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Biomedical subjects

B Goldstein

Publications and source records attributed to B Goldstein.

At least 199 records · Page 11Linked to original sources

Some quantitative aspects of the passive sensitization of human basophils.

We review the theory for the binding of IgE to Fc receptors on basophil surfaces. We then use the theory to analyze binding experiments of Malveaux et al. and T. Ishizaka on the passive sensitization of basophils from a patient with chronic myelocytic leukemia and 75% basophilia. From their data we determine that the forward rate constant for the binding of human IgE to receptors on these human basophils is (3.0 +/- 1.0) x 10(4) M-1 sec-1.

Basophils↗

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↗

The breeding and use of specific pathogen-free (SPF) rats.

Bronchiectasis is common in older rats and is a serious complication when the lungs are repuired for research purposes. SPF rats do not develop this complication, but special isolated accommodation must be provided and care of the animals must avoid introduction of outside micro-organisms. Animals removed from the isolated accommodation for experimental work are not returned, but can be kept in the general animal house provided there are no conventionally-bred rats.

Animal Husbandry↗

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↗

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↗

A computer method for determining plaque size and plaque morphology.

We describe a computer method for determining plaque size and morphology from photographs of hemolytic plaques. The method eliminates any inter-measurer and intra-measurer inconsistencies that may arise when manual measurements are made on plaques whose boundaries are poorly defined. For circular plaques inner and outer plaque radii are determined. In addition the computer generates a density profile for each plaque, i.e., a plot of the film density versus the radial distance from the antibody forming cell. We demonstrate the use of the method by analyzing a time study of the growth of a single plaque.

Animals↗

Antigen modulation of antibody forming cells: the relationship between direct plaque size, antibody secretion rate and antibody affinity.

Using the mathematical theory of direct plaque growth, we have analyzed the expected variation of plaque size with IgM affinity and secretion rate. We use the theory to comment on recent effector cell blockage experiments and show how the theory can be used to determine the change in the secretion rate of a single antibody-forming cell subjected to blockage by a multivalent antigen. We also argue, using the mathematical theory, that under the usual experimental conditions employed in the plaque assay, cells that produce low affinity IgM antibodies will give rise to smaller plaques than cells that produce high affinity IgM antibodies.

Antibody Formation↗