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Biomedical subjects

S S Shapiro

Publications and source records attributed to S S Shapiro.

At least 145 records · Page 8Linked to original sources
PubMed1974

Fibrinogen Philadelphia. A hereditary hypodysfibrinogenemia characterized by fibrinogen hypercatabolism.

A new, autosomally inherited abnormal fibrinogen associated with hypofibrinogenemia has been described in several members of a family. Plasma fibrinogen measured either as thrombin-clottable protein or by immunodiffusion revealed a fibrinogen level ranging between 60 and 90 mg/100 ml. The thrombin time of plasma or purified fibrinogen was prolonged and only partially corrected by the addition of calcium. Purified fibrinogen prolonged the thrombin time of normal plasma. Fibrinopeptide release by thrombin was normal in rate and amount, but fibrin monomer aggregation was grossly disturbed, especially in a high ionic strength medium. We have designated this fibrinogen "fibrinogen Philadelphia." Acrylamide gel electrophoresis of mixtures of [121I]normal and [125I]abnormal fibrinogens revealed a slight increase in the anodal mobility of fibrinogen Philadelphia. Similarly, DEAE-cellulose chromatography showed slightly stronger binding of fibrinogen Philadelphia than normal. To elucidate the mechanism responsible for the low plasma fibrinogen concentration, simultaneous metabolic studies of autologous (patient) and homologous (normal) fibrinogen, labeled with 125I and 121I, respectively, were performed in two affected subjects. Autologous fibrinogen half-life was short and the fractional catabolic rate was markedly increased in both family members. In contrast, homologous fibrinogen half-life and fractional catabolic rate were normal. These metabolic studies demonstrate that rapid degradation of fibrinogen Philadelphia is largely responsible for the depressed levels of a plasma fibrinogen. This represents the first example of a mutant plasma protein in which the molecular defect is associated with an altered catabolism.

Adolescent↗
PubMed1969

Human prothrombin metabolism in normal man and in hypocoagulable subjects.

The metabolism of human prothrombin labeled with radioactive iodine was studied in seven normal subjects and four hemophilic patients. Results in the normal subjects were: plasma volume, 37.6+/-3.8 ml/kg; plasma prothrombin concentration, 303+/-40 U/ml (0.153+/-0.02 mg/ml); prothrombin half-life, 2.81+/-0.51 days; total plasma prothrombin pool, 5.72+/-0.62 mg/kg, representing 64.1+/-9.1% of total body prothrombin; fractional catabolic rate, 42.5+/-12.4% of the plasma pool per day; prothrombin synthesis rate, 2.43+/-0.76 mg/kg per day. Results in the hemophilic patients did not differ significantly from normal. Circulating products of prothrombin activation could not be demonstrated in normal individuals or hemophilic subjects. The data suggest that continuous physiologic activation of the blood coagulation mechanism plays only a small part, if any, in the normal catabolism of prothrombin.

Adult↗
PubMed1969

Congenital dysprothrombinemia: an inherited structural disorder of human prothrombin.

A large family has been studied, 11 of whose members have half-normal plasma concentrations of biological prothrombin activity. The pattern of inheritance is autosomal. By use of a specific immunoassay, affected family members have been shown to possess normal quantities of immunoreactive prothrombin, whose immunologic properties seem identical with those of the normal zymogen. Prothrombin isolation from the plasma of one such individual gave normal yields of protein but half-normal amounts of prothrombin activity. Activation of this material in the "intrinsic" and "extrinsic" systems, in concentrated sodium citrate, or by trypsin, gives rise to half, or less, of the thrombin clotting and esterase activities expected from a comparable normal prothrombin preparation. During the clotting of blood from an affected individual, all material with the mobility of prothrombin disappears. Immunoelectrophoresis of the serum reveals a normal nonthrombin "pro piece," and an additional activation product with an electrophoretic mobility intermediate between that of prothrombin and of "pro piece." These results suggest that affected individuals are heterozygotes in whom half the prothrombin molecules synthesized are structurally abnormal, since they undergo some alterations during activation, but are incapable of releasing the active enzyme, thrombin.

Adolescent↗
PubMed1968

Human prothrombin activation.

Antiserums to human prothrontbin contain antibodies directed against at least two different antigenic sites. During blood coagulation, prothrombin is cleaved into two major antigenically distinct fragments-thrombin and a "pro" fragment. The latter is present in normal seruim, whereas thrombin loses its immunologic reactivity, presumably because of its combination with the natural thrombin inhibitors in blood.

Antigen-Antibody Reactions↗