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Biomedical subjects

C E Wright

Publications and source records attributed to C E Wright.

142 records · Page 8Linked to original sources
PubMed1980

Use of a gradient intensifying screen for scoliosis radiography.

A gradient intensifying screen composed of rare earth phosphors and calcium tungstate was developed. It provides uniform film density when there is a graded increase in subject density. Use of this screen for scoliosis radiography provides an improved image and reduces radiation exposure.

Absorptiometry, Photon↗
PubMed1979

Genetics of cell fusion: human chromosome 10 assignment of a gene (FUSE) that promotes polykaryocyte formation.

FUSE, a human gene which promotes polykaryocyte formation, has been identified and examined in cocultivation assays between rat XC cells and human-mouse hybrids retaining different combinations of human chromosomes. Polykaryocyte formation was never detected when parental cells of hybrids were cocultivated with XC cells. Somatic genetic synteny analysis employing different hybrid sets demonstrated that FUSE was coexpressed with the chromosome 10 markers glutamate oxaloacetate transaminase (GOTs) and an external membrane protein (EMP-130). Cytogenetic analysis confirmed this assignment to human chromosome 10. FUSE was expressed by hybrids made with both human leukocytes and fibroblasts from several individuals, indicating the gene is found in different tissues and may be ubiquitous. Only XC cells were involved in polykaryocyte formation as demonstrated by 33258 Hoechst staining and the absence of heteropolymers between rat and cell hybrid multimeric enzymes. Evidence suggests that the gene FUSE produces a nondiffusible and noninfectious product that is associated with the human-mouse hybrid surface.

Animals↗
PubMed1977

The combining site of the dinitrophenyl-binding immunoglobulin A myeloma protein MOPC 315.

Magnetic-resonance techniques are used to refine the model of the combining site of the Fv fragment of the dinitrophenyl-binding mouse myeloma protein MOPC 315 constructed by Padlan, Davies, Pecht, Givol & Wright (1976) (Cold Spring Harbor Symp. Quant. Biol.41, in the press). Light-absorption studies indicate a dinitrophenyl-tryptophan interaction in the Fv fragment of the type occurring in free solution. The Dnp-aspartate-tryptophan complex is therefore used as a starting point for the n.m.r. (nuclear-magnetic-resonance) analysis of the dinitrophenyl-Fv fragment interaction. Ring-current calculations are used to determine the geometry of the complex. The specificity of complex-formation between dinitrophenyl and tryptophan is confirmed by the lack of ring-current shifts of the dinitrophenyl resonances when tryptophan is replaced by any other aromatic amino acid. Proton n.m.r. difference spectra (at 270MHz), resulting from the addition of a variety of haptens to the Fv fragment, show that the combining site is highly aromatic in nature. Calculations on the basis of ring-current shifts define the geometry of the combining site, which involves a dinitrophenyl ring in van der Waals contact with four aromatic amino acid residues on the protein. The observation of a nuclear Overhauser effect on the H((3)) resonance of the dinitrophenyl ring provides additional constraints on the relative geometry of the H((3)) proton and an aromatic amino acid residue on the Fv fragment. The specificity of the Fv fragment for dinitrophenyl ligands arises from a stacking interaction of the dinitrophenyl ring with tryptophan-93(L), in an ;aromatic box' of essentially tryptophan-93(L), phenylalanine-34(H) and tyrosine-34(L); asparagine-36(L) and tyrosine-34(L) also contribute by forming hydrogen bonds with the nitro groups on the dinitrophenyl ring. The n.m.r. results also confirm that the antibody-hapten reaction may be visualized as a single encounter step. An Appendix shows the method of calculation of ring currents for the four aromatic amino acids and their use in calculating structures.

Binding Sites, Antibody↗
PubMedDate not supplied

Synthesis and biological characterization of a series of analogues of omega-conotoxin GVIA.

The 27-residue polypeptide omega-conotoxin GVIA (omega-CgTx), from the venom of the cone shell Conus geographus, blocks N-type neuronal calcium channels. It contains three disulphide bridges. We report here the synthesis and biological characterization of a series of analogues in which one disulphide has been replaced by substitution of appropriate Cys residues with Ser, viz. [Ser1,16]-omega -CgTx, [Ser8,19]-omega-CgTx, [Ser15,26)-omega-CgTx, [Ser16]-omega-CgTx8-27 and [Ser15]-omega-CgTx1-19. All syntheses were conducted manually using either Boc or Fmoc methodology. Deprotected peptides were oxidized to their bridged forms using either aerial oxidation or aqueous dimethyl sulphoxide. Peptides were purified using RP-HPLC, and their purity and identity were checked by RP-HPLC, capillary electrophoresis and mass spectrometry. Inhibition of neuronal N-type calcium channels was assessed as the inhibition of the twitch responses of rat vas deferens stimulated with single electrical pulses at 20 second intervals. None of these analogues was biologically active, suggesting that the disulphides play an important role in maintaining biological activity.

Amino Acid Sequence↗
PubMedDate not supplied

Techniques to study the pharmacodynamics of isolated large and small blood vessels.

Techniques are described for the mounting of large artery and vein ring segments on wire hooks in an organ bath chamber. Each vessel is set to normalised conditions of passive force directly determined from its circumferential length-tension relationship. This rigorous set up follows the normalisation routine established by Mulvany and Halpern for small resistance arteries mounted under isometric conditions on a wire myograph. Techniques for electrical field stimulation, and simultaneous force and membrane potential (Em), are described. An example of electrical field stimulation is given for the unravelling of the role of ATP in sympathetic co-transmission in rat mesenteric small arteries. Other techniques described include isobaric, isotonic mounting of small vessels, their morphology and receptor characterisation. Examples include human buttock skin arteries, small coronary arteries (CAs), and vasa vasorum arteries taken at coronary bypass graft operations. The underlying philosophy is that every segment of blood vessel constituting the intact resistance bed has its own pharmacology. There is no 'ideal' preparation. Whether the vessel is studied under isometric, isotonic, or isobaric conditions, the experimentalist must be wary of the influence of the methodology on the pharmacodynamics. These influences may not be the same between normal and diseased vessels.

Acetylcholine↗
PubMedDate not supplied

Techniques to measure pharmacodynamics in the intact vasculature.

Techniques are described for the intravenous, close intraarterial, or perivascular delivery of drugs in conscious or anaesthetized animals. Examples of the determination of pharmacodynamic parameters such as regional blood flow, large artery diameter, resistance, conductance, and blood pressure are given for conscious rabbits and anaesthetized dog preparations. An important issue is how to determine the direct vascular action of an injected drug in the light of rapid and powerful autonomic reflex buffering effects especially in healthy conscious animals. The methods of measurement of drug action on the baroreceptor-heart rate reflex and postural adaptation (90 degrees tilt) reflex in the conscious rabbit are explained. Finally, the changes to large and small artery morphology are explored in the rabbit hindlimb following conduit femoral artery ligation to induce arteriogenesis and angiogenesis. This work aims to highlight approaches to exploring drug action in vivo, a much neglected skill in the repertoire of the modern cardiovascular pharmacologist.

Animals↗
PubMedDate not supplied

Effect of injection volume on the bioavailability of sterile medroxyprogesterone acetate suspension.

The influence of injection volume on the absorption and bioavailability of medroxyprogesterone acetate (MPA) was studied. A single i.m. injection of MPA 400 mg was administered to 24 healthy men; 12 of the subjects received 4 ml of a 100 mg/ml suspension of the drug, and the other 12 subjects were given 1 ml of a 400 mg/ml suspension. Blood samples for MPA determinations were collected periodically during a 202-day period after drug administration. Mean steady-state serum concentrations of MPA were simulated from single-dose data to reflect those achieved after standard dosage regimens. Values for area under the serum concentration-time curve and time required to reach peak serum concentrations were compared between subjects receiving different injection volumes of MPA. Mean peak serum concentration were significantly higher and occurred significantly sooner in subjects receiving the 4-ml injection of MPA than in those given the 1-ml injection. No significant differences in areas under the serum concentration-time curve were noted in subjects receiving different injection volumes. The rate but not the extent of absorption of injectable MPA suspension is enhanced by increasing the injection volume of equivalent doses from 1 ml to 4 ml.

Adult↗
PubMedDate not supplied

Single- and multiple-dose pharmacokinetics of oral alprazolam in healthy smoking and nonsmoking men.

The effect of tobacco smoking on alprazolam pharmacokinetics is investigated. Ten healthy men (five smokers and five nonsmokers) between 19 and 42 years old received a single oral 1-mg alprazolam dose followed 48 hours later by alprazolam 0.5 mg every eight hours for six days. Multiple serum samples were collected following the initial dose and after the last 0.5-mg dose and analyzed by gas-liquid chromatography for alprazolam. Pharmacokinetic values were calculated, and mean data from the smoking and nonsmoking groups were compared. Mean plasma alprazolam concentrations during the single-dose phase were comparable between groups. During the multiple-dose phase, mean plasma concentrations were 15-30% lower in the smokers. Total body clearance of alprazolam was 24% greater and the apparent volume of distribution was 17% less in smokers. The elimination half-life was 49% greater in nonsmokers. These differences were not significant. Changes were not observed in elimination half-life or clearance after alprazolam cessation. Steady-state pharmacokinetic values during the multiple-dose phase correlated with values observed following the single dose. Although not significantly different, alprazolam elimination was more rapid in smokers than in nonsmokers.

Adult↗