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C DeLisi

Publications and source records attributed to C DeLisi.

18 recordsLinked to original sources

Quantitative aspects of a unified model of diffusion mediated receptor--cyclase coupling.

A quantitative model is presented of diffusion mediated coupling of adenylate cyclase to multivalent plasma membrane receptors which accounts for a wide range of phenomena including non linear occupation-activation plots with either positive or negative second derivatives, spare receptors, silent receptors, and negative and positive binding cooperativity. A non linear least square fit of the predicted equation for cyclase activation to available data predicts translational diffusion coefficients in the range of (10(-10) - 10(-11))cm2/s.

Adenylyl Cyclases

The influence of cell surface receptor clustering on the thermodynamics of ligand binding and the kinetics of its dissociation.

We show that an equilibrium model for the clustering, by divalent ligand, of homogeneous plasma membrane-bound divalent receptors that do not change conformation predicts Scatchard plots with positive second derivatives (concave up). The result is thermodynamically indistinguishable from predictions based upon receptors that are heterogeneous for ligand, or that change conformation in a negatively cooperative way when ligand binds. A more general formulation of the theory, which allows application to dissociation kinetics, predicts that the dissociation of labeled ligand is accelerated in the presence of excess cold ligand and, moreover, that the accelerated dissociation has at least two components. The theory is briefly illustrated by fitting five different sets of data, at several temperatures for two different systems, with parameter values that are well within physically meaningful ranges. The model presented is the simplest and least ad hoc explanation thus far proposed as the basis for the kinetic phenomena, and raises the possibility that the numerous experiments in which such data are observed are primarily minifestations of cell surface clustering.

Insulin

Secretion rate independent evaluation of IgM antibody avidity at the level of single immunocytes.

The hemolytic plaque inhibition assay has been performed on spleen cells from mice immunized with TNP-HRBC to evaluate avidity of anti-TNP IgM antibodies. At different times after immunization direct plaques were inhibited by soluble TNP-EACA, TNP61-BGG, or anti-mu antiserum. Analysis of the inhibition data provided independent estimates of antibody avidity and secretion rate. Avidity was found to increase with time, to reach a maximum when the antibody response attained the peak value, and then to decline as the response was waning. There was a decrease followed by increase of the secretion rate concomitant with the rise and fall of the antibody response and avidity.

Aminocaproic Acid

Method for quantitating tumor cell removal and tumor cell-invasive capacity in experimental metastases.

An improved method is presented for analyzing the decay of i.v.-injected labeled tumor cells in the lung. A simple compartment analysis yields quantitative values for (a) the rate at which tumor cells are lost or cleared from the lung, and (b) the "invasion" rate at which tumor cells colonize the interstitial space. Statistical methods are outlined for testing the significance of the contribution of each rate to the overall shape of the decay curve and for testing whether or not a given rate is altered significantly during an experiment. The usefulness of the method is demonstrated in analysis of experiments involving perturbations of the host or of the injected tumor cells.

Animals

Some physical chemical aspects of receptor-ligand interactions.

Quantitative evaluations of a variety of binding reactions of interest to immunologists have usually assumed that the reactants are homogenously dispersed in solution for purposes of calculation. In fact, many of these reactions involve cell-bound "receptors" which are present at exceedingly high local concentrations on discrete particles. We describe how such a distribution can influence the experimentally measured binding constants. We also briefly consider the additional complexities introduced when multipoint attachment between the ligand and cell-bound receptors is possible, and discuss the possible biological implications.

Binding Sites, Antibody

Hemolytic plaque inhibition: the physical chemical limits on its use as an affinity assay.

An analysis of the fundamental physical chemical limits of hemolytic plaque inhibition as a method for obtaining thermodynamic and kinetic information is presented. It is shown that inhibition curve characteristics will be sensitive functions of reaction affinities only when the antibody inhibitor and antibody red blood cell reaction mechanisms are related in certain ways. It is further shown that conditions which are most sensititive to IgG affinity changes will generally not be the best for detecting changes in IgM affinity. The apparently conflicting reports on IgM maturation are completely explicable in terms of experimental requirements imposed by physical chemical characteristics of the reaction. Experiments in which maturation is observed are found to conform to the most sensitive conditions of the assay, whereas those in which it is not observed are found to conform to relatively insensitive conditions, and would therefore be capable of registering changes only when affinity shifts are large.

Binding Sites, Antibody