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F Fouque

Publications and source records attributed to F Fouque.

16 recordsLinked to original sources
PubMed1992

Pyruvate dehydrogenase activity is stimulated by growth hormone (GH) in human mononuclear cells: a new tool to measure GH responsiveness in man.

Human peripheral mononuclear cells (PMC) were used to examine the effects of hGH and insulin on the activity of the pyruvate dehydrogenase (PDH) complex. Incubation of PMC with 10(-7) mol/L hGH or insulin increased basal PDH activity. Hormonal effects were maximal (50-60% above control values) at 15 min. Later on, activation progressively decreased and was no longer detectable at 30 min. Total PDH activity was unaffected by hormonal treatment. PMC were subfractionated into lymphocytes and monocytes to assess the sensitivity of each cell types to the hormones. hGH significantly increased basal PDH activity in lymphocytes and monocytes (38% and 70% above control values, respectively), whereas insulin increased basal PDH activity only in monocytes (151% above control value). PMC from healthy subjects aged 1-45 yr were incubated for 15 min with 10(-7) mol/L hGH or insulin before PDH measurement. An increase of enzyme activity higher than 20% was observed in 26 patients out of 29 with hGH, and in 15 out of 18 with insulin. In conclusion, hGH is able to stimulate PDH activity of human mononuclear cells. This hormonal effect allows rapid evaluation of the cellular responsiveness of hGH in various pathophysiologic situations.

Adolescent↗
PubMed1992

Role of acidic subcellular compartments in the degradation of internalized insulin and in the recycling of the internalized insulin receptor in liver cells: in vivo and in vitro studies.

Upon interaction with liver cells, insulin is internalized along with its receptor into nonlysosomal endocytic structures termed endosomes. In this work, the biochemical evidence supporting the role of endosomal acidity in the degradation of internalized insulin and in the recycling of the internalized insulin receptor is described. Treatment of rats by chloroquine and/or quinacrine, two acidotropic drugs, increases by 5-10 fold the amount of endogenous insulin associated with endosomal fractions and, in rats injected by 125I-labeled or native insulin, the endosomal uptake of these ligands at late times after injection. With 125I-insulin, these drugs inhibit the degradation of internalized hormone as judged on physical, biological and immunological criteria. Chloroquine and quinacrine treatment also increases the insulin receptor content of endosomal fractions and, in rats injected by native insulin, the ligand-induced accumulation of receptors in endosomal fractions at late times after injection. Subfractionation of endosomal fractions on Percoll gradients shows that chloroquine treatment shifts the distribution of both insulin and the insulin receptor towards higher densities, the receptor shift being slightly more pronounced in insulin-injected rats. Incubation of isolated endosomes containing internalized insulin at 30-37 degrees C results in a rapid degradation of this ligand, with a maximal at pH 5-6. Addition of ATP, by decreasing the endosomal pH, stimulates insulin degradation above pH 7, whereas addition of chloroquine and quinacrine, by elevating endosomal pH, exerts opposite effects. These data indicate that endosomal acidity is required for optimum degradation of internalized insulin within endosomes and recycling of the internalized receptor.

Animals↗
PubMed1991

Activation of rat liver adenylate cyclase by cholera toxin requires toxin internalization and processing in endosomes.

Involvement of acidic cell compartments in processing and action of cholera toxin (CT) in rat liver has been examined using subcellular fractionation. Liver cell fractions prepared various times after CT injection display, after a lag phase, a progressive increase in adenylate cyclase activity, detectable earlier in Golgi-endosomal fractions (20 min) than in plasma membrane fractions (30 min), with a maximum (3-fold basal activity) achieved by 60-90 min. Endosomes containing in vivo internalized CT display a time-dependent increase in their ability to bind anti-A-subunit antibodies and to stimulate exogenous adenylate cyclase, which kinetically parallels the generation of A1 peptide, suggesting a translocation of A-subunit (or A1 peptide) across the endosomal membrane. In vivo chloroquine treatment inhibits endocytosis of CT taken up into the liver, lengthens the lag phase for adenylate cyclase activation by CT, and reduces by 3- to 10-fold the apparent affinity of the toxin for the enzyme. Incubation of endosomes containing internalized toxin at 37 degrees C under isotonic conditions results in a pH-dependent increase in generation of A1 peptide, membrane translocation of A-subunit (or A1 peptide), and degradation of toxin, with a maximum at pH 5. Addition of ATP, by decreasing the internal endosomal pH, stimulates both generation of the A1 peptide and degradation of toxin at pH 6-8. It is concluded that activation of adenylate cyclase by CT in intact liver requires association and subsequent processing of toxin in an acidic cell compartment, presumably endosomal.

Adenosine Triphosphate↗
PubMed1991

Characterization of a liver low Michaelis-Menten constant 3',5'-cyclic adenosine monophosphate phosphodiesterase activity sensitive to thyroid status.

These studies were undertaken to assess the subcellular distribution and some biochemical properties of the hepatic cAMP phosphodiesterase(s) whose activity is modulated by the thyroid status in the rat. Thyroidectomy led to a 2-fold increase in low Michaelis-Menten constant (Km) cAMP phosphodiesterase activity in Golgi-endosomal fractions, but little affected this activity in crude particulate fractions. On analytical sucrose density gradients, an increase in cAMP phosphodiesterase activity in particulate elements which equilibrated at densities 1.17-1.22 was also observed. Acute insulin treatment did not further increase cAMP phosphodiesterase activity in Golgi-endosomal fractions of thyroidectomized rats. Up to 75% of the cAMP phosphodiesterase activity associated with Golgi-endosomal fraction of euthyroid and hypothyroid rats was inhibited by cGMP (IC50, 10 microM and 1 microM, respectively). Activity was also potently inhibited by griseolic acid, cilostamide, and cilostazole (IC50, less than 1 microM) but was much less sensitive to R0-20-1724 (IC50, 1 mM). Treatment of Golgi-endosomal fractions by a hypotonic extract of rat liver lysosomes led to the solubilization of 50% of low Km cAMP phosphodiesterase activity. On sucrose density gradients, the solubilized activity migrated as a slightly asymmetrical peak with a sedimentation coefficient of 6 S in euthyroid rats and 6.9 S in hypothyroid rats. On nondenaturing polyacrylamide gel electrophoresis, the activity migrated as two majors peaks with Rf values of 0.23 and 0.50; only the activity associated with the fast-moving peak was increased by thyroidectomy. On diethylaminoethyl-Sephacel chromatography, four peaks of cAMP phosphodiesterase activity, two of which were cGMP-inhibitable, were resolved. Thyroidectomy increased the activity associated with one of the cGMP-inhibitable peaks (eluted at 0.7-0.9 M sodium acetate) and led to the appearance of a new peak of activity (eluted at 0.4 M), which was not sensitive to cGMP. These results show that the low Km phosphodiesterase activity associated with liver Golgi-endosomal fractions, previously shown to be increased in hyperinsulinemic rats, is also increased in hypothyroid animals. They also suggest that, based on pharmacological and physical criteria, the enzyme species affected by the thyroid status belongs to the cGMP-and cilostamide-inhibited subclass of low Km cAMP phosphodiesterases.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Characterization of insulin degradation products generated in liver endosomes: in vivo and in vitro studies.

The degradation products generated from A14 and B26 125I-labelled insulins in liver endosomes in vivo and in vitro have been isolated by high-performance liquid chromatography and cleavages in the B chain have been identified by automated radiosequence analysis. In rats sacrificed various times after injection of each of the 125I-labelled insulins, two major degradation products slightly less hydrophobic than intact iodoinsulins were identified; these accounted, at 8 min. for about 45% (A14 125I-labelled insulin) and 15% (B26 125I-labelled insulin) of the total radioactivity recovered, respectively. The products generated from A14 125I-labelled insulin contained an intact A chain, whereas those generated from B26 125I-labelled insulin contained a B chain cleaved at the B16-B17 bond. With B26 125I-labelled insulin, two minor products, with cleavages at the B23-B24 and B24-B25 bonds, were also observed. In vivo chloroquine treatment did not alter the nature but caused a decrease in the amount of insulin degradation products associated with endosomes. When endosomal fractions isolated from iodoinsulin injected rats were incubated at 30 degrees C in isotonic KCl, a rapid degradation of iodoinsulin, maximal at pH 6, was observed. With A14 125I-labelled insulin, the two major degradation products identified in vivo were generated along with monoiodotyrosine, but with B26 125I-labelled insulin monoiodotyrosine was the main product formed. Addition of ATP, presumably by decreasing the endosomal pH, shifted the medium pH for maximal iodoinsulin degradation to about 7-8. These studies have allowed a direct identification of two previously suggested cleavage sites in the B chain. They have also shown that the degradation products generated in cell-free endosomes under conditions that promote endosomal acidification are similar to those identified in vivo.

Animals↗
PubMed1990

Antigen-dependent activation of alveolar macrophages from ovalbumin-sensitized guinea-pigs: relevance of the route of administration and the amount of antigen provided.

Alveolar macrophages from guinea-pigs sensitized by different amounts of ovalbumin, administered either by subcutaneous injection or aerosol exposure, liberate increased amounts of arachidonic acid and thromboxane B2 when challenged in vitro with ovalbumin. This antigen-dependent activation of macrophages was immunospecific. The comparison between different sensitization procedures showed that the aerosol exposure was the most efficient with respect to the activation of macrophages, as cells from guinea-pigs sensitized subcutaneously were poorly activated by the antigen unless high doses were used for sensitization. The antigen-dependent activation of macrophages was affected by acid and neutral washings, suggesting the involvement of a loosely bound antibody that could not be identified. These observations suggest that, as mast cells and basophils, alveolar macrophages from actively sensitized guinea-pigs contribute to the allergic reaction by an antibody-mediated mechanism.

Aerosols↗
PubMed1989

Selective inhibition of adrenaline-induced human platelet aggregation by the structurally related Paf antagonist Ro 19-3704.

1. Two non-lipid antagonists of platelet-activating factor acether (Paf), BN 52021 and WEB 2086, at concentrations which completely blocked Paf-induced platelet aggregation, failed to interfere with aggregation by adrenaline. In contrast, Ro 19-3704, a structurally related antagonist of Paf, inhibited concentration-dependently aggregation induced by adrenaline or by the simultaneous addition of submaximal concentrations of adrenaline and Paf. Reversal of aggregation was obtained when Ro 19-3704 was added to the platelet suspension after adrenaline. 2. Ro 19-3704 was selective for Paf and adrenaline since it failed to interfere with platelet aggregation induced by arachidonic acid or ADP. CV-3988, an antagonist of Paf structurally similar to Ro 19-3704, also inhibited adrenaline-induced aggregation. However, a morpholine analogue (MA) of Paf, which has no anti-Paf activity, failed to interfere with the aggregation induced by adrenaline. This suggests that the effect of Ro 19-3704 and CV-3988 on adrenaline is not simply due to their lipid structure. 3. Experiments on plasma membrane preparations showed that Ro 19-3704 inhibited [3H]-yohimbine binding with an inhibition constant (Ki) of 7 +/- 3 microM. In contrast, BN 52021 and MA did not interfere with [3H]-yohimbine binding. Equilibrium binding experiments showed that Ro 19-3704 increased the apparent KD of [3H]-yohimbine binding from 2.02 +/- 0.15 to 7.3 +/- 0.4 nM. The Paf antagonist Ro 19-3704 interacts specifically with the alpha 2-adrenoceptor and may thus prevent the early steps involved in the mechanism of adrenaline-induced platelet activation.

5-Hydroxytryptophan↗
PubMed1987

Potentiation and inhibition by clonidine of PAF-acether-induced human platelet activation.

PAF-acether (platelet-activating factor) and adrenaline synergized to induce aggregation of human platelets in whole blood and in platelet-rich plasma (PRP) irrespective of the use of citrate, of heparin or acid-citrate dextrose (ACD) as anticoagulants, whereas the partial adrenoceptor agonist clonidine imitated adrenaline in a limited number of cases and only when blood was collected in ACD. Whether added to ACD-PRP or ingested by the blood donors, aspirin suppressed the synergic effect of clonidine plus PAF-acether in plasma but failed to block the potentiated aggregation of adrenaline plus PAF-acether. Clonidine alone had no effect on plasma-free platelet suspensions and also failed to synergize with PAF-acether under conditions where the latter's association to adrenaline consistently induced full aggregation. Added before adrenaline or before adrenaline plus PAF-acether, clonidine reduced the aggregation to the level of that due to PAF-acether alone irrespective of cyclooxygenase inhibition with aspirin. The alpha 2-adrenoceptor antagonist yohimbine blocked the synergistic effects of adrenaline or clonidine associated to PAF-acether, reducing aggregation to that due to PAF-acether alone. Clonidine has dual effects on human platelets, since it can imitate adrenaline and synergize with PAF-acether in some subjects, and can also block aggregation induced by adrenaline alone or in combination with PAF-acether.

Aspirin↗
PubMed1987

[Thyroid hormones in rats receiving increasing doses of lithium].

Thyroid hormones were determined in rat serum, thyroid, liver and kidney tissues; the animals were fed for 40 days an equilibrate diet and various amounts of lithium carbonate were added to drinks. Serum lithium levels were related to their absorption. There was no change in rats drinking 300 mg Li2CO3/l solution for 5 weeks or 600 mg/l for 2 weeks, when compared to control rats. But 600 mg/l solutions for 5 weeks led to hormone increase in thyroid tissue. With 1200 mg/l acute hormonal decrease was seen in serum (thyroxine, T4: 3.2 micrograms/dl and control: 4, triiodothyronine T3: 54.8 ng/dl and control: 64) in liver tissue T3: 2.6 ng/g and control: 3.5), and in kidney tissue (T3: 4.8 ng/g and control: 6.4). In some animals receiving 600 or 1200 mg, lithium concentration was very high, body weights were very much reduced and there was large hormonal decrease in serum (T4: 1.4 micrograms/dl, T3: 48.5 ng/dl) in liver tissue (T4: 10.5 ng/g and control: 20.7; T3: 2.1 ng/g) and in kidney tissue (T4: 6.9 ng/g and control: 13.5 and T3: 3.3 ng/g). Hormonal changes were parallel to tubular kidney damage. These results are similar to those described in patients receiving lithium treatment.

Animals↗
PubMed1986

First-month variations in total iodine content of human breast milks.

In 183 samples of breast milk from 23 young mothers we found the mean total iodine content to be 47 ng/ml, a value that is not dependent on length of gestation. There is a progressive increase in iodine concentration from colostrum to transitional and mature milk. The results show that breast milk sometimes contains an amount of iodine barely necessary to make thyroid hormones, which is around 10 micrograms in the first days of life rising to about 15-20 micrograms after four weeks. Secondly, nursing mothers should be watched, because if their daily breast milk contains more than 50 micrograms iodine for several consecutive days, they may be on a negative balance.

Adult↗
PubMed1986

[Effect of dietary supply of calcium on thyroid function in rats].

To determine if calcium had a goitrogenic effect on the thyroid function in rats, weanling rats were fed, for three weeks, a diet containing either 0.5 microgram or 0.04 microgram iodine per gram of diet, or an adequate (0.47%) or an excessive (2%) amount of calcium. With an adequate iodine diet, the calcium load did not induce an increase in the weight of the thyroid or a decrease in serum thyroid hormone concentration. However, the rats given a calcium load had a lighter body weight and a lower iodine content in the thyroid tissue; they also had a higher thyroxine (T4) content in the liver and kidney tissues than the rats receiving an adequate calcium diet. With a low iodine diet, the calcium load brought out a decrease in growth and a lower serum triiodothyronine (T3) concentration and liver and kidney T3 contents. These changes suggest that the calcium load might have acted on the thyroid function through an inhibition of T4-T3 conversion in the serum as well as in liver and kidney tissues.

Animals↗
PubMed1985

Adrenaline/PAF acether synergism on human platelets: involvement of Hydergine.

Adrenaline stimulates platelet aggregation via the alpha 2-adrenergic receptor; the resultant aggregation is blocked by aspirin. In conjunction with low concentrations of PAF-acether, adrenaline induces aggregation which is not susceptible to blockade by aspirin. Hydergine and other alpha 2-adrenergic antagonists block the specific aggregant action of adrenaline as well as the synergic effect in the presence of PAF-acether.

Adenosine Triphosphate↗
PubMed1980

Carrageenan-induced activation of human platelets is independent of phospholipase A2 and of formation of thromboxanes.

Aggregation of washed rabbit platelets by thrombin and by carrageenan is accompanied by the activation of phospholipase A2 and by the synthesis of thromboxanes. Accordingly, aggregation, the accompanying release reaction and the activation of phospholipase are blocked by p-bromophenacyl bromide and by CB 874 (2,3-dibromo (4'-cyclohexyl-3'-chloro)-phenyl-4-oxo-butyric acid), two recognized inhibitors of the enzyme. Since these two reagents also inhibit aggregation and the release reaction induced by thrombin and by carrageenan on washed human platelets, it might have been anticipated that the mechanisms of aggregation of the platelets from the two species are similar. Nevertheless, no thromboxanes A2 or B2, nor activation of phospholipase A2 could be demonstrated with the use of carrageenan on human platelets, under conditions where thrombin was effective. It is concluded that carrageenan activates the human platelets by phospholipase A2- and thromboxane A2-independent mechanisms, and that the inhibitors of phospholipase A2 may block platelet functions by mechanisms other than inhibition of the expected enzyme.

Adenosine Diphosphate↗
PubMed1979

Mechanisms of bronchoconstriction and of thrombocytopenia induced by collagen in the guinea pig.

Collagen injected to guinea pigs i.v. increased the pulmonary resistance to inflation (bronchoconstriction) and induced thrombocytopenia. Immune platelet depletion protected against the effects of collagen, and has been shown not to prevent bronchoconstriction induced by the prostaglandin/thromboxane A2 precursor arachidonic acid. Use of inhibitors demonstrated that histamine, serotonin, acetylcholine and bradykinin were not involved with the effects of collagen in the guinea pig. Aspirin and indomethacin inhibited collagen-induced bronchoconstriction completely and thrombocytopenia partly, supporting the hypothesis that the former is prostaglandin cyclo-oxygenase dependent, whereas the latter has a thromboxane A2-independent mechanism as well. Carrageenan, heparin and reserpine inhibited the in vivo effects of collagen to various extents, but their precise mechanism of action could not be discovered. Collagen-induced bronchoconstriction is strictly platelet and thromboxane A2-dependent.

Airway Resistance↗
PubMedDate not supplied

[Biological and immunological researches on snake venom. V. Application of the immunochemical technics to the titration of specific antibodies to the alpha toxin of Naja nigricollis venom (author's transl)].

In order to establish a simple method to titrate antitoxin antibodies in the antivenom sera, we suggest a new immunochemical technic. To a constant dose of a pure toxin extracted from a snake venom, increasing volumes of specific immune serum are added so as an excess of toxin remains free. This residual toxin is titrated by electroimmunodiffusion technic according to Laurell or by radial immunodiffusion method of Mancini. The experimental results in vitro are compared to those obtained in vivo. If a given volume of immune serum neutralize X microgram of toxin by the in vivo technic it will combine in vitro to 2 X or 1.2 X of the same toxin, respectively if we refer to electroimmunodiffusion or to radial immunodiffusion technic results.

Animals↗