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Biomedical subjects

A E Beezer

Publications and source records attributed to A E Beezer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Flow microcalorimetric assay of antibiotics--IV. Polymyxin B sulphate, neomycin sulphate, zinc bacitracin and their combinations with Escherichia coli suspended in buffer plus glucose medium.

Flow microcalorimetric assays for polymyxin B sulphate and neomycin sulphate have been developed using Escherichia coli as the test organism, suspended in a glucose plus buffer medium. These assays have a better reproducibility (relative standard deviations 3.2 and 2.0%, respectively), and require a shorter time (1 h including time required for preparation of the calorimeter) than do conventional microbiological assays, but are not as sensitive. It is suggested that a screening programme might produce a small group of more suitable (i.e. more sensitive) test organisms, which could be used to develop rapid and reproducible flow microcalorimetric assays for a wide range of antibiotics by the procedure described. The effect of combinations of polymyxin B sulphate, neomycin sulphate and zinc bacitracin (the antibiotic components of the commercial preparation Trisep, ICI, Macclesfield, UK) on the power output of cells suspended in glucose plus buffer medium is also reported. In defined combinations, the effects of neomycin sulphate appeared to be exerted before those of polymyxin B sulphate.

Bacitracin↗
PubMed1989

Studies on the mechanisms of the synergistic effects of ethambutol and other antibacterial drugs on Mycobacterium avium complex.

Synergistic effects of combinations of anti-mycobacterial drugs on Mycobacterium avium complex (MAC) in vitro was studied by radiometric respirometry. Pronounced synergy was seen for several drug combinations where ethambutol was found to be the key drug in the synergistic potentiation. Microcalorimetric studies show that a very rapid physico-chemical interaction occurs between the cell-surface of MAC and ethambutol. When MAC cells were pretreated with ethambutol and then subjected to streptomycin the thermal response significantly differed from that seen with MAC cells which had not been pretreated. The typical thermal effects of the interaction of ethambutol with live and UV-killed MAC cells was not seen with heat-killed MAC cells. It is proposed that specific cell-surface protein(s) act as receptors in the initial interaction with ethambutol.

Anti-Bacterial Agents↗
PubMed1988

Microcalorimetric determination of the kinetics of substrate utilisation by non-growing suspensions of Neisseria sicca.

The metabolism of various substrates by non-growing suspensions of Neisseria sicca was investigated by a flow-microcalorimetric technique. Substrate utilisation showed Michaelis kinetics allowing determination of saturation constants (Km) and maximum specific rates of substrate utilisation (Vmax). Pyruvate, lactate, a number of tricarboxylic acid cycle intermediates, and amino acids (aspartate, glutamate and proline) were rapidly metabolised [Vmax 5-35 mumol (g dry wt cells)-1 min-1]; Km values were between 4 and 20 microM. Glucose, glycerol, acetate and the other amino acids investigated gave only a slight or no increase in power. The pattern of substrate utilisation is discussed in relation to the role of carbonic anhydrase in N. sicca.

Acetates↗
PubMed1987

A thermodynamic analysis of the Collander equation and establishment of a reference solvent for use in drug partitioning studies.

A thermodynamic analysis of the Collander equation, ln PI = a + b ln PII (I and II refer to two different partitioning systems with partition coefficients PI and PII, respectively), is given and applied to three forms of correlation. The intercept, a, is shown to have no general fundamental significance whereas the slope, b is shown to reflect differences in non-aqueous solvent properties; b is also shown to be of use in scaling solvent behaviour to select solvents which closely represent biological membrane properties for use in partitioning studies. Laboratory and literature data are subjected to the analysis.

Liposomes↗
PubMed1986

A vacuum microbalance technique for studies on the wettability of powders.

A vacuum microbalance technique has been used to evaluate the wettability of powders. The rate of uptake, and equilibrium weight of uptake, of water vapour onto outgassed powder samples, of differing wettabilities, were determined at different known temperatures. Standard techniques of data analysis were used to establish the enthalpy, entropy and Gibb's free energy of the activation and adsorption processes. The values obtained appeared to be in the correct order of magnitude and those for activation clearly reflected the relative wettability of the powders. Tests for compensation demonstrated that with the exception of phenobarbitone, there was probably a common mechanism producing the adsorption.

Adsorption↗
PubMed1986

Growth of Mycoplasma mycoides subspecies mycoides on media containing various sugars and amino sugars: an ampoule microcalorimetric study.

The growth of Mycoplasma mycoides subspecies mycoides strain T1 on media containing various sugars, tryptose, yeast extract, salts and either pig or calf-serum or a mixture of bovine serum albumin (BSA) plus lipid was followed by ampoule microcalorimetry. Power-time (p-t) curves were reproducible and showed details of growth not observable by conventional microbiological techniques. In media with metabolisable sugars p-t curves typically showed three periods of exponential increase in power separated by transient declines or plateaux. Maximum power (Pmax) was dependent upon the nature and concentration of sugar, whether ampoules were capped in air or nitrogen, and whether the medium contained pig or calf-serum or BSA plus lipid. The highest Pmax was observed in pig-serum medium with glucose, in ampoules capped in air. Decline in power from Pmax was essentially exponential.

Acetylglucosamine↗
PubMed1986

A nystatin-resistant mutant of Saccharomyces cerevisiae: isolation and characterization by electron microscopy and chemical analysis of whole cells, cell-walls and protoplasts.

A mutant of Saccharomyces cerevisiae NCYC 239 with a high minimum inhibitory concentration (35 micrograms ml-1) for nystatin, compared to that of the parent strain (2 micrograms ml-1), was derived by a series of subcultures in media containing increasing antibiotic concentrations. In the absence of nystatin, the growth rate of the mutant was significantly lower than the parent strain, although mean cell-size and size-distribution were similar. No differences between strains were detectable by electron microscopy. Analysis of whole cells showed the total sterol present and the ratio of ergosterol:24(28)dehydroergosterol was similar. However, there were marked differences in amino acid content and chain-length of fatty acids in the cell wall, and protoplasts from resistant cells had decreased amounts of unsaturated fatty acids. It is suggested that alterations in cell wall components in the mutant may be directly linked to the mechanism of nystatin resistance.

Amino Acids↗
PubMed1986

Uptake of nystatin by sensitive and resistant cells of Saccharomyces cerevisiae.

The uptake of nystatin by sensitive and by resistant cells of Saccharomyces cerevisiae was studied as a function of nystatin concentration, temperature and pH. The presence or absence of glucose in nystatin uptake experiments was also studied. The rate data, effects of glucose and the derived activation energies for nystatin uptake revealed significant differences in response between sensitive and resistant cells. The role of the cell wall in the uptake process is discussed.

Drug Resistance, Microbial↗
PubMed1986

Uptake of nystatin by protoplasts of sensitive and resistant cells of Saccharomyces cerevisiae.

The uptake of nystatin by protoplasts derived from sensitive and resistant cells of Saccharomyces cerevisiae has been studied as a function of nystatin concentration, temperature and pH. The presence or absence of glucose in the uptake experiments was also studied. Activation energies (Ea) for nystatin uptake revealed profound differences between protoplasts derived from sensitive and resistant cells. Those for the latter closely resembled their whole cell counterparts. The values of Ea for the uptake of nystatin under all the conditions studied indicate the importance of the cell wall in the uptake process.

Biological Transport↗
PubMed1985

The effect of chemical modification of Saccharomyces cerevisiae on electrophoretic mobility, cell-wall structure and amphotericin B uptake.

Saccharomyces cerevisiae NCYC 239 suspended in solutions of NaCl showed two distinct plateaus in plots of electrophoretic mobility vs. pH, corresponding to pKa values of approx. 2 and 5. This is in contrast to cells suspended in buffer where only a single pKa (4) can be determined. Modification of cells with KI/I2 or nitrous acid led to altered electrophoretic mobility, indicating the presence of sulphydryl and amino groups, respectively, in the yeast cell surface, whereas uranyl nitrate modification had little effect, suggesting phosphate groups to be absent. Electron micrographs showed visible effects of KI/I2 and nitrous acid modification on cell membrane structure, and in these modified cells amphotericin B uptake was rapid. It is suggested that diffusion through the cell wall is the rate-limiting step for amphotericin B uptake. An activation energy of 20 kJ X mol-1 was determined for uptake of amphotericin B by unmodified cells.

Amphotericin B↗
PubMed1985

Kinetics of utilization of organic substrates by Mycoplasma mycoides subsp. mycoides in a salts solution: a flow-microcalorimetric study.

The metabolism of various organic substrates by suspensions of Mycoplasma mycoides subsp. mycoides in a salts solution was followed by microcalorimetry. Enthalpy changes associated with metabolism were in good agreement with theoretical values. Substrate utilization showed Michaelis kinetics, allowing saturation constants (Km) and maximum specific rates of substrate utilization (Vmax) to be determined. In cells grown on a complex medium containing glucose, Km values were: glucose, fructose, N-acetylglucosamine, glycerol and pyruvate, less than 5 microM; lactate, 20 microM; glucosamine, 130 microns, and mannose, 1 mM. Values of Vmax for glycerol, pyruvate and lactate were similar and approximately twice those for glucose, mannose, glucosamine and N-acetylglucosamine; Vmax for fructose was one-quarter of that for glucose. In cells grown on complex medium in which glucose was replaced by mannose, glucosamine or N-acetylglucosamine, Vmax and Km for the respective growth sugars and for glucose were not significantly affected. However, in cells grown in the presence of fructose, Vmax for fructose increased to the value observed for glucose. It is suggested that M. mycoides is adapted to, and is constitutive for, the utilization of a single sugar (glucose), and a single amino sugar (N-acetylglucosamine), but that in the presence of fructose a fructose-utilizing pathway is induced.

Acetylglucosamine↗
PubMed1983

Study of the interaction of Saccharomyces cerevisiae with glucose by particle microelectrophoresis.

Saccharomyces cerevisiae NCYC 239 in the presence of glucose at temperatures under 303 K shows a time-dependent lowering of electrophoreric mobility v. At temperatures above 303 K, this time-dependent change in v is in the direction of increased mobilities. Cells suspended in buffer indicate a surface pKa of less than 4, whereas for cells suspended in buffered glucose it is impossible to derive a surface pKa. A kinetic study of the interaction of S. cerevisiae with glucose as a function of temperature allows calculation of an activation energy of 140 kJ X mol-1 for the combined processes of (i) uptake of glucose onto the cell wall, (ii) transfer through the cell wall and membrane, and (iii) the establishment of a steady glucose flux through the wall and membrane.

Biological Transport, Active↗
PubMed1983

Oscillations in some linear free energy relationships derived from partition coefficients of phenols between octanol and water.

In the partition of some resorcinol alkyl ethers between water and 1-octanol, the values of delta Gtrs do not increase in a regular way. Odd and even chain alkyl compounds show different, regular increases in delta Gtrs for addition of each methylene group. The unrecognized occurrence of this phenomenon in earlier data is pointed out, and its possible significance in medicinal chemistry is discussed.

1-Octanol↗
PubMed1983

Enthalpies of solution of a series of m-alkoxy phenols in water, n-octanol and water-n-octanol mutually saturated: derivation of the thermodynamic parameters for solute transfer between these solvents.

Enthalpies of solution in both water and n-octanol have been determined for a series of phenols, in a microcalorimeter modified for titration. The thermodynamic data for solution in n-octanol and in water, as well as for transfer between the two, have been calculated from the free energies of transfer, based upon partition coefficients, and the free energies of solution, based upon solubility data. The results are discussed in terms of solute-solvent interactions in both phases and are used to assess, critically, the use of n-octanol as lipid-like solvent in QSAR studies.

1-Octanol↗
PubMed1982

Microcalorimetry as an immunological tool: preliminary studies with beef heart mitochondrial adenosine triphosphatase and its antiserum.

The calorimetric technique was applied to a complex immunological system based upon purified beef heart mitochondrial adenosine triphosphatase (ATPase). Whole serum containing antibodies to the ATPase was obtained from a rabbit and used to study the antigen-antiserum interaction in comparison with control serum pooled from 50 non-immune rabbits. The results suggest that the immunological interaction may be accompanied by complex processes which were not detectable by other immunological methods. It was shown that kinetic analysis of the calorimetric data may resolve an apparently complex process of interaction into different component stages of reaction. The advantages of this type of application of calorimetry are discussed.

Adenosine Triphosphatases↗
PubMed1982

On the uptake of nystatin by saccharomyces cerevisiae. 5 The release of amino acids.

The release of amino acids from Saccharomyces cerevisiae under the action of nystatin has been studied. The kinetic results do not show any dependence upon molecular size but do support earlier results suggesting that interactions depend upon slow diffusion processes through the cell wall. The effects of temperature, sterol concentration and the presence of calcium ion have also been investigated.

Alanine↗