Search PubMed⌕ Search

Biomedical subjects

C Soria

Publications and source records attributed to C Soria.

At least 163 records · Page 9Linked to original sources
PubMed1989

Plasma factor VII, triglyceride concentration and fibrin degradation products in primary hyperlipidemia: a clinical and laboratory study.

There is evidence that the increase in coagulation factor VII (FVII) represents a predictive risk factor of arterial thrombosis in coronary heart disease. Its relative contribution to this multifactorial process and its relationship to other risk factors, namely cholesterol and triglycerides, is yet a matter of investigation. In this study we aimed to clarify whether FVII synthesis or activation correlated with plasma lipid concentrations. For this, we assayed the plasma levels of FVII antigen (FVII:ag) and FVII coagulant activity (FVIIc) in types IIa, IIb and IV hyperlipidemic individuals, together with the levels of cholesterol, triglycerides, high-density lipoproteins and apolipoprotein B. FVII activation state (FVIIa) was then assessed by FVIIc/FVII:ag. In order to assess the possible correlation of FVII levels with the generation of thrombin and formation of fibrin, we also assayed the plasma concentration of fibrin degradation products (D-dimers) in these patients. Considering all the patients studied, there was a fair correlation between FVIIc and FVII:ag (r = 0.704; p less than 0.01). The mean levels of FVIIc and FVII:ag were significantly higher in type IV hyperlipidemia than in controls (t = 4.260; p less than 0.001 and t = 3.015; p less than 0.01, respectively) and other types of hyperlipidemia. We also found that FVIIc and FVII:ag significantly correlated to triglyceride concentration. We could not detect an evident activation of FVII in these patients since FVIIc/FVII:ag was not elevated in comparison with controls, nor did it correlate with any of the lipid determinations in any of the types of hyperlipidemia studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗
PubMed1989

Coagulation factor VII and plasma triglycerides. Decreased catabolism as a possible mechanism of factor VII hyperactivity.

High circulating levels of coagulation factor VII (FVII) are known to be associated with elevated concentrations of blood lipids. More specifically, hypertriglyceridemia is correlated with raised FVII coagulant activity (FVIIc). Recently, evidence has been described which suggests that elevation in FVIIc might reflect an increase in the total concentration of FVII, as evaluated by quantitation of FVII antigen (FVIIag). It is also known that FVIIc represents a risk factor for cardiovascular death, but the prediction of cardiovascular risk based on triglyceride estimation is the subject of conflicting results. Since dyslipidemia featuring abnormal triglyceride metabolism is pathophysiologically heterogeneous, we analyzed the possible relationships between FVII and triglyceride further and under standardized postprandial conditions. For this purpose we studied FVIIc and FVIIag in relation to triglyceridemia after a standardized test meal. Our results confirm that FVIIc and FVIIag levels are strongly correlated with each other (r = 0.714; p = 0.01). In addition, both were significantly increased (p less than 0.02) in patients who exhibited abnormal triglyceride levels 8 h after a standardized test meal, as compared to those who displayed normal triglyceridemia. Furthermore, we found that apolipoprotein B levels were also increased in such patients. The deficient postprandial catabolism of triglycerides, therefore, appears to be related to an increase in total FVII concentration, suggesting that some association between the metabolism of triglyceride-rich lipoproteins and FVII might underlie the mechanism of the elevation in FVII. Given the important contribution of FVII to hypercoagulability, then our results may be relevant to the understanding of the role of postprandial triglyceride in atherogenesis and in consideration of the circadian prevalence of cardiovascular thrombosis.

Adult↗
PubMed1989

Modulation of platelet function by SIN-1A, a metabolite of molsidomine.

Molsidomine or its active metabolite SIN-1A have antithrombotic properties in experimental models. This effect seems to be related, at least in part, to their antiplatelet activities. SIN-1A inhibited platelet adhesion to collagen, platelet aggregation, and the release reaction in in vitro experiments. SIN-1A acts as an early step of platelet activation by inhibiting calcium influx and phospholipase activity, which leads to inhibition of thromboxane formation and fibrinogen binding. Antiplatelet properties were observed after oral absorption in healthy volunteers and in patients with myocardial infarction after intravenous infusion.

Collagen↗
PubMed1989

[Neutrophilic dermatosis in inflammatory intestinal disease].

The neutrophilic dermatosis are a group of cutaneous diseases that share similar clinical and histopathologic features. They frequently occur in association with other diseases, particularly idiopathic inflammatory bowel disease. We present herein three cases of neutrophilic dermatosis and inflammatory bowel disease. We emphasize the atypical cutaneous findings and we discuss their nosologic situation.

Adult↗
PubMed1989

[The biology of fibrinogen. The role of pentoxifylline].

Recent epidemiological studies have shown that an increase in fibrinogen level (even a slight increase) is an important risk factor for vascular disease. Consequently, drugs which induce a decrease in fibrinogen are of great importance. Pentoxifylline given in patients with vascular disease or in those with high risk of thrombosis (diabetes, arteritis) induces a significant decrease in plasma fibrinogen level. Furthermore, in patients with arteritis, the decrease in fibrinogen level after pentoxifylline is correlated with the improvement in the walking distance. Several hypotheses may be taken into account to explain the decrease in fibrinogen induced by pentoxifylline. The hypothesis based upon a decrease of fibrinogen synthesis seems very fascinating since pentoxifylline, inducing a decrease in Interleukin 1 activity on leukocytes, might be responsible also for a decrease in interleukin 1 activity as fibrinogen stimulating factor. Furthermore, the effect of pentoxifylline on fibrinolysis, reported by some authors, is also of importance for the prevention of thrombotic disorder.

Fibrinogen↗
PubMed1989

Phospholipase C sensitive FVII activity and FVII antigen in hypertriglyceridemia.

An increase in factor VII coagulant activity (FVIIc) was found in patients with high thrombotic risk and in hyperlipidemias, namely in Fredrickson's types IIb and IV. This elevation was correlated with the level of total cholesterol and triglyceride concentrations. It has been suggested that this increase is due to higher FVII coagulant activity related to the formation of a complex between factor VII (FVII) and phospholipids, since it was shown that FVIIc returns to normal levels after incubation of plasma with phospholipase C. In this respect we have studied the activity of FVII before and after phospholipase C plasma treatment and FVII related antigen (FVIIag) in patients with types IIa, IIb and IV hyperlipidemias. An elevation of FVIIc was found in hyperlipidemic patients compared to normal controls. FVIIag values were also higher in type IV patients, implicating an increase in FVII total concentration and not only an activation of FVII. Furthermore, Phospholipase C action on patients' plasma samples lowered FVIIc to levels very similar to those of FVIIag. In normal controls the same action was noted and it seems therefore likely that the proposed phospholipid contribution to FVIIc hyperactivity plays only a minor role in FVII changes in primary hyperlipidemia. Instead, FVIIag increase seems to be the major mechanism of FVII increase in primary hypertriglyceridemic patients.

Adult↗
PubMed1988

High frequency of plasminogen activator secretion by malignant human lymphoid cell lines of T-cell type origin.

Diffuse defibrination is rarely observed in acute lymphoblastic leukemia (ALL). Clinical and immunologic data suggest that it is more likely to occur in T cell derived ALL. The current investigation involved the secretion of plasminogen activators (PA) of tissue type (t-PA) or urokinase type (U-PA) by testing supernatants of 21 permanent human leukemic cell lines originating from various hematopoietic lineages and one induced lymphoblastoid cell line. (LCL) The amount of PA in each supernatant was determined by biologic and immunoenzymologic assays. The correspondence with the expected molecular weight (MW) according to the PA type was checked by zymography. PA secretion of U-PA type was observed in the three myeloid cell lines. Except for the normal LCL, no B-lymphoid lineage related cell lines of various levels of differentiation displayed PA secretion, whereas PA activity was observed in the supernatant of six of nine malignant T-cell lines. The T-leukemic cell lines CCRF CEM, KE 37, HUT 78, and HUT 102 released U-PA-like activity. Peer released t-PA-like activity and CCRF-HSB2 supernatant showed both types of PA activity. These findings are discussed in view of the natural history of these diseases and the stage of differentiation of the cell lines.

Humans↗
PubMed1988

Localization of the inhibitory site(s) of pentosan polysulphate in blood coagulation.

We studied the inhibitory effect of pentosan polysulphate (PPS, Hémoclar) on thrombin formation in blood coagulation. In contrast to a current hypothesis the antithrombin III independent effect of PPS on blood coagulation is not caused by preventing the binding of the factors IX, IXa, X, Xa, VIII, V, Va and II onto procoagulant phospholipids. We investigated the activation by thrombin of factors I, V and VIII. A strong inhibitory effect of PPS on factor VIII activation could be observed. Inhibition of the activation of factor V to the same extent requires about 30-fold higher concentrations of PPS, whereas the activation (clotting) of fibrinogen is not inhibited. The effect of PPS on factor VIIIa is two-fold: A) it inhibits its formation and B) it inhibits its function probably by the formation of a factor VIIIa-PPS complex. Prothrombinase, constituted of purified factors Xa, Va and phospholipids was not inhibited by PPS, neither were incomplete forms of this enzyme, lacking phospholipids or factor Va. The complete factor X activating enzyme (factors IXa, VIIIa and phospholipids), however, was strongly inhibited, but incomplete forms, lacking factor VIII, were not. The inhibition of the complete enzyme can be explained by reversible binding of PPS to factor VIIIa (causing an inhibition of its function) and it is not an effect on the enzymatic function of the complete enzyme. On saturation of the enzyme with an excess of factor VIIIa no inhibition by PPS is noticed. We postulate therefore that the antithrombin III independent inhibitory effect of PPS on thrombin generation on blood coagulation is by interaction with factor VIIIa. This effect is additional to the heparin-like action of PPS, i.e. potentiation of the activity of antithrombin III and/or heparin cofactor II.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗
PubMed1988

New carbohydrate site in mutant antithrombin (7 Ile----Asn) with decreased heparin affinity.

A mutant antithrombin was isolated from the plasma of a patient with pulmonary embolism. The new protein, which accounted for 55% of the antithrombin, had decreased heparin affinity and contained two components when analysed on the basis of either charge or molecular mass. Sialidase and endo-beta-N-acetylglucosaminidase F treatment suggested that this heterogeneity was due to a partial glycosylation occurring at a new carbohydrate attachment sequence. Peptide mapping by reverse-phase HPLC showed that the abnormality involved the N-terminal tryptic peptide. Sequence analysis demonstrated that the underlying mutation was 7 Ile----Asn which introduces a new Asn-Cys-Thr glycosylation sequence. This new oligosaccharide attachment site occupies the base of the proposed heparin-binding site, and the finding explains the consequent decrease in heparin affinity.

Antithrombin III↗
PubMed1988

Parallel induction of fibrinolysis and receptors for plasminogen and urokinase by interferon gamma on U937 cells.

A new cell sorter technique was employed to study the role of interferon gamma (INF gamma) in fibrinolysis induced by U937 monocytic cells. INF-gamma induced the differentiation of U937 cells as evidenced by the appearance of CD 14 antigen on the cell surface. Scatchard analysis and dose response curves showed a parallel increase in the number of receptors on U937 cells capable of accepting exogenous plasminogen and urokinase (UPA) synthetized by differentiating U937 monocytic cells. This would favour an activation of plasminogen by UPA. This adds a new parameter in the regulation of cell-mediated fibrinolysis and may be important in a number of biological processes.

Cell Line↗
PubMed1988

Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells--inhibition of thrombomodulin-dependent protein C activation.

We have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient's IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient's IgG. The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient's IgG or Fab' fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient's IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.

Animals↗
PubMed1988

Changes in plasma fibrin degradation products as a marker of thrombus evolution in patients with deep vein thrombosis.

The level of fibrin degradation products (fdp) as a marker of fibrin clot dissolution was studied prospectively in 51 patients with phlebographically identified deep vein thrombosis (DVT). For this purpose a highly sensitive fdp assay using an anti D neo monoclonal antibody (McAb) was used. At the onset of the hospitalization, in 47 (92%) of the 51 patients tested, the plasma fdp level performed was high, but does not reflect the size of the thrombus, demonstrating that spontaneous thrombus lysis varies from one patient to another. During 10 days of standard heparin or low molecular weight heparin treatment, two different patterns of fdp evolution could be identified in these patients, independent of the type of heparin used. The first was characterized by a gradual decrease in fdp level and a corresponding reduction in the thrombus size. The second pattern showed a persistence of high levels of fdp after 10 days of therapy although the phlebographic score reveals a poor or partial response indicating that fibrinolysis or the balance of thrombus formation/fibrinolysis did not insure total thrombus dissolution. The 4 patients whose initial plasma fdp levels were only slightly increased during the 10 days, seem to have poor thrombolysis, as was shown by the unmodified phlebographic score after 10 days of treatment. Consequently, we conclude that the investigation of plasma fdp levels with a highly sensitive assay should contribute to the evaluation of thrombus evolution in DVT.

Enzyme-Linked Immunosorbent Assay↗
PubMed1988

Factor VII hyperactivity in acute myocardial thrombosis. A relation to the coagulation activation.

It has been shown that coagulation factor VII (FVII) has an increased coagulant activity (FVIIc) in cardiovascular high risk patients and that it is a important risk factor for the development of ischaemic heart disease (IHD) and cardiovascular death. In this study, we measured FVII coagulant (FVIIc) and immunological (FVIIag) activities during the acute phase of unstable angina (UA) and acute uncomplicated and complicated myocardial infarction (AMI). We have also studied its changes in relation to thrombin formation and coagulation activation, as assessed by determination of thrombin-antithrombin circulating complexes (T-AT) at the same time. Our results show a marked increase in FVIIc in all patients, with highest significant levels in complicated AMI. In fact, this increase was also different between groups, complicated AMI showing a significant degree of increase in FVIIc in relation to UA and uncomplicated AMI. FVIIag did not vary between groups and controls, implicating a progressive activation of FVII. As expected, we found comparable levels of T-AT in UA and in AMI patients, suggesting that a common thrombotic process is involved in both situations. FVIIc was strongly correlated to T-AT in all patients (r = 0. 750; p less than 0.001) and also within groups. This study underlines the important positive contribution of FVIIc to IHD and to the prognosis of its thrombotic acute events, and shows that the increase in FVII activity is associated with an increase of a thrombotic marker (thrombin-antithrombin). Further studies are needed to evaluate if FVII activation is the cause or the consequence of the thrombotic processes.

Angina, Unstable↗
PubMed1988

Enhanced expression of urokinase activity on U 937 cell line by 1,25-dihydroxyvitamin D3 induction.

1,25 Dihydroxyvitamin D3 is a differentiation inducer for monocytic cell. It can induce a monoblastic cell line U937 to differentiate. In this paper, we report that by inducing the differentiation of U937, 1,25-dihydroxyvitamin D3 increased urokinase activity expression on U937 cell surfaces. After incubation of the cell with various concentrations of 1,25-dihydroxyvitamin D3, the cell line showed a remarkable progressively increasing membrane-associated urokinase activity in a dose dependent manner. On the contrary, plasminogen activator inhibitor activity which was found in the culture medium is not modified by the 1,25-dihydroxyvitamin D3 induction. This results suggests another role of 1,25-hydroxyvitamin D3 in the treatment of myelofibrosis, since enhanced plasmin generation can accelerate the activation of procollagenase. The induced plasmin and collagenase activities surrounding the monocytic cells may participate in the physiological and pathological events, especially in the connective tissue degradation.

Calcitriol↗
PubMed1988

Defective thrombolysis due to collagen incorporation in fibrin clots.

The migration of fibroblasts into a clot may be responsible at least in part, for its organization, thus leading to a defective thrombolysis. We have shown that collagen incorporated in a fibrin clot induces a dramatic decrease in fibrinolysis. Despite the fact that plasminogen binds to collagen, tissue plasminogen activator induced plasminogen activation in the presence of fibrin is only slightly decreased by the presence of collagen. This rather suggests that collagen induces a modification in clot structure, by rendering fibrin less accessible to fibrinolytic enzyme.

Animals↗
PubMed1988

Association between coagulation factors VII and X with triglyceride rich lipoproteins.

The association between the concentration of different plasma lipoproteins and plasma factor VII (F VII) was analysed by isolating plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) lipoproteins and assessing their in vitro interaction with F VII by immunoenzyme assay using peroxidase labelled anti-factor VII immunoglobulins to determine whether F VII coagulant activity is prognostic for cardiovascular mortality. F VII bound to triglyceride rich lipoproteins, the fixation being stronger on chylomicrons and VLDL fractions than on LDL fractions. In our experiments HDL did not bind to F VII. The fixation of coagulation factor X (FX) tested by the same method is comparable with that of F VII. The nature of this fixation seemed to arise from hydrophobic interaction as calcium was not necessary and the use of Tween 20 inhibited the interaction. The binding of factors VII and X was increased when lipids were previously treated by phospholipase C and the interaction seemed to be completely dependent on the lipid part of the lipoproteins. Hyrophobic fixation is a possible mechanism of interaction of plasma lipoproteins and F VII and X, and it may be of importance in the covariance of triglyceride concentrations and the activity of vitamin K dependent coagulation factors.

Adult↗
PubMed1988

Proposed heparin binding site in antithrombin based on arginine 47. A new variant Rouen-II, 47 Arg to Ser.

Antithrombin Rouen-II, a new inherited variant of antithrombin-III, was found in two members of a family with no definite history of thrombosis. The subjects had normal antigenic concentrations of antithrombin and normal progressive inhibitory activity. However, the variant had defective heparin and heparan sulfate cofactor activities, and was not activated by a synthetic pentasaccharide representing the minimum heparin sequence. The abnormal antithrombin was isolated using heparin-Sepharose chromatography, and on electrophoresis at pH 8.6 migrated more anodally than normal. Two-dimensional peptide mapping of tryptic and Staphylococcus aureus V8 protease digests was performed and the abnormal peptide was located by tryptophan staining. Amino acid sequence studies demonstrated a substitution of arginine at residue 47 by a serine. Evidence strongly suggests that arginine 47 is a prime heparin binding site in antithrombin and that it forms part of a proposed positively charged linear site (to which heparin binds) that stretches across the surface of the molecule from the A to the D helix.

Adult↗