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Biomedical subjects

S E Phillips

Publications and source records attributed to S E Phillips.

At least 73 records · Page 4Linked to original sources
PubMed1993

Functional endoscopic surgery in children: a retrospective analysis of results.

The impact of chronic sinusitis on children has become more apparent as the awareness of the disease has increased. Consequently, the knowledge of its effect in the pediatric patient has expanded dramatically. Functional endoscopic sinus surgery (FESS) has become the primary surgical modality for treatment of this illness in children who have not responded to optimal medical management. A retrospective study was conducted in patients from 7 months to 17 years of age who were treated with FESS for chronic sinusitis refractory to medical therapy. Using a comprehensive parental questionnaire and a review of the medical charts, results were analyzed from these post-FESS children. Parents of the children were interviewed with a mean follow-up time of 21.8 months postoperatively. Factors discussed included chronic nasal obstruction, purulent nasal discharge, postnasal drip, chronic cough, halitosis, headaches, behavioral problems, allergies, and asthma symptoms. This preliminary investigation suggests that FESS is effective in treating medically recalcitrant severe chronic sinusitis in children.

Adolescent↗
PubMed1993

The simplified V-slope method of detecting the gas exchange threshold.

A simplified V-slope method was used to visually determine the first point of departure from linearity of carbon dioxide output (VCO2) plotted against oxygen uptake (VO2). The point at which VCO2 departed from a line with a slope equal to 1.00 was visually selected as the gas exchange threshold during incremental exercise. The simplified method of threshold detection was compared with a computerized V-slope method. Both methods were used to determine the gas exchange threshold during incremental cycling (10 W.min-1) in 17 untrained female subjects. The thresholds occurred at 41.1% and 45.1% of VO2max using the computerized and simplified V-slope methods, respectively. The correlation between the oxygen uptake measured at the threshold using the two methods was 0.95. Power output, VO2, and heart rate values determined at the gas exchange threshold using the simplified V-slope method were significantly higher than the corresponding values obtained using the computerized V-slope method. The simplified V-slope method consistently placed the gas exchange threshold at the work rate that was about 10 W above the power output determined by the computerized method. Although the two methods were highly correlated, the simplified V-slope method tended to overestimate threshold values determined from a computerized gas exchange method.

Adaptation, Physiological↗
PubMed1992

Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography.

The principal protein excreted in male rat urine, urinary alpha 2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine. Urinary alpha 2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha 2-globulin in lysosomes in the kidney, followed by the induction of renal cancer. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 A resolution) and rat urinary alpha 2-globulin (at 2.8 A resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding.

Alpha-Globulins↗
PubMed1992

Crystal structure of the met repressor-operator complex at 2.8 A resolution reveals DNA recognition by beta-strands.

The crystal structure of the met repressor-operator complex shows two dimeric repressor molecules bound to adjacent sites 8 base pairs apart on an 18-base-pair DNA fragment. Sequence specificity is achieved by insertion of double-stranded antiparallel protein beta-ribbons into the major groove of B-form DNA, with direct hydrogen-bonding between amino-acid side chains and the base pairs. The repressor also recognizes sequence-dependent distortion or flexibility of the operator phosphate backbone, conferring specificity even for inaccessible base pairs.

Bacterial Proteins↗
PubMed1992

Probing met repressor-operator recognition in solution.

The three-dimensional crystal structure of the Escherichia coli methionine repressor, MetJ, complexed with a DNA operator fragment is described in an accompanying article. The complex exhibits several novel features of DNA-protein interaction. DNA sequence recognition is achieved largely by hydrogen-bond contacts between the bases and amino-acid side chains located on a beta-ribbon, a mode of recognition previously hypothesized on the basis of modelling of idealized beta-strands and DNA, and mutagenesis of the Salmonella phage P22 repressors Arc and Mnt. The complex comprises a pair of MetJ repressor dimers which bind to adjacent met-box sites on the DNA, and contact each other by means of a pair of antiparallel alpha-helices. Here we assess the importance of these contacts, and also of contacts that would be made between the C-helices of the protein and DNA in a previous model of the complex, by studying mutations aimed at disrupting them. The role of the carboxy-terminal helix face in operator binding was unclear, but we demonstrate that recognition of operator sequences occurs through side chains in the beta-strand motif and that dimer-dimer interactions are required for effective repression.

Base Sequence↗
PubMed1992

Crystallization and initial X-ray analysis of the C2-subunit of crustacyanin.

Crystals of the C2-subunit of crustacyanin have been grown from solutions containing ammonium sulphate and 2-methyl-2,4-pentanediol as co-precipitants. The crystals belong to space group P2(1)2(1)2(1) (a = 42.0 A, b = 80.9 A, c = 110.8 A) with two subunits per asymmetric unit and diffract beyond 2.2 A resolution.

Carrier Proteins↗
PubMed1992

Three-dimensional structure of galactose oxidase: an enzyme with a built-in secondary cofactor.

Galactose oxidase is a copper-containing enzyme, which catalyses stereospecific oxidation of primary alcohols. The three-dimensional structure of the enzyme has been determined in this study by X-ray crystallography at high resolution. The molecule is almost entirely composed of beta-structures and consists of three domains. The arrangement of 28 beta-strands in the second domain is of particular interest, having seven four-stranded antiparallel beta-sheets with pseudo-sevenfold symmetry. The copper site has square-pyramidal coordination with two histidines, one tyrosine and one exogenous ligand at the equatorial sites and another tyrosine at the axial site. The most intriguing structural feature is a covalent bond between C epsilon 1 of Tyr-272, which is one of the equatorial ligands, and S gamma of Cys-228. This unexpected thioether bond, and Trp-290 stacked above it, strongly supports the presence of a tyrosine free radical in the enzyme as a 'built-in' secondary cofactor. Calculation of the molecular surface shows a small pocket at the copper site and suggests a substrate-binding model, which can explain the substrate specificity. A model for the catalytic mechanism, involving a tyrosine free radical and basic tryptophan, is also proposed.

Amino Acid Sequence↗
PubMed1992

Confirmation of true mosaic trisomy 20 in a phenotypically normal liveborn male.

A new case of prenatally detected mosaic trisomy 20 (79% trisomy 20 cells in amniocyte cultures) that was confirmed in newborn tissue is presented. A healthy male infant was delivered at term, with no dysmorphology or apparent malformations; this baby is developing normally. Twenty-five percent of foreskin and 17% of fetal cord cells also showed trisomy 20, while no trisomic cells were detected in newborn blood. High frequency mosaicism for trisomy 20 in this case was thus due to true embryonic origin. Extensive counseling and prenatal follow-up in this case led to an unaffected liveborn, and guarded optimism may be warranted for future cases of mosaic trisomy 20 detected prenatally.

Amniocentesis↗
PubMed1991

Crystallographic refinement of the three-dimensional structure of the FabD1.3-lysozyme complex at 2.5-A resolution.

The three-dimensional crystal structure of the complex between the Fab from the monoclonal anti-lysozyme antibody D1.3 and the antigen, hen egg white lysozyme, has been refined by crystallographic techniques using x-ray intensity data to 2.5-A resolution. The antibody contacts the antigen with residues from all its complementarity determining regions. Antigen residues 18-27 and 117-125 form a discontinuous antigenic determinant making hydrogen bonds and van der Waals interactions with the antibody. Water molecules at or near the antigen-antibody interface mediate some contacts between antigen and antibody. The fine specificity of antibody D1.3, which does not bind (K alpha less than 10(5) M-1) avian lysozymes where Gln121 in the amino acid sequence is occupied by His, can be explained on the basis of the refined model.

Amino Acid Sequence↗
PubMed1991

Crystallization of and preliminary X-ray data for the mouse major urinary protein and rat alpha-2u globulin.

Crystals of the mouse major urinary protein (MUP) and rat alpha-2u globulin (AMG) have been grown from solutions of polyethylene glycol 3350 and CdCl2, respectively. The crystals differ both in their morphologies and space groups but have very similar unit cell sizes. AMG crystallized in P2(1) (a = 56.6 A, b = 103.8 A, c = 62.7 A, beta = 95.1 degrees) with four subunits/asymmetric unit, while MUP gave crystals in P4(1)2(1)2 or P4(3)2(1)2 (a = 57.3 A, c = 109.9 A) with one subunit/asymmetric unit. Both crystal forms diffract beyond 2.8 A resolution.

Alpha-Globulins↗
PubMed1991

Novel thioether bond revealed by a 1.7 A crystal structure of galactose oxidase.

Galactose oxidase is an extracellular enzyme secreted by the fungus Dactylium dendroides. It is monomeric, with a relative molecular mass of 68,000, catalyses the stereospecific oxidation of a broad range of primary alcohol substrates and possesses a unique mononuclear copper site essential for catalysing a two-electron transfer reaction during the oxidation of primary alcohols to corresponding aldehydes. Recent evidence arguing against a Cu(III)-Cu(I) couple implies the existence of a second redox-active site proposed to involve pyrroloquinoline quinone or a tyrosine radical. We now report the crystal structure of galactose oxidase at 1.7 A resolution. This reveals a unique structural feature at the copper site with a novel thioether bond linking Cys 228 and Tyr 272 in a stacking interaction with Trp 290. We propose that these molecular components stabilize the protein free-radical species essential for catalysis and thus provide a 'built-in' secondary cofactor. This feature may represent a new mechanism for mediating electron transfer in metalloenzymes in the absence of exogenous cofactors.

Binding Sites↗
PubMed1990

Reversible inhibition of rat hepatic glutathione S-transferase 1-2 by bilirubin.

The inhibition of rat hepatic glutathione (GSH) S-transferase 1-2 by bilirubin exhibited pseudo first-order kinetics with k(obs) values of 0.0214 +/- 0.0005 and 0.040 +/- 0.008 sec-1 at 4 and 8 microM bilirubin, when followed to 72 and 84% completion respectively. These correspond to calculated second-order rate constants of 5.3 +/- 0.1 x 10(3) and 5.0 +/- 1.0 x 10(3)/M.sec. The extent of inhibition of the transferase increased with bilirubin concentration, with half-maximal inhibition at 4 microM bilirubin. Inhibition was reversed by 10-fold dilution of bilirubin or by increasing the pH from 6.0 to 7.4. Premixing 0.2 to 0.5 microM albumin, hemoglobin or aldolase with bilirubin prevented inhibition of GSH S-transferase 1-2. Protection by these proteins occurred at a selected high concentration (0.2 to 0.4 microM) at which they reduced free bilirubin to concentrations (less than 0.5 microM) that did not inhibit isoenzyme 1-2 significantly. No protection was afforded by a selected low protein concentration (0.001 to 0.01 microM) which did not strikingly reduce bilirubin levels in solution. We conclude that bilirubin inhibition of GSH S-transferase 1-2 appears to be a second-order process; the reaction is clearly first-order with respect to GSH S-transferase and appears also to be first-order with respect to bilirubin. It is proposed that (a) inhibition of GSH S-transferase 1-2 results from slow, reversible bilirubin binding, and (b) added proteins appear to prevent GSH S-transferase inhibition by binding high molar ratios of bilirubin.

Albumins↗
PubMed1990

Bacteremia detected by lysis direct plating in a neonatal intensive care unit.

The density of bacteremia was determined in 787 neonatal blood specimens by using the 1.5-ml Isolator microbial tube. Coagulase-negative staphylococci were the organisms isolated most frequently from both true-positive cultures (25 of 50) and contaminated cultures (57 of 131). Based on the first positive culture in an episode of sepsis, there were no cases of coagulase-negative staphylococcal sepsis associated with counts of less than or equal to 5 CFU/ml. Indwelling intravascular lines were associated with the majority of the episodes of sepsis. The distribution of pathogens causing sepsis in this neonatal population was similar to the distribution of microorganisms associated with cannula-related sepsis in other hospitalized patients.

Bacteriological Techniques↗
PubMed1989

Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor.

The three-dimensional crystal structure of met repressor, in the presence or absence of bound corepressor (S-adenosylmethionine), shows a dimer of intertwined monomers, which do not have the helix-turn-helix motif characteristic of other bacterial repressor and activator structures. We propose that the interaction of met repressor with DNA occurs through either a pair of symmetry-related alpha-helices or a pair of beta-strands, and suggest a model for binding of several dimers to met operator regions.

Apoproteins↗
PubMed1989

Cooperative tandem binding of met repressor of Escherichia coli.

We present biochemical and genetic data to support the hypothesis that the Escherichia coli met repressor, MetJ, binds to synthetic and natural operator sequences in tandem arrays such that repression depends not only on the affinity of the DNA-protein interaction, but also on protein-protein contacts along the tandem array. This represents a novel form of regulatory switch. Furthermore, there seems to be homology between the organization of the met and trp operators.

Apoproteins↗