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Biomedical subjects

D Feldman

Publications and source records attributed to D Feldman.

At least 253 records · Page 14Linked to original sources
PubMed1978

Glucocorticoids and regulation of phosphoenolpyruvate carboxykinase activity in rat brown adipose tissue.

Studied were performed to examine the factors that might regulate phosphoenolpyruvate carboxykinase (PEPCK) activity in rat brown adipose tissue (BAT) and to determine the role played by glucocorticoids in regulating this enzyme. Comparison was made to white adipose tissue (WAT) where PEPCK activity is known to be glucocorticoid regulated. PEPCK activity in BAT did not respond to adrenalectomy or dexamethasone, whereas WAT activity was increased and decreased, respectively, by these maneuvers. Three conditions were found in which BAT PEPCK activity was stimulated: 1) fasting, 2) feeding a high-fat/low-carbohydrate diet, and 3) during the neonatal period. In each case glucocorticoid treatment prevented the stimulation in PEPCK activity and restored the enzyme to base-line levels. In conditions 1 and 2, enzyme activity was also stimulated in WAT, but in contradistinction to BAT, glucocorticoid administration reduced activity to low levels significantly below base-line activity. Two conditions were found which suppressed PEPCK activity in BAT: exposure to a cold environment and feeding a high-protein/low-fat diet. WAT PEPCK was unaltered by exposure to cold. Thus, differences in PEPCK regulation between BAT and WAT were demonstrated, and the response to glucocorticoids was unique in BAT.

Adipose Tissue↗
PubMed1978

19-Nor deoxycorticosterone (19-nor DOC): mineralocorticoid receptor affinity higher than aldosterone, electrolyte activity lower.

By screening urine extracts from rats with adrenal regeneration hypertension, Gomez-Sanchez et al. found a steroid, subsequently identified as 19-nor DOC, with high affinity for tritiated aldosterone (3HA) binding sites in rat kidney cytosol. We here report studies on the affinity of authentic 19-nor DOC for mineralocorticoid receptors, its binding in plasma and its activity in the rat urinary mineralocorticoid assay. When kidney slices from adrenalectomized rats were incubated in protein-free buffer with 3HA, 19-nor DOC consistently competed better (approximately 140%) for 3HA binding sites than did equivalent concentrations of non-radioactive aldosterone. Under identical conditions, save for the inclusion of 20% adrenalectomized rat plasma in the incubation medium, 19-nor DOC shows only approximately 40% the potency of aldosterone in displacing 3HA. Determination of renal binding of 3HA after injection of 3HA +/- aldosterone +/- 19-nor DOC in vivo similarly shows 19-nor DOC to be approximately one third as potent a competitor for 3HA binding sites as aldosterone. In the rat urinary bioassay, 19-nor DOC shows no antagonist activity when injected with aldosterone; in the absence of aldosterone, 19-nor DOC acts as a mineralocorticoid agonist, with an apparent potency 10-30% that of aldosterone. Conclusions of the study are therefore (i) at a molecular level, 19-nor DOC has a higher affinity than aldosterone for mineralocorticoid receptors, (ii) in vivo, its potency in terms of receptor occupancy is markedly lower than that of aldosterone, due to higher levels of plasma binding, (iii) in effector terms, 19-nor DOC is a full agonist without antagonist activity.

Aldosterone↗
PubMed1978

[Herpes gestationis. Ultrastructural and immunologic data, about two cases (author's transl)].

Herpes gestationis, a rare vesiculobullous dermatitis of pregnancy and the postpartal period, can be more easily identified today thanks to recent immunologic and ultrastructural researches. Comparing two new case reports with the data provided by the literature, underlines the individuality of the disease, in spite of the analogies it shows with bullous pemphigoid. Clinically, the illness only appears during pregnancy or the postpartal period and generally responds well to vitamin B6. Histologically the bullae at the dermal-epidermal junction are accompanied by extra- and intra-cellular epidermal edema and vacuolation of the basal cells. Ultrastructural examination shows that the initial alteration affects the plasmatic membrane of the basal cells. The immunologic mechanism of the disease is specific as the usual indirect in vitro immunofluorescent methods cannot reveal factor B.

Diagnosis, Differential↗
PubMed1978

Stereomicroscopic and ultrastructural characterization of propionitrile-induced duodenal ulcer in the rat.

Acute duodenal ulcer produced by subcutaneous injection of propionitrile in rats was studied by stereo, light, and electron microscopy in order to gain insight into the localization and mechanism of initial cell injury. Stereomicroscopy revealed an initial fissuring and splitting of the tips of the villus folds within 4 hours after two injections of propionitrile. This was followed by sloughing of the epithelium, shortening and effacement of the villus folds, and within 24 hours the appearance of discrete ulcers in the mucosa of the proximal duodenum. In most of the rats, two ulcers developed: the first and larger ulcer was on the antimesenteric side of the duodenum, and the other, a small and more superficial one, was on the opposite wall. Ultrastructural lesions appeared in the absorptive epithelial cells of the proximal duodenum within 5 hours following a single dose of propionitrile. The cytoplasmic changes of cellular injury were preceded and/or accompanied by beading and loss of microvilli. The initiation of propionitrile-induced alterations at the tip of the villi in the proximal duodenum suggests that the ulcerogenic agent acts from the luminal side of the duodenum and probably originates from the stomach.

Animals↗
PubMed1978

Infective endocarditis: a review. I. Incidence, etiology, pathology and clinical features.

In this paper demographic characteristics, etiology, pathology and clinical features of infective endocarditis are reviewed simultaneous presentation of the data from our series of 50 cases with infective endocarditis. The peak incidence of infective endocarditis is between 11 and 15 years. Both sexes are equally affected. Patients with congenital or acquired heart disease tend to have hemodynamic trauma to the endocardium and vascular endothelium. These sites form the nidus for circulating bacteria of either spontaneous origin or the result of any oro-dental, genitourinary or other surgery or procedures and produce vegetations characteristic of infective endocarditis. The location of the vegetation is dependent upon the predisposing cardiac lesion. Embolic phenomenon is another cardinal feature of endocarditis and may occur in any organ system. Although a large variety of microbes have been known to cause endocarditis, streptococci and staphylococci remain the most frequent offenders. Clinical diagnosis of infective endocarditis is difficult because of the insidious onset and varied clinical features. A high degree of suspicion is essential for early diagnosis. Any patient with known heart disease and unexplained fever should be suspect for endocarditis. Splenomegaly, petechiae and embolic phenomena support this diagnosis. New or changing murmurs, splinter hemorrhages, Osler's nodes. Janeway's lesions and Roth's spots may be present. Elevated sedimentation rate, microscopic hematuria, leukocytosis with a shift-to-the-left and anemia may further support the diagnosis. Congenital or acquired heart disease and fever are all that will be present in many cases. Only isolation of the causative agent from the blood can confirm the diagnosis.

Adolescent↗
PubMed1977

Glucocorticoid receptors in adipose tissue.

Although adipose tissue appears to be a target organ for glucocorticoid hormones, previous studies have failed to detect glucocorticoid receptors in this tissue. In the present study, the addition of thioglycerol and trasylol to the homogenization medium provided an enuironment in which receptors were successfully demonstrated. [3H]Dexamethasone binding studies were carried out at 0 C in cytosol from various adipose tissues of adrenalectomized rats and bound hormone was separated from free by Sephadex chromtography. Despite the presence of protein protective agents, receptor binding decayed significantly over 24 h but appeared stable from 1 to 5 h. Epididymal fat pad cytosol had an apparent Kdiss at 0 C for dexamethasone of approximately 6 nM and a binding capacity of approximately 200 fmol per mg protein. To prove that the receptors were located in fat cells and not in surrounding connective tissue, isolated adipocytes were prepared by collagenase digestion and receptors were demonstrable in the cytosol from these cells as well. The affinity of series of steroids for the receptor was in the sequence: dexamethasone greater than corticosterone greater than progesterone greater than aldosterone greater than cortexolone greater than testosterone greater than estradiol. Receptors of roughly the same affinity but somewhat fewer binding sites on the basis of cytosol protein were also found on other fat depots including peri-renal, peri-scrotal and popliteal. Of interest is the fact that interscapular brown fat and human subcutaneous fat also possessed similar these receptors, the higher competitive capacity of dexamethasone indicated that the binding was to glucorticoid rather than mineralocorticoid receptors. The data suggest that fat cells contain glucocorticoid receptors which are similar to those seen in other glucocorticoid targets. Presumably these receptors mediate the effects of glucorticoids on adipose tissue.

Adipose Tissue↗
PubMed1977

Glucocorticoid receptors and inhibition of bone cell growth in primary culture.

We have previously identified glucocorticoid binding proteins in cytosol of cells dispersed from fetal rat calvaria by collagenase digestion. The present study, employing primary culture of these cells, provides further evidence that these binding proteins represent glucocorticoid receptors. [3H]Dexamethasone bound to cytoplasmic extracts of cultured cells with an apparent Kdiss of 6.8 nM and exhibited approximately 8500 binding sites/cell. Nuclear translocation of [3H]dexamethasone was demonstrated with approximately 50% of bound steroid extractable from the nuclear pellet after incubation at 37 C; little nuclear transfer occurred at 0 C. The specificity of these binding site was characterized by competition studies with other steroids in whole cells, the order of affinities being: triamcinolone acetonide greater than dexamethasone greater than progesterone greater than cortisol greater than corticosterone = cortexolone. Non-glucocorticoids except progesterone competed only poorly. Sedimentation analysis of [3H]dexamethasone-protein complexes on sucrose gradients revealed a cytoplasmic peak of 6.5 S in salt-free gradients and 3.8 S in 0.3 M KCl gradients. Dexamethasone addition to the culture medium resulted in a dose-dependent inhibition of cell growth with approximately 40% reduction in cell number at 13 nM. That this inhibition was receptor mediated was substantiated by the partial blockade of the dexamethasone effect in the presence 1.3 microM progesterone. Functionally, dexamethasone inhibits the growth of these cells. These data provide evidence for receptor mediated inhibitory effects of glucocorticoids directly at the level of the bone cell.

Animals↗
PubMed1976

C-type virus particle formation in erythroblastic islands in spleens of C3Hf mice injected with erythropoietin.

Previous studies suggested a possible association between C-type virus particle formation and erythropoiesis. In this experiment, normal C3Hf mice were injected with erythropoietin in order to increase the rate of erythropoiesis. Sections of spleen from these animals revealed extensive areas of erythroblasts. C-type particles, budding from erythroblasts, were often observed in such areas of spleen from every mouse injected with erythropoietin. In contrast, in sections of spleen from control mice, zones of erythropoiesis were limited, and only a few scattered C-type virus particles were observed in some of the animals examined.

Animals↗
PubMed1976

Agonist and antimineralocorticoid activities of spirolactones.

To investigate the mechanism of action of antimineralocorticoids, a series of spirolactone analogues was evaluated for both mineralocorticoid antagonist and agonist activity. Antagonist activity was assessed by inhibition of aldosterone stimulated sodium transport employing toad bladder short-circuit current (SCC) measurements. Agonist activity was assessed in the same system by the direct effect of spirolactones on SCC. Opening of the gamma-lactone ring of a spirolactone dramatically decreased antagonist activity in the compound studied. Several C-7 chi-substitutions resulted in either enhanced or diminished activity, whereas deletion of the C-10 methyl group (i.e., 19-nor compound) had only minimal effects on antagonist potency. Agonist activity was demonstrable for three of the analogues studied: the 19-nor compound, and those containing a C-7 chi-substitution with a carboxyl isopropyl ester or a C-6-7 cyclopropyl linkage. The functional activity in toad bladder was compared to previous measurements of the relative binding affinity of the same spirolactones for mineralocorticoid receptors in rat kidney. Although there was some correlation between binding to rat kidney receptors and antagonist activity in the toad bladder, the results did not coincide in the case of the three spirolactones that possessed partial agonist activity. Some of the discrepancy may have resulted from differences between mammalian and amphibian receptors; however, intrinsic agonist activity limits antagonist potency and thus may cause a divergence between binding and functional studies limited to antagonist activity alone. Binding affinity, although indicative of total activity, fails to distinguish agonist from antagonist potency.

Aldosterone↗
PubMed1976

Intrinsic mineralocorticoid agonist activity of some nonsteroidal anti-inflammatory drugs. A postulated mechanism for sodium retention.

Because some nonsteroidal anti-inflammatory drugs (NSAID) induce salt and water retention and exhibit other steroid-like actions, studies were performed to ascertain whether these drugs possess intrinsic mineralocorticoid agonist activity. In vitro competitive binding assays utilizing tissue from adrenalectomized rats demonstrated that some NSAID can displace [3H]-aldosterone from renal cytoplasmic mineralocorticoid receptors. Displacement potency for these sites was in the sequence: aldosterone greater than spironolactone greater than phenylbutazone (PBZ) greater than aspirin (ASA) greater than indomethacin (IDM). Concentration ratios required to obtain significant displacement of [3H]aldosterone were high but clearly within the therapeutic range for PBZ and ASA but not IDM. The analogues oxyphenbutazone (OBZ) and sodium salicylate (SS) were similar in binding activity to PBZ and ASA, respectively. Lineweaver-Burk analysis revealed that the inhibition of [3H]aldosterone binding was competitive in nature. In addition, PBZ was shown to prevent the nuclear binding of [3H]aldosterone. In vivo injection of PBZ and ASA resulted in competition for [3H]aldosterone renal binding comparable to the in vitro studies. Administration of PBZ and OBZ to adrenalectomized rats resulted in significant salt retention whereas ASA and SS did not differ significantly from controls. Salt retention elicited by PBZ and OBZ was inhibited by spironolactone, a competitive mineralocorticoid antagonist. These data suggest that, despite nonsteroidal structures, PBZ and OBZ induce salt retention via a receptor-mediated mineralocorticoid pathway analogous to aldosterone action.

Aldosterone↗
PubMed1976

16Beta-hydroxydehydroepiandrosterone: the dichotomy between renal receptor binding and urinary electrolyte activity.

Excessive production of 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA) has been suggested as a cause of low-renin essential hypertension. The mineralocorticoid effect of 16beta-OH-DHEA was reported to be one-fortieth that of aldostereone in the rat bioassay. Using kidney slices from adrenalectomized rats, the affinity of 16beta-OH-DHEA and a series of related compounds for mineralocorticoid receptors has been determined. In studies done at both 4 C and 37 C, the affinity of 16beta-OHDHEA for mineralocorticoid receptors was found to be less than 0.1% that of aldosterone (P less than 0.01). Various related steroids and/or potential metabolites similarly showed negligible affinity for the aldosterone receptor. In addition, In addition, 16beta-OHDHEA showed no significant affinity for renal dexamethasone-binding sites (Type II glucocorticoid receptors), corticosterone-binding sites (Type III glucocorticoid receptors), dihydrotestosterone binding sites, or estradiol binding sites. In in vivo competition experiments, the concurrent administration of 50 mug deoxycorticosterone reduced (3H)aldosterone binding to 20-30% of control levels; 50 mug 16beta-OH-DHEA did not compete for (3H)aldosterone binding sites. In in vivo bioassay electrolyte excretion was found-in contrast to that of aldosterone-to be variable. Within a given group, certain rats reproducibly responded to 16beta-OH-DHEA by sodium retention and kaliuresis; in others no response was observed. In vitro binding studies comparing "responders" with "non-responders" demonstrated that in neither group did 16beta-OH-DHEA have significant affinity for renal mineralocorticoid receptors. Accordingly, the mechanism whereby 16beta-OHDHEA produces changes in urinary electrolyte excretion appears independent of classical mineralocorticoid effector mechanisms. The conditions under which this effect is seen await eludication.

Aldosterone↗