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Biomedical subjects

N P Goncharov

Publications and source records attributed to N P Goncharov.

At least 19 recordsLinked to original sources
PubMed2006

[Dehydroepiandrosterone and the cerebral functions].

Of all steroidal hormones, dehydroepiandrosterone (DHEA) and its sulphate form, DHEAS, are synthesized by the adrenal glands in the biggest quantities. In this review the authors consider the ways of the synthesis of the neurosteroids, possible mechanisms of the regulation of these processes, and their dynamics under stressful conditions. The paper presents analysis of experimental and clinical data on the role of DHEAS in the manifestation of different cerebral functions. The authors pay special attention to the results of substitutive therapy with DHEA(S) in patients with such CNS functional disorders, as Alzheimer's disease, depression, age-relative memory and sleep disturbances, etc.

Adjuvants, Immunologic↗
PubMed2005

[Dehydroepiandrosterone and brain functioning].

The adrenal glands synthesize dehydroepiandrosterone (DHEA) and its sulphate form (DHEAS) more intensively than they do other steroid hormones. Researchers are interested in these hormones for several reasons. Firstly, for some years they have been trying to find the reason for DHEA and DHEAS to be synthesized and present in the organism in such high concentrations. Secondly, their attention have been attracted by age-dependent regression of DHEA, which is strictly determined. Thirdly, despite longstanding efforts of scientists, the physiological role and spectrum of the biological activity of DHEA is still unclear. Evidence of that DHEA and DHEAS can be synthesized in situ in the brain tissue, received in rat experiments, urged researchers to clarify the role of these neurosteroids in the CNS. The presented review covers ways of neurosteroid synthesis, possible mechanisms of the regulation of these processes, and their dynamics under the condition of stress. The authors analyze experimental and clinical observations undertaken with a goal to clarify a possible role of DHEA in the manifestation of various brain functions. Special attention is payed to ambiguous results of modern studies, dedicated to replacement therapy of various disorders of CNS functioning (Alzheimer's disease, depression, age-specific memory impairment, sleep disturbance etc.) with DHEAS.

Adult↗
PubMed2005

[Localization of genes controlling spherical grain and compact ear in Triticum antiquorum Heer ex Udacz].

The inheritance of two taxonomically important characters was studied in hexaploid wheat species (2n = 6x = 42). The monogenic control of spherical grain was demonstrated for Triticum antiquorum Heer ex Udacz. The recessive gene controlling spherical grain in this species was assigned to chromosome 3D by monosomic genetic analysis and was shown to be allelic to the s gene determining the same character in the endemic Indian species T. sphaerococcum Perciv. The T. antiquorum and T. sphaerococcum dominant genes controlling compact ears proved to be nonallelic to the corresponding T. compactum Host. gene and were designated as C2. Problems of phylogeny and classification of hexaploid wheats are discussed.

Chromosomes, Plant↗
PubMed2004

Effect of dehydroepiandrosterone on avoidance behavior of adult male rats.

We studied the effect of repeated intraperitoneal treatment with dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response activity and behavior of adult male rats. The effect of dehydroepiandrosterone on learning was estimated in conditioned active and passive avoidance response paradigms. Chronic administration of dehydroepiandrosterone in low and high doses had no effect on retention of conditioned passive avoidance response in adult male rats 24 h after learning. However, chronic administration of dehydroepiandrosterone in low dose impaired acquisition of the conditioned active avoidance response. It should be emphasized that chronic administration of dehydroepiandrosterone in high dose did not modulate acquisition and retention of this reaction.

Animals↗
PubMed2003

Genetics of growth habit (spring vs winter) in common wheat: confirmation of the existence of dominant gene Vrn4.

The number of dominant Vrn genes in common wheat, Triticum aestivum L., is estimated. Data were obtained supporting Pugsley's and Gotoh's data on the presence of a dominant gene Vrn4 in near-isogenic line 'Triple Dirk F'. The presence of a dominant gene Vrn4 in line 'Gabo-2' of cultivar 'Gabo', which was used by Pugsley as a donor of the gene Vrn4 for the near-isogenic line 'Triple Dirk F', was also confirmed. The Vrn2 and Vrn4 relationship and their chromosomal location are discussed. It was demonstrated that the dominant Vrn8 gene which was introgressed from Triticum sphaerococcum to common wheat by Stelmakh and Avsenin is allelic to Vrn4. While genes Vrn6(sc) and Vrn7(sc) which were introgressed from rye, Secale cereale L., by the above-mentioned authors are not allelic to the genes Vrn1, Vrn2, Vrn3 and Vrn4.

Alleles↗
PubMed2003

[Inheritance of awn absence in tetraploid wheat species].

Awn absence was shown to be inherited as a dominant character in the tetraploid wheat species Triticum dicoccum (Schrank) Schuebl. and T. durum Desf. but as a recessive one in T. aethiopicum Jakubz. The monogenic control of the character was demonstrated for all studied species. In accessions of emmer and durum wheat, the character is controlled by the dominant gene B1, located on chromosome 5A, and in Ethiopian wheat, by a recessive gene, which we designated as awn. The recessive awn gene was localized on chromosome 3B of T. aethiopicum with the use of D-genome disomic substitution lines of cultivar Langdon.

Chromosomes, Plant↗
PubMed2003

[Localization of genes, determining quantitative traits in wheat: amendment to the "catalog of chromosomal mapping of genes in domestic cultivars of wheat"].

An amendment to the catalog of chromosome location of genes in Russian wheat cultivars was constructed with the published data of the recent decade. The results of chromosomal localization were summarized and analyzed by methods of multivariate statistics. Chromosomes critical for 40 quantitative traits under study proved to cluster according to their homeology, i.e., by homeological groups. The hypotheses providing an explanation for this finding are considered. It is suggested that quantitative traits are similarly controlled by genes located on homeological chromosomes in common wheat, making it possible to isolate a limited number of major genes for each particular quantitative trait.

Chromosome Mapping↗
PubMed2002

Inheritance of dense spike in diploid wheat and Aegilops squarrosa.

The individuals of diploid wheat Triticum boeoticum, T. monococcum and T. sinskajae and goatgrass Aegilops squarrosa were picked out with screening the dense spike characteristics. The dense-spike accessions were discovered in diploid wheat (T. sinskajae) and Ae. squarrosa. Inheritance of the dense spike was studied. The trait was found to be controlled by a recessive gene in T. sinskajae and by an incomplete dominant gene in Ae. squarrosa. The dosage effect of dominant gene C was detected in interspecific pentaploid F1 hybrid plants T. compactum x T. palmovae (2n =35, A(u)A(b)BDD genome). The spike of pentaploid hybrid was not so dense as compared to hexaploid wheat T. compactum. This is the first report showing similarity of the expression of dominant gene C on D genome of the hexaploid wheat to that of dense spike gene in Ae. squarrosa. The existence of dense-spike accessions of Ae. squarrosa allows us to hypothesize that the origin of T. compactum is independent from that of common wheat.

Diploidy↗
PubMed2001

[Sex hormones and behavioral reactions].

The paper provides a comparative analysis of the effects of imbalance of gonadal hormones on behavioral processes in rats of both sex. Learning was assesses in active and passive avoidance paradigms, behavior was evaluated in the "open field" test. Hemigonadectomy in male rats or hemiovariectomy in female rats was found to fail to modify the dynamics of acquisition and reproduction of active avoidance and passive reactions as compared to the controls, but to affect the pattern of animal behavior in the "open field" test. Castration of rats of both sex impaired the acquisition and retention of active avoidance performance. Excess of testosterone in male rats significantly inhibited the ability of the animals to form an active avoidance response. Excessive estradiol levels in female rats accelerated the acquisition of active avoidance performance and greatly attenuated extinction of this performance. Gonadal hormonal treatment did not alter the reproducibility of passive avoidance performance. The lack of estrogens resulted in amnesia of passive avoidance performance while that of androgens failed to destroy passive avoidance performance. Excessive estradiol in female rats or its lack in male rats significantly modified the pattern of animal behavior in the "open field" test. The absence of estrogens or their excess did not affect the behavior of rats with exception of individual components.

Animals↗
PubMed1998

Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

Adolescent↗
PubMed1998

A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD), including growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH) in children is now considered a heterogeneous syndrome. Recent findings on expression of mouse pituitary-specific homeodomain factors demonstrate dependence of adenopituitary ontogeny on interactive expression of these factors, suggesting their involvement in etiology of CPHD. Prophet of Pit-1 (Prop-1) gene, a novel pituitary-specific homeodomain factor, was analyzed in 14 Russian children with CPHD, in whom Pit-1 gene was intact. We found a mutational hot spot in three patients from two families in homeodomain part of the second exon of Prop-1 gene. The common 2-base pair deletion (GA296) in the homozygous state resulted in a Serine to Stop codon (S109X) substitution and generated a truncated Prop-1 protein. Parents were phenotypically normal and heterozygous for GA296 deletion, indicating an autosomal recessive inheritance. These results demonstrate a novel type of Prop-1 gene mutation as one of the causes of CPHD in Russian patients.

Amino Acid Sequence↗
PubMed1998

Endocrine and reproductive health status of men who had experienced short-term radiation exposure at Chernobyl.

Hormonal and semen parameters in 416 men aged 25-45 years were examined: 328 were men who cleaned the territory around the Chernobyl nuclear reactor (called 'liquidators') and 88 were healthy age-matched controls. The dose of radiation received by the liquidators was 0.16 +/- 0.08 Gy. LH, FSH, prolactin, testosterone and cortisol levels were assayed using WHO-matched reagents. Semen analyses were performed according to the WHO Manual (1992). The mean concentration of all hormones in liquidators and controls were within the WHO-defined normal range. The mean levels of LH and cortisol in liquidators were significantly lower (p = 0.013 and p < 0.001, respectively) and testosterone significantly higher (p = 0.023) than in controls. The variations in hormone levels in liquidators were not correlated with the acquired doses of radiation as measured by personal dosimeters (film badges). Semen parameters in a subgroup of 70 liquidators were within the normal WHO-defined range. The percentage of normal forms of spermatozoa in liquidators (35.0 +/- 13.1%) was significantly lower (p < 0.015) than in a control group (42.8 +/- 8.9%). The study has shown that exposure of men to relatively short-term radiation did not cause long-lasting disruption of their endocrine status and spermatogenesis. The study was 7-9 years retrospective and it is therefore impossible to infer what the immediate effects of the radiation exposure were on these parameters.

Adult↗
PubMed1998

Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.

Mutations in the prophet of Pit-1 gene (PROP1) have been shown to be responsible for combined pituitary hormone deficiency (CPHD) with deficiencies of growth hormone (GH), Prolactin (Prl), thyroid-stimulating hormone (TSH) and gonadotropins. We previously reported that homozygosity for a 2bp deletion in exon 2 (296delGA) accounted for CPHD in three patients from two Russian families. Here we report a second mutational hot spot in exon 2. This 2bp 149delGA deletion results in a frame shift that leads to the same serine to stop codon change at codon 109 (S109X). The predicted proteins are each truncated at residue 108 but diverge from the wild type sequence at different points in the homeodomain. Compound heterozygosity for the two mutations (149delGA/296delGA) was detected in 5 of 14 CPHD children from 4 families (36%). This provides the first evidence of heterozygosity for two common deletions as a cause of CPHD in Russian children.

Adolescent↗
PubMed1995

A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: I. Dose-finding study.

This study in adult male baboons was conducted to establish the dose of a long-acting progestogen, levonorgestrel butanoate, and that of a long-acting androgen, testosterone buciclate, which, when combined, would achieve optimal and prolonged suppression of spermatogenesis. Two intramuscular injections of levonorgestrel butanoate at 3-month intervals and in the dose range 1-8 mg/kg reduced sperm production and plasma concentrations of testosterone, LH and FSH for periods of up to 6 months. The suppression of sperm production was greatest and most prolonged in the 4 mg/kg group. Two intramuscular injections of testosterone buciclate at 3-month intervals, and at doses of 4 and 8 mg/kg, induced variable changes in circulating levels of testosterone, elevated by the higher dose, and caused sperm suppression, in some animals to azoospermia. It was concluded that 8 mg/kg testosterone buciclate would provide adequate androgen replacement when combined with 4 mg/kg levonorgestrel butanoate as a putative male contraceptive regimen.

Adrenal Cortex Hormones↗
PubMed1995

A non-human primate study (baboon; Papio hamadryas) to determine if a long-acting progestogen, levonorgestrel butanoate, combined with a long-acting androgen, testosterone buciclate, can suppress spermatogenesis: II. Efficacy study.

Two combined injections of levonorgestrel butanoate (4 mg/kg) and testosterone buciclate (8 mg/kg) at 3-month intervals to adult male baboons initiated a decrease in sperm concentration from baseline values of 490x10(6)/ml to minimum values of 17x10(6/ml. This suppression was sustained until week 32, during which time between one and three azoospermic samples were collected from each of four out of five treated baboons in the period 10-24 weeks. Circulating plasma levels of LH and testosterone decreased to approximately 20-75% of baseline values. Plasma levels of cortisol declined to significantly reduced levels at weeks 22 and 36-44. All values returned to the baseline range by week 48. The combined administration of progestogen and androgen induced a more marked and sustained suppression to severe oligozoospermia or azoospermia than did the equivalent dose of progestogen alone (Goncharov et al., 1995). Although the dose of testosterone buciclate used did not maintain peripheral levels of testosterone in the normal range, it did not restimulate spermatogenesis. It was concluded that a combination drug regimen based on the novel long-acting levonorgestrel and testosterone esters could provide a contraceptive option for men.

Animals↗
PubMed1995

[Steroidogenesis in patients with various adrenal and gonadal dysfunctions].

The paper deals with the results of investigations of steroidogenesis in patients with ACTH-dependent Icenko-Cushing's disease (CD), congenital adrenal hyperplasia (CAH), and stromal hyperthecosis (SH). Along with the traditional methods of evaluating the activity of steroid-producing glands (diurnal variations of steroid hormones and their precursors in the peripheral blood, their mean daily concentrations), the authors used a simultaneous selective catheterization technique for adrenal and ovarian veins. No pronounced circadian rhythms were revealed in most of the steroids measured in patients with CD. A sharp rise in the mean daily serum 17-hydroxypregnenolone concentrations coupled with the steady-state 17-hydroxyprogesterone level is considered to reflect the activation of steroid biosynthesis via the delta 5-pathway. CD patients were demonstrated to exhibit great differences in the daily pattern of aldosterone secretion depending on the development of essential hypertension. CAH patients had high 17-hydroxypregnenolone and 17-hydroxyprogesterone levels. Like 17-hydroxyprogesterone, 17-hydroxypregnenolone may be used as a diagnostic marker of CAH. Hyperandrogenism in this disorder was largely due to enhanced adrenal production of testosterone and delta 5 androgens DHA and DHA-S. Unlike CAH, SH was not associated with excessive secretion of either DHA or DHA-S, but the ovaries of these patients released greater amounts of testosterone, which led to hyperandrogenism.

17-alpha-Hydroxypregnenolone↗