[Biological activity of the poly(G).poly(C) complex, modified by divalent platinum compounds]. / Biologicheskaia aktivnost' kompleksa poli(G).poli(C), modifitsirovannogo soedinenimi dvukhvalentnoi platiny.

Modification of poly(G).poly(C) with cys-diaminodichloroplatinum (cys-DDP) at the level of rb = 0.02 increased the in vivo antiviral and interferon-inducing activity of the complex, in contrast to the data reported for complex poly(G).poly(C). Antiinfluenza activity in this case depends on the method of modification and increases more intensively when a ready complex is treated with cys-DDP, as against treatment of poly(G) alone before the formation of a complex with poly(C). If rb is increased, the activity reduces again. Modification with trans-DDP at rb = 0.02 also leads to an increase of antiinfluenza activity of poly(G).poly(C), but mainly after pretreatment of poly(G).

Biophysical studies of the complexes of polyriboguanylic acid with brominated and chlorinated polyribocytidylic acids.

Conformation of double-stranded complexes of polyriboguanylic acid with halogenated polyribocytidylic acid [poly(C)] was studied with the aid of differential pulse polarography, terbium fluorescence and circular dichroism spectrometry. It was shown that halogenation at C(5) of cytosine residues in poly(C) disturbed the ordered structure of the double-helical complex. In addition, this halogenation does not improve antiviral activity of the polynucleotide complex studied in the system of vesicular stomatitis virus and the cell culture of chicken embryos. It was concluded that the regularity of the secondary structure of synthetic RNAs might play an important role in the mechanism of biological activity of these biomacromolecules.

Biophysical studies of the modification of poly(rG) . poly(rC) by cisplatin. Relations to the biological activity of the complex.

The integrity of the double-stranded complex polyriboguanylic.polyribocytidylic acid [poly(rG).poly(rC)] modified by antitumour cis-diamminedichloroplatinum(II)(cis-DDP) was studied with the aid of differential pulse polarography and terbium fluorescence measurement. The modification was made to level corresponding to rb = 0.05 (rb is defined as the number of platinum atoms covalently bound per one nucleotide residue). Two modes of the modification of the polynucleotide complex were employed: The action of cis-DDP on poly(G) before formation of the complex with poly(C) and on the complex already formed from non-modified polynucleotides. It was shown that in the latter case modification disordered the integrity of the complex only negligibly. while in the former case the modification resulted in a noticeably more extensive disturbance of the double-stranded polynucleotide complex. Moreover, the modification of the complex (after its formation) at rb = 0.02 led to improved interferon-inducing and antiviral activity of poly(rG).poly(rC) tested on mice infected by influenza virus. It was suggested that the combined effects of interferon-inducing and antiviral activities of poly(rG).poly(rC) and antiviral activity of cis-DDP may result in an increased effect over and above what may be expected from the actions of the two modalities separately.

Modification of duplex poly(G).poly(C) by platinum (II) compounds.

The modification of the double-stranded poly(G).poly(C) complex by cis-diamminedichloroplatinum(II) was studied by two modes: the action of cis-DDP on poly(G) before formation of the duplex with poly(C) and that on the prepared duplex. It was shown that in the latter case modification disordered the integrity of the duplex only negligibly at rb less than or equal to 0.05 and led to improved interferon-inducing and antiviral activity tested on mice infected by Influenza and Herpes viruses.

[Dependence of the antiviral activity of the poly(G).poly(C) complex on the size of the continuous poly(C)segments]. / Zavisimost' protivovirusnoi aktivnosti kompleksa poli(G).poli(Ts) ot razmera nepreryvnykh uchastkov poli(Ts).

Modification of poly(C) by various frequency treatment with adenosine non-complementary to guanosine has produced poly(G) X poly (C.A) complexes with continuous double-stranded areas the length of which is determined by C/A ratio. Studies of the antiviral activity of poly(G).poly(C,A) complexes with C/A from 10:1 to 90:1 and poly(G).poly(C) in vesicular stomatitis virus-infected chick embryo cell cultures and in experimental tick-borne encephalitis of mice demonstrated that the maximum activity is achieved at an average lengths of double-stranded areas of 90 nucleotide pairs. At the same time, a low but statistically significant antiviral activity is observed at a length of double-stranded areas of 10-30 nucleotide pairs.

Complexes of polyriboguanylate with modified polyribocytidylate.

It was established minimal length of continuous poly(C) sequence of poly(G).poly(C) complex required for effective interferon induction by investigation poly(G).poly(C,A) with different molar ratios of C:A varying from 10:1 to 90:1. The minimum length of the double-stranded sequence of the macromolecule complex poly(G).poly(C) is equal to at least 90-100 nucleotides. The effect of 5-halogen-polyribocytidilates on the properties of the complexes has been also investigated.

[Combined antiviral effect of synthetic polyribonucleotide interferonogens and specific antiviral antibodies in arbovirus infections]. / Kombinirovannyi protivovirusnyi éffekt sinteticheskikh poliribonukleotidnykh interferonogenov i spetsificheskikh protivovirusnykh antitel pri arbovirusnykh infektsiiakh.

A model of tick-borne encephalitis in BALB/c mice was used to investigate the protective anti-viral effect of an interferon inducer, poly(G).poly(C), and specific gamma-globulin administered to the animals together or separately in small doses 24 hours before or after virus inoculation. Administration to the animals of poly(G).poly(C) alone or gamma-globulin alone was shown to produce a poor protective effect. Simultaneous administration of both preparations resulted in a significant decrease of mouse mortality after infection. As a result of the pretreatment of chick embryo cell cultures with poly(G).poly(C) before inoculation and the addition of specific immune serum to the agar overlay after the Sindbis virus inoculation, its multiplication was inhibited much more than after treatment of the cells with interferon inducer alone or antibody alone. Possible mechanisms of the observed additive antiviral effects of the interferon inducer and antibody, including those associated with the influence on the virus-induced interferon production, as well as the possibility of their combined use for the prevention and treatment of viral infections are discussed.

[Risk of intrauterine infection of the human fetus with Coxsackie viruses in pregnancy complicated by late toxicosis and pyelonephritis]. / O riske vnutriutrobnogo zarazheniia ploda cheloveka virusami Koksaki pri beremennosti, oslozhnennoi pozdnim toksikozom i pielonefritom.

During virological examinations of 144 pregnant women including 85 women with complicated course of pregnancy Coxsackie A viruses were isolated from the blood or identified in the cells of urinary tracts in 60.3% of the cases of nephropathy, in 68.3% of the pregnant women with pyelonephritis, and in 8.5% of normal subjects. The groups of the pregnant women under comparison did not differ significantly in the rate of finding of other viruses. Coxsackie A viruses were also isolated from the placenta and amniotic fluid in 3 out of 4 cases examined in late toxicosis, were found in the kidneys of the fetus from a woman with pyelonephritis and in cells of the urinary tracts of 13 out of 19 babies (68.4%) born to women with complicated course of pregnancy. The hypothesis of the etiological association of nephropathy and pyelonephritis in pregnant women with activation of chronic Coxsackie virus infection and of the high risk of infection of the fetus with these viruses in the described complications of pregnancy is discussed.

[Modification of the poly G-poly C complex by incorporation of adenosine in the purine chain]. / O modifikatsii kompleksa poli(G)-poli(Ts) vkliucheniem adenozina v purinovuiu nit'.

Antiviral and interferonogenic activity of the complexes of poly(G,A) . poly(C) and poly(G) . poly(C) was studied in mice and cell cultures. Three out of 4 complexes of poly(G,A) . poly(C) had insignificant antiviral and interferonogenic activity in chick embryo cells. One of the complexes induced low levels of interferon production in mice and decreased the rate of their death from experimental forest-spring encephalitis. The activity of poly(G) . poly(C) in the above cell systems was much more pronounced. Unlike this complex, some complexes of poly(G,A) . poly(C) showed a noticeable activity in the cells of Primates. The effect of the noncomplementary base in the purine thread of poly(G) . poly(C) on its biological activity and nucleotide composition is discussed.

[Induction of plant resistance to the tobacco mosaic virus with a double-stranded poly(G)-poly(C) complex]. / Induktsiia ustoichivosti rastenii k virusu tabachnoi mozaiki dvunitevym kompleksom poli(G)-poli(Ts).

Inoculation of double-stranded polyribonucleotide poly(G) . poly(C) complex in a concentration of 50-200 micrograms/mg into tobacco and thornapple leaves was found to produce resistance of the plants to subsequent infection with tobacco mosaic virus (TMV) manifested in decreased number and size of local virus lesions. The induced resistance may spread over the plant and be found in the upper untreated leaves. The level of systemic resistance, however, is much lower than that of the resistance demonstrated in the injected leaves. Actinomycin D (5 micrograms/ml) had no significant effect on the number but stimulated the growth of lesions developing in leaves injected with poly(G) . poly(C) as well as increased their number in the upper leaves of the same plants proximal to the treated ones. Development of tobacco resistance to TMV was accompanied by changes in the activity of terminal oxidases, particularly peroxidase. Possible mechanisms of formation of induced resistance are discussed.

[On the role of virus infection in the pathogenesis of vulvovaginitis in young girls]. / Ob uchastii virusnoi infektsii v patogeneze vulvovaginitov u devochek.

The antigens of a number of widely prevalent viruses and changes typical of the cytopathic effect of these viruses were found in the epithelial cells of vaginal secretes in 44 out of 49 examined young girls with protracted forms of vulvovaginite. Mixed virus infection of the vaginal mucosa was diagnosed in 22 girls. More frequently than others, parainfluenza (57.1%) and adenovirus (59.2%) infections were detected in the patients. In girls of the control group, parainfluenza infection was diagnosed in 5.9% and adenovirus infection in 32.3%. Antigens of Coxsackie A and B (16.3%), influenza A2 and B (6.1%) and respiratory syncytial (6.1%) viruses were found in the vaginal mucosa in patients with vulvovaginitis only. A possible role of virus infection in the pathogenesis of vulvovaginitis in childhood is discussed.

[Comparison of reactivities or uridine- and cytidine-2',3'-cyclophosphates as donors and uridine and cytidine as acceptors of phosphate under dinucleoside monophosphate synthesis catalyzed by RNAase A]. / Sravenenie reaktsionnoi sposobnosti uridini tsitidin-2',3'-tsiklofosfata kakdonorov, uridina i tsitidina kak aktseptorov fosfata v sinteze dinukleozidmonofosfatov, kataliziruemom RNKazoi A.

In order to determine the relative activity of pyrimidine nucleoside-2',3'-cyclophosphates as donors and nucleosides as acceptors of phosphate in the reaction of the internucleotide bond formation catalyzed by RNAase A (EC 3.4.1.22), a comparative synthesis of dinucleoside monophosphates UpU, UpC, CpU and CpC at three different enzyme concentrations (20, 40 and 70 mkg/ml) and two temperatures (0 degrees and -15 degrees) was carried out. The conversion rate of donor (U greater than p and C greater than p) during the synthesis and in the competitive reaction of hydrolysis strongly depends on the type of acceptor activity as compared to uridine. Based on the data of synthesis and simultaneous hydrolysis of U greater than p and C greater than p it may be concluded that in the both cases the latter donor is more reactive. The approaches to the determination of the substrate activity of the donors and acceptors for the evaluation of optimal conditions of the dinucleoside monophosphate synthesis depending on the donor--acceptor combination are discussed.

3-Ribosyl-6-methyluracil as a phosphate acceptor in the synthesis of the internucleotide bond catalyzed by pancreatic ribonuclease.

The synthesis of uridylyl-(3'-5')-3-ribosyl-6-methyluracil (UprmU) catalyzed by pancreatic ribonuclease (EC 3.4.1.22) has been performed using uridine 2', 3'-cyclic phosphate (U greater than p) as phosphate donor and 3-ribosyl-6-methyluracil (rmU) as phosphate acceptor. The rate of synthesis of UprmU is much higher than that of uridylyl-(3'-5')-uridine (UpU) in a control experiment under the same conditions with uridine as acceptor. The yields of UpU and UprmU were 20 and 17% respectively. The competitive hydrolysis of the initial U greater than p also proceeds faster when rmU is used as the acceptor. The relationship between the conformation of this nucleoside and its acceptor activity in the enzymatic synthesis of the internucleotide bond is discussed.