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Biomedical subjects

O V Smirnova

Publications and source records attributed to O V Smirnova.

At least 55 records · Page 3Linked to original sources

[Ultrastructure of liver cells of shrews].

It was established that the hepatocytes of least shrew (Sorex minutissimus) contained 1-2 nucleus with wide nuclear pores and big nucleolus. There are abundant mitochondria with numerous crists in their matrix (many organelles were divided along the crists). Each mitochondrion was surrounded by the cistern of granular endoplasmic reticulum. The ultrastructure of Golgi complex (1-2 flat cisterns, small vesicles] indicated that the bile was secreted often, by small portions, that was the adaptation to repeated fractional feeding. There were many peroxisomes in the cytoplasm of hepatocytes. Lipid droplets were absent, glycogen granules were not at all hepatocytes. Sinusoidal cells had the usual structure. All sinusoids were open and consisted of the erythrocytes, fragments of hepatocyte cytoplasm and myelin figures in its lumen.

Animals↗

[Purified sulfur as an agent to relieve the side effects in the radiation therapy of cervical cancer].

The theoretical basis of this work is the development of autosensitization in exposure to ionizing radiation and well-known desensitizing action of sulphuric agents. To reduce clinical manifestations of a reaction to combined radiotherapy 34 women with diagnosis of cervical cancer (stages I and II) were given 0.5-1 g of purified sulphur mixed with 0.25 g of glucose in the morning every 2-3 hours before irradiation, per os; 24 patients received placebo (a mixture of egg powder with glucose), in 21 patients no protective means were used. All 79 patients were given unified adjuvant therapy (polyvitamins, leukogens, folic acid) and diet No 15. A significant decrease in the reaction to therapeutic irradiation was noted in the study group. No side-effects were observed.

Animals↗

[Regularities in androgen reception in rat liver and its role in realizing direct androgenous effects].

The content of androgen receptors (AR) in the cytosol and nuclear fractions of rat liver cells was studied by using the radioligand method. It was found that the nuclear AR content depends on the sex of animals as well as on the initial level of AR in the cytosol fraction. Elevation of AR concentration (p less than 0.05) in liver nuclei of different groups of animals was noted one hour after injection of 100 micrograms of methyltrienolone (R-1881). This elevation correlated positively with the initial level of AR in the cytosol. The accumulation of AR in liver nuclei was more pronounced in intact males than in females. A direct positive correlation between the initial level of cytosol AR and the final regulatory effect of androgens on the hepatic AR content (r = 0.955, n = 6, p less than 0.02) and on the content of the hepatic unusual estrogen-binding protein (UEBP) (r = 0.957, n = 9, p less than 0.001) were found. It is concluded that androgens induce in liver nuclei the accumulation of AR whose level correlates with that of the initial cytosolic AR. The latter reflects the efficiency of the direct effect of androgens on liver cells.

Animals↗

In vivo and in vitro estimations of the direct effect of estrogen on rat hepatocytes tested by the changes in the unusual estrogen-binding protein content.

The direct effect of estradiol (E2) on the hepatocytes of mature male rats has been examined by measuring the changes in the unusual estrogen-binding protein (UEBP) content and parallel measuring the level of liver estrogen receptors (ER). The content of UEBP (NUEBP) and ER (NER) in the liver were determined using the quantitative methods for differential specific determination of the E2-binding sites of these proteins. It has been shown that the administration of E2 in vivo induced a considerable decrease in hepatic NUEBP not only in intact males, but also in hypophysectomized males during the initial period after the operation (when the content of hepatic ER was still high) and produced no effect in hypophysectomized males during the later period (when liver ER were depleted). Repeated administration of human growth hormone (hGH) (twice a day) resulted in a considerable increase in NER in hypophysectomized males and restored the sensitivity to the subsequent inhibitory effect of E2 on UEBP. We also used rat hepatocytes after a 4-day primary culturing. These cells had a stable morpho-functional status, high ER level, and sex-differentiated UEBP content. Culturing of mature male rat hepatocytes in the medium containing E2 at concentrations close to physiological levels (10(-10)-10(-7) M) decreased NUEBP in a dose-dependent manner. Hexestrol (10(-7) M) but not cholesterol (10(-5) M) also exhibited a direct effect on NUEBP in cultured rat hepatocytes. The effect of E2 was reversible: statistically significant increase in NUEBP was observed 3 days after 10(-9) M E2 had been removed from the culturing medium. It was concluded that hepatocytes may be a primary target for E2 under physiological conditions and that GH may modulate the direct effect of E2 at the hepatic level by modifying the content of liver ER.

Animals↗

[The effect of androgens and somatotropic hormone on the expression of the level of special estrogen-binding protein in the hepatocytes].

The possibility of direct androgen determination of high unusual estrogen-binding protein (UEBP) level in female rat hepatocytes to the level typical to the males was studied. The direct effect of androgen (A) on the UEBP content in hepatocytes of ovariectomized female rats was shown by estimation in vivo and on hepatocyte culture. It has been revealed that the permissive action of growth hormone (GH) is necessary for normal expression of direct androgen effect. The latter has been stable after cessation of hormone action. High concentration of GH was found to possess positive regulatory effect on the UEBP in hepatocytes of ovariectomized rats. Effect of GH quickly disappeared after hormone withdrawal and was under negative regulation by physiological concentrations of A. It was concluded that A owing to its direct action together with permissive influence of GH is capable of determining stable expression of male phenotype of the UEBP level in hepatocytes of females.

Animals↗

[Destructive and restorative processes of the liver in rats under intensive physical loading].

The ultrastructure of rat liver cells after running exercise was investigated. When rats were trained for a month and sacrificed immediately after the last exercise it was revealed that the number of liver cells mitochondria increased, but many of them had alterations: mitochondria became swollen, had lucid matrix. There were some variations in degree of alterations between different mitochondria: a) in the same hepatocyte, b) in different hepatocytes of the same animal, that was connected with individual sensitivity of organelles on the levels of the cell and of the organ. Rough endoplasmic reticulum bore few ribosomes. Glycogen was absent. There were abundant vesicles of smooth endoplasmic reticulum, autophagic vacuoles and peroxisomes in the liver cell cytoplasm. Adaptation of rat liver to the exercise programme becomes evident by 1.5 month of exercise. Mitochondria and rough endoplasmic reticulum were numerous and of normal structure. There were many peroxisomes and glycogen granules in the cytoplasm of hepatocyte. The presence of large autophagic vacuoles in the cytoplasm of some hepatocytes were obviously connected with more rapid destruction of some organelles, than in control.

Animals↗

[Estimation of a direct regulatory effect of estrogens on hepatocytes, evaluated according to the change in the level of free estrogen-binding protein in primary cell culture].

Male rat hepatocyte cultures have been obtained. The culturing hepatocytes had a stable level of some morphological and functional properties. A high level of estrogen receptors (ER) and E2-sensitive unusual estrogen-binding protein (UEBP) was found. A direct dose-dependent inhibiting effect of physiological (10(-10)-10(-7) M) concentrations of E2 on UEBP content was established in cell cultures incubated with the hormone for 3 days. Hexestrol (but not cholesterol) was found to exert a direct inhibiting effect. The inhibiting effect of E2 (10(-9) M) was observed after a 24 hour incubation of hepatocytes with the hormone but was less pronounced. In this case a significant increase in UEBP concentration in hepatocytes was noted 72 hours after the removal of E2. It is concluded that physiological concentrations of E2 can exert a direct regulatory influence on certain functions of culturing hepatocytes acting via hepatocyte ER.

Animals↗

[Lipid peroxidation and the mechanisms of hepatocyte damage and protection in chronic hepatitis and cirrhosis].

A study was made of the indices of lipid peroxidation (LPO)--conjugated dienes (CD) and diene ketones (D), cyclic nucleotides (CN)--cAMP and cGMP, prostaglandins (PG) E and F2 alpha in biopsy tissue of the liver in 55 patients with chronic hepatitis (CH) and liver cirrhosis (LC). LPO was determined by spectrophotometry, CH and LC--by a radioimmunoassay. In patients with CPH and CAH the indices of LPO and cGMP were normal, cAMP, PG and PGE/PGF2 alpha were raised. In a severe fast progressive liver lesion disorder of coordination activity of the cell membranous systems was characterized by a high LPO activity, a decrease in cAMP and relative deficit of liver PG.

Adolescent↗

[Molecular and hormone-binding properties of a partially purified preparation of androgen receptors from the liver of male rats].

Liver cytosol of mature male rats was found to contain androgen receptors (AR). These AR were purified 7--10-fold, and their molecular and hormone-binding properties were investigated. It was found that the AR molecules have a sedimentation coefficient of 9.3 +/- 0.15 and 4.7 +/- 0.11 S, Stokes radius of 6.5 +/- 0.25 and 3.2 +/- 0.08 nm, Mr of 263000 and 65700 Da and friction coefficient ratio of 1.55 and 1.22 for low and high ionic strength media, respectively. The values of rate constants of [3H]methyltrienolone (R1881) association with AR and for the dissociation of the complexes formed are equal to (0.66 +/- 0.29). .10(5) M-1 s-1 and to (0.68 +/- 0.08).10(-5) s-1, respectively, whereas those of equilibrium association constant--to (1.4 +/- 0.3).10(9) M-1 at 0-4 degrees C. It was shown that R1881, 5 alpha-dihydrotestosterone and testosterone strongly compete with 3H-R1881 for the binding with AR (as can be judged from the relative competitive activity of 35 nonlabeled hormonal agents); 19-nortestosterone and delta1-testosterone are more weak, whereas 5 alpha-androstandiols, some hydroxy derivatives of testosterone, cyproterone acetate, estradiol and progesterone are moderate competitors. Other natural testosterone, estradiol and progesterone metabolites as well as corticosteroids do not compete or weakly compete with 3H-R1881 for the binding to AR. It is concluded that the properties of AR are similar to those of classical type AR and that they can intermediate most of the direct effects of androgens on the liver.

Androgens↗

[Identification of receptors in a system of functionally heterogeneous proteins specifically bound to androgens in rat liver cytosol].

The methods of androgen receptor (RA) isolation and identification in rat liver cytosol were studied. It was shown that male rat liver contains a system of specific androgen (A)-binding proteins consisting of at least three main components: RA, delta 4-androstendione (delta 4-A)-binding component and an unusual estrogen-binding protein interacting also with A and the first two components in females. The identity of one of A-binding components to RA was proved by cumulative properties of this component which are similar to those of RA from other tissues. These properties are as follows: 1) high values of apparent association constant, Ka, for 3H-R1881 (2.8 +/- 0.3 X 10(8) M-1) and 3H-5 alpha-dihydrotestosterone (3H-DHT) (5.0 +/- 0.4 X 10(8) M-1); 2) low binding capacity--approximately 10 fmol/mg of protein of nonfractionated cytosol; 3) pronounced specificity of affinity for active A (DHT, R1881, testosterone); 4) large size of the protein molecule (6.5 +/- 0.25 nm); 5) ability to decrease this size to 3.2 +/- 0.08 nm in a high ionic strength buffer; 6) precipitation at low concentrations of ammonium sulfate: 7) strong interaction with heparin-Sepharose. The properties of the delta 4-A-binding component do not coincide with those of RA: it has a low Ka for 3H-delta 4-A (1.15 +/- 0.5 X 10(6) M-1), a high binding capacity (1.22 +/- 0,12 pmol/mg of protein of nonfractionated cytosol) and can bind various delta 4-3-ketosteroids irrespective of the degree and nature of their biological activity. It was concluded that preliminary isolation of rat liver RA on heparin-Sepharose can be used for differential identification and characterization of this protein.

Androgen-Binding Protein↗

[Effect of antibodies against the specific estrogen-binding protein in the rat liver on the hormone-binding activity of this protein and steroid hormone receptors].

The effects of rabbit polyclonal antibodies (AB) against an unusual estrogen-binding protein (UEBP) isolated from rat liver by immunoadsorption on the interaction of [3H]estradiol with UEBP, estrogen receptors of uterus and other tissues, of [3H]dihydroxytestosterone with prostate androgen receptors, of [3H]progesterone with uterine progesterone receptors and of [3H]dexamethazone with rat thymus glucocorticoid receptors were investigated. It was shown that preincubation of cytosol of the above tissues with AB decreases the ability of UEBP, estrogen and androgen receptors to bind the corresponding ligands. The hormone-binding activity of progesterone and glucocorticoid receptors in the presence of AB remains thereby unchanged. The binding activity of UEBP in the presence of ABUEBP diminishes due to the decrease in the concentration of protein binding sites, whereas that of estrogen and androgen receptors decreases due to the diminution of affinity for their ligands which, in turn, is the result of reduction of the association rate constant. A cross influence of AB on the activity of uterine estrogen receptors of rabbit, guinea pig and mouse was observed. It was assumed that the structure of UEBP and sex steroid receptors has some similar elements.

Androgens↗

The unusual estrogen-binding protein (UEBP) of rat liver: the role of sex steroids and hypophysis in its regulation.

The number of estradiol (E2) binding sites of rat liver unusual estrogen-binding protein (NUEBP) was measured, using a novel modification of the quantitative method of specific UEBP determination. In liver cytosol of mature male and female rats, NUEBP amounted to 6.83 +/- 0.49 and less than 0.05 pmol/mg protein, respectively. Neonatal administration of testosterone-propionate (TP) and TP injections at later periods of ontogenesis increased NUEBP in female rat liver in a similar fashion. The elevated NUEBP was found in the liver of mature ovariectomized females 30 days after cessation of TP injections. Hypophysectomy (but not adrenalectomy or thyroidectomy) prevented TP induction of elevated NUEBP in pubertal females. E2 injections reversibly decreased NUEBP in the liver of all animals under study except of hypophysectomized males. A stimulating regulatory effect of TP on NUEBP in male rat liver was observed only in the case of endogenous androgen deficiency and low NUEBP. TP prevented the E2-dependent decrease of NUEBP upon their simultaneous injections and increased the E2-reduced NUEBP when injected after E2. Hypophysectomy led to a decrease of NUEBP in pubertal males but only slightly affected that in castrated animals. After TP injections to hypophysectomized males, NUEBP returned to a level next to the initial one. It was concluded that estrogen-androgen regulation of the UEBP level led to the maintenance of sex differences in the UEBP content.

Animals↗

[Role of sex steroids and the pituitary in regulating the level of a specific estrogen-binding protein in rat liver].

The effects of androgens (A), estrogens (E) and hypophysectomy on the content of an unusual rat liver estrogen-binding protein (UEBP) were studied by the differential quantitative method of the UEBP content measurement. The UEBP content was shown to increase during maturation of male rats. After A injections the UEBP content was high only in the liver of prepubertal but not of mature or immature males. Castration or hypophysectomy of mature males equally caused a decrease in the UEBP content in mature males whereas subsequent administration of A made it completely return to normal. Hypophysectomy of castrated males did not alter the UEBP content. A single injection of E provoked an appreciable reduction in the UEBP level after several days. Administration of A interfered with the inhibitory action of E after simultaneous injection of A and E and recovered the E-induced lowering of the UEBP content upon administration of A following E. Hypophysectomy of castrated males did not affect significantly the UEBP level. The UEBP content was insensitive to the direct action of pituitary factors. The pituitary is necessary for the realization of the effects of E alone but not A. It is suggested that the regulatory role of A consists in the maintenance of the constant optimal UEBP level in rat liver.

Animals↗

[Changes in the microflora of the intestine after administration of antibiotics to animals maintained conventionally].

A series of experiments were performed on mice and rats subjected to total decontamination by oral administration of 3 antibiotics: gentamicin, ristomycin and nystatin. The results of experiments are summarized. It was shown that under the conventional conditions the decontamination was effective, when the intervals between the experiments were 3-5 months. When the intervals were less or the experiments were performed in the same room without intervals, the efficacy of the decontamination markedly decreased or it was ineffective. The results are discussed from the standpoints of the necessity of observing definite requirements for performance of such procedures in hospitals and laboratories.

Animals↗

The unusual estrogen-binding protein (UEBP) of male rat liver: structural determinants of ligands.

The unusual estrogen-binding protein (UEBP) found in a male rat liver is a sex dependent protein which differs from other known receptor and transport proteins by the high lability of its complexes with estradiol (E2) and also the unique specificity of affinity for hormones. In this work values of relative binding affinity (RBA) of the UEBP for 57 steroids and their analogs were determined. The affinity of steroids was characterised by the amount of the unlabeled compound needed for 50% inhibition of [3H]-E2 binding with the UEBP. A number of derivatives of estrane and androstane possess an ability to interact with this protein, in contrast to the derivatives of pregnane, stilbene and triphenylethane. Characterized by RBA values, natural steroids are found to have the following order: estriol larger than or equal to E2 greater than 16 alpha-hydroxyestrone = 2 alpha-hydroxytestosterone greater than 16-epiestriol greater than or equal to estetrol greater than or equal to 17-epiestriol greater than or equal to 2-methoxyestradiol greater than or equal to 5 alpha-androstane-3 alpha,17 beta-diol greater than or equal to estrone greater than testosterone greater than or equal to 2 beta-hydroxytestosterone greater than 5 alpha-dihydrotestosterone. Affinity of estrogens and androgens for the UEBP diminishes abruptly after removal of 3- and 17-hydroxy groups, masking of these by ether bonds or changing of 17 beta-hydroxyl to 17 alpha. All the investigated 17 oxo-C19-steroids, 5 beta-derivatives of testosterone, its 6 beta- and 16 alpha-hydroxy metabolites as well as 5 alpha-androstane-3 beta,17 beta-diol and 19-nortestosterone exhibit no essential affinity for the protein. On the basis of the results obtained it is suggested that the binding sites for estrogens and androgens in the UEBP molecule overlap but do not completely coincide.

Androgens↗

[Hormonal specificity of the affinity of specific estrogen-binding protein in the rat liver].

The ability of 57 steroids and their analogs to compete with 3H-estradiol for binding sites of an unusual estrogen-binding protein (UEBP) of the male rat liver was studied. The magnitudes of the equilibrium constants of association of 3H-estradiol, 3H-estriol, and 3H-5 alpha-androstane-3 alpha, 17 beta-diol with the UEBP were measured. It was shown that the derivatives of estrane and androstane, in contrast to those of pregnane, stilbene and triphenylethane, can effectively interact with the UEBP. The ability of estrogens and androgens to interact with the UEBP primarily depends on oxygen functions of the A and D rings and on general conformation of the steroid molecule. It is suggested that there are 2 subcenters for the steroid A and D rings both at the estrogen and androgen sites of the UEBP molecule. These subcenters for the two types of sex steroids either do not coincide or coincident are only subcenters for the ligand A rings.

Androgens↗