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Biomedical subjects

C Soria

Publications and source records attributed to C Soria.

At least 19 recordsLinked to original sources
PubMed1996

Evidence of involvement of CD44 in endothelial cell proliferation, migration and angiogenesis in vitro.

Angiogenesis is essential for tumor growth and metastasis. In the process of angiogenesis, the interaction between adhesive proteins of endothelial cells and extracellular matrix components plays an important role by mediating cell attachment, which is indispensable for their motility, and by transmitting the regulatory signals for cell locomotion and proliferation. In this study, we examined the hypothesis that CD44 expressed on the endothelial cell surface is involved in the angiogenesis process. The experiments using calf pulmonary artery endothelial cells (CPAE) and a human microvascular endothelial cell line (HMEC-1) show that a monoclonal antibody against CD44 (clone J 173) inhibits endothelial cell proliferation by about 30% and migration by 25-50%, and abolishes the stimulating effect of hyaluronan polysaccharides on endothelial cell migration and proliferation. This antibody also suppresses the capillary formation of CPAE in an in vitro model of angiogenesis using fibrin matrix. These results provide evidence of the involvement of endothelial-cell-associated CD44 in angiogenesis.

Animals↗
PubMed1996

The relationship between the fibrinogen D domain self-association/cross-linking site (gammaXL) and the fibrinogen Dusart abnormality (Aalpha R554C-albumin): clues to thrombophilia in the "Dusart syndrome".

Cross-linking of fibrinogen at its COOH-terminal gamma chain cross-linking site occurs in the presence of factor XIIIa due to self-association at a constitutive D domain site ("gammaXL"). We investigated the contribution of COOH-terminal regions of fibrinogen Aalpha chains to the gammaXL site by comparing the gamma chain cross-linking rate of intact fibrinogen (fraction I-2) with that of plasma fraction I-9, plasmic fraction I-9D, and plasmic fragment D1, which lack COOH-terminal Aalpha chain regions comprising approximately 100, approximately 390, and 413 residues, respectively. The cross-linking rates were I-2 > I-9 > 1-9D = D1, and indicated that the terminal 100 or more Aalpha chain residues enhance gammaXL site association. Fibrinogen Dusart, whose structural abnormality is in the COOH-terminal "alphaC" region of its Aalpha chain (Aalpha R554C-albumin), is associated with thrombophilia ("Dusart Syndrome"), and is characterized functionally by defective fibrin polymerization and clot structure, and reduced plasminogen binding and tPA-induced fibrinolysis. In the presence of XIIIa, the Dusart fibrinogen gamma chain cross-linking rate was about twice that of normal, but was normalized in proteolytic fibrinogen derivatives lacking the Aalpha chain abnormality, as was reduced plasminogen binding. Electron microscopy showed that albumin-bound Dusart fibrinogen "alphaC" regions were located in the vicinity of D domains, rather than at their expected tethered location near the fibrinogen E domain. In addition, there was considerable fibrinogen aggregation that was attributable to increased intermolecular COOH-terminal Aalpha chain associations promoted by untethered Dusart fibrinogen aC domains. We conclude that enhanced Dusart fibrinogen self-assembly is mediated through its abnormal alphaC domains, leads to increased gammaXL self-association and gamma chain cross-linking potential, and contributes to the thrombophilia that characterizes the "Dusart Syndrome."

Dextrans↗
PubMed1996

Blockage of urokinase receptor reduces in vitro the motility and the deformability of endothelial cells.

The binding of urokinase (u-PA) to its cell surface receptor (u-PAR) is critical for tumor cell invasion. Here, we report that the distribution of this binding by a u-PAR antagonist ATF-HSA inhibits in vitro the motility of endothelial cells in a dose-dependent manner. This inhibition was also observed when the cells were first stimulated with potent angiogenic factors, including bFGF or VEGF. [3H]thymidine incorporation assay demonstrated that ATF-HSA did not affect the cell proliferation. ATF-HSA was more potent than plasmin inhibitors, suggesting that it exerts its effects not solely by inhibiting the remodeling of the extracellular matrix. In fact, analysis of the cell shape change during migration revealed for the first time that its effect is related to a decrease in cell deformability. These results suggest that u-PAR antagonist may be a new approach to control angiogenesis.

Aprotinin↗
PubMed1996

Fibrinogen binding and platelet retention: relationship with the thrombogenicity of catheters.

One of the major problems in the use of catheters is their thrombogenicity, since the embolization of clots near the central nervous system or the coronary arteries can cause permanent damage. In this work we have compared the in vivo thrombogenicity of four different angiography catheters and their in vitro activation of fibrinogen binding and platelet retention. The thrombogenicity of catheters has been evaluated in angiographic conditions by kinetic evaluation of the reduction of blood flow rate through the catheters. The binding of adhesive proteins (fibrinogen and von Willebrand factor [vWF] was studied in vitro using a direct-ELISA technique after circulation of anticoagulated whole blood through sections of catheters. The retention of platelets was studied in vitro using 111Indium-labelled platelets. Fibrinogen binding and platelet retention both seem to be good predictors of catheter thrombogenicity, fibrinogen being the better of the two. The most thrombogenic material has the highest fibrinogen and platelet retention rate. This study also confirms the inefficiency of albumin precoating for the prevention of fibrinogen deposition. The determination of fibrinogen deposition by direct-ELISA technique and platelet retention rate is very useful for preclinical testing of catheters.

Biocompatible Materials↗
PubMed1996

Fibrinogen Dusart: electron microscopy of molecules, fibers and clots, and viscoelastic properties of clots.

Ultrastructural perturbations resulting from defects in polymerization of fibrinogen Dusart, a congenital dysfibrinogenemia with the amino acid substitution A alpha 554 arginine to cysteine, were investigated by a variety of electron microscope studies. Polymerization of this mutant fibrinogen on addition of thrombin is impaired, producing clots with decreased porosity and increased resistance to fibrinolysis, resulting in thrombotic complications in the family members with this dysfibrinogenemia. Electron microscopy of rotary-shadowed individual molecules revealed that, in contrast to control fibrinogen, most of the alpha C domains of fibrinogen or fibrin Dusart appeared to be free-swimming appendages that do not exhibit intra- or intermolecular interactions either with each other or with the central domains. The location of albumin on the alpha C domains was demonstrated by electron microscopy using anti-albumin antibodies. Electron microscopy of negatively contrasted fibrin Dusart fibers indicated that they were less ordered than control fibers and had additional mass visible. Electron microscopy of freeze-dried, unidirectionally shadowed fibers showed that they were twisted with a shorter pitch. Scanning electron microscopy revealed that intact clots were made up of thin fibers with many branch points and very small pore sizes. The viscoelastic properties of Dusart fibrin clots measured with a torsion pendulum indicated a marked increase in stiffness consistent with the structural observations.

Biomechanical Phenomena↗
PubMed1996

Down-regulation of fibrinogen biosynthesis by IL-4, IL-10 and IL-13.

High levels of fibrinogen are recognized as an important vascular risk factor; however, it is not known if the increase of plasma fibrinogen is directly responsible for this risk, or is only a marker of vascular inflammation. To support this second hypothesis, Oncostatin M (OSM) is a potent stimulator of fibrinogen biosynthesis and induces smooth muscle cell proliferation. In the same way, we analysed whether interleukin-4 (IL-4), interleukin-10 (IL-10) or interleukin-13 (IL-13), which protect vessel walls from monocytes injuries leading to atherosclerosis, could influence fibrinogen biosynthesis. The two levels of regulation of fibrinogen biosynthesis were tested: firstly, the direct effect of these cytokines on fibrinogen production by the hepatoma cell line Hep G2, and secondly their effect on the secretion of hepatocyte stimulating factor (HSF) activity in the supernatant of lipopolysaccharide (LPS)-activated monocytes. IL-4 and IL-13 added to Hep G2 cells down-regulated both the increase of fibrinogen secretion induced by IL-6 and fibrinogen mRNA levels, this effect being more pronounced when Hep G2 were preincubated with the two cytokines before IL-6 addition. The effect of IL-10 was evidenced only on mRNA expression. IL-10 and IL-13 dose-dependently decrease HSF activity secreted by LPS-activated monocytes, whereas IL-4 had no effect. However, the three cytokines decreased HSF activity when monocytes were incubated with the cytokines before LPS activation. The effects of these cytokines on HSF activity are related to variations of IL-6 and OSM secretion. Our data strengthen the hypothesis that the fibrinogen level is a marker of vascular disease, since cytokines which have a protective vascular effect down-regulate fibrinogen production.

Animals↗
PubMed1995

An autoradiographical saturation kinetic study of the different benzodiazepine binding sites in rat brain by using [3H] flunitrazepam as a radioligand.

The present study reports on the equilibrium association constant (KD) and receptor density (Bmax) values of a number of brain areas from the mesencephalon, cerebral cortex, hippocampus, and cerebellum for the overall benzodiazepine (BZ) binding sites as well as for benzodiazepine binding site subtype 1 (BZ1) and subtype 2 (BZ2), determined by autoradiographical procedures using [3H] flunitrazepam. The differences between BZ1 and BZ2 binding sites were analyzed using the specific BZ1 agonist zolpidem as inhibitor of the radioligand. Statistically significant differences in the affinities of BZ2 with respect to BZ and BZ1 binding site were mainly found in cortical layers when pKD (negative logarithms of KD values) values were compared (ANOVA-SNK test). The distribution of Bmax, as well as the percentages of BZ1 and BZ2 and Hill coefficients which, surprisingly, are always close to 1 (> 0.9) for all the saturation kinetics analyzed, are also described. The possibility of heterogeneity related to anatomical distribution in the different subtypes is discussed.

Analysis of Variance↗
PubMed1995

The effect of platelets on invasiveness and protease production of human mammary tumor cells.

Interaction of tumor cells with platelets facilitates metastasis of tumor cells. It has been proposed that platelets protect tumor cells against the host's immune defense and enhance tumor-cell extravasation. In the present work we show that platelets increase the invasiveness of 3 mammalian cell lines (MCF-7, ZR-51 and MDA-MB231) through extracellular matrix, and propose this as an additional mechanism by which platelets facilitate metastasis. Since gelatinase and urokinase have both been implicated in degradation of the extracellular matrix and cell migration, and therefore in tumor invasion, we have also analyzed whether the interaction of platelets with tumor cells can modify the secretion of these proteases by tumor cells. MDA-MB231, which was the most invasive cell line among the 3 tested and was the most potent in inducing platelet aggregation, secreted the highest level of urokinase and was the only one in which gelatinase was detected. While platelets had no significant effect on the urokinase activity expressed by these cells, they induced in MDA-MB231 an important increase in the secretion of gelatinase, which can be reproduced by both platelet membrane and platelet releasate of activated platelets. This increase in gelatinase could be responsible, at least in part, for the increased invasiveness of these cells, since added TIMP-1 significantly reduced the number of cells which traversed matrigel.

Blood Platelets↗
PubMed1995

Expression of elastase and fibrin in venous leg ulcer biopsies: a pilot study of pentoxifylline versus placebo.

The pathogenesis of venous leg ulcers is based on the leakage of fibrinogen leading to a pericapillary fibrin cuff and plugging of capillaries by white blood cells. On the basis of a previous work, we had assumed that the key event in the pathogenesis of venous leg ulcers is related to inflammation generated by activated white blood cells that accumulate under unrelieved blood pressure, because in ulcer biopsies we had detected the presence of tumor necrosis factor-alpha (TNF-alpha) in intracapillary monocytes, elastase in the polymorphonuclear leukocytes near the vessels, and a pericapillary undegraded fibrin cuff causing a diffusion barrier to oxygen. This concept was developed because TNF-alpha synthesized by activated monocytes is responsible for many deleterious effects. It has a potent mitogenic effect on fibroblasts, leading to new collagen deposition and angiogenesis, it induces an increase in collagenase production, it acts through upregulation of an intracellular adhesion molecule (ICAM-1), leading to leukocyte sequestration and consequently a release of toxic metabolites by the polymorphonuclear cells, an early step in chronic inflammation, it activates the coagulation pathway via a marked increase in monocyte-associated tissue factor (TF) procoagulant activity, and it inhibits fibrinolysis by promoting the release of PAI-1, contributing to undegraded fibrin deposition. Therefore, we were interested in evaluating, in patients with venous leg ulcers, the effect of pentoxifylline administered at 1,200 mg daily (versus placebo) for 2-months, as this drug induces a decrease in TNF-alpha synthesis and also blocks its activity. This pilot assay was performed in blind. Evolution of several parameters in ulcer biopsies are analyzed: TNF-alpha, intact fibrin, fibrin degradation products, ICAM-1, TF, and elastase. Pentoxifylline administration induced a decrease of local elastase and of fibrin deposit. These results support the hypothesis that accumulation of activated leukocytes is the key event in venous leg ulcers.

Antibodies, Monoclonal↗
PubMed1995

Severe arterial thrombosis in a congenitally factor VII deficient patient.

We report a patient with congenital factor VII deficiency who developed severe arterial thrombosis. A 63-year-old-woman presented low factor VII clotting activity, amidolytic activity and antigen level < 4%. Activated factor VII plasmatic level was < 0.03 ng/ml compared to 4 ng/ml for the control value. She developed severe aorto-iliac thrombosis. 7 d before the thrombotic event, factor VII replacement therapy had been infused. Successful low molecular weight heparin therapy led to total disappearance of the aorto-iliac thrombus without bleeding complications. This suggests that factor VII infusion might have a thrombogenic effect in vivo and might be responsible for thrombosis.

Aortic Diseases↗
PubMed1994

Blockage of the urokinase receptor on the cell surface: construction and characterization of a hybrid protein consisting of the N-terminal fragment of human urokinase and human albumin.

Receptor-bound urokinase is likely to be a crucial determinant in both tumor invasion and angiogenesis. We report here that a yeast-derived genetic conjugate between human serum albumin and the 1-135 N-terminal residues of urokinase (u-PA) competitively inhibits the binding of exogenous and endogenous u-PA to its cell-anchored receptor (u-PAR). This hybrid molecule (ATF-HSA) also inhibits in vitro pro-urokinase-dependent plasminogen activation in the presence of u-PAR bearing cells. These effects are probably responsible for the observed in vitro inhibition of tumor cell invasion in a reconstituted basement membrane extract (Matrigel).

Cell Line↗
PubMed1994

Identification of beta-adrenoceptors in rat lymph nodes and spleen: an autoradiographic study.

The anatomical localization of beta 1 and beta 2-adrenoceptors was studied in rat lymphoid tissues by quantitative autoradiography using [125I]cyanopindolol as a ligand. In lymph nodes, a significant density of these receptors was found in the medullary cords and the interfollicular cortex, while only low densities were observed in the paracortex. No detectable binding appeared in the remaining areas. In the spleen, these receptors were mainly localized in the capsule, marginal zone of white pulp and red pulp, while the labelling over the white pulp was extremely low. The subtype beta 2 was predominant in both lymph nodes and spleen. The results suggest that beta-adrenoceptors are present in mature cells in lymphoid tissues and are probably not involved in homing mechanisms.

Adrenergic beta-Antagonists↗
PubMed1994

Effect of morphine and abstinence syndrome on [3H]bromoxidine binding to alpha 2-adrenoceptors in rat brain.

At 4 days after the implantation of two subcutaneous 75 mg morphine pellets in the back skin, rats were morphine-dependent. In the three layers studied in the occipital cortex we found that the values of the alpha 2-adrenergic agonist [3H]bromoxidine binding increased with respect to animals implanted with placebo pellets. Typical behavioral and physiological symptoms of the abstinence syndrome appeared 30 minutes after administration of naloxone, [3H]bromoxidine binding values being similar to those obtained in animals implanted with placebo pellets. The pattern of response of the [3H]bromoxidine binding was similar in the hippocampus and the superficial gray layer of the superior colliculus of the mesencephalon, but the differences were not statistically significant in these areas. This paper concludes that exist brain regional differences in the alpha 2-adrenoceptors response under morphine-treatment and possibly under naloxone-induced morphine abstinence syndrome.

Adrenergic alpha-Agonists↗
PubMed1994

Recombinant hirudin: a specific thrombin inhibiting anticoagulant for hemodialysis.

The first experience with hirudin as an alternative anticoagulant for heparin in hemodialysis is reported. Recombinant hirudin (HBW 023) was administered in 20 patients as a bolus before dialysis with low flux polysulfone dialyzers (PS400), the dosage being adapted stepwise from patient to patient by 0.02 mg/kg to the occurrence of clotting or bleeding. Four different administration schedules were studied. The first three schedules (0.02 mg/kg, N = 1; 0.04 mg/kg, N = 1; 0.06 mg/kg, N = 4) were discontinued because of clotting. The 0.08 mg/kg schedule was maintained without clotting event in 14 patients. Bleeding was not observed. Plasma hirudin averaged 503.9 +/- 214.0 and 527.7 +/- 217.1 ng/ml after two and four hours of dialysis, and decreased during an interdialytic interval of 44 hours to 223.2 +/- 86.2 ng/ml. Modified antithrombin III (P < 0.05) and activated partial thromboplastin times were lower (P < 0.01) under hirudin compared to heparin; these coagulation parameters were closer to normal during hirudin treatment. The patients developing clotting could be distinguished from those without clotting by the registration of the activated clotting times (9.2 +/- 3.0 vs. 18.7 +/- 3.2 min after 2 hr, P < 0.01; 8.1 +/- 3.0 vs. 16.2 +/- 3.8 min after 4 hr of dialysis, P < 0.05); cut-off value below which clotting is to be expected was 12 min). It is concluded that administration of hirudin as a bolus before the start of dialysis, at a dosage of 0.08 mg/kg, is not complicated by clotting or by bleeding. Coagulation tendency can optimally be monitored by the registration of the activated clotting time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Value of PCR detection of TCR gamma gene rearrangement in the diagnosis of cutaneous lymphocytic infiltrates.

In this study, we analyzed the reliability and usefulness of the polymerase chain reaction (PCR) for the detection of T-cell receptor (TCR)gamma gene monoclonal rearrangement. We first tested for the specificity and sensitivity of this strategy, against the classical criteria of Southern blot analysis (SBA). Of the 27 samples tested, results agreed in all but two. Broader analysis of these cases demonstrated the high specificity (absence of false positives) of the PCR strategy, together with its limited sensitivity (10% of false negatives). The usefulness of this PCR approach was then tested on a panel of 28 biopsy specimens of cutaneous lymphocytic infiltrates. Monoclonal TCR gamma rearrangement was detected in seven of eight cases of early stage mycosis fungoides (MF), one of two Sezary syndrome (SS) cases, two of two non-MF T-cell lymphoma, and two of three lymphomatoid papulosis. Monoclonality was not detected in any of the 11 benign cases (parapsoriasis and inflammatory dermatosis). Results obtained with this new molecular strategy provide additional support for the hypothesis of a monoclonal origin for most early stage T-cell MF. They also suggest the heterogeneous nature of some lymphomatoid papulosis lesions. Therefore, due to the difficulty in detecting T-cell monoclonality by immunohistochemical techniques, PCR can be a useful alternative strategy to SBA. It could also be used as a complementary technique in the routine diagnosis of T-cell cutaneous infiltrates.

Adolescent↗