The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform

Viktor Magdolen - One of the best experts on this subject based on the ideXlab platform.

  • The human Fibrinolytic System is a target for the staphylococcal metalloprotease aureolysin.
    The Biochemical journal, 2008
    Co-Authors: Nathalie Beaufort, Jan Potempa, Piotr Wojciechowski, Christian P. Sommerhoff, Grzegorz Szmyd, Grzegorz Dubin, Sigrun Eick, Josef Kellermann, Manfred Schmitt, Viktor Magdolen
    Abstract:

    The major opportunistic pathogen Staphylococcus aureus utilizes the human Fibrinolytic System for invasion and spread via plasmin(ogen) binding and non-proteolytic activation. Because S. aureus secretes several proteases recently proposed as virulence factors, we explored whether these enzymes could add to the activation of the host's Fibrinolytic System. Exposure of human pro-urokinase [pro-uPA (where uPA is urokinase-type plasminogen activator)] to conditioned growth media from staphylococcal reference strains results in an EDTA-sensitive conversion of the single-chain zymogen into its two-chain active form, an activity not observed in an aureolysin-deficient strain. Using purified aureolysin, we verified the capacity of this thermolysin-like metalloprotease to activate pro-uPA, with a 2.6 x 10(3) M(-1) x s(-1) catalytic efficiency. Moreover, activation also occurs in the presence of human plasma, as well as in conditioned growth media from clinical isolates. Finally, we establish that aureolysin (i) converts plasminogen into angiostatin and mini-plasminogen, the latter retaining its capacity to be activated by uPA and to hydrolyse fibrin, (ii) degrades the plasminogen activator inhibitor-1, and (iii) abrogates the inhibitory activity of alpha(2)-antiplasmin. Altogether, we propose that, in parallel with the staphylokinase-dependent activation of plasminogen, aureolysin may contribute significantly to the activation of the Fibrinolytic System by S. aureus, and thus may promote bacterial spread and invasion.

  • The human Fibrinolytic System is a target for the staphylococcal metalloprotease aureolysin
    Biochemical Journal, 2008
    Co-Authors: Nathalie Beaufort, Jan Potempa, Piotr Wojciechowski, Christian P. Sommerhoff, Grzegorz Szmyd, Grzegorz Dubin, Sigrun Eick, Josef Kellermann, Manfred Schmitt, Viktor Magdolen
    Abstract:

    The major opportunistic pathogen Staphylococcus aureus utilizes the human Fibrinolytic System for invasion and spread via plasmin(ogen) binding and non-proteolytic activation. Because S. aureus secretes several proteases recently proposed as virulence factors, we explored whether these enzymes could add to the activation of the host's Fibrinolytic System. Exposure of human pro-urokinase (pro-uPA) to conditioned growth media from staphylococcal reference strains results in an EDTA-sensitive conversion of the single-chain zymogen into its two-chain active form, an activity not observed in an aureolysin-deficient strain. Using purified aureolysin, we verified the capacity of this thermolysin-like metalloprotease to activate pro-uPA, with a 2.6 x 10 3}M -1}s -1} catalytic efficiency. Moreover, activation also occurs in the presence of human plasma, as well as in conditioned growth media from clinical isolates. Finally, we establish that aureolysin (i) converts plasminogen into angiostatin and mini-plasminogen, the latter retaining its capacity to be activated by uPA and to hydrolyze fibrin, (ii) degrades the plasminogen activator inhibitor-1, and (iii) abrogates the inhibitory activity of α 2}-antiplasmin. Altogether, we propose that, in parallel to the staphylokinase-dependent activation of plasminogen, aureolysin may contribute significantly to the activation of the Fibrinolytic System by S. aureus, and thus may promote bacterial spread and invasion.

Torbjörn K. Nilsson - One of the best experts on this subject based on the ideXlab platform.

  • Enalapril related changes in the Fibrinolytic System in survivors of myocardial infarction.
    European journal of clinical pharmacology, 1993
    Co-Authors: J. -h. Jansson, K. Boman, Torbjörn K. Nilsson
    Abstract:

    Disturbances of the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE-inhibitor (enalapril) and a placebo on the Fibrinolytic System have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other Fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease.

  • Effects of doxazosin and atenolol on the Fibrinolytic System in patients with hypertension and elevated serum cholesterol.
    European journal of clinical pharmacology, 1991
    Co-Authors: J. -h. Jansson, K. Boman, B. Johansson, Torbjörn K. Nilsson
    Abstract:

    Disturbances in the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the Fibrinolytic System have been evaluated.

J. -h. Jansson - One of the best experts on this subject based on the ideXlab platform.

  • Enalapril related changes in the Fibrinolytic System in survivors of myocardial infarction.
    European journal of clinical pharmacology, 1993
    Co-Authors: J. -h. Jansson, K. Boman, Torbjörn K. Nilsson
    Abstract:

    Disturbances of the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE-inhibitor (enalapril) and a placebo on the Fibrinolytic System have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other Fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease.

  • Effects of doxazosin and atenolol on the Fibrinolytic System in patients with hypertension and elevated serum cholesterol
    European Journal of Clinical Pharmacology, 1991
    Co-Authors: J. -h. Jansson, K. Boman, B. Johansson, T. K. Nilsson
    Abstract:

    Disturbances in the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha_1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the Fibrinolytic System have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The Fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the Fibrinolytic System in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.

  • Effects of doxazosin and atenolol on the Fibrinolytic System in patients with hypertension and elevated serum cholesterol.
    European journal of clinical pharmacology, 1991
    Co-Authors: J. -h. Jansson, K. Boman, B. Johansson, Torbjörn K. Nilsson
    Abstract:

    Disturbances in the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the Fibrinolytic System have been evaluated.

Nathalie Beaufort - One of the best experts on this subject based on the ideXlab platform.

  • The human Fibrinolytic System is a target for the staphylococcal metalloprotease aureolysin.
    The Biochemical journal, 2008
    Co-Authors: Nathalie Beaufort, Jan Potempa, Piotr Wojciechowski, Christian P. Sommerhoff, Grzegorz Szmyd, Grzegorz Dubin, Sigrun Eick, Josef Kellermann, Manfred Schmitt, Viktor Magdolen
    Abstract:

    The major opportunistic pathogen Staphylococcus aureus utilizes the human Fibrinolytic System for invasion and spread via plasmin(ogen) binding and non-proteolytic activation. Because S. aureus secretes several proteases recently proposed as virulence factors, we explored whether these enzymes could add to the activation of the host's Fibrinolytic System. Exposure of human pro-urokinase [pro-uPA (where uPA is urokinase-type plasminogen activator)] to conditioned growth media from staphylococcal reference strains results in an EDTA-sensitive conversion of the single-chain zymogen into its two-chain active form, an activity not observed in an aureolysin-deficient strain. Using purified aureolysin, we verified the capacity of this thermolysin-like metalloprotease to activate pro-uPA, with a 2.6 x 10(3) M(-1) x s(-1) catalytic efficiency. Moreover, activation also occurs in the presence of human plasma, as well as in conditioned growth media from clinical isolates. Finally, we establish that aureolysin (i) converts plasminogen into angiostatin and mini-plasminogen, the latter retaining its capacity to be activated by uPA and to hydrolyse fibrin, (ii) degrades the plasminogen activator inhibitor-1, and (iii) abrogates the inhibitory activity of alpha(2)-antiplasmin. Altogether, we propose that, in parallel with the staphylokinase-dependent activation of plasminogen, aureolysin may contribute significantly to the activation of the Fibrinolytic System by S. aureus, and thus may promote bacterial spread and invasion.

  • The human Fibrinolytic System is a target for the staphylococcal metalloprotease aureolysin
    Biochemical Journal, 2008
    Co-Authors: Nathalie Beaufort, Jan Potempa, Piotr Wojciechowski, Christian P. Sommerhoff, Grzegorz Szmyd, Grzegorz Dubin, Sigrun Eick, Josef Kellermann, Manfred Schmitt, Viktor Magdolen
    Abstract:

    The major opportunistic pathogen Staphylococcus aureus utilizes the human Fibrinolytic System for invasion and spread via plasmin(ogen) binding and non-proteolytic activation. Because S. aureus secretes several proteases recently proposed as virulence factors, we explored whether these enzymes could add to the activation of the host's Fibrinolytic System. Exposure of human pro-urokinase (pro-uPA) to conditioned growth media from staphylococcal reference strains results in an EDTA-sensitive conversion of the single-chain zymogen into its two-chain active form, an activity not observed in an aureolysin-deficient strain. Using purified aureolysin, we verified the capacity of this thermolysin-like metalloprotease to activate pro-uPA, with a 2.6 x 10 3}M -1}s -1} catalytic efficiency. Moreover, activation also occurs in the presence of human plasma, as well as in conditioned growth media from clinical isolates. Finally, we establish that aureolysin (i) converts plasminogen into angiostatin and mini-plasminogen, the latter retaining its capacity to be activated by uPA and to hydrolyze fibrin, (ii) degrades the plasminogen activator inhibitor-1, and (iii) abrogates the inhibitory activity of α 2}-antiplasmin. Altogether, we propose that, in parallel to the staphylokinase-dependent activation of plasminogen, aureolysin may contribute significantly to the activation of the Fibrinolytic System by S. aureus, and thus may promote bacterial spread and invasion.

K. Boman - One of the best experts on this subject based on the ideXlab platform.

  • Enalapril related changes in the Fibrinolytic System in survivors of myocardial infarction.
    European journal of clinical pharmacology, 1993
    Co-Authors: J. -h. Jansson, K. Boman, Torbjörn K. Nilsson
    Abstract:

    Disturbances of the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE-inhibitor (enalapril) and a placebo on the Fibrinolytic System have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other Fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease.

  • Effects of doxazosin and atenolol on the Fibrinolytic System in patients with hypertension and elevated serum cholesterol
    European Journal of Clinical Pharmacology, 1991
    Co-Authors: J. -h. Jansson, K. Boman, B. Johansson, T. K. Nilsson
    Abstract:

    Disturbances in the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha_1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the Fibrinolytic System have been evaluated. Eighty four subjects with previously untreated mild to moderate hypertension and elevated serum cholesterol were randomized to receive atenolol or doxazosin in a double-blind study over 6 months. Tissue plasminogen activator(tPA) and plasminogen activator inhibitor (PAI-1) were measured in citrated plasma samples before and after venous occlusion before and at the end of the study period. tPA activity after venous occlusion and tPA capacity were significantly increased after doxazosin as compared to pretreatment values. The Fibrinolytic variables did not change in the atenolol group. Thus, doxazosin but not atenolol, improved the activity of the Fibrinolytic System in patients with hypertension and an elevated serum cholesterol level. This effect of doxazosin warrants consideration when selecting a first-line antihypertensive drug.

  • Effects of doxazosin and atenolol on the Fibrinolytic System in patients with hypertension and elevated serum cholesterol.
    European journal of clinical pharmacology, 1991
    Co-Authors: J. -h. Jansson, K. Boman, B. Johansson, Torbjörn K. Nilsson
    Abstract:

    Disturbances in the Fibrinolytic System have been associated with cardiovascular disease and its risk factors. In the present study the effects of an alpha1-adrenoceptor inhibitor (doxazosin) and a selective beta-adrenoceptor blocker (atenolol) on the Fibrinolytic System have been evaluated.