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R Edwards

Publications and source records attributed to R Edwards.

At least 199 records · Page 11Linked to original sources

Fascin, an echinoid actin-bundling protein, is a homolog of the Drosophila singed gene product.

A cDNA for fascin, an actin-bundling protein in echinoderms, has been cloned, sequenced, and expressed. The predicted mass of the protein is approximately 55 kDa, similar to that observed for fascin purified from sea urchin eggs. Bacterially expressed fascin reacts with antibodies prepared against sea urchin egg fascin. Fascin has a strong sequence similarity to the singed gene (sn) product in Drosophila and has similarities with a 55-kDa human actin-bundling protein. No extensive similarities were found with other known actin-binding/bundling proteins, indicating that this is a separate gene family.

Amino Acid Sequence↗

Changes in synaptosomal glutamate release during postnatal development in the rat hippocampus and cortex.

The effectiveness of K+ depolarisation in inducing the release of [3H]L-glutamate from preloaded hippocampal and cortical synaptosomes was examined in rats aged from postnatal day 4 (PND 4) to adult. In the lower age groups studied (PND 4-PND 15), the response to depolarisation was always smaller than that seen in the adult. From PND 15, the sensitivity of the release process increased steadily to a maximum level in the adult. The relatively small amounts of glutamate released in response to K(+)-depolarisation in the younger age groups may be a factor which contributes to the relative insensitivity of neonatal brain to ischaemic damage. Discrete variations in the sensitivity to K+ depolarisation observed in animals aged from PND 4 to PND 15 may be involved in plastic changes in neural activity which are known to occur during this important development period.

Aging↗

In-vitro characteristics of glycopeptide resistant strains of Staphylococcus epidermidis isolated from patients on CAPD.

The low-level resistance of three clinical isolates of Staphylococcus epidermidis to glycopeptide antibiotics was found to be constitutive, not inducible, and was not increased by passage in the presence of either vancomycin or teicoplanin. There was no loss of resistance on repeated passage in antibiotic-free broth. In contrast, the susceptibility to these antibiotics declined for S. epidermidis NCTC 6513 that been sequentially passaged in either vancomycin or teicoplanin whereas the variants reverted to being susceptible on further passage in antibiotic-free broth. Antibiotic activity was almost completely abolished when cultures of the resistant S. epidermidis strains were exposed overnight to sub-MIC concentrations. No evidence of drug-modifying activity was obtained. Experiments of antibiotic-binding activity indicated that the resistant strains exhibited an increased ability to sequester antibiotics which was particularly rapid in stationary phase cultures when most of the antibiotic activity disappeared from the growth medium within 30 min of exposure to the drugs. Teicoplanin was sequestered more efficiently than vancomycin and some loss of activity was also observed when stationary phase cultures of S. epidermidis NCTC 6513 were exposed to glycopeptides. These results suggest that glycopeptide-resistant isolates of S. epidermidis are able to bind large amounts of these antibiotics, possibly at sites unassociated with the D-alanyl-D-alanine target, and that teicoplanin is bound more avidly than vancomycin.

Anti-Bacterial Agents↗

Characterization of bovine ovary angiotensin II receptors using subtype-selective antagonists.

Angiotensin-II (AII) receptors have been classified as AT1 and AT2 subtypes based on selective antagonists. AII binding sites in bovine ovary membranes were characterized using the radiolabeled AII antagonist, [125I]Sar1,Ile8-AII ([125I]SIA). The binding was specific and saturable with dissociation constant (Kd) and maximum binding (Bmax) of 0.18 +/- 0.08 nmol/l and 32.5 +/- 1.3 fmol/mg, respectively. Pretreatment of ovarian membranes with dithiothreitol (10 mumol/l) doubled the specific binding of [125I]SIA twofold to 63.5 +/- 2.8 fmol/mg. Guanine nucleotide had no significant effect on the affinity of agonist (AII) to compete for [125I]SIA binding. AII and a series of AII-related analogs were used in competition binding experiments, and the data were compared with those obtained with membranes prepared from bovine adrenal cortex and bovine cerebellum. The membranes from ovary and cerebellum showed similar binding characteristics, but they differed from those of adrenal cortex. CGP42112A and WL-19, AT2-subtype selective antagonists, inhibited [125I]SIA binding to ovarian membrane with IC50 values of 28 +/- 4 and 26.7 +/- 2.8 nmol/l, respectively. SK&F 108566 and DuP 753, AT1-subtype-selective antagonists, had very little effect on [125I]SIA binding to ovarian membranes. These data directly demonstrate that bovine ovary membranes have predominantly AT2-subtype AII receptors.

Acrylates↗

Characterization of [3H]SK&F 108566 as a radioligand for angiotensin type-1 receptor.

Rat aortic smooth muscle cells were used as a model system to characterize the binding properties of [3H]SK&F 108566, an angiotensin type-1 (AT1) receptor antagonist. The binding was specific, saturable and reversible. The association and dissociation rates of [3H]SK&F 108566 binding to smooth muscle cells were monophasic and Scatchard analysis of equilibrium binding data yielded a linear plot indicating a homogenous population of binding sites. The maximum binding (Bmax) and apparent dissociation constant (Kd) were 22,000 +/- 6000 sites/cell and 0.83 +/- 0.08nM respectively. The pharmacological specificity of [3H]SK&F 108566 binding to smooth muscle cells is consistent with that observed for AT1 and confirms AT1 receptor specificity of this radioligand. High affinity binding was observed in membranes prepared from bovine adrenal cortex, rat liver and rat kidney glomeruli. COS cells transfected with cDNA encoding human AT1 angiotensin II receptors also displayed high affinity binding site for [3H]SK&F 108566. No specific binding could be detected on membranes prepared from bovine cerebellum, a tissue rich in the angiotensin type-2 (AT2) receptor. These observations indicate that [3H]SK&F 108566 binds to sites which have pharmacological characteristics of angiotensin II AT1 subtype receptors and can be used as a subtype-selective radioligand to characterize AII receptors in various systems.

Acrylates↗

Safety of vancomycin with or without gentamicin in neonates.

Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations. Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone. No immediate side effects were noted. Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction. Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment. Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding. Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved. In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe. The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended.

Drug Monitoring↗

Percutaneous transluminal renal angioplasty in the management of hypertension and renal failure in patients with renal artery stenosis.

Percutaneous transluminal renal angioplasty (PTRA) is an accepted method of treatment of hypertension resulting from renal artery stenosis. There is less information on the role of PTRA in patients with renal artery disease and renal impairment. We report on 30 patients who underwent PTRA for renal artery stenosis (13 had uncontrolled hypertension and normal renal function and 17 had hypertension and renal insufficiency; 26 patients had atheromatous disease, fibromuscular dysplasia was diagnosed in 2 and 2 patients had renal artery stenosis to a transplant kidney). These 30 patients had 43 PTRA procedures, with the 'initial technical success' rate of 81% and the 'overall success' rate of 79% after ten months. Results of renal PTRA on BP showed the initial benefit in 88% of patients: 71% 'cured' and 17% 'improved'. After ten months only 38% of patients could still be considered 'cured' and 33% 'improved'. Renal function 'improved' in 68% of patients who presented with renal insufficiency. An improvement of BP control or renal function was less likely in patients with bilateral severe atheromatous disease. PTRA is an effective treatment for renal artery stenosis. Satisfactory improvement of BP control and improvement or prevention of further deterioration of renal function may be achieved in a high proportion of patients.

Adult↗

Substantial urinary concentrations of material resembling beta-core fragment of chorionic gonadotropin beta-subunit in mid-menstrual cycle.

We measured the day-to-day variations in concentrations of beta-core, luteinizing hormone (LH), and alpha-subunit in urine during the menstrual cycle. The alpha-subunit concentrations showed a pattern similar to that of the LH concentrations. beta-Core-like material was increased during and up to 3 to 4 days after the surge in urine LH. The urine LH concentration was associated with the presence of beta-core immunoreactivity during the urine LH peak. Chromatography showed that, at the peak LH concentration and at 2 days after the LH peak, beta-core immunoreactivity could be accounted for by the presence of a peptide of low molecular mass similar to the beta-core molecule of hCG, but probably originating from the degradation of LH. The prolonged excretion of gonadotropin metabolites in the midcycle must be considered when beta-core is being assessed as a tumor marker.

Adult↗

Identification, purification, and characterization of S-adenosyl-L-methionine: isoliquiritigenin 2'-O-methyltransferase from alfalfa (Medicago sativa L.).

An O-methyltransferase (OMT) which methylates the 2'-hydroxyl of isoliquiritigenin (2',4,4'-trihydroxychalcone) was identified in alfalfa (Medicago sativa L.) seedlings and cell cultures. The OMT activity increased during early stages of seedling development and was predominantly located in roots. Treatment of alfalfa cell cultures with an elicitor from yeast resulted in a fivefold increase in chalcone OMT activity, whereas treatment of seedlings with CuCl2 caused a reduction in activity. The chalcone OMT was purified to near homogeneity from elicited alfalfa cell cultures. Only one form of the enzyme was found. It consisted of an active monomer of subunit Mr 43,000 which could be photoaffinity labeled with S-adenosyl-L-[methyl-3H]methionine. The purified OMT had a pH optimum of 9.0, pI of 4.7, and was highly specific for the 2'-hydroxyl of 2',4,4'-trihydroxychalcone, with essentially no activity toward narigenin chalcone, caffeic acid, or daidzein. Kinetic analysis indicated a sequential bi bi mechanism with Km values of 2.2 and 17.7 microM for 2',4,4'-trihydroxychalcone and S-adenosyl-L-methionine, respectively. S-Adenosyl-L-homocysteine was a potent inhibitor. The chalcone OMT represents the third distinct OMT isolated from alfalfa cell cultures.

Affinity Labels↗