Th.--Sci. phys.--Grenoble--I.N.P., 1980. N°: DE 87.

The mechanism and regulation of prothrombinase function in the activation of prothrombin and prethrombin-1 were studied. In addition, the kinetics of plasmin-mediated fibrin degredation were determined. First, the mechanism of prothrombin activation by prothrombinase was investigated using two models – a one-form model which posits a single form of prothrombinase and a two-form model which posits the existence of two, equilibrating forms of prothrombinase each specific for either activation cleavages. In summary, the two-form model fit the data better, as well as predict the initial rates of prothrombin activation better than the one-form model, and thus better represents the mechanism of prothrombinase on prothrombin activation. Second, the differences observed in the activation kinetics of prethrombin-1 by prothrombinase consisting of either human or bovine factor Va (FVa) was investigated. The difference was due to the species origin of the heavy chain. Because the conserved domains show high sequence homology, the carboxy-terminus was studied. The calculated pI of the ten carboxy-terminal residues are 12.5 for human and 4.26 in bovine, suggesting that with bovine FVa, the net negative charge of the ten residues augments the negative charge of DSDYQ, thus facilitating the FVa-prethrombin-1 interaction required for Arg320 cleavage. Third, the kinetics of activated protein C (aPC)-mediated inactivation of FVa in real-time, during prothrombin activation was investigated. A profound protection of FVa from aPC was observed (>100-fold), which was much greater than the individual protection with either factor Xa (3 to 10-fold) or prothrombin (10-fold) alone. The addition of protein S, the cofactor for aPC, resulted in a two-fold increase in the rate constant, but did not ameliorate the protection. Lastly, the kinetics of plasmin-mediated lysis of fibrin clots was investigated. The clot lysis by plasmin showed a low Km (1 to 2uM) suggesting zero-order kinetics. In contrast, the clot formation showed first-order kinetics. These results suggest that as the concentration of fibrinogen increases, especially above the physiologic level, the balance between fibrinolysis and clotting shifts toward the latter, thus providing a biochemical rationale for the increased risk of cardiovascular disease associated with elevated level of fibrinogen. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2009-09-04 16:11:07.151

Graduation date: 1972

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 8 uppsatser. På diss.-titelbl. felaktigt disputationsår.

Thesis (M.S.)--University of Wisconsin--Madison, 1971. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

M.Tech.

No description available.

No description available.

Hydrous aluminum oxide colloids of 0.5 Am diameter were used to study the coagulation of submicron particles under water-treatment conditions. The research was aimed at understanding the effects of pH and ligands (organic and inorganic) on precipitation of the added coagulant and their influences on incorporation of the colloids into larger flocs. The reduction in the concentration of submicron particles as a result of alum coagulation was monitored by conventional jar-test experiments. Scanning electron microscopy was used for submicron particle counting. Up to three orders of magnitude reduction in submicron particle concentrations were observed in jar-test experiments. Higher pH (i.e., 7.5) and alum dose (i.e., 1.0 mg L⁻¹) favored homogeneous precipitation of aluminum hydroxide, whereas heterogeneous precipitation occurred at lower pH (i.e., 6.5) and alum dose (i.e., 0.5 mg L⁻¹). Homogeneous precipitation, involving formation of Al(OH)₃(s) from aqueous species, formed large masses of light-weight flocs that can effectively remove submicron particles by subsequent coagulation. Heterogeneous precipitation, which involves precipitation on the surfaces of the seed particles, resulted in destabilized particles that can efficiently coagulate with each other. The presence of ligands, inorganic (e.g., HCO₃⁻) and organic (e.g., functional groups of humic substances) inhibited the coagulation process, reducing particle removal up-to 250 fold. While these ligands inhibit coagulation by modifying particle surfaces, they may enhance the precipitation reactions of aluminum hydroxide. The presence SO₄²⁻ enhanced precipitation relative to NO₃⁻. Electrophoretic mobility values were used to derive equilibrium constants for aluminum speciation and precipitation reactions, both on the surface of particles and in solution. The adsorption of ligands lowered the pHiep, by almost 2 pH units in the presence of HCO₃⁻, and to a pH of less than 3 in the presence of organics. Aluminum species elevated the pHiep by 1 pH unit. Stoichiometric ratios of aluminum hydroxide precipitation were determined using a pH stat. This ratio (1.9 to 3.7) is a function of pH, and concentrations of particles and organics. These results were modeled as spherical precipitates (OH/A1 =3) with adsorbed aluminum species (OH/A1 = 1 to 4). The results of this research suggest that the aluminum precipitation pathway dictates the removal of submicron particles. Submicron particles provide most of the surfaces from particulate matter, thus suggesting the importance of surface precipitation for their removal. Samples from water treatment plants indicated 1.5 to 2.0 log removal of submicron particles. These plants were operating at higher pH values (above 7.5) relative to that of maximum removal experiments in laboratory. Plant operations can be optimized by careful control parameters affecting supersaturation ratio, thus improving removal of submicron particles.Such optimization should include efficient rapid mixing to achieve uniform upersaturation ratios, proper coagulant dose, and possibly better pH control.

A descriptive study was conducted to test the null hypothesis: There will be no statistically significant difference between serum activated partial thromboplastin time (aPTT) obtained by two methods; venipuncture and large bore femoral arterial catheter. The convenience sample consisted of seventeen adults who had undergone percutaneous transluminal coronary angioplasty (PTCA) for the treatment of coronary artery disease. After the PTCA procedure, patients returned to an intensive care unit with a femoral intra-arterial catheter in place. Seventeen pairs of serum samples were obtained; one by venipuncture and one through the femoral intra-arterial catheter. Prior to obtaining the sample from the femoral intra-arterial catheter, 6.0 milliliters (3 times the deadspace of the catheter) of blood was withdrawn and discarded. aPTT samples were analyzed. T-tests were used to compare the results. Findings revealed that there was no statistically significant difference in the aPTT value when drawn from venipuncture versus the femoral intra-arterial catheter.