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

To determine the possible role of vascular factors in the bleeding tendency of uraemic patients, three major factors of the haemostatic system normally present in vascular tissues were studied. Factor VIII-related protein (F VIII) was detected on the vascular intima of 13 patients and 10 normal subjects. Comparable values of plasminogen activator (PA) were found in tissue slices from 7 patients and 7 controls. In contrast, prostacyclin like (PGI2) activity, measured as platelet aggregation inhibitory potency, was significantly higher in specimens from 15 patients with either acute or chronic uraemia than in 10 controls. The latter abnormality, leading to impaired platelet-vessel wall interaction, might contribute to the disturbed haemostasis of uraemic patients.
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PMID:Vascular factors in the pathogenesis of uraemic bleeding. 36 87

Two groups of specifically presensitized Macaca speciosa monkeys received renal allografts via anastomosis to an indwelling arteriovenous (A-V) shunt. One group was pretreated with heparin (2 mg/kg) intravenously and the other was also treated with constant heparin infusion (1 mg/kg/hr) directly into the renal artery. These studies were performed to evaluate the effects of heparin within the kidney on total and compartmental blood flow, complement (C3) levels, sequestration of formed elements, and activation of the coagulation, fibrinolytic, and kinin-forming systems during the initial 3 hours of hyperacute rejection. The results are compared with those previously reported in unmodified control allografts. Heparin prolonged blood clotting time to infinity, markedly prolonged total renal venous blood flow, and normalized compartmental distribution in both groups despite antibody deposition similar to that in controls. With heparin pretreatment only, initial morphologic injury was much reduced but then progressed rapidly. Marked initial cortical cyanosis with mottling appeared to change constantly and was associated with fluctuations in renal turgor, total blood flow, and sequestration of formed elements, all of which suggested repetitive local cortical arterial spasm and incremental destruction of the grafts. Activation of coagulation Factors II and XII was also revealed and marked net Factor VIII activity was observed in the venous effluent. The latter reflects either formation and release of this factor by the injured kidney, or provides in vivo documentation of the "hyperactivation" of Factor VIII by thrombin known to occur in vitro. The addition of intrarenal artery heparin infusion resulted in greater improvement in early total blood flow rates and more uniformly progressive cyanosis and loss of turgor, but the diffuse initial morphologic injury suggested more uniform perfusion of injured areas. Intrarenal consumption of C3 and sequestration of formed elements was similar to that in controls. Paradoxically, prompt activation and consumption of all coagulation factors, plasminogen, and prekallikrein were observed, but formed fibrin was sparse. The exess amount of Factor XIIa present during heparin blockade may have been diverted to production of plasminogen activator and kallikrein formation. The enormous numbers of neutrophils observed within vessels of grafts which showed the greatest kallikrein activation provide the probable in vivo demonstration of the chemotactic properties of kallikrein noted by others in vitro. Heparin-induced platelet aggregation may have played an important role in the failure of these grafts. These studies elucidate the intrarenal effects of heparin during hyperacute rejection and again suggest that vasoconstriction is the most important early determinant of graft failure, as blood flow appeared unrelated to the degree of vascular injury and apparent obstruction. Also, heparin may exer a beneficial effect on blood flow by other than its known action on coagulation.
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PMID:Hyperacute renal allograft rejection in the primate. Intrarenal effects of heparin and associated net release of factor VIII activity and kallikrein activation. 109 75

Primary cultures of peripheral lung lobes were grown in a highly supplemented medium. Human lung endothelial cells (HLE) were isolated from the mixed population by FACS. The cells proliferated rapidly and were serially cultivated for at least 16 passages. Both early and late passage cells were positive for the standard endothelial markers. Factor VIII related-antigen (Factor VIII R-Ag), angiotensin-converting enzyme, acetylated low-density lipoprotein labeled with 1,1'-dioctadecyl-1,3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL) uptake, and bound the lectin Ulex europaeus agglutinin (UEA). Prostaglandin E2 was the major cyclooxygenase product of HLE, in contrast to human umbilical vein endothelial cells (HUVE), which synthesized PGI2 in excess of PGE2. Factor VIII R-Ag exhibited a diffuse cytoplasmic as well as an extracellular fibrillar distribution in HLE, in contrast to a vesicular (Weibel-Palade body) cytoplasmic distribution in HUVE. The HUVE did demonstrate some extracellular fibrillar Factor VIII R-Ag as well. Urokinase was the predominant plasminogen activator (PA) secreted by HLE, whereas tissue PA was predominant in HUVE cultures. HLE formed tube-like structures within 2 h of plating on a Matrigel matrix whereas HUVE formed larger tube-like structures only after 1 or more days. The properties described here indicate that human lung microvessel endothelium can be isolated and continuously grown from small tissue segments and express a number of properties that differ from those of HUVE. These studies provide further support for the concept that endothelial cells from different sources can exhibit considerable heterogeneity relating to their phenotypic and biochemical properties.
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PMID:Isolation, cultivation, and partial characterization of microvascular endothelium derived from human lung. 133 46

The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alpha 1-antitrypsin (alpha 1AT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (VIII:C) and von Wildebrand antigen (vWf:Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (p less than 0.05), while values were unchanged in the control group. Hematocrit, platelet counts, and alpha 2-plasmin inhibitor (alpha 2PI) activities also decreased in the physical training group (p less than 0.05). In contrast, these variables increased in the control group (p less than 0.05). Activated partial thromboplastin time (aPTT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-alpha 2PI complex (PIC), thrombin-antithrombin III complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-1), VII:C, and P-C activities had significantly decreased after one month of physical training (p less than 0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to suppress coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, alpha 2PI, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.
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PMID:Blood coagulability and fibrinolytic activity before and after physical training during the recovery phase of acute myocardial infarction. 162 56

A 2.4 kb fragment of hCMV (Towne strain), containing the 5' end of the major immediate-early gene, has been cloned, sequenced, and used to construct a series of mammalian cell expression plasmids. The effects of regulatory regions present on this fragment were assessed using human glycoproteins as reporter molecules. We compared secreted levels of Factor VIII, t-PA, and HIV-1 envelope glycoproteins in cells transfected with plasmids in which intron A of the immediate-early gene was present or absent. Secretion of several glycoproteins was significantly higher when cells were transfected with intron A-containing plasmids. Mutation of three basepairs in the strong nuclear factor 1 (NF1) binding site in intron A led to reduced transient expression levels, but not to the level observed in the absence of intron A. Reduced expression from NF1 mutant plasmids was roughly correlated with reduced binding in vitro of NF1 proteins to a synthetic oligonucleotide containing the mutation. The evidence indicates that sequences in intron A positively regulate expression from the hCMV immediate-early enhancer/promoter in transformed monkey kidney cells.
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PMID:Effect of intron A from human cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells. 165 Apr 59

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.
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PMID:Haemostatic responses and vasopressin release during colonoscopy in man. 165 70

It has been suggested that growth hormone (GH) plays a role in the regulation of Factor VIII-von Willebrand factor complex and other parameters associated with haemostasis and vascular integrity. However, limited information is available on these features in GH-deficient patients. We therefore examined, in a double-blind, placebo-controlled crossover design, the effects of 4 months' replacement therapy with biosynthetic human GH in 22 GH-deficient adults on circulating haemostatic parameters and capillary fragility. A non-significant increase in the plasma levels of von Willebrand factor antigen (p = 0.09), Factor VIII antigen (p = 0.6), fibrinogen (p = 0.4) and fibronectin (p = 0.2) was observed at the end of the GH treatment period along with a non-significant decrease in tissue-type plasminogen activator (p = 0.2). Capillary fragility tended to decrease during GH therapy (p = 0.2). All variables remained within the reference range following both the placebo and the GH treatment period. It is concluded that GH-deficient patients display normal levels of the haemostasis parameters recorded, and that 4 months of GH therapy in a conventional replacement dose does not significantly affect these values.
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PMID:Growth hormone (GH) therapy in GH-deficient patients, the plasma factor VIII-von Willebrand factor complex, and capillary fragility. A double-blind, placebo-controlled crossover study. 211 72

Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) fo the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, beta-thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non-affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti-urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of beta-thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p less than 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p less than 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.
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PMID:Cutaneous and plasma fibrinolytic activity in systemic sclerosis. Evidence of normal plasminogen activation. 212 82

Management of cirrhosis with massive ascites involves particular difficulties. The introduction of a peritoneovenous shunt and reinfusion of concentrated ascitic fluid techniques allows increased diuresis and improves renal function. However, these procedures have frequently been associated with disseminated intravascular coagulation and/or activation of fibrinolysis. Factor VIII activity, antigen and ristocetin cofactor, plasminogen, antiplasmin, plasminogen activator activity and plasmin-antiplasmin complex were investigated both in the ascitic fluid and plasma of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicated that no hyperfibrinolysis was seen in the plasma of cirrhotic patients and that activation of fibrinolysis exists in ascites. Significantly higher levels of plasmin-antiplasmin complex and plasminogen activator activity were found in ascitic fluid than in plasma. In post-reinfusion much higher levels of all three Factor VIII components were observed in cirrhotic plasma than in normal plasma. In conclusion, activation of fibrinolysis could explain coagulation complications occurring after ascites reinfusion. Antifibrinolytic treatment could render the concentration-reinfusion technique more acceptable.
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PMID:Fibrinolytic study in plasma and ascitic fluid of cirrhotic patients before and after ascites concentration; reinfusion technique. 241 33

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.
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PMID:Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated preparation. 249 11


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