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M Oram

Publications and source records attributed to M Oram.

27 records · Page 2Linked to original sources
PubMed1990

DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli.

The gyrA genes isolated from three ciprofloxacin-resistant clinical isolates of Staphylococcus aureus carried codon 84 (serine----leucine) and/or codon 85 (serine----proline) mutations that were absent in pretreatment susceptible strains. These substitutions occur in a region of the gyrase A protein wherein directly analogous mutations of serine 83----leucine and alanine 84----proline in Escherichia coli confer quinolone resistance. Thus, DNA gyrase A subunit mutations are implicated in resistance to ciprofloxacin in S. aureus.

Amino Acid Sequence↗
PubMed1990

DNA cloning and organization of the Staphylococcus aureus gyrA and gyrB genes: close homology among gyrase proteins and implications for 4-quinolone action and resistance.

Staphylococcus aureus gyrA and gyrB genes, which encode the DNA gyrase A and B proteins, have been isolated and found to map contiguously. DNA sequence analysis revealed close homology between the S. aureus gyrase subunits and their counterparts in Bacillus subtilis and Escherichia coli, including several conserved amino acid residues whose substitution in E. coli confers resistance to 4-quinolones. These results are discussed in regard to quinolone resistance mechanisms in S. aureus.

Amino Acid Sequence↗
PubMed1982

Metabolic oxidation of methaqualone in extensive and poor metabolisers of debrisoquine.

The metabolism of methaqualone to the glucuronides of 5 C-monohydroxy metabolites and to the N-oxide has been studied in 2 groups of healthy young adults phenotyped as extensive and poor metabolisers of debrisoquine. No significant interphenotype differences were observed with respect to the excretion of any of the 6 metabolites. It is probable that the genetic regulation of the pathways leading to these metabolites is at a locus other than that which is responsible for the regulation of the oxidation of debrisoquine, guanoxan, phenacetin, phenytoin and sparteine.

Adult↗
PubMed1982

The influence of the menstrual cycle on the metabolism and clearance of methaqualone.

1 The rate of methaqualone metabolism in women was shown to be significantly increased at the time of ovulation. 2 The apparent first order rate constants for the formation of five C-monohydroxy metabolites of methaqualone on day 15 of the menstrual cycle were approximately double that on day 1. 3 The N-oxidation of methaqualone showed considerable inter-individual variation in its sensitivity to the menstrual cycle, and in a group of ten women the difference in N-oxide excretion between days 1 and 15 was not statistically significant. 4 The serum clearance of methaqualone on day 15 was higher (mean value 94.6 ml min-1 on day 1, 176.0 ml min-1 on day 15), serum half-life shorter (mean t1/2 beta 16.3 h on day 1, 11.6 h on day 15) and the AUC alpha smaller (mean value 44.0 micrograms ml-1 h on day 1, 24.4 micrograms ml-1 h on day 15) than on day 1. 5 The relative importance of the five hydroxy metabolites was unchanged during the menstrual cycle but the C/N oxidation ratio was greater on day 15 than on day 1. 6 The data for methaqualone metabolism in a control group of men was similar to than in women on day 1 of a menstrual cycle.

Adult↗
PubMed1982

The influence of oral contraceptives on the metabolism of methaqualone in man.

1 Oral contraceptives were shown to suppress the mid-cycle increase in methaqualone metabolism observed in premenopausal women not receiving oral contraceptive therapy. No women were identified in whom this suppression was not observed. 2 Combined oestrogen-progestogen contraceptives produced the effect in all nine women studied. The effect was also observed in one woman who was receiving progestogen-only contraceptives. 3 The effect of the combined contraceptives was observed within one month of the commencement of the contraceptive therapy. 4 The results emphasise the need to monitor the effect of the menstrual cycle in women not receiving oral contraceptive therapy when the effects of such therapy is studied. 5 These effects are more likely to be the consequence of an inhibition of hormonal control of hepatic metabolic activity by the synthetic steroids than they are to simple inhibition of hepatic metabolism.

Adult↗
PubMed1981

The kinetics of the urinary excretion of the N-oxide and glucuronides of methaqualone in man.

The urinary excretion of the N-oxide and the glucuronides of five C-monohydroxy metabolites of methaqualone has been studied following the oral administration of a single dose of the drug. The apparent first order rate constants for the excretion of each metabolite (kme) were shown to be numerically smaller than the overall elimination rate constant for methaqualone (k10). The Kme values tended to be greater than or equal to the corresponding apparent first order rate constants for the formation of the metabolite (km) but corresponding kme and km values were always of the same order magnitude. The kme values for the glucuronides were much smaller than the literature kme value for paracetemol glucuronide. The rate of renal elimination of the metabolites was variably sensitive to urine flow but over a period of time of 8 hours or greater the total amount of metabolite recovered in the urine was was independent of the total urine volume.

Adult↗
PubMedDate not supplied

The effect of age on the competitive C- and N-oxidative pathways of methaqualone in women.

The urinary excretion of the N-oxide and the glucuronides of five C-monohydroxy metabolizes of methaqualone has been studied in a group of young women aged 24-34 years and in a group of elderly women aged 85-87 years. The rate of appearance of the metabolites in the urine was slower in the elderly group but the relative importance of the six metabolites was the same in the two groups. There were differences in some metabolite ratios between the two groups, but only one difference approached statistical significance. The metabolite excretion in a 80 year old woman who had received methaqualone daily for over ten years was consistent with that of the elderly group. The results indicate that the ageing process per se and chronic weak hepatic enzyme induction in the elderly are not accompanied by changes in the relative importance of competitive metabolic pathways.

Adult↗