Biomedical subjects

N V Kovaleva

Publications and source records attributed to N V Kovaleva.

At least 19 recordsLinked to original sources

PubMed2003

[Chromosome 21 mosaicism. A review].

Despite the great efforts contributed to studies on the trisomy 21 etiology, basic mechanisms of nondisjunction are still poorly understood. Even less is known about mosaic variant of trisonomy 21. In this paper, some problems of masaicism are considered: (1) estimation of the prevalence of mosaicism in patients affected with Down syndrome, (2) determination of population rate of parental mosaicism, (3) evaluation of the role of ovarian mosaicism in etiology of Down syndrome, (4) origin of the extra chromosome, (5) mechanisms of production of mosaic lines, (6) phenomenon of skewed sex ratio (female predominance, in fetuses particularly), (7) effect of maternal age.

Chromosomes, Human, Pair 21↗

PubMed2002

[Results of estimation of mutation rates for translocation trisomy 21].

Among 1332 cases of trisomy 21 born within 1979-1999 in St. Petersburg, 76(5.7%) were carriers of a translocation between chromosome 21 and other acrocentrics. Among 43 Dq; 21q translocations, 17 were inherited from the mother, and one was inherited from the father, 16 were of sporadic occurrence, and in 9 cases the mode of inheritance was not established. Out of 31 cases displaying Gq;21 translocation, 23 were mutants and 8 of unknown origin. One case of non-Robertsonian translocation 21;22 was maternal in origin. It was assumed that the proportion of sporadic cases among translocations of unknown origin is the same as that among translocations of the known origin. However, it is conceivable that the parents of a child with a sporadic anomaly, previously having an uncomplicated reproductive history and healthy children, tend to avoid cytogenetic examination more often than the carriers of translocation. Hence, the reported proportion of de novo cases (-0.6) might be underestimated. The analysis of pregnancy outcomes in mothers of children with Down syndrome, who inherited translocation (n = 12), sporadic translocation (n = 12) and translocation of unknown origin (n = 8), supports this suggestion. Analysis of the data from 8 reports, where the origin of Dq;21 was specified, revealed that in those samples, where the origin was traced in almost all families, the proportion of de novo cases (0.75-0.82) was higher than in samples where an appreciable part of families was not examined (0.46-0.73). Therefore, with the aim of correct determination of mutation rate for Dq;21 translocation, the true proportions in D;21 cases merit evaluation. Meanwhile, using average estimation from all the above mentioned reports (0.67), the mutation rate for translocations Dq;21 in St. Petersburg was calculated to be 1.2 x 10(-5) and 0.8 x 10(-5) in 1980-1989 and 1990-1999, respectively. For Gq;21 translocations/isochromosomes, the corresponding figures were 1.6 x 10(-5) and 1.5 x 10(-5).

Adult↗

PubMed1999

[O,O-dialkyl-S-bromomethylthiophosphates--inhibitors of mammalian choline- and carboxyl esterases: structure-activity relationship].

The interaction kinetics of potential pesticides, O,O-dialkyl S-bromomethylthiophosphates (RO)2P(O) SCH2Br (R = Et, i-Pr, n-Pr, n-Bu, or n-Am) with acetylcholinesterase, butyryl cholinesterase, and carboxyl esterase from warm-blooded animals was studied. All the compounds irreversibly inhibit these esterases, with k1 (M-1 min-1) being 1.8 x 10(4) - 1.9 x 10(6) for acetylcholinesterase, 2.0 x 10(6) - 4.1 x 10(7) for the more sensitive butyryl cholinesterase, and 2.3 x 10(7) - 2.3 x 10(8) and higher for the most sensitive carboxyl esterase. By using the Hansch and Kubinyi technique of multiple regression analysis, we quantitatively analyzed the relationship between the structure and inhibiting activity of these substances toward acetylcholinesterase and butyryl cholinesterase. Hydrophobic interactions were found to be important for the inhibition of both enzymes but are more pronounced in the case of butyryl cholinesterase. On the other hand, steric factors were much more significant in the inhibition of acetylcholinesterase. For both enzymes, the steric hindrances affect the phosphorylation stage of the enzyme.

Animals↗

PubMed1999

[Antiesterase activity and toxicity of O,O-dialkyl-S-ethoxycarbonylbromomethylthiophosphates].

The interaction of potential pesticides, O,O-dialkyl S-ethoxycarbonylbromomethylthiophosphates (RO)2P(O)SCH(Br)COOC2H5 (R = Et, i-Pr, n-Pr, n-Bu, n-Am, or n-Hx) with the esterases of warm-blooded animals [acetylcholinesterase (ACE), butyryl cholinesterase (BCE), and carboxyl esterase (CE)] was studied. The acute toxicities of these compounds for mice were determined. All the compounds were non-hydrolyzable by CE and capable of irreversible inhibition of all these esterases with ki (M-1 min-1) of 1.2 x 10(5)-6 x 10(6), 2.0 x 10(6)-1.5 x 10(8), and 2.0 x 10(8), respectively. By using multiple regression analysis, we found that the steric factor plays a significant role in the inhibition of ACE, with the steric hindrances manifesting themselves even at the sorption stage. On the other hand, hydrophobic interactions predominate in the case of BCE, while steric properties of its substituents exert a markedly weaker effect and manifest themselves at the phosphorylation stage. We suggested the presence of an electrophilic region in the active site of ACE, which can interact with the ethoxycarbonyl group of the thiophosphates under study. The decrease in toxicities and the affinities to BCE and CE were found to correlate with an increase in the length of n-alkyl substituents of the compounds studied. This suggests that the unspecific esterases play a significant role as a buffer system in the exhibition of toxic effects by the thiophosphates under consideration.

Animals↗

PubMed1999

[Karyological characteristics of Down's syndrome: clinical and theoretical aspects].

These data have been collected from St. Petersburg Down Syndrome Register that comprises information on 1778 liveborn children with the Down syndrome, including three twin sets, ascertained within 1970-1996. Karyotypes were obtained in 1223 cases, of which 1119 (90.7%) displayed regular trisomy. Mosaicism was found in 44 cases (3.6%), including 21 males and 24 females, and among these one familial case of mosaicism in a daughter and in a healthy mother. Of 70 cases of translocations, 41(5.7%) were Robertsonian D ones. 21 (17 inherited, 16 de novo and 8 of unknown origin), 28 translocations of isochromosomes 21q; 21q (1 inherited translocation 21; 22, 22 de novo and 5 of unknown origin). One child received the anomaly from his 46XX/45XX, t(D;G) mother-carrier. In 6 cases, free trisomy 21 was associated with structural or numerical anomalies: 46XY,t(13;14)mat + 21 in twins, 47XY,t(C;C) + 21, 47XY,t(10;15)pat + 21, 47XY,inv(19)mat + 21, 47XX + 21/48XX + 21 + ring, 48XXX + 21. In 12 families parental mosaicism was shown or suspected. In 6 families one parent had chromosome anomaly, in three cases it was not inherited: t(15;22) and t(6;21) in mothers and an additional small marker in a father. In cases confirmed cytogenetically an increased sex ratio was shown (679 males and 551 females, SR = 1.23), but it was not shown in patients not tested cytogenetically (264 males and 275 females, SR = 0.96, different from the expected 297 males and 242 females, P < 0.01).

Chromosome Aberrations↗

PubMed1994

[The polymorphism of heterochromatin regions and aneuploidy in man (a review of the literature)].

Data over a 20-year period of investigation on C-polymorphism in parents of children with chromosome abnormalities, in couples with reproductive failures, and in patients with chromosome abnormalities are reviewed. The majority of the relevant evidence is suggestive of a relationship between C-polymorphisms and an enhanced risk of aneuploid progeny. It is suggested that phenomenon of "interchromosomal effect" of C-variants is accounted for by meiotic non-homologous co-orientation. Data on accumulation of marker variants in patients with chromosome abnormalities implicate the involvement of some prevalent segregation mechanism which is out of the limits of the models of meiosis considered.

Adult↗

PubMed1994

[Increase in the incidence and risk of birth of children with Down's syndrome in Leningrad (1982-1989)].

Among 559,286 infants born in Leningrad in 1982-1989, there was revealed 744 infants (1.33/1000) with Down's syndrome (DS). The age distribution for their mothers as well as for 79,571 parturient women in the general population was investigated. The data regarding the period studied was compared with the results of a similar investigation conducted during of 1945-1961. A decrease in maternal age in the population was demonstrated. This was more pronounced for the mothers of affected infants. A 1.4- to 2.2-fold increase of birth risks for DS was found in all maternal age groups. The doubling of the risk value occurred by the age of 30-34, in contrast to 35-39 in 1945-1961.

Adult↗

PubMed1994

[Mutational level of translocated variants of Down's syndrome in Leningrad (1982-1991)].

Karyological study of 644 newborns with Down's syndrome (DS) revealed 37 translocation cases (5.7%). Translocations were inherited in 8 cases, in 17 cases they were sporadic, and in 12 cases parents were not examined. Total mutation rate per gamete per generation (2.7.10) and mutation rates of D/21 and G/21 translocations in different female age groups were calculated. The obtained data are in good agreement with results of research in other world regions. Literature data on the parental origin of de novo translocations for DS are presented. The role of meiotic coorientation of nonhomologous chromosomes in anomalies of spermatogenesis is discussed.

Chromosomes, Human, Pair 14↗

PubMed1993

[Acrocentric chromosomal associations in the families of children with Down's disease].

Acrocentric chromosome associations were studied in 373 persons: children with Down's syndrome, their parents and in controls. In parents with nondisjunction in the first meiotic division (M1) and in children with trisomy 21 due to parental nondisjunction in the M1 the increase of association activity of chromosome 21 was found out, compared with the parents-donors of the extrachromosome due to meiotic 2 (M2) errors, their children and control. The increased frequency of chromosome 21 associations in the whole group of parents (without taking into consideration the origin of odd chromosome) is also observed. It is particularly stressed that under studying the extrachromosome origin by cytological method the accumulation of marker variants of chromosome 21 occurs in groups of donors of the extrachromosome and their partners. This causes the absence of differences in association frequency between donors and donors' partners and prevents to study the integral picture of various factors contribution in the etiology of nondisjunction.

Adult↗

PubMed1993

[Polymorphism of C-heterochromatin chromosome regions in the etiology of human aneuploidy].

Cytogenetic study of the C-heterochromatic polymorphisms in 202 individuals from the Down's syndrome families and in 31 control individuals was undertaken. In 58 families the source of an additional chromosome was taken into account. It was shown that in the donors of extra chromosome, due to nondisjunction in the Ist meiotic division, the frequency of heteromorphism was higher (0.61) than in other groups: donors with the 2nd meiotic nondisjunction (0.44), partners of donors (0.48) and controls (0.46). Also, increase in heteromorphism rate was found in a group of young mothers (0.56) compared with a group of old mothers (0.45). The role of heterochromatic regions in chromosome nondisjunction is discussed from the point of view of meiotic nonhomologues coordination.

Adult↗

PubMed1992

[Age and chromosome nondisjunction].

The parental age in 77 families of Down syndrome (DS) children with the known origin of extra chromosome 21 and in 12 families of DS children resulting from de novo translocation (more probable than not in 2 meiotic division) was studied. It was shown that when nondisjunction occurred in the 1st meiotic division, both in oogenesis (n = 30) and spermatogenesis (n = 12), mean parental ages and age distributions were different from that of control (400 couples with normal children). The mean age and age distribution were found to differ from control when nondisjunction occurred in the 2nd meiotic division of oogenesis (n = 19). On the basis of our information and the previously published data, lack of the effect of parental age on chromosome segregation in the Ist meiosis may be inferred. It is chromatid disjunction in the 2nd meiosis which is more probably age-dependent. The reasons preventing elucidation of real associations are under debate.

Adult↗

PubMed1992

[Distributive pairing of chromosomes and aneuploidy in man].

The up-to-date state of human cytogenetics allows to turn back to hypothesis of distributive pairing as a strongly fruitful for resolving a number of problems concerning etiology of chromosome aneuploidy. Distributive pairing could account for such phenomena as: 1. Prevalence of nondisjunction (ND) in the first meiosis, compared with the second; 2. Excess of males among children with the Down syndrome; 3. Recurrent cases of aneuploidy, including aneusomies for different chromosomes; 4. Appearance of individuals with double aneusomies; 5. High recurrent risk for young parents; 6. Increased chance of ND for chromosomes not involved in rearrangement in carriers of balanced translocations; 7. Increased frequency of ND of autosomes in individuals with quantitative and structural sex chromosome anomalies; 8. The role of heterochromatic regions in ND; 9. Increased frequency of spontaneous abortions in couples having children with chromosome anomalies and in persons with unusual heterochromatic variants. The hypothesis could predict: 1. Essential contribution of errors in gonial cells to the origin of aneuploidy; 2. Important role of the factors influencing the prophase; 3. The possibility of offering forecast for sex chromosome anomalies rate on the basis of trisomy 21 rate, due to the fact that both autosomal and gonosomal aneuploidies have to be induced by the same factors.

Aneuploidy↗

PubMed1991

[The associations of acrocentric chromosomes in the parents of Down's syndrome children (a review of the literature)].

A point of view has been recently maintained that, as data are accumulated, the role of the association activity as a cause of acrocentric chromosome nondisjunction is not confirmed. Data are reviewed concerning all the studies available in the literature on the frequency and pattern of acrocentric associations in parents of the Down's syndrome patients. From these data it is evident that the nucleolar organizing activity is an important factor in etiology of trisomy 21. Reasons of some negative results occasionally reported are discussed.

Adult↗

PubMed1990

[Inhibition of cholinesterase activity with fluorine-containing derivatives of alpha-aminophosphonic acid].

A series of O,O-diethyl-1-(N-alpha-hydrohexafluoroisobutyryl)aminoalkylphos phonates (APh) has been synthesized and their interaction with human erythrocyte acetylcholinesterase (AChE) and with horse serum butyrylcholinesterase (BuChE) studied. Most of the APhs inactivated the cholinesterases irreversible through formation of the enzyme-inhibitor intermediate. The inactivation rate constants and the enzyme-inhibitor intermediate dissociation constants are calculated. The quantitative structure-activity relationships including both hydrophobic and calculated steric parameters of substituents are developed for APh--ChE interactions. Molecular mechanics (programme MM2) was used for determining steric parameters (Es). On the basis of QSAR models analysis it was concluded that hydrophobic interactions play an essential role in APh--AChE binding, whereas for APh--BuChE binding steric interactions are essential. Presence of at least two APh binding centres on the surface of AChE and BuChE is suggested.

Acetylcholinesterase↗

PubMed1989

[Double satellites do not increase the risk of chromosome 21 nondisjunction].

The hypothesis concerning the increase of the risk of appearance of offsprings with trisomy 21 in parents having double satellite acrocentric chromosomes is checked. Chromosomes of 266 parents having offsprings with Down's disease were examined, including 73 donors of extrachromosome 21. The frequency of chromosomes with dNORs in the total and in the donor groups did not differ from that of the control group. From 42 donors of extrachromosome, who demonstrated a nondisjunction in the first meiotic division, double satellites were revealed only once. In addition, data on the frequency of Dp+ and Gp+ variants are presented and discussed.

Cells, Cultured↗

PubMed1988

[The origin of an extra chromosome 21 in families of children with Down syndrome].

These are the first studies on the origin of nondisjunction of trisomy 21 in the USSR. Parental contribution was established in 84 of 140 families observed. In 66% cases the nondisjunction took place in oogenesis and in 34% cases - in spermatogenesis. Among the children, who inherited the additional chromosome from father, boys predominate. Compilative work on all the data available concerning the origin of the 21 nondisjunction has been performed; the factors favouring nondisjunction in I and II mitotic divisions in female meiosis, both genetical and age-dependent, have been considered. The great importance of the disturbances taking place in spermatogenesis for etiology is emphasized. It is proved that somatic hyperploidy does not serve as an indicator of predisposition for chromosome nondisjunction in meiosis.

Adult↗

PubMed1986

[Differential condensation of human chromosomes 9 and Y].

Some differences were observed in the mitotic condensation of regions composing human chromosomes 9 and Y: regions 9p, 9h and Y nf are characterized by an intense condensation by the end of the spiralization interval studied (the length of the repair chromosome 3 varying from 5.4 to 2.9 mkm). At the same time, the condensation of regions 9q-h (region 9q without heterochromatic block) is slowing in the initial spiralization interval (the length of chromosome 3 varying from 16.6 to 5.5 mkm). The Yf-block of Y-chromosome is condensing faster than nf-region. The condensation parameters of Q-heterochromatic blocks are most variable while the euchromatic regions are most stable. The dynamics of 9h and of f-block condensation are independent within one karyotype. Based on the data obtained we doubt the correctness of studies on linear dimensions of the constitutive heterochromatin blocks for the evaluation of its quantity in the karyotype. A possible association of differential mitotic condensation with the chromosome segregation disturbances is discussed.

Chromosome Banding↗

PubMed1986

[Characteristics of the morphology and mitotic condensation of human Y chromosomes with structural rearrangements].

Parameters of the length and mitotic condensation were investigated in the following cases of Y-chromosome aberrations: isodicentric Y(q), Y-chromosome without heterochromatic block, and Y-chromosome with satellites. In the Ydic we revealed some differences between f-block, that is located near the inactive kinetochore, and the block near the active centromere. Satellites exert no influence on the mitotic function of Y chromosome, presumably owing to the presence of C-heterochromatic material. With the absence of heterochromatic region, a decline in condensation of the non-fluorescent segment was observed in addition to a simultaneous increase in its length. The mechanism of functioning of the structural heterochromatin is discussed.

Adult↗