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Biomedical subjects

A R White

Publications and source records attributed to A R White.

At least 73 records · Page 4Linked to original sources

Xyloglucan glucosyltransferase in Golgi membranes from Pisum sativum (pea).

Cell membranes from etiolated Pisum sativum (pea) tissues were separated by ultracentrifugation on linear sucrose density gradients and assayed for membrane marker and glycosyltransferase activity. Membrane fractions were shown to incorporate glucose from UDP-D-[14C]glucose into polysaccharides with glycosyl linkages consistent with synthesis of xyloglucan. A combined assay using g.c., radiogas proportional counting and m.s. was employed to determine the identities of 14C-labelled glycosyl residues and the glycosyl linkages between them. In glucan synthase I assays, membrane fractions enriched for Golgi membranes showed 14C incorporation into 4- and 4,6-glucose residues, with minor incorporation into 3-glucose residues. In glucan synthase II assays, all 14C incorporation was into 3- and 3,4-glucose. There was a shift in glycosyl linkage of 14C incorporation from predominantly 4-glucose at low UDP-glucose concentration to predominantly 3- and 3,4-glucose at high UDP-glucose concentrations. Mn2+ stimulated incorporation of radioactivity into 4,6-glucose residues characteristic of xyloglucan polysaccharides. Addition of exogenous UDP-xylose to assay mixtures stimulated incorporation into 4,6-glucose, with a maximum at 15 microM UDP-xylose.

Carbon Radioisotopes↗

Activity of human extravascular temocillin concentrations simulated in an in-vitro kinetic model against beta-lactamase producing gram-negative bacilli.

An in-vitro kinetic model was used to demonstrate the bactericidal activity of concentrations of temocillin achieved in extravascular body fluids following a 1 g intravenous dosage in man. Concentrations of temocillin attainable in peripheral lymph were bactericidal for ampicillin-resistant strains of Escherichia coli, Enterobacter cloacae and Klebsiella oxytoca. Likewise, concentrations of temocillin achieved in human blister fluid following a 12-hourly dosage regimen were bactericidal for cultures of Ent. cloacae and K. oxytoca which were resistant, respectively, to simulated blister fluid concentrations of cefotaxime and aztreonam. The bactericidal activity of extravascular concentrations of temocillin against these multiresistant, Gram-negative bacteria was a reflection of the beta-lactamase-stability and good pharmacokinetic properties of temocillin.

Anti-Bacterial Agents↗

Effect of low concentrations of clavulanic acid on the in-vitro activity of amoxycillin against beta-lactamase-producing Branhamella catarrhalis and Haemophilus influenzae.

Concentrations of amoxycillin/clavulanic acid achievable in the respiratory tract following oral dosage were assessed for in-vitro activity against beta-lactamase-producing strains of Branhamella catarrhalis and Haemophilus influenzae. In agar-dilution studies, 8 mg amoxycillin/l was required to inhibit 45 strains of beta-lactamase-producing B. catarrhalis, whereas all the strains were inhibited by 0.5 mg amoxycillin/l in the presence of 0.01 mg clavulanic acid/l. Similarly, 0.1 mg amoxycillin plus 0.05 mg clavulanic acid/l were bactericidal against beta-lactamase-producing strain of B. catarrhalis and prevented regrowth within 24 h. In tests against 43 beta-lactamase-producing strains of H. influenzae, concentrations of up to 128 mg amoxycillin/l were required for inhibition, whereas 32 strains (75%) were fully sensitive to amoxycillin (MIC 0.5 mg/l) in the presence of 0.12 mg clavulanic acid/l. These concentrations of amoxycillin/clavulanic acid were also bactericidal for a beta-lactamase-producing strain of H. influenzae. The study therefore showed that amoxycillin/clavulanic acid, at concentrations similar to those likely to be achieved in the respiratory tract following oral dosage, was bactericidal in vitro for beta-lactamase-producing isolates of B.catarrhalis and H. influenzae.

Amoxicillin↗

Antibacterial activity of resolved temocillin epimers.

The antibacterial activity of pure resolved R and S epimers of temocillin was determined in a variety of in-vitro test systems, including those that allowed measurement of activity during the early period following exposure to the agents, thus minimising the effect of epimerization. In conventional agar- and broth-dilution susceptibility tests involving incubation at 37 degrees C for 18 h, little difference was evident between the activities of the individual epimers. In contrast, in other tests of antibacterial activity, such as time-kill and turbidimetric studies, the R epimer and temocillin (R/S mixture 1.8:1.0) were shown to be more rapidly bactericidal than the S epimer. Overall, the R epimer and temocillin (R/S) exhibited a similar degree of bactericidal activity in vitro.

Bacteria↗

Antibacterial activity of ticarcillin in the presence of clavulanate potassium.

The antibacterial effects produced by ticarcillin disodium plus clavulanate potassium, a combination of the broad-spectrum penicillin ticarcillin, and the beta-lactamase inhibitor clavulanic acid as the potassium salt, have been measured in vitro and in experimental infection studies. The presence of clavulanic acid resulted in a significant enhancement of the activity of ticarcillin against a wide range of beta-lactamase-producing bacteria. These included ticarcillin-resistant strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, Yersinia enterocolitica, and the anaerobe Bacteroides fragilis. In addition, beta-lactamase-producing isolates of Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, and Staphylococcus aureus were susceptible to ticarcillin and clavulanate. Clavulanic acid did not influence the activity of ticarcillin against ticarcillin-susceptible bacteria. The bactericidal effects of the antibiotic combination were measured in an in vitro kinetic model in which the drug concentrations were varied to simulate those measured in humans after intravenous dosing with ticarcillin (3.0 g) and clavulanate potassium (100 mg clavulanic acid). In these tests, ticarcillin plus clavulanic acid had pronounced bactericidal activity against ticarcillin-resistant bacteria. The protection of ticarcillin by clavulanic acid from inactivation by bacterial beta-lactamases in vivo was demonstrated in experimental infection models in which the efficacy of the ticarcillin plus clavulanic acid combination against infections caused by beta-lactamase-producing bacteria was correlated with the presence of effective concentrations of both antibiotic and inhibitor at the site of infection.

Animals↗

Bactericidal effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid in in-vitro kinetic models.

The bactericidal effects of amoxycillin and ticarcillin in the presence of clavulanic acid against beta-lactamase-producing bacteria were investigated in in-vitro kinetic models. Amoxycillin/clavulanic acid was rapidly bactericidal as a simulated intravenous 1.2 g bolus dose, against a strain of Klebsiella pneumoniae highly resistant to amoxycillin. Similarly, ticarcillin/clavulanic acid at concentrations similar to those achieved with a 30 min iv infusion of ticarcillin/clavulanic acid (5.0 g/200 mg) produced bactericidal effects against a ticarcillin-resistant strain of Pseudomonas aeruginosa. Addition of gentamicin to the system resulted in a further enhancement of activity.

Amoxicillin↗

Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use.

Mupirocin (pseudomonic acid A), an antibiotic produced by Pseudomonas fluorescens, showed a high level of activity against staphylococci and streptococci and against certain gram-negative bacteria, including Haemophilus influenzae and Neisseria gonorrhoeae, but was much less active against most gram-negative bacilli an anaerobes. Nearly all clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, including multiply resistant strains, were susceptible (mupirocin MIC, less than or equal to 0.5 microgram/ml). There was no cross-resistance between mupirocin and clinically available antibiotics, and the selection of resistant variants in vitro occurred at a low frequency. Mupirocin was highly bound (95% bound) to the protein of human serum, and activity was reduced 10- to 20-fold in the presence of human serum. The activity of mupirocin was not greatly influenced by inoculum size but was significantly enhanced in acid medium. In tests of bactericidal activity, MBCs were 8- to 32-fold higher than MICs and the antibiotic demonstrated a slow bactericidal action in time-kill tests, resulting in 90 to 99% killing after 24 h at 37 degrees C.

Anti-Bacterial Agents↗

Temocillin. In vitro antibacterial activity.

Temocillin, a 6-alpha-methoxy penicillin derivative, was tested in vitro against 516 recent clinical isolates of Enterobacteriaceae. The compound exhibited good antibacterial activity, with 95% of isolates inhibited by a range 2 to 16 mg/L. Further studies, against selected isolates resistant to ticarcillin, piperacillin and cefuroxime (Klebsiella oxytoca, 25; Enterobacter species, 34; and Citrobacter species, 5), showed about half of the isolates of K. oxytoca (11/25) to be resistant to aztreonam (MIC range 16-greater than or equal to 128 mg/L), but susceptible to temocillin, cefotaxime and latamoxef. In general, the resistant strains of Enterobacter species tested were not susceptible to cefotaxime (MIC range 16-128 mg/L), or aztreonam (MIC range 1.0-64 mg/L), and many exhibited reduced susceptibility to latamoxef (MIC range 2-128 mg/L). In contrast, all the strains were susceptible to temocillin (MIC range 4-16 mg/L). The bactericidal activity of temocillin was confirmed against selected aztreonam-resistant strains of K. oxytoca and Enterobacter cloacae by conventional time-kill studies, and against a strain of E. cloacae in an in vitro model system designed to simulate the temocillin concentration profiles attained in extravascular fluid such as peripheral lymph. In the time-kill studies, temocillin concentrations of 16 and 32 mg/L were shown to effectively reduce the numbers of viable bacteria by 99 and 99.9%, respectively, within 12 hours. In the in vitro model system the numbers of bacteria were reduced 99.9% over the initial 4-hour period. In combination with aminoglycoside antibiotics, temocillin exerted a synergistic or partially synergistic effect (sigma FIC less than or equal to 0.75) against the majority of strains of Pseudomonas aeruginosa tested. When combined with piperacillin, cefotaxime or latamoxef, temocillin, unlike cefoxitin, exhibited no antagonism against strains of Enterobacteriaceae producing inducible cephalosporinases.

Anti-Bacterial Agents↗

Human pharmacokinetics and antimicrobial activities of the temocillin epimers.

The pharmacokinetics of the epimers of temocillin were investigated in 4 healthy male subjects following intravenous administration of 1g of temocillin disodium (free acid) which contains a R : S epimer ratio of approximately 65 : 35. The R epimer had a 2-fold greater total plasma clearance, a 23% larger volume of distribution and a shorter beta half-life than the S epimer. Intermediate values were obtained for total temocillin (R + S) from high pressure liquid chromatography (HPLC) data. In each plasma sample, the unbound fraction of the R epimer was generally 2-fold higher than that of the S epimer, which is suggested as the reason for the differences in the pharmacokinetic properties of the epimers. The temocillin pharmacokinetic parameters obtained from the microbiological assay data reflect most closely those for the R epimer derived from HPLC data. The resolved R epimer exhibited twice the potency of the S epimer against the microbiological assay organism Pseudomonas aeruginosa NCTC 10701. However, in tests for antibacterial susceptibility, for instance minimum inhibitory concentration (MIC) determinations involving prolonged incubation, there was little difference in the inhibitory activities of the resolved R and S epimers compared with temocillin (R + S), presumably as a consequence of the epimerization of the individual epimers. In contrast, in rapid tests for bactericidal activity, which minimise the effect of epimerization, the R epimer exhibited greater bactericidal activity than the S epimer.

Adult↗

Long-term hemodialysis at reduced dialysate flow rates.

20 stable hemodialysis patients were maintained on a dialysate flow rate of 300 ml/min (QD 300) to determine the safety of prolonged reductions in dialysate flow rate. After 24 months, QD 300 compared to QD 500 resulted in no change in weight, blood pressure, BUN, hematocrit, creatinine, bicarbonate, potassium, cholesterol, or calcium. Serum phosphate concentration increased between month 13 and month 17 but then stabilized. No adverse symptoms developed. EEGs and motor nerve conduction studies following 24 months at QD 300 were normal. We conclude that QD 300 does not impair dialysis efficiency for most small molecules and saves $1.38 per patient per dialysis.

Adult↗

Specialty hospitals: the challenge of the 1980s.

Specialty care institutions will face many concerns during the remainder of this decade. Increased intermediary and community education, establishing reliable benchmarks, understanding and dealing with a competitive marketplace, and establishing improved professional productivity are some of the major challenges.

Community Health Services↗

Alteration of in vivo cellulose ribbon assembly by carboxymethylcellulose and other cellulose derivatives.

In vivo cellulose ribbon assembly by the Gram-negative bacterium Acetobacter xylinum can be altered by incubation in carboxymethylcellulose (CMC), a negatively charged water-soluble cellulose derivative, and also by incubation in a variety of neutral, water-soluble cellulose derivatives. In the presence of all of these substituted celluloses, normal fasciation of microfibril bundles to form the typical twisting ribbon is prevented. Alteration of ribbon assembly is most extensive in the presence of CMC, which often induces synthesis of separate, intertwining bundles of microfibrils. Freeze-etch preparations of the bacterial outer membrane suggest that particles that are thought to be associated with cellulose synthesis or extrusion may be specifically organized to mediate synthesis of microfibril bundles. These data support the previous hypothesis that the cellulose ribbon of A. xylinum is formed by a hierarchical, cell-directed, self-assembly process. The relationship of these results to the regulation of cellulose microfibril size and wall extensibility in plant cell walls is discussed.

Acetobacter↗

Improvement in disequilibrium symptoms during dialysis with low glucose dialyzate.

This study compares the frequency of dialysis disequilibrium symptoms (DDS), in 17 stable non-diabetic chronic hemodialysis patients, during a period using low glucose (200 mg/100 ml) dialyzate to a similar period using a glucose free dialyzate. There was a significant decrease in the total number of symptoms as well as the frequency of headache and post-dialysis fatigue during the low glucose period as compared to the glucose free period. The decrease in nausea or vomiting, and cramps was not significant while frequency of hypotension was unchanged. Evaluation of serum sodium, potassium, BUN, glucose and osmolarity did not reveal significant differences during the two periods. Dialysis with a low glucose bath produces less DDS than glucose free dialyzate.

Blood Urea Nitrogen↗

Enzymatic hydrolysis of cellulose: Visual characterization of the process.

Cellulose from the Gram-negative bacterium Acetobacter xylinum has been used as a model substrate for visualizing the action of cellulase enzymes from the fungus Trichoderma reesei. High-resolution electron microscopy reveals that A. xylinum normally produces a ribbon of cellulose that is a composite of bundles of crystalline microfibrils. Visual patterns of the process of cellulose degradation have been established. Enzymes are initially observed bound to the cellulose ribbon. Within 10 min, the ribbon is split along its long axis into bundles of microfibrils which are subsequently thinned until they are completely dissolved within 30 min. Incubations with purified components of the cellulase enzyme system produced less dramatic changes in ribbon structure. Purified 1,4-beta-D-glucan cellobiohydrolase I (D) (EC 3.2.1.91) produced no visible change in cellulose structure. Purified endo-1,4-beta-D-glucanase IV (EC 3.2.1.4) produced some splaying of ribbons into microfibril bundles. In both cases, whole ribbons were present even after 60 min of incubation, visually confirming the synergistic mode of action of these enzymes.

Journal Article↗

Experimenter naiveté and imaginal judgments.

Finke and Kurtzman report that fields of resolution increase with increases in the diameter of both perceived and imagined circular patterns. Their study apparently was conducted by an experimenter who was aware of the hypotheses under test. In contrast to these results, we find no such increase for imagined circular patterns when the experimenter is not aware of the experimental predictions, even though our subjects received imagery training as extensive as that used by Finke and Kurtzman. Our results cannot readily be attributed to differences between the experiments, other than those associated with experimenter naiveté, for we replicated Finke and Kurtzman's observations that (a) the fields of resolution in perception increase with both the diameter and the relative brightness of the patterns and (b) the fields of resolution in imagery do not increase with the relative brightness of the patterns. Our results also challenge Finke and Kurtzman's contentions that imagery and perception are treated as functionally equivalent at area-processing levels of the visual system but not at contrast-processing levels.

Discrimination Learning↗