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Biomedical subjects

D E Davies

Publications and source records attributed to D E Davies.

13 recordsLinked to original sources
PubMed1992

Multidomain binding of transforming growth factor alpha to the epidermal growth factor receptor.

Solubilized epidermal growth factor receptor (EGF-R) has been used in an extension of the Geysen epitope mapping protocol in order to provide additional insight into the amino acid residues in human transforming growth factor alpha (hTGF alpha) which are critical to recognition and binding. Overlapping heptapeptides which encompassed the 50 amino acid primary sequence of hTGF alpha were synthesized on a polyethylene solid phase, and the amount of detergent-solubilized EGF-R bound to each peptide was measured using ELISA. EGF-R appeared to bind reproducibly to four heptapeptides cognate to sequences in both the N- and C-domains of hTGF alpha (residues 22-28, 28-34, 36-42, and 44-50). Visualization of these four regions on three-dimensional solution phase structures of hTGF alpha, derived from 1H NMR measurements [Kline, T.-P., Brown, F.K., Brown, S.C., Jeffs, P.W., Kopple, K.D., & Mueller, L. (1990) Biochemistry 29, 7805-7813], indicated that the peptide segments are located on a single face of the protein and suggested the presence of a potential receptor binding cavity. If peptide segments within both the N- and C-domains of hTGF alpha are involved in binding to EGF-R, then this has direct consequences for possible molecular mechanisms by which receptor activation might take place. For example, the observed conformational flexibility in the six NMR-derived hTGF alpha structures due to variations in the main-chain torsion angles of Val-33, in combination with the involvement of residues from both domains in the proposed binding cavity, may imply that receptor activation results from interdomain reorientation in the protein ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Use of the rat air pouch model of inflammation to evaluate regional drug delivery.

We have used the rat inflammatory air pouch model to investigate some of the pharmacokinetic and pharmacodynamic issues relating to regional drug delivery. S(+)Ibuprofen was administered either intravenously or directly into the air pouch at the same time as the irritant (carrageenan). Serial samples of exudate and plasma were then taken and assayed for drug concentrations and various efficacy markers. Ibuprofen given intrapouch, was found to inhibit in a dose-dependent manner the concentration of prostaglandin E2 and the number of white cells in the exudate. Plasma and pouch concentration-time profiles are described for s(+)Ibuprofen: there is evidence for greater drug retention in the pouch than in plasma following regional and systemic delivery.

Animals↗
PubMed1991

Small unilamellar liposomes from mixed natural and polymeric phospholipids: stability and susceptibility to phospholipase A2.

The concept of the uncorkable liposome composed of phase-separated mixtures of a polymerized phospholipid and an enzymically digestible phospholipid has been investigated, using small unilamellar vesicles composed of mixtures of (polymerized) dienoylphosphatidylcholine (DENPC) and dimyristoylphosphatidylcholine (DMPC). Mixed liposomes, even those containing only 10% DENPC, were much more stable than DMPC liposomes, as indicated by the release of entrapped [3H]inulin or [14C]glucose. DMPC liposomes released entrapped solute on exposure to phospholipase A2, whereas mixed vesicles were resistant. The results are compared with those of an earlier study on monolayers of similar compositions. It is concluded that the liposomes, like the monolayers, are phase-mixed, and that uncorkable liposomes cannot be constructed from the phospholipid mixture employed. It is proposed that, until further experimental evidence is produced, the enzymatically uncorkable liposome must be regarded as a theoretical construct.

Carbon Radioisotopes↗
PubMed1990

Quantitation of pinocytosis in human monocytes during in vitro maturation into macrophages.

Methods are reported for the quantitative measurement of pinocytosis in human monocytes isolated from peripheral blood. The cells, in adherent culture in plastic wells, were exposed for periods of up to 48 h to culture medium containing 125I-labelled polyvinylpyrrolidone (50 micrograms/ml) and the pinocytosis enhancer suramin (500 micrograms/ml). Uptake of radiolabel was linear with time and was inhibited by colchicine (100 micrograms/ml), results that are consistent with uptake of radiolabelled substrate by pinocytosis but not with superficial adsorption of radiolabel. Similar results were obtained using a 125I-labelled vinylamine-vinyl-pyrrolidone copolymer as radiolabelled substrate. The rates of pinocytotic uptake of 125I-labelled polyvinylpyrrolidone (in the presence of suramin) and of 125I-labelled copolymer were measured at various stages of in vitro monocyte-to-macrophage maturation. In contrast to an earlier report, we found no consistent differences in pinocytotic activity between cells at different stages of differentiation.

Cell Differentiation↗
PubMed1990

Mixed monolayers of natural and polymeric phospholipids: structural characterization by physical and enzymatic methods.

This study has focused on physical characterization and enzymatic hydrolysis of mixed monolayers of a natural phospholipid substrate and a polymerizable phospholipid analogue. Such a mixed system presents the possibility to stabilize model biomembranes, vary the molecular environment within the layer through polymerization and simultaneously examine these influences on monolayer structure. Phospholipase A2 was used here as a sensitive probe of the molecular environment within these mixed, polymerizable monolayers to complement information obtained from isotherm and isobar data. The results clearly show a strong influence of molecular environment on phospholipase A2 activity, even if differences in the physical state of mixed monolayers are not detectable with isotherm and isobar measurements. Physical characterization indicated that both monomeric and polymeric mixed monolayers were phase-mixed. Enzyme hydrolysis, however, showed large differences in the ability of the enzyme to selectively hydrolyze the natural phosphatidylcholine component from the monomeric as opposed to the polymeric mixtures. This demonstrates a high sensitivity of phospholipase A2 to distinguish subtle differences in molecular arrangement within mixed monolayers on a molecular level.

Chemical Phenomena↗
PubMed1990

Urinary epidermal growth factor (hEGF) levels in patients with carcinomas of the breast, colon and rectum.

A specific two-site ELISA for human epidermal growth factor (hEGF) has been used to measure urinary hEGF/creatinine ratios in 30 normal subjects, 30 hospital in-patients with breast cancer and 30 hospital in-patients with colonic or rectal cancer. There was no significant difference between patients with breast cancer and controls. Although a statistically significant difference between patients with colorectal cancer and controls was observed, the biological significance of this observation is doubtful. No clear effect of the presence of breast or colorectal carcinoma on the urinary excretion of hEGF has been observed.

Adult↗
PubMed1990

Co-operation between interleukin-1 and the fibrinolytic system in the degradation of collagen by articular chondrocytes.

1. The interaction between interleukin 1 (IL-1) and the fibrinolytic system in the control of collagen degradation by rabbit chondrocytes has been investigated in a tissue-culture system where cells are grown on a 14C-labelled collagen matrix. 2. Culture of rabbit chondrocytes in the presence of human recombinant IL-1 beta at a concentration of 57pM for 48 h led to the presence of procollagenase but not active collagenase in the medium. The latent collagenase could be activated by incubation with an organomercurial, aminophenylmercuric acetate (APMA). 3. Addition of IL-1 beta to chondrocytes grown on a 14C-labelled collagen matrix did not increase the degradation of the matrix compared to control over a 48 h period. However, in the presence of plasmin (200 micrograms ml-1) or plasminogen (100 micrograms ml-1), IL-1 beta (57 pM) caused almost complete degradation of the collagen matrix. Plasmin or plasminogen alone caused only slight degradation of the collagen matrix. 4. Tissue inhibitor of metalloproteinases (TIMP) or the selective metalloproteinase inhibitor, SC44463, inhibited the degradation induced by IL-1 beta and plasminogen in a concentration-related manner and at concentrations that were correlated with inhibition of collagenase. 5. When concentrations of IL-1 beta which caused only minimal degradation of the matrix in the presence of plasminogen were combined with fibrin (1 microgram ml-1), there was almost total degradation of the matrix by 48 h. 6. These results indicate there is a synergistic interaction between IL-1 and the fibrinolytic system in the degradation of collagen by rabbit chondrocytes in culture.

Amides↗
PubMed1989

Monocyte-to-macrophage transition in vitro. A systematic study using human cells isolated by fractionation on Percoll.

Improved density-gradient methods, using Percoll or Nycodenz, have recently been introduced for the isolation of human monocytes, but the capacity of cells thus isolated to differentiate into macrophages has not been systematically studied. We have compared Percoll and Nycodenz methods for the isolation of monocytes from human blood. The Nycodenz method yielded a monocyte population of high purity, but the yield was low. The Percoll method gave almost quantitative yield of monocytes, and the contaminating cells, mostly lymphocytes, were readily washed away after allowing the monocytes to adhere to a plastic surface. The Percoll method was then successfully scaled up, providing a simple method to obtain the monocytes from 180 ml blood. These monocytes were maintained in culture and their capacity to mature into macrophages was studied, using the following criteria: increase in cell size and protein content, increase in specific activity of hexosaminidase, differential hexosaminidase release on exposure to opsonized zymosan and unopsonized polystyrene beads, loss of peroxidase activity, and development of fluoride-insensitivity by the cells' cytochemically demonstrable esterase. The cells also displayed morphological changes typical of the monocyte-to-macrophage transition. The procedures reported constitute a simple and reliable method for the production of human macrophages in increased yield.

Acetylglucosaminidase↗
PubMed1986

Human renin: a new class of inhibitors.

A new class of human renin inhibitor is described, containing a novel analogue of the peptide bond. High inhibitory potency was observed for octapeptide-length substrate analogues but inhibition progressively weakened as the molecule was shortened from the amino terminal end.

Amino Acid Sequence↗
PubMed1986

A preliminary investigation of the electrochemical properties of a nitrided stainless steel for dental applications.

A comparison has been made of the electrochemical behaviour of investment cast coupons of a 20Cr, 25Ni, Ti stabilized stainless steel (in the nitrided and un-nitrided conditions) with a cobalt-chromium alloy in order to make a preliminary assessment from the point of view of corrosion of the nitrided material for dental and other biomedical applications. Electrochemical tests have been carried out in vitro in artificial saliva and in Ringer's solution, with some additional tests carried out in natural saliva. Both the potential-time behaviour and the magnitude of the breakdown potential on anodic polarization suggest that the protective properties of the passivating film are substantially improved in the case of the nitrided stainless steel alloy.

Biocompatible Materials↗
PubMed1978

Clinical therapeutic evaluation of methylcysteine hydrochloride in patients with chronic obstructive bronchitis: a balanced double-blind trial with placebo control.

A double-blind, between-patient, placebo controlled trial was carried out to investigate the effects of methylcysteine hydrochloride in patients with chronic obstructive bronchitis. After a 2-week washout period on placebo, 30 patients were allocated at random to treatment for 6 weeks with either methylcysteine (1200 mg daily in Week 1, 800 mg daily in Week 2, then 600 mg daily) or with identical placebo tablets on the same regimen. During the post-treatment period, all patients returned to a single-blind placebo regimen (6 tablets daily) for a further 14 days. Assessments were made at the start, at regular intervals during the trial, and at the end of the post-treatment period, of subjective and objective measures of clinical response, and measurements of pulmonary function and certain physico-chemical properties of sputum. The results showed that methylcysteine increased sputum volume, reduced the viscidity of sputum, and significantly improved the subjective assessments of ease of expectoration and severity and frequency of cough, leading to a definite improvement in the patients' clinical state. No side-effects of clinical significance were reported and no abnormalities were found in any of the haematological, hepatic and renal function tests carried out.

Adult↗