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Biomedical subjects

R Margalit

Publications and source records attributed to R Margalit.

70 records · Page 4Linked to original sources

Spectroscopic studies on the tyrosine residues of canavalin.

Canavalin is a tetramer with 6 tyrosines per subunit. In the work presented here, we have classified these tyrosines by their spectrophotometric and fluorometric pH titration and their ability to be quenched I-. Of the 6 residues, 2 were found to be exposed to the solvent. One (pK = 10.2) contributes 28% of the total fluorescence intensity; the second has a pK of 11.50, and a lower quantum yield, contributing only 16% of the total intensity. The remaining 4 residues (pK = 12.5, contributing 54% of fluorescence intensity) are buried; their titration is irreversible, requiring protein denaturation.

Chemical Phenomena↗

A rapid screening test for reduced fibrinolytic activity of plasma: streptokinase activated lysis time.

A simple screening method for determining the fibrinolytic activity of plasma is described. A streptokinase activated system is used, which measures the result of the interplay of all components of the fibrinolytic system with the exception of activators, which are added in excess. Mean lysis time and standard deviation with this method is 6.9 +/- 1.4 min. The sensitivity of the method in detecting minor delays in clot lysis time is demonstrated.

Blood Coagulation Tests↗

A new method for the determination of plasma activators fibrinolysis.

The term "effective activator" of plasminogen is proposed, to denote the resultant of activator-antiactivator interaction, and a method for the determination of the level of these activators is described. By adding axcess plasminogen to the euglobulin fraction of plasma the influence of the level of endogenous plasminogen and of the antiplasmin is eliminated. It is shown that the level of fibrinogen has very little bearing on the results. An effective activator unit is defined as equal to 1 CTA unit of urokinase activity on a fibrinogen-plasminogen substrate.

Fibrinogen↗

Effect of myocardial infarction on components of fibrinolytic system.

A systematic investigation of the fibrinolytic system during the period after acute myocardial infarction in 42 patients showed a progressive reduction of fibrinolytic activity, with the longest lysis times on days 4 to 5 after the event. There is a concomitant rise in the levels of fibrinogen, plasminogen, and antiplasmin; only the latter parallels the delay in lysis. After 12 to 15 months, normal lysis times and fibrinogen levels were found in 24 patients re-examined. It is concluded that the reduced fibrinolytic activity in these patients was a transient phenomenon after myocardial infarction.

Adult↗

Angiogenic response of MCF7 human breast cancer to hormonal treatment: assessment by dynamic GdDTPA-enhanced MRI at high spatial resolution.

Dynamic gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI was followed during growth and regression of MCF7 human breast tumors implanted in nude mice in the presence of estrogen and tamoxifen, respectively. Gradient-echo and spin-echo sequences were applied at a temporal resolution of 12 and 100 seconds, respectively, and a spatial resolution of 195 x 390 x 1000 microns. Maps of initial rates of contrast enhancement demonstrated stimulation of local growth of permeable microcapillaries at regions bordering necrotic areas, resulting from tamoxifen treatment. This localized angiogenic stimulation was confirmed by immunohistochemical staining of endothelial cells. After 1 week of tamoxifen treatment, the fraction of tumor pixels exhibiting rapid initial rate of contrast enhancement increased significantly from .28 +/- .05 to .46 +/- .06. In parallel, the fraction of tumor area showing contrast enhancement 3 minutes after Gd-DTPA injection also increased significantly, from .42 +/- .06 to .58 +/- .06. On the basis of these changes, it was possible to assess the response to tamoxifen therapy at an early stage.

Analysis of Variance↗

High resolution MRI of MCF7 human breast tumors: complemented use of iron oxide microspheres and Gd-DTPA.

The differential capacity of iron oxide microspheres and of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) to serve as contrast agents that can map the microcirculation of MCF7 human breast cancer implanted in nude mice has been examined by high resolution MRI. Modulation of signal intensity in T2*-weighted, gradient-echo images after iron oxide administration and the temporal signal enhancement after Gd-DTPA administration were monitored and analyzed at a spatial resolution of 98 x 98 x 500 microm and 195 x 390 x 1,000 microm, respectively. The pathophysiologic features revealed in the contrast-enhanced images were analyzed in reference to those obtained from the corresponding high resolution T2-weighted, spin-echo images and from histologic sections stained with hematoxylin and eosin and with an endothelial cell marker. The results showed that iron oxide microspheres can aid in the characterization of gross histopathologic features and in the assessment of the distribution of the microvasculature, whereas Gd-DTPA estimates the permeability of the microvessels to this agent and determines the cellularity (cell volume fraction) in the vicinity of the vessels.

Animals↗

Albumin microspheres as delivery systems for photodynamic drugs: physico-chemical studies and their implications for in vivo situations.

The potential of albumin (bovine serum) microspheres as delivery systems for haematoporphyrin and/or its zinc derivative was probed at the molecular level. The microspheres, prepared by heat denaturation, were stable to detergents and organic solvents but could be degraded by proteolytic enzymes. Drug loading was either by encapsulation during microsphere formation or by binding to preformed microspheres. The efficiency of encapsulation was found to depend on the initial drug/protein ratio with a saturable pattern. Binding of both drugs, or each alone, indicated the presence of two types of affinities of each drug to the microspheres. The leakage (release) of drug(s) from the microspheres into the aqueous medium over a period of several hours showed biphasic behaviour for each type of preparation, bound and encapsulated, for one or both drugs. A model assuming the microsphere-bound drug is distributed into two pools, differing in their drug-microsphere affinities, with no interference between the two drugs if both were bound, was found to account well for the equilibria data. Binding constants for respective pools were found to be similar for both drugs, of the order of 0.10 and 2 x 10(-4) ml/micrograms protein for the high and low affinity pools, respectively. The low affinity pools had the higher drug population. The two-pool model also fits well with the kinetic data, the pools differing in the rates of release. Rate constants for both drugs were found to be similar, of the order of 0.3 per min and 0.025 per hour for the fast and slow releasing pools, respectively. The population of the slow-releasing pool was higher, the high-affinity pool being the fast-releasing one, the low-affinity pool being the slow-releasing one. Implications for the microsphere-mediated delivery of these drugs in vivo are discussed.

Drug Carriers↗