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M Dembo

Publications and source records attributed to M Dembo.

65 records · Page 4Linked to original sources
PubMed1979

Some invariant properties of IgE-mediated basophil activation and desensitization.

We investigate certain general properties of antigen induced degranulation of sensitized basophils by analyzing two types of experiments: Experiments in which we expose basophils to two antigens sequentially and then determine the fraction of histamine released; and experiments in which we obtain time-dependent release and desensitization curves. To analyze the latter type of experiments we introduce a new way to plot release and desensitization data that depends on the nature of the interactions of histamine-containing units (histamine quanta) with themselves or the cells degranulation apparatus, but not on any specific properties of the antigen. From our analysis we conclude that: 1) A fraction of histamine within a population of basophils is nonreleasable by antigenic stimulation. 2) When a basophil degranulates the initial release of histamine appears to inhibit subsequent release. 3) The rate of histamine release is proportional to the amount of releasable histamine remaining in the cells when the amount remaining is small, as expected if release of histamine granules is a stochastic process. 4) There is no dependence of desensitization on the extracellular calcium concentration.

Antigens↗
PubMed1978

Theory of equilibrium binding of symmetric bivalent haptens to cell surface antibody: application to histamine release from basophils.

We present a theory of equilibrium binding of symmetric bivalent haptens to cell surface antibody in the presence or absence of monovalent hapten. Bivalent haptens can link together antibodies to form linear chains or rings on cell surfaces. We show how to calculate the amount of any complex of bound bivalent hapten, monovalene fraction of antibody involved in complexes made up of two or more antibodies, i.e., the fraction of antibody that is cross-linked (Xpoly). We treat the case when the antibody on the cell surface, which is specific for the hapten, is homogeneous. For this case we prove a number of general properties about Xpoly: 1) Xpoly approaches zero at both high and low bivalent hapten concentration. 2) Xpoly becomes a maximum when the bivalent hapten concentration equals Amax, where Amax = 1/H + B/2. H is twice the equilibrium constant for the binding of a single hapten site to a single antibody site and B is the monovalent hapten concentration. 3) a plot of Xpoly vs the log of the bivalent hapten concentration is symmetric about the maximum value of Xpoly. We use these and other properties of Xpoly in this paper to clarify the relationship between cross-link formation and histamine release.

Antigen-Antibody Complex↗
PubMed1978

Histamine release due to bivalent penicilloyl haptens: control by the basophil plasma membrane.

We describe the characteristics of in vitro histamine release from human basophils passively sensitized with serum from a penicillin-allergic individual. The histamine release is induced by a synthetic bivalent hapten, bis benzylpenicilloyl 1,6 diaminohexane (BPO)2. We present data on the effect of a monovalent hapten, benzylpenicilloyl formyl-L-lysine (BPO)1, on the histamine release. We also examine how histamine release depends on the concentration of serum used for passive sensitization, the source of cells used for passive sensitization, and the time allowed for histamine release. We interpret these experiments in terms of a theory of equilibrium binding of bivalent haptens to cell surface antibody that is presented in the previous paper. The results are consistent with the idea that the amount of histamine release is controlled by the number of cross-linked IgE molecules on the cell surface. In particular, the histamine dose-response curve rises because cross-links rise, has a maximum because the cross-links are a maximum, and falls because the cross-links fall.

Basophils↗
PubMed1977

The facilitated diffusion of oxygen by hemoglobin and myoglobin.

We have clarified the use of Wyman's differential equation for the facilitated oxygen flux through a slab of solution of myoglobin or hemoglobin by showing that there is a unique choice of boundary condition on the carrier concentration to be employed in conjunction with it. The singular perturbation solution of Wyman's equation, due to Murrayand Mitchell and Murray, has been extended. By means of it, the paradox of Wittenberg, that the facilitated oxygen flux per mole of heme is apparently independent of the protein carrier, has been resolved.

Diffusion↗
PubMed1977

A kinetic model of cooperativity in aspartate transcarbamylase.

A relatively simple kinetic model is proposed to account simultaneously for data on the binding of carbamyl phosphate and succinate to aspartate trans carbamylase (ATCase), and for the relaxation spectrum associated with this binding. The model also accounts for measurements of the initial velocity of the reaction of ATCase with respect to aspartate and carbamyl phosphate. The principal assumption made is that ATCase consists of three identical noninteracting cooperative dimers. Ordered binding and both sequential and concerted conformational changes in the dimers are needed to account for the properties of ATCase. The values of the parameters of this model can be determined by fitting to existing experimental evidence. Various new quantitative predictions are made that can serve as additional tests of the proposed theory.

Adenosine Triphosphate↗
PubMed1976

Antifolate transport in L1210 leukemia cells. Kinetic evidence for the non-identity of carriers for influx and efflux.

The kinetics of methotrexate transport in L1210 cells are described. Data derived from the measurmenets of initial influx, the complete time-course of uptake, intracellular steady-state level and unidirectional efflux were found to be consistent with a simple empirical equation containing three constants. Properties of the system include the following: (1) saturability of initial influx: (2) approach to steady state during uptake is exponential; (3) the half-time for drug uptake is independent of external concentration and equal to half-time for efflux; and (4) transport is concentrative at low external concentrations, whereas the reverse is true at high external concentrations. These observations are incorporated into a kinetic model which quantitatively accounts for the data on the basis of the hypothesis that influx and efflux take place via different carriers.

Animals↗
PubMedDate not supplied

Kinetics of cell detachment: effect of ligand density.

Cell adhesion to substratum is often mediated by binding between cell surface receptors and substrate ligands. Substrates can be derivatized with different types and densities of ligands, but how substrate chemistry determines cellular function, such as adhesion strength, has not been demonstrated quantitatively. We employ a numerical methodology developed by Dembo and colleagues (9), who investigated membrane peeling under conditions of excess ligand density, to investigate the kinetics and strength of cell peeling from ligand coated surfaces for arbitrary ligand density. We show there are two asymptotic limits to peeling strength, as quantified by the critical tension: a high ligand density limit, where the critical tension is independent of ligand density and depends logarithmically on the receptor density; and a low ligand density limit, in which the critical tension depends logarithmically on the ligand density but is independent of receptor density. In between these limits, we numerically determine the critical tension. The critical tension is always a weak function of the dissociation constant between ligand and receptor. Furthermore, we show how the rate of peeling, for tensions above the critical tension, depends on ligand density and the mechanical properties of the receptor-ligand bonds. Interestingly, we illustrate when small increases in ligand density should alter cellular behavior, inducing a change to spreading onto a substrate from peeling up from a substrate. In total the predictions of this paper provide criteria for the design of ligand-coated substrate that provide for the proper adhesion strength and dynamics of detachment of cells from surfaces.

Animals↗
PubMedDate not supplied

Modeling chemoattractant-elicited relocalization of myosin filaments in Dictyostelium.

Dictyostelium myosin is able to assemble into filaments that, when visualized under normal conditions, appear to be uniformly distributed throughout the cytoplasm. After stimulation by the chemoattractant cAMP, these filaments quickly diminish in the cellular medulla and accumulate in the cortex. A general hypothesis to explain the mechanism of this relocalization proposes that one or more of the chemical coefficients governing filament polymerization is precisely regulated by some sort of intracellular second messenger. To investigate this hypothesis we formulated a simple theoretical model of myosin polymerization and then used this model to analyze the resting state of the cell and various scenarios for initializing a transition to the activated state. In general, we found that the relocalization of filaments could be realized if a second messenger increased the elongation and (or) the nucleation coefficients for filament assembly in cortical ectoplasm and (or) if the messenger decreased these parameters in the cellular medulla. By comparing these limiting cases with experimental observations, we concluded that models in which redistribution of myosin is achieved by decreasing filament stability in the medulla are the most likely candidates.

Animals↗