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Biomedical subjects

K E Taylor

Publications and source records attributed to K E Taylor.

44 records · Page 3Linked to original sources

A continuous spectrophotometric method for monitoring phospholipase D-catalyzed reactions of physiological substrates.

A continuous spectrophotometric method for monitoring phospholipase D-catalyzed hydrolysis of long acyl chain phosphatidylcholines has been formulated at pH 8.0 in a mixed detergent system using the coupling enzymes choline oxidase and peroxidase. Standard curves for phosphatidylcholine determination in both end-point and rate modes are presented and applied to the estimation of that phospholipid in a solubilized human erythrocyte membrane sample. In rate mode the method is suitable for kinetic study of phospholipase D with physiological substrates in micellar form.

Catalysis↗

Trifunctional agents as a design strategy for tailoring ligand properties: irreversible inhibitors of A1 adenosine receptors.

The 1,3-phenylene diisothiocyanate conjugate of XAC (8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]- oxy]phenyl]-1,3-dipropylxanthine, a potent A1 selective adenosine antagonist) has been characterized as an irreversible inhibitor of A1 adenosine receptors. To further extend this work, a series of analogues were prepared containing a third substituent in the phenyl isothiocyanate ring, incorporated to modify the physiochemical or spectroscopic properties of the conjugate. Symmetrical trifunctional cross-linking reagents bearing two isothiocyanate groups were prepared as general intermediates for cross-linking functionalized congeners and receptors. Xanthine isothiocyanate derivatives containing hydrophilic, fluorescent, or reactive substituents, linked via an amide, thiourea, or methylene group in the 5-position, were synthesized and found to be irreversible inhibitors of A1 adenosine receptors. The effects of the 5-substituent on water solubility and on the A1/A2 selectivity ratio derived from binding assays in rat brain membranes were examined. Inhibition of binding of [3H]-N6-(2-phenylisopropyl)-adenosine and [3H] CGS21680 (2-[2-[4-carboxyethyl)phenyl]ethyl]amino] adenosine-5'-N-ethylcarboxamide) at central A1 and A2 adenosine receptors, respectively, was measured. A conjugate of XAC and 1,3,5-triisothiocyanatobenzene was 894-fold selective for A1 receptors. Reporter groups, such as fluorescent dyes and a spin-label, were included as chain substituents in the irreversible binding analogues, which were designed for spectroscopic assays, histochemical characterization, and biochemical characterization of the receptor protein.

Adenosine↗

Dyslexia in adults is associated with clinical signs of fatty acid deficiency.

Developmental dyslexia is a complex syndrome whose exact cause remains unknown. It has been suggested that a problem with fatty acid metabolism may play a role, particularly in relation to the visual symptoms exhibited by many dyslexics. We explored this possibility using two self-report questionnaires, designed on the basis of clinical experience, to assess (1) clinical signs of fatty acid deficiency; and (2) symptoms associated with dyslexia in known dyslexic and non-dyslexic subjects. Dyslexic signs and symptoms included the auditory-linguistic and spoken language difficulties traditionally associated with the disorder, as well as visual problems (both with reading and more generally) and motor problems. Fatty acid deficiency signs were significantly elevated in dyslexic subjects relative to controls, particularly within males (P<0.001). In addition, the severity of these clinical signs of fatty acid deficiency was strongly correlated with the severity of dyslexic signs and symptoms not only in the visual domain, but also with respect to auditory, linguistic and motor problems. The pattern of relationships differed somewhat between dyslexic and control groups, and sex differences were also observed. Our findings support the hypothesis that fatty acid metabolism may be abnormal in developmental dyslexia, and indicate the need for further studies using more objective measures.

Adult↗

Visual function, fatty acids and dyslexia.

There is mounting evidence that developmental dyslexia is a neurodevelopmental disorder which involves abnormalities of fatty acid metabolism, particularly with respect to certain long-chain highly unsaturated fatty acids (HUFAs). Psychophysical evidence also strongly suggests that dyslexics may have visual deficits as well as phonological problems. Specifically, these visual deficits appear to be related to the magnocellular pathway, which is specialized for processing fast, rapidly-changing information about the visual scene. It remains unclear how these two aspects of dyslexia - fatty acid processing and visual magnocellular function - could be related. We propose some hypotheses - necessarily speculative, given the paucity of biochemical research in this field to date - which address this question.

Brain↗

Preservation and structural adaptation of endothelium over experimental foam cell lesions. Quantitative ultrastructural study.

To assess the extent to which endothelial cell (EC) structure is modified by hyperlipidemia and by the formation of intimal plaques, we undertook a quantitative ultrastructural study of aortic EC of cynomolgus monkeys after 3 or 6 months on an atherogenic diet. We compared EC in lesion-free areas (LFA) with EC overlying focal discrete foam cell accumulations (FDA) or covering multilayered confluent plaques (MCP). There was a 15% increase in cross-sectional lumen surface profile length over FDA or MCP compared to LFA (p less than 0.005) corresponding to the bulging contours of immediately underlying foam cells. There was, however, no increase in the number of EC per unit of surface area (26.2 +/- 4.47 per 10(4) mm2 for LFA and 26.0 +/- 4.22 for FDA) or, on cross-section, per 100 microns length of underlying internal elastic lamina (8.79 +/- 2.42 for LFA, 8.26 +/- 2.01 for MCP). Nor did the number of surrounding cells contacted by each cell over LFA or MCP differ from normolipemic controls (6.56 +/- 0.85 for LFA and 5.58 +/- 0.86 for MCP). Most ECs were markedly attenuated over lesions, and while the extent and complexity of lateral contact regions between adjacent EC was diminished, the number and complexity of basilar projections was greatly increased. These structures extended among the intimal foam cells to insert on the internal elastic lamina or on intimal matrix fibers, resulting in a 2.7-fold increase in the length of the abluminal portion of the EC profile. The perimeter of the transverse EC profiles was thereby increased from 41.4 +/- 2.12 microns in LFA to 82.2 +/- 5.21 microns over MCP (p less than 0.0001). Polarization of EC in the direction of flow diminished as lesions developed. The ratio of length to width, as well as the standard deviation of the ratio, decreased from 3.51 +/- 3.92 in LFA to 2.35 +/- 0.25 over MCP, due mainly to increases in the proportion of the cell perimeter exposed to the lumen. Lesion localization bore no relationship to the orientation of EC in corresponding locations in the normolipemic controls or in LFA immediately adjacent to plaques. Organelles of EC in hyperlipidemic animals showed features suggestive of increased metabolic activity in all regions, and stress filaments were increased in the EC attenuated over lesions. There was no evidence of EC degeneration, necrosis, or sloughing regardless of lesion location, size, or complexity.

Animals↗

Enzyme-catalyzed removal of phenol from refinery wastewater: feasibility studies.

Phenols are present in petroleum refining wastewater. An enzymatic method for removing phenols from industrial aqueous effluent has been developed in the past several years. In this method, a peroxidase enzyme catalyzes the oxidation of phenol by hydrogen peroxide generation of phenoxyl radicals. These radicals diffuse from the active center of the enzyme into solution and react nonenzymatically to eventually form higher oligomers and polymers, which can be removed from wastewater by conventional coagulation and sedimentation or filtration. In this study, Arthromyces ramosus peroxidase (ARP) was applied to treat a petroleum refining wastewater containing 2 mM (188 mg/L) phenol in a batch and continuous-flow system. The latter consisted of a plug-flow reactor (PFR) where the reaction took place between phenol and hydrogen peroxide catalyzed by the enzyme in the presence of polyethylene glycol (PEG). A flocculation tank followed the PFR where alum and sodium hydroxide were added and then the polymers formed were settled in a sedimentation tank and removed from the system. Most (95 to 99%) of the phenol was removed by the same dose of ARP required for the treatment of synthetic wastewater containing an equal amount of phenol. Polyethylene glycol, as an additive, reduced enzyme inactivation and consequently reduced the enzyme dose and the cost of the treatment process. Step feeding of hydrogen peroxide was not effective in reducing the enzyme requirement. A significant removal of chemical oxygen demand was achieved when using PEG to reduce the enzyme dose.

Bacteria↗