Interaction of thrombin with endothelial cells in the presence of fibrinogen and alpha 2-macroglobulin.

Binding of thrombin to cultured endothelial cells has been studied in the presence of fibrinogen and alpha 2-macroglobulin. Both fibrinogen and alpha 2-macroglobulin inhibit the interaction of thrombin with endothelial cells. Whereas fibrinogen decreases the rate of activation by the thrombin-thrombomodulin complex of protein C, thrombomodulin inhibits the rate of inactivation by alpha 2-macroglobulin thrombin.

Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization.

We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30-70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 degrees C and 4 degrees C, and shows minimal inhibition of binding in the presence of 40% canine serum.

Thrombin-induced activation of calcium transport pathways and their role in platelet functions.

In human platelets thrombin-induced calcium release from intracellular stores, the consequent influx of extracellular calcium, as well as their role in the aggregation and ATP-secretion reactions were examined. In indo-1-loaded platelets intracellular calcium release was studied in the presence of excess EGTA in the incubation medium, while calcium influx was followed after a rapid repletion of external calcium. After thrombin-stimulation both calcium release and calcium influx produced about the same peak levels of cytoplasmic free calcium but in the first case it was only a transient response, while in the latter one a sustained calcium signal was observed.

Effect of chronic hypoxia on 45Ca and 86Rb uptake in aortic smooth muscle from spontaneously hypertensive rats (SHR).

The effect of chronic hypobaric hypoxia equivalent to a simulated high altitude of 4000 m was investigated on the Ca2+ and Rb+ uptake in vascular smooth muscle. The decline in systolic blood pressure in SHR due to hypoxia was associated with a significant decrease in 45Ca uptake and ouabain-insensitive 86Rb uptake as well as the tissue Ca2+ and K+ content. It seems likely that the reduction of the higher vascular tone in SHR by chronic hypoxia is due to the alteration of the transmembrane ion fluxes in the vascular smooth muscle cells.

Volume regulatory mechanisms of human granulocytes in hypoosmotic media.

Human neutrophil granulocytes, when placed into hypoosmotic media, first swell, than show a regulatory volume decrease (RVD) reaction. This RVD is the most effective at pH 7.5 when inosine is used as a metabolic substrate.

Effects of calcium channel-blocker tokolysis on the foetal circulation.

The Ca++-antagonist nifedipine has been successfully employed in the treatment of non-gravid hypertension, and was found to inhibit uterine contractions in the perimenstrual period, as well as during premature labour in animal models. The use of antihypertensive drugs in pregnancy introduces the possibility of iatrogenic foetal distress. It has been established that nifedipine crosses the placental barrier in the sheep and causes a fall in mean arterial pressure and tachycardia in both the ewe and the foetus.

Effect of beta-adrenoceptor stimulation or blockade on regional myocardial function and regional O2 consumption during myocardial ischemia.

The purpose of this study was to determine the effect of beta-adrenoceptor activation and blockade on the relationship between regional myocardial function and regional O2 consumption in ischemic and nonischemic myocardium. Myocardial regional segmental function was assessed in 28 open chest, anesthetized dogs using subepicardial dimension gauges. Ten min after LAD (left anterior descending coronary artery) occlusion, dogs were given i.

Beta-adrenoceptor stimulation and blockade during myocardial ischemia in dogs: effect on cardiac O2 supply and consumption.

The effect of beta-adrenoceptor blockade and activation on ischemic regional and microregional myocardial O2 supply/consumption parameters was assessed in 28 open chest, anesthetized dogs. Ten minutes after LAD occlusion, dogs were given i.v.

Incorporation of the carbocyclic analogue of (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-triphosphate into a synthetic DNA.

The carbocyclic analogue of (E)-5-(2-bromovinyl)-2'-deoxyuridine, C-BVDU, is a very potent and selective anti-herpes-virus compound. In order to synthesize and study the properties of a DNA that contains C-BVDU, the 5'-triphosphate, C-BVDUTP was prepared and evaluated as a potential substrate of the E. coli Klenow DNA polymerase enzyme.

Conditions of formation of the heparin-fibronectin-collagen complex and the effect of plasmin.

The formation and composition of the insoluble heparin-fibronectin-collagen complex and its degradation by proteolysis was investigated. At fixed concentrations of the other molecular components of the complex, the maximal rate of complex formation, measured turbidimetrically, was reached at a concentration of 4 microM heparin and 0.9 microM collagen, while the rate of complex formation was linearly related to concentrations of fibronectin as high as 3 microM.

Interaction of antithrombin III and thrombin-antithrombin III complex with cultured aortic endothelial cells.

The binding of antithrombin III, thrombin, thrombin-antithrombin III complex to endothelial cells was investigated. While the rate of the binding of thrombin to these cells was very rapid, that of antithrombin III was relatively slow and the thrombin-antithrombin III complex was intermediate. Binding kinetics indicated that antithrombin III, like thrombin, showed high affinity to endothelial cells; with a Kd of 3 X 10(-8) M and with 5 X 10(4) binding sites per cell.

A comparison of the conformations adopted by some 5-bromovinyl-2'-deoxyuridines and a correlation with their antiviral properties: an X-ray study.

Crystal structures of (Z)-5-(2-bromovinyl)-2'-deoxyuridine, 3',5'-di-O-acetyl-(E)-5-(2-bromovinyl)-2'-deoxyuridine and 3',5'-di-O-p-chlorobenzoyl-5-(2-dibromovinyl)-2'-deoxyuridine are compared with each other and with that of the most potent antiviral agent (E)-5-(2-bromovinyl)-2'-deoxyuridine (E-BVDU) reported earlier. A comparison of the conformation of 3',5'-di-O-acetyl-pyrimidine nucleoside structures in which intermolecular hydrogen bond network formation is minimized, with those of their parent compounds has shown that the greatest change in rotation about the glycosyl bond and in the sugar ring pucker is exhibited by E-BVDU. Upon acylation this molecule changes from C2'-endo/C3'-exo conformation to C3'-endo/C4'-exo conformation.

Substrate specificity of DNA polymerases. I. Enzyme-catalysed incorporation of 5-'1-alkenyl)-2'-deoxyuridines into DNA.

A series of (E)-5-(1-alkenyl)-dUTPs as well as 5-vinyl-and (Z)-5-(1-propenyl)-dUTP have been synthesized to study steric requirements in DNA polymerase reactions. Experiments were carried out in E. coli DNA polymerase I Klenow fragment enzyme system.

Substrate specificity of DNA polymerases. II. 5-(1-Alkynyl)-dUTPs as substrates of the Klenow DNA polymerase enzyme.

A structure-activity relationship study was carried out with a sequence of 5-(1-alkynyl)-dUTPs in Klenow DNA polymerase enzyme-catalyzed reactions. Ability of modified dUTPs examined (up to the octynyl derivative) to serve as a substrate depended on both the length of substituent and the structure of DNA primer-template used.

Endoscopic control of gastroduodenal hemorrhage.

Several methods of endoscopically controlling acute, nonvariceal upper gastrointestinal bleeding have been developed. Some, such as the laser, heater probe, and bipolar electrocoagulation, have been evaluated in controlled clinical trials. The purpose of this paper is to discuss endoscopic control of nonvariceal gastroduodenal hemorrhage and to consider whether improvement in outcome is likely with any of these devices.

The effect of an oral evening dose of nizatidine on nocturnal and peptone-stimulated gastric acid and gastrin secretion.

An evening oral dose of nizatidine, a new H2-receptor antagonist, was tested for its ability to suppress nocturnal gastric acid secretion and to inhibit food stimulated acid secretion the following day. Using a double-blind, randomized, cross-over design, nizatidine 30, 100, and 300 mg and placebo were compared in 8 male subjects with basal acid secretion greater than or equal to 3 mmol/h. Continuous nasogastric suction was started 2 h after oral dosing, and acid secretion was measured hourly overnight.

Effects of isoproterenol on rubidium transport in slow- and fast-twitch muscles from euthyroid and hyperthyroid rats.

The influence of experimental hyperthyroidism on the catecholamine induced stimulation of rubidium ion transport in the soleus (SOL), a slow-twitch muscle and the extensor digitorum longus (EDL), a fast-twitch skeletal muscle of rats was studied. Thyroxine administration (800 micrograms/kg/day), for ten days induced a rise of ouabain-sensitive 86Rb uptake in SOL muscle, without affecting the ouabain-insensitive uptake, whereas both fractions of 86Rb uptake were increased in EDL muscle from hyperthyroid rats. Isoproterenol (5 mumol/l) caused a two-fold rise in ouabain-sensitive Rb uptake of euthyroid SOL muscle, while in hyperthyroid SOL it could stimulate only the ouabain-insensitive fraction of 86Rb influx.

Inhibition of sodium for sodium exchange by phlorizin in frog sartorius muscle.

The effects of phlorizin (2 X 10(-3) mol X l-1) on the Na transport of frog (Rana esculenta) sartorius muscle were investigated in glucose-free medium. Phlorizin decreased the rate coefficient of 24Na efflux by about 40%. The degree of inhibition was comparable to that caused by ouabain (10(-4) mol X l-1).