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Biomedical subjects

M J Lawrence

Publications and source records attributed to M J Lawrence.

At least 37 records · Page 2Linked to original sources

Aggregation and surface properties of synthetic double-chain non-ionic surfactants in aqueous solution.

Double-chain non-ionic surfactants have been synthesized with the general formula 2CnMPEG750, where n is the number of carbons in the alkyl chains and 750 is the molecular weight of the monomethoxypolyoxyethylene (MPEG) head group. The aggregation and surface properties in dilute aqueous solution (< 1.0% w/w) of surfactants with n = 8, 10 and 12 have been determined. Each of the surfactants formed clear, foaming, non-birefringent solutions. Total-intensity light scattering indicated the presence of micelles with aggregation numbers of 36, 68 and 74 for the 2C8, 2C10 and 2C12 surfactants, respectively, whereas photon-correlation studies yielded radii, assuming spherical aggregates, of 59-103 A. Surface-tension measurements gave critical micelle concentrations for the surfactants in the range 1.15-7.24 x 10(-6) M; these, as expected, decreased when the number of carbon atoms in the alkyl chains was increased. Such studies are important in the design of new surfactants as vehicles for drug delivery because it is imperative to be able to predict the type of aggregate formed by a surfactant.

Light↗

Molecular analysis of two functional homologues of the S3 allele of the Papaver rhoeas self-incompatibility gene isolated from different populations.

The S3 allele of the S gene has been cloned from Papaver rhoeas cv. Shirley. The sequence predicts a hydrophilic protein of 14.0 kDa, showing 55.8% identity with the previously cloned S1 allele, preceded by an 18 amino acid signal sequence. Expression of the S3 coding region in Escherichia coli produced a form of the protein, denoted S3e, which specifically inhibited S3 pollen in an in vitro bioassay. The recombinant protein was ca. 0.8 kDa larger than the native stigmatic form, indicating post-translational modifications in planta, as was previously suggested for the S1 protein. In contrast to other S proteins identified to date, S3 protein does not appear to be glycosylated. Of particular significance is the finding that despite exhibiting a high degree of sequence polymorphism, secondary structure predictions indicate that the S1 and S3 proteins may adopt a virtually identical conformation. Sequence analysis also indicates that the S1 and S3 proteins may adopt a virtually identical conformation. Sequence analysis also indicates that the P. rhoeas S alleles share some limited homology with the SLG and SRK genes from Brassica oleracea. Previously, cross-classification of different populations of P. rhoeas had revealed a number of functionally identical alleles. Probing of Western blots of stigma proteins from plants derived from a wild Spanish population which contained an allele functionally identical to the Shirley S3 allele with antiserum raised to S3e, revealed a protein (S3s) which was indistinguishable in pI and Mr from that in the Shirley population. A cDNA encoding S3s was isolated, nucleotide sequencing revealing a coding region with 99.4% homology with the Shirley-derived clone at the DNA level, and 100% homology at the amino acid level.

Alleles↗

Cloning and expression of a distinctive class of self-incompatibility (S) gene from Papaver rhoeas L.

We present the identification, cloning, and characterization of a self-incompatibility (S) gene from Papaver rhoeas that has no significant homology to any previously reported gene sequences, including S genes from other species. This result suggests that a different self-incompatibility mechanism may be operating in this species and has important implications for the evolutionary relationships between the S genes. The S1 cDNA was cloned by using an oligonucleotide based upon N-terminal amino acid sequence data from stigmatic proteins that show complete linkage with the S1 gene. The single-copy gene has been expressed in Escherichia coli to test biological activity. Although the recombinant S1 protein (S1e) is not processed in the same way as the protein produced in the plant, it exhibits, in vitro, the specific pollen inhibitory activity expected of an S gene product; pollen carrying the S1 allele is inhibited, whereas pollen not carrying S1 is not inhibited. These results provide definitive demonstration that the product of a cloned S gene has S-specific pollen inhibitory activity.

Alleles↗

Analysis and modelling of the structures of beta-cyclodextrin complexes.

A systematic computer graphics study of all available beta-cyclodextrin crystal structures has been carried out specifically to aid in the modelling and design of beta-cyclodextrin-drug complexes. The analyses show that the basic conformation of the molecule remains constant among natural, mono-substituted and partially permethylated beta-cyclodextrins, with major changes observed only in the case of full permethylation. In all the structures, however, there are no significant perturbations caused by guest molecule inclusion. On the basis of these observations models are proposed for the structures of beta-cyclodextrin-indomethacin complexes, the principal features of which are shown to be consistent with the data obtained in 1H-NMR studies.

Carbohydrate Sequence↗

A comparison of the incorporation of model steroids into non-ionic micellar and microemulsion systems.

The incorporation of testosterone and two of its esters, and progesterone and one of its esters (log Poct varying from 3.3 to 6.9) into 2% w/w soybean oil/Brij 96 microemulsions and Brij 96 surfactant systems has been examined. Possible sites of incorporation have been investigated. The drug carrying improvement of an oil-in-water microemulsion over a micellar system appears to depend on the solubility of the drug in the dispersed oil phase and is significant only for very lipophilic drugs.

Chemical Phenomena↗

VESICA: computer graphics modeling of lipid vesicles.

A vesicle simulation and computer analysis program, VESICA, is described which employs spherical projections of triangularly tessellated icosahedra to produce molecular graphics models of the three-dimensional structures of lipid vesicles. The program is used to analyze the molecular architecture of small unilamellar vesicles of dipalmitoyl-phosphatidylcholine and is demonstrated as a worthwhile investigative tool for determining the factors that govern the minimum vesicle size.

1,2-Dipalmitoylphosphatidylcholine↗

Effect of structural variations of non-ionic surfactants on surface properties: surfactants with semi-polar hydrophobes.

The surface properties of a series of non-ionic surfactants in which a polar group (either an ether or a keto group) has been introduced into a hydrocarbon chain of octadecylpolyoxyethylene glycol monoether (C18E17-19) have been investigated. Surface tension measurements indicated that the critical micelle concentrations for these semi-polar surfactants in aqueous solution were all significantly higher than those of C18E22, the corresponding unsubstituted octadecylpolyoxyethylene glycol monoether. The minimum areas per molecule of the semi-polar surfactants in the surface monolayer were all larger than the area obtained for C18E22, from which it was concluded that the hydrophobe, and not the polyoxyethylene chain was the main determinant of surface area.

Micelles↗

Effect of structural variations of non-ionic surfactants on micellar properties and solubilization: surfactants with semi-polar hydrophobes.

Novel non-ionic surfactants have been synthesized in which a polar group (either an ether or a keto group) has been introduced into the hydrocarbon chain of an octadecylpolyoxyethylene glycol monoether (C18En) with an oxyethylene chain length, n, of 17-18 units. Light scattering studies have indicated aggregation numbers for these semi-polar surfactants in aqueous solution of between 55-65% of that of an unsubstituted octadecylpolyoxyethylene glycol monoether, C18E22. The solubilizing capacities of the semi-polar surfactant micelles for test compounds which were mainly solubilized at the polyoxyethylene/core interface were lower than those of C18E22 whilst solubilizates which exhibited a reasonable degree of solubility in both the interface and the micellar core showed an increased solubilization.

Chemical Phenomena↗

Airborne contact urticaria due to sodium benzoate in a pharmaceutical manufacturing plant.

Three workers exposed to airborne contact with sodium benzoate (SB) in a pharmaceutical plant developed transient urticaria related to skin contamination with SB. Patch test responses to SB and benzoic acid (BA), without occlusion, were similar to those of three previously unexposed controls in keeping with the nonimmunologic nature of the reaction. Sweating, which lowers skin pH and increases topical BA concentration, appeared to increase the susceptibility to urticaria in two of the three workers. Ventilation and hygiene control methods designed to reduce SB skin contamination eliminated the problem in the workplace.

Adult↗

Allergic contact dermatitis due to nonylphenol ethoxylate (nonoxynol-6).

The non-ionic emulsifier "nonoxynol-6" found in an industrial waterless hand cleanser induced allergic contact dermatitis on the upper extremities of a uranium mill maintenance worker. The chemical is an irritant for the rabbit. It was not shown to be a cutaneous sensitizer for the albino guinea pit using the guinea pig maximization test.

Animals↗

A fibre optic ring illumination system for use in low-powered dark field (including Rheinberg method) video, cine and photomicrography.

A fibre optic ring illuminator normally used as a reflected light source with a low-powered microscope is here used as a substage illuminator with a stereo zoom microscope, to give uniform dark field (dark ground) illumination. This development was primarily for use in colour video recordings giving good contrast pictures but can also be used successfully in cine and photomicrography, at magnifications ranging from X 1.5 to X 124. Its application is particularly suitable for the observation of biological specimens.

Animals↗

Surfactant systems: microemulsions and vesicles as vehicles for drug delivery.

Although surfactants have been widely used as pharmaceutical adjuvants for many years, it is only relatively recently that their phase structures have been seriously considered as drug delivery vehicles per se. This review highlights the work to date investigating the potential of microemulsions as drug carriers and also reports on preliminary studies performed on the use of vesicles formed from nonionic surfactants.

Chemistry, Pharmaceutical↗