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Biomedical subjects

S Niewiarowski

Publications and source records attributed to S Niewiarowski.

At least 181 records · Page 10Linked to original sources
PubMed1977

Significance of the intact polypeptide chains of human fibrinogen in ADP-induced platelet aggregation.

The presence of human fibrinogen in suspensions of washed human platelets is a requirement for ADP-induced platelet aggregation. Digestion of fibrinogen with plasmin destroys this function of the protein. The high solubility fraction of Kabi fibrinogen, fragment X (stage 1) and framgent X (stage 2), are two, eight, and ten times, respectively, less potent in promoting ADP-induced platelet aggregation, as compared with intact fibrinogen. Fragments Y and D and the mixture of reduced and carboxymethylated chains of human fibrinogen do not support ADP-induced platelet aggregation at all. SDS polyacrylamide gel electrophoresis of nonreduced and reduced fibrinogen and its derivatives indicates that the intact fibrinogen molecule is essential for ADP-induced platelet aggregation. It is suggested that the carboxy-terminal part of the Aalpha chain and possibly also the amino-terminal part of the Bbeta chain are required for the platelet aggregation-promoting function of fibrinogen.

Adenosine Diphosphate↗
PubMed1976

Thrombogenic activity of mouse and human tumors: effects on platelets, coagulation, and fibrinolysis, and possible significance for metastases.

Twelve mouse tumors and 29 human malignancies were assayed in vitro for their capacity to aggregate platelets and induce release of radiolabelled serotonin, and for their ability to coagulate blood plasma and digest the fibrin clot. It was discovered that many human and mouse tumors can induce release of radiolabelled serotonin but that the quantitative relationships between this activity of tumors and their capacity to aggregate platelets was variable, permitting tumors to be classified into 3 different types. The procoagulant and fibrinolytic activity was also quite variable. Since no correlation was found between the 4 assayed tumor activities they appear to be independent, separate thrombogenic properties of tumors. Although the information gathered by this study is still fragmentary, some speculations can be made about the role of these activities in treatment of malignant tumors and in determing patterns of body distribution and control of metastases.

Animals↗
PubMed1976

Fibrin clot retraction by human skin fibroblasts: effects of ADP and thrombin.

Thrombin stimulated human skin fibroblasts to retract fibrin clots. When Bothrops marajoensis thrombinlike enzyme was substituted for thrombin, no retraction occurred. Fibroblasts were found to contain 12 nmole of ATP and 3.6 nmole of ADP/mg of protein, a value closely resembling that of nonmetabolic adenine nucleotides in platelets. Thrombin caused neither release of adenine nucleotides from the suspension of fibroblasts harvested enzymatically nor did addition of ADP stimulate fibroblasts to retract fibrin clots.

Adenosine Diphosphate↗
PubMed1976

Platelet antiplasmin: its extrusion during the release reaction, subcellular localization, characterization, and relationship to antiheparin in pig platelets.

Antiplasmin activity was shown to be released from washed pig platelets by thrombin following a time course similar to that of 3H-serotonin. Antiheparin activity (platelet factor 4) appeared to be released by thrombin at a slower rate than 3H-serotonin or antiplasmin activity. Subcellular fractionation of pig platelets showed that the storage site for antiplasmin is probably the dense (amine storage) granules. Antiheparin was distributed among all of the subcellular particulate fractions except the fraction rich in dense granules. Material released from washed pig platelets and concentrated by ZnSO4 precipitation (crude antiheparin) was found to be rich in antiplasmin activity. Gel filtration on Sephadex G-150, DEAE cellulose column chromatography, and polyacrylamide gel electrophoresis showed that pig platelet antiplasmin is a low molecular weight (approximately 30,000 d) material of alpha1-globulin electrophoretic mobility. It was found to be heat labile and also inhibitory to the caseinolytic activity of trypsin but had no effect on the action of thrombin on fibrinogen. These data indicate that platelet antiplasmin is distinct from platelet antiheparin.

Animals↗
PubMed1976

Immunoassay of human platelet factor 4(PF4, antiheparin factor) by radial immunodiffusion.

Human platelet factor 4 antigen (PF4 antigen) was measured in platelets and in plasma by means of single radial immunodiffusion. Anti-PF4 antibody obtained in rabbits by injecting highly purified human PF4 was monospecific in double immunodiffusion and in quantitative "rocket" immunoelectrophoresis. A high degree of correlation was observed between the precipitation zones in the radial immunodiffusion method and the amount of purified PF4 (in the range of 0.6 to 50.0 mug per milliliter) or the number of platelets in plasma (in the range of 5 x 10(6) to 1.6 x 10(8) platelets per milliliter applied. The sensitivity of the method was 30 to 125 times higher as compared with clotting assay (antiheparin activity) and the standard error of the method was 2.3 per cent. The method was specific for the antigen present in platelets since human leukocytes and erythrocytes gave negative results. Release of PF4 antigen from washed platelets challenged with thrombin, collagen, ADP, and antigen-antibody complexes was measured by the radial immunodiffusion assay. It usually paralleled the release of 3H-serotonin but PF4 antigen was a more sensitive marker for platelet release reaction. Release of PF4 antigen was usually 2 to 4 times higher than release of the antiheparin activity as measured by clotting assay when both were compared as percentage of total content in platelets. The level of PF4 antigen was determined in platelet-rich plasma (PRP) and platelet-free plasma (PFP) obtained from 12 healthy volunteers. While the mean level of extraplatelet pool of PF4 antigen in PFP was 0.72 +/- 0.92 mug per milliliter, PRP contained 80 +/- 22 mug of PF4 antigen per 10(9) platelets. Addition of thrombin (1 U. per milliliter) liberated all of the PF4 antigen (78 +/- 24 mug) present in PRP but ADP (50 muM) released only 31 +/- 22 mug of PF4 antigen per 10(9) platelets. The presence of heparin did not interfere with the assay of intraplatelet or extraplatelet PF4 by single radial immunodiffusion. The method described represents a simple, sensitive, quantitative, and specific assay for human PF4 antigen possessing antiheparin activity.

Adenosine Diphosphate↗
PubMed1975

ADP, thrombin, and Bothrops atrox thrombinlike enzyme in platelet-dependent fibrin retraction.

Clots formed upon the addition of thrombin to human platelet-rich plasma (PRP) retracted readily but the clotting enzyme from Bothrops atrox venom did not cause retraction in PRP unless ADP, collagen, epinephrine, or low concentrations of thrombin (0.1 U) were added. The latter type of retraction was inhibited by apyrase and creatine phosphate kinase in the presence of creatine phosphate, but that induced with higher concentration of thrombin (2 U) was not. In a system composed of washed human platelets and purified fibrinogen, Bothrops marajoensis (BM) thrombinlike enzyme (highly purified preparations of viper venom) did not cause clot retraction. Addition of ADP to the platelet-fibrinogen mixture prior to BM enzyme resulted in stimulation of clot retraction that could be dissociated from the release of platelet constituents. Addition of low concentrations of thrombin (0.1 U/ml) caused retraction associated with a considerable release of adenine nucleotides that was inhibited by potato apyrase. Electron micrographs showed platelet-fibrin aggregates in all types of retracted clots. Nonretracted clots formed in the presence of potato apyrase contained discoidal platelets that were not in close association with fibrin. It has been postulated that platelet-dependent fibrin clot retraction induced by collagen, epinephrine, and low concentration of thrombin is mediated by ADP. High concentrations of thormbin may possibly promote clot retraction independently of ADP.

Adenosine Diphosphate↗
PubMed1975

Pathological implications of cell aging in vitro.

The replicative capacity of cultured human fibroblasts is discussed in relation to three areas, diabetes mellitus, expression of HL-A antigens, and interactions with polymerizing fibrin. The replicative capacity of cells is dimished in diabetes mellitus and certain related disorders such as progeria and Werner's syndrome, all of which feature accelerated aging. Expression of HL-A antigens is reduced in progeria fibroblasts compared to normal cultures at corresponding stages of passage. Normal cells show more subtle alteration during aging in vitro probably related to clonal heterogeneity and/or selection within mass cultures. Early-passage fibroblasts interact rapidly with polymerizing fibrin to form a mature clot which is then retracted by a process dependent on cellular integrity and active metabolism. Late-passage cultures are less active in both parameters as are fibroblasts from a subject with progeria. These observations, in total, may relate to altered self-recognition and certain autoimmune concomitants of aging in vivo. They may also help to explain impaired wound healing and increased predisposition to atherothrombosis in aging and diabetic individuals. This system of cultured human fibroblasts should serve as an excellent model to investigate the cellular and molecular basis of diabetes mellitus, aging and related pathology.

Adolescent↗
PubMed1975

Inihibition of human platelet aggregation by dipyridamole and two related compounds and its modification by acid glycoproteins of human plasma.

The inhibitory effect of dipyridamole (RA 8) and its two derivatives (RA 233 andSH 869) on platelet aggregation in platelet-rich plasma (PRP) AND IN SUSPENSIONSOF WASHED PLATELETS WAS EVALUATED USING 3 AGGRESSING STIMULI: ADP, thrombin, and collagen. Mean effective dose (ED'30) of RA 8 causing 50 percent inhibition of plateletaggregation of washed human platelets by ADP, collagen, or thrombin varied from 1.2 x 10'-7 to 1.8 x 10'-7M. On the other hand, RA 8 caused little inhibition aggregation in human PRP. RA 233 and SH 869 produced similiar degrees of inhibition ofplatelet aggregation in human PRP and in suspensions of washed human platelets.Platelet-poor plasma, fraction VI-acid glycoproteins, or purified alpha'1-acid glycoprotein complex was isolated by means of Sephadex G-25 gel filtration. It is postulated that the formation of this complex leads to the blocking of the capacity of RA 8to inhibit platelet aggragation. RA 233 and SH 869 had little capacity to form complexes with acid glycoproteins of human plasma. This may explain the effectiveness of these compounds in inhibiting platelet aggregation in PRP.

Adenosine Diphosphate↗
PubMed1975

Antigenic and antiheparin properties of human platelet factor 4 (PF4).

Platelet factor 4 (PF4, a heparin-neutralizing protein) was isolated from washed human platelets. It was found to be homogenous by SDS-polyacrylamide gel electrophoresis, immunodiffusion, and immunoelectrophoresis, when tested with monospecific antibody produced in rabbits. PF4 is a heat-stable protein, but its antiheparin activity and antigenicity are destroyed by trypsin. The molecular weight of PF4 as calculated by amino acid analysis is approximately 8000 and by SDS-polyacrylamide gel electrophoresis with beta-mercaptoethanol, 7100 daltons. PF4 migrated to the cathode at pH 8.6. The interaction of PF4 with heparin resulted in the formation of a complex which migrated to the anode, as tested by immunoelectrophoresis. Incubation of purified PF4 with its antibody at 37 degrees C resulted in a loss of antiheparin activity. The presence of antiheparin activity and of PG4 antigen in material released during platelet aggregation by various agents and at various stages of the preparative procedure closely correlated. It has been concluded that PF4 antigen and antiheparin activity are two properties of the same protein. Comparison of human and pig PF4 revealed significant biochemical and antigenic differences.

Amino Acids↗