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Biomedical subjects

E Tomlinson

Publications and source records attributed to E Tomlinson.

17 recordsLinked to original sources
PubMed1991

Design of site-specific protein drugs.

The ability to clone and express proteins at high levels of abundance and purity has led to their increasing consideration as therapeutic agents. The use of various protein engineering and recombinant DNA techniques has enabled progression to where proteins can be tailored so that they have not only the ability to interact with a unique (extra)cellular component in order to produce a pharmacological effect, but their structure can be altered so as to achieve a selective biological disposition. This ability to control the biological dispersion of proteins is becoming a key element in the design of therapeutic polypeptides and proteins, finding application in modalities intended for treating HIV infections, accessible tumor masses, and diseases of the hematopoietic system, etc. For recombinant site-specific systems to be successfully introduced into the clinic, radically different approaches are required during their development and clinical testing. These relate not only to the pharmacokinetics and receptor availability of the drug, but also its pharmacodynamics, its analytics and its safety pharmacology. This contribution examines how the control of the biological disposition of proteins may be achieved using both site-directed mutagenesis, sequence re-ordering, hybrid protein formation, protein resurfacing, as well as synthetic adduction to polymers.

Chromosome Deletion↗
PubMed1979

Ion-pair high-performance liquid chromatography: the use of low concentrations of long-chain alkylbenzyldimethylammonium chlorides for resolving anionic solutes.

The qualitative and quantitative determination of large anionic solutes, including the drug sodium cromoglycate, by an ion-pair high-performance liquid chromatographic technique using alkylbenzyldimethylammonium chlorides as pairing ions is described. The method provides a sensitive and selective assay for the solutes examined in both simple aqueous solutions and in complex biological fluids, and requires no pre-extraction step. Retention mechanisms are discussed.

Anions↗
PubMed1979

Surfactant ion-pair high-performance liquid chromatography of tryptophan and some of its metabolites in biological fluids.

A rapid, sensitive assay for tryptophan and some of its metabolites in urine, plasma and saliva has been developed using sodium dodecylsulphate as a pairing ion in a surfactant ion-pair high-performance liquid chromatography technique. The method is highly selective for tryptophan which is separated from its main indoleamine metabolites, 5-hydroxytryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, and from kynurenine. The usefulness of the assay has been demonstrated in plasma level and urinary excretion studies of orally administered tryptophan.

Biological Availability↗
PubMed1979

Sensitivity of Pseudomonas aeruginosa envelope mutants to alkylbenzyldimethylammonium chlorides.

A series of stepwise polymyxin-resistant envelope mutants of Pseudomonas aeruginosa was used to test the activity of a homologous series (C10-C18) of alkylbenzyldimethylammonium chlorides. A sterilization kinetics procedure in deionized water was devised to avoid amounts quaternary compound above the critical micelle concentration. In all cases, there was a linear relationship between the logarithm of the rate of change of the colony count with time and the logarithm of the homolog concentration. For all strains, there was a linear relationship between alkyl chain length and the concentration required to reduce the colony count to 10% in 2 hr. The stepwise series of polymyxin-resistant strains increased in resistance to polymyxin about threefold for each step. In general, this increase resulted in a similar increase in resistance to the quaternary compound. It is proposed that death in this system may primarily be a consequence of damage to the outer membrane rather than to the cytoplasmic membrane.

Anti-Infective Agents, Local↗
PubMed1979

A new look at pleoptics.

Sixty-four patients who did not respond adequately to passive conventional occlusion were treated with active pleoptic therapy, and followed with orthoptic therapy when fusion potential was demonstrated. Patients ranged in age from 4 to 17 years, and ranged in visual acuity from 20/30 to 20/100. Seventeen patients had some fusion prior to starting pleoptics. All 64 patients achieved an immediate post-therapy acuity of 20/30 or better; 25 were fusing and demonstrated some stereopsis. Twenty-seven patients were followed for a period of one to ten years, including the 25 patients who were fusing at completion of therapy. Twenty-four (88%) maintained visual acuity of 20/30 or better. All fused either normally or with ARC. Three patients, whose visual acuity dropped to 20/50, had no fusion. Only one patient who had fusion at the completion of therapy was unable to maintain it. We conclude, therefore, that pleoptics retains values in the treatment of amblyopic patients with steady and unsteady central fixation, in those situations where conventional occlusion in unsuccessful.

Adolescent↗
PubMed1978

Acquisition and performance difference between normal and mentally handicapped adults on a complex assembly task.

Several single studies concerned with work training with the mentally handicapped have been reported in the literature (Bitter & Bolanovich, 1966; Huddle, 1967; Gold, 1969; Screven, Straka & Lafond, 1971). Most have been concerned with issues of acquisition and motivation to perform. No studies have been reported which focus on the evaluation of different techniques of training or which assess rate of acquisition against that of non-handicapped controls. The aim of this experiment is twofold. It uses a complex task, analysed by MTM-2, to enable comparison between the performances of mentally handicapped adults and adults from a 'normal' population, in the acquisition of new work skills. Various strategies of training were compared and the increase in the rate and quality of performance following acquisition was measured for both, in terms of speed and accuracy of production. Results add further support for the notion that the potential of mentally handicapped individuals is commonly underestimated. It is hoped that the findings provide a basis from which further experiments can be developed and evaluated.

Adult↗
PubMed1977

Effect of colloidal association on the measured activity of alkylbenzyldimethylammonium chlorides against Pseudomonas aeruginosa.

The antibacterial activities of a homologous series (C8-C18) of alkylbenzyldimethylammonium cholorides (ABDAC) against Pseudomonas aeruginosa have been measured using both a minimum inhibitory concentration (MIC) procedure and a sterilization kinetics test carried out in deionized water. There was a log-linear relationship between activity measured by kinetics and carbon number. With MIC there was a log-linear relationship up to C14, when there was a turndown in activity. Consideration of the colloidal association of ABDAC in deionized water and in a simple salts growth media leads us to suggest that use of high concentrations of nutrient salts in MIC tests will lower the effective concentration of the surface active agents. This change may be responsible for the turndown in activity observed in MIC tests, and that in such circumstances the MIC test does not give a true reflection of the intrinsic activity of the compounds. Literature reports of parabolic relationships between ABDAC alkyl chain length and antimicrobial activity are reinterpreted on this basis.

Benzalkonium Compounds↗
PubMed1975

Chromatographic hydrophobic parameters in correlation analysis of structure-activity relationships.

The use of RM and delta RM parameters as indices of hydrophobicity for inclusion in quantitative structure activity relationships has been studied. The relationship between these parameters and other free-energy related parameters is illustrated theoretically and experimentally. It is suggested that the chromatographically obtained parameters could find a wider applicability in structure-activity relationships, and that their use would result in improved correlation of data.

Absorption↗