Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities.

Many essential biological pathways, including cell growth, development, and metabolism, are regulated by thyroid hormones (THs). TH action is mediated by intracellular receptors that belong to a large family of ligand-dependent transcription factors, including the steroid hormone and retinoic acid receptors. So far it has been assumed that TH receptors (TRs) regulate gene transcription only through the classical protein-DNA interaction mechanism.

Antagonism between retinoic acid receptors.

In the developing mouse, retinoic acid receptors (RARs) beta and gamma 1 are expressed in characteristic spatiotemporal patterns which are correlated with different developmental fates of the respective tissues. Understanding the cues that regulate the expression of the various RARs may therefore provide insights into the process of tissue diversification. Transcription of RAR beta is rapidly upregulated through a retinoic acid-responsive element (here referred to as the beta RARE) in its promoter.

Regulatory functions of a non-ligand-binding thyroid hormone receptor isoform.

Gene regulation by thyroid hormones is mediated through multiple nuclear receptors. Only some of these thyroid hormone receptor (TR) isoforms become transcriptional enhancers in the presence of the thyroid hormone T3. Here we analyze the regulatory function of the human TR alpha 2 isoform.

Thyroid hormone receptors repress estrogen receptor activation of a TRE.

The identification of hormone response elements in the promoter regions of hormonally regulated genes has revealed a striking similarity between the estrogen response element (ERE) and a palindromic thyroid hormone response element (TRE) derived from the GH gene promoter. In addition, this TRE was described as a strong retinoic acid receptor response element for all three subtypes: alpha, beta, and gamma. We show here that the TRE in the absence of thyroid hormone receptor (TR) behaves similarly to imperfect EREs, which can synergize to mediate a strong estrogen-dependent activation of transcription.

Ligand-binding domain of thyroid hormone receptors modulates DNA binding and determines their bifunctional roles.

We report here that the thyroid hormone receptors TR alpha and TR beta, and the retinoic acid receptor, RAR, can bind cooperatively to the thyroid hormone response elements (TRE) in both the presence and absence of ligand. Although the transcriptional synergism induced by such cooperative DNA binding could also be influenced by the position of the DNA-binding site on the promoter, the strength of the receptor-DNA interaction in the absence of the cognate ligand of each receptor was in general correlated with the repression activity. The strong-binding TRs, but not the weaker-binding RAR, allowed repression of a constitutive promoter.

A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter.

The morphogen retinoic acid (RA) regulates gene transcription by interacting with specific nuclear receptors that recognize DNA sequences near responsive promoters. While much has recently been learned about the nuclear receptor proteins, little is known about the genes that are directly regulated by RA and their cis-acting response elements recognized by these receptors. Here we have analyzed the RA receptor-beta (RAR beta) gene promoter that is controlled by RA.

The human estrogen receptor has transcriptional activator and repressor functions in the absence of ligand.

Most studies on the cloned human estrogen receptor (hER) have been conducted with a mutant receptor in which Gly400 is changed to Val. Here we describe two novel regulatory functions of wild-type hER that are hormone independent: (i) a constitutive activator function and (ii) a repressor activity. Mutations in the hormone-binding domain, including the Val400 mutation, impair both of these functions.

[Biological availability of ibuprofen in Imbun 500 suppositories].

Concentration of ibuprofen in rabbit blood was found to be considerably higher after application of Imbun-500 suppositories, containing 500 mg of ibuprofen lysine salt equivalent to 292.6 mg of free ibuprofen, than after application of ibuprofen dragees containing 400 mg of the free drug. Parameters characterizing biological availability of ibuprofen in Imbun-500 suppositories (AUC, Cmax, tmax) were determined.

[Afterloading contact therapy in childhood tumors].

Two examples are presented to apply high dose rate afterloading therapy in treatment of tumors in childhood. The AL-therapy can be indicated in tumors in natural or artificial openings of the body that are limited locoregionally or were operated in sano. Applying brachytherapy radiogenic late-effects can be prevented in normal tissue like gonads and skeleton predominantly.

Non-Hodgkin's lymphomas--prognostic analysis and therapeutic recommendations.

The total non-Hodgkin's lymphoma-population between 1960 and 1985 treated by means of radiotherapy or combined radio-chemotherapy in the Medical Academy Dresden was analysed prognostically. 247 patients were classified according to previous scheme, 79 were subdivided on the basis of the recommendations of the Kiel-classification. The remission rates and survival curves achieved bear comparison with international literature (remission rates for the low-malignancy group = 85.

Investigation of the corticosteroid receptor system in rat hippocampus by ion exchange fast protein liquid chromatography.

In order to study the receptor system for adrenocortical steroids, hippocampal cytosolic preparations--containing both type I and type II receptors--were subjected to anion exchange fast protein liquid chromatography (FPLC). With running buffer containing Tris, EDTA, and glycerol three peaks (1-3) were eluted from the column at 220, 400 and 560 mM NaCl respectively regardless of whether [3H]corticosterone or [3H]RU 28362 had been used as radiotracer. None of the peaks was caused by serum transcortin as revealed by control studies.

Specific inhibitors implicate a soluble metalloendoproteinase in exocytosis.

1. Previous studies have demonstrated that exocytosis in adrenal chromaffin cells appears to require zinc-dependent endoproteinase activity. 2.

Photoaffinity labeling with [3H]RU 28362: a powerful tool for the study of rat brain glucocorticoid receptors.

In order to study the receptor system for adrenocortical steroids in rat brain the synthetic glucocorticoid RU 28362 (11 beta, 17 beta-dihydroxy-6-methyl-17 alpha-(1-propynyl) androsta-1,4,6-trien-3-one) has been used for photoaffinity labeling. Competition and dissociation studies revealed a single class of binding sites for RU 28362 in rat brain cytosol. Photoaffinity labeling was performed by u.

Novel polyether antibiotics X-14873A, G and H produced by a Streptomyces: taxonomy of the producing culture, fermentation, biological and ionophorous properties of the antibiotics.

Novel polyether antibiotics X-14873A, X-14873G, and X-14873H are produced by the fermentation of Streptomyces sp. X-14873 (ATCC 31679). This report presents taxonomic studies and fermentation conditions for the antibiotic producing culture.

Interactions of vasodilators with calcium entry- and beta-blockers in patients with coronary heart disease.

Combinations of antianginal drugs may be used for an additive effect against angina, but also to off-set unwanted effects of one drug with another, either by direct effects or by a reduction of dosage of each drug. Based on earlier studies with separate drugs we have now examined the effect of 150 mg bupranolol combined with 40 mg isosorbide dinitrate (ISDN) in one retarded tablet, given twice daily. 22 patients with CHD entered the study, 11 of those with and 11 without signs of ischemia during exercise.

Kinetics of azathioprine metabolism in fresh human blood.

Azathioprine (AZA) is transformed in the whole fresh human blood in vitro to 6-mercaptopurine (6-MP). The rate of the above reaction was followed as a function of time at 25, 30 and 37 degrees C. Pseudo-first-order rate constants and thermodynamic parameters were calculated.

Pharmacokinetics of elimination of 6-mercaptopurine in the urine of children with acute lymphoblastic leukemia.

6-Mercaptopurine (6-MP)-induced sodium azide--iodine reaction was adapted for determination of 6-MP in urine of four children treated with single oral doses of the drug in tablets. Open one-compartment body model was assumed, and first-order elimination rate constants (K) and biological half-life times (t0,5) were calculated, and their precision was determined by statistical treatment.

Mutants of Aspergillus nidulans blocked at an early stage of sporulation secrete an unusual metabolite.

Mutants of Aspergillus nidulans defective in conidiation (asexual sporulation) can be classified according to whether they are blocked before or after induction of conidiation. Mutants blocked before induction (preinduction mutants) appear to be unable to respond to the inducing stimulus and thus are defective in one of the earliest events in the sporulation process. Three preinduction mutants have been isolated and characterized.

Preparation, properties and biological activity of natural and semisynthetic urethanes of monensin.

Conversion of the monovalent polyether antibiotic monensin into a series of urethane derivatives substituted at C-26 causes a ten-fold increase in the cation transporting properties of the antibiotic as well as making the resulting semisynthetic urethanes divalent ionophores. These changes must in part account for the enhanced antimicrobial activities of the urethanes. The most active derivatives are the phenylurethanes which are ten times more active in vitro against Gram-positive bacteria and unlike monensin are active against Candida albicans and Penicillium digitatum.

Laccase localized in hulle cells and cleistothecial primordia of Aspergillus nidulans.

Several species of the genus Aspergillus form sexual spores within minute (approximately 0.2 mm) spherical shells (cleisthothecia) which are woven from specialized hyphae. Aspergillus nidulans cleistothecia are uniquely characterized by their dark red coloration and an envelope of thick-walled globose cells (hulle cells).