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Biomedical subjects

G Beck

Publications and source records attributed to G Beck.

At least 109 records · Page 6Linked to original sources
PubMed1989

Binding studies of the antiglucocorticoid RU38486 in Daudi and Raji lymphoma cells.

The activity of RU38486 has been studied in Burkitt's lymphoma cells which are Epstein-Barr virus (EBV) positive. The early antigens (EA) of the virus are induced by dexamethasone (DXM) in Daudi but not in Raji cells, whereas a growth factor (transforming growth factor-beta, TGF-beta) induces the EA in both cell lines. RU38486 blocks the EA induction obtained by DXM or by TGF-beta in either cell line. In order to understand the interaction of RU38486, we considered its binding to specific receptors. We first investigated the binding of the antagonist in whole cells at 22 degrees C. A number of specific binding sites higher for RU38486 than for DXM was found, suggesting that RU38486 may bind to the glucocorticoid receptor and also to other cellular structures which we called the antiglucocorticoid binding sites ("AGBS"). To support this hypothesis, competition experiments have been conducted between RU38486 and other steroid hormones (progesterone and testosterone) since it is known that RU38486 is also able to interact with their cognate receptors. Binding studies of RU38486 in vitro at 4 degrees C in the presence of cytosolic extracts from Daudi and Raji cells led to conclusions similar to those drawn from the whole cell experiments: more complexes were formed with RU38486 than with DXM. Finally, the steroid-receptor complexes were incubated with DNA-cellulose. Since the binding measured for RU38486 was higher than for DXM, we suspect that sites different from the classical glucocorticoid receptor sites are also able to interact with DNA. The blockage exerted by RU38486 on the EA induced by glucocorticoids or by non-steroidal molecules and the lack of responsiveness to glucocorticoids in Raji cells are discussed in the light of the present findings.

Binding, Competitive↗
PubMed1989

Interrelationship between RU38486 and the P450 activities in rat liver.

Microsomal P450 monooxygenases contribute actively to the biotransformation of the antiglucocorticoid RU38486, an 11 beta-substituted nor-steroid. Pretreatment of adult rats by inducers of specific forms, belonging to different P450 subfamilies, affects the ability of liver microsomes to metabolize RU38486. Phenobarbital and pregnenolone 16 alpha-carbonitrile increase the metabolic activity of liver microsomes whereas methylcholanthrene decreases their capacity to oxidize the steroid. Thus P450 forms IIIA, IIB1,2 and IIC7 are good candidates to be involved in the degradation of this peculiar molecule. Our study has been completed by investigating whether RU38486 would influence the P450 spectrum. Whereas the treatment of rats with either a glucocorticoid (cortisol, dexamethasone) or an antiglucocorticoid (pregnenolone 16 alpha-carbonitrile) has been shown to induce the P450 activity by increasing the hepatic concentration of form IIIA, we observed a slight decrease of the P450 activity by treating the animals with RU38486. Moreover RU38486 was able to antagonize the P450 induction by the other steroids as well as it inhibits the synthesis of various liver enzymes induced by glucocorticoids (for instance tyrosine aminotransferase). These findings may be important for the therapeutic use of RU38486 since its inhibitory effect on P450 activity may be at the origin of drug interactions by modifying the endogenous hormonal status.

Animals↗
PubMed1989

Effects of glucocorticoids on plasma catecholamines in depression.

To explore corticosteroid-catecholamine interactions in depression, plasma dopamine, norepinephrine, and epinephrine concentrations were studied both before and after dexamethasone in 16 patients during depression and after recovery, and in 28 healthy controls. Dexamethasone had a significant suppressive effect on plasma epinephrine levels in depressed patients and controls, while dopamine and norepinephrine levels were not significantly affected following dexamethasone administration. Levels of norepinephrine, epinephrine, and cortisol were positively correlated, while dopamine showed no correlation with cortisol values. These findings point to differentiated interrelations between certain catecholamines and glucocorticoids which possibly are affected during depressive illness.

Adult↗
PubMed1989

Characterization of interleukin-1 activity in tunicates.

1. Eight North American species of tunicates were examined for the presence of interleukin-1 (IL-1) like activity. 2. The tunicates studied produce molecules with readily detectable lymphocyte activation factor (LAF) activity. 3. G50 column chromatography separated molecular species that were directly mitogenic for thymocytes (mol. wt greater than 50,000) from those that were comitogenic in an IL-1 assay (mol. wt 20,000). 4. Tunicate fractions with LAF activity induced increased vascular permeability in rabbit skin. 5. Tunicate LAF activity was neutralized by polyclonal anti-human IL-1 antisera. 6. These data further support the conclusion that IL-1 is an ancient and functionally conserved molecule.

Animals↗
PubMed1989

Streptococcus pneumoniae and Staphylococcus aureus surface properties in relation to their adherence to human buccal epithelial cells.

Adherence to host cells by pathogenic bacteria is achieved through both specific and non-specific mechanisms. The former involve bacterial adhesin and corresponding cell receptors (Gibbons and Van Houte, 1980), while the second include electric charges and hydrophobicity of bacterial cell walls. In a previous study (Beck et al., 1988), we showed that these two cell surface characteristics vary during growth of Staphylococcus aureus in a manner which should promote adherence to host cells. The aims of the current study were to assess: (1) whether the same growth-related variations in surface properties were present in another bacterial species, Streptococcus pneumoniae; (2) whether the adherence of the two types of bacteria to epithelial cells was in fact different at different growth times; and (3) whether such differences were consistent with the observed surface properties.

Bacterial Adhesion↗
PubMed1989

[Selective abortion under sonographic control in multiple pregnancy].

Selective embryocide was performed at 9 weeks in a patient with a quadruplet pregnancy. No complications occurred and the patient was delivered of healthy triplets at 31 3/7 weeks of pregnancy. This procedure may be offered to patients with pregnancies with more than four embryos.

Abortion, Eugenic↗
PubMed1989

Adherence of Pseudomonas aeruginosa to respiratory epithelium and the effect of leucocyte elastase.

The tracheobronchial secretions from patients with cystic fibrosis often contain high amounts of free proteases. To evaluate whether human leucocyte elastase (HLE) can favour the persistence of bacterial airways infection, we exposed the frog palate mucosa to HLE and then to radiolabelled Pseudomonas aeruginosa and followed the sequence of events by scanning electronmicroscopy. In response to HLE there was a marked outpouring of mucus and a desquamation of the epithelium. P. aeruginosa was shown to adhere to recently secreted granules of mucus and to the exposed submucosal underlying connective tissues. For the eight different bacterial strains studied, a significative adherence to HLE-injured mucosa was observed only in strains that possessed internal haemagglutinating activity. Neither the presence of fimbriae, nor of the mucoid exopolysaccharide, nor of the bacterial surface haemagglutinating activity could be related to adherence of P. aeruginosa to the injured mucosa. These results support the hypothesis that HLE enhances bacterial infection of the respiratory mucosa both by inducing mucus hypersecretion and by exposing receptors to the microbial adhesins. It is also suggested that P. aeruginosa internal lectins may be implicated in adherence to host tissues.

Animals↗
PubMed1989

Blunted adrenocorticotropin but normal beta-endorphin release after human corticotropin-releasing hormone administration in depression.

Since the discovery of CRH in 1981, several investigators have reported abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in response to direct stimulation of the corticotroph cells in patients with psychiatric disorders. To further explore HPA system integrity in major depressive disorders, 13 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 100 micrograms synthetic human CRH as an iv bolus dose. Compared to that in the normal subjects, in the depressed patients a significant attenuation of the net ACTH release after CRH administration (772 +/- 597 vs. 263 +/- 286 pmol/min.L; P less than 0.02) was observed, while beta-endorphin and cortisol responses did not differ significantly between the groups. The magnitudes of ACTH and cortisol release were negatively correlated in the patient group only (r = -0.67; P less than 0.01). Thus, the blunted ACTH response to CRH in depression might be related to hypercortisolemia, while the implications of the apparent dissociation of ACTH and beta-endorphin after CRH administration still remain unclear. Our data support the hypothesis that the hyperactivity of the HPA system in depression most likely is a consequence of CRH hypersecretion, the origin of which may be explained by abnormal central glucocorticoid receptor or neurotransmitter regulation.

Adrenocorticotropic Hormone↗
PubMed1989

Isolation of interleukin 1 from joint fluids of patients with Lyme disease.

To investigate the role of interleukin 1 (IL-1) in Lyme arthritis we assayed synovial fluids (SF) for the presence of IL-1 activity. Crude SF from patients with Lyme disease showed IL-1-like activity. Chromatography of joint fluids revealed activity at 15-20,000 daltons. Two populations of cells were grown, which produced significant IL-1 activity when stimulated with the Lyme disease spirochete or its lipopolysaccharide. IL-1 activity from SF or stimulated cells was neutralized with an antihuman IL-1 antibody. Our results suggest IL-1 is important in the pathogenesis of Lyme arthritis, and is similar to other arthritides.

Borrelia↗
PubMed1988

Inhibition of hepatoma cell growth by a steroid anti-hormone.

The antiproliferative effect of the potent antiglucocorticoid and antiprogestin RU38486, an 11 beta-substituted nor-steroid, was investigated on the HTC cell line. Its action clearly visualized in absence of serum, is reversible. Dexamethasone does whereas progesterone does not protect the cells against the cytostatic effect. Thus, the latter rather depends on the antiglucocorticoid- and not on the antiprogestin-function of RU38486. Taking into account the antiproliferative action on HTC cells together with the antiglucocorticoid behaviour in hepatocytes and hepatomas, our results suggest that RU38486 might represent a potential drug for liver tumour therapy.

Animals↗
PubMed1988

Role of leukotrienes in acute gastric lesions induced by ethanol, taurocholate, aspirin, platelet-activating factor and stress in rats.

This study was designed to determine the role of leukotriene C4 (LTC4) in the formation of acute gastric lesions induced by 100% ethanol, acidified taurocholate (TC), acidified aspirin (ASA), platelet-activating factor (PAF), and water-immersion and restraint stress. Exogenous LTC4 alone administered in gradually increasing doses (5-20 micrograms/kg/hr) caused only mild hemorrhagic lesions in the gastric mucosa but when combined with 100% ethanol, acidified TC, acidified ASA, or stress, it increased significantly the mean lesion area and lesion number as compared to those produced by these ulcerogens alone. FPL 55712, a LTC4 antagonist, given orally (2.5-10 mg/kg) reduced dose-dependently the extent of gastric lesions in all experimental models used and completely prevented the deleterious effects of exogenous LTC4 on gastric mucosa. PAF augmented the mucosal lesions induced by 100% ethanol, and this was also reduced by the pretreatment with FPL 55712. FPL 55712-induced gastroprotection against various ulcerogens was reversed, in part, by indomethacin, indicating that it could be attributed not only to the LTC4 antagonism but also to increased biosynthesis of PGs. This study provides evidence that LTC4 is involved in the formation of acute gastric damage and the antagonism of LTC4 may protect the mucosa against various ulcerogens.

Animals↗
PubMed1988

Antagonistic action of RU38486 on the activity of transforming growth factor-beta in fibroblasts and lymphoma cells.

Transforming growth factor-beta (TGF-beta) is a multifunctional protein involved in the control of proliferation, differentiation and other functions in many cell types. The anchorage-independent growth of some established lines of untransformed fibroblasts in soft agar is induced by TGF-beta and requires in addition exogenous EGF for certain target cells, notably rat NRK-49 cells. The formation of colonies of NRK-49F cells is completely inhibited by the synthetic 11-beta substituted nor-steroid RU38486 added at a final concentration of 1.3 X 10(-5) M. We also explored the effect of TGF-beta on Daudi and Raji lymphoma cells by measuring the production of Epstein-Barr Virus (EBV) early antigens (EA). In Daudi cells an induction capacity giving rise to 10-16% positive EA-cells was observed; in Raji cells the induction only reached between 6 and 8%. The induction was partially inhibited by the anti-steroid RU38486 in both systems. Thus, RU38486 not only antagonizes the glucocorticoid hormone action but also interferes with the effects of TGF-beta in fibroblasts and in lymphoma cells. The molecular basis of the interactions observed was investigated by considering (1) the binding to specific receptors, (2) transfection experiments, in order to examine if the interference of the anti-steroid with TGF-beta activities occurs at the transcriptional level as in the case of glucocorticoid induction. The results suggest that the blocking by antiglucocorticoids of the effects of TGF-beta and glucocorticoids, in fibroblasts and lymphoma cells, occurs by different mechanisms.

Animals↗
PubMed1988

Structural and immunochemical properties of rat liver tyrosine aminotransferase.

Our results show for the first time sequence data of the N-terminal part of tyrosine aminotransferase. This unblocked form of TATase, which has never been detected before, starts with a serine. This serine was found at position 29 of the primary structure of the enzyme deduced from the cDNA. We suggest that this free N-terminal amino acid is the extremity of a TATase form generated by proteolysis during the process of purification. Thus, proteolysis does not occur at the C-terminal as has been suggested before, but rather at the N-terminal region of the enzyme. To confirm this possibility, a peptide corresponding to the sequence of the seven carboxy-terminal amino acids of TATase was synthesized. It was coupled to ovalbumin or keyhole limpet hemocyanin, and the resulting conjugates were used to raise anti-peptide antibodies. The crude sera obtained were purified and their abilities to recognize TATase in ELISA and dot-blot experiments were proven. Our results demonstrate that the C-terminal part of the enzyme is present and well-recognized by the anti-peptide serum prepared. Furthermore, the anti-peptide serum reacts with TATase without inhibiting its enzymatic activity.

Amino Acid Sequence↗