Search PubMed⌕ Search

Biomedical subjects

M Cannon

Publications and source records attributed to M Cannon.

At least 73 records · Page 4Linked to original sources
PubMed1990

A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives.

Chloramphenicol, thiamphenicol and three fluorinated derivatives, Sch 24893, Sch 25298 and Sch 25393, were studied with respect to inhibition of the growth of selected bacterial strains and cell-free translation systems. Thiamphenicol was the least potent inhibitor in the former experiments, but behaved similarly to chloramphenicol and Sch 25298 in the latter, thereby displaying selective inhibition of prokaryotic protein synthesis. Thiamphenicol and Sch 25298 were shown to be like chloramphenicol in inhibiting peptidyl transferase activity specifically on 70 S ribosomes, but the antibiotics bound to their common ribosomal-receptor site with different efficiencies in the order chloramphenicol greater than thiamphenicol greater than Sch 25298. Selected bacterial strains highly resistant to chloramphenicol and thiamphenicol because of chloramphenicol acetyltransferase production were, in contrast, highly sensitive to inhibition by the fluorinated antibiotics. Thus Sch 24893, Sch 25298 and Sch 25393 may have important uses in veterinary and clinical medicine.

Chloramphenicol↗
PubMed1989

Diagnosis of sulfonamide hypersensitivity reactions by in-vitro "rechallenge" with hydroxylamine metabolites.

STUDY OBJECTIVE: To determine whether differences in in-vitro detoxification of sulfonamide-reactive metabolites can be detected among the lymphocytes from controls, patients with sulfonamide hypersensitivity reactions, and patients with nonhypersensitivity reactions to the sulfonamide agents. DESIGN: In-vitro toxicity assay on lymphocytes. SETTING: Clinics for adverse drug reactions in an adult and pediatric tertiary care center. PATIENTS: Peripheral blood lymphocytes were obtained from 46 normal volunteers and 76 patients referred to the clinic for assessment of adverse drug reactions to sulfonamide agents. Thirty-one patients had clinical histories consistent with a diagnosis of hypersensitivity reaction, whereas 45 patients had clinical histories felt to be inconsistent with a diagnosis of hypersensitivity reaction. INTERVENTIONS: Lymphocytes were assayed with tetrazolium to determine toxicity from the hydroxylamine of sulfamethoxazole. MEASUREMENTS AND MAIN RESULTS: The lymphocytes from patients with a history of hypersensitivity reactions showed markedly increased toxicity across a tenfold-concentration toxicity-concentration curve compared with those from controls and patients with a history of nonhypersensitivity reactions. These differences were highly significant (P less than 0.01). No difference was found between the toxicity shown by the lymphocytes from controls and that shown by the lymphocytes from patients with a history of nonhypersensitivity reactions. CONCLUSIONS: Metabolic differences in the production and detoxification of reactive metabolites of sulfonamide agents are important determinants of hypersensitivity reactions to these agents. These results suggest that the hydroxylamine derivative of sulfamethoxazole may be a reactive metabolite mediating these reactions. Sulfonamide hydroxylamines are useful in the diagnosis and study of the pathogenesis of hypersensitivity reactions to sulfonamide agents.

Adult↗
PubMed1988

Myomycin: mode of action and mechanism of resistance.

Myomycin is an unusual pseudodisaccharide antibiotic with a beta-lysyl oligopeptide ester side chain that has structural similarities with kasugamycin, streptomycin and streptothricin. We show that the mode of action of myomycin in vivo and in vitro closely resembles that of streptomycin; in addition, spontaneous myomycin-resistant mutants of Escherichia coli are essentially indistinguishable from streptomycin-resistant mutants at the rRNA and r-protein level. Myomycin is not a substrate for the known streptomycin-modifying enzymes and could be useful in the characterization of natural streptomycin-resistant isolates and in counterselecting against the presence of streptomycin-modifying enzymes. The relationship between structure and inhibition of protein synthesis has been examined for a series of derivatives of myomycin.

Aminoglycosides↗
PubMed1988

Drug metabolite toxicity assessed in human lymphocytes with a purified, reconstituted cytochrome P-450 system.

Evaluation of idiosyncratic drug reactions in predisposed individuals is limited by ethical concerns arising from rechallenge with the suspected offending agent. A previously developed in vitro method using human lymphocytes and a murine microsomal drug metabolizing system has been used to examine toxicity due to acetaminophen (APAP), sulfonamide antibiotics and aromatic anticonvulsants. An improved method is described in which toxic APAP metabolites are generated by a purified and reconstituted cytochrome P-450 system, minimizing the amount of exogenous detoxification enzymes in the assay. Toxicity is assessed by an objective, automated method based on the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to an insoluble purple formazan by the mitochondria of viable cells and correlates with that based on trypan blue exclusion. Toxicity required cytochrome P-450 and NADPH, and was inhibited by SKF 525A. Exogenous glutathione also decreased toxicity in a concentration-dependent manner. Lymphocytes from a glutathione synthetase-deficient patient exhibited markedly enhanced toxicity to APAP exceeding the 95% CL of 10 control subjects over a concentration range of 10 to 1000 micrograms/ml. The data are consistent with the generation of cytochrome P-450-dependent reactive metabolites which subsequently can be detoxified by glutathione. This method allows one to address specifically individual differences in detoxification pathways. The use of an automated assessment of cell viability may prove useful in preclinical screening of new compounds for their propensity to cause "idiosyncratic" drug reactions in a predisposed population.

Acetaminophen↗
PubMed1987

A rapid and preparative method for the separation of yeast ribosomal proteins by using high-performance liquid chromatography.

Ribosomal proteins from the yeast Saccharomyces cerevisiae were separated, on a preparative scale, by ion-exchange h.p.l.c. Proteins from the small and large ribosomal subunits were resolved, respectively, into 33 and 23 peaks, and most of the proteins present in these peaks were identified by using one- and two-dimensional gel electrophoresis. Several of the peaks appeared to contain a single protein uncontaminated by other species. Ribosomal proteins were also separated by using reverse-phase h.p.l.c. Analysis of the peaks resolved indicated that the order of elution for the proteins of both ribosomal subunits is, in certain cases, different for each of the two h.p.l.c. techniques used. Thus a combination of the two chromatographic methods employed here has the potential to facilitate the rapid and preparative separation of each of the proteins present in yeast ribosomes.

Chromatography, High Pressure Liquid↗
PubMed1987

Comparative organization of nitrogen fixation-specific genes from Azotobacter vinelandii and Klebsiella pneumoniae: DNA sequence of the nifUSV genes.

In the facultative anaerobe Klebsiella pneumoniae 17 nitrogen fixation-specific genes (nif genes) have been identified. Homologs to 12 of these genes have now been isolated from the aerobic diazotroph Azotobacter vinelandii. Comparative studies have indicated that these diverse microorganisms share striking similarities in the genetic organization of their nif genes and in the primary structure of their individual nif gene products. In this study the complete nucleotide sequence of the nifUSV gene clusters from both K. pneumoniae and A. vinelandii were determined. These genes are identically organized on their respective genomes, and the individual genes and their products exhibit a high degree of interspecies sequence homology.

Aerobiosis↗
PubMed1986

Application of high-performance liquid chromatography to the purification and characterization of ribosomal protein L3 from trichodermin-resistant yeast mutants.

A new h.p.l.c. cation-exchange method has been used to separate proteins from 60S ribosomal subunits prepared from strains of Saccharomyces cerevisiae sensitive or resistant to trichodermin. Ribosomal protein L3 was identified in column eluates by one-dimensional and two-dimensional gel electrophoresis and purified further by reverse-phase h.p.l.c. The protein was cleaved with CNBr and the products were analysed, again by reverse-phase h.p.l.c. A marked difference was observed in the peptide profiles between preparations from trichodermin-sensitive and trichodermin-resistant yeast strains. These results provide the first direct demonstration that, in yeast, mutationally induced resistance to trichodermin can alter the covalent structure of ribosomal protein L3. They convincingly demonstrate the potential of the experimental technique for the rapid and preparative separation of a selected yeast ribosomal protein and its subsequent characterization.

Chromatography, High Pressure Liquid↗
PubMed1985

A molecular genetic study of nif expression in Klebsiella pneumoniae at the level of transcription, translation and nitrogenase activity.

A comprehensive study of nif expression in Klebsiella pneumoniae at the level of transcription, translation and nitrogenase activity during derepression and repression by NH+4 and O2 revealed that (1) transcription and translation rates remained coupled under all conditions; (2) these rates reached a peak during derepression and then decreased to a low level; (3) the transcription profile of nifLA had two peaks; the first was at 1 h before and the second coincided with that of the other operons; and (4) the peaks of nif transcription coincided with a trough in the profile of stringent regulation of RNA synthesis. Our results provide strong evidence that nif-specific repression by NH+4 and O2 occurs exclusively by transcription inhibition and that repression by O2 is independent of transcriptional regulation of the nifLA operon. We have also found evidence which together with the results of previous work shows that O2 repression of nifA mediated transcription involves the nifL gene product.

Ammonia↗
PubMed1985

Extra early physical contact and aspects of the early mother-infant relationship.

We tested the hypothesis that extra early physical contact between mother and infant enhances aspects of their early relationship. Healthy, middle-class mothers and their healthy, firstborn, singleton infants delivered vaginally at full-term were randomly assigned to receive either regular contact (RC; N = 39) or extra early physical contact (EC; N = 39) following delivery. RC infants remained in cribs beside their mothers' beds, while EC infants and mothers had a mean of 46 min of physical contact in the recovery room. There was no difference between EC and RC subjects for the following outcome measures: amount of time mothers chose to have infants with them during the postpartum hospital stay; quality of mother-infant interaction at two days and one month; concern mothers expressed for the infant at one month; mothers' perception of their postpartum adjustment; mothers' perception of the infant at two days and one month, and of the infant's temperament at eight months; and extent of mothers' assisting with and soothing the child during a physical examination at 13 months. EC children cried significantly less during the examination at 13 months. These findings do not support the hypothesis that extra early physical contact between mother and infant enhances their relationship.

Adaptation, Psychological↗