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Biomedical subjects

A Horovitz

Publications and source records attributed to A Horovitz.

43 records · Page 3Linked to original sources

The saliva of the medicinal leech Hirudo medicinalis--II. Inhibition of platelet aggregation and of leukocyte activity and examination of reputed anaesthetic effects.

1. Leech saliva inhibits platelet aggregation induced by collagen, ADP and epinephrine. 2. Leech saliva inhibits superoxide production by neutrophils stimulated by tetradecanoyl phorbol acetate or polyhistidine. The effect is due in part at least to eglin. 3. Reputed anaesthetic effects of leech saliva were not detected.

Adenosine Diphosphate↗

An accurate method for determination of receptor-ligand and enzyme-inhibitor dissociation constants from displacement curves.

Receptor-ligand dissociation constants are usually calculated from the displacement curve of a radioactively labeled ligand bound to the receptor. The formula used is restricted to cases in which the concentration of receptor is negligible compared to the concentration of both the displacing ligand and the radioactive ligand used. In this study, we rigorously derive a simple equation that can be used for calculating receptor-ligand dissociation constants for any set of experimental conditions. A linearized form of this equation provides a convenient plot from which the dissociation constant of the displacing ligand can be directly obtained. The plot is also a test for the competitive mode of binding. This exact equation now allows us to estimate the error incurred by the conventionally used equations. Similarly, we show that for competitive inhibition in enzymology, one can derive the analogous formula. Our new formula is free of the usual restrictions--namely, that the enzyme concentration is very small compared to the concentration of both the substrate and the inhibitor. It may therefore be applied to any set of experimental conditions.

Enzyme Inhibitors↗

Measures of cooperativity in the binding of ligands to proteins and their relation to non-additivity in protein-protein interactions.

The analogy between cooperativity in the binding of ligands to proteins and non-additivity in protein-protein interactions is demonstrated and discussed in terms of the Wong and the Hill coefficients. A measure of non-additivity, the interaction constant, is rigorously derived for four thermodynamic cycles, involving the binding of small molecules to proteins and protein association. It is the reciprocal of the 'defect factor' of Laskowski et al. in Proteinase inhibitors: medical and biological aspects (ed. N. Katunuma et al.), pp. 55-68 (1983), and its logarithm is the Wong measure of cooperativity. These three measures are thus here given a common theoretical basis. The Hill coefficient for an asymmetric dimer that binds two different ligands which do not compete for the same site, at 50% saturation of each site, is derived. It is shown to be a function of the interaction constant and of the fraction of protein to which ligand is bound at both sites. These relations for protein-ligand interactions are then discussed in the context of non-additivity in protein-protein interactions.

Binding Sites↗

Protein-protein interactions: additivity of the free energies of association of amino acid residues.

Additivity of contributions to the free energies of association of ovomucoid third domain inhibitors with elastase, chymotrypsin and subtilisin (Laskowski, 1980; Laskowski et al., 1981, 1983; Empie & Laskowski, 1982) is fully demonstrated by applying the mathematical method of Free and Wilson (1964) for calculating the effects of substitutions in a family of drugs. Also demonstrated is the ability to predict the activity of third domain sequences. Sensitive regions in the contact area of inhibitor and enzyme are mapped, and a sequence is suggested for a new, more powerful and selective ovomucoid third domain inhibitor of subtilisin.

Amino Acid Sequence↗

Hyperechoic foci in the gallbladder wall as a sign of microabscess formation or diverticula.

Abdominal sonography in 7 patients with acute biliary disease revealed focal echo collections within the wall of the gallbladder in addition to cholelithiasis and diffuse mural thickening. A prospective study was conducted, comparing in vivo and in vitro sonography of the gallbladder with histopathological findings. In 3 patients, microscopy of the hyperchoic tissue showed microabscesses. In 4, intramural diverticula containing inspissated bile, small stones, or cholesterol crystals were seen. The authors caution that hyperchoic foci within the wall of the gallbladder may indicate intrinsic disease separate from cholelithiasis or cholecystitis.

Abscess↗