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Y Nemerson

Publications and source records attributed to Y Nemerson.

At least 127 records · Page 7Linked to original sources
PubMed1974

Self-damping mechanism in blood coagulation.

Two reactions of the extrinsic pathway of coagulation, the activations of Factor X and prothrombin, have been studied in purified systems and shown to be self-damping. Factor X was activated by the tissue factor-Factor VII complex, and prothrombin by two systems: the coagulant protein of Taipan venom, and the physiological complex of activated Factor X, Factor V, lipid, and calcium ions. In each case the yield of enzyme, activated Factor X or thrombin, is a function of the concentration of activator. These and other observations are considered as a basis for a control mechanism in coagulation.

Blood Coagulation↗
PubMed1973

Activation of a proteolytic system by a membrane lipoprotein: mechanism of action of tissue factor.

One pathway of blood coagulation, the extrinsic system, is initiated by a specific interaction between tissue factor, which is a membrane lipoprotein, and factor VII, one of the plasma coagulation factors. Factor VII was prepared from bovine plasma by adsorption onto and elution from BaSO(4). The eluate was chromatographed on DEAE-Sephadex and purified by preparative disc-gel electrophoresis. Factor VII complexed with purified bovine-brain tissue factor and, when eluted from the complex, factor VII had a greater mobility in acrylamide-gel electrophoresis in the presence of sodium dodecyl sulfate, i.e., it had a reduced molecular weight. Factor VII was also cleaved in the presence of orthophenanthroline, an inhibitor of the peptidase activity of tissue factor. Prior treatment of factor VII with diisopropylphosphorofluoridate, however, completely blocked its cleavage and the development of coagulant activity, although factor VII treated with diisopropylphosphorofluoridates complexed equally well as the native protein with tissue factor. Factor VII in whole bovine plasma was also inhibited by the drug. Factor VII labeled with [(32)P]diisopropylphosphorofluoridate and radioautographed after electrophoresis in gels showed two major components, only one of which was labeled. We conclude that tissue factor initiates blood coagulation by facilitating a proteolytic attack within the factor VII "complex." The most likely mechanism is proteolysis of one form of factor VII by the diisopropylphosphorofluoridate-sensitive enzyme, although additional intramolecular proteolysis may be involved.

Animals↗
PubMed1972

Tissue factor (thromboplastin): localization to plasma membranes by peroxidase-conjugated antibodies.

Peroxidase-conjugated antibodies were used to determine the histologic and cytologic localization of bovine and human tissue factor (thromboplastin). Tissue factor antigen was found in highest concentration in the intima of blood vessels, particularly in the plasma membranes of endothelial cells and in human atheromatous plaques. Tissue factor was also found limited to the plasma membranes of many cell types. The presence of tissue factor in the plasma membranes of endothelial cells and atheromata suggests that it may play a significant role in hemostasis and thrombosis.

Animals↗
PubMed1969

Characteristics and lipid requirements of coagulant proteins extracted from lung and brain: the specifity of protein component of tissue factor.

Soluble proteins were prepared from bovine lung and brain which, when combined with phospholipids, had the biological characteristics of tissue factor. The proteins were solubilized from delipidated (heptane; butanol-extracted) acetone powders with deoxycholate, and precipitated by (NH(4))(2)SO(4) (30-60% saturation). These soluble proteins, which contained less than 1% phospholipid, were essentially inert in an assay for tissue factor. When they were recombined with phospholipids, however, activity increased by a factor of 500-1000. Phosphatidylethanolamine was the most active specific phospholipid, followed by phosphatidylcholine. Phosphatidylserine was inert. Mixed phospholipids were from two to four times more active than phosphatidylethanolamine. Maximum activity was obtained at phospholipid to protein ratios of 1.5:1 (wt/wt), and when relipidation was performed in deoxycholate followed by dialysis against 0.05 M imidazole-0.375 M NaCl, pH 7.2. The proteins were characterized by gel filtration on Sephadex G-200; the activity eluted as a single peak with an apparent mol wt of 425,000. The brain and lung activities were recovered from chromatography on triethyl-aminoethyl-cellulose as single peaks, although the salt concentration required for elution was different for each protein. This suggests that within each organ there is one tissue factor-protein, but there may be molecular differences between brain and lung tissue factor. Alternatively, the chromatographic differences may simply reflect charge differences imparted to the proteins by residual lipids.

Animals↗
PubMed1968

The phospholipid requirement of tissue factor in blood coagulation.

Using a coagulation assay specific for tissue factor, we found that removal of 95% of the tissue factor-phospholipid resulted in a loss of 98% of its biological activity. The activity could be restored, with yields in excess of 100% by combining the extracted tissue factor with either mixed brain phospholipids or highly purified phospholipids. Phosphatidylethanolamine was the most active, followed by phosphatidylcholine. Phosphatidylserine, phosphatidylinositol, and sphingomyelin had little or no activity. In addition, a requirement for unsaturation and the presence of two fatty acids was demonstrated. The activity of phosphatidylcholine was also dependent on the presence of the base. Furthermore, it was shown that activity was not a function of binding of phospholipids to tissue factor, as both active and inactive lipids were equally bound.

Journal Article↗