[CHARACTERISTIC OF ALTERATIONS OF ARTERIES IN PATIENTS WITH ISCHEMIC HEART DISEASE AND CHRONIC HEPATITIS C].

The article presents an assessment of degree and type of atherosclerosis of coronary and non-coronary vessels in old patients with ischemic heart disease associated with chronic viral hepatitis C (VHC), the incidence of myocardial infarction and the possibility of participation chronic VHC in atherogenesis. Patients with ischemic heart disease have correlation of atherosclerosis of arteries with age, hypercholesterinemia. Patients without chronic VHC more often give a higher risk of myocardial infarction, especially in early period (1-1,5 years) of onset of ischemic heart disease clinical implications.

[Clinico-immunologic characteristics of appendicitis in children].

Inflammation of the appendix is primarily a local process with the development of localized subcompensation of immunogenesis in simple appendicitis. Decompensation of immunogenesis and a destructive process develop in progressive insufficiency of immune reactions, in immune reactions of considerable intensity the inflammation is arrested spontaneously, but atrophy of lymphoid tissue remains as a consequence. Frequent (48.

[Increased substrate selectivity during transition from Ca2+-activated to K+,EDTA-activated nucleoside triphosphatase activity of heavy meromyosin].

A comparison of kinetic parameters (Km(app) and V) of hydrolysis by heavy meromyosin of natural (ATP and ITP) and modified nucleoside triphosphates showed that in the K+, EDTA-ATPase conformation the enzyme exhibited a higher selectivity towards the structure of the substrate nucleoside moiety than in the case of the Ca2+-stimulated nucleoside triphosphatase activity. In the presence of Ca2+, all the N1- and N6-substituted analogs of ATP as well as ITP, etheno-ATP and the dialdehyde derivative of ATP were hydrolyzed at a high rate irrespective of their markedly decreased affinity for heavy meromyosin. In the presence of K+, EDTA the ATPase activity showed a tendency for a total decrease of the analog affinity for nucleoside triphosphates, i.

[Several peculiarities of the purine-base fixation of the substrate in the active sites of myosin Ca2+-ATPase].

A comparative study of kinetic parameters (Km and V) of hydrolysis by heavy meromyosin of several synthetic ATP analogs with substituents at positions N(1) and N(C6) of the purine ring was carried out. Analysis of changes in the Km values suggests that the purine base of ATP is fixed in the active center due to the formation of a hydrogen bond between N1 and the proton donor group of the protein as well as between the 6-NH2-amino group of the nucleotide and the proton acceptor group of the protein. It was shown that the rate of catalytic conversion of the substrate is determined by the mode of binding of its purine ring.

[cAMP-dependent protein kinase from pigeon breast muscle. Isolation of regulatory subunits by affinity chromatography and study of the topography of the cAMP binding site using cAMP analogs].

The cAMP-dependent protein kinase from the soluble fraction of pigeon breast muscle is represented by two forms, PK I and PK II. The ratio of the phosphotransferase activity of the two forms is 35-40% and 60-65% for PK I and PK II, respectively. The regulatory subunit of PK I was isolated in a homogeneous state by affinity chromatography on 8-(2-oxoethylthio)-cAMP immobilized on epoxy-activated Sepharose 4B.

[Interaction of N1-, N6- and C8-substituted derivatives of adenosine-5'-triphosphate with the catalytic subunit of cAMP-dependent protein kinase from rabbit skeletal muscles].

In order to investigate the structure of the active site of the cAMP-dependent protein kinase catalytic subunit a synthesis of several previously unknown adenosine-5'-triphosphate (ATP) derivatives containing substituents of various nature at N(1), N(C6) and C(8) positions of the purine base was carried out. The interaction of these derivatives with a homogeneous preparation of the catalytic subunit of rabbit skeletal muscle cAMP-dependent protein kinase was investigated. All the nucleotide analogs were found to inhibit the enzyme activity; the inhibition was competitive with respect to ATP.

[Interaction between cyclic adenosine-3':5'-monophosphate phosphodiesterase and structural analogs of the substrate].

The interaction between synthetic structural analogs of cyclic adenosine-3':5'-monophosphate (3':5'-AMP) and rat liver 3':5'-AMP phosphodiesterase was studied. Various groups, including those capable of covalent binding to the protein, were injected into certain sites of the 3':5'-AMP molecule. All the compounds tested exerted an inhibiting effect; in seven cases this effect was irreversible.

[Interaction of Na,K-ATPase with modifying ATP analogs and chloromethylphosphonic acid].

The interaction of synthetic ATP analogs, containing active groups in the triphosphate moiety and in the 8-position of the nucleotide molecule, with highly purified Na, K-ATPase from the medullar layer of porcine kidney was studied. It was found that 11 out of 17 ATP analogs studied irreversibly inhibit the ATPase activity of the enzyme. The pH optimum of the enzyme inactivation by adenosine-5'-(beta-chloroethylphosphate) and adenosine-5'-(p-fluorosulfonylphenylphosphate) beside the pronounced protective effect of ATP suggests possible covalent blocking of histidine and dicarboxylic amino acid residues in the enzyme active center.

[Effect of alkylating derivatives of cyclic adenosine-3' ,5'-monophosphate on proliferation of mouse bone marrow stem cells].

The effect of the physiological concentration of cyclic adenosine-3' ,5'-monophosphate (cAMP) analogues on the proliferation of mouse bone marrow stem hemopoietic cells (CFUs) was examined. The stimulating effect was estimated from the decrease in CFUs expressed in the percentage derived from comparing the number of spleen colonies in the control and experimental groups treated with hydroxyurea 10(-3) M (incubation with hydroxyurea resuted in the cell death in S-phase). Cyclic AMP stimulted the proliferation of CFUs by 60%, while its analogues such as 8-(N-chloroacetylaminoethylamino)-cAMP, 1-(N-chloroacetylaminoethyoxy)-cAMP and 1-(N-(p-fluorosulfonyl)-benzoylaminoethoxy)-cAMP stimulated the proliferation by 39.

[Effects of some protein kinases, cyclic nucleotides and specific inhibitors of phosphorylation on the mitotic cycle of Physarum polycephalum].

The true slime mould Physarum polycephalum was treated with various agents by spraying them upon the cell surface 4 hrs before the second synchronous mitosis. The onset of mitosis was considerably approximated after the plasmodium treatment with protein kinases from rat hepatoma or Ph. polycephalum at the late G2 phase.

[Some properties of the catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase from pigeon breast muscle].

A method for the preparation of a homogenous catalytic subunit of adenosine 3':5'-monophosphate-dependent protein kinase from pigeon breast muscle was developed. The molecular weight of the enzyme as determined by electrophoresis in the presence of sodium dodecyl sulfate was found to be 42000. The pH optimum of the catalytic subunit was around 8.

[Nuclear magnetic resonance study of the conformation in nucleotides, oligonucleotides, and their analogs. I. Conformation of adenosine-3',5'-cyclic phosphate and its analogs in aqueous solutions].

Conformation in aqueous solution of adenosine-3',5'-cyclophosphate, 8-(beta-aminoethylamino) adenosine-3',5'-cyclophosphate, 8-(beta-oxiethylamino) adenosine-3',5'-cyclophosphate, 8-(carboxymethylamino) adenosine-3',5'-cyclophosphate and their non-cyclic analogs has been studied by NMR spectroscopy. The conformational situation in the model of dynamic equilibrium of sin- and anti-states has been described on the basis of spinlattice relaxation times and temperature dependences of chemical shifts. Adenosine-3',5'-cyclophosphate has been demonstrated to exist mainly in anti-conformation while 8-substituted analogs -- in sin-conformation.

[Reaction between adenosine-5'-chloromethylphosphonate and the allosteric center of phosphorylase B].

The interaction between phosphorylase B and an AMP analog, adenosine-5'-chloromethylphosphonate, is found to be irreversible. Their binding stechiometry is calculated from the differential absorption spectrum. Maximal inhibition is reached when 1,3--1,5 moles of the analogue is bound per mole of monomer phosphorylase B.

[Inhibition of leucyl-tRNA-synthetases by modified ATP analogs].

The interaction between modifying ATP analogs containing alkylating or phosphorylating groups in the polyphosphate moiety of the ATP molecule and leucyl-tRNA synthetases from cytoplasm and chloroplasts of Euglena gracilis (strain Z) was studied. It was shown that most of the ATP analogs irreversibly inhibit the cytoplasmic enzyme, having no inhibiting effect on the chloroplast synthetase. The kinetic constants K1 and k2 for the interaction between the most effective irreversible inhibitors and the cytoplasmic enzyme were determined.

[Interaction of 8-substituted derivatives and adenosine-3',5'-cyclophosphate esters with protein kinase from pig brain].

A synthesis of previously unknown 8-substituted derivatives and alkyl esters of cyclic adenosine-3',5'-monophosphate, containing reactive groups, was carried out. The interaction of the compounds obtained with a homogeneous preparation of protein kinase from pig brain was studied. It was found that all compounds, with the exception of neutral esters of 3',5'-AMP, activate the enzyme and competitively inhibit 3H-labelled 3',5'-cAMP binding by the regulatory subunit of protein kinase.

[A new method for synthesis of some nucleoside 5'-phosphonate esters].

A new method for synthesis of nucleoside-5'-phosphonates containing a reactive halogen atom in the phosphonate residue has been developed. In order to achieve selective inhibition of individual enzymes and to elucidate the structure of their active sites, the synthesis of 5-'chloromethyl-, 5'-(beta-bromoethyl)-and 5'-(N-chloroacetylaminomethyl)-phosphonate esters of adenosine and previously unknown analogous derivatives of uridine have been carried out. The method described may also be used to synthesize 5'-phosphonate esters of nucleosides, which contain radioactive labels.

[Conformation study of cyclic adenosine-3',5'-monophosphate and some of its derivatives by means of circular dichroism].

Circular dichroism spectra of adenosine and cyclic adenosine-3',5'-monophosphate (cAMP) and their derivatives, having different substituents in 8-position of heterocycle, are studied, cAMP is suggested to have preferable anti-conformation in the solution, while its derivatives with substituents in 8-position of purine base are preferable in sin-conformation. An exception is 8-(beta aminoethylamine-)cAMP, which has an anti-conformation within pH range from 4.5 to 9.

[Interaction of adenosin-3',5'-cyclosulfate with adenosine-3'5'-cyclophosphate dependent protein kinase and phosphodiesterase].

Interaction of adenosine-3',5'-cyclosulphate (cAMS) cAMP analogue, having sulphur atom instead of phosphorus in a six-term cyclic system with pig brain proteinkinase and rabbit skeletal muscle phosphodiesterase is studied. The affinity of proteinkinase to cAMS was found to be in 25000 times lower than the affinity of cAMP, the affinity of cAMS to the active site of phosphodiesterase being high enough. It is suggested that in the regulatory subunit of proteinkinase positive kationic group participates in nucleotide binding by interacting with negative oxygen atom of six-term cyclophosphate system.

[Structure of the active center of the catalytic subunit of histone kinase].

A number of unknown ATP analogues is isolated when studying the structure of the active site of catalytic histonekinase subunit. Adenosine-5'-chloromethanepyrophosphonate adenosine-5'-(beta-bromoethanepyrophosphonate) and adenosine-5'-(p-fluorosulphonylphenylphosphate) were isolated under the reaction of chloromethanephosphonic acid, beta-bromoethanephosphonic acid and n-phenolsulphofluoride respectively with AMP imidazolide. Adenosine-5'-(beta-chloroethylphosphate) was obtained from AMP morpholide and ethylenechorohydrine.