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Biomedical subjects

C Soria

Publications and source records attributed to C Soria.

At least 109 records · Page 6Linked to original sources
PubMed1993

Urinary acidification response to furosemide administration in patients on low-dose cyclosporine therapy.

The response of urinary acidification parameters and electrolytes to furosemide administration was prospectively studied in 9 psoriatic patients treated with a low-dose cyclosporine A schedule (initial dose: 5 mg/kg body weight) before beginning cyclosporine A, after 3 months on cyclosporine A and 1 month after cyclosporine A withdrawal. The test was also performed in 29 psoriatic patients after 3 months on 5 mg/kg body weight cyclosporine A treatment. There were no significant differences between before and after cyclosporine A treatment regarding furosemide-induced changes in urinary volume, sodium or potassium excretion. Contrarily, the post-furosemide urinary pH decrease and ammonium and titrable acid increase were significantly lower in cyclosporine-A-treated patients. Five of the 29 studied patients showed abnormal furosemide tests (17%). These patients had lower total serum CO2, urea and creatinine but similar serum potassium and fractional potassium excretion. We conclude that some patients treated with low-dose cyclosporine A therapy develop an abnormal tubular distal response to furosemide administration, suggesting an alteration in the H(+)-ATPase pump or a voltage-dependent mechanism.

Adult↗
PubMed1993

Molecular basis for fibrinogen Dusart (A alpha 554 Arg-->Cys) and its association with abnormal fibrin polymerization and thrombophilia.

The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C-->T) in the A alpha-chain gene, resulting in the amino acid substitution A alpha 554 Arg-->Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen-albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (A alpha 554 Arg-->Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals.

Adult↗
PubMed1993

[Fibrinogen, a vascular risk factor].

Epidemiological studies have consistently correlated plasma fibrinogen level to the risk of coronary heart disease (CHD) and acute ischemic stroke. Several mechanisms have been proposed such as the role of fibrinogen in the viscosity of blood, the participation of fibrinogen in both fibrin clot formation and platelet aggregation. However, there is no evidence that the increase in fibrinogen is directly responsible for the vascular disease since the cytokines which participate to the synthesis of fibrinogen by the hepatocytes, such as interleukin 6, could also induce an endothelial cell damage by increasing tumor necrotic factor (TNF) production. In these conditions fibrinogen increase could therefore only represent a marker of cytokine production which in turn is responsible for vascular injury. In addition, for the pathogenesis of atherosclerosis, the influence of fibrinogen is not only mediated by way of increased fibrinogen concentration but could be due to a structurally variant fibrinogen. The recent epidemiological studies have shown that the variation at the beta locus of fibrinogen is associated with an increase risk of peripheral atherosclerosis. The finding concerning dysfibrinogenemia and thrombosis (Dusart and Tampere) create further opportunities to enrich knowledge of the link between the association of abnormal gel structure and thrombotic diseases such as myocardial infarction or stroke at young age. This abnormal clot structure could contribute to thrombogenicity by decreasing the capacity of these clots to be degraded by fibrinolytic enzymes or by decreasing thrombin binding since fibrin is considered as a "thrombin trap".(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrinogen↗
PubMed1993

Potent activity of peripheral blood lymphocytes in inducing hepatocyte stimulating factor and urokinase in monocytes.

As fibrinogen is an independent risk factor for arterial thrombosis we were interested in analysing the mechanism controlling fibrinogen biosynthesis. In this work, we showed that incubation of monocytes with lymphocytes increased hepatocyte stimulating factor (HSF) production. Different mechanisms are involved and our results demonstrated that this effect is in part mediated by an increase in interleukin 6 (IL-6) production. However, IL-6 cannot account for the whole effect and other cytokines could be implicated. In addition, we observed a stimulation of urokinase-type plasminogen activator (u-PA) associated with monocytes when these cells were incubated with lymphocytes for 18 h at 37 degrees C. By producing fragment D (fibrinogen degradation product) and D-dimer (fibrin degradation product) this fibrinolytic activity might also contribute to fibrinogen biosynthesis by hepatocytes.

Cells, Cultured↗
PubMed1993

Incubation of monocytes with adriamycin increases secretion of hepatocyte stimulating factor for fibrinogen biosynthesis.

This work provides evidence that the production by monocytes of hepatocyte stimulating factor(s) for fibrinogen biosynthesis was dramatically increased when monocytes were exposed to Adriamycin. This effect was related to an increased production of leukaemia inhibiting factor (LIF), a cytokine known to stimulate fibrinogen biosynthesis by hepatic cells. Adriamycin also induces an increase in membrane-associated urokinase on monocytes. These results are consistent with the clinical observation in patients with ovarian cancer that when the CA-125 tumour marker decreases during chemotherapy, an increased level of D-dimer is a marker of good prognosis.

Cells, Cultured↗
PubMed1993

The polymerization of fibrinogen Dusart (A alpha 554 Arg-->Cys) after removal of carboxy terminal regions of the A alpha-chains.

The six polypeptide chains of normal fibrinogen are covalently linked by interchain disulphide bonds, and there are no free sulphydryl groups. Fibrinogen Dusart is a congenital fibrinogen variant in which A alpha 554 Arg is replaced by Cys; albumin is disulphide linked to these fibrinogen molecules, possibly at A alpha 554 Cys. Functionally, Dusart fibrinogen displays markedly abnormal fibrin polymerization, characterized by delayed lateral fibril association and matrix fibre bundles that are thinner than normal fibrin bundles. These observations are consistent with experiments suggesting that the carboxy terminal region of the A alpha-chain contains a polymerization domain that participates in lateral fibril associations. In order to investigate the location and the effect of albumin binding to Dusart fibrinogen, we examined the fibrinogen by electron microscopy, and compared the polymerization and ultrastructure of fibrin prepared from normal fibrinogen containing intact A alpha-chains (fraction I-2) or plasmin degraded fibrinogen molecules lacking carboxy terminal regions of A alpha-chains (fraction I-9D), with fibrin prepared from Dusart fraction I-2 and I-9D. Most bound albumin was released from Dusart fibrinogen by plasmin degradation involving the A alpha-chains. Nevertheless, we were able to visualize albumin molecules remaining covalently bound to Dusart I-9D as well as to Dusart I-2 fibrinogen, as distinct globular domains situated near the fibrinogen D domain. The presence of albumin in these fractions was confirmed by Western blotting using anti-albumin. Dusart fibrin polymerized much more slowly than normal I-2, as previously reported, whereas polymerization of Dusart I-9D fibrin was faster than Dusart I-2 and nearly the same as normal I-9D fibrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1992

Plasminogen activators in the neuromuscular system of the wobbler mutant mouse.

Wobbler, the neurological mutant mouse, carries an autosomal recessive gene (wr) and has been characterized as a model of lower motoneuron disorders with associated muscle atrophy, denervation and reinnervation. During normal murine neuromuscular development a decrease in muscle plasminogen activator (PA) activity accompanies synapse maturation. In contrast, experimental denervation in adult mice leads to an increase in muscle PA activity. The purpose of the present study was to determine the possible involvement of PAs in the denervation/reinnervation phenomena and motoneuron degeneration that characterize the wobbler mutant mouse. We determined the degree of innervation and its characteristics in wobbler mice by measuring choline acetyltransferase (ChAT) activity. We measured ChAT in the spinal cord as well as in two different muscles known to be differentially affected, biceps brachii and gastrocnemius. We found a sharp decrease of ChAT activity in both muscles but not in spinal cord extracts. We estimated the extent of sprouting by the silver/cholinesterase stain. Motoneuron terminal sprouting, not detected in normal animals, was present in 40% of the neuromuscular junctions in wobbler mice. We estimated specific PA activities in biceps brachii and gastrocnemius muscle extracts, as well as spinal cord extracts, using both an amidolytic assay and fibrin zymography. Increased PA, predominantly urokinase-PA (uPA), was observed in wobbler mouse muscle. A greater uPA was detected in biceps brachii muscle than in gastrocnemius muscle, which is less impaired by the mutation. There was no change in spinal cord PA, although tissue type PA (tPA) is the predominant PA type there.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗
PubMed1992

D-dimer and CA 125 levels in patients with ovarian cancer during antineoplastic therapy. Prognostic significance for the success of anti-cancer treatment.

In patients with ovarian cancer before they receive chemotherapy, the level of fibrin degradation products (D-dimer), is correlated with the tumor load. In this study, the evolution of D-dimer was compared in patients receiving antineoplastic therapy with the evolution of the disease. The patients could be classified into three groups. In Group 1 (nine patients), both plasma CA 125 (a tumor-associated antigen) and D-dimer remained elevated; the prognosis was always poor. In Group 2 (eight patients), CA 125 and D-dimer decreased simultaneously, complete remission was observed in two patients, and significant residual tumor was observed in the others. In Group 3 (nine patients), despite an important decrease in CA 125, D-dimer remained elevated during therapy. In this group, complete remission was observed in six patients, and three others showed a large decrease in their tumor load. The combination of a decrease in CA 125 levels with a continuous enhanced level of D-dimer during chemotherapy identified a subgroup of patients with a favorable prognosis.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Effect of heparin and enoxaparin on platelet interaction with fibrin clots.

It has been recently shown that platelet-rich thrombi are particularly resistant to thrombolysis. Since unfractionated heparin was reported to enhance fibrinogen binding to platelets responsible for the hyperaggregating effect of this drug, the purpose of this work was to determine whether or not heparin could also modulate platelet interaction to whole blood clot. We have therefore investigated the retention to a standard clot of 111In-labelled platelets suspended in plasma in presence of saline (control), heparin or a low molecular weight heparin (Enoxaparin). We have shown that the platelet interaction to the clot was significantly increased by heparin but not by enoxaparin used at the same anti Xa activity. In conclusion, this difference may favor the use of enoxaparin over heparin in clinical situation associated with platelet retention to fibrin clot, such as thrombolysis.

Blood Platelets↗
PubMed1992

Subclinical impairment of distal renal acidification induced by low-dose cyclosporin A therapy.

Twenty-nine psoriasis patients on 5 mg/kg cyclosporin A (CyA) therapy were studied for 3 months using the furosemide test. Five of them (17%) showed an abnormal renal acidification capacity after furosemide administration: The urinary pH did not sink under 5.3 after furosemide, while the ammonium and titrable acid levels were significantly low. There were no significant differences from controls regarding the serum potassium or fractional potassium excretion. Nevertheless, the transtubular potassium gradient was lower in patients with an abnormal furosemide test result. We conclude that some patients treated with a low dose CyA therapy developed an abnormality in the distal tubular acidification.

Adult↗
PubMed1992

True histiocytic lymphoma (monocytic sarcoma)

The clinical, histological, immunophenotypic, and genotypic characteristics of two cases of cutaneous genuine histiocytic lymphoma are described. Both cases presented as cutaneous lesions. Both patients remain alive and free of disease at 26 and 10 months after the diagnosis and after having been treated with polychemotherapy. Neither peripheral blood nor bone marrow infiltration was detected in either case. Histological and immunophenotypic examination showed dense, diffuse dermic infiltrates of mononuclear cells with positive macrophage-associated markers (CD11c, CD68), and negative T- or B-cell-associated antigens. A germline configuration of both T-cell receptor and immunoglobulin genes was observed in gene rearrangement studies. Although most of the cases that have been diagnosed as histiocytic lymphoma or malignant histiocytosis in the past turned out to be B- or T-large-cell lymphomas, a small number of cases (two in our consecutive series of 350 cases) show characteristics of monocyte-macrophage tumors. We stress the importance of the CD68 marker in the diagnosis of true histiocytic lymphoma, suggest a therapeutic approach based on similarities with monocytic leukemia, and propose the use of the term monocytic sarcoma for this clinicopathological presentation.

Female↗
PubMed1991

[Serologic and genomic markers of the hepatitis C virus in transfusion recipients with non-A, non-B hepatitis].

BACKGROUND: The exclusion of donors with antibodies against the c-100 protein of the hepatitis C virus (HCV) has permitted a considerable reduction in post transfusional (PTH) non A non B hepatitis in those receiving transfusions. However, the risk has not been completely eliminated and there is evidence that some HCV carriers do not present detectable antibodies against protein c-100. In these cases a new diagnostic methodology, named polymerase chain reaction (PCR), permits the detection of the viral genome. METHODS: One hundred fifty eight prospective transfusion recipients were studied. Nineteen (12%) developed non A non B PTH criteria. The presence of anti c-100 and the viral genome were investigated by PCR in 17 of the patients. RESULTS: Nine of the 17 receptors (53%) with non A non B PTH presented antibodies against the HCV. In all patients and in two seronegative patients genomic sequences of HCV were detected by PCR. CONCLUSIONS: By a combination of genomic (PCR) and serological technique, 11 of the 17 transfusion recipients (64%) with non A non B PTH demonstrated evidence of HCV infection. In two cases the infection was seronegative. Although the HCV appeared to be the principal agent of the non A non B PTH in this study it could not be recognized in a third of the recipients who developed non A non B PTH.

Adult↗
PubMed1991

Hemostasis in patients undergoing extracorporeal circulation: the effect of aprotinin (Trasylol).

The administration of aprotinin during extracorporeal circulation (ECC) reduces blood loss. To explore the mechanism of this effect, a placebo-controlled double-blind study was performed in 20 patients (10 were administered with a high dose of aprotinin, 10 with placebo) undergoing a primary, elective operation of coronary artery bypass grafting (CABG) with ECC. Biological tests were performed at 4 different time points during the operation. A marked reduction in the placebo group of ristocetin-induced platelet agglutination (binding of von Willebrand factor [vWF] to platelet glycoprotein [GP] Ib) was shown during ECC and at the end of surgery, but not in the aprotinin group. This abnormality is not related to the hydrolysis of vWF or GP Ib, since washed platelets were resuspended in pooled normal plasma which provided a constant amount of vWF in this test and since the plasma concentration of the fragment of GP Ib (glycocalicin) did not correlate with this abnormality. Despite a high concentration of heparin (5-7 IU/ml) in patient's plasma during bypass, activation of blood coagulation in both groups was evidenced by an increase in ATm (thrombin-modified antithrombin III) level. The level of ATm in the placebo group reached a maximum at the end of ECC during rewarming, while in the aprotinin group, ATm level at this time point was significantly lower than in the control group. In comparison to the placebo group, the generation of the fibrin degradation products (DDE complexes) was inhibited by aprotinin during ECC, but the level of DDE complexes in the aprotinin group was slightly elevated after ECC, although much less than in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1991

Temperature dependence of plasmin-induced activation or inhibition of human platelets.

It is known that at 37 degrees C plasmin may have two opposite effects on platelets: at high concentrations (greater than 1.5 caseinolytic units [CU]/mL), plasmin activates platelets; at lower concentrations (0.1 to 1.0 CU/mL) it inhibits platelet activation induced by thrombin, collagen, or calcium ionophore A23187. In this study, we report that when lowering the incubation temperature to 22 degrees C, plasmin at low concentrations (0.1 to 0.5 CU/mL) fully activated platelets. When platelets were treated with 0.2 CU/mL of plasmin, lowering the incubation temperature from 37 degrees C to 22 degrees C resulted in an increase in the expression of fibrinogen receptors, in platelet release and aggregation. Thromboxane A2 was not generated by plasmin treatment at either temperature. Ultrastructural studies showed that platelets responded to low-dose plasmin at 37 degrees C by forming pseudopods, centralizing granules without fibrinogen release, whereas at 22 degrees C the same dose of plasmin caused platelet degranulation with the appearance of alpha-granule fibrinogen within the lumen of the surface connected canalicular system. In addition, at 22 degrees C plasmin at doses insufficient to induce platelet aggregation potentiated platelet response to thrombin. Thus, we suggest that plasmin may initiate both activating and inhibitory processes within platelets and that the change of temperature could influence this balance. These results may be of clinical relevance, because the fibrinolytic system was found activated during cardiopulmonary bypass in which the temperature of patient's blood circulation was reduced. This temperature-dependent behavior is also an interesting model for a further study on platelet response to serine proteinases.

Antibodies, Monoclonal↗
PubMed1991

Differential redistribution of platelet glycoproteins Ib and IIb-IIIa after plasmin stimulation.

The subcellular localization of the platelet membrane receptors glycoproteins (GP) Ib and IIb/IIIa [corrected] has been studied within resting platelets by a combination of biochemical and cytochemical techniques. While both GPIb and GPIIb/IIIa are localized within the plasma membrane and surface-connected canalicular system (SCCS) membranes, only GPIIb/IIIa is present within the internal face of alpha-granular membranes. Previous studies demonstrated that plasmin can induce platelet stimulation and also decrease ristocetin-induced platelet aggregation; it was suggested that this was because of GPIb degradation by plasmin. In this study, the respective localizations of both GPIb and GPIIb/IIIa were visualized during in vitro plasmin stimulation of platelets. Generally, plasmin induced shape change, pseudopod formation, organelle centralization either with or without alpha-granule release depending on the conditions of stimulation. Plasmin treatment of platelets at 37 degrees C resulted in the disappearance of GPIb from the cell surface and its subsequent redistribution into the channels and vesicles of the SCCS with no significant modification of GPIIb/IIIa remaining on the plasma membrane. Within degranulated platelets, GPIIb/IIIa was expressed on the plasma membrane and within membranes of large vacuoles containing the alpha-granule proteins. GPIb was virtually absent from these structures and mainly restricted to the SCCS. Addition of cytochalasin D inhibited the migration of GPIb to the SCCS. Biochemical measurements confirmed that no important hydrolysis of GPIb had occurred because only very little amounts of glycocalicin were generated during the reaction. In conclusion, in plasmin-treated platelets GPIIb/IIIa is externalized to the plasma membrane while GPIb is internalized into the SCCS. Although previous studies have suggested that plasmin degrades GPIb, the reduction in ristocetin-induced aggregation may be explained by its apparent redistribution within the membranes of the SCCS.

Blood Platelets↗
PubMed1991

Role of active center and lysine binding sites of plasmin in plasmin-induced platelet activation and disaggregation.

Previous studies have shown that plasmin can activate platelets and can also disperse platelet aggregates by degradation of fibrinogen bound to platelets. In this study, the role of the active center and the lysine binding sites (LBS) of human plasmin in activating platelets and in dispersing platelet aggregates is investigated using aprotinin and the tripeptide Val-Phe-Lys-CH2Cl to inhibit the active center and using epsilon-aminocaproic acid (EACA) to specifically block the LBS. Our results show that the catalytic activity of plasmin is indispensable both for activating platelets and for dispersing platelet aggregates. Binding of plasmin to platelets through the LBS enhances its activating potential, since both EACA (1 mM) and Lys-plasminogen (molar ratio of plasminogen:plasmin at 2:1 to 4:1) inhibit plasmin-induced platelet activation, whereas Glu-plasminogen at a molar ratio of 15:1 had no effect. Furthermore, plasmin which lacks the LBS (miniplasmin), is about 3 fold less effective in activating platelets. However, plasmin binding through the LBS is not absolutely required to disperse platelet aggregates, since EACA at 30 mmol/l was unable to prevent disaggregation by plasmin (half disaggregation time: 40 min in the presence of EACA against 27 min in its absence). It also appeared that fibrinogen receptors on activated platelets are resistant to plasmin degradation, and that disaggregation of plasmin-induced platelet aggregates was much slower than the degradation of fibrinogen by plasmin.

Amino Acid Sequence↗
PubMed1991

Modulation of endothelial cells fibrinolytic activity by platelets.

Interaction between endothelial cells (EC) and platelets in culture was shown to regulate the fibrinolytic system of the aortic EC. Untreated porcine EC from aorta exhibited almost no net fibrinolytic activity and zymographic assay have shown a single fibrin lysis band of 105 kDa corresponding to a tPA-PAI complex. Incubation of aortic EC with intact platelets stimulated a cell-associated fibrinolytic activity of the urokinase type as evidenced by a plasminogen-dependent fibrin independent amidolytic activity, and the appearance of a new 48 kDa lysis band on zymography. However, in the culture medium of platelet-treated aortic EC, a new lysis band of 92 kDa appeared with no associated amidolytic activity suggesting that the 48 kDa plasminogen activator secreted by the aortic EC after treatment with platelets is complexed to the inhibitor PAI1. This modulation of fibrinolytic activity depends on the EC origin since it is not observed with pulmonary artery EC, and represents a new concept in fibrinolysis regulation by cell-cell interaction.

Animals↗