Search PubMed⌕ Search

Biomedical subjects

S J Harris

Publications and source records attributed to S J Harris.

At least 73 records · Page 4Linked to original sources
PubMed1989

Equilibrium partition studies of the myofibrillar interactions of glycolytic enzymes.

The interactions of several glycolytic enzymes with muscle myofibrils in imidazole-chloride buffer (pH 6.8, I 0.158) have been investigated by equilibrium partition studies. Results for aldolase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and phosphofructokinase are interpreted in terms of a myofibrillar capacity of 76 nmol/g protein and a single intrinsic association constant for each tetravalent enzyme with matrix sites. The existence of separate myofibrillar sites for aldolase and glyceraldehyde-3-phosphate dehydrogenase is established by demonstrating independence of the binding of each enzyme upon the presence of the other. Although this investigation provides further physicochemical support for myofibrillar adsorption of glycolytic enzymes in the cellular environment, its findings are incompatible with the proposition (B. I. Kurganov, N. P. Sugrobova, and L. S. Mil'man (1985) J. Theor. Biol. 116, 509-526) that the phenomenon reflects the formation of a specific multienzyme complex attached to the myofibril.

Animals↗
PubMed1989

Effect of calcium ion on the interaction of aldolase with rabbit muscle myofibrils.

A partition equilibrium study has shown calcium ion to be a noncompetitive inhibitor of aldolase adsorption by rabbit muscle myofibrils. This inhibition is interpreted quantitatively in terms of a 10-fold decrease in the intrinsic association constant for the aldolase-myofibril interaction upon Ca2+ binding to either or both of the low-affinity troponin sites associated with regulation of muscle contraction.

Animals↗
PubMed1988

Graphical analysis of binding data reflecting competition between two ligands for the same acceptor sites.

A theoretical expression is derived for the analysis of results from competitive binding studies in which two multivalent ligands compete for acceptor sites, and a linear transform is suggested for simple graphical representation and assessment of experimental results. The protocol is illustrated by application to competitive binding data, obtained by ultrafiltration, on the interactions of bovine serum albumin with two structurally similar organic anions, methyl orange and methyl red. In a second experimental study the present approach is then used to establish that lactate dehydrogenase and aldolase compete for the same myofibrillar sites of bovine cardiac muscle. Finally, numerically simulated behavior of systems with additional binding sites for either ligand is used to emphasize that the criterion for classical (complete) competition is agreement between an experimentally determined equilibrium constant for ligand binding and the apparent value deduced from competitive binding studies. Nevertheless, the present analysis of competitive binding data should still offer considerable scope for screening quantitatively the cross-reactivities of drug and antigen analogs for their respective specific protein-acceptor sites.

Animals↗
PubMed1988

Thermodynamic nonideality as a probe of allosteric mechanisms: preexistence of the isomerization equilibrium for rabbit muscle pyruvate kinase.

Sedimentation velocity studies in the presence and absence of an inert space-filling solute, sucrose, have been used to establish preexistence of the isomerization equilibrium responsible for the allosteric behavior of rabbit muscle pyruvate kinase. Whereas the inclusion of phenylalanine (5 mM) with enzyme gives rise to a decrease of 0.3 S in the sedimentation coefficient of pyruvate kinase, the corresponding effect of phosphoenolpyruvate is to increase the sedimentation coefficient by 0.03 S. Consideration of these findings to signify the existence of an isomeric equilibrium between compact and expanded forms of the enzyme is substantiated by the finding that inclusion of sucrose (0.1 M) also brings about the change in sedimentation coefficient effected by phosphoenolpyruvate. By demonstrating that rabbit muscle pyruvate kinase undergoes isomerization in the absence of substrate, this study removes any necessity to consider the existence of an isomerization equilibrium that is substrate-induced; and thereby provides experimental support for adoption of the Monod model of allostery to interpret enzyme kinetic data for pyruvate kinase [R. W. Oberfelder, B. G. Barisas, and J. C. Lee (1984) Biochemistry 23, 3822-3826].

Animals↗
PubMed1987

Enzyme kinetic evidence of active-site involvement in the interaction between aldolase and muscle myofibrils.

The interaction of aldolase with the myofibrillar matrix of rabbit skeletal muscle has been investigated by means of its effect on kinetic parameters for the enzyme-catalyzed cleavage of fructose 1,6-bisphosphate. Involvement of the active site in the enzymic interaction with the thin filament of muscle is indicated, the association constant for competitive inhibition of catalysis (420,000 M-1) being in excellent agreement with the value of 410,000 M-1 obtained under the same conditions (pH 6.8, I 0.16) from partition equilibrium studies of the aldolase-myofibril interaction (Kuter, M.R., Masters, C.J. and Winzor, D.J. (1983) Arch. Biochem. Biophys. 225, 384-389). A second kinetic study, designed to take into greater account the inhibitory effects of substrate and other phosphate-containing metabolites on the interaction of enzyme with myofibrils, has substantiated further the concept of aldolase existing as an equilibrium mixture of cytoplasmic and filament-bound forms in muscle tissue.

Animals↗
PubMed1986

Background adaptation in human infants.

Human infants' thresholds for detecting 10 degrees diameter 50 and 1000 msec stimuli in the dark adapted condition and in the presence of steady red backgrounds were determined using a preferential looking method. Dark adapted sensitivity and the slope of the linear portion of the increment threshold function increased with age. The slope was 0.5 at 4 weeks, but by 10 weeks it was not different from the adult value (approximately 1.0). At all ages the eigengrau was approximately the same as that of adults (-2.3 log scot. td). These results suggest that visual mechanisms involved in detection of flashes and adaptation to steady background lights mature postnatally.

Adult↗
PubMed1986

Assessment of acuity of amblyopic subjects using face, grating, and recognition stimuli.

For amblyopic subjects, square-wave gratings, such as those used in preferential looking tests of infants' vision, yield more optimistic estimates of visual acuity than complex stimuli such as letters. A complex stimulus--a schematic face pattern--has recently been shown (Harris et al, IOVS 25:782, 1984) to permit preferential looking estimates of acuity of infants with normal eyes. In the present study, older amblyopic subjects had acuities measured with the face stimulus as well as gratings and standard recognition tests. Acuities measured with the face stimulus agreed better with the results of the standard recognition tests than did those obtained with gratings. Thus, if amblyopia of infants and young children affects spatial vision in a manner similar to that of older children and adults, one would anticipate that complex stimuli, such as the face pattern, would complement current assessments of young pediatric patients.

Adolescent↗
PubMed1985

Retinal degenerations and brain abnormalities in infants and young children.

Of 51 infants and children who presented with visual impairment, developmental delays, and suspected brain abnormalities, 28 (55%) had clinical, electroretinographic, and cranial computed tomographic results indicative of cerebroretinal disorders. This report concentrates on the electroretinographic and psychophysical results from 12 patients who had evidence of progression of both brain and retinal disease. We believe these patients represent human cerebroretinal degenerative disorders that have yet to be completely characterized.

Brain↗
PubMed1985

Effect of thermodynamic nonideality on the subcellular distribution of enzymes: adsorption of aldolase to muscle myofibrils.

An expression is derived whereby allowance may be made for the effects of thermodynamic nonideality on the biphasic interaction of a macromolecular solute with an immobilized reactant. This quantitative description, written in terms of activity coefficients expressed as virial coefficients on the basis of excluded volume, also takes into account the space-filling effect of an inert macromolecule present in the reaction mixture. Advantage is then taken of the theory to consider the effect of bovine serum albumin on the interaction of aldolase with bovine cardiac muscle myofibrils in I 0.158 imidazole-chloride buffer, pH 6.8. Partition equilibrium studies are used to establish that inclusion of a moderate concentration (14 mg/ml) of serum albumin in reaction mixtures leads to a 35-40% increase in the apparent binding constant written in terms of reactant molarities, and that the enhancement is attributable entirely to nonideality inasmuch as the same thermodynamic binding constant pertains. This investigation of thermodynamic nonideality arising from the space-filling effects of inert macromolecules on enzyme partition reinforces the possibility that some enzymes may be distributed between soluble and adsorbed states in the highly concentrated macromolecular environment of the cell cytoplasm.

Adsorption↗
PubMed1985

Pharmacokinetics of flunixin meglumine in the cow.

Plasma levels of flunixin were measured in heifers after a single intravenous injection (1.1 mg kg-1), using high performance liquid chromatography. Plasma concentration versus time curves were best described by a two compartment model. The distribution phase (alpha) half-life was 0.294 hours, the elimination phase (beta) half-life was 8.12 hours and the volume of distribution was 1050 ml kg-1.

Animals↗
PubMed1984

Use of deputising services and night visit rates in general practice.

Examining all of the claim forms for night visits submitted to the Nottingham Family Practitioner Committee over a three month period allowed us to calculate the night visit rate for all 184 practices in Nottinghamshire. To take all of the practices together the mean night visit rate (covering all visits requested and made between 11 00 pm and 7 00 am) was 15.5 visits per 1000 patients a year, range 1.2 to 46.1. Whether or not a deputising service is used accounted for 12% of the total variance detected, while the other factors studied, such as area of practice, patient list size, and number of partners, accounted for approximately 1% each. The local deputising service responds to 97% of night calls with a visit to the patient, whereas the patient's own doctor is more likely to provide advice over the telephone. The ability to provide telephone advice, however, will vary according to the breakdown of the practice by age and social class.

England↗
PubMed1984

Pregnancy-specific-beta 1-glycoprotein: effect on lymphocyte proliferation in vitro.

The effects of three different preparations of pregnancy-specific-beta 1-glycoprotein (SP1) were investigated in parallel with progesterone, oestradiol and human chorionic gonadotrophin (hCG) on the proliferative response of lymphocytes in the mixed lymphocyte reaction (MLR), and to the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). A dose-related inhibition of the MLR was obtained with SP1 at 2.5-10 mg/l. SP1 also inhibited the PHA response at 10 mg/l, but had no effect on the PWM response at these concentrations. Progesterone and oestradiol inhibited all systems at 10-20 mg/l while hCG inhibited all systems at 1500-3000 IU/ml. The observations suggest that SP1 selectively inhibits the proliferative responses of T lymphocytes at the concentrations studied.

Chorionic Gonadotropin↗