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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 325 records · Page 18Linked to original sources
PubMed1980

Effects of hyperbaric oxygen on the growth and properties of Pseudomonas aeruginosa.

Growth of Pseudomonas aeruginosa in 2 atmospheres absolute of 100% oxygen at 37 degrees C produced two types of abnormal colonies--stunted, rough colonies, termed dwarfs, and large, domed, mucoid colonies, termed giants. The occurrence of these variants depended upon the partial pressure of oxygen and the inoculum size. Subculture of dwarf or giant colonies produced a mixture of both colony types after incubation in hyperbaric oxygen, and colonies of normal appearance after incubation in air. Electron micrographs of ultrathin sections showed that cells from dwarf colonies had a more clearly defined envelope region than cells from normal colonies. Giant colony and normal colony-derived cells were of similar appearance. Whole cells from giant colonies contained more carbohydrate, readily extractable lipid, neutral lipid and free fatty acid than cells from normal colonies; the two cell types showed similar contents of 2-keto,3-deoxyoctonic acid and total phospholipid, but different proportions of individual phospholipids. Cells from dwarf, giant and normal (air-grown) colonies were incubated in air on nutrient agar containing either polymyxin, tetracycline or phenoxyethanol. Relative to cells from normal colonies, cells from dwarf colonies showed enhanced resistance to all three agents and cells from giant colonies showed enhanced resistance to polymyxin and tetracycline only. The resistance of cells from variant colonies was lost following a single subculture in air in the absence of antibacterial agents. It was concluded that the envelopes of cells from dwarf and giant colonies differed both from each other and from those of normal cells. These differences, and the formation of variant colonies, appeared to result from bacterial adaptation to hyperbaric oxygen rather than from mutation.

Atmospheric Pressure↗
PubMed1979

Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue.

A new long-acting octapeptide analogue of somatostatin, Des AA1,2,4,5,12,13 D Try8 somatostatin, has been tested in 8 patients with pancreatic endocrine tumours. The analogue given subcutaneously suppressed the tumour-derived hormones in patients with insulinomas, glucagonomas, and gastrinomas for up to 24 h. The prolonged action appeared to be the result of slow release from the injection site. No side-effects were observed. Studies of long-term administration of this new peptide are now warranted.

Adult↗
PubMed1979

Bombesin-like immunoreactivity in the avian gut and its localisation to a distinct cell type.

The distribution of a bombesin-like immunoreactive peptide in the avian gastro-intestinal tract was analysed by combined radioimmunoassay and immunocytochemistry. Radioimmunoassay of tissue extracts showed that the largest quantities of bombesin-like immunoreactivity were present in the proventriculus (64.5 +/- 6.0 pmol/g) with smaller but still considerable amounts in the gizzard (40.0 +/- 6.0 pmol/g). Immunocytochemically the extractable bombesin-like immunoreactivity was localised in numerous endocrine cells. These, in the proventriculus, were found mainly in the deeper layers of the mucosa. Further study of these cells by the semi-thin/thin technique revealed the presence of characteristic secretory granules. The functional name BN is proposed for this cell type.

Animals↗
PubMed1979

Sensitivity of Pseudomonas aeruginosa envelope mutants to alkylbenzyldimethylammonium chlorides.

A series of stepwise polymyxin-resistant envelope mutants of Pseudomonas aeruginosa was used to test the activity of a homologous series (C10-C18) of alkylbenzyldimethylammonium chlorides. A sterilization kinetics procedure in deionized water was devised to avoid amounts quaternary compound above the critical micelle concentration. In all cases, there was a linear relationship between the logarithm of the rate of change of the colony count with time and the logarithm of the homolog concentration. For all strains, there was a linear relationship between alkyl chain length and the concentration required to reduce the colony count to 10% in 2 hr. The stepwise series of polymyxin-resistant strains increased in resistance to polymyxin about threefold for each step. In general, this increase resulted in a similar increase in resistance to the quaternary compound. It is proposed that death in this system may primarily be a consequence of damage to the outer membrane rather than to the cytoplasmic membrane.

Anti-Infective Agents, Local↗
PubMed1979

Interrelation of DNA replication, specific growth rate and growth temperature in the sensitivity of Escherichia coli to cold shock.

Escherichia coli W3110 was grown in a chemostat under conditions of carbon limitation at various temperatures and specific growth rates (mu). Exponential survivor-time curves following cold osmotic shock were biphasic. These could be described by the sum of two exponential functions representing the survival of sensitive and resistant fractions of the population where the size of the sensitive fraction was directly proportional to mu. Decimal reduction times for the more resistant fraction were unaffected by mu yet decreased with increasing growth temperature. Sensitivity to cold shock was evaluated for an E. coli CR34 mutant, temperature-sensitive in initiation of DNA replication. When grown in the chemostat at the non-restrictive temperature (30 degrees C) sensitivity was directly proportional to mu. Following a rise in the incubation temperature to 42 degrees C, sensitivity decreased markedly and reached a minimum 45 to 60 min after the temperature increase. Sensitivity of the E. coli mutant grown at 30 degrees C and raised to 42 degrees C for 1 h was low and relatively unaffected by growth rate.

Cold Temperature↗
PubMed1979

Effect of R plasmid RPI on the nutritional requirements of Escherichia coli in batch culture.

The minimal nutritional requirements of Escherichia coli have been quantitatively determined in batch culture for cells with (R+) and without (R-) the R plasmid RP1. In these conditions R+ cells have a greater requirement than R- for several nutrients, particularly Mg2+, K+, Fe2+ and PO43-. The maximum growth rate in a simple salts medium was the same for R+ and R- cells. At low concentrations of phosphate, the specific growth rate of R+ cells differed from that found for R- cells. The R plasmid was stable in simple salts medium, irrespective of the nutrient ultimately depleted by growth, but, on storage, R+ cells survived for a shorter time than R- cells.

Culture Media↗
PubMed1979

Additivity of action between polysorbate 80 and polymyxin B towards spheroplasts of Pseudomonas aeruginosa NCTC 6750.

When polymyxin B and polysorbate 80 were used together against spheroplasts of Pseudomonas aeruginosa, the activities were found to be additive. These substances have previously been reported to act synergistically against P. aeruginosa, but little or no intrinsic activity towards intact cells has been attributed to polysorbate 80. We suggest that in addition to enhancing polymyxin B penetration to the cytoplasmic membrane, polysorbate 80 may also act as an antimicrobial agent when polymyxin-induced damage to the outer membrane facilitates the surfactant's passage through the cell envelope.

Polyethylene Glycols↗
PubMed1979

Influence of suspending media upon the susceptibility of Pseudomonas aeruginosa NCTC 6750 and its spheroplasts to polymyxin B.

The lytic and bactericidal actions of polymyxin B on whole cells and spheroplasts of Pseudomonas aeruginosa varied markedly with the suspending media, and there was little correlation between them. Relative rates of lysis of these preparations and also of Bacillus megaterium protoplasts suggested that polymyxin causes progressive damage to the cytoplasmic membrane, such that membrane permeability towards various ions increased as follows: K(+) > Na(+) > NO(3) (-) > Cl(-), Ca(2+), H(2)PO(4) (-)/HPO(4) (2-). Impermeant compounds, such as NaCl and sucrose, protected whole cells against lysis but not against death. It is suggested that lysis of whole cells by polymyxin is a secondary effect, resulting from entry of solutes normally excluded by the cytoplasmic membrane and the fragility of the damaged outer membrane. Because the degree of lysis varies with the external solutes, it should be treated with caution as a descriptor of polymyxin activity.

Bacillus megaterium↗
PubMed1978

Bombesin, bombesin analogues, and related peptides: effects on thermoregulation.

The synthesis and biological evaluation on thermoregulation of 39 peptides related to bombesin (structural analogues or other naturally occurring peptides) are described. The bioassay system reported measures the ability of peptides injected intracisternally to lower body temperature of cold (4 degrees C) exposed rats. The most potent analogues of bombesin were those in which positions one to five (not included) were altered, indicating that the decapeptide C terminal was sufficient for full potency. Gln at the seventh position and Gly at the 11th position could be replaced by D-Gln and D-Ala (but not D-Pro or D-Phe), respectively, without any change in potency. Methionine at the 14 position could be replaced with its D isomer with retention of 10% biological activity. Any other alteration of the C terminus (deletions or free acid with the exception of the N-methylamide) drastically reduced the biological potency of those peptides. Among other naturally occurring peptides, alytesin was found to have 100% of bombesin potency whereas litorin, neurotensin, xenopsin, substance P, physalaemin, and eledoisin were found to be in the order of 10(4) times less potent. The shortest peptide found to have full biological activity is the octapeptide des-Glp-Gln-Arg-Leu-Gly-Asn[D-Glp7, D-Ala11]-bombesin.

Amino Acids↗
PubMed1978

Bomebesin: specific binding to rat brain membranes.

The binding of a radiolabeled bomebesin analogue to rat brain membranes was studied. [125I-Tyr4]Bombesin bound with high affinity (KD = 3 nM) to a single class of non-interacting sites. Binding was specific, saturable (3.8 pmol of sites/g of wet tissue), and reversible. Regional and subcellular distribution studies showed that the density of sites was 7-fold greater in the hippocampus than the medulla/pons and greater in synaptosomal fractions than in mitochondrial or nuclear fractions. The abilities of numerous bombesin analogues to induce hypothermia and to inhibit [125I-Tyr4]bombesin-binding activity correlate well. Numerous amino acid residues near the CONH2-terminal are required for high-affinity binding and biological potency.

Animals↗
PubMed1978

Influence of R-plasmid RP1 of Pseudomonas aeruginosa on cell wall composition, drug resistance, and sensitivity to cold shock.

R-plasmid RP1 was transferred to Pseudomonas aeruginosa cells, as indicated by their resistance to carbenicillin, ampicillin, cephaloridine, kanamycin, and tetracycline, and by the presence of a periplasmic beta-lactamase. The wild-type cells (RP1-) were lysed by ethylenediaminetetraacetic acid but not by ethylene-glycol-bis(2-aminoethyl ether)-N,N-tetraacetic acid, whereas cells carrying the plasmid (RP1+) were resistant to both these chelating agents. RP1+ and RP1- strains were both sensitive to the lytic action of polymyxin B and the lethal action of cold shock, but the effect was less marked in the RP1+ cultures. A proportion of the RP1+ cells surviving cold shock lost resistance to carbenicillin, tetracycline, and kanamycin. The chemical composition of whole cells and cell walls of RP1+ differed from that RP1- in the content of cation, phospholipid, and markers for lipopolysaccharide and peptidoglycan. Differences in cell wall composition, response to ethylenediaminetetraacetic acid and polymyxin B, and the effects of cold shock are all compatible with the hypothesis that RP1 confers changes in the cell envelope, probably in the outer membrane, of P. aeruginosa.

Ampicillin↗
PubMed1978

Effect of growth environment on Pseudomonas aeruginosa killing by rabbit polymorphonuclear leudocytes and cationic proteins.

Pseudomonas aeruginosa grown in a chemostat under carbon- and magnesium-limited conditions showed varying resistance to killing by rabbit peritoneal exudate polymorphonuclear leukocytes. Slow-growing (D = 0.05 h-1), magnesium-limited cells were significantly more resistant to the lethal effects of the phagocytes than were fast-growing magnesium-limited cells and carbon-limited cells (D = 0.05 h-1 and D = 0.5 h-1, respectively). The resistance of magnesium-limited cells to killing by cationic proteins isolated from the leukocytes was shown to be growth-rate dependent, the slowest-growing (D = 0.05 h-1) cells being the most resistant. Carbon-limited cells were sensitive to killing by the cationic proteins at all growth rates tested. Antisera raised in rabbits to all types of cells and commercial anti-Pseudomonas serum rapidly agglutinated magnesium-limited cells but failed to agglutinate carbon-limited cells. There was some indication that slow-growing (D = 0.05 h-1), magnesium-limited cells agglutinated most readily with both types of antisera. No difference was detected in the mouse toxicity of heat-killed cells grown under the various conditions.

Animals↗