Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute respiratory failure (ARF) in an 11-year-old child with pre-T acute lymphoblastic leukemia (ALL) at the beginning of induction therapy was observed, connected with a pulmonary thrombosis and not with an infective origin. A systematic search for this pathology identified six other children with the same pulmonary complication, five of whom where in the early phase of acute nonlymphoblastic leukemia (ANLL) and one in induction therapy for ALL in marrow relapse. At the beginning of the symptomatology, all children presented severe hypoxia and hypercapnia, with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement. In all patients the arteriography and nuclear imaging studies confirmed the diagnosis. The causes of the thrombi could be connected with neoplastic emboli after cell lysis and/or with the vascular damage resulting from antiblastic therapy. Intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children.
 ...
PMID:Acute respiratory failure and pulmonary thrombosis in leukemic children. 198 61

We have previously observed that soluble urokinase plasminogen activator receptor (suPAR) prevents impairment of cerebrovasodilation induced by hypercapnia and hypotension after hypoxia/ischemia (H/I) in the newborn pig. In this study, we investigated the role of low-density lipoprotein-related protein (LRP) receptor and the ERK isoform of mitogen activated protein kinase (MAPK) in uPA-mediated impairment of vasodilation after H/I in piglets equipped with a closed cranial window. CSF uPA increased from 9+/-2 to 52+/-8 and 140+/-21 ng/ml at 1 and 4 h after H/I, respectively. The LRP antagonist receptor associated protein (RAP) and anti-LRP antibody blunted the increase in CSF uPA at 1 h (17+/-2 ng/ml) but not 4 h post insult. uPA detectable in sham-treated cortex by immunohistochemistry was markedly elevated 4 h after H/I. Phosphorylation (activation) of CSF ERK MAPK was detected at 1 and 4 h post H/I and blocked by RAP. Exogenous uPA administered at 4 h post H/I further stimulated ERK MAPK phosphorylation, which was blocked by RAP. Pre-treatment of piglets with RAP, anti-LRP, and suPAR completely prevented, and the ERK MAPK antagonist U 0126 partially prevented, impaired responses to hypotension and hypercapnia post H/I, but none of these antagonists affected the response to isoproterenol. These data indicate that uPA is upregulated after H/I through an LRP-dependent process and that the released uPA impairs hypercapnic and hypotensive dilation through an LRP- and ERK MAPK dependent pathway. These data suggest that modulation of uPA upregulation and/or uPA-mediated signal transduction may preserve cerebrohemodynamic control after hypoxia/ischemia.
 ...
PMID:uPA impairs cerebrovasodilation after hypoxia/ischemia through LRP and ERK MAPK. 1865 57

Cerebral hypoxia (10 min) followed immediately by ischemia (20 min) (H/I) impairs cerebrovasodilation in response to hypercapnia and hypotension in the newborn pig; exogenous urokinase plasminogen activator (uPA) potentiates this effect, whereas the blockade of endogenous uPA-mediated vasoactivity prevents it completely. This study investigated the role of integrin alpha(V)beta(3) in the uPA-mediated impairment of cerebrovasodilation after H/I in piglets equipped with a closed cranial window. Pial artery dilation induced by hypercapnia (Pco(2), 75 mmHg) and hypotension (mean arterial blood pressure, decreased by 45%) was blunted after H/I, reversed to vasconstriction in piglets treated with uPA (10(-7) M), a concentration observed in cerebrospinal fluid after H/I, but reverted to a dilation no different than preinsult in piglets administered an anti-alpha(V)beta(3) antibody (10 ng/ml) in addition to uPA (26 +/- 1, 9 +/- 1, -10 +/- 3, and 22 +/- 3% for hypercapnia before H/I, after H/I, after H/I with uPA, and after H/I with combined uPA and anti-alpha(V)beta(3) antibody, respectively). Responses to isoproterenol were unchanged after H/I and combined uPA and anti-alpha(V)beta(3) antibody. Similar results were obtained for the combined administration of uPA with the alpha(V)beta(3) antagonist Arg-Gly-Asp-d-Phe-Val and Arg-Gly-Asp-Ser, but not for the inactive analog Arg-Gly-Asp-Glu-Ser acetate. These data show that the activation of the integrin alpha(V)beta(3) contributes to the uPA-mediated impairment of pial artery dilation after H/I. These data suggest that the inhibition of uPA and integrin signaling may preserve cerebrohemodynamic control after H/I.
 ...
PMID:Inhibition of integrin alphavbeta3 prevents urokinase plasminogen activator-mediated impairment of cerebrovasodilation after cerebral hypoxia/ischemia. 1916 22