Biomedical subjects
Publications and source records attributed to F Svec.
We believe this is the first reported case of seminoma in a patient with the 48,XXYY variant form of Klinefelter's syndrome. Moreover, the seminoma in this patient occurred in a normally descended testis. We report this case because patients with 48,XXYY Klinefelter's syndrome are often confined to institutions, where the diagnosis of testicular tumor may not be recognized as readily.
The initial goal of this work was to examine directly the properties of glucocorticoid receptors bound with antagonists. Cortexolone, progesterone, and R-5020 were the antagonists studied. The tritiated agonists, dexamethasone and triamcinolone acetonide, served as controls. Although the three antiglucocorticoids interfered with agonist binding to the glucocorticoid receptor, direct binding of the tritiated antagonists could not be reproducibility demonstrated using either a charcoal assay or rapid techniques like high performance liquid chromatography or vertical tube rotor ultracentrifugation. Ultraviolet radiation was used to attach covalently tritiated steroid to the receptor. This technique allowed the identification of species that bound agonist or antagonist. That the two classes of steroids bound to the same receptor was shown using a monoclonal antibody directed against the glucocorticoid receptor. These labeled species had the same physical properties upon ultracentrifugation, DEAE cellulose chromatography, and high performance liquid chromatography. It is concluded that although the interaction of antiglucocorticoids like progesterone with the glucocorticoid receptor may be fleeting, antagonists do interact with the glucocorticoid receptor and form complexes with grossly similar properties as those derived from an interaction with agonists.
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Spherical particles of porous poly(2-hydroxyethyl methacrylate) have been used in the treatment of patients suffering from focal alterations of the liver, namely haemangioma and hypervascular tumour. The treatment consisted of the preoperative endovascular occlusion of branches of the hepatic artery using these spherical particles, and was followed by an operation. The main merit of the preoperative occlusion of blood vessels is that it substantially reduces blood loss during surgery. In order to determine the optimal time for the operation on the liver, indicators of the coagulation system were examined in successive terms of the postemboilization period. Reaction of the organism to endovascular occlusion is reflected in hypercoagulation changes in the coagulation system.
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Regional fat distribution is an important risk factor for the development of diabetes and hypertension in white females; those with fat cells in the upper part of the body have a higher prevalence of diabetes and hypertension than those with similar degrees of obesity in the lower parts of the body. Whether this observation is relevant for the general population of black females is not known. In this article, we report the results of a study of fat distribution in black females and its correlation with the prevalence of diabetes and hypertension. One hundred black females who attend the Charity Hospital System of Louisiana were studied. Anthropometric measurements were taken, and the prevalence of both diabetes and hypertension determined by review of the medical record and patient interview. In this study, the waist to hips ratio was the index of fat distribution. Waist to hips ratio was found to increase with age. The observed prevalence of diabetes, hypertension, and both together was higher in those with upper body obesity: 40% of those in the lower quartile had diabetes, whereas 80% of those in the highest quartile had diabetes. The mean waist to hips of diabetic patients (0.95) was higher than the ratio for nondiabetics (0.90). Hypertensives also had a higher ratio (0.95) than nonhypertensives (0.89). This is the first study to show that waist to hips ratio in blacks correlates with the prevalence of diabetes and hypertension. This suggests that the measurement of waist to hips ratio is an important part of the physical evaluation and may be a predictor of morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)
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Obesity is a major health problem that can be defined as an excess of body fat, associated with hypertension, diabetes and coronary heart disease. Several groups have evaluated the clinical significance of variations in fat cell distribution on these complications. A frequently used index of fat cell distribution is the waist to hips ratio (W/H). A high W/H ratio is said to reflect upper body fat cell distribution while a low waist to hips ratio reflects a lower body type fat cell distribution. Studies have shown that those whose W/H ratio indicate upper body fat cell distribution had a higher prevalence of diabetes and hypertension than those with the lower type. Over the years cortisol has attracted considerable interest as a possible factor in the development and maintenance of obesity. The clinical findings associated with upper body type of obesity are in many ways similar to those of the hypercortisol state. Our hypothesis is that upper body obesity forms a unique subgroup of the obese population and their regional fat distribution is associated with mild cortisol excess. In humans, studies have reported that some obese subjects hypersecrete cortisol and have an increase in the cortisol production rate. Although recent studies would tend to discount any influence of cortisol in human obesity, several factors should be taken into consideration. It is difficult to measure cortisol economy in obese subjects because among other things the measurements are less than precise; and cortisol secretion changes during the day and in response to outside stimuli. Further, obesity is a heterogeneous disorder and not all obese subjects may have the same disorder.(ABSTRACT TRUNCATED AT 250 WORDS)
Although glucocorticoids are known to regulate their own receptor number, the physiologic significance of this process is not known. In order to assess this process in intact animals the effects of adrenalectomy, stress, and exogenous glucocorticoid on the number of hepatic glucocorticoid receptors in Swiss-Webster mice were evaluated. In males 24 hr after adrenalectomy there was a clear 2- to 2.5-fold increase (upregulation) in glucocorticoid receptor number. Conversely, 24 hr after the ip administration of exogenous corticosterone there was a clear downregulation of receptor number. In each case (upregulation and downregulation) female mice were much less responsive than males. Three stressors were used to evaluate the effect of the endogenous secretion of glucocorticoids on downregulation. Male mice were exposed to ether, vibration, and confinement either once or daily for periods up to 3 days. Animals were sacrificed 24 hr after the last stress and hepatic receptor number was compared to an unstressed control. Cytosolic receptor number was not influenced by any of these stimuli. It is concluded that although glucocorticoids clearly regulate glucocorticoid receptor number, as demonstrated by adrenalectomy and the administration of steroids to adrenalectomized animals, the physiologic significance of this process is uncertain as receptor number does not appear to be changed by stimuli of adrenal glucocorticoids in the intact animal.
The ability of nonradioactive progesterone to accelerate the dissociation of tritiated dexamethasone from the agonist-binding site of the glucocorticoid receptor was used as a probe for the existence of a second antagonist steroid site. The goal was to evaluate if this second site was on the glucocorticoid receptor and, if so, on what region of that protein. The magnitude of acceleration of dissociation was assessed during purification of the receptor as well as with the untransformed (multimeric), transformed (monomeric), and mero-receptor. In each preparation progesterone caused a statistically significant increase in the rate of agonist dissociation. The documentation of acceleration of dissociation during purification suggests that progesterone one is interacting with a site on the glucocorticoid receptor and not with another protein. Evidence for the second binding site was found using each form of the receptor, untransformed, transformed, and mero-receptor, suggesting that the second binding site resides on the steroid-binding domain of the receptor which is on the carboxy-terminus, topographically close to the agonist-binding site.
The physico-chemical properties of glucocorticoid receptors bound with tritiated corticosterone were compared to those of the triamcinolone acetonide glucocorticoid receptor complex. The goal was to determine whether the natural agonist forms complexes similar to those generated by the synthetic agonist. Structure was probed using three techniques; diethylaminoethyl-cellulose (DEAE) chromatography, vertical tube rotor sucrose gradient ultracentrifugation (SGU) and high performance liquid chromatography (HPLC). These techniques are all fast enough to allow analysis of the labile corticosterone receptor complexes. Results showed that complexes generated by both classes of ligands were similar. They eluted from DEAE cellulose and HPLC columns at similar positions and sedimented similarly in sucrose gradients. This was true for both the untransformed and transformed species. It is concluded that natural and synthetic glucocorticoid agonists interact with glucocorticoid receptors to form indistinguishable complexes. Thus synthetic agonists are appropriate probes of events which take place with natural glucocorticoids.
The effect of dexamethasone administered intraperitoneally on hepatic glucocorticoid receptor binding capacity was measured in adrenalectomized male Swiss Webster mice. The liver content of dexamethasone was also measured. Within 30 min of a 5 micrograms injection, the hepatic content of dexamethasone reached a maximum and fell quickly thereafter. By 6 h the hepatic content of dexamethasone had decreased to 25% of maximum and by 24 h the liver did not contain detectable dexamethasone. At this 24 h point, the glucocorticoid binding capacity was reduced to 50% of control. This decrease reflected down-regulation. Other studies revealed that only glucocorticoids caused this effect and doses of dexamethasone as low as 0.5-5 ng caused a clear down-regulation in binding capacity. Doses that cause receptor down-regulation are also effective at inducing tyrosine aminotransferase, suggesting that dexamethasone down-regulates its own receptors over a physiologically meaningful dosage range. It is concluded that dexamethasone causes a dose-dependent down-regulation of the glucocorticoid receptor in mouse liver.
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In this study we report the results of toxicological, histological and haematological experiments on radiopaque spherical particles based on poly(2-hydroxyethyl methacrylate). These particles have been developed for endovascular occlusion of various organs. Radiopacity was attained by two independent methods: the chemical attachment of radiopaque substances to the hydrogel or the precipitation of radiopaque substances in the hydrogel network. The first method yields particles that appear to have uniformly-distributed contrast material, but in the particles prepared by the second procedure the contrast material is predominantly located on the surface. The visibility of such particles by X-rays makes possible controlled embolus introduction and inspection of the polymer for long periods after embolization. Radiopaque contrasting changes the morphology and reduces the porosity of the material but supports quick thrombus formation. Embolic material implanted in rabbits becomes surrounded by a thin fibrous capsule and undergoes partial organization. This and other results of medico-biological investigations have fully demonstrated the biocompatibility of radiopaque spherical emboli, which can now be used clinically.
Patients with the acquired immunodeficiency syndrome (AIDS) often have signs and symptoms suggestive of adrenal insufficiency. Reports in the literature suggest that adrenal insufficiency may be relatively common in patients with AIDS based on the finding of destructive adrenal lesions in a large number of the patients studied. In no series, however, has standard testing for adrenal reserve been done in an unselected population of patients with AIDS. We found a normal response to a standard, short adrenocorticotropic hormone test in 11 consecutive patients with AIDS (P less than .0005). Thus, although adrenal involvement by various destructive lesions may be common in patients with AIDS, clinically significant adrenal insufficiency does not appear to be common.
Ketoconazole and RU 486 are both antagonists of glucocorticoid hormone action at the target cell level. Both inhibit the binding of agonists to the receptor, although RU 486 is many-fold more potent. As reported here, ketoconazole, like all naturally occurring steroidal antiglucocorticoids, enhances the rate at which agonists dissociate from the glucocorticoid receptor. This indicates that this antiglucocorticoid interacts with the receptor at a site other than the agonist-binding site. RU 486, on the other hand, does not accelerate dissociation, suggesting that it does not interact with the putative allosteric regulatory site on the glucocorticoid receptor. Combining these findings with previous reports leads to the hypothesis that glucocorticoid antagonists can be divided into two classes: those that act through a second regulatory site on the glucocorticoid receptor and those that act by direct competition with agonists at the agonist-binding site.