We analyzed the secretory dynamics of tissue plasminogen activator (tPA) in EA.hy926 cells, an established vascular endothelial cell (VEC) line producing GFPtagged tPA, using total internal reflectionfluorescence (TIR-F) microscopy. tPAGFP was detected in small granules in EA.hy926 cells, the distribution of which was indistinguishable from intrinsically expressed tPA. Its secretory dynamics we...

The serine protease tissue-type plasminogen activator (tPA) is used as a thrombolytic agent in the management of ischemic stroke, but concerns for hemorrhagic conversion greatly limits the number of patients that receive this treatment. It has been suggested that the bleeding complications associated with thrombolytic tPA may be due to unanticipated roles of tPA in the brain. Recent work has su...

Purpose: Catheter drainage of intra-abdominal abscesses has shown to be effective in reducing sepsis and mortality. We sought to determine whether or not tissue plasminogen activator (tPA), a fibrinolytic, is safe and facilitates resolution when used as an adjunct during drainage of intra-abdominal abscesses. Methods: A single-blinded, prospective, multi-center, randomized control trial was per...

BACKGROUND AND PURPOSE Tissue plasminogen activator (tPA) is an effective treatment for stroke, but its utility is limited by fear of cerebral hemorrhage. Tenecteplase (TNK), a genetically modified form of wild-type tPA, exhibits a longer biological half-life and greater fibrin specificity, features that could lead to fewer cerebral hemorrhages than wild-type tPA in stroke patients. METHODS W...

BACKGROUND AND PURPOSE We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials. METHODS Patients were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours. Within...

67 INTRODUCTION 67 MOLECULAR MECHANISM OF TUMOR PROMOTION BY TPA 68 TPA activates phosphorylation of serine/threonine 68 TPA induces oxidative stress 69 TPA activates early response genes 71 ANTI-CARCINOGENESIS OF SEVERAL NATURAL POLYPHENOLIC COMPOUNDS 72 CURCUMIN INHIBITS TUMOR PROMOTION THROUGH BLOCKING SIGNAL TRANSDUCTION 73 DISCUSSION 74 ACKNOWLEDGEMENTS , 74 REFERENCES 74 CHINESE ABSTRACT 81

Tissue-type plasminogen activator (tPA) a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins, and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central...

Treatment with tissue plasminogen activator (tPA) beyond the therapeutic time window (>4.5 hours post stroke) may produce hemorrhagic transformation (HT). Strategies that could extend the narrow time window of tPA will benefit a significant number of stroke patients. Male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAo) and given vehicle, tPA (10 mg/kg), or tPA and granuloc...

Improving tissue-type plasminogen activator (tPA) thrombolytic therapy is a high priority in stroke research. The ability of tPA to convert plasminogen efficiently into clot-dissolving plasmin relies on an endogenous fibrinolytic assembly via a triple complex formation of tPA, annexin A2, and plasminogen. Annexin A2 is a cell-surface protein, which, in complex with its binding partner p11, form...

The extracellular protease cascade of tissue plasminogen activator (tPA) and plasminogen has been implicated in neuronal plasticity and degeneration. We show here that unstimulated expression of tPA in the mouse hippocampus is concentrated in the mossy fiber pathway, with little or no expression within the perforant path, the Schaffer collaterals, or neuronal cell bodies. tPA protein is also ex...