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Biomedical subjects

N Ardaillou

Publications and source records attributed to N Ardaillou.

At least 55 records · Page 3Linked to original sources
PubMed1983

Response of adenylate cyclase to parathyroid hormone and prostaglandins by human isolated glomeruli.

A role for hormonal substances and other biochemical messengers in the regulation of the glomerular filtration rate has been inferred from the results of micropuncture studies in the rat and from the demonstration of hormone-responsive adenylate cyclase activity in glomeruli isolated from the renal cortex of rats and rabbits. To investigate whether such hormonal factors may contribute to the regulation of glomerular function in humans, we studied the response of adenylate cyclase activity to the administration of human PTH-(1-34) and prostaglandins (PG) by glomeruli isolated from the renal cortex of four human kidneys. PTH and PGs (PGE2, PGI2, and, to a lesser extent, PGF2 alpha) stimulated human glomerular adenylate cyclase activity. Basal adenylate cyclase activity ranged from 0.2-1.2 nmol 20 min-1 mg-1. For each agonist, the percent increase above basal values (at the maximum concentration tested) and the concentration of the agonist that elicited 50% of the maximum stimulation (ED50) were as follows: for PTH 300-460% (10,000 mIU/ml); ED50, 100-550 mIU/ml; for PGE2, 160-380% (10 microM); ED50, 0.4-1.6 microM; and for PGI2, 180-650% (10 microM); ED50, 0.09-0.46 microM. The synthetic guanylnucleotide 5'-guanylylimidodiphosphate [Gpp(NH)p] potentiated the effect of PTH and PGI2, since the combined effects were greater than the sums of the effects of the individual agonists, and there was a significant interaction between Gpp(NH)p and PTH or PGI2, as indicated by three-factor analysis of variance. Additivity, but not potentiation, was observed for PGE2. The effects of PTH plus PGE2 or PGI2 were also additive, a finding that suggests that PTH and PGs are not linked to the same pool of adenylate cyclase. In contrast, the combination of PGE2 and PGI2 resulted in a significantly lower effect than the sum of their individual effects, a finding indicating that these PGs share in part a common pool of adenylate cyclase. Demonstration of PTH- and PG-dependent adenylate cyclase activity in human isolated glomeruli suggests a role for these agonists in the regulation of the glomerular filtration rate in man.

Adenylyl Cyclases↗
PubMed1982

[Protective effect of procyanidolic oligomers on the heterologous phase of glomerulonephritis induced by anti-glomerular basement membrane antibodies].

Treatment by procyanidolic oligomers can significantly decrease the proteinuria indiced in the Rat by intravenous injection of anti glomerular basement membranes antibodies. Immunohistological analysis shows that procyanidolic oligomers do not interfere with the mechanisms of immunopathological injury involved in this model (antibody binding to glomerular basement membrane, complement activation, glomerular influx of polymorphonuclear leucocytes). Their protective effect may be due to an increased resistance of the glomerular capillary to the inflammatory mediators released by neutrophils.

Animals↗
PubMed1982

The binding of fibrinogen to its platelet receptor.

Specific receptors for fibrinogen can be induced on platelets by a variety of stimuli. In this study, two independent approaches have implicated the D domain of fibrinogen in its interaction with the platelet. Immunochemically purified Fab fragments of anti-fibrinogen and anti-D inhibited 125I-fibrinogen binding to platelets in a dose-dependent fashion and platelet aggregation. In contrast, Fab fragments of anti-E produced only a slight inhibition of fibrinogen binding and nonimmune Fab fragments had no effect. Fibrinogen was digested with plasmin in the presence of 5 mM calcium and fragment D and E of Mr 100,000 and 50,000, respectively, were isolated. This D fragment inhibited 125I-fibrinogen binding to platelets in a concentration-dependent fashion, whereas the E fragment was ineffective. With 125I-fibrinogen at 0.17 microM, nonlabeled fibrinogen inhibited binding by 50% at 0.7 microM, whereas 170 microM fragment D was required to produce 50% inhibition. D fragment of Mr 80,000, generated in the absence of calcium, was noninhibitory. These observations provide strong evidence for the participation of the D domain in the binding of fibrinogen by its platelet receptor and suggest that the recognition site is lost in the conversion of the Mr 100,000 to 80,000 D species.

Adenosine Diphosphate↗
PubMed1982

Potential role of the A alpha chain in the binding of calcium to human fibrinogen.

The binding of Ca2+ to human fibrinogen was investigated. Molecules with intact A alpha chain possessed three high-affinity binding sites but fibrinogen samples with partially degraded A alpha chain exhibited only two sites. It is therefore suggested that the integrity of this chain is required for the interaction between the protein and this cation.

Binding Sites↗
PubMed1982

In vitro prostaglandin synthesis by human glomeruli and papillae.

We have investigated in vitro prostaglandin synthesis by human isolated glomeruli and papillary homogenates and compared the results with those obtained in parallel studies using rat material. Prostaglandins were measured by two methods, namely radiometric high performance liquid chromatography after incubation with 14C arachidonic acid and radioimmunoassay. The relative abundance of various prostaglandins synthesized by glomeruli was different in man (6 keto PGF1 alpha greater than TXB2 greater than PGF2 alpha greater than PGE2) and in the rat (PGE2 greater than or equal to PGF2 alpha greater than TXB2 greater than 6 keto PGF1 alpha). Unidentified peaks eluting between 6 keto PGF1 alpha and TXB2 were observed only in rat glomeruli. These peaks were suppressed by indomethacin. Direct radioimmunoassay of prostaglandins in the incubation medium of human glomeruli confirmed the predominance of 6 keto PGF1 alpha synthesis and showed its stimulation by arachidonic acid, its progressive decrease with time and its linear relationship with glomerular protein at low concentrations. On the contrary, the profile of prostaglandin synthesis by the papilla was similar in man and in the rat, PGE2 and PGF2 alpha being the major products in both species. However, related to one mg of protein, papillary synthesis of these two prostaglandins was greater in the rat. These results show that PGI2 is the major prostaglandin synthesized in human glomeruli and suggest a role for this prostaglandin in glomerular physiology in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Angiotensin II receptors in human isolated renal glomeruli.

125I-Labeled angiotensin II ([125I]A II) binds specifically to glomeruli isolated from human kidneys that were obtained at nephrectomy or early autopsy. Equilibrium was reached after 30 min, and specific binding represented more than 90% of the total binding. Dissociation after dilution with the addition of an excess of unlabeled hormone was more rapid than after dilution alone. The effect increased as a function of the A II concentration. The Scatchard plot derived from saturation experiments was curvilinear, with an upward concavity. Two groups of receptor sites could be defined by the Kd values (0.1 and 2 nM, respectively) and the number of receptor sites (40 and 300 fmol mg glomerular protein-1, respectively). Alternatively, binding could be considered to follow a negative cooperative type of hormone-receptor interaction. [Asn1, Val5]A II, [Asp1,Ile5]A II, [des, Asp1,Ile5]A II, [Sar1, Ala8]A II, and [Sar1, Ile8]A II were all equally effective as competitive inhibitors of [125I]A II binding. Both calcium and magnesium (0.5-5 mM) produced an increase in [125I]A II specific binding, whereas guanylylimidodiphosphate, an analog of GTP, inhibited it. Degradation of the [125I]A II present in the incubation medium was estimated by three different techniques. It increased linearly with time and reached 20% at 30 min. Specific binding of A II to human glomeruli at plasma concentrations observed in man under physiological conditions and during the iv administration of A II demonstrates that human renal glomeruli include target cells for A II and thus suggests a role for A II in regulation of the glomerular filtration rate in man.

Adult↗
PubMed1980

Catabolism of human fibrinogen fragment D in normal subjects and patients with liver cirrhosis.

The catabolism of human fragment D, (FgD), obtained by plasmin digestion of fibrinogen has been investigated in normal subjects and patients with liver cirrhosis and the results compared with those obtained for fibrinogen (Fg). Fg was labelled with I-125 and Fg D with I-131 using the chloramine T method. The plasma disappearance curves of both labelled proteins fitted a two exponential curve. In controls the plasma clearance rate of Fg D was greater than that of Fg as shown by the marked difference between the half-lives of these two tracers: 8,9 and 83,5 hours for Fg D and Fg respectively. The fractional catabolic rate of Fg D was 3.38 times the plasma pool per day. In nine patients with liver cirrhosis, catabolism of Fg was not modified. In contrast, catabolism of Fg D was significantly reduced with a half life of 13.0 hours and a low fractional catabolic rate. These results suggest the role of the liver in the catabolism of Fg D in man.

Adult↗
PubMed1979

Urinary excretion of factor VIII after renal transplantation.

The urinary excretion of factor-VIII-related antigen (VIIIRAg) was measured in 72 patients with kidney transplants and compared with that of two end-products of fibrin-fibrinogen lysis (fragments D and E) to assess their usefulness in monitoring the onset of rejection episodes. Specific and sensitive radioimmunoassays were used to measure the three proteins. Unconcentrated urine samples of 24-hour collections were obtained from 20 healthy subjects, 48 patients with stable transplants, and 24 patients with recent transplants serially followed up from the day of transplantation. Factor VIIIRAg and fragments E and D were not detectable in the urine from healthy subjects but were present in 39%, 60%, and 100% respectively of samples from patients with stable transplants. During 33 acute rejection episodes in 19 patients with recent transplants factor VIIIRAg and fragments E and D were significantly increased above the values observed in patients with stable transplants in 82%, 73%, and 64% of samples respectively; in patients with recent transplants showing no clinical sign of rejection increased excretion of these proteins was observed in 11%, 26%, and 22% of samples respectively. The presence of factor VIIIRAg in urine from patients with kidney allografts suggests that endothelial cell-factor VIII-platelet interactions might pay a key part in the pathogenesis of acute rejection. The results suggest that the assay of factor VIIIRAg in urine is more useful than assays of fragments D and E as a corroborative index of transplant rejection.

Antigens↗
PubMed1979

Fluid-phase immunoradiometric assay for the detection of qualitative abnormalities of factor VIII/von Willebrand factor in variants of von Willebrand's disease.

Antigenic reactivity of F.VIII/WF in variants of von Willebrand's disease (vWd) was studied with both fluid-phase and solid-phase immunoradiometric assays. Two different (rabbit and goat) 125I-labeled specific antibodies against purified F.VIII/WF were used in both their divalent (IgG) and their monovalent (Fab fragment) forms. Dose-response curves obtained by reacting a constant amount of antibody with serial dilutions of plasmas from normal or homozygous vWd demonstrated the specificity of the test. The accuracy was significantly higher with 125I-Fab fragments of goat anti-F.VIII/WF antiserum that intact goat IgG or rabbit IgG or Fab fragments. The significant decrease of the slope of the dose-response curves obtained with plasma from variants of vWd has been interpreted as due to the presence of abnormal F.VIII/WF molecules with decreased antigenic reactivity. A similar anomaly was found in cryosupernatant prepared from normal plasma, paralleling similarities demonstrated between variants of vWd and cryosupernatant. Results of experiments performed by reacting constant plasma dilutions from control or variants of confirmed the decreased antigenic reactivity of variant F.VIII/WF.

Blood Coagulation Factors↗
PubMed1977

The half-life of plasmic degradation products of human fibrinogen in rabbits.

Human fibrinogen and purified plasmic degradation fragments X (stages 1 and 2), D and E were labelled with 125-I using the lactoperoxidase method. The chromatographic, electrophoretic and immunologic properties of the labelled proteins were found to be similar to those of non-labelled fragments. All the degradation products diffused rapidly (T 1/2 0.27-0.75 hours) from the intravascular space of rabbits, as compared with fibrinogen (4.26 hours). In addition, the metabolic half-life was found to be 49.3 hours for fibrinogen, as compared with only 5.6, 6.1, 2.3 and 1.4 for fragments X (stage 1), X (stage 2), D and E, respectively. The metabolic half-life roughly reflects the molecular size of the degradation products.

Animals↗
PubMed1977

[Von Willebrand's syndrome (author's transl)].

The biological syndrome in von Willebrand's disease is presently defined by four parameters: bleeding time, factor VIII coagulant activity (VIII:C), Willebrand factor activity (VIIR:WF) and factor VIII related antigen (VIIR:AG). The study of 48 patients from 25 families confirms the heterogeneity of the von Willebrand's syndrome including both quantitative as well as qualitative defects. Classical von Willebrand's disease results from the quantitative decrease of a plasma protein named "Willebrand factor" which is the primary gene-product of an altosomal chromosome. Both severe and moderate forms can be observed. In very severe forms, the apparent lack of the VIIIR:AG as measured by an immunoradiometric assay suggest the possibility that some patients are homozygous. "Variants" of von Willebrand's disease have been recently described in some patients, based on the discrepancy between the observed subnormal levels of VIIIR:AG and low levels of VIIIR:WF. The qualitative abnormality of the factor VIII/Willebrand protein can be assessed by different methods such as double cross immuno-electrophoresis, or immunoradiometric assay.

Antigens↗
PubMed1977

Heterogeneity of von Willebrand's disease: study of 40 Iranian cases.

Forty Iranian patients with von Willebrand's disease were tested for bleeding time, platelet retention to glass beads, ristocetin-induced platelet aggregation, and assay of factor VIII procoagulant activity (VIII:C), Willebrand factor activity (VIIIR:WF), and factor VIII-related antigen (VIIIR:AG) by two methods (Laurell and immunoradiometric assay). In 22 cases from 11 families, levels of VIII:C, VIIIR:WF and VIIIR:AG (Laurell) were below 5% and the immunoradiometric assay showed total lack of VIIIR:AG in all cases (sensitivity of the method 0.01%). In 10 of these families, the parents were related, raising th;e possibility that these patients are homozygous. The occurrence of precipitating antibodies to factor VIII was demonstrated in one of these severe patients. In seven cases from five families the anomaly was less severe, with results of VIII:C between 5 and 17%. In 11 cases from six families VIII:C was normal or moderately decreased, contrasting with lower levels of VIIIR:WF and VIIIR:AG. The presence of an abnormal factor VIII/von Willebrand factor protein was assessed by double-cross immunoelectrophoresis and gel filtration.

Adolescent↗