scholarly journals Thromboelastographic study of fibrin clot and molecular basis of maximum clot firmness

2021 ◽  
Vol 93 (2) ◽  
pp. 62-70
Author(s):  
D. S. Korolova ◽  
◽  
Y. M. Stohnii ◽  
V. I. Gryshchuk ◽  
S. I. Zhuk ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Fibrin Clot ◽  
Maximum Clot Firmness

Herpesviruses Enhance Fibrinogen Clot Lysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1153-1153 ◽  
Author(s):  
Edwin S Gershom ◽  
Amanda Vanden Hoek ◽  
Michael R Sutherland ◽  
Ed L.G. Pryzdial
Keyword(s):  
Virus Infection ◽  
Vascular Disease ◽  
Molecular Basis ◽  
Independent Predictor ◽  
Fibrin Clot ◽  
Host Cells ◽  
Annexin Ii ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasminogen Activation

Abstract Abstract 1153 Background: Members of the Herpesvirus family have been implicated in vascular disease. To explain the correlation on a molecular basis we have shown that the virus envelope contains anionic phospholipid derived from host cells, and proteins encoded by the host (tissue factor) as well as the viral (glycoprotein C) genomes, which initiate blood coagulation. This suggests that virus infection should be a strong independent predictor of vascular disease. Nevertheless, the clinical correlation is relatively weak, becoming more significant in combination with other risk factors. To explain this discrepancy, the current work is based on our additional report that at least one Herpesvirus (cytomegalovirus (CMV)) has host-genome-encoded annexin II on its surface. Annexin II is known to accelerate tissue plasminogen activator (tPA)-mediated activation of plasminogen to plasmin because of C-terminal lysines that interact with both plasminogen and tPA. Plasmin is the primary fibrinolytic protease, and is necessary for physiological clot dissolution. Thus, these viruses may facilitate clearance of the fibrin they generate. Hypothesis: We hypothesize that Herpesviruses enhance tPA-mediated plasmin generation and this mechanism correlates to the presence of annexin II on the virus. Methods: Purified herpes simplex virus type 1 (HSV1) and 2 (HSV2) and CMV were quantified by electron microscopy. Annexin II expression varies between cell types, therefore HSV1 was propagated in several cell lines. Virus-dependent plasmin generation was followed in the presence of purified plasminogen and tPA using a chromogenic assay. The contribution of viruses to fibrin clot lysis using purified proteins was investigated by light scattering. Plasminogen-conjugated horse radish peroxidase (plasminogen-HRP) and western blots were used to identify plasminogen-binding species and annexin II associated with the virus, respectively. The effect of plasmin-mediated signalling on virus infection was determined using cytopathic plaque assays. Results: Chromogenic experiments demonstrated that HSV1, HSV2 and CMV enhanced plasminogen activation in a dose-dependent manner by up to 5-fold, regardless of the parental cell line. Prolonged incubation confirmed the requirement for exogenous tPA. Plasminogen-HRP bound to a number of virus-associated proteins and was shown to be C-terminal lysine-dependent by complete inhibition with epsilon-aminocaproic acid (EACA). Annexin II was demonstrated to be associated with purified HSV1 cultured in different cells except when propagated in a melanoma (A7) line that did not express annexin II. An annexin II antibody inhibited binding of plasminogen-HRP to viral annexin II. HSV1, HSV2 and CMV accelerated fibrin clot lysis, which was inhibited in the presence of EACA and aprotinin, a plasmin inhibitor. However, in contrast to the chromogenic experiment for plasmin generation, each virus also exhibited a clot lysis mechanism independent of added tPA. As we have previously identified for thrombin, incubation of host cells with purified plasmin during inoculation enhanced virus infection by over 3-fold. Conclusion: Cumulatively these data demonstrate that HSV1, HSV2 and CMV accelerate tPA- mediated plasmin generation in the absence of fibrin and identify annexin II as one of several plasminogen binding partners. These viruses furthermore enhance the rate of fibrin clot lysis. However, in the presence of fibrin, purified HSV1, HSV2 and CMV are capable of facilitating clot dissolution in the absence of exogenous tPA. The molecular basis for this novel mechanism is not yet known, but requires plasminogen activation. The finding that purified plasmin enhances infection suggests these viruses may have evolved to initiate plasmin generation. Hence, the virus-mediated activation of fibrinolysis may compensate for its ability to trigger coagulation and attenuate potential contributions as an independent predictor of vascular disease. Disclosures: No relevant conflicts of interest to declare.

Regulation by alpha 2-antiplasmin and fibrin of the activation of plasminogen with recombinant staphylokinase in plasma

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1175-1183
Author(s):  
K Silence ◽  
D Collen ◽  
HR Lijnen
Keyword(s):  
Human Plasma ◽  
Binding Sites ◽  
Molecular Basis ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activation ◽  
Plasma Clot ◽  
Fibrinolytic Agent ◽  
No Activation

The effects of alpha 2-antiplasmin and fibrin on the activation of plasminogen by recombinant staphylokinase (STAR) were studied in an effort to elucidate further the molecular basis of the fibrin- specificity of this fibrinolytic agent. In purified systems consisting of 1.5 mumol/L intact or low-M(r) plasminogen and 3 mumol/L alpha 2- antiplasmin, at 37 degrees C and in the absence of fibrin, STAR did not induce plasminogen activation and plasmin-alpha 2-antiplasmin complex (PAP) formation. Addition of a purified fibrin clot (30% vol at a concentration of 3 mg/mL) to mixtures containing intact plasminogen caused approximately 40% plasminogen activation within 2 hours, whereas in mixtures containing low-M(r) plasminogen, no activation was observed. In contrast, 10 nmol/L streptokinase (SK) induced 74% to 100% plasminogen activation within 2 hours in mixtures containing either intact or low-M(r) plasminogen, in both the absence and the presence of fibrin. In citrated human plasma in the absence of fibrin, 30 nmol/L STAR did not induce measurable plasminogen activation and PAP formation (< 1.5% within 2 hours), whereas addition of a plasma clot (12% vol) resulted in complete clot lysis and conversion of 19% +/- 8% of the plasminogen to PAP within 2 hours. Addition of a second plasma clot produced 23% +/- 2% additional plasminogen activation. Equipotent concentrations for plasma clot lysis of SK (100 nmol/L) induced 54% +/- 11% plasminogen activation in the absence and 49% +/- 16% in the presence of fibrin. Addition of 50 mmol/L 6-aminohexanoic acid (6-AHA) abolished the effect of fibrin on plasminogen activation with STAR, but not on activation with SK. In alpha 2-antiplasmin-depleted human plasma in the absence of fibrin, 30 nmol/L STAR did not induce fibrinogen breakdown (> 90% residual fibrinogen after 6 hours), whereas 30 nmol/L preformed plasmin-STAR complex induced extensive fibrinogen degradation (70% within 20 minutes). Thus, in the absence of fibrin, alpha 2- antiplasmin inhibits the activation of plasminogen by STAR, by preventing generation of active plasmin-STAR complex. Fibrin stimulates plasminogen activation by STAR via mechanisms involving the lysine- binding sites of plasminogen, probably by facilitating the generation of plasmin-STAR complex and by delaying its inhibition at the clot surface.

scholarly journals Regulation by alpha 2-antiplasmin and fibrin of the activation of plasminogen with recombinant staphylokinase in plasma

Blood ◽  
1993 ◽  
Vol 82 (4) ◽  
pp. 1175-1183 ◽  
Author(s):  
K Silence ◽  
D Collen ◽  
HR Lijnen
Keyword(s):  
Human Plasma ◽  
Binding Sites ◽  
Molecular Basis ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activation ◽  
Plasma Clot ◽  
Fibrinolytic Agent ◽  
No Activation

Abstract The effects of alpha 2-antiplasmin and fibrin on the activation of plasminogen by recombinant staphylokinase (STAR) were studied in an effort to elucidate further the molecular basis of the fibrin- specificity of this fibrinolytic agent. In purified systems consisting of 1.5 mumol/L intact or low-M(r) plasminogen and 3 mumol/L alpha 2- antiplasmin, at 37 degrees C and in the absence of fibrin, STAR did not induce plasminogen activation and plasmin-alpha 2-antiplasmin complex (PAP) formation. Addition of a purified fibrin clot (30% vol at a concentration of 3 mg/mL) to mixtures containing intact plasminogen caused approximately 40% plasminogen activation within 2 hours, whereas in mixtures containing low-M(r) plasminogen, no activation was observed. In contrast, 10 nmol/L streptokinase (SK) induced 74% to 100% plasminogen activation within 2 hours in mixtures containing either intact or low-M(r) plasminogen, in both the absence and the presence of fibrin. In citrated human plasma in the absence of fibrin, 30 nmol/L STAR did not induce measurable plasminogen activation and PAP formation (< 1.5% within 2 hours), whereas addition of a plasma clot (12% vol) resulted in complete clot lysis and conversion of 19% +/- 8% of the plasminogen to PAP within 2 hours. Addition of a second plasma clot produced 23% +/- 2% additional plasminogen activation. Equipotent concentrations for plasma clot lysis of SK (100 nmol/L) induced 54% +/- 11% plasminogen activation in the absence and 49% +/- 16% in the presence of fibrin. Addition of 50 mmol/L 6-aminohexanoic acid (6-AHA) abolished the effect of fibrin on plasminogen activation with STAR, but not on activation with SK. In alpha 2-antiplasmin-depleted human plasma in the absence of fibrin, 30 nmol/L STAR did not induce fibrinogen breakdown (> 90% residual fibrinogen after 6 hours), whereas 30 nmol/L preformed plasmin-STAR complex induced extensive fibrinogen degradation (70% within 20 minutes). Thus, in the absence of fibrin, alpha 2- antiplasmin inhibits the activation of plasminogen by STAR, by preventing generation of active plasmin-STAR complex. Fibrin stimulates plasminogen activation by STAR via mechanisms involving the lysine- binding sites of plasminogen, probably by facilitating the generation of plasmin-STAR complex and by delaying its inhibition at the clot surface.

scholarly journals Molecular Basis of Fibrin Clot Elasticity

Structure ◽  
2008 ◽  
Vol 16 (3) ◽  
pp. 449-459 ◽  
Author(s):  
Bernard B.C. Lim ◽  
Eric H. Lee ◽  
Marcos Sotomayor ◽  
Klaus Schulten
Keyword(s):  
Molecular Basis ◽  
Fibrin Clot

Renilla Bioluminescence: A Morphologic Approach to the Location of Photocytes

1974 ◽  
Vol 32 ◽  
pp. 208-209
Author(s):  
Ben O. Spurlock ◽  
Milton J. Cormier
Keyword(s):  
Excited State ◽  
Ground State ◽  
Molecular Basis ◽  
Light Emission ◽  
Chemical Basis ◽  
Electronic Excited State ◽  
Colonial Form ◽  
The Common ◽  
Eighteenth And Nineteenth Centuries ◽  
Catalyzed Oxidation

The phenomenon of bioluminescence has fascinated layman and scientist alike for many centuries. During the eighteenth and nineteenth centuries a number of observations were reported on the physiology of bioluminescence in Renilla, the common sea pansy. More recently biochemists have directed their attention to the molecular basis of luminosity in this colonial form. These studies have centered primarily on defining the chemical basis for bioluminescence and its control. It is now established that bioluminescence in Renilla arises due to the luciferase-catalyzed oxidation of luciferin. This results in the creation of a product (oxyluciferin) in an electronic excited state. The transition of oxyluciferin from its excited state to the ground state leads to light emission.

Androgen-induced plasticity at a “vocal” neuromuscular synapse

1994 ◽  
Vol 52 ◽  
pp. 32-33
Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman
Keyword(s):  
Xenopus Laevis ◽  
Motor Neurons ◽  
Sexual Differentiation ◽  
Molecular Basis ◽  
Neuromuscular Synapse ◽  
Sexually Dimorphic ◽  
Intracellular Protein ◽  
Developmental Program ◽  
Androgen Action ◽  
Clawed Frog

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.

A molecular basis for opiate action

1998 ◽  
Vol 33 ◽  
pp. 65-77 ◽  
Author(s):  
Dominique Massotte ◽  
Brigitte L. Kieffer
Keyword(s):  
Molecular Basis

Emerging Nutrition Gaps in a World of Affluence - Micronutrient Intake and Status Globally

2011 ◽  
Vol 81 (4) ◽  
pp. 238-239 ◽  
Author(s):  
Manfred Eggersdorfer ◽  
Paul Walter
Keyword(s):  
Developing Countries ◽  
Human Health ◽  
Old Age ◽  
Molecular Basis ◽  
Health Benefit ◽  
Developed Countries ◽  
Micronutrient Deficiencies ◽  
New Science ◽  
Health And Nutrition ◽  
Micronutrient Intake

Nutrition is important for human health in all stages of life - from conception to old age. Today we know much more about the molecular basis of nutrition. Most importantly, we have learnt that micronutrients, among other factors, interact with genes, and new science is increasingly providing more tools to clarify this interrelation between health and nutrition. Sufficient intake of vitamins is essential to achieve maximum health benefit. It is well established that in developing countries, millions of people still suffer from micronutrient deficiencies. However, it is far less recognized that we face micronutrient insufficiencies also in developed countries.

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