Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A direct and indirect detection of plasmin in native CSF was not possible by the thrombelastographic and hot fibrin agar plate method and by electroimmunodiffusion analysis using Laurell's method of fibrin degradation product determination, respectively. The same method was used to determine concentrations of plasminogen and fibrinogen. The CSF, which were retrospectively judged to be normal, neither showed plasmin activity nor exhibited plasminogen and fibrinogen concentrations. Therefore, the liqour possesses only a plasminogen activator protein and does not represent a fibrinolytically active CSF.
 ...
PMID:[In-vitro experiments on the clarification of the fibrinolytic activity in normal cerebrospinal fluid]. 14 59

The pattern of expression of urokinase type plasminogen activator (PA) in granulocyte-macrophage-CSF transgenic mice and their normal littermates was studied using RNAse protection assays and a plasminogen-dependent fibrinolytic assay for PA. Urokinase type PA mRNA was expressed at a high level in transgenic peritoneal cells and at a lower level in transgenic eye tissue and spleen, but not in equivalent tissue from the normal mice. Enzymically active PA was detectable in protein extracts from peritoneal cells taken from transgenic mice of less than 8 wk of age (young mice) but not from normals. Paradoxically, extracts from transgenic mice of more than 12 wk of age (old mice) showed little detectable PA activity despite continuing transcription in some mice of this age. The production of PA by peritoneal cells may be responsible for the spontaneous i.p. bleeding which is a feature of the transgenic mice and production in other tissues may help explain the local pathologic changes.
 ...
PMID:Plasminogen activator in granulocyte-macrophage-CSF transgenic mice. 143 Nov 38

The activity of human osteoblast-like cells cultured in vitro is regulated by a number of factors, which include systemic hormones as well as agents that can be produced locally within bone. Several cytokines and growth factors have been demonstrated to be produced by osteoblasts themselves, and this includes granulocyte-macrophage colony-stimulating factor (GM-CSF). In this report we show that recombinant human GM-CSF (rhGM-CSF) modulates the activities of osteoblast-like cells derived from human trabecular bone in vitro. rhGM-CSF stimulated the proliferation of the cultured human osteoblast-like cells, but antagonised the induction by 1,25(OH)2D3 of osteocalcin synthesis and alkaline phosphatase activity, two characteristic products of osteoblasts. rhGM-CSF however, had no appreciable effect on the production of prostaglandin E2, or on the plasminogen activator activity associated with human osteoblast-like cells. These results are the first report of which we are aware of an apparently direct action of GM-CSF on cells of the osteoblast phenotype. These studies indicate that GM-CSF represents another haematological factor that can potentially exert regulatory actions on human osteoblast-like cells. GM-CSF may therefore be a potential paracrine/autocrine regulator of osteoblast activity.
 ...
PMID:The effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on human osteoblast-like cells. 265 92

CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. J774 cells are a monocyte precursor-like macrophage cell line. This transformed macrophage cell line exhibits specific 125I-CSF-I-binding activity similar to that of normal murine macrophages, although its survival and growth is independent of CSF-1. At 0 degrees C, saturation of binding sites was achieved at 240 pM 125I-CSF-1. At 37 degrees C, the bound 125I-CSF-1 was rapidly internalized and degraded by the target cells with a T1/2 of approximately 30 min; degradation was inhibited by the addition of NH4Cl. The addition of CSF-1 to cultures caused dose-dependent inhibition rather than stimulation of [3H]thymidine uptake by J774 cells. Whereas CSF-1 stimulated the clonal growth of normal mouse peritoneal exudate macrophages, it inhibited the clonal growth of J774 cells in agar cultures. Furthermore, CSF-1 exhibited a concentration-dependent enhancement of the production of plasminogen activator (PA) by J774 cells. The enhanced production of PA was detected 6 hr after the addition of CSF-1 and was inhibited by the simultaneous addition of the anti-inflammatory drug. It appears that the effects of CSF-1 on cell proliferation and PA production by CSF-1 receptor-bearing cells are mediated by distinct intracellular pathways albeit through the same receptor.
 ...
PMID:Colony-stimulating factor (CSF-1): its enhancement of plasminogen activator production and inhibition of cell growth in a mouse macrophage cell line. 632 11

Among the reasons for intensified research into the CSF haemostatic pathway were the clinical case reports stating that special importance must be attached to the CSF for the high incidence of rebleeding and the intraoperative haemorrhage rate in SAH patients, which, among other things, may be regarded as the reasons for mortality. Extensive analyses of the coagulation and fibrinolysis enzyme systems were carried out and constitute the basic concept for the conservative AFT aiming at restoring to normal haemostasis and wound healing which had been disturbed by local fibrinolytic activity in the area of operation or trauma. The programme of investigation, first served as basic research and was then directed towards the clinical situation for recording the partly contradictory or still unknown haemostasis values in the CSF. This necessitated that the immunochemical, enzymatic, enzymatic-fluorometric, biophysical and chromogenic substrate methods should be adapted to low quantities of protein for the quantitative determination of activators, inhibitors, zymogens, enzymes, the fibrin substrate and its degradation products. The results obtained with the prospective series of tests applying selective methods with objective data recording confirm the operating hypothesis that, on principle, a distinction must be made between the proteins of normal CSF in cases of intact BBB and the pathological protein patterns, not typical of CSF, caused by disturbances of permeation. The CSF space, therefore, must be regarded as a compartment largely insulated by the BBB. That is why the unqualified interpretation is wrong, when it states that the CSF, in general, shows a fibrinolytic activity, no matter whether the CSF is formed under physiological or pathological conditions, or whether it represents a mixture of blood and CSF. CSF formed when the BBB is normal has no fibrinolytic activity. The plasminogen activator antigen always present in CSF does not become effective because the quantity of plasminogen in CSF is well below normal for the measurable fibrinolytic activity. In the case of diseases accompanied by disturbance of the BBB, the proteins of the fibrinolytic system in the CSF increasingly penetrate in proportion to the disturbance of BBB, and thus enable the CSF to some extent to become a fibrinolytically active fluid. A temporarily limited breakdown of the BBB in the case of bleeding into the CSF space permits the unhampered transfer of all the factors required for the fibrinolytic system, as well as the inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Haemostasis in cerebrospinal fluid. Basic concept of antifibrinolytic therapy of subarachnoid haemorrhage. 639 43

Tissue type plasminogen activator (tPA) plays a role in differentiation of neurones and activity-dependent structural changes in neurones. We hypothesised that tPA would also be present in CSF during fibrinolysis after intraventricular haemorrhage. We measured tPA antigen in CSF from 13 normal newborn infants and 14 infants with post-haemorrhagic ventricular dilatation (PHVD). tPA was undetectable or at the limit of detection (1 microgram/l) in normal CSF. The CSF tPA concentration ranged from 1.3 to 3.5 micrograms/l in the infants with PHVD. Serial tapping in one infant showed persistence of tPA in the CSF from 3 to 8 weeks of age. We conclude that endogenous tPA may be part of the physiological response to intraventricular haemorrhage or may be present as a result of passive diffusion into the CSF.
 ...
PMID:Endogenous tissue plasminogen activator in neonatal cerebrospinal fluid. 877 26

Previous studies have indicated that intraventricular administration of tissue-type plasminogen activator (TPA) might improve the prognosis of patients with intraventricular haemorrhage (IVH). In aneurysmal IVH, fibrinolytic treatment was always preceded by surgical repair of the aneurysm, since the risk of recurrent haemorrhage from a non-occluded aneurysm was estimated to be high. We reviewed a series of patients with IVH secondary to ruptured aneurysms (n = 4) or arteriovenous malformation (AVM; n = 1) who underwent emergency intraventricular administration of TPA before repair of the bleeding source. Fibrinolysis resulted in rapid decrease of haematoma volume and of ventricular dilatation, and prevented ventricular catheters from becoming obstructed. No intracranial haemorrhages or other complications occurred. The results suggest that the presence of recently ruptured aneurysms or AVM is not necessarily a contraindication for intraventricular administration of TPA. The potentially life saving benefits might outweigh the inherent risks of recurrent haemorrhage in carefully selected patients with massive IVH, in whom ventricular distension, periventricular brain compression, obstruction of CSF flow, and elevated ICP appear to be major determinants for the outcome.
 ...
PMID:Fibrinolytic treatment of intraventricular haemorrhage preceding surgical repair of ruptured aneurysms and arteriovenous malformations. 1061 79

This experimental study evaluated the effect of intrathecal injection of tissue-type plasminogen activator followed by cisternal drainage in the ultra-early stage of aneurysmal subarachnoid haemorrhage to prevent vasospasm. Twenty Japanese white rabbits were divided into five groups. Either tPA (groups A, B, and E) or saline (groups C and D) was injected intrathecally 1 hour (groups A, B, C, and D) or 21 hours (group E) after the intrathecal injection of blood. Cerebrospinal fluid was drained 2, 4, and 6 hours after the intrathecal injection of blood (groups A, C, and E). On day 4, the angiographic caliber of the basilar artery in each group was as follows (mean +/- SD): A, 85.9 +/- 5.0%; B, 74.6 +/- 5.3%; C, 69.1 +/- 2.7%; D, 64.0 +/- 4.9%; E, 80.2 +/- 2.7% (compared with baseline). In the two groups in which CSF was drained (groups A and C), fibrinolysis with tPA significantly suppressed vasospasm. In the two groups treated with tPA (groups A and B), cisternal drainage significantly suppressed vasospasm. In the two groups treated with saline (groups C and D), however, cisternal drainage did not suppress vasospasm. Examination of the series of CSF samples (groups A and C) showed that fibrinolysis with tPA effectively cleared clots early. In the two groups treated with tPA and CSF drainage (groups A and E), early removal of subarachnoid clots reduced the degree of vasospasm. Early fibrinolysis with tPA and early removal of subarachnoid clots by drainage is effective for preventing vasospasm.
 ...
PMID:Experimental study of intracisternal administration of tissue-type plasminogen activator followed by cerebrospinal fluid drainage in the ultra-early stage of subarachnoid haemorrhage. 1067 5

1. Fenestrated vessels can be reversibly induced in brain by agents that stimulate urokinase production. This plasminogen activator, like vascular endothelial growth factor and metalloproteinases, is secreted by tumor cells and may account for induction of fenestrated vessels. Why only some of the brain's barrier vessels are converted to fenestrated vessels is unknown. 2. The structures responsible for the filtering of solutes by fenestrated vessels may be the same as those of continuous, less permeable vessels: the glycocalyx on the surfaces of the endothelial cells and the subendothelial basal lamina. 3. Solutes leaving the cerebral ventricles immediately enter the interstitial clefts between the cells lining the ventricles. A fraction of a variety of solutes, injected into CSF compartments, is retained by subendothelial basal lamina, from which the solutes may be released in a regulated way. 4. The brain's CSF and interstitial clefts are the conduits for nonsynaptic volume transmission of diffusible signals, e.g., ions, neurotransmitters, and hormones. This type of transmission could be abetted by a parallel, cell-to-cell volume transmission mediated by gap junctions between astrocytes bordering CSF compartments and parenchymal astrocytes. 5. The width and contents of the interstitial clefts in fetal brain permit cell migration and outgrowth of neurites. The contents of the narrower and different interstitial clefts of mature brain permit solute convection but must be enzymatically degraded in order for cells to migrate through it.
 ...
PMID:Permeable endothelium and the interstitial space of brain. 1069 5

Fibrinolytic activity in the inner ear of human beings and guinea pigs was assayed qualitatively and quantitatively. It was found that fibrinolytic activity of the stria vascularis was caused by a conversion of plasminogen to plasmin by tissue plasminogen activator and was moderate in degree compared with that of other organs in both species. In human beings, endolymph showed higher plasminogen activator activity than that of CSF. Plasminogen activator activity was not detected in either endolymph or perilymph of guinea pigs. Thrombin infusion diminished plasminogen activator activity in the stria vascularis of guinea pigs.
 ...
PMID:Fibrinolytic activity in the inner ear of human beings and guinea pigs. 1099 33


1 2 Next >>