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A study was made of the function of beta-adrenoreceptors and Chinese hamster fibroblast cAMP during their desensitization to isoproterenol. Desensitization of adenylate cyclase was demonstrated to lead to the reduction of both the cAMP response to isoproterenol and isoproterenol capacity to protect the cells from ionizing radiation. This did not entail any changes in the number of beta-adrenoreceptors or in the dissociation constant of the beta-antagonist. It is assumed that desensitization provokes functional dissociation of the beta-receptor and adenylate cyclase. Intact adenylate cyclase is an absolute must for realization of the antiradiation potency of isoproterenol.

A metabolic selective system has been proposed for the selection of hybrid hybridomas (tetradomas) based on the introduction in one of the parental cell lines of two traits simultaneously--a recessive one (resistance to 8-azaguanine) and a dominant one (multidrug resistance). Tetradomas were selected in the presence of two selective agents: aminopterin and actinomycin D. Using this approach we produced tetradomas secreting bispecific MAbs to horseradish peroxidase and human alpha-fetoprotein.

Immunization of DMBA-treated mice by the glycoprotein fraction from mammary glands of mice BALB/c did not decrease the frequencies of induction of mammary tumors. This is in contrast to the results obtained during immunization by the formaldehyde treated preparation of Mouse Mammary Tumor Virus (MMTV). EcoRI and HindIII cleaved DNA from the DMBA-induced mammary tumors did not contain the additional virus specific fragments. In mammary tumors the expression of p27 MMTV was registered in contrast to normal mammary glands and mammary epithelium cultures in which the proteins of MMTV are not expressed even after induction.

Variations in the intrinsic activity of 1-isoproterenol and in the percentage of high affinity beta-receptor complexes have been studied under a changes in the macrostructure of reticulocyte plasma membranes. The fluid lipid fraction have been reduced in the membranes for this by phospholipase A2/BSA treatment. It was accompanied by a progressive decrease in the fraction of beta-receptors that are able to form the high affinity complexes with 1-isoproterenol (receptor--regulatory N-protein complexes). Evaluated with the ability to activate the adenylate cyclase, the intrinsic activity of 1-isoproterenol was decreased from 1 to 0 under with conditions. This variations proved to correlate strongly with each other. Thus, changes in the membrane macrostructure may directly determine an efficiency of hormone actions.

Hormonal activation of the adenylate cyclase complex is associated with lateral mobility of proteins constituting this complex. Modification of interaction of the adenylate cyclase complex proteins due to variations in the "fluid" lipid fraction in cell membranes was studied. The decrease of percentage of "fluid" lipids in rat reticulocyte plasma membranes resulted in a decrease (up to a full stop) of interaction of beta-adrenoreceptors with regulatory N-proteins. The interaction of N-proteins with catalytic proteins was also blocked. On the other hand, an increase in the "fluid" lipid fraction led to a more intensive interaction. The observed phenomena do not result from functional damages of interacting proteins. Analysis of experimental results within the framework of the percolation theory suggests that hormonal activation of the adenylate cyclase complex depends on the "fluid" lipid fraction in the membrane and that the interacting proteins diffuse at distances comparable with the size of the cell membrane. The intrinsic activity of the beta-agonist isoproterenol changes from 1 to 0, depending on the "fluid" lipid fraction. The experimental data also suggest that there are no beta-receptors precoupled with N-proteins in rat reticulocyte membranes in vitro.

A new method is described, which enables one to follow the blood concentration of CyA in patients living in remote regions, being far away from the transplantation hospitals. The method is based on the use of chromatographic paper FN-17 intended for application of the patients' blood spots. The pieces of paper with dried blood spots are sent by post to the laboratory where CyA is extracted from the spots, followed by the CyA concentration measurement with the aid of RIA. A procedure has been elaborated, permitting the measurement of the CyA concentration in patients with a poor access to the veins.

Six cloned DNA fragments representing different portions of the genomic region amplified in multidrug resistant Djungarian hamster cells were used to study amplicon variations in a large number of the resistant cell lines. Expressed correlation exists between the degree of 3 cloned sequences amplification and the level of multidrug resistance. Three other cloned regions amplify coordinately with the latter ones at the initial steps of selection. Later their amplification halts and they mao even eliminate from amplicons of highly resistant cells. The rates and order of elimination of these sequences vary among different independently derived series of multidrug resistant cell lines.