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Biomedical subjects

P B McGinlay

Publications and source records attributed to P B McGinlay.

7 recordsLinked to original sources
PubMed1998

Cyclic modulation of epithelial glycosylation in human and baboon (Papio anubis) endometrium demonstrated by the binding of the agglutinin from Dolichos biflorus.

Glycoconjugate expression in endometrial epithelium varies in a cycle-dependent manner in many species and is probably fundamental to the establishment of a receptive uterine environment for the implanting embryo. We have examined the distribution of N-acetyl galactosamine (GalNAc)-containing sequences bound by Dolichos biflorus agglutinin (DBA) in the cycling endometrium of the human and baboon (Papio anubis). In the human, DBA binding was absent in the proliferative and early secretory phases of the cycle, increasing thereafter both in glands and on the surface epithelium. In contrast, DBA binding in the baboon was maximal in the proliferative phase, diminishing to almost indistinguishable levels in the late secretory phase. Treatment of early to mid-secretory-phase baboons with the antiprogestin Onapristone caused staining to revert to the proliferative-phase pattern, confirming the importance of progesterone in the decrease in DBA staining. Investigations with other GalNAc-binding lectins indicated that epithelial GalNAc residues were present throughout the cycle. Variation in steroidally dependent 1,2 fucosyl transferase activity may therefore be responsible for the appearance of the new, DBA-binding, nonreducing terminal structure GalNAcalpha1,3(Fucalpha1,2)-Galbeta1,4GlcNAcbeta1++ + in the human during the mid-secretory phase and in the baboon during the late proliferative phase.

Acetylgalactosamine↗
PubMed1989

The kinetics of adsorption of human immunoglobulin G to poly(vinyl chloride) enzyme-linked-immunoadsorbent-assay vessel walls.

Experiments were performed to measure the effect of pH, ionic strength, temperature, organic solvents, pretreatment with gelatin and Tween 20 on the rate and extent of binding of human IgG to the walls of poly(vinyl chloride) e.l.i.s.a. vessels. It is demonstrated that, over a wide range of experimental conditions, the binding is controlled by rate-limiting diffusion to the walls, followed by a rapid and irreversible adsorption. A mathematical model is derived and shown to give a good fit to the experimental data points.

Adsorption↗
PubMed1987

The use of non-linear regression analysis and the F test for model discrimination with dose-response curves and ligand binding data.

Computer fitting of binding data is discussed and it is concluded that the main problem is the choice of starting estimates and internal scaling parameters, not the optimization software. Solving linear overdetermined systems of equations for starting estimates is investigated. A function, Q, is introduced to study model discrimination with binding isotherms and the behaviour of Q as a function of model parameters is calculated for the case of 2 and 3 sites. The power function of the F test is estimated for models with 2 to 5 binding sites and necessary constraints on parameters for correct model discrimination are given. The sampling distribution of F test statistics is compared to an exact F distribution using the Chi-squared and Kolmogorov-Smirnov tests. For low order modes (n less than 3) the F test statistics are approximately F distributed but for higher order models the test statistics are skewed to the left of the F distribution. The parameter covariance matrix obtained by inverting the Hessian matrix of the objective function is shown to be a good approximation to the estimate obtained by Monte Carlo sampling for low order models (n less than 3). It is concluded that analysis of up to 2 or 3 binding sites presents few problems and linear, normal statistical results are valid. To identify correctly 4 sites is much more difficult, requiring very precise data and extreme parameter values. Discrimination of 5 from 4 sites is an upper limit to the usefulness of the F test.

Binding Sites↗
PubMed1987

Conditions when statistical tests for model discrimination have high power. Some examples from pharmacokinetics, ligand binding, transient and steady-state enzyme kinetics.

The situation where data pairs xi, yi are actually generated by a true model, f(delta, x), but erroneously fitted by a deficient model, g(phi, x), is explored. A function, Q(delta), is described which is the average squared distance between f(delta, x) and the best-fit false model, g(phi, x). For a range of x covering 5-95% 'saturation' of f(delta, x), Q(delta) is calculated numerically for sums of exponentials, binding functions and rational functions. In each case, the region of delta when the second model in the series can be reliably differentiated from the first by statistical tests is described.

Enzymes↗
PubMed1983

Inhibition of enzyme-catalysed reactions by excess substrate. A theoretical and Monte Carlo study of turning points in v(S) graphs.

Some difficulties associated with observing and defining substrate inhibition curves are discussed. Then a new method for measuring the steepness of substrate inhibition curves is derived and a parameter, lambda, is defined to measure the steepness of descent from a maximum or steepness of ascent from a minimum in v(S) plots. A mathematical theorem is presented to show how the magnitude of lambda is limited by the degree of the rate equation. Conditions for satisfactory Monte Carlo simulations of enzyme mechanisms are explored and the constraints necessary to generate v(S) curves with profiles in physiological ranges of substrate concentrations are investigated using 16 enzyme mechanisms. The probability of detecting substrate inhibition is estimated. It is shown that there exists a lower limit to the substrate concentration at which maxima can occur in v(S) plots but no upper limit and also that enzyme mechanisms can approach but never achieve the maximum steepness of descent possible for arbitrary rational functions with non-negative coefficients.

Enzyme Inhibitors↗
PubMed1981

Deviations from Michaelis-Menten kinetics. Computation of the probabilities of obtaining complex curves from simple kinetic schemes.

1. It is possible to calculate the intrinsic probability associated with any curve shape that is allowed for rational functions of given degree when the coefficients are independent or dependent random variables with known probability distributions. 2. Computations of such probabilities are described when the coefficients of the rational function are generated according to several probability distribution functions and in particular when rate constants are varied randomly for several simple model mechanisms. 3. It is concluded that each molecular mechanism is associated with a specific set of curve-shape probabilities, and this could be of value in discriminating between model mechanisms. 4. It is shown how a computer program can be used to estimate the probability of new complexities such as extra inflexions and turning points as the degree of rate equations increases. 5. The probability of 3 : 3 rate equations giving 2 : 2 curve shapes is discussed for unrestricted coefficients and also for the substrate-modifier mechanisms. 6. The probability associated with the numerical values of coefficients in rate equations is also calculated for this mechanism, and a possible method for determining the approximate magnitude of product-release steps is given. 7. The computer programs used in the computations have been deposited as Supplement SUP 50113 (21 pages) with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem, J. (1978) 169, 5.

Binding Sites↗