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Biomedical subjects

M R Brown

Publications and source records attributed to M R Brown.

At least 343 records · Page 19Linked to original sources
PubMed1978

Effect of R-plasmid RP1 and nutrient depletion on the gross cellular composition of Escherichia coli and its resistance to some uncoupling phenols.

The resistance of Escherichia coli batch cultures depleted of carbon (C-dep), magnesium (Mg-dep), or phosphate (P-dep) against low concentrations of 3-chlorophenol, 4-chlorophenol, or 2-phenoxyethanol varied. C-dep cultures were always significantly more sensitive than Mg-dep or P-dep cultures. The presence of R-plasmid RP1 increased the sensitivity of C-dep cultures to 3- and 4-chlorophenol, yet had little effect on those cultured depleted in magnesium or phosphate ions. Cultures with R-plasmid RP1 had increased levels of beta-polyhydroxybutyrate irrespective of the nature of the depleting nutrient. P-dep bacteria had less than one-third of the phospholipid of other cell types, this deficiency being compensated for by increases in fatty acid and neutral lipid content. The reduction in phospholipid content of P-dep cultures was entirely accounted for by decreased diphosphatidylglycerol and phosphatidylethanolamine levels in these cells.

Carbon↗
PubMed1978

Influence of growth rate and nutrient limitation on the gross cellular composition of Pseudomonas aeruginosa and its resistance to 3- and 4-chlorophenol.

Concentrations of 3-chlorophenol and 4-chlorophenol below their minimal inhibitory concentrations were found to increase the permeability of Pseudomonas aeruginosa cells to protons. Levels of such activity were assessed in suspensions of cells prepared from chemostat-grown cultures, limited by either magnesium (Mg-lim) or glucose (G-lim), with the use of five growth rates. Drug concentrations required to produce the same levels of proton translocation varied with the growth rate and the nutrient limiting growth. Fast-growing cultures were more sensitive than slower-growing ones, and G-lim cells were generally more sensitive than Mg-lim ones. 3-Chlorophenol had greater activity than 4-chlorophenol at slow growth rates, but at faster rates of growth their activity was similar. Variation in these iso-effective concentrations for different cells probably reflected an alteration in the ease of drug penetration of the outer envelope. Uptake of the compounds by cells in suspension varied, drug-sensitive bacteria absorbing more than resistant ones. This variation in uptake persisted when bacteria were solvent-extracted to remove readily extractable lipids (REL). Since no significant alteration in cell size was observed among the growth conditions studied, variation in absorption probably resulted from an altered affinity of the cells to the drug, with little involvement of REL. Overall REL content did not alter significantly with growth rate or nutrient limitation. However, total phospholipid content decreased and fatty acid content increased with increasing growth rate. For G-lim and Mg-lim cultures phosphatidylcholine content remained constant, yet phosphatidylethanolamine and phosphatidylglycerol content decreased with increasing growth rate. Diphosphatidylglycerol content decreased with increasing growth rate for Mg-lim cultures and remained relatively constant for G-lim cultures. Lipopolysaccharide content of the cells was higher in Mg-lim than in G-lim cultures and decreased with increasing growth rate in both cases. Lipopolysaccharide content correlated significantly with drug uptake and sensitivity, and it appeared to determine the degree of penetration of the cell envelope by these chlorinated phenols.

Chlorophenols↗
PubMed1977

Mast cell binding of neurotensin. II. Molecular conformation of neurotensin involved in the stereospecific binding to mast cell receptor sites.

Systematic substitution of the natural L-amino acids in neurotensin by their D isomers reveals that the COOH-terminal portion of this tridecapeptide is required for binding to mast cell receptors: D-amino acid replacements from Pro10 through Leu13 substantially decrease that binding. Either blockage of the COOH-terminal carboxyl group as with N-methylamidation, or formation of a cyclic structure by the inclusion of a disulfide bond, a Cys2,13 substitution, markedly reduces the specific binding to mast cell receptor sites. Modifications in the NH2-terminal portion of neurotensin do not affect the binding to mast cells. However, D-Arg8 and D-Arg9 substitutions increase binding by factors of 5- to 6-fold. The hydroxyl group at position 3 or 11 is not essential for binding since Phe3 or Phe11 is equivalent to Tyr3 or Tyr11. The COOH-terminal penta- and hexapeptides are able to displace approximately 70% 125I-neurotensin relative to the intact peptide. Of 18 other biologically active peptides tested, only xenopsin, a naturally occurring COOH-terminal analog of neurotensin, and bradykinin effectively compete in the binding assay to an extent of 60 and 100%, respectively. Histamine, diphenhydramine, and noradrenaline are ineffective in this regard.

Animals↗
PubMed1977

Mast cell binding of neurotensin. I. Iodination of neurotensin and characterization of the interaction of neurotensin with mast cell receptor sites.

Neurotensin was iodinated at equimolar concentrations of peptide, iodide, and chloramine-T, producing a labeled peptide with a specific activity of 1000 to 2000 Ci/mmol. Rat mast cells specifically and reversibly bound 1.27 pmol of neurotensin/10(6) cells with a reversible affinity, KD, of 154 nM. Optimum specific binding occurred betwen pH 6.8 and 7.2 under hypotonic conditions and dropped sharply as buffer concentration increased beyond 10 mM. The divalent cations Ca2+ and Mg2+ prevented binding with 50% inhibition at 1.5 and 4 mM, respectively. Binding was strongly and equally inhibited by the sodium and potassium salts of chloride, bromide, and iodide, and to a lesser degree by LiCl. Maximum binding of 125I-neurotensin occurred within 10 min at 0 degrees, and within 1.5 to 2 min binding was reduced to half-maximum in the presence of excess unlabeled neurotensin or upon 20-fold dilution in buffer. Both CaCl2 and NaCl were able to dissociate 60% of the total bound neurotensin: half the label bound was removed in 4 to 6 min. EDTA inhibited the binding only at high concentrations and no requirement was found for sulfhydryl groups, ATP, or a glycoprotein in the binding of neurotensin.

Animals↗
PubMed1977

Effect of colloidal association on the measured activity of alkylbenzyldimethylammonium chlorides against Pseudomonas aeruginosa.

The antibacterial activities of a homologous series (C8-C18) of alkylbenzyldimethylammonium cholorides (ABDAC) against Pseudomonas aeruginosa have been measured using both a minimum inhibitory concentration (MIC) procedure and a sterilization kinetics test carried out in deionized water. There was a log-linear relationship between activity measured by kinetics and carbon number. With MIC there was a log-linear relationship up to C14, when there was a turndown in activity. Consideration of the colloidal association of ABDAC in deionized water and in a simple salts growth media leads us to suggest that use of high concentrations of nutrient salts in MIC tests will lower the effective concentration of the surface active agents. This change may be responsible for the turndown in activity observed in MIC tests, and that in such circumstances the MIC test does not give a true reflection of the intrinsic activity of the compounds. Literature reports of parabolic relationships between ABDAC alkyl chain length and antimicrobial activity are reinterpreted on this basis.

Benzalkonium Compounds↗
PubMed1977

Neurotensin analogues. Structure--activity relationships.

A series of neurotensin (NT) analogues in which each amino acid has been successively replaced by its D isomer, as well as analogues involving modifications at positions 3 and 11 and a cyclic compound [Cys2,13]-NT, has been synthesized by solid-phase methodology. After purification by conventional techniques the compounds were characterized by thin-layer chromatography, amino acid analysis, and optical rotation. Further characterization of the analogues by high-pressure liquid chromatography demonstrates the high resolving power of this new method. Each analogue was studied for its ability to induce hypothermia in cold-exposed rate (4 degrees C) in vivo and to bind to mast cells in vitro. Although close correlation in potencies was not found for all the analogues tested in both assay systems, they substantiate the basic observation that substitutions in positions 1-9 produced active peptides whereas modification of residues 10-13 considerably decreased biological response in vitro and in vivo. One exception is the higher potency of [D-Phe11]-NT and [D-Tyr11]-NT in vivo. The differences between the efficacies of these analogues in vivo and in vitro are discussed.

Animals↗
PubMed1976

Tyrosylated analogues of somatostatin.

The total synthesis of [tyr1]-, [tyr6]-, E1Tyr7], [d-tyr8]-, [tyr11]-,and [tyr1,D-Trp8]somatostatin is described. The biological potencies of these analogues in vitro (inhibition of spontaneous secretion of radioimmunoassayable growth hormone by cultured rat anterior pituitary cells) as compared with that of somatostatin (100) were found to be 116, 29, 108, 10, 65, and 400, respectively; in vivo, in the rat, these peptides were assayed for their ability to inhibit the spontaneous release of insulin and glucagon. No statistically significant discrepancies were observed in the potency values obtained in vitro and in vivo further indicating similarities of specificities and sensitivities of the pituitary and pancreatotropic receptors.

Animals↗
PubMed1976

Liver tests, HB-Ag and HB-Ab in asymptomatic drug addicts.

One hundred eighty-eight asymptomatic addicts were studied to determine the frequency of a history of hepatitis (previous episodes of jaundice), abnormalities of liver tests (serum bilirubin, alkaline phosphatase, serum albumin, serum glutamic oxalacetic transaminase) and incidence of HB-Ag and HB-Ab. Seventy-four were white and 114 were nonwhite. A history of hepatitis was obtained in only 38%. One hundred and fifty-two of the 188 addicts (81%) had one or more abnormal liver tests. The bilirubin was abnormal in 5%, akkaline phosphatase in 28% and serum glutamic oxalacetic transaminase in 55%. HB-Ag was positive in 2.6% using radioimmunoassay and HB-Ab was found in 66%. There was a higher incidence of elevated serum glutamic oxalacetic transaminase, HB-Ab and history of hepatitis among white, compared to nonwhite addicts.

Adolescent↗