Inhibition of Clotting as the Result of Plasminogen Activation by Streptokinase

1960 ◽  
Vol 04 (03) ◽  
pp. 507-519 ◽  
Author(s):  
P Glas ◽  
F. K Beller
Keyword(s):  
Human Plasma ◽  
Plasma Source ◽  
The Other ◽  
Plasminogen Activation ◽  
Human Fibrinogen ◽  
Lysis Time ◽  
The One

SummarySamples of an activation mixture, consisting of fibrinogen, streptokinase and plasma (source of pro-activator) were added to thrombin at intervals of 1 minute and subjected to lysis time determinations; the absence of clotting was noted after a certain period of incubation. At this point, the lysis time was no longer measurable.Inhibition of coagulation was not observed if either bovine fibrinogen or human plasma were incubated with streptokinase alone. If, however, human fibrinogen was used instead of bovine fibrinogen, this effect occurred even if only fibrinogen and streptokinase were incubated.The mechanism of the process described was investigated by varying the different streptokinase- and fibrinogen concentrations, using either undiluted or diluted plasma.It was evident that there is a relationship between the concentrations of fibrinogen and streptokinase on the one hand, and the degree of plasma dilution on the other.Fibrinogenolysis is caused by activation of the pro-enzyme contained in the fibrinogen preparations. During this process, fibrinogen is altered to a non-coagulable protein.

Distinction of Plasma Inhibitor of Activator-Induced Clot Lysis from Antiplasmins

1975 ◽  
Author(s):  
N. Aoki ◽  
M. Matsuda ◽  
M. Moroi ◽  
N. Yoshida
Keyword(s):  
Affinity Chromatography ◽  
Human Plasma ◽  
Gel Filtration ◽  
Plasminogen Activators ◽  
Inhibitory Effect ◽  
Clot Lysis ◽  
Plasminogen Activation ◽  
Lysis Time ◽  
Α2 Macroglobulin ◽  
Clot Lysis Time

A fraction of human plasma prolongs the activator-induced clot lysis time and inhibits plasminogen activation by the plasminogen activators derived from various sources (urine and tissues). This fraction, designated as antiactivator fraction, was separatid from antiplasmin fractions (α2-macroglobulin and α1-antitrypsin) by gel filtration and affinity chromatography on Sepharose coupled with IgG of antiserum to α1-antitrypsin. Anti-activator fraction thus obtained exerted little antiplasmin activity but inhibited strongly activator-induced clot lysis.Inhibitory effect of plasma on urokinase-induced clot lysis (antiactivator activity) was assayed in various diseases and compared with antiplasmin activity. No correlation was found between the two activities, and it was concluded that the two activities are independent and are ascribed to two different entities.

Inhibition of Clotting as the Result of Plasminogen Activation by Streptokinase

1960 ◽  
Vol 04 (03) ◽  
pp. 520-533 ◽  
Author(s):  
F. K Beller ◽  
P Glas
Keyword(s):  
The Other ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Clotting Factors ◽  
Lysis Time ◽  
Viii And Ix ◽  
The Moment ◽  
The One ◽  
Time Required ◽  
Recalcification Time

SummaryInvestigations of the clotting mechanism were carried out by lysis time determinations when plasminogen was activated by streptokinase and the following results were obtained:1. The recalcification time during the period of activation showed an initial decrease of the clotting time, followed by a prolongation.The thrombin time method showed only a prolongation up to the moment when inhibition of coagulation occurred.2. The clotting factors II, V, VII, VIII and IX remained unaffected in this system.3. The clotting activity, as well as the time required for the inhibition of coagulation, were dependent on the streptokinase concentration on the one hand, and on the fibrinogen concentration on the other.4. An antithrombin-like inhibitor could be excluded as the cause of incoagulability.5. In our system, inhibition of coagulation was caused by fibrinogenolysis, by which fibrinogen was altered to a biologically inactive globulin. The latter could still be demonstrated in large amounts by means of certain protein estimations. But the proteolytic activity is assumed to be not strong enough to destroy the other clotting factors as well.This system is, therefore, especially useful for studying the isolated “anti-fibrinogenic“ effect of plasmin.

Characterization Of The Active Site Of Urokinase With A Series Of Potent Inhibitory Amidines

1981 ◽  
Author(s):  
J D Geratz ◽  
S R Shaver ◽  
R R Tidwell
Keyword(s):  
Active Site ◽  
Factor Xa ◽  
Selective Inhibition ◽  
The Other ◽  
Plasminogen Activation ◽  
Steric Factors ◽  
The Difference ◽  
The One ◽  
Striking Contrast

Twenty amidine-substituted indole-like heterocycles were synthesized and examined for their blocking effect against human urokinase and a number of related arginine- or lysine- directed proteases. Kinetic analyses were carried out with the help of peptide anilide substrates and revealed a reversible competitive inhibitory pattern with each compound. The Ki values were therefore interpreted to reflect binding conditions at the active site of the enzymes.A highly potent inhibitor of urokinase was discovered in 5-amidino-l-(4-amidinobenzyl)indole which proved to be 18 times more effective on a molar basis than p-aminobenzamidine and 150 times more effective than benzamidine. The Ki value at 37°C and pH 8.3 was determined as 3.2 × 10-6 M. In striking contrast to the findings with the other proteases studied, urokinase was very sensitive to inhibition by 6-amidinoindoline (Ki 1.8 × 10-5 M), yet was much less susceptible to inhibition by the fully unsaturated analog 6-amidinoindole. Steric factors resulting from the difference in planarity between the two compounds are held responsible for this observation. In plasminogen activation assays the antiurokinase effect of the heterocycles mirrored their potency in the assays employing the synthetic urokinase substrate.The significant differences in the inhibitory activities of amidines against urokinase, on the one hand, and plasmin, thrombin and factor Xa, on the other hand, will be useful for experiments where selective inhibition of plasminogen activation is to be achieved. The compounds will also be of help in characterizing other tissue activators with respect to urokinase.

scholarly journals Amino Acid Sequence Studies on the β-Chain of Human Fibrinogen

1977 ◽  
Author(s):  
K. Watt ◽  
D. Goldbaum ◽  
B. A. Cottrell ◽  
T. Takagi ◽  
R. F. Doolittle
Keyword(s):  
Disulfide Bonds ◽  
Coiled Coil ◽  
Enzymatic Digestion ◽  
The Other ◽  
Human Fibrinogen ◽  
Parent Molecule ◽  
General Arrangement ◽  
The One ◽  
Β Chain

The β-chain of human fibrinogen contains 480 ± 15 residues, sixteen of which are methionines. In this vein, we have isolated and characterized all seventeen cyanogen bromide peptides. The arrangement of most of these fragments has been achieved by the identification of key overlap peptides derived from enzymatic digestion of β-chains, on the one hand, and a characterization of β-chain fragments isolated from fragments D and E, on the other. In some cases the alignment is based only on homologies with the α- and/or γ-chains, and in a few instances some definite ambiguities still exist. For the most part, however, the general arrangement is in hand. Of particular interest is the plasmin-sensitive segment which is a part of the inter-domainal connection, which in turn we believe is a three-stranded coiled-coil punctuated by an unusual arrangement of disulfide bonds. The positioning of the other cysteine residues in the β-chain is also of considerable interest, since it sheds light on the extent of connections between portions of the three non-identical chains in the parent molecule.

scholarly journals Thrombolytic properties of staphylokinase

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 925-929
Author(s):  
O Matsuo ◽  
K Okada ◽  
H Fukao ◽  
Y Tomioka ◽  
S Ueshima ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
Plasminogen Activator ◽  
The Other ◽  
Tissue Type ◽  
Plasminogen Activation ◽  
Plasma Clot ◽  
Tissue Type Plasminogen Activator ◽  
Other Hand ◽  
Type Plasminogen Activator

We evaluated the properties of recombinant staphylokinase in comparison with those of tissue-type plasminogen activator (t-PA) and streptokinase (SK). The presence of fibrin(ogen) fragment FCB-2 in the reaction mixture increased plasminogen activation by staphylokinase more than 20-fold. Such characteristics are similar to those of t-PA. On the other hand, SK was not affected by the presence of FCB-2. The thrombolytic properties of staphylokinase were studied in a system consisting of a radioactive human plasma clot (125I-fibrinogen-labeled) suspended in the circulating citrated plasma. Significant thrombolysis (50% in 3 hours) was obtained with 2 micrograms/mL of staphylokinase and 4.45 micrograms/mL t-PA, as compared with 12 micrograms/mL for SK. The relative molar potency of staphylokinase, calculated from the molecular weight, was about two times more effective than that of SK, but about half of that of t-PA. Systemic fibrinolytic activation and fibrinogen breakdown was not observed with staphylokinase or t-PA, but was observed with SK. The thrombolytic efficiency of staphylokinase, which was calculated as the ratio of the degree of thrombolysis/the degree of fibrinogenolysis, was about five times greater than that of SK, and about half of that of t-PA. These findings suggest that staphylokinase has higher specific thrombolytic properties and lesser fibrinogenolytic properties than those of SK.

scholarly journals Evidence for the Presence in Human Plasma of a Streptokinase Co-Factor -Separable from Plasminogen

1977 ◽  
Author(s):  
K. Korsan-Bengtsen ◽  
M. Johnsen ◽  
G. Gustavsson
Keyword(s):  
Affinity Chromatography ◽  
Human Plasma ◽  
Proteolytic Activity ◽  
The Other ◽  
Plasminogen Activation ◽  
Factor Activity ◽  
Peptide Substrate ◽  
Original Observation

Our original observation was that plasma made plasminogen-free by lysine sepharos chromatography accelerated the streptokinase activation of purified plasminogen when measured by means of a chromogenic peptide substrate. The substance with this property is preciptable from plasma with 3-5 % polyethylen-glycol (PEG) , it is eluted near the front on Sepharos 6 B gelfiltration and does not move on electrophoresis at pH 8.6. The activity is not lost on heating to 65°C for 10 min. Traces of immunoglobulins, C-3, C-4, alfa and betalipoproteins present in the purified co-factor preparations were removed by means of affinity chromatography without loss of co-factor activity. The co-factor does not in itself have any proteolytic activity and it cannot be activated with streptokinase or urokinase to give proteolytic activity. It is a potent accelerator of the streptokinase plasminogen activation. One of the two tested commercial streptokinase preparations was found to be influenced more than the other by the co-factor. When this preparation was run on a Sephadex 200 column a certain fraction with a high co-factor “sensitivity” was identified. We have not been able to separate two distinct activities from the streptokinase preparation.

scholarly journals Thrombolytic properties of staphylokinase

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 925-929 ◽  
Author(s):  
O Matsuo ◽  
K Okada ◽  
H Fukao ◽  
Y Tomioka ◽  
S Ueshima ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
Plasminogen Activator ◽  
The Other ◽  
Tissue Type ◽  
Plasminogen Activation ◽  
Plasma Clot ◽  
Tissue Type Plasminogen Activator ◽  
Other Hand ◽  
Type Plasminogen Activator

Abstract We evaluated the properties of recombinant staphylokinase in comparison with those of tissue-type plasminogen activator (t-PA) and streptokinase (SK). The presence of fibrin(ogen) fragment FCB-2 in the reaction mixture increased plasminogen activation by staphylokinase more than 20-fold. Such characteristics are similar to those of t-PA. On the other hand, SK was not affected by the presence of FCB-2. The thrombolytic properties of staphylokinase were studied in a system consisting of a radioactive human plasma clot (125I-fibrinogen-labeled) suspended in the circulating citrated plasma. Significant thrombolysis (50% in 3 hours) was obtained with 2 micrograms/mL of staphylokinase and 4.45 micrograms/mL t-PA, as compared with 12 micrograms/mL for SK. The relative molar potency of staphylokinase, calculated from the molecular weight, was about two times more effective than that of SK, but about half of that of t-PA. Systemic fibrinolytic activation and fibrinogen breakdown was not observed with staphylokinase or t-PA, but was observed with SK. The thrombolytic efficiency of staphylokinase, which was calculated as the ratio of the degree of thrombolysis/the degree of fibrinogenolysis, was about five times greater than that of SK, and about half of that of t-PA. These findings suggest that staphylokinase has higher specific thrombolytic properties and lesser fibrinogenolytic properties than those of SK.

Note on Selection of Coordinate Systems for Geodynamics

1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen
Keyword(s):  
Sea Level ◽  
The Other ◽  
Coordinate Systems ◽  
Mean Sea Level ◽  
The Earth ◽  
The One ◽  
Static Systems ◽  
Selection Of

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.

Stories and the Self

2020 ◽  
Vol 32 (2) ◽  
pp. 47-58 ◽  
Author(s):  
Stefan Krause ◽  
Markus Appel
Keyword(s):  
Meta Analysis ◽  
The Self ◽  
The Other ◽  
Lower Degree ◽  
Contrast Effects ◽  
Self Perception ◽  
Self Perceptions ◽  
Other Hand ◽  
The One ◽  
Implicit And Explicit

Abstract. Two experiments examined the influence of stories on recipients’ self-perceptions. Extending prior theory and research, our focus was on assimilation effects (i.e., changes in self-perception in line with a protagonist’s traits) as well as on contrast effects (i.e., changes in self-perception in contrast to a protagonist’s traits). In Experiment 1 ( N = 113), implicit and explicit conscientiousness were assessed after participants read a story about either a diligent or a negligent student. Moderation analyses showed that highly transported participants and participants with lower counterarguing scores assimilate the depicted traits of a story protagonist, as indicated by explicit, self-reported conscientiousness ratings. Participants, who were more critical toward a story (i.e., higher counterarguing) and with a lower degree of transportation, showed contrast effects. In Experiment 2 ( N = 103), we manipulated transportation and counterarguing, but we could not identify an effect on participants’ self-ascribed level of conscientiousness. A mini meta-analysis across both experiments revealed significant positive overall associations between transportation and counterarguing on the one hand and story-consistent self-reported conscientiousness on the other hand.

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

2005 ◽  
Vol 44 (03) ◽  
pp. 107-117
Author(s):  
R. G. Meyer ◽  
W. Herr ◽  
A. Helisch ◽  
P. Bartenstein ◽  
I. Buchmann
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Primary Tumour ◽  
The Other ◽  
Haematopoietic Stem Cell ◽  
Other Hand ◽  
Primary Reduction ◽  
The One ◽  
Acute Myeloid

SummaryThe prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

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