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Biomedical subjects

R G Mason

Publications and source records attributed to R G Mason.

At least 55 records · Page 3Linked to original sources
PubMed1977

The endothelium: roles in thrombosis and hemostasis.

The renewed interest in endothelial function is based partly on success with tissue culture of endothelial cells. Endothelium functions primarily in the control of blood vessel wall permeability and in the provision of a blood-compatible lining surface. Recent findings indicate that endothelial cells are active metabolically in ways that may help prevent thrombosis. Endothelium actively degrades several different vasoactive compounds that circulate in blood and that can serve as platelet-aggregating agents. Endothelium also contains an inhibitor of platelet function and an activator of plasminogen, both of which can be released from the cell in response to appropriate stimuli. While intact endothelium functions primarily in prevention of thrombosis, damaged endothelium can contribute greatly to thrombus formation. Release of prostaglandins, adenine nucleotides, and other intracellular components from damaged endothelium can enhance platelet aggregation. Damaged endothelium may not function effectively in removal of vasoactive agents and may not release effective quantities of the inhibitor of platelet function or the activator of plasminogen. Altered endothelium exhibits tissue-factor activity, which can activate the extrinsic blood coagulation-system cascade. Finally, altered endothelial cells may contract and expose basement membrane to blood, thus enhancing thrombosis.

Blood Coagulation↗
PubMed1977

A concise method for study of the binding of thrombin to human platelets.

A rapid and sensitive technique is described for use in the study of the binding of 125I-thrombin to human platelets. The procedure involves the separation of free thrombin from platelet-bound thrombin by passage of this mixture through a discontinuous sucrose density gradient at low centrifugal force (1,500xg). Results obtained by this method are shown to be comparably to data obtained by two other conventional methods. This technique may facilitate further kinetic study of the binding of thrombin to human platelets.

Blood Platelets↗
PubMed1976

The subcellular distribution and partial characterization of cholinesterase activities of canine platelets.

The multiple cholinesterase activities in canine platelets have been investigated. Platelets were homogenized by rapid decompression under nitrogen, glass tube/Teflon pestle, and glycerol lysis techniques. Rapid decompression under nitrogen technique was found to be the most efficient and gentle method for cell disruption. Homogenates were subfractionated using sodium diatrizoate density gradients. Marker enzyme assays and pulse labeling experiments with 5-hydroxyl[14C] tryptamine and [125I] thrombin on prepared subcellular fractions confirmed that the soluble, plasma membrane and the granule-1 fractions were all in reasonably pure form. Furthermore, labeling of the plasma membrane with [125I] thrombin is cited as the first successful attempt at attaining significantly bound marker for this structure. Cholinesterase activity distributions measured in these fractions indicated that about 30% of the activity was present in the plasma membrane, 50% in granule-1 and 5% in soluble fractions. Kinetic data of cholinesterase activities obtained from intact platelets, plasma membrane preparations and platelet release supernatants indicated that they are strikingly similar.

Acetylglucosaminidase↗
PubMed1976

Multiple active forms of thrombin: binding to platelets and effects on platelet function.

The effect of various forms of thrombin on certain platelet functions has been investigated. Partially purified bovine thrombin which is a mixture of multiple active forms of thrombin, was chromatographed to yield molecular species termed alpha-, beta-, and gamma-thrombin, each of which has varying degrees of fibrinogen clotting and esterase activities. A direct correlation was observed between the ability of the different forms of thrombin to clot fibrinogen and to influence platelet function. In general, thrombin with high fibrinogen clotting activity was also a potent inducer of platelet aggregation and the release reaction, while those species with low clotting ability were poor inducers of aggregation and release.

Binding Sites↗
PubMed1976

Adhesion of human blood platelets to glass polymer surfaces. II. Demonstration of the presence of a natural platelet adhesion inhibitor in plasma and serum.

Adhesiveness of washed platelets resuspended in citrated plasma, serum, or several different media has been investigated. A method specific for quanititation of adhesion was used. Platelets suspended in saline of Tyrode's solution were found to be highly adhesive to glass, polyethylene, polyvinyl chloride, or Cuprophane. This adhesiveness of platelets to test surfaces decreased by nearly 50% when plasma was the suspension medium. When the suspension medium was serum, the decrease in adhesion was nearly 75%. Cohn fraction V also decreased the adhesiveness of platelets significantly, but highly purfied albumin had only a small effect. Several pharmacologic agents decreased platelet adhesiveness when added to platelets suspended in plasma or serum, but had negligible effect on the adhesiveness of platelets suspended in artificial media devoid of proteins. Normal washed platelets, when suspended in citrated plasma obtained from an afibrinogenemic donor or in normal serum, showed a significant decrease in adhesion compared to the same platelets suspended in normal citrated plasma. Addition of fibrinogen to afibrinogenemic plasma or normal serum restored the adhesiveness of platelets to normal levels. Normal platelets resuspended in plasma obtained from a thrombasthenic donor exhibited normal adhesiveness. These observations suggested that while fibrinogen promotes platelet adhesion, plasma or serum possess also an adhesion-inhibiting activity.

Afibrinogenemia↗
PubMed1976

Sickle cell syndromes. I. Hemoglobin SC-alpha-thalassemia.

Hematologic and globin synthesis studies were performed in a black American family in which the genes for alpha-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait + alpha-thalassemia; mother, HbC trait + alpha-thalassemia, propositus, HbSC + alpha-thalassemia; older sibling, alpha-thalassemia trait; and younger sibling, hemoglobin H disease. The child with HbSC-alpha-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2, 3-diphosphoglycerate (2, 3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin H disease exhibited 26% Bart's (gamma4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin H disease appeared, with HbH making up 6.5% of the total hemoglobin.

Anemia, Sickle Cell↗
PubMed1976

Lindholm blood coagulation test values of some glow-discharge polymer surfaces.

An ultrathin layer (approximately 500A) of glow-discharge polymer that is strongly bonded to a polymer film substrate can be sued to modify the blood compatibility of the polymer surface. Glow-discharge polymers of tetrafluoroethylene, hexamethyldisiloxane, ethylene-N2, and allene-N2-H20 were deposited onto Mylar film and subjected to Lindholm whole blood coagulation tests. Lindholm tests were performed in a manner that permitted statistical analysis. This was done by repeating the preparation of samples as well as the coagulation tests a number of times. Results showed that Lindholm tests values were useful in obtaining information pertinent to compatibility of surfaces with fresh human blood and to reproducibility of sample preparation by glow-discharge polymerization. The study also revealed that glow-discharge polymerization is a promising method to impart blood compatibility without altering other bulk properties of substrate polymers.

Blood Coagulation↗
PubMed1976

Blood components deposited on used and reused dialysis membranes.

Hemodialysis cartridges used once and reused once or twice were examined by scanning and transmission electron microscopy. Blood deposits consisting of leukocytes, platelets, and amorphous material covered 15 to 25% of the dialysis membrane surface of cartridges used once. This deposit increased somewhat with cartridge reuse but did not appear to impair the dialysis efficiency of membranes significantly. Leukocytes formed a major part of the blood deposit and spreading of these cells upon dialysis membranes was marked. Single and aggregated platelets were adherent to the dialysis membranes, to leukocytes, and to amorphous debris. Few erythrocytes were present, and fibrin was not identified. There was little evidence for build up or layering of the blood deposit with cartridge reuse. The procedures for dialysis cartridge rinsing used in these studies appear to be highly efficient in removal of adherent blood components.

Blood↗
PubMed1976

Ultrastructural aspects of interactions of platelets with microcrystalline collagen.

Whole blood anticoagulated with EDTA was stirred with high concentrations of a microcrystalline bovine dermal collagen preparation in order to study the interactions of blood cells with collagen at the ultrastructural level. Blood from normal subjects and from patients congenitally deficient in Factors VIII or XII or with thrombasthenia or von Willebrands disease was used. In scanning and transmission electron microscopic studies with blood from normal subjects and patients, platelets were seen to adhere to collagen, develop cell surface undulations, form pseudopods, and undergo morphologic changes suggestive of the release reaction. Although thrombasthenic platelets adhered to collagen, pseudopods formed by these cells were remarkably angulated and nodular. Relatively few von Willebrands platelets adhered to collagen, but those platelets that did adhere underwent the usual sequence of morphologic changes.

Blood Coagulation Disorders↗
PubMed1976

Dynamics of thrombus formation on an artificial surface in vivo. Effects of antithrombotic agents.

A nonhuman primate model for in vivo evaluation of antithrombotic agents is described. In this model, the formation of a thrombus on a segment of Silastic tubing placed in the vena cava of a rhesus monkey is utilized to evaluate the effectiveness of antithrombotic agents. Thrombus formation in this model was found to occur rapidly, but this initial deposit quickly was followed by a reduction in thrombus weight. Eventually, after 2 hours of implantation of the test device, thrombus weight again increased and reached an apparent plateau. Three different antithrombotic agents were evaluated with this model. Warfarin therapy was found to decrease the thrombus weight in approximate proportion to its effect on the prothrombin time. Aspirin and dextran each produced a decrease in thrombus weight in 2 of 3 animals tested. Individual differences in response to thrombotic agents are apparent, but despite this, the model appears to offer advantages for in vivo evaluation of antithrombotic agents.

Animals↗
PubMed1976

A nonhuman primate vascular shunt model for thrombus generation.

A nonhuman primate model for thrombus generation was developed. Three different types of test devices constructed of polystyrene or polyethylene-Silastic were exposed to flowing blood in arterioarterial or arteriovenous vascular shunts in rhesus monkeys. The test device design included a simple tube, a vortical flow device, and a turbulent flow device. The amount of thrombus deposited within each individual test device after a 15-minute exposure to blood flowing through the shunt was determined gravimetrically. These studies indicate that a test device designed to include an area of vortical flow generated the greatest amount of thrombus. Test devices fabricated from polystyrene consistently generated larger thrombus deposits than did similar test devices fabricated from polyethylene-Silastic. Arteriovenous shunts proved superior to arterioarterial shunts in that flow was predictable in the former and unpredictable in the latter; venovenous shunts thrombosed quickly. Hematologic studies indicated a progressive fall in platelet count during the 4-hour test interval in all animals, whereas in only a few animals were there a shortening of partial thromboplastin time values, a fall in fibrinogen levels, and the appearance of fibrin degradation products. An optimal model for thrombus generation appears to include vortical flow test devices fabricated of polystyrene exposed to flowing blood in an arteriovenous shunt.

Animals↗
PubMed1976

Effects of antithrombotic agents evaluated in a nonhuman primate vascular shunt model.

The effects of aspirin, cyproheptadine, dextran, dipyridamole, and sulfinpyrazone on thrombus deposition were determined. These antithrombotic agents were evaluated in a nonhuman primate model for thrombus generation that employed test devices exposed to blood in an arteriovenous shunt. Thrombus deposition on test devices was quantitated gravimetrically. Of the antithrombotic agents tested, cyproheptadine was found to be the most effective, and aspirin, dextran, and dipyridamole were each somewhat less effective. Sulfinpyrazone had only a slight antithrombotic effect. Ultrastructual studies of thrombus deposited in test devices showed that the various antithrombotic agents tested did not prevent completely the formation of fibrin, aggregation of platelets, or adhesion and spreading of platelets and leukocytes. This model for thrombus generation is felt to be a more efficient means for evaluating antithrombotic agents than previously described nonhuman primate models.

Animals↗