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Biomedical subjects

A Beg

Publications and source records attributed to A Beg.

5 recordsLinked to original sources
PubMed1999

The combined absence of the transcription factors Rel and RelA leads to multiple hemopoietic cell defects.

Individual Rel/NF-kappaB transcription factors, although dispensable for the development and maturation of most hemopoietic cells, are critical regulators of normal immune function. Redundancy among these proteins prompted us to examine the role of Rel and RelA in hemopoiesis by using mice that lack both subunits. Because of the death of double-mutant fetuses at day 13.5 of gestation (E13.5), E12 fetal liver hemopoietic progenitors were used for in vitro cultures and for repopulating stem cell studies in lethally irradiated normal recipient mice. Most striking, Rel/RelA-deficient hemopoietic precursors failed to promote the survival of myeloablated mice. This phenotype was associated with several defects including a reduction of spleen colony-forming unit progenitors, impaired erythropoiesis, and a deregulated expansion of granulocytes. In vitro progenitor assays also revealed that Rel or RelA serves an antiapoptotic role during monocyte differentiation. Despite the combined loss of Rel and RelA leading to these hemopoietic defects, c-rel(-/-)rela(-/-) stem cells contributed to the development of all lineages in mice engrafted with double-mutant fetal liver cells and normal bone marrow cells, albeit in a reduced fashion compared with controls. Collectively, these data indicate the loss of Rel and RelA does not appear to affect pluripotent stem cells; rather, Rel and RelA serve redundant functions in regulating differentiation and survival of committed progenitors in multiple hemopoietic lineages.

Animals↗
PubMed1998

The methylglutamate, SYM 2081, is a potent and highly selective agonist at kainate receptors.

The methylglutamate analog (2S,4R)-4-methylglutamate (SYM 2081) has been shown to potently displace high affinity [3H]kainate binding to cortical tissue and to recombinant kainate receptors, and to evoke rapidly desensitizing responses in electrophysiological recordings. We have used two electrode voltage clamp recordings to compare the potency and efficacy of SYM 2081 with other alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate receptor agonists at homomeric kainate and AMPA receptors expressed in Xenopus oocytes. In the presence of concanavalin A to reduce agonist induced desensitization at kainate receptors, SYM 2081 was a potent agonist at homomeric kainate receptors composed of the GluR5 and GluR6 subunit, with an EC50 of 0.12 +/- 0.02 and 0.23 +/- 0.01 microM, respectively. SYM 2081 was highly selective for kainate receptors, the EC50 for activation of AMPA receptors composed of the GluR1 and GluR3 subunits was 132 +/- 44 and 453 +/- 57 microM, respectively. Other methylglutamate analogs were tested for kainate receptor agonist activity. Methylglutamate compounds with the methyl group at the 2 or 3 position of glutamate were inactive indicating that positioning of the methyl group at the 4 position was essential for agonist activity. Of the four stereoisomers of 4-methylglutamate, SYM 2081 (2S,4R) was the most potent agonist. The (2R,4R) isomer was estimated to be 20-fold and the (2S,4S)-isomer approximately 1000-fold less potent than SYM 2081. These results indicate that SYM 2081 is a potent and selective agonist at kainate receptors, and thus will be a useful ligand for evaluating the role of kainate receptors in central nervous system function and disease.

Animals↗
PubMed1987

Determination of teicoplanin concentration in serum using a bioassay technique.

An accurate and sensitive bioassay for determining concentrations of teicoplanin in serum has been developed using modifications of procedures described for assaying vancomycin. A linear relationship (r = 0.9983) was obtained between the diameter of the zone of inhibition and log10 teicoplanin concentration over the range 0.25-32 micrograms/ml. The medium used was Antibiotic Medium No. 1 (Oxoid, UK) adjusted to pH 5.5-5.7 by the addition of hydrochloric acid and containing sodium chloride to a final concentration of 3%. The indicator organism used was a Bacillus subtilis ATCC 6633 (NCTC 10400). Teicoplanin was assayed: (i) in the presence of beta-lactams and cephalosporins, including ceftazidime, by prior treatment of serum with broad-spectrum beta-lactamase mixtures (Genzyme Laboratories, UK); (ii) in the presence of aminoglycosides by prior treatment of serum with cellu-ion phosphate (100 mg/ml) followed by centrifugation; (iii) in the presence of sulphamethoxazole and/or trimethoprim by the addition of p-aminobenzoic acid and/or thymidine to the assay medium. Teicoplanin was assayed in the presence of either rifampicin or erythromycin by using a rifampicin-resistant, erythromycin-resistant clinical isolate of Staphylococcus aureus as indicator organism. The lower limit of sensitivity of this assay was 1 microgram/ml. The presence of undeclared, broad-spectrum antimicrobials was detected by screening serum samples for antimicrobial activity using an assay plate seeded with Escherichia coli NCTC 10418.

Anti-Bacterial Agents↗