguishes between two sorts of data obtained from competition experiments using position effect variegation. The two sorts of data differ as to whether there is a change in the attractiveness of sites in addition to an effect from different sites competing for the same constituents of heterochromatin. Subject to the fact that some of its parameters are not known precisely, this model replicates data from several experiments and can give predictions in other cases.

Animals

Long-term antiarrhythmic therapy with acetylprocainamide.

Nineteen patients whose arrhythmias were initially suppressed with acetylprocainamide underwent long-term treatment with this drug. Eleven patients were still taking the drug at the end of 12 months. Drug withdrawal with substitution of a placebo caused an increase in ventricular premature beats. Thus, suppression of ventricular premature beats persisted for 1 year. The eight withdrawals from the study were due to death during the year (n = 6) or recurrence of arrhythmias. The deaths occurred in patients who were in New York Heart Association functional class II (one patient), III (three patients) and IV (two patients). Ventricular performance, assessed from systolic time intervals, improved with drug therapy and declined during drug withdrawal. Symptomatic effects were common, with seven patients requiring a reduction in dosage or discontinuation of therapy. Three patients treated for 3 years continued to show drug suppression of ventricular premature beats compared with the level during placebo substitution. Small amounts of procainamide were present in all patients because of in vivo deacetylation of acetylprocainamide. Many patients with good initial responses to this drug had recurrent arrhythmias during long-term therapy. For this reason, the usefulness of acetylprocainamide as an antiarrhythmic drug appears to be limited.

Acecainide

The clinical pharmacology and antiarrhythmic efficacy of acetylprocainamide in patients with arrhythmias.

The actions of acetylprocainamide, the major metabolite of procainamide in man, were studied in a placebo-controlled oral-dose-ranging trial in 16 persons with arrhythmias. The occurrences of arrhythmias decreased in 15 patients receiving acetylprocainamide and increased subsequently in 10 of 13 patients given placebo. The frequency of arrhythmias was reduced by more than 75 percent in nine patients. Antiarrhythmic effects were dependent on dose and serum drug concentrations, with levels of 10 to 24 microgram/ml observed in patients with a reduction of more than 70 percent in premature ventricular complexes. The ratio of preejection period to left ventricular ejection time decreased during therapy. Side effects of light-headedness, insomnia, nausea and diarrhea occurred in six patients at serum levels ranging from 11 to 22 microgram/ml. The serum half-life of acetylprocainamide lengthened from 7 to 21 hours as the creatinine clearance decreased from 105 to 35 ml/min. Acetylprocainamide has antiarrhythmic efficacy, but causes side effects in human beings. This compound appears to contribute to the effects of procainamide therapy and may be useful as an antiarrhythmic drug.

Acecainide