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Biomedical subjects

R M Hall

Publications and source records attributed to R M Hall.

At least 109 records · Page 6Linked to original sources

Variation in nucleotide sequences coding for the N-terminal regions of the matrix and nonstructural proteins of influenza A viruses.

Nucleotide sequences have been determined for complementary DNA transcribed from the 3' ends of RNA segments 7 (matrix gene) and 8 (nonstructural gene) from a number of human influenza A viruses isolated over a period of 43 years and representing H0N1, H1N1, H2N2, and H3N2 subtypes. The pattern of nucleotide variation in both genes suggests that RNA segments 7 and 8 were conserved during the reassortment events which were responsible for the antigenic shifts H1N1 leads to H2N2 and H2N2 leads to H3N2. During the 23-year period between the isolation of A/PR/8/34(H0N1) and A/RI/5-/57(H2N2), substitutions have occurred at 7 of 230 nucleotides in RNA segment 7 and 13 of 220 nucleotides in RNA segment 8, and in 20 years A/RI/5-/57(H2N2) to A/Canberra Grammar/77(H3N2) substitutions have occurred at 5 of 230 nucleotides in RNA segment 7 and 12 of 220 nucleotides in RNA segment 8. These give rise to 2 of 67, 5 of 64, 1 of 67, and 5 of 64 amino acid changes, respectively. The number of nucleotide and amino acid changes observed is of the same order of magnitude as that which occurs over a comparable period of drift in RNA segments 4 and 6, which code for the variable antigenic determinants hemagglutinin and neuraminidase.

Antigens, Viral↗

High tracheal bifurcation.

A case study is reported, outlining abnormal tracheobronchial anatomy in an adult male presented for thoractomy. The anesthetic technique is described. Ureteric catheters were used as introducers for the selective intubation of each main bronchus. The problems encountered postoperatively are also discussed.

Anesthesia, General↗

Enflurane today.

Explore the source record for details and available documents.

Anesthesia, Inhalation↗

The action of structural analogues of ethidium bromide on the mitochondrial genome of yeast.

We have studied the effects on the yeast mitochondrial genome of four analogues of ethidium bromide, in which the phenyl moieyt has been replaced by linear alkyl chains of lengths varying from seven to fifteen carbon atoms. These analogues are more efficient than ethidium bromide in inducing petite mutants in Saccharomyces cervisiae. The drugs also cause a loss of mtDNA from the cells in vivo; however these analogues are in fact less effective inhibitors of mitochondrial DNA replication per se, as shown by direct in vitro studies. It is concluded that these analogues are more efficient than ethidium bromide in causing the fragmentation of mitochondrial DNA in S. cervisiae.

DNA, Mitochondrial↗

Replicative deoxyribonucleic acid synthesis in isolated mitochondria from Saccharomyces cerevisiae.

The characteristics of a system for the in vitro synthesis of mitochondrial deoxyribonucleic acid (mtDNA) in mitochondria isolated from Saccharomyces cerevisiae are described. In this system the exclusive product of the reaction is mtDNA. Under optimal conditions the initial rate of synthesis is close to the calculated in vivo rate; the rate is approximately linear for 20 min but then decreases gradually with time. DNA synthesis proceeds for at least 60 min and the de novo synthesis of an amount of mtDNA equivalent to 15% of the mtDNA initially present is achieved. The rate and extent of synthesis observed with mitochondria isolated from grande and petite (rho(-)) strains were similar. The mode of DNA synthesis is semiconservative; after density labeling with 5-bromodeoxyuridine triphosphate, in vitro, the majority of labeled DNA fragments of duplex molecular weight, 6 x 10(6), are of a density close to that calculated for hybrid yeast mtDNA. The density label is incorporated into one strand of the duplex molecules. These properties indicate that the synthesis resembles replicative rather than repair synthesis. This system therefore provides a convenient method for the study of mtDNA synthesis in S. cerevisiae. The observation that mtDNA synthesis is semiconservative in vitro suggests that the dispersive mode of synthesis observed in S. cerevisiae in vivo labeling studies is the result of some other process, possibly a high recombination rate.

Adenosine Triphosphate↗

Biogenesis of mitochondria. XLII. Genetic analysis of the control of cellular mitochondrial DNA levels in Saccharomyces cerevisiae.

The proportion of total cell DNA which is mitochondrial DNA was measured in haploid, diploid and tetraploid strains of S. cerevisiae grown under a standard set of conditions. For all strains tested the mitochondrial DNA level was in the range 16%-25% of total cell DNA. Repeated measurements of the cellular level of mitochondrial DNA in two haploid strains showed that these strains have measurably different cellular mitochondrial DNA levels (17% and 24% of total DNA, respectively) under our conditions. These two grande strains were used to investigate the role of the mitochondrial and nuclear genomes in the regulation of the mitochondrial DNA level. We have shown by genetic analysis that the difference between these two strains is determined by at least two nuclear genes. The mitochondrial genome is not involved in the regulation of cellular mitochondrial DNA levels. A number of purified petite clones derived from independent spontaneous petite isolates of the grande strain which contained 24% mitochondrial DNA were also studied. The mitochondrial DNA levels in all but one of these petites fell in the range 20-25% of total cell DNA. From these results we conclude that, in general, the mitochondrial DNA level in petite strains is controlled by the same mechanism as operates in grande strains. We propose a general model for the control of the cellular mitochondrial DNA level, in which the amount of mitochondrial DNA per cell is determined by regulation of the number of mitochondrial DNA molecules per cell. This regulation is mediated through the availability of a set of nuclear coded components, possibly a mitochondrial membrane site, which are required for the replication of mitochondrial DNA.

Aneuploidy↗

Factors affecting petite induction and the recovery of respiratory competence in yeast cells exposed to ethidium bromide.

When growing cultures of S. cerevisiae are treated with high concentrations of ethidium bromide (greater than 50 mug/ml), three phases of petite induction may be observed: I. the majority of cells are rapidly converted to petite, II. subsequently a large proportion of cells recover the ability to form respiratory competent clones, and III. slow, irreversible conversion of all cells to petite. The extent of recovery of respiratory competence observed is dependent on the strain of S. cerevisiae employed and the temperature and the carbon source used in the growth medium. The effects of 100 mug/ml ethidium bromide are also produced by 10 mug/ml ethidium bromide in the presence of the detergent, sodium dodecyl sulphate, and recovery is also observed when cells are treated with 10 mug/ml ethidium bromide under starvation conditions. Genetic analysis of strain differences indicates that a number of nuclear genes influence petite induction by ethidium bromide. In one strain, S288C, petite induction by 100 mug/ml ethidium bromide is extremely slow under certain conditions. Mitochondria isolated from from S288C lack the ethidium bromide stimulated nuclease activity found in D243-4A, a strain which shows triphasic kinetics of petite formation. This enzyme may, therefore, be responsible for the initial phase of rapid petite formation.

Acriflavine↗

Biogenesis of mitochondria. 43. A comparative study of petite induction and inhibition of mitochondrial DNA replication in yeast by ethidium bromide and berenil.

The action of ethidium bromide and berenil on the mitochondrial genome of Saccharomyces cerevisiae has been compared in three types of study: (i) early kinetics (up to 4 h) of petite induction by the drugs in the presence or absence of sodium dodecyl sulphate; (ii) genetic consequences of long-term (8 cell generations) exposure to the drugs; (iii) inhibition of mitochondrial DNA replication, both in whole cells and in isolated mitochondria. The results have been interpreted as follows. Firstly, the early events in petite induction differ markedly for the two drugs, as indicated by differences in the short-term kinetics. After some stage a common pathway is apparently followed because the composition of the population of petite cells induced after long-term exposure are very similar for both ethidium bromide and berenil. Secondly, both drugs probably act at the same site to inhibit mitochondrial DNA replication, in view of the fact that a petite strain known to be resistant to ethidium bromide inhibition of mitochondrial DNA replication was found to have simultaneously acquired resistance to berenil. From consideration of the drug concentrations needed to inhibit mitochondrial DNA replication in vivo and in vitro it is suggested that in vivo permeability barriers impede the access of ethidium bromide to the site of inhibition of mitochondrial DNA replication, whilst access of berenil to this site is facilitated. The site at which the drugs act to inhibit mitochondrial DNA replication may be different from the site(s) involved in early petite induction. Binding of the drugs at the latter site(s) is considered to initiate a series of events leading to the fragmentation of yeast mitochondrial DNA and petite induction.

Amidines↗

Evidence for a functional association of DNA synthesis with the membrane in mitochondria of Saccharomyces cerevisiae.

We have studied the effect of membrane fatty acid composition on replicative DNA synthetic activity in mitochondria isolated from Saccharomyces cerevisiae. Cells containing different levels of membrane unsaturated fatty acids were obtained by growth of a fatty acid desaturase mutant of Saccharomyces cerevisiae in glucose-limited chemostat cultures supplemented with various concentrations of Tween 80. Arrhenius plots of DNA synthetic activity in isolated mitochondria show a discrete discontinuity at specific temperature which are dependent on the membrane unsaturated fatty acid content of the mitochondria. This indicates a functional association of DNA replication with the mitochondrial membrane in Saccharomyces cerevisiae.

Calorimetry↗

Genetic analyses of the polarity alleles in recombinants from mitochondrial genetic crosses.

A number of minority recombinant and parental types from a heterosexual cross were analyzed for the omega allele they carry. It was found that recombinant progeny can be omega(-), that minority parental types among the progeny can be omega(+) rather than omega(-), and, finally, that certain of the results suggest that the omega locus may not be at the proximal end of the mitochondrial genetic map (Bolotin et al., 1971; Grivell et al., 1973) but rather may lie between the [cap1-r/cap-s] and [ery1-r/ery-s] loci.

Alleles↗