Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P00750 (PLA)
16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some patients with von Willebrand's disease do not respond to stimuli such as venous occlusion and infusion of a vasopressin analogue DDAVP. In these patients, fibrinolytic activity is not enhanced and von Willebrand's factor is not released into the blood. Skin biopsies and cryostat sections were used to study the fibrinolytic activity of skin vessels and localization of tissue plasminogen activator (t-PA) in three patients with severe form of von Willebrand's disease. On fibrin films, no fibrinolysis developed around the skin vessels of the patients; however, using specific polyclonal and monoclonal antibodies to t-PA, and peroxidase coupled specific IgG, presence of t-PA antigen was demonstrated in endothelial cells (EC) of all of them. In plasma no t-PA activity was detected either before or after venous occlusion although t-PA inhibitor activity was in a normal range. Small amounts of t-PA antigen was measured in blood by ELISA. From these results, it is concluded that in patients with severe forms of von Willebrand's disease, t-PA present in EC is not functional and can not transform plasminogen into plasmin.
...
PMID:Absence of functional activity of tissue plasminogen activator in patients with severe forms of von Willebrand's disease. 311 91

DDAVP was administered at 0.4 microgram kg-1 intravenous (i.v.) and subcutaneous (s.c.) routes to 6 healthy subjects in a double blind crossover study. Both study treatments were well tolerated. Flushing occurred after both treatments but was more prominent after i.v. than after s.c. DDAVP. Mild transient local discomfort at the s.c. injection site occurred in 5 of 6 subjects. The mean peak factor VIII (FVIII) response was 369% and 247% of baseline after i.v. and s.c. DDAVP respectively and the maximum increase in FVIII occurred earlier with the i.v. route. Changes in FVIII antigen (FVIII:Ag) and von Willebrand factor antigen (vWF:Ag) were also monitored. Tissue-type plasminogen activator (t-PA) activity measured by a chromogenic assay employing soluble fibrin had a median peak value of 2.9 IU ml-1 at 20 min after i.v. and of 1.9 IU ml-1 at 60 min after s.c. DDAVP. t-PA antigen was also measured so that the specific activity of circulating t-PA could be determined. Preinjection median values of 14,650 and 13,700 IU mg-1 increased to peak median values of 236,200 IU mg-1 at 20 min after i.v. and 202,400 IU mg-1 at 60 min after s.c. DDAVP. Plasminogen activator inhibitor (PAI) activity fell following DDAVP and became undetectable in some subjects during the sampling period. The ratio of maximum fibrinolytic response was similar to the ratio of maximum haemostatic responses obtained by two routes of injection. Our results indicate that s.c. DDAVP might successfully replace i.v. DDAVP in several applications such as confirmation of haemostatic or fibrinolytic responsiveness in patient groups; for obtaining FVIII enriched plasma; as well as its obvious potential usefulness in home treatment of haemophilia A and von Willebrand's disease.
...
PMID:Fibrinolytic and haemostatic responses to desamino-D-arginine vasopressin (DDAVP) administered by intravenous and subcutaneous routes in healthy subjects. 312 7

The effect of alpha-tocopherol on various endothelial cell functions was evaluated in vitro using cultures of human umbilical vein endothelial cells. Prostacyclin synthesis, plasminogen activator activity and von Willebrand factor activity were evaluated in control and alpha-tocopherol supplemented cultures. Alpha-tocopherol produced stimulation of prostacyclin production which peaked at or near 0.5 mM. Plasminogen activator activity was markedly reduced by the addition of alpha-tocopherol. Von Willebrand factor activity showed a significant decrease of processed and cellular forms that was dose-dependent. The incorporation of alpha-tocopherol into endothelial cells could be demonstrated by measuring intracellular levels of the vitamin in washed endothelial cells. Our results show that alpha-tocopherol has a profound effect on multiple endothelial cell functions which are intimately involved in hemostasis.
...
PMID:Alpha-tocopherol, a potent modulator of endothelial cell function. 313 80

Studies on the effect of DDAVP both in vitro and in vivo are reported. In order to define the extent of the DDAVP induced rise of circulating endothelial cell proteins in normal individuals and the endothelial cell defect in von Willebrand's disease (vWd) we have measured the effect of intravenous DDAVP on a range of possible endothelial cell markers in normal subjects and in patients with mild haemophilia and vWd. In a series of double blind cross over studies on normal volunteers we have tested the effect of naloxone, DDAVP or saline on circulating levels of factor VIII related activities (VIIIR) and plasminogen activator (PA). The results confirmed the effect of DDAVP on circulating levels of VIIIR and PA but showed that it did not induce release of these activities from cultured endothelial cells in vitro nor did it influence circulating levels of other endothelial cell markers including fibronectin, antithrombin III and platelet factor 4. Infusion of nalaxone did not significantly alter circulating levels of VIIIR or PA nor the response of these to DDAVP suggesting that normally these activities are not subjected to a vasopressin drive.
...
PMID:The effect of desamino-D-arginine vasopressin (DDAVP) and naloxone infusions on factor VIII and possible endothelial cell (EC) related activities. 643 Mar 37

Deamino-8-D-argenine vasopressin (DDAVP) was given by intravenous infusion to normal subjects, haemophiliacs and patients with von Willebrand's disease (vWd) and the factor VIII and plasminogen activator response was studied. In normal subjects and most patients with mild haemophilia and mild (intermediate) von Willebrand's disease there was an increase in plasminogen activator and all factor VIII related activities. In patients with mild vWd the prolonged bleeding time was shortened by DDAVP despite only a modest rise in factor VIII related Ristocetin cofactor activity (VIIIR:RiCoF). Sub-groups of patients have been characterized in whom atypical responses was observed. In two brothers with clinically severe haemophilia, but with 5--6 u/dl procoagulant factor VIII (VIIIC), there was an increase in VIIIC but no rise of the corresponding antigen, suggesting increased release of an antigenically abnormal poorly functioning molecule. A patient with intermediate vWd was studied in whom neither DDAVP, adrenaline infusion, nor venous occlusion resulted in an increase in either plasminogen activator or factor VIII related antigen (VIIRAg), although there was a significant increase in VIIIC. In a further patient with severe vWd, DDAVP failed to elicit any plasminogen activator or VIII response. The results obtained from these two patients suggested that in some individuals the presumed endothelial cell abnormality in vWd may be more extensive than a defect in VIIIRAg synthesis. Sub-groups of patients have been identified for whom treatment with factor VIII concentrates would be more appropriate than DDAVP prior to minor surgery.
...
PMID:Factor VII and fibrinolytic response to deamino-8-D-argenine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrand's disease. 677 73

The aim of this study was to compare the secretory response of the vascular wall in vivo to DDAVP (i.v. 0.3 microgram/kg, 30 min) and to venous occlusion (VO, 20 min) in control healthy subjects, patients with von Willebrand's disease type I (vWd I) and patients with von Willebrand's disease type III (vWd III). In controls (n = 10) and vWd I (n = 12), DDAVP induced a 2 to 3-fold rise in plasma von Willebrand factor antigen (vWf: Ag), factor VIII coagulant activity (VIII: C) and tissue--type plasminogen activator antigen (t-PA:Ag). VO was less effective in increasing vWf: Ag and VIII:C but produced a greater rise in t-PA:Ag. Large increments (over 10-fold) were observed in plasmin-alpha 2-antiplasmin complexes following both stimuli. In vWd III (n = 10), DDAVP and VO failed to increase vWf:Ag, VIII:C and t-PA:Ag. No significant changes in plasmin-alpha 2-antiplasmin complexes were observed in this group. Moreover, the baseline t-PA:Ag values were significantly lower in vWd III (2.17 +/- 1.13 ng/ml) than in controls (4.84 +/- 1.97 ng/ml, p < 0.001). A significant increase in urokinase--type plasminogen activator antigen (u-PA:Ag) was found only in controls after VO. Neither controls nor patients with vWd showed any changes in plasma fibronectin levels following DDAVP. The low t-PA:Ag results and the abnormal fibrinolytic response to DDAVP and VO in patients with severe (type III) vWd indicate that their endothelial cell abnormality is more extensive than the defect in the synthesis or release of vWf.
...
PMID:Secretory response of the vessel wall to DDAVP and venous occlusion in von Willebrand's disease. 799 99

Some well-described similarities exist between tissue plasminogen activator (t-PA) and von Willebrand factor (vWf) which may suggest a link in either the synthesis or release of both proteins from endothelial cells. To investigate this relationship further immunocytochemical localization of t-PA and vWf was performed in normal tissues and in skin obtained from patients with type I and type III von Willebrand's disease (vWd). Components of the fibrinolytic system were measured at baseline and after venous occlusion in healthy controls and patients with vWd. Patients with severe vWd received intravenous vWf concentrate, followed by desmopressin (DDAVP), to study the plasma response of vWf and t-PA. By immunocytochemical staining, t-PA was demonstrated in endothelial cells of normal skin, kidney and liver and also in the skin of patients with type I and type III vWd. vWf was localized in endothelial cells of all tissues except the specimens from an individual with severe vWd. Basal plasma levels of fibrinolytic components were normal in patients with vWd. Venous occlusion resulted in a rise of fibrinolytic activity in controls and patients with type I, but not type III, vWd. No rise in plasma t-PA was observed following DDAVP in severe vWd, even though near-normalization of plasma vWf levels had been obtained by prior infusion of vWf concentrate. It is concluded that the synthesis of t-PA and vWf is probably regulated by independent processes. Constitutive and regulated release of both proteins occur through different mechanisms and the basal secretion of t-PA is intact in severe vWd.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Study of endothelial t-PA and vWf in normal subjects and in von Willebrand's disease. 807 4

In a recent prospective study of allogenic bone marrow transplantation we reported that decreases in factor VII and protein C were predictive markers for high risk of veno-occlusive disease (VOD). In order to determine the relative involvement of endothelial and hepatocyte injury in the genesis of VOD, 34 consecutive patients undergoing autologous bone marrow transplantation (BMT) were studied. Conditioning was performed by chemotherapy alone or associated with total body irradiation (TBI). Protein C and factor VII, the endothelial markers Von Willebrand factor (vWF and t-PA, fibrinogen and fibronectin were measured weekly before and after BMT. Protein C and factor VII were within the normal range before BMT, decreased significantly on day 7 to 73 and 64% respectively (p < .01) and then returned to normal values. Fibrinogen increased to 7 g/l (p < .001) on day 7 but then returned to normal levels. Fibronectin was abnormally high (p < .001) before BMT and decreased thereafter, while vWF increased (p < 0.001) for three consecutive weeks. t-PA was low (p < 0.001) before conditioning but increased thereafter. These results demonstrate the presence of endothelial lesions before BMT and acute hepatic and endothelial lesions after conditioning. Although VOD was never observed in our patients, this complication could well arise from preexisting vascular lesions due to previous chemotherapy and/or from acute hepatocytic injury, which could also be of endothelial origin, after conditioning.
...
PMID:Changes in protein C, factor VII and endothelial markers after autologous bone marrow transplantation: possible implications in the pathogenesis of veno-occlusive disease. 833 49

The aim of this study was to design a simple laboratory method that can screen the overall haemostatic potential in plasma (OHPP) when a hyper- or hypocoagulable state is present. A fibrin time curve was made via spectrophotometric registration of fibrin generation and lysis in plasma, to which exogenous thrombin and tissue type plasminogen activator was added. The area under the curve, calculated by the sum of absorbance (ABS-sum), varied in correlation to the concentrations of platelets or purified pro-/anticoagulants: tissue factor, von Willebrand factor, fibrinogen, antithrombin, plasminogen, or plasminogen activator inhibitor type 1. The ABS-sums also changed in positive relation to the haemostatic function investigated in 16 menopausal women and 14 young healthy nonpregnant women (controls). The findings imply that the ABS-sums not only offer a general information about fibrin generation and lysis in vitro, but also reflect the OHPP (i.e., final combined effects of platelet activity, coagulation, and fibrinolysis in vivo). Preliminary results were satisfactory; the levels of OHPP, expressed as the ABS-sums, were higher in normal pregnant women than in the controls, and even higher in preeclamptic patients than in pregnant women with no complications, which corresponds to the different grades of hypercoagulability in the three groups. Moreover, the level of OHPP was considerably lower in an untreated infant with von Willebrand's disease type 3 and in factor VIII- or factor IX-deficient plasma samples.
...
PMID:A laboratory method for determination of overall haemostatic potential in plasma. I. Method design and preliminary results. 1057 92

Von Willebrand factor (vWf) is a glycoprotein involved in primary hemostasis and synthesized in endothelial cells (EC). vWf is stored in secretory granules specific for EC called Weibel-Palade bodies (WPb). Studies on the molecular mechanisms of vWf storage and acute release are hampered by the limitations of the available endothelial cell culture models. We created a suitable model by stable transfection of the vWf-negative ECV304 endothelial cell line with pro-vWf cDNA. Pro-vWf was normally cleaved to mature vWf and stored in WPb. Acute vWf release occurred in response to the calcium ionophore A23187. Thus, vWf expression is sufficient to restore functional secretory granules in ECV304 cells. We used this model to study the role of WPb in the storage of tissue-type plasminogen activator (t-PA), a key fibrinolytic enzyme that is acutely released by EC, but whose intracellular storage compartment is still a matter of debate. We observed that restoration of WPb in ECV304 cells results in the targeting of t-PA to these storage granules.
...
PMID:Regulated von Willebrand factor (vWf) secretion is restored by pro-vWf expression in a transfectable endothelial cell line. 1063 36


<< Previous 1 2 3 Next >>

---