FibrinolysisPub Date : 1996-08-01DOI: 10.1016/S0268-9499(96)80782-X
S. Hayashi, G.V. Ishizaki, A. Wakizaka
{"title":"20. Epitope determination of monoclonal antibodies which recognize alpha-chain of fibrinogen and inhibit plasminogen binding to fibrin(ogen)","authors":"S. Hayashi, G.V. Ishizaki, A. Wakizaka","doi":"10.1016/S0268-9499(96)80782-X","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80782-X","url":null,"abstract":"","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 ","pages":"Page 8"},"PeriodicalIF":0.0,"publicationDate":"1996-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80782-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71857976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FibrinolysisPub Date : 1996-07-01DOI: 10.1016/S0268-9499(96)80020-8
K. Soon Song, A. Lee, Q. Eun Park, S. Moo Lee, O. Hun Kwon
{"title":"The relationship between cytokine concentrations and hemostatic abnormalities in patients with liver cirrhosis of postviral or cryptogenic origin","authors":"K. Soon Song, A. Lee, Q. Eun Park, S. Moo Lee, O. Hun Kwon","doi":"10.1016/S0268-9499(96)80020-8","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80020-8","url":null,"abstract":"<div><p><em>Background:</em> Elevated thrombin/antithrombin III (TAT) complex and elevated D-dimer levels have been reported in liver cirrhosis, indicating that cirrhotics have both increased thrombin generation and increased plasmin formation. A number of factors that are elevated in various inflammatory and vascular diseases, including the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), endotoxin (LPS), transforming growth factor-β (TGF-β), and thrombin, can stimulate plasminogen activator inhibitor (PAI-1) production by endothelial cells in vitro. Moreover, both in vitro and in vivo investigations have suggested that TNF is an important mediator of the activation of coagulation. However, the relationship between cytokines and hemostatic abnormalities in liver cirrhosis is unknown.</p><p>Methods: Plasma concentrations of TNF-α, IL-6, TAT, and PAI-1 were determined, by using enzyme linked immunosorbent assay, in 50 patients with cirrhosis (alcoholic=1, postviral=35, cryptogenic=14) who were at different stages (A=3, B=21, C=26) of Child classification and results were compared to those obtained in 24 healthy subjects.</p><p><em>Results:</em> The IL-6 and TNF-α levels in patients with cirrhosis were significantly increased compared with those in healthy subjects (median [interquantile ranges]: 15.96 [8.69–49.79] vs 0.73 [0.37–1.52] pg/ml, <em>P</em><0.0001; 5.30 [3.60–10.85] vs 1.10 [0.77–2.67] pg/ml, <em>P</em><0.05, respectively). The TAT and PAI-1 levels in patients with cirrhosis were also significantly increased compared with those in healthy subjects (3.95 [3.2–9.15] vs 2.35 [2.20–2.65] μg/l, <em>P</em><0.001; 32.45 [17.5–49.8] vs 12.25 [4.7–24.9] ng/ml, <em>P</em><0.001, respectively). The TNF-α level was positively correlated with TAT (<em>r</em>=0.5979, <em>P</em><0.001). The IL-6 level was also positively correlated with those of TNF-α (<em>r</em>=0.3436, <em>P</em><0.05) and TAT (<em>r</em>=0.3982, <em>P</em><0.05). However, the PAI-1 level did not show any correlation with cytokines or TAT.</p><p>There was significant difference of IL-6 levels between postviral group (22.69 [1.52–101.48] pg/ml) and cryptogenic group (64.89 [7.73–209.67] pg/ml) (<em>P</em>=0.006).</p><p><em>Conclusion:</em> We conclude from this study that TNF-α could play an important part in the activation of hemostatic mechanism in liver cirrhosis, a condition commonly associated with intravascular coagulation. Our results suggest that the presence of increased plasma levels of TNF-α and IL-6 in these patients probably reflects chronic secretion which could be induced or perpetuated by endotoxins or other factors associated with host-defense immune mechanisms.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 4","pages":"Pages 249-254"},"PeriodicalIF":0.0,"publicationDate":"1996-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80020-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71870095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FibrinolysisPub Date : 1996-07-01DOI: 10.1016/S0268-9499(96)80017-8
P. Carmeliet, D. Collen
{"title":"Targeted gene manipulation and transfer of the plasminogen and coagulation systems in mice","authors":"P. Carmeliet, D. Collen","doi":"10.1016/S0268-9499(96)80017-8","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80017-8","url":null,"abstract":"<div><p>The blood coagulation and the fibrinolytic (or plasminogen/plasmin) systems determine the balance between the formation and dissolution of blood clots, but also contribute to the pathogenesis of various cardiovascular disorders such as thrombosis, atherosclerosis, and restenosis. Furthermore, they participate in a variety of other (patho)biological processes such as embryonic development, reproduction, wound healing, cancer, and brain function. Two recently developed technologies, gene targeting and gene transfer, which allow the manipulation of the genetic balance of these proteinase systems in a controllable manner, have resulted in a clearer elucidation of the biological role of these systems. This review summarizes the insights that have been obtained from the gene targeting studies and discusses the use of adenovirus-mediated transfer of fibrinolytic genes to study and the possibility of developing novel strategies for the treatment of restenosis and thrombosis.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 4","pages":"Pages 195-213"},"PeriodicalIF":0.0,"publicationDate":"1996-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80017-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71870454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FibrinolysisPub Date : 1996-07-01DOI: 10.1016/S0268-9499(96)80021-X
S. Mirshahi , J. Soria , L. Nelles , C. Soria , J.P. Faure , Y. Pouliquen , M. Mirshahi
{"title":"Plasminogen activators in human corneal fibroblasts: secretion, cellular localization, and regulation","authors":"S. Mirshahi , J. Soria , L. Nelles , C. Soria , J.P. Faure , Y. Pouliquen , M. Mirshahi","doi":"10.1016/S0268-9499(96)80021-X","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80021-X","url":null,"abstract":"<div><p>Plasminogen activators (PA) play an important role not only in fibrinolysis but also in a variety of processes including tissue remodelling. The stroma of the cornea is a dense connective tissue characterized by its transparency. Healing, degenerative, and inflammatory processes lead to corneal opacification. In an attempt to determine the role of PA in corneal physiology, we have analysed the secretion of PA and plasminogen activator inhibitor (PAI-1) by corneal fibroblasts in vitro. We show that in contrast to other adult fibroblasts, corneal fibroblasts secrete both tissue-type plasminogen activator (t-PA) and urokinase-plasminogen activator (u-PA). Epithelial growth factor and basic fibroblast growth factor stimulated t-PA secretion whereas transforming growth factor-β decreased t-PA and increased PAI-1 secretion. t-PA was secreted in the surrounding medium while u-PA remained mostly associated to the cell surface. The production and secretion of t-PA are characteristic of corneal fibroblasts and could be implicated in matrix remodelling and the maintenance of corneal transparency.</p></div>","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 4","pages":"Pages 255-262"},"PeriodicalIF":0.0,"publicationDate":"1996-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80021-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71869477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FibrinolysisPub Date : 1996-07-01DOI: 10.1016/S0268-9499(96)80019-1
T. Pietrucha , J. Golański , Z. Baj , H. Tchórzewski , J. Greger , C. Watala
{"title":"Flow cytometric analysis of the prevention of platelet activation by tissue type plasminogen activator and streptokinase","authors":"T. Pietrucha , J. Golański , Z. Baj , H. Tchórzewski , J. Greger , C. Watala","doi":"10.1016/S0268-9499(96)80019-1","DOIUrl":"https://doi.org/10.1016/S0268-9499(96)80019-1","url":null,"abstract":"<div><p>The therapeutic success of plasminogen activators in recanalizing occluded coronary arteries may be impaired by their action on blood platelets, and some conflicting reports claim both platelet activation and inhibition. To elucidate the interactions responsible for inhibition of platelets activation in whole EDTA-anticoagulated blood, preincubated with pharmacological and subpharmacological doses of recombinant tissue type plasminogen activator (rt-PA) or streptokinase (SK), 35 healthy donors were selected for the experiments in which we employed flow cytometry to monitor the exposure of the glycoprotein complex α<sub>IIb</sub>β<sub>3</sub> and PADGEM-140 antigen in surface membranes of platelets. The EDTA-induced increase in the expression of the latter antigen, which is a commonly known marker of the increased platelet activation and release reaction, became greatly depressed when blood cells were incubated with either rt-PA (by up to 60%, <em>P</em><0.0001) or SK (by 58%, <em>P</em><0.0001). The effects of the highest protection of platelet activation by rt-PA and SK occurred at their bolus injection doses (2 μg/ml and 600 U/ml blood, respectively). Likewise, both activators significantly reduced the expression of PADGEM-140 antigen (by 12%, <em>P</em><0.0004 and 16%, <em>P</em><0.003, respectively) and the platelet membrane integrin α<sub>IIb</sub>β<sub>3</sub> (by up to 34%, <em>P</em><0.00002 and 9%, <em>P</em><0.001, respectively). Also, the lowerings in the fractions of platelet aggregates were noted in the presence of the increasing concentrations of rt-PA and SK (<em>P</em><0.04 and <em>P</em><0.05). The spontaneous EDTA-induced platelet activation was even augmented in the presence of apyrase (up to 1.0 U/ml) and became significantly reduced by the addition of rt-PA. Furthermore, the addition of apyrase notwithstanding, the plasminogen activators added or not, significantly augmented the fraction of platelet microparticles (rt-PA <em>P</em><0.04, SK <em>P</em><0.05) and reduced platelet aggregates (rt-PA <em>P</em><0.023, SK <em>P</em><0.04). We conclude that both rt-PA and SK prevent platelet activation and release reaction in a whole blood system. These effects of plasminogen activators seem to occur <em>via</em> plasmin generation rather than the action of plasminogen activators themselves, although the detailed mechanism of plasmin interaction with platelets membrane receptors remains unclear. Our findings suggest that the pharmacological doses of either t-PA or SK are not directly responsible for platelet activation observed as the result of a thrombolytic treatment. Since both plasminogen activators inhibit the spontaneous platelet activation, it seems that the activation associated with the use of plasminogen activators might be rather attributed to thrombin released in the vicinity of superimposed thrombi. Hence, in the effective prevention of reocclusions the strategies directed tow","PeriodicalId":84750,"journal":{"name":"Fibrinolysis","volume":"10 4","pages":"Pages 239-248"},"PeriodicalIF":0.0,"publicationDate":"1996-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0268-9499(96)80019-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71869479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}