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Biomedical subjects

D Duval

Publications and source records attributed to D Duval.

At least 127 records · Page 7Linked to original sources

Arterial glucocorticoid receptors: the binding of tritiated dexamethasone in rabbit aorta.

Current concepts of the mechanism of the physiological action of both mineralocorticoids and glucocorticoids include an initial step in interaction between the steroid and specific receptors in the cytoplasm of target tissue cells. Using cells from rabbit aorta as a model system, we have studied the cytoplasmic binding of 3H-dexamethasone and 3H-aldosterone. Aorta cells appear to contain binding sites with a high affinity (Kd 4 degrees C approximately 1.3 X 10(-8) mol) for dexamethasone, and with specificity appropriate for glucocorticoid receptors. Under similar experimental conditions, mineralocorticoid receptors could not be demonstrated.

Aldosterone↗

Glucocorticoid receptors in corticosensitive and corticoresistant thymocyte subpopulations. I. characterization of glucocorticoid receptors and isolation of a corticoresistant subpopulation.

1. Separation of mouse thymocytes by centrifugation on a discontinuous bovine serum albumin gradient leads to the isolation of four subpopulations of cells. 2. The study of I13H]uridine incorporation in vitro by these subpopulation in the presence of steroid shows that one of them is corticoresistant. 3. However, the binding capacity of these subpopulations measured by incubation with [3H]dexamethasone is very similar. 4. It is therefore concluded that in mouse thymus, in contrast with lymphoma cells, corticoresistance may not be explained by a defect of cytoplasmic glucocorticoid receptors.

Animals↗

Changes in cardiac and hepatic glucocorticoid receptors after adrenalectomy.

1. The total number of specific dexamethasone-binding sites in rat heart and liver cytosol was measured at intervals after adrenalectomy. 2. Between 12 and 48 h after adrenalectomy there was a significant increase in the number of binding sites in both heart and liver cytosol. Affinity was unchanged. 3. Of the [3H]corticosterone bound to liver cytosol proteins after an intravenous injection 98% disappeared within 2 h in vivo. Dissociation of endogenous corticosterone-receptor complexes in liver cytol will thus be substantially complete some hours before the number of receptors increases. 4. It was concluded that there is a true increase in the number of glucocorticoid receptors occurring principally between 12 and 48 h after suppression of endogenous steroids.

Adrenalectomy↗

[The binding of tritiated dexamethasone to lymphocytes of normal and leukemic subjects].

Specific binding sites for 3H-dexamethasone, possessing the characteristics of glucocorticoid receptors, were demonstrated in normal human circulating lymphocytes. The number of glucocorticoid receptors was found different from normal in half of the acute or chronic lymphoid leukaemias studied. A correlation between the number of glucocorticoid receptors and the therapeutical benefit of the glucocorticoid administration will be performed, including these preliminary observations.

B-Lymphocytes↗

Effect of glucocorticoids on arachidonic acid metabolism and prostaglandin secretion by cultures of newborn rat heart cells.

We described that oxygen deprivation induced in cultures of heart muscle cells, biochemical events similar to those described in ischemic tissue: arachidonic acid liberation, loss of membrane phospholipids and increase in neutral lipids. Since glucocorticoids have been described to inhibit phospholipase activity and to exert beneficial effects during myocardial infarction, we studied in our experimental model the action of dexamethasone on the metabolism of arachidonic acid and on the synthesis of immunoreactive prostaglandins. Our results show that heart muscle cells produce prostaglandin E2 and 6-keto-prostaglandin-F1 alpha. This synthesis, inhibited by dexamethasone (70% inhibition), decreased after oxygen-deprivation (-45%). The effect of oxygen deprivation and dexamethasone (-60%) are not additive. Moreover, steroid treatment failed to counteract the loss of polyunsaturated fatty acids from the phospholipids, the increase in neutral lipids and the liberation of arachidonic acid induced by oxygen deprivation in muscle cells. These results may indicate that the cardiovascular effects of glucosteroids are not the consequence of a direct effect on heart metabolism at cellular level.

6-Ketoprostaglandin F1 alpha↗

Synthesis of 7 alpha- and 7 beta-carboxymethyl-9(11)-ene derivatives of estrone and estradiol.

As part of a search for derivatives designed to conjugate to amino groups, either of a protein carrier for antibody production or of an immobilized side-chain on a polymer for affinity chromatography, functionalized estrone and estradiol analogues were prepared. These modified steroids were obtained via the introduction of a carboxymethyl side-chain at the C-7 alpha and C-7 beta position on an adrenosterone derivative and were then aromatized on the A ring. These new compounds are unsaturated at the C-9 (11) position, which could be useful for a second modification.

Androstenes↗

Quantification of lamivudine (3TC) by competitive immunoassay.

Lamivudine or 3TC, the (-) eniantiomer of 2'-deoxy-3'-thiacytidine, is a prototype of a novel class of levogyre dideoxynucleosides analogues used in treatment of HIV and HBV infection. We describe a method corresponding to the first enzyme immunoassay for quantifying this antiviral drug. This technique use an enzyme conjugate that not require the use of radioactive labelling. In this study, anti-3TC antibodies were raised in rabbits by immunising with 3TC-HS-kelhoyle limpet hemocyanin (KLH) conjugate.

Anti-HIV Agents↗

Vaccine-associated immune-mediated hemolytic anemia in the dog.

Vaccination has been incriminated as a trigger of immune-mediated hemolytic anemia (IMHA) in dogs and in people, but evidence to support this association is lacking. In a controlled retrospective study, idiopathic IMHA was identified in 58 dogs over a 27-month period. When compared with a randomly selected control group of 70 dogs (presented for reasons other than IMHA) over the same period, the distribution of cases versus time since vaccination was different (P < .05). Fifteen of the dogs (26%) had been vaccinated within 1 month (mean, 13 days; median, 14 days; range, 1 to 27 days) of developing IMHA (P < .0001), whereas in the control group no marked increase in frequency of presentation was seen in the first month after vaccination. The dogs with IMHA were divided into 2 groups based on time since vaccination: the vaccine IMHA group included dogs vaccinated within 1 month of developing IMHA; the nonvaccine IMHA group included dogs that developed IMHA more than 1 month after vaccination. The recently vaccinated dogs with IMHA (vaccine IMHA group) had significantly lower platelet counts (P < .05) and a trend towards increased prevalence of intravascular hemolysis and autoagglutination when compared with the nonvaccine IMHA group. Similar mortality rates were seen in teh vaccine IMHA group (60%) and the nonvaccine IMHA group (44%), with the majority of fatalities (> 75%) occurring in the first 3 weeks after presentation. Persistent autoagglutination was a negative prognostic indicator for survival in both groups (P < .05). Presence of icterus and hyperbilirubinemia were negative prognostic indicators for survival in the nonvaccine IMHA group (P < .0001 and P < .01, respectively) but not in the vaccine IMHA group. In the recently vaccinated dogs, combination vaccines from various manufacturers against canine distemper, adenovirus type 2, leptospirosis, parainfluenza, and parvovirus (DHLPP) were involved in each case. Vaccines against rabies virus, Bordetella spp, coronavirus, and Lyme Borrelia were administrated concomitantly to some dogs. This study provides the first clinical evidence for a temporal relationship of vaccine-associated IMHA in the dog.

Anemia, Hemolytic↗