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Biomedical subjects

M W Mosesson

Publications and source records attributed to M W Mosesson.

At least 163 records · Page 9Linked to original sources
PubMed1973

Degradation of human fibrinogen by plasms alpha2-macroglobulin-enzyme complexes.

This study demonstrates that human plasma alpha(2)-macroglobulin preparations possess an enzymic activity that degrades fibrinogen, resulting in the formation of products whose structure resembles that of circulating fibrinogen catabolites. The sequence of degradation is similar to that observed in plasmin-catalyzed digests, in that Aalpha-chain fragmentation precedes that of Bbeta-chain. The addition of plasminogen activators to plasma induced an increase in the N-alpha-tosyl-l-arginine methyl ester HCl esterase and fibrinogenolytic activity associated with alpha(2)-macroglobulin purified from this plasma, indicating that the enzymic activity of the complex was preserved and could be increased in the presence of other plasma enzyme inhibitors. Immunochemical studies demonstrated that an alpha(2)-macroglobulin-plasmin complex had formed in urokinase-treated plasma. This alpha(2)-macroglobulin preparation manifested an esterolytic profile like that of a complex prepared from plasmin and purified alpha(2)-macroglobulin. After complex formation with alpha(2)-macroglobulin in plasma, plasmin retained less than 0.1% of its fibrinogenolytic activity. That plasmin expressed its activity while bound to alpha(2)-macroglobulin was suggested by immunoprecipitation of this activity with alpha(2)-macroglobulin antibody and by the demonstration that pancreatic trypsin inhibitor did not effectively inhibit its fibrinogenolytic or esterolytic activity. These results raise the possibility that, in addition to its activity as a major plasma proteolytic enzyme inhibitor, alpha(2)-macroglobulin may modulate enzyme-substrate interactions, such as those resulting in the formation of circulating fibrinogen catabolites, by providing a mechanism for the preservation and protection of a portion of the enzymic activity in the presence of other circulating inhibitors.

Acetates↗
PubMed1969

Chromatographic, ultracentrifugal, and related studies of fibrinogen "Baltimore".

Chromatographic, ultracentrifugal, and related studies of the fibrinogen of a patient with a congenital disorder of fibrinogen (fibrinogen "Baltimore" have provided evidence of structural differences from normal.Diethylaminoethyl-cellulose (DEAE-cellulose) gradient elution chromatography demonstrated two major peaks in the elution pattern of fibrinogen Baltimore as was the case for normal fibrinogen. However, the first peak of fibrinogen Baltimore was somewhat broader and more symmetrical and was eluted significantly later in the chromatogram than the corresponding peak of normal fibrinogen. Additionally, in some elution patterns, a shoulder on the ascending limb of peak 1 was present, suggesting the presence of chromatographically "normal" fibrinogen. Thrombin time determinations of eluted column fractions from a chromatogram of propositus fibrinogen supported this conclusion by demonstrating that fibrinogen from the ascending portion of peak 1 behaved functionally more like normal than that later in the chromatogram. Chromatograms of mixtures of propositus and normal fibrinogen confirmed the ability of this technique to distinguish normal from Baltimore fibrinogen. Chromatograms of fibrinogen isolated from two affected daughters displayed the characteristic increased anionic binding of peak 1 fibrinogen. Sedimentation velocity experiments indicated that the S(o) (20, [unk]) of fibrinogen Baltimore was slightly greater (8.13S vs. 7.85S) than that of normal fraction I-4. Differences in concentration dependence (- 0.65 c vs. - 1.30 c for normal) of the sedimentation coefficient could be attributable in part to spatial conformational differences. Molecular sieving experiments in acrylamide gels indicated that the molecular weight of propositus fraction I-2 was about the same as that of normal fibrinogen of comparable solubility (i.e. I-4, mol wt 325,000). Studies of the UV spectra, tyrosine/tryptophan ratios, sialic acid and hexose content, and N-terminal amino acids demonstrated no consistent significant differences from normal fraction I-4.

Amino Acids↗
PubMedDate not supplied

The covalent structure of factor XIIIa crosslinked fibrinogen fibrils.

When factor XIIIa-mediated crosslinking of fibrin or fibrinogen occurs, reciprocal intermolecular isopeptide bonds form first between paired carboxy terminal gamma chain donor-acceptor sites in outer molecular D domains, resulting in gamma chain dimers. Their location in the fibrin polymer is not certain, but some evidence suggests they are situated at the outermost ends of the D domains of linearly aligned molecules comprising each strand of double-stranded fibrils ("DD-long"). Other experiments indicate that gamma chain bonds are located between D domains in opposing fibril strands ("transverse"). To distinguish between these possible arrangements, we evaluated the ultrastructure of fibrils and fibers found in factor XIIIa-fibrinogen crosslinking mixtures, based on this reasoning: if DD-long bonding occurs, single-stranded fibrils should result, whereas transverse positioning will result in double-stranded fibrils. Fibrils formed in partially cross-linked fibrinogen solutions consisted of two parallel strands, as discerned visually from scanning transmission electron microscopic images and confirmed by mass per unit length fibril measurements. Neighboring fibrinogen D domains in each fibril strand were aligned end-to-end and were in register with a fibrinogen E domain in the opposite strand, creating a half-staggered molecular arrangement with approximately 22.5-nm periodicity corresponding to half the length of fibrinogen. Ribbon-like fibrinogen fibers, like fibrils, displayed 22.5-nm periodicity, as expected from laterally associated double-stranded fibrils with D domains in register. Taken together, these results indicate that carboxy terminal gamma chain bonds are positioned transversely between strands and are represented by thin filamentous structures bridging the D domains of opposing fibril strands--it follows that the same gamma chain crosslink arrangement occurs in fibrin.

Chromatography, Gel↗
PubMedDate not supplied

Evaluation of factor VIII-rich cryoprecipitate and the plasma fibronectin-rich, heparin-precipitable fraction prepared from single-donor plasma units.

A plasma fibronectin-rich component was prepared by heparin-induced 4 degrees C precipitation of fresh or stored (21 days at 4 degrees C), single-donor plasma. The recovery of plasma fibronectin was 45 percent at a concentration of 0.05 mg heparin per ml (7.5 units/ml) and 75 percent at 0.1 mg per ml (15 units/ml). The biologic activity of plasma fibronectin, as assessed by the spreading of Chinese hamster ovary cells or attachment of monocytes to gelatin-coated surfaces, was similar to that of plasma fibronectin concentrates made from fresh or stored plasma. Only 20 to 30 percent of the factor VIII activity in fresh plasma was recovered in cryoprecipitate produced after the heparin-induced precipitate containing fibronectin was removed. Cryoprecipitate prepared from the supernatant plasma that remains after heparin-induced cold precipitation in the presence of CaCl2 (5 mM) contained approximately 50 percent less factor VIII. The relatively low recovery of factor VIII in cryoprecipitate prepared from fibronectin-depleted plasma makes cryoprecipitation an unsuitable method of producing fibronectin-rich and factor VIII-rich components effectively from a single unit of fresh plasma. However, heparin-induced cold precipitation provides an efficient method for preparing plasma fibronectin concentrates from small plasma pools or single units of stored or fresh plasma.

Blood Preservation↗
PubMedDate not supplied

Hemostatic evaluation of Sarns/3M-VAD implantation in calves.

The authors evaluated the potential for thrombotic complications arising from implantation of a ventricular assist device (Sarns/3M-VAD) in four calves. Coagulation screening tests (prothrombin time [PT], partial thromboplastin time [PTT], thrombin time [TT]), fibrinogen levels, and antithrombin III functional activity were found to be of little value as predictors of the degree of activation of the hemostatic system. However, platelet counts, adenosine diphosphate (ADP)- and collagen-induced platelet aggregation, and thromboxane (TXB2) levels were good indicators of changes in platelet reactivity. Platelet counts (initial value 6 x 10(5) rose, and were associated with increased rate and extent of ADP- and collagen-induced platelet aggregation, which remained elevated during the entire 25 day postimplantation period. The first 5 days postimplantation revealed a typical acute inflammatory response, with increased platelet levels, but with TXB2 levels significantly decreased during this period. A monoclonal antibody based bovine D-dimer assay and Western blot studies indicated a small but significant increase in circulating bovine D-dimer, indicating localized fibrin formation and its dissolution.

Animals↗