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Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 235 records · Page 13Linked to original sources

Isolation and structural characterization of alkali-labile oligosaccharides from bovine milk-fat-globule membrane.

Treatment of sialoglycopeptides derived from bovine milk-fat-globule membrane with alkaline borohydride released a reduced oligosaccharide fraction from which a tetrasaccharide and two trisaccharides were isolated. Periodate-oxidation studies coupled with methylation analysis and g.l.c.-mass spectrometry established their structures as: N-acetylneuraminyl-(2 leads to 3)-beta-D-galactopyranosyl-(1 leads to 3)-[N-acetylneuraminyl-(2 leads to 6)]-N-acetyl-D-galactosaminitol, N-acetylneuraminyl-(2 leads to 3)-D-glactopyranosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol and beta-D-galactopyranosyl-(1 leads to 3)-[N-acteylneuraminyl-(2 leads to 6)]-N-acetyl-D-galactosaminitol respectively.

Animals↗

Reaction of the aminic form of aspartate transaminase with difluoro-oxaloacetate.

Addition of difluoro-oxaloacetate to the aminic form of aspartate transaminase causes a rapid shift of absorbance maximum of the enzyme from 332 nm to 328 nm, followed by a much slower shift to 360 nm corresponding to complete conversion of the aminic form of the enzyme into the aldimine form or a species with similar spectral parameters in rapid equilibrium with it. Kinetic analysis of both the initial fast reaction and the overall slow reaction by using repeated spectral scanning and stopped-flow techniques allows formulation of a basic reaction mechanism involving at least two intermediate enzyme complexes. Computer simulation of the progress curves of the initial fast reaction based on the suggested reaction mechanism gives kinetic parameters that are consistent with all the data obtained by other methods. A molecular reaction scheme involving a ketimine Schiff-base intermediate is proposed.

Aspartate Aminotransferases↗

[19F]fluorine nuclear-magnetic-resonance study of the interaction of difluoro-oxaloacetate with aspartate transaminase.

Difluoro-oxaloacetate interacts with the aldimine form of aspartate transaminase to give a complex, the dissociation constant of which has been determined spectrophotometrically and by 19F n.m.r. (nuclear magnetic resonance). The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of the aldimine form of the enzyme both show inflexion points in the pH5 and pH8 regions, which may arise from variations in the binding of difluoro-oxaloacetate as specific groups on the enzyme are successively protonated. Difluoro-oxaloacetate also interacts with apoenzyme to form a complex, the dissociation constant of which was determined by 19F n.m.r. The 19F n.m.r. line-width-pH and chemical-shift-pH profiles of difluoro-oxaloacetate in the presence of apoenzyme show a single inflexion point in the region of pH8. The absence, in this case, of an inflexion in the pH5 region indicates that the latter, present in the corresponding profiles for the aldimine form of the enzyme, results from ionization of an enzyme group associated with the pyridoxal phosphate cofactor.

Aspartate Aminotransferases↗

Interaction of difluoro-oxaloacetate with aspartate transaminase.

Diffluoro-oxaloacetate behaves as a competitive inhibitor of 2-oxoglutarate and as an uncompetitive inhibitor with respect to aspartate in steady-state kinetic experiments with cytoplasmic aspartate transaminase. In the presence of high concentrations of aspartate transaminase, difluoro-oxaloacetate is slowly transaminated to difluoro-aspartate, suggesting its use as a kinetic probe to study the reactions of the aminic form of the enzyme.

Animals↗

Clonidine. Effects of a topically administered solution on intraocular pressure and blood pressure in open-angle glaucoma.

A double-blind crossover study to determine the effects on intraocular pressure (IOP) and blood pressure of topically instilled 0.125% and 0.25% solutions of clonidine hydrochloride by comparison with a 2% pilocarpine hydrochloride solution and placebo was carried out in a total of 21 patients with open-angle glaucoma, each of whom received a single drop of each preparation in the same glaucomatous eye on separate days. Both clonidine solutions were effective in lowering the IOP; the 0.25% solution was more effective than the 0.125% solution, and the former was slightly less potent than pilocarpine. Pupil diameter was essentially unchanged in all but one of the patients after clonidine. Pilocarpine reduced pupil diameter in all patients. One eye treated with placebo also showed a reduction in pupil size. Both systolic and diastolic blood pressure showed a statistically significant reduction after clonidine, but the magnitude of the change was small. We do not regard the minor blood pressure changes as being a threat to the optic nerve but further studies in this aspect of topical clonidine therapy are required.

Administration, Topical↗

Plasma 20 alpha-dihydroprogesterone, progesterone and 17-hydroxyprogesterone in normal human pregnancy.

The peripheral plasma levels of 20alpha-dihydroprogesterone (20alpha-DHP), progesterone (P) and 17-hydroxyprogesterone (17-OHP) were measured by radioimmunoassay techniques in 440 samples during normal human pregnancy between weeks 4 and 41. The levels of 20alpha--DHP in plasma from the 4th to the 6th week were between 6.0 and 6.6 ng/ml. From then until the 21st week the average plasma 20alpha-DHP concentrations remained at the same level between 4.0 and 6.3 ng/ml; they then rose significantly to and beyond term, levels reaching over 40 ng/ml. The range of mean plasma concentration of P during the first trimester of pregnancy fell to a nadir in the 9th week (170 ng/ml) then rose with increased gestation until the 39th week (190.4 ng/ml) followed by a slight and not significant drop. Single measurements of plasma 17--OHP from the 4th to the 6th week of pregnancy gave value between 2.8 and 3.6 ng/ml, but from the 7th week the mean plasma 17--OHP levels gradually declined, then from week 30 the 17-OHP concentration increased to reach a mean level of 7.63 ng/ml in the 41st week. The ratio P/20alpha--DHP increased from the 4th (3.5:1) to the 24th week (15.6:1) and then decreased from 25th week (7.9:1) towards term (3.2:1).

20-alpha-Dihydroprogesterone↗

Dehydrogenation of the phosphonate analogue of glucose 6-phosphate by glucose 6-phosphate dehydrogenase.

6,7 -Dideoxy-alpha-D-gluco-heptose 7-phosphonic acid, the isosteric phosphonate analogue of glucose 6-phosphate, was synthesized in six steps from the readily available precursor benzyl 4,6-O-benzylidene-alpha-D-glucopyranoside. The analogue is a substrate for yeast glucose 6-phosphate dehydrogenase, showing Michaelis-Menten kinetics at pH7.5 and 8.0. At both pH values the Km values of the analogue are 4-5 fold higher and the values approx. 50% lower than those of the natural substrate. The product of enzymic dehydrogenation of the phosphonate analogue at pH8.5 is itself a substrate for gluconate 6-phosphate dehydrogenase.

Deoxy Sugars↗