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tPA Point Mutation at Autolysis Loop Enhances Resistance to PAI-1 Inhibition and Catalytic Activity.

Recombinant tissue-type plasminogen activator (r-tPA) was approved by U.S. Food and Drug Administration as a thrombolytic drug. However, a high dose of r-tPA (up to 100 mg/person) is typically used in clinical applications. Such high dosage leads to severe side effects including haemorrhage and neurotoxicity, which can be fatal. To improve the proteolytic properties of tPA to enhance thrombolytic therapy, we designed a series of mutants in tPA serine protease domain (tPA-SPD) based on the crystal structure of tPA-SPD:plasminogen activators inhibitor-1 (PAI-1) complex that we determined recently. We found that the A146Y substitution in tPA-SPD(A146Y) enhanced resistance to PAI-1 inactivation by 30-fold compared with original tPA-SPD. Interestingly, the tPA-SPD(A146Y) variant showed fivefold higher activation for plasminogen compared with tPA-SPD. The variant also demonstrated thrombolytic activity stronger than tPA-SPD in a clot lysis assay. In vivo, we showed tPA-SPD(A146Y) possessed higher thrombolytic efficacy in a pulmonary embolism model compared with original tPA-SPD. Furthermore, a mouse tail bleeding assay showed that tPA-SPD(A146Y) did not increase bleeding risk compared with clinical drug r-tPA. Together, our findings reveal novel functions of A146Y variant, which not only increases the catalytic efficiency of the enzyme, but also enhances resistance to PAI-1 inhibition, and demonstrating that tPA-SPD (A146Y) variant is a much improved agent for thrombolytic therapy.

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Use of tissue plasminogen activator in the treatment of shunt blockage secondary to intraventricular haemorrhage.

A 51-year-old woman with a history of idiopathic aqueduct stenosis, treated initially with insertion of a ventriculo peritoneal shunt, presented to our institution with shunt dysfunction. She had previously undergone multiple shunt revisions for shunt infection, shunt blockage and low-pressure symptoms, most recently with conversion to a ventriculo atrial (VA) shunt. Her VA shunt was again revised, with replacement of the ventricular catheter, however surgery was complicated by a large intraventricular haemorrhage (IVH) requiring placement of an external ventricular drain (EVD). Prior to eventual removal of her EVD it was determined that the VA shunt had blocked as a result of the IVH. Subsequently alteplase, a recombinant tissue plasminogen activator (tPA), was administered into the shunt reservoir, resulting in successful return of shunt function, therefore avoiding the need for further shunt revision. This is the first description of the use of tPA to unblock a shunt obstructed by blood.

1639 related Products with: Use of tissue plasminogen activator in the treatment of shunt blockage secondary to intraventricular haemorrhage.

FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Head & Neck cancer test t FDA Standard Frozen Tissu Mouse anti-Tissue type Pl Rabbit Anti-Mouse Tissue Mouse Anti-Human Tissue P T-2 Toxin Mycotoxins ELIS Human tissue plasminogen Oral squamous cell cancer

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Thrombolysis by chemically modified coagulation factor Xa.

Essentials Factor Xa (FXa) acquires cleavage-mediated tissue plasminogen activator (tPA) cofactor activity. Recombinant (r) tPA is the predominant thrombolytic drug, but it may cause systemic side effects. Chemically modified, non-enzymatic FXa was produced (Xai-K), which rapidly lysed thrombi in mice. Unlike rtPA, Xai-K had no systemic fibrinolysis activation markers, indicating improved safety.

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Human coagulation Factor Recombinant Human Coagula Human coagulation Factor Custom Human Coagulation Human Coagulation Factor Mouse anti human Coagulat Native Human Coagulation Human coagulation Factor Human coagulation Factor Mouse anti human Coagulat Native Human Coagulation Contact Factors: Human co

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The story of an exceptional serine protease, tissue-type plasminogen activator (tPA).

The only acute treatment of ischemic stroke approved by the health authorities is tissue recombinant plasminogen activator (tPA)-induced thrombolysis. Under physiological conditions, tPA, belonging to the serine protease family, is secreted by endothelial and brain cells (neurons, astrocytes, microglia, oligodendrocytes). Although revascularisation induced by tPA is beneficial during a stroke, research over the past 20 years shows that tPA can also be deleterious for the brain parenchyma. Thus, in this review of the literature, after a brief history on the discovery of tPA, we reviewed current knowledge of mechanisms by which tPA can influence brain function in physiological and pathological conditions.

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Mouse anti-Tissue type Pl Rabbit Anti-Human Tissue Rabbit Anti-Mouse Tissue Rat monoclonal anti mouse Mouse Anti-Human Tissue P FDA Standard Frozen Tissu Rat monoclonal anti mouse FDA Standard Frozen Tissu Mouse Anti-Ca19.9 Sialyl Normal rat multiple organ FDA Standard Frozen Tissu Human tissue plasminogen

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Protocol Deviations before and after Treatment with Intravenous Tissue Plasminogen Activator in Community Hospitals.

Protocol deviations before and after tissue plasminogen activator (tPA) treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict protocol deviations. We examined predictors of protocol deviations and the effects of protocol violations on symptomatic intracerebral hemorrhage (sICH).

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Mouse anti-Tissue type Pl Rabbit Anti-Human Tissue Rabbit Anti-Mouse Tissue Human tissue plasminogen Mouse Anti-Human Tissue P Human tissue plasminogen Esophageal cancer test ti Lung cancer tissue array, Lung cancer tissue array Brain tumor tissue array Liver cancer tissue array Thyroid cancer and normal

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The Naïve Murine Cornea as a Model System to Identify Novel Endogenous Regulators of Lymphangiogenesis: TRAIL and rtPA.

In the murine cornea, which is an established model for analyzing pathologic lymphatic vessel growth, phenotypic heterogeneity of the endogenous lymphatic vessels in the limbus of the cornea was previously described. In this study, the cornea of BALB/c, C57BL/6, and FVB mice with different limbal lymphangiogenic phenotypes was analyzed to identify novel candidates potentially influencing lymphatic vessel growth.

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Sulforhodamine 101, Red f Human Vitronectin Total A MarkerGeneTM Live Cell Lu ENZYMATIC ASSAY KITS (CH Human Plasminogen Total A Total Mouse uPA Antigen A Total Antioxidant Capacit  EpiQuik Total Histone H FDA Standard Frozen Tissu Total Mouse PAI-1 Antigen Glutathione (GSH/GSSG/Tot  EpiQuik Total Histone H

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Tissue-type plasminogen activator-binding RNA aptamers inhibiting low-density lipoprotein receptor family-mediated internalisation.

Recombinant tissue-type plasminogen activator (tPA, trade name Alteplase), currently the only drug approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of cerebral ischaemic stroke, has been implicated in a number of adverse effects reportedly mediated by interactions with the low-density lipoprotein (LDL) family receptors, including neuronal cell death and an increased risk of cerebral haemorrhage. The tissue-type plasminogen activator is the principal initiator of thrombolysis in human physiology, an effect that is mediated directly via localised activation of the plasmin zymogen plasminogen at the surface of fibrin clots in the vascular lumen. Here, we sought to identify a ligand to tPA capable of inhibiting the relevant LDL family receptors without interfering with the fibrinolytic activity of tPA. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to isolate tPA-binding RNA aptamers, which were characterised in biochemical assays of tPA association to low density lipoprotein receptor-related protein-1 (LRP-1, an LDL receptor family member); tPA-mediated in vitro and ex vivo clot lysis; and tPA-mediated plasminogen activation in the absence and presence of a stimulating soluble fibrin fragment. Two aptamers, K18 and K32, had minimal effects on clot lysis, but were able to efficiently inhibit tPA-LRP-1 association and LDL receptor family-mediated endocytosis in human vascular endothelial cells and astrocytes. These observations suggest that coadministration alongside tPA may be a viable strategy to improve the safety of thrombolytic treatment of cerebral ischaemic stroke by restricting tPA activity to the vascular lumen.

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Rat monoclonal anti mouse Mouse anti-Tissue type Pl High density (208 cases 2 Mouse Anti-Human Tissue P High density (188 cases 2 High density (188 cases 2 Rabbit Anti-Mouse Tissue Human tissue plasminogen High density tissue array TMA BLOCK of high density Rabbit Anti-Human Tissue High density (208 cores),

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Tissue plasminogen activator promotes postischemic neutrophil recruitment via its proteolytic and nonproteolytic properties.

Neutrophil infiltration of the postischemic tissue considerably contributes to organ dysfunction on ischemia/reperfusion injury. Beyond its established role in fibrinolysis, tissue-type plasminogen activator (tPA) has recently been implicated in nonfibrinolytic processes. The role of this serine protease in the recruitment process of neutrophils remains largely obscure.

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Reduction of steroid-induced intraocular pressure elevation in sheep by tissue plasminogen activator.

To investigate whether tissue plasminogen activator (tPA) can prevent and/or reverse steroid-induced IOP elevation in an ovine model.

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Human tissue plasminogen Mouse Anti-Human Tissue P Human tissue plasminogen Mouse anti-Tissue type Pl Rabbit Anti-Mouse Tissue Rabbit Anti-Human Tissue Small intestine adenocarc Stomach cancer tissue arr Prostate cancer tissue ar Liver cancer tissue array Brain tumor test tissue a Sheep Anti-Human Plasmino

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Mechanisms of tissue-type plasminogen activator (tPA) clearance by the liver.


1918 related Products with: Mechanisms of tissue-type plasminogen activator (tPA) clearance by the liver.

Mouse anti-Tissue type Pl Human tissue plasminogen Rabbit Anti-Human Tissue Liver tissue, type B hepa Rabbit Anti-Mouse Tissue Mouse Anti-Human Tissue P Human tissue plasminogen Rat monoclonal anti mouse Multiple organ tumor tiss Stomach adenocarcinoma ti High density liver cancer FDA Standard Frozen Tissu

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