[Successful treatment of a patient with perforation of bleeding gastric tumor].
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Biomedical subjects
Publications and source records attributed to B L Vaĭsman.
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It was found that in patients with gastroduodenal hemorrhage the number of serotonin-, histamine-, and melatonin-producing apudocytes in the gastric mucosa increases while the number of cells producing gastrin, adrenaline, and noradrenaline reduces. In timely arrest of hemorrhage, the primarily increased number of melatonin-producing apudocytes diminishes with time from the onset of bleeding and reaches normal values gradually. The essential differences in the content of melatonin- and noradrenaline- producing apudocytes in patients with and without hemorrhage allow this morphological sign to be used as diagnostic and prognostic criteria in gastroduodenal hemorrhages.
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The human growth hormone gene, containing mouse metallothionein gene promotor, was injected into the male pronuclei of fertilized mouse ova. The progeny of transgenic mice included animals with both accelerated and inhibited growth. Radioimmunochemical analysis has revealed human growth hormone synthesis in both groups of transgenic mice. The molecular weight of the hormone synthesized in liver cells was 25,000 daltons. A possible mechanisms of foreign hormone effect on the growth of transgenic mice is discussed.
In mice obtained after microinjection into the male pronucleus of fertilized eggs of the plasmid, containing the bacterial gene of dihydrofolate reductase (DHFR), under the control of the early promotor of the simian virus 40 (SV40), an integration of the foreign DNA into the mouse genome is found. About 30% of the treated animals contain the integrated plasmid DNA sequences, i.e. are transgenic. In 2 of 7 mice, containing the introduced plasmid in their genome, the methotrexate-resistant DHFR activity is found in the kidney and spleen, which may be due to the expression of gene DHFR. The plasmid DNA sequences and the ability to synthesise the methotrexate-resistant enzyme DHFR are transmitted to the next generation of mice.
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.
The embryos with trisomy for chromosome 19 were obtained in the crosses of mice heterozygous by two different Robertsonian translocations. The development of these embryos was markedly delayed, in some of them abnormalities of the cranial region of nervous tube and the eyes were observed. The rate of 3H-uridine incorporation into 28S and 18S rRNA in the trisomic embryos both in the in vivo and in vitro experiments was decreased in 1.3-1.4 times, on the average, as compared with th control embryos. The concentration of cytoplasmic RNA in the tissue of trisomic embryos suffered no significant changes. The absence of active nucleolus-forming regions in chromosome 19 upon translocation Rb(5; 19)1Wh and the preservation of nucleolus-forming function of chromosome 19 involved in the centric fusion RB(9;19)163H were demonstrated by means of specific staining with silver nitrate. Possible causes of developmental delay of the trisomic embryos and of absence of the dose effect of ribosomal genes in them are discussed.
Trisomy for autosome No. 19 in mouse embryos (days 12-14 of development) was accompanied by a 1.5-fold increase in specific activity of cytoplasmic glutamate-oxaloacetate transaminase whose gene is known to be located in the 19th chromosome. Specific activity of cytoplasmic malate dehydrogenase remained unchanged under these circumstances, while activity of lactate dehydrogenase increased 1.1-fold.
Biotransformation of cyclophosphamide to teratogenous products in the presence of the rat hepatic microsomal fractions and NADP.H2 was carried out in the medium for cultivation of postimplantational rat embryos. Nontoxic concentrations of all components participating in the reaction and threshold concentrations of cyclophosphamide were defined. The results obtained were compared with the data of the drug action on the embryos of the same age developing in the maternal body. The developmental anomalies appeared to be similar in both cases. The method for detecting the teratogenous products of cyclophosphamide bioactivation in the culture has been demonstrated to be highly sensitive as compared with the standard biological tests.
A method for the determination of relative values (%) of two pathways of thymidine-5'-phosphate (dTMP) formation, e.g. via de novo biosynthesis and through thymidine reutilization (salvage pathway), is proposed. It is shown that the relative values of dTMP formation through the salvage pathway in the mesometrial part of developing decidua in pregnant rats (9-11th day of ppregnancy) are 1.5-3.4 times higher as compared to those in the antimesometrial part. When dTMP biosynthesis is suppressed by aminopterine, up to 80% of total DNA thymind is synthesized at the expense of thymidine reutilization. The incorporation of 3H-thymidine into DNA was thereby increased approximately 8-fold irrespective of the decrease in the DNA synthesis rate (approximately 2.4 times). The dependence of the relative values of the thymidine reutilization pathway on the correlation of the thymidylate synthetase and thymidine kinase activities in the tissue is discussed. The ability of the cells to reutilize thymidine is interpreted in terms of their relative resistance to the effect of folic acid antagonists.
DNA synthesis in the decidual tissue of rats on the 9-10th day of pregnancy has been studied in intact rats and under the effect of chloridin by means of radioautography and biochemical methods. The decidual cells of antimesometral and mesometral regions were shown to differ both by morphological features and intensity of 3H-thymidine utilization and activity of thymidylate synthetase and thymidine kinase. Under the conditions of the block of dihydropholate reductase, differences between the antimesometral and mesometral regions of deciduoma manifest themselves still more markedly. The decidual tissue consists of a heterogenous population of cells which differ by the ratio of different ways of thymidylate synthesis. An estimate is given for the ratio of two ways of thymidine monophosphate synthesis in the antimesometral regions of the decidual tissue.
Specific activity of thymidylate synthetase (TMS) under normal conditions and after the action of pyrimethamine was investigated in antimesometrial (A) and mesometrial (M) parts of rat decidua. On the 9th-11th days of pregnancy specific activity of TMS in the A part proved to be higher than in the M part of decidua, and the former one reached its maximum by the 10th day. Specific activity of TMS in the M part decreased gradually from the 9th to 11th days of gestation. Pyrimethamine, applied on the 9th day of pregnancy caused a wave-like increase in the specific activity of TMS in the A part; this elevation was not so pronounced in the M part; A study of the physico-chemical properties of TMS from the decidua and the embryos of rats showed that the enzyme had a molecular weight of 58000, an optimal pH of 6.9, and could be quickly inactivated by heating.
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The fertilized mouse eggs obtained after the hormonal stimulation of the females were denuded by pronase and incubated for 1 h at 37 degrees in the culture medium with cytochalasin B (5 micrograms/ml) and, then, centrifuged 20 min (12,000 g) at ca. 31 degrees in Ficoll gradient added with cytochalasin B. Under these conditions the eggs were divided in anuclear (cytoplasts) and nuclear (karyoplasts) fragments. The cytoplasts kept their shape and ability for protein synthesis during cultivation and the karyoplasts performed one cell division. The viable cyto- and karyoplasts obtained from the eggs may be used in the experiments on cell hybridization and production of embryos-cybrids.
Two transgenic rabbits which carried human apolipoprotein A-1 (apo A-1) cDNA under mouse ribosomal protein L/32 promoter were obtained. The effectiveness of transgenosis was confirmed by DNA dot/blot and Southern blot hybridizations. Both transgenic animals had paralyses of fore or fore and high limbs. Electron microscopy demonstrated distinct degradative changes of those parts of spinal cord which were responsible for leg skeletal muscle innervation. RNA dot/blot hybridization showed transgene expression in liver and brain but not in kidney of adult transgenic animal. However, analysis of blood serum lipids and immunochemical determinations gave no indications of the presence of human apo A-1 in adult transgenic rabbit. The data obtained allow us to suggest that the observed pathology was due to interference of native and foreign protein products of apo A-1 gene expression in CNS in the course of embryo development. This suggestion was supported by results of in situ hybridization of 5- and 9-week human embryo sections with apo A-1 cDNA, showing effective expression of apo A-1 gene in neural cells of CNS. Results of transgenosis may be viewed as modeling of the neurological syndrome of human Tangier disease.