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Biomedical subjects

V S Shapot

Publications and source records attributed to V S Shapot.

At least 19 recordsLinked to original sources

[Thermography with glucose loading in the examination of women at high risk of developing breast cancer].

Thermography of the breast with pharmacological GTT was performed in 260 women; cancer was diagnosed in 150 of them, benign breast diseases in 110. A significant increase in temperature asymmetry after GTT was shown in breast cancer patients as compared to patients with benign diseases. Data on the sensitivity of the mammographic and thermographic methods to identify risk groups were presented.

Adult

[Change in activity of enzymes for purine metabolism and RNA and DNA biosynthesis in macrophages, reflecting impairment of their functions in neoplastic growth].

The changes in the biochemical parameters of peritoneal macrophages and their coupling to the secretory and phagocytic functions in CH3A mice during the growth of the reinoculated solid hepatoma 22a were studied. The DNA and RNA synthesis during the active tumour growth was more intense than that in resident macrophages. The activity of uridine kinase increased up to 156.0 +/- 12.0 nmol/hour/10(8) but was absent in resident macrophages. This was accompanied by a 7.2-fold increase of interleukin-1 synthesis as determined by the [3H]thymidine incorporation into thymocyte DNA in response to concanavalin A administration to C3H mice. Similar changes were observed in peptone-stimulated macrophages. A specific feature of macrophages from tumour-bearing mice was the impairment of activity of purine exchange enzymes and the efficiency of phagocytosis that were unobserved in peptone-stimulated macrophages. The activity of adenosine deaminase and purine nucleoside phosphorylase was inhibited as a result of their preincubation with zymosan, a phagocytosis-stimulating agent. This was accompanied by a significant decrease of the first chemiluminescence peak resulting from disturbances in Fc-reception. Macrophages of tumour-bearing animals possessed an increased 2.2-fold activity of membrane-bound AMP 5'-nucleotidase concomitant with the lack or decrease of the amplitude of the second chemiluminescence peak reflecting the disturbances in digestion resulting from phagocytosis.

5'-Nucleotidase

[The pool of free purine and pyrimidine nucleosides and bases in the thymocytes, and splenic T- and B-lymphocytes of C3HA mice during the growth of solid hepatoma 22a].

Using reverse phase ion pair high performance liquid chromatography, the levels of free adenosine, inosine, adenine, xanthine, hypoxanthine, guanine and deoxycytidine in thymocytes and splenic T- and B-lymphocytes of C3HA mice, were studied under normal conditions and at different times (5 hrs, 1, 2, 3, 4, 5, 8 and 20 days) after transplantation of solid hepatoma 22a. The adenosine and inosine levels in thymus and spleen lymphocytes were 5 to 10 times as low as that of purine bases. Inosine was totally absent in T-and B-lymphocytes. The absolute content of adenine and guanine in thymus and spleen lymphocytes was higher compared to purine bases. It was shown that in all cases studied the decrease in hypoxanthine, xanthine and guanine levels in T- and B-lymphocytes during maximal tumour growth, i.e., on the 5th and 8th post-inoculation days as well as at the terminal period (20th day), was correlated with the decrease in the adenosine deaminase and functional activities of these cells. The level of free adenine in thymocytes and spleen T-lymphocytes during tumour growth showed a 2-4-fold increase in comparison with normal values. A dramatic decrease of intracellular concentration of deoxycytidine was observed in thymocytes and spleen T- and B-lymphocytes beginning with the 5th hour and over the whole subsequent period. The key role of the deoxycytidine decline during tumour growth as a possible cause of simultaneous impairment of DNA synthesis and purine deoxyribonucleoside phosphorylation in lymphocytes is discussed.

Adenine

[Preferential modification of replicating DNA by benz(a)pyrene)].

The nuclei of cells from regenerating rat liver were incubated with benzo(a)pyrene and the concentrations of the metabolites that covalently bound to DNA of different nuclear fractions were compared. It appeared that DNA associated with nuclear matrix (containing replicating DNA) is modified most intensively. The synchronized mouse embryo cells were incubated with benzo(a)pyrene during S phase and the levels of modifications in short and long single-stranded DNA fragments were compared. It has been observed that replicating DNA is represented in short fragments. These short DNA fragments were found to be modified by benzo(a)pyrene 4-9 times more intensively than total DNA. The possible mechanisms of both the increase in the number of DNA modifications in proliferating cells and the reason for the enhancement of carcinogenic effect on dividing cells are being discussed.

Animals

[Criteria of the sensitivity of Zajdela and Morris hepatoma cells to glucocorticoids].

Glucocorticoids induce tyrosine aminotransferase synthesis in 7777 Morris hepatoma but fail to do so in Zajdela hepatoma. This internal property indicates the resistance to the hormone. However, both hepatoma cell lines do respond to the triamcinolone acetonide in a similar way, as judged by some other criteria, e. g. interaction with the immobilized hormone on the inert carrier, adhesion to glass and kinetic parameters of alkaline phosphodiesterase I activity. Moreover, both cell types respond to glucocorticoids by modification of synthesis of some proteins, as revealed previously by two-dimensional electrophoresis. The results show that in case of tumour cells which retain their specific receptor apparatus but do not respond to glucocorticoids by usual criteria, the conclusion whether tumour cells are hormone-sensitive or not has to be drawn from the analysis of their multiple response judging by several assays.

Animals

[Autogenic regulation of the sensitivity of liver cells to glucocorticoids during prolonged hormonal stimulation].

The mechanisms of reversible decrease of hormone-dependent induction of tyrosine aminotransferase (TAT) by rat liver cells after prolonged administration of the glucocorticoid was studied. It was shown that the main links of the glucocorticoid action mechanism (i.e., the formation of a cytoplasmic hormone-receptor complex and the hormone accumulation in the nuclei) do not change under these conditions. It was found also that one of the necessary prerequisites for the decrease of the hormone-dependent induction of TAT is the constant production by liver cells of large amounts of TAT irrespective of whether this process is induced by the glucocorticoid or by a non-hormonal inducer, e.g., tryptophan. Using the dot-hybridization technique, it was demonstrated that the inhibition of hormone-dependent induction of TAT is correlated with the reduction of mRNA TAT. It was supposed that the main links in the mechanism of inhibition of the hormone-dependent induction are the formation of a large excess of the inducible protein--TAT--in the cells as well as the accumulation of end products of the TAT-catalyzed transamination reaction which cause a feed-back repression of the de novo synthesis of TAT. Studies with cell cultures of Morris hepatoma which is known to be sensitive to glucocorticoids revealed the ability of glucose, the end product of gluconeogenesis reactions, to provide for selective inhibition of the hormone-induced accumulation of mRNA TAT in hepatoma cells.

Adrenalectomy

[Combination of immunodepression and disorders in nucleic acid metabolism of lymphoid tissue as a manifestation of a paraneoplastic syndrome].

Several physiological, biochemical, and molecular biological approaches to the study of factors determining immunodepression in tumor-bearing animals are considered. Cancer cells release substances of nucleic and peptide nature that suppress the functional activity of macrophages and lymphocytes and stimulate cell proliferation in organs and tissues of the host. Suppressor T cells capable of inhibiting the function of helper T cells and impairing the differentiation of killer T cells are activated. The suppression of T- and B-cell-mediated immunity in the tumor host involves disturbances of nucleic acid metabolism in those cells as well as hypersecretion of glucocorticoids. The impairments of lymphocyte proliferation and differentiation that result in reduced immune responsiveness are attributable to drastic alterations in the metabolism of purine and pyrimidine nucleotides and to the damage sustained by the lymphocyte's DNA.

Animals

[Relation between disorders of glucose metabolism, secretion of somatotropic hormone, thyroxine, thyrotropin and hematocrit indices in rats with transplanted hepatomas].

The levels of growth hormone (GH) in the blood of rats with ascite Zajdela hepatoma and hepatoma 27 (H-27) are shown to increase during the tumour growth. Stimulation of the GH secretion is a result of the hypoglycaemic stress. An increase in the blood GH secretion is also observed in the fasting rats. To reveal the predominance of catabolic GH effects over the anabolic ones in the tumour host determination of the molar insulin/GH ratio in the blood is suggested. A direct correlation is found between reduction of this index, glycaemia and the content of liver glycogen. A short-term induced hyperglycaemia evokes a paradoxical reaction in terms of GH secretion. In contrast to control fasting rats, in tumour-bearing animals no correlation between thyrotropin and thyroxine blood concentration could be observed. Anaemia increasing progressively in the course of the tumour growth may be the cause of the above phenomenon.

Animals

[Relation between the structural, metabolic and "adhesive" properties of nuclear and cytoplasmic non-ribosomal RNA].

Nuclear RNAs release from nucleoproteins of isolated nuclei absorbed on a celite column in a wide range of dissociating conditions (from 1 M LiCl--2 M urea at 2 degrees C to 4 M LiCl--8 M urea at 70-80 degrees C) was demonstrated. Such a high "adhesive" heterogeneity of nuclear RNAs (i.e., variations in the tightness of RNA-protein bonds) appears to be due to the association of nuclear matrix proteins. A direct correlation was found to exist between the metabolic turnover of RNA and the tightness of its association with the nuclear matrix. Actually, the pulse label which rapidly incorporates into the RNAt greater than 50 degrees, the RNA fraction being most tenaciously bound to the matrix, could be chased later into RNAs weakly bound to it. As the RNA-matrix binding weakens, the metabolic and structural properties of a given RNA change, e.g., sedimentation coefficients decrease, while the poly(A)+-RNA content and stability increase. The "adhesive" heterogeneity was found to be inherent in not only nuclear RNAs but also in cytoplasmic non-ribosomal RNAs, showing the same correlation, i.e., the tighter the RNA--protein complex, the higher the rate of RNA turnover. Cytoplasmic RNAs which differ in their adhesiveness may fulfil various intracellular functions, since polyribosomal mRNPs and informosomal mRNPs appear to be enriched in tightly and weakly bound RNA fractions, respectively. The interrelationships between nuclear and cytoplasmic RNAs are discussed.

Adhesiveness

Some biochemical mechanisms underlying the impairment of T and B cell immunity in C3HA mice during hepatoma growth.

In thymocytes of C3HA mice carrying the transplantable and ortoaminoazotoluene induced hepatomas at the time of their intense growth a drastic decrease in adenosine deaminase activity set in and 3-4-fold augmentation of intracellular concentration of dATP and dGTP, potential inhibitors of ribonucleoside diphosphate reductase was observed, leading to the reduction of the DNA synthesis. The latter event was evidenced by a suppressed 14C-thymidine incorporation into thymocytes DNA in vitro, decreased thymidine kinase activity, intracellular dTTP and depletion of dCTP pools. Only in the terminal period of hepatocarcinogenesis (12 months) a 4-fold increase in the corticosterone serum concentration was observed. As for the mice carrying transplantable 22a hepatoma, serum hormone levels augmented 4-fold as early as 24 h after tumor implantation and thereafter kept increased two fold. An elevated activity of terminal deoxynucleotidyl transferase in mouse thymocytes has been shown to be characteristic of the late periods of tumor growth reflecting the arrest of the immature cortical thymocyte differentiation. By the time hepatomas emerged in the course of hepatocarcinogenesis in spleen T and B lymphocytes a significant drop in the activity of adenosine deaminase (3-4-fold) and purine nucleoside phosphorylase (2-8-fold) was noted--the events directly correlated with the weakening of cell immune functions. The disorders described were accompanied by the accumulation of dGTP in spleen T lymphocytes, dATP in B lymphocytes and inhibition of DNA synthesis, predominantly in T lymphocytes. In the latter instance the pool of dCTP was found to be depleted. In spleen T and B lymphocytes of mice carrying solid 22a hepatoma when the peak of its growth was reached (day 5) the rate of DNA synthesis dropped. Later on (from day 8 to the animal death), however, in spite of the suppression of immune function and the decrease in adenosine deaminase activity a drastic stimulation of DNA synthesis in spleen T and B lymphocytes was observed. The increase in spleen T suppressor activity in the course of intense growth of the both types of hepatomas coincided in the time with the stimulation of the CTP-dependent thymidine kinase isoenzyme activity in total T lymphocyte population of the same organ.

Adenosine Deaminase

[Proteins from nuclear fractions with different contents of active genes].

The protein content in four nuclear fractions was compared. The nuclear fraction of rat liver deficient in active genes was characterized by a very low content of non-histone proteins whose mobility is less than that of histone H1.. The predominant protein of this fraction is an acid-soluble protein (Mr = 41 +/- 1 kD) designated as 41K. This protein was detected in acid nuclear extracts of rat lungs, kidney and spleen but was absent (or practically absent) in four murine and rat hepatomas under study. The decreased content of protein 41K was correlated with the diminution of the content of histone H1(0) fraction. It was shown that proteins HMG 14 and 17 are readily washed off during fractionation of nuclei and they bind to DNA fragments passing into solution irrespective of whether they contain active or inactive genes. The nuclear matrix fraction rich in active genes was heterogeneous according to its protein composition. Differences in the intensity of staining and in electrophoretic mobility of some polypeptides of this nuclear fraction in normal and hepatoma cells were revealed.

Animals

[Activation of lipolysis and ketogenesis in tumor-bearing animals as a reflection of chronic stress states].

In order to elucidate the peculiarities of brain metabolism in tumour-bearing organisms, the arterio-venous (A-V) content of glucose, acetoacetate (Ac-Ac), beta-hydroxybutyrate (beta-HB) and non-esterified fatty acids (NEFA) in growing Zajdela ascite hepatoma (ZAH) and solid hepatoma 27 (H-27) was compared. Analysis of metabolic patterns of healthy, starving and fed recipients (ZAH and H-27) revealed the inadequacy of the concepts on anorexia as being the cause of carbohydrate-lipid metabolic disturbances. In tumour-bearing organisms lipolysis and ketogenesis reflect the tumour-induced chronic stress. Absorption of beta-HB and release of Ac-Ac by brain were observed at all stages of malignant growth. This is probably due to a partial switch-over of brain metabolism to non-carbohydrate energy sources. Besides, certain stages of tumour growth are associated with active assimilation of NEFA by brain. A correlation between the A-V difference with respect to glucose and Ac-Ac as well as between the glucose and NEFA contents was established. It was assumed that the A-V difference in glucose is the main regulator of ketone body metabolism.

Acetoacetates

[Characteristics of disorders of water-electrolyte homeostasis in rats with transplantable hepatomas].

The growth of ascitic Zajdela and solid 27 hepatomas in vivo is accompanied by significant changes in parathyroid hormones, calcitonin and aldosterone blood levels. In periods close to terminal ones, their level decreases presumably as a result of energy deficiency in the endocrine glands. The arising hormonal shifts are a result of a "metabolic stress" caused by the growing tumour.

Aldosterone

[Change in tissue glycogen reserves in tumor bearers as a reflection of a hypoglycemic stress syndrome].

Glycogen content in the brain, liver and skeletal muscles of rats bearing ascite Zajdela hepatoma (AZH) and solid 27 hepatoma (27-H) has been studied. Serum glucose levels directly correlated with liver glycogen reserves. In the terminal stage of tumor growth depletion of liver glycogen was observed, while the stores of muscle glycogen did not diminish. Within 1-4 days (AZH) and 15-30 days (27-H) after implantation the stores even exceeded those of control healthy rats. In the terminal stage, in spite of hypoglycaemia development, the content of brain glycogen was significantly elevated in both groups of animals.

Animals

[Ability of virus SV40 T-antigen to simulate the effect of specific T lymphocyte growth factor--interleukin-2].

The entering of T-lymphocytes into the DNA-synthesizing phase was marked by three consecutive signals, i.e., antigenic influence, interleukin-2, a specific T-lymphocyte cell growth factor, and non-specific serum growth-promoting factors, in the first place, transferrin. This system was used for the study of effects of virus SV40 T-antigen on cell mitotic cycle. Purified T-antigen was injected consecutively into T-lymphocytes, using erythrocyte ghost vesicles instead of one of control signals. It was shown that T-antigen cannot simulate the antigenic response but simulates the effect of interleukin-2, a specific growth-promoting factor. However, both normally proliferating T-lymphocytes and T-antigen-induced lymphocytes showed an absolute requirement for transferrin and, apparently, for other nonspecific growth-promoting factors. It was assumed that the polymorphism of tumours induced by papovaviruses is determined by the ability of their "early" proteins to imitate the effects of their specific growth-promoting factors on the cells.

Antigens, Viral, Tumor

[Changes in the lymphoid cells of DNA and purine nucleotide synthesis and sensitivity to glucocorticoids associated with impairment of differentiation and immune function during tumor growth in mice. Thymocytes].

Some biochemical mechanisms underlying the impairments of cellular immunity were studied in C3Ha mice in the course of growth of transplantable and induced (ortoaminoazotoluol) solid hepatomas. During intensive hepatoma growth, the adenosine deaminase activity in host thymocytes was shown to be drastically (6 times) reduced, resulting in the elevation of dATP and dGTP concentrations (6- and 7-fold, respectively), the potential inhibitors of ribonucleoside diphosphate reductase. Consequently, the rate of DNA synthesis was reduced as can be evidenced by the decrease of (a) thymidine kinase activity, (b) 14C-thymidine incorporation into DNA, and (c) dTTP and dCTP pools. By the terminal period of hepatoma growth (both transplantable and induced one), the serum corticosterone content increased 3- and 8-fold, respectively. At the same time, specific binding of [3H]triamsinolone acetonide by thymocytes was augmented and the activity of terminal deoxynucleotidyl transferase increased the latter alterations, which can be regarded as a reflection (including other parameters mentioned) of the arrest of T-lymphocyte differentiation at the level of immature cortex thymocytes.

Adenosine Deaminase

[Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes].

Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol-induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T-lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B-lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T-suppressors in the same organ.

Adenosine Deaminase