Search PubMed⌕ Search

Biomedical subjects

S Niewiarowski

Publications and source records attributed to S Niewiarowski.

At least 163 records · Page 9Linked to original sources
PubMed1980

Secreted platelet proteins with antiheparin and mitogenic activities in chronic renal failure.

The levels of secreted platelet antigen (LA-PF4/beta TG) were measured by radioimmunoassay in samples of PPP obtained from human blood collected on EDTA and inhibitors of platelet release reaction. These levels in plasma of 17 normal individuals, 18 nondialyzed patients with chronic renal failure, and nine patients on hemodialysis were 31.9 +/- 2.8 ng/ml, 135.1 +/- 21.4, and 291.8 +/- 26.3, respectively. No significant differences were observed in platelet counts and in the levels of this antigen in PRP of these three groups of individuals. The levels of PF4 in PPP of eight normal individuals and in plasma of seven patients with chronic renal failure were 7.41 +/- 0.67 and 7.53 +/- 1.11 ng/ml, respectively. During processing of blood samples in the absence of platelet release inhibitors, platelets of patients with chronic renal failure released less LA-PF4/beta TG antigen than did normal platelets. The mean levels of LA-PF4/beta TG antigen excreted in urine of six normal individuals and 10 patients with chronic renal failure were 57.75 and 1461.5 ng/100 mg of creatinine per day, respectively. After 3 hr hemodialysis, LA-PF4/beta TG antigen levels in PPP increased from 291.8 +/- 26.3 ng/ml to 505.3 +/- 87.3. By contrast, this antigen in three patients with successful kidney transplants rapidly returned to levels close to normal following graft function. Immunoreactive material from pooled urine of patients with chronic renal failure was isolated by isoelectric focusing. This material focused at pH 10.0 to 10.8 and induced DNA biosynthesis in 3(3 swiss cells, indicating its similarity to PBP. It is proposed that elevation of LA-PF4/beta TG antigen observed in plasma of patients with chronic renal failure resulted from the impaired handling of this protein by the kidney.

Adult↗
PubMed1980

Products of tissue injury. Their induction of venous endothelial damage and blood cell adhesion in the dog.

To investigate the effects of the continuous entry into the circulation of selected products of tissue injury, histamine, serotonin, and bradykinin were infused intravenously for four hours into anesthetized dogs. Infusion of Tyrode's solution served as the control. Arterial blood pressure and ECG were unchanged at the levels of agents used. In jugular veins, test agents but not Tyrode's solution caused subtle changes over the endothelial sheet and multiple parallel tears of endothelium near valves and side branches. Numerous leukocytes and erythrocytes, and occasional platelets, adhered singly or in small patches to intact but altered endothelium. Masses of leukocytes, erythrocytes, and some platelets accumulated on areas of disrupted endothelium. Arterial endothelium from treated dogs was the same as from controls and was free of blood cells. Jugular veins and carotid arteries were free of noncellular material except for two of six veins from dogs receiving histamine. Thus, the continuous entry of low levels of histamine, bradykinin, and serotonin caused venous damage and blood cell accumulation, both of which have been implicated in initiation and propagation of venous thrombosis.

Animals↗
PubMed1979

Thrombocytin, a serine protease from Bothrops atrox venom. 1. Purification and characterization of the enzyme.

Thrombocytin, a platelet-activating enzyme from Bothrops atrox venom, has been purified to homogeneity by precipitation with sodium salicylate and chromatography on heparin--agarose. Thrombocytin is a single-chain glycoprotein with a molecular weight of 36 000 which contains 5.6% carbohydrate. It causes platelet aggregation, release of platelet serotonin, and activation of factor XIII. The most sensitive substrate for the amidolytic activity of thrombocytin was Tos-Gly-Pro-Arg-p-nitroanilide hydrochloride. The activity of thrombocytin on this substrate and on platelets was inhibited by diisopropyl fluorophosphate (DFP), soybean trypsin inhibitor, and several arginine chloromethyl ketones. Active site titration with nitrophenyl guanidinobenzoate demonstrated that approximately 86% of the preparation was in the active form. These experiments demonstrate the presence of serine and histidine in the active site of thrombocytin and suggest that thrombocytin is a classical serine protease with a platelet-activating activity similar to thrombin.

Amidohydrolases↗
PubMed1979

Thrombocytin, a serine protease from Bothrops atrox venom. 2. Interaction with platelets and plasma-clotting factors.

Thrombocytin, a serine protease from Bothrops atrox venom, caused platelet aggregation and release of platelet constituents at a concentration of 10(-7) M and clot retraction at a concentration of 2 x 10(-9) M. Thrombocytin was slightly more active when tested on platelets in plasma than on washed platelets suspended in Tyrode--albumin solution. Thrombin was 5 times more active than thrombocytin when tested on platelets in plasma and 50 times more active when tested on washed platelets. The patterns or release induced by thrombocytin and thrombin were similar. Prostaglandin E1 (10(-5) M) produced complete inhibition of platelet release induced by thrombocytin and thrombin. Indomethacin (10(-4) M) was without any effect. Antithrombin III, in the presence of heparin, inhibited the action of thrombocytin on platelets and on a synthetic peptide substrate (Tos-Gly-Pro-Arg-pNA.HCl). formation of an antithrombin III--thrombocytin complex was demonstrated on NaDodSO4--polyacrylamide gel electrophoresis. Hirudin and alpha 1-antitrypsin did not inactivate thrombocytin. Thrombocytin had a low fibrinogen-clotting activity (less than 0.06% that of thrombin). Thrombocytin also caused progressive degradation of the alpha chain of human fibrinogen, and it cleaved prothrombin, releasing products similar to intermediate 1 and fragment 1 produced by thrombin. Thrombocytin activated factor XIII by limited proteolysis and increased the procoagulant activity of factor VIII in a manner analogous to that of thrombin.

Animals↗
PubMed1977

Function of human platelets during extracorporeal circulation.

The interaction between human platelets and nonbiologic surfaces was studied during in vitro recirculation of 500 ml of fresh, heparinized human blood in four different perfusion circuits. Circuits differed in surface area (0.1 m2 or 0.9 m2) and in surface composition. No important differences were observed between standard silicone-rubber and filler-free, silicone-rubber surfaces. Platelet counts decreased to 85% of control in 0.1- m2 circuits, but retained normal sensitivity to aggregating agents and released only small amounts of platelet factor 4 (PF4). In contrast, platelet counts in 0.9-m2 circuits decreased to 20% of control within 2 min and platelet sensitivity was depressed out of proportion to the fall in platelet count. Plasma PF4 progressively increased and platelet PF4 content progressively decreased during 6 h of recirculation. The results indicate that human platelets may exist in three conditions during extracorporeal circulation. Some platelets are unaltered, some are less sensitive to aggregating agents, and others have undergone extensive release. The ratio of blood volume to surface area appears to be an important determinant of platelet-surface interaction.

Adenosine Diphosphate↗
PubMed1977

Binding of dipyridamole to human platelets and to alpha1 acid glycoprotein and its significance for the inhibition of adenosine uptake.

The interactions of dipyridamole with alpha(1) acid glycoprotein of plasma and with human platelets are related to inhibition of adenosine uptake by platelets. Binding studies by equilibrium gel filtration suggested that 1 mol of dipyridamole binds per mol of alpha(1) acid glycoprotein with a dissociation constant of 1.6 muM. Platelets contain two populations of binding sites, one with high and another with lower affinity for the drug. The binding of dipyridamole to the high-affinity sites follows a Michaelis-Menten binding pattern with a dissociation constant of 0.04 muM. Approximately 2 x 10(4) dipyridamole molecules are bound at the high-affinity sites of each platelet. The lower affinity sites bind the drug with a dissociation constant of 4 muM. In the presence of alpha(1) acid glycoprotein of plasma, the binding of dipyridamole to human platelets is inhibited. Correspondingly, the dipyridamole inhibition of adenosine uptake by platelets is reduced 1,000-fold by purified alpha(1) acid glycoprotein. The binding of dipyridamole to human platelets was found to be essential for its inhibition of adenosine uptake by platelets. Dipyridamole decreases the incorporation of [(14)C]adenosine radioactivity in platelet nucleotides and reduces the [(14)C]-ATP to [(14)C]ADP ratio. Purified alpha(1) acid glycoprotein reverses these effects of dipyridamole on adenosine metabolism of platelets in a concentration-dependent manner. An equilibrium of dipyridamole binding to alpha(1) acid glycoprotein and to platelets is proposed.

Adenine Nucleotides↗