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Biomedical subjects

D Duval

Publications and source records attributed to D Duval.

At least 109 records · Page 6Linked to original sources

7 alpha- and 7 beta-carboxymethyl-derivatives of 17-hydroxyprogesterone and 11-deoxycortisol. Synthesis and immunogenic properties.

7 alpha- and 7 beta-carboxymethyl-derivatives of 17-hydroxyprogesterone and 11-deoxycortisol have been synthesized. After coupling to bovine serum albumin, they were used to elicit antibodies in rabbits. No major difference in the steroid specificity of the antisera was observed when either 7 alpha- or 7 beta-epimers were used for immunization. In both cases, highly specific antisera were obtained which may possibly be used to assay human plasma 17-hydroxyprogesterone and 11-deoxycortisol without chromatographic purification.

17-Hydroxycorticosteroids↗

Release of platelet-activating factor (PAF-acether) from alveolar macrophages by the calcium ionophore A23187 and phagocytosis.

Platelet-activating factor (PAF-acether) was recovered from rabbit, rat and human alveolar macrophages stimulated with the Ca++ ionophore A23187. PAF-acether release was also obtained from rat and rabbit macrophages in the presence of zymosan, but not from human alveolar preparations in spite of the phagocytic activity exhibited by the latter cells. Observed releases were active, Ca++ dependent, and plateaued at 45 min. No PAF-acether was released from lungs washed out of their macrophages, another argument against the mastocyte origin of this mediator. Given the potent bronchoconstrictive activity of PAF-acether, its release from alveolar macrophages may provide an alternative explanation for non IgE-dependent asthmas and the implication of platelets in pulmonary diseases.

Animals↗

Heterogeneity of the in vitro responses to glucocorticoids in acute leukemia.

In leukocyte population freshly isolated from the blood of 26 patients with acute leukemia, we have measured several parameters including glucocorticoid receptors, nucleoside incorporation, percentage of cells in S phase, and steroid-induced cell lysis. In addition, in some cases, the short-term response to steroid therapy was determined. Although, in all the patients studied, leukocytes were found to contain glucocorticoid receptors, we failed to demonstrate any correlation between the level of binding sites and the in vitro or in vivo response to glucocorticoids. This absence of correlation could be in part explained by the marked heterogeneity of the steroid response demonstrated in leukocyte subpopulations. It appears, however, that the degree of steroid action in vitro as well as the extent of spontaneous and dexamethasone-induced cell death may be related to the number of cells in the S phase of the cell cycle.

Age Factors↗

Glucocorticoid receptors in thymocytes of fetus, newborn, and adult CBA mice.

[3H]Dexamethasone binding was studied in vitro in cell suspensions of thymus from fetal and newborn mice. The number of glucocorticoid receptors appeared to be identical in fetal, newborn, and adult CBA mice. The affinities of these receptors, calculated by Scatchard analysis, were similar in the three groups of animals. The extent of in vitro steroid-induced inhibition of [3H]uridine incorporation by fetal and adult thymocyte suspensions was very similar. These results suggest that no significant variations in glucocorticoid receptors occur in thymic tissue during the neonatal period.

Aging↗

Mechanism of glucocorticoid-induced inhibition of prostaglandin synthesis.

In order to study the mechanism of steroid-induced inhibition of prostaglandin (PG) secretion, we have used rat renomedullary interstitial cells grown in tissue culture as an in vitro model. These cells have been shown by radio-immunoassay to produce high amounts of prostaglandins, mainly PGE2 and PGF2 alpha. Using (3H) dexamethasone, we have demonstrated in our cultures the existence of glucocorticoid binding sites which exhibit all the characteristics of physiological glucocorticoid receptors. Comparison between the biological activity (i.e. the ability to inhibit PG secretion) of the various steroids tested (dexamethasone, corticosterone, aldosterone, progesterone and estradiol) and their affinities for the glucocorticoid binding sites reveals a striking correlation between these two parameters. Steroids which bind to the receptors also inhibit prostaglandin secretion whereas testosterone and estradiol, which have a very weak affinity for the glucocorticoid binding sites do not inhibit PG secretion. In addition, actinomycin D (0.1 microgram/ml) and cycloheximide (0.1 microgram/ml) are able to abolish the inhibitory effect of dexamethasone on PG secretion. Our results indicate that the action of corticosteroids on prostaglandin secretion, which is believed to be the basis of their anti-inflammatory properties, is mediated through receptor occupancy and requires RNA and protein synthesis.

Animals↗

Human thymus cells: effects of glucocorticoids in vitro.

The level of glucocorticoid receptors and the effects of dexamethasone on 3H-Uridine and 3H-Thymidine incorporation have been determined in normal human thymus cells. Under the experimental conditions employed human thymocytes appear more steroid-sensitive in vitro than human circulating lymphocytes.

Animals↗

[Macrophage origin of platelet activating factor].

Platelet-activating factor (P.A.F.) is a mediator of anaphylaxis released from human and Rabbit basophils which causes aggregation of platelets and release of their vasoactive amines. We have induced the release of P.A.F. from Rat peritoneal cells (P.C.) with ionophore A 23187. After fractionation of P.C. on 5-15% Ficoll gradients, P.A.F. was obtained from macrophage-rich but not from mastocyte-rich fractions and from adherent cells but not from non adherent cells. These data suggest an important new function for the macrophage: aggregation of platelets and release of their vasoactive amines and others mediators of inflammation.

Animals↗

Chronic lymphatic leukaemia: cellular effects of glucocorticoids in vitro.

Glucocorticoid receptor levels and steroid induced inhibition of nucleic acid precursors have been examined in lymphocytes from 27 patients at different stages of chronic lymphatic leukaemia. No correlation can be found between the level of glucocorticoid receptors and the stage of the disease. On the other hand, a significant difference (P less than 0.02) was found between stage O and stage III/IV patients, in terms of the in vitro effect of dexamethasone on [3H] uridine incorporation.

Adult↗

Prognostic value of steroid receptor determination in leukemia.

Determinations of steroid receptors have been used to predict steroid sensitivity in various neoplastic tumors. It appears, however, that simple steroid binding measurements are not sufficient for that purpose in lymphoid tumors. This conclusion is based on a literature survey showing, first, that numerous factors are capable of modulating cellular steroid receptor content; second, that the results of steroid receptor determinations are critically dependent on experimental procedures; and, third, that the correlation between steroid receptor content and sensitivity is not obligatory in animal or human leukemic cells.

Animals↗

Pharmacological findings on cetiedil.

The molecule of cetiedil (Stratène) has strong papaverine-like and weak atropine-like properties. It brings about peripheral vasodilation at doses which do not affect arterial blood pressure, heart beat and cardiac efficacy; this new drug increases the activity of beta-adrenergic stimulants. There may be different hypotheses to explain the therapeutic effect of cetiedil; beside its papaverinic and synergistic beta-stimulant properties, it increases the haemodynamic coefficient, plays a role in the process of membrane Ca++ exchange and inhibits phosphodiesterase and platelet aggregation.

Animals↗

Glucocorticoid receptors in corticosensitive and corticoresistant thymocyte subpopulations. II. Studies with hydrocortisone-treated mice.

In vitro studies of the residual thymocyte population isolated 48 h after in vivo hydrocortisone injection showed: 1. These cells are partly sensitive to steroid as demonstrated by uridine incorporation inhibition. 2. This residual cell fraction appears heterogeneous after centrifugation on a bovine serum albumine gradient. 3. These cells exhibit low steroid binding and DNA synthesis capacities.

Animals↗