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The effects of intra-amniotic administration of 1-desamino-8-D-arginine-vasopressin (DDAVP) at 14 days of embryogenesis on movement asymmetry in neonatal and mature mongrel white rats were studied. Controls consisted of intact and sham-operated animals, as well as rats given intra-amniotic saline. The population profile of asymmetry was assessed in terms of the tail position of rats aged two days, and also in terms of the direction of excursions in a T-maze in three-months males. The proportion of animals showing asymmetrical tail poses was no more than 36% in controls; the ratio of left-asymmetrical and right-asymmetrical intact rats was 2:1. DDAVP increased the number of rats with asymmetrical tail poses by a factor of 1.5-2.6, and right-asymmetrical individuals became predominant. This effect was demonstrated graphically as a bell-shaped dose-response curve with a peak response at doses of 3 x 10(-8) and 3 x 10(-6) mg. The selection probability for the right-hand side of the maze in experimental animals was 0.71 +/- 0.06, which was significantly higher than in animals of the three control groups, which showed no preference for the direction of excursions. These results indicate lateralization of the action of DDAVP in the developing central nervous system, leading to a predominance of right-sided motor responses in neonatal and mature rats.

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Vasopressin administration induced a right-sided bias in the rat litter, the asymmetry being similar to a right-sided bias in the turning behaviour of adult male rats in the T-maze. The findings suggest the nigrostriatal system to be responsible for the lateralising effect of vasopressin in the brain.

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Against the background of the induced iron deficit ethanol (6.4 g/kg) causes aggravation of the embryolethal effect and anomalies in 15% of embryos in 14-day pregnant rats. Changes in the genome of rat males and females after the injection of the plasmid with a foreign gene at the stage of two pronuclei and the subsequent crossing with intact animals account for the increase in sensitivity of embryos to subteratogenic doses of sodium salicilate. The maternal organism disturbances have a more pronounced effect than the paternal ones.

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An immunocytochemical analysis of hormonal status of transgenic rats containing human growth hormone gene has been done. The enhanced expression of the endogenous growth hormone gene was demonstrated with poly- and monoclonal antibodies inside somatatropes of pituitary. No activity of the heterologous growth hormone gene was revealed in kidney, pancreas or liver as it might be expected according to specificity of MT1 and TAT promotors. Transgenic animals of F0, F1 and F2 generation exhibited disturbance of functional morphology of glucagon and insulin producing cells. Lymphocyte infiltration was found in pancreatic islets. The transgenic rabbits and swine with the gene of releasing factor of human growth hormone did not reveal any severe disturbance. Although one swine demonstrated alterations in glucagon producing cells and one rabbit revealed a disturbed morphology of the stomach tissues. The data are discussed in relation to general problems of transgene activity and interaction with endogenous homolog.

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The exposure of rat fetuses to ethanol by direct intra-amniotic injection in the afternoon of the 14th day of embryogenesis resulted in developmental anomalies (34%), the defects located mostly in the left extremities. Intraperitoneal injections of ethanol at the same period of pregnancy resulted in analogous injuries but only in occasional fetuses. There was no embryotoxic effect after exposure to high doses of ethanol by per os. It was concluded that even a single dose of ethanol in certain periods of pregnancy and in certain homeostasis disorders in the maternal organism could induce the fetal alcohol syndrome (FAS) in the newborns.

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Amniotic fluid from women was injected intra-amniotically to rats at the 14th day of pregnancy in a dose 0.3 ml. Morphological and functional parameters of embryonic development of rats and EMG activity of rat puppies at the age of 30-34 days differed from control ones with respect to the degree of maturity and motor disturbances of newborn babies. The data obtained reveal not only evident but also masked forms of motor pathology which was observed in children later, namely to 6-9 months. Chronic motor pathology in rat puppies was unilateral with central motor disturbances in babies being directly related to the degree of these disturbances.

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Transgenic rats and mice carrying Bos taurus beta-casein gene were obtained using microinjection into the male pronucleus. Integration, inheritance and expression of the gene in transgenic animals were studied.

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Susceptibility to the effect of teratogen chloridine of three generations produced from transgenic rats with human growth hormone gene was investigated. The offsprings were shown to reveal elevated teratogenic injury as compared with intact animals.

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Embryos of the laboratory rats and mice at the two-cell stage were frozen in different media with 1.5 M DMSO at a rate of 0.5-0.7 degrees/min to -40 degrees and the transferred into liquid nitrogen. Temperature of the crystallization initiation was -6 degrees. After thawed embryos were transplanted to foster mothers, these latter gave birth to normal offspring. The best results (38% of the total number of transplanted embryos in mice and 55% in rats) were obtained when using modified Whitten's medium for cryopreservation. Survival of the rat embryos in the NT-6 medium fell to 36% due, supposedly, to changes in pH accompanying the decrease in temperature. These results allow us to recommend modified Whitten's medium and the developed conditions of freezing-thawing for cryopreservation of the rat and mouse embryos.

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The immunogenic properties of isolated subunits of influenza A/FM/1/47 (H1N1) virus hemagglutinin were studied. The antihemagglutinating serum was tested by the CFT, HI, competitive solid-phase radioimmunoassay, and biological neutralization test. The antiserum was found to contain populations of antibodies to the three main antigenic determinants of hemagglutinin identical to the determinants of the intact virion, as well as antibodies to the antigenic components of host cells. The antiserum to hemagglutinin as well as monospecific antibodies to individual antigenic determinants of hemagglutinin exhibited a high virus-neutralizing activity for the homologous virus.

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A preparation of isolated subunits of influenza A (H1N1) virus hemagglutinin was examined for antigenic properties by four serological tests: radioimmunoassay, radial immunodiffusion test, complement fixation test, and hemagglutination inhibition test with hyperimmune polyclonal serum to intact virion as well as with monospecific antibodies to individual antigenic determinants obtained by adsorption technique. In isolated hemagglutinin subunits, radioimmunoassay identified three main virus-specific antigenic sites identical to antigenic determinants in the hemagglutinin of the intact virion. No neuraminidase was found in the hemagglutinin preparation but increased serological activity of host cell antigens was observed.

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In the interepidemic period of late 1983 in Alma-Ata, influenza viruses with hemagglutinin of the swine subtype and neuraminidases N1 and N2 were isolated from humans. One of the strains, A/Alma-Ata/1044/83 (Hsw1N1), was isolated from the lungs of a man of 65 with the diagnosis of influenza and disseminated intravascular syndrome who had had communal and occupational contacts with swine. In paired sera of a sick child, and in seroepidemiological screening for influenza antibodies to swine influenza virus in low titres were detected in 34% of cases in subjects under 40. Radioimmunoassay of blood clots from subjects of the same focus revealed in one specimen the presence of swine influenza antigen.

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In the period of epidemic rise of the morbidity level in 1983-1984, 207 specimens of nasopharyngeal washings from patients with influenza were analysed by solid-phase radioimmunoassay. Test sera containing a wide range of antihemagglutinating antibodies to different drift variants of influenza type A and type B viruses were used as diagnostic ones. The results indicate the predominance of influenza B infection (18.4%). Influenza A accounted for 14.5%, 9.2% of it being subtype H1N1. Noteworthy is a considerable portion (23.2%) of mixed influenza A and B infection. The results of this study are compared with analysis of paired sera from the same patients by the HI test.

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High sensitivity and specificity of solid-phase radioimmunoassay (SPRIA) in identification of influenza A (H1N1 and H2N2) viruses in the infected allantoic culture were demonstrated. Mixtures of influenza hyperimmune sera free from antibodies to host cell antigens and antineuraminidase antibodies were used as active test sera. The test serum a-H1N1 consisted of antisera to A/FmI/47, A/Netherlands/36/56, and A/USSR/090/77 strains; it detected practically all tested variants of H1N1 virus isolated in 1947-1982 in allantoic cultures containing virus-specific protein in amounts of 1.4 to 0.7 ng/ml. For the detection of H2N2 subtype viruses (1957-1967), a mixture of antisera to A/Singapore/1/57, A/Leningrad/2/63, A/Gorkiy/62/65, and A/Tokyo/3/67 viruses was used. This test serum could detect H2N2 virus in the allantoic fluid containing 0.7-035 ng/ml of virus protein.

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It has been demonstrated that thalidomide is capable of a noticeable stabilization of the enzymes from rabbit, pig and guinea-pig liver microsomal fractions. Administration of thalidomide to guinea-pigs resulted in an increase of microsomal hydroxylase activity measured by the aniline test. The growth of the activity of microsomal enzymes led to an abrupt drop of ascorbic acid concentration in guinea-pig organs. It is suggested that thalidomide has a teratogenic action on the species which are incapable of the synthesis of ascorbic acid by making this vitamin deficiency in embryonal tissues. Probably, it is the deficiency of ascorbic acid that inhibits the synthesis of collagen in embryonal limbs and disturbs their sensory ganglia.

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After administration to rats in a dose of 200-400 mg/kg on days 14 and 15 of the pregnancy the hypnotic drug glutethimide induces in the rat progeny variations in the orienting-motor activity, latent period of runnings and raises the frequency of urinations upon training in a maze. The effect of glutethimide on the orienting-motor behavior was seen only in the first generation of the animals and was absent from the second generation animals.

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A study was made of the effect of ethanol (6.5-108 mM) and its immediate metabolite, acetaldehyde (4.5 microM-45 mM) on 9.5-day-old rat embryos cultivated in vitro. Biotransformation of the nontoxic concentration of ethanol (17 mM) to teratogenic products was made by addition to the culture medium of a soluble fraction of the rat liver (0.2-0.55 mg protein/ml), NAD (0.25 mM) and sodium pyruvate (2.3 mM). Malformations obtained after biotransformation of ethanol were similar to those obtained after direct action of acetaldehyde. The roles of acetaldehyde and ethanol in the etiology of fetal alcoholic injury are discussed.

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Rat and mouse embryos at the stage of the first somites formation (1-5 pairs) cultivated in human blood serum demonstrated its embryolethal and teratogenic effect. The embryos taken at a later stage (11-18 pairs of somites) developed normally and could be compared with the development of the rat embryos in homologous blood serum. There was no difference in the development when the embryos were cultivated either in male or female blood serum. The stage of embryogenesis 11-18 pairs of somites is recommended for in vitro experimental revealing in the human serum of embryotoxic factors induced by certain external influences.

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