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Biomedical subjects

M Kirsch-Volders

Publications and source records attributed to M Kirsch-Volders.

At least 109 records · Page 6Linked to original sources

Mercury chloride--and methyl mercury chloride--induced inhibition in NOR activity.

Previous work has raised the question of whether mercury compounds inhibit the activity of the nucleolar organizing genes. For that reason we performed a cytophotodensitometric analysis on silver-stained interphase nuclei from human peripheral blood lymphocytes exposed to various concentrations of HgCl2 (0-150 X 10(-6) M), CH3HgCl (0-50 X 10(-6) M), and actinomycin D (0-0.1 microgram/ml). The last compound was used as a positive control. The cells were exposed to the compounds either during G1-early S phase, allowing recovery after the exposure, or from G1 until harvest; thus no recovery was allowed in this case. Like actinomycin D, both mercury compounds were shown to inhibit the NOR activity. This inhibition was furthermore more evident during the short exposure experiment. Our results do confirm that mercury compounds may, to a certain extent, influence some factors regulating the nucleolus-organizing activity.

Adult↗

C heterochromatin variation in couples with recurrent early abortions.

The possible influence of the high polymorphic C heterochromatic regions of human chromosomes 1, 9, 16, and Y on meiotic chromosome segregation was investigated. Faulty chromosome segregation may be the result of either an abnormal quantity of C heterochromatin on the homologues, or disequilibrium between the homologues. The aim of our study was to determine whether either a variation in the amounts of total C heterochromatin or differences in the amounts of C heterochromatin between homologues could lead to faulty chromosome segregation. The study was performed on C banded metaphases obtained from peripheral lymphocyte cultures of 15 couples with recurrent early abortions and 15 control couples, all Caucasians. Analysis of variance was first performed on separate metaphases to measure intra-individual, inter-individual, and between population variation in a hierarchical model. Since the significant intra-individual differences covered the other parameters we performed, secondly, a one way analysis of variance on the mean values of metaphases per person in order to measure the inter-individual and between population variation. The results did not show a relationship between C heterochromatin lengths and occurrence of recurrent abortions.

Abortion, Habitual↗

Comparison of chromosome associations in human lymphocytes arrested by colcemid, nocodazole, or cycloheximide.

The method of "generalized distances" was applied to compare the effects on homologous interchromosomal distances of colcemid, the routinely used tubulin inhibitor with the effects of two other metaphase arrestants: nocodazole, also a tubulin inhibitor and cycloheximide, an inhibitor of protein synthesis which preserves somatic association. More homologous pairs were associated in the cycloheximide treatment than in the other two procedures; however, while several chromosomes which tend to lie toward the center of the metaphase plate showed somatic association in the various treatments, we found no evidence for somatic association of the larger, more peripherally located chromosomes in human cells in any of our treatments (chromosome pair 7 excepted in the colcemid sample).

Benzimidazoles↗

Is there a predisposition for meiotic nondisjunction that may be detected by mitotic hyperploidy?

The aneuploidy frequencies have been studied in vitro in lymphocytes from couples with recurrent abortions, from parents of a trisomic child and from control couples with at least two normal children; c-heterochromatin variants have been analysed on the same samples by length measurements. A significant increase of hyperploid cells has been observed in the lymphocytes from parents of a trisomic child and couples with recurrent abortions as well. However, no consistent correlation has been found so far between c-heterochromatin variants and an increase of aneuploidy.

Abortion, Habitual↗

Comparison of two measuring methods for the evaluation of C-heterochromatin in human chromosomes.

In this study two different methods for evaluating the size of the C heterochromatin blocks of human chromosomes 1, 9, 16, and Y were compared. The first method measured the lengths of both the euchromatin and the C heterochromatin parts of the p and q arms of chromosomes 1, 9, 16, and Y. The second method analyzed the same chromosome segments, but by measuring the areas. In the comparison, the relative C heterochromatin value (length or surface) of each chromosome, the mean for each individual, the standard deviation, and the coefficient of variation were taken into account. It is proposed that the best estimation for the size of a C heterochromatin segment is the ratio of its length to the total length of the chromosome; accurate estimation requires at least 20 metaphases.

Chromosome Banding↗

The central localization of the small and early replicating chromosomes in human diploid metaphase figures.

Centromere-center distances are analyzed in 700 metaphase plates, which belong to four different samples. The descriptive analysis of the chromosome distribution shows that smaller, earlier replicating, genet-dense chromosomes are preferentially found near the metaphase plate center, surrounded by longer chromosomes which finish their replication rather late during S phase. This general pattern is highly constant in diploid metaphase samples and independent of sex, culture time, and number of individuals used in the sample. There is accumulating evidence that this overall distribution is not the result of technical artifacts. The metaphase plate data are complementary to the concept of an interphase nucleus structure in which late-replicating, genetically less active chromatin is accumulated at the periphery of the nucleus, while other, earlier replicating chromatin is connected with the intranuclear matrix. Although the currently available data should not be overinterpreted, an extension of the "bodyguard" hypothesis, which was suggested for C heterochromatin, provides a functional interpretation for these data: The peripherally localized, late-replicating genetic material protects the centrally localized euchromatin against mutagens, clastogens, and maybe also against viruses.

Adult↗

Chromosome distribution studies in XXY karyotypes.

The method of 'generalised distances' was applied to characterise the relative position of the metaphase chromosomes in a population of XXY subjects (180 metaphases from 28 subjects). The most striking observation was that the presence of an extra gonosome coincided with a disturbance of the normally stable centromere-centre distribution pattern. The distribution analysis gave no clear cut evidence for the induction of gonosomal trisomy XXY by chromosome association. No significant association was observed between X and X or X and Y but there was a smaller distance between X and Y in XXY karyotypes than in XY karyotypes. As far as autosomes are concerned, the XXY karyotypes were characterised by a less central location of the acrocentrics without a clear decrease of association frequencies of these acrocentrics, and the C heterochromatin rich chromosomes were more often associated than in the XX and XY control populations. These data do not support the idea that gonosomal trisomies result from chromosome associations, but favour the hypothesis that spindle degeneration as a result of intrafollicular ageing of C heterochromatin polymorphism may be responsible for non-disjunctions.

Cells, Cultured↗

Mutagenicity study on mice given mercuric chloride.

The mutagenic activity of different concentrations of mercuric chloride (0, 2, 4 and 6 mg HgCl2 per kg body wt) has been analysed in Swiss Albino mice at several periods (12, 24, 36 and 48 h) after intraperitoneal injection. No increased frequency of chromosomal aberrations was observed in bone marrow cells or in spermatogonia.

Animals↗

Telomere and centromere association tendencies in the human male metaphase complement.

"Generalized distances" between centromeres and between telomeres were statistically analyzed (chi 2 tests) in 100 trypsin-banded metaphase figures derived from normal males. Analysis of association tendencies on the first column of obtained c-c, p-p, q-p, and p-q histograms showed significant heterochromatin attraction not only between nonacrocentrics and acrocentrics but also between two nonacrocentric chromosome pairs (1 and 16). However since not all c-heterochromatin-rich chromosomes were involved in associations (pair 5), and conversely, since chromosomes without an important centromeric heterochromatin block were involved in associations (pairs 8 and 11), it is probable that centromeric heterochromatin is not the only factor responsible for chromosome association. Moreover associations occur not only at the centromeres; in our circle analysis of the binding capacity of the telomeres or centromere of one chromosome pair with the telomeres or the centromeres of all other chromosome pairs, we also found preferential associations for T(4,13), T(9,15), T(11,15), T(13,19), T(15,19), T(17,18), T(17,22), and T(19,20). We therefore suggest that heterochromatin is not the only reason for chromosome association and that telomeres may also play an important part in this process.

Adult↗

Chromosome distribution studies after inorganic lead exposure.

We studied the chromosome distribution in persons professionally exposed to inorganic lead. The degree of lead exposure was evaluated by biochemical measurements and cytogenetic analysis. The chromosome distribution was analyzed from trypsin banded karyotypes; in particular we studied centromere distances (delta2) and centromere-metaphase-center distances (d2) which were obtained by computer-aided mathematical transformation of the individual metaphase coordinates. Higher concentrations of blood lead and urine delta-ALA and a statistically significant increase in aneuploidy, hypoploidy, and type-B chromosome aberrations revealed appreciable exposure although none of the subjects showed signs of excessive lead absorption. However study of the chromosome distribution showed no major differences with that of the controls indicating that lead acts preferentially (directly or indirectly) on the chromosomes rather than on the spindle apparatus. A dissociation of the acrocentric chromosomes was observed in the lead group when compared with the controls. This is thought to reflect a secondary action of lead on the nucleolar organiser regions.

Adult↗

Chromosome distribution studies in phenyl mercury acetate exposed subjects and in age-related controls.

Peripheral blood lymphocytes of phenyl mercury acetate exposed persons and a control population of the same age were cultured for 48 h. In both populations 100 metaphases were trypsin-banded and caryotyped. The relative position of the metaphase chromosomes was studied by means of centromere--centromere distances (delta2) and centromere--metaphase centre distances (d2) obtained by computer-aided mathematical transformation of the individual metaphase coordinates. By comparing both investigated cell populations we mainly observed that the chromosome combinations which statistically differ in mercury-exposed workers from the controls show an increase of centromere-centromere distances after mercury exposure. From the data we may suggest that phenyl mercury acetate influences at first the position of particular chromosomes; especially D-group chromosomes which are involved in nucleolus organisation. This may be due to a greater density of SH-wearing molecules in that region or to a possible inhibition of specific enzymes regulating the nucleolar activity. The exposure level is however too low to allow definite conclusions in this respect.

Adult↗

Non-random association of trypsin-banded human acrocentric chromosomes.

This paper deals with a computer-aided study of the associations between acrocentric chromosomes as well as between those other chromosomes which in our investigations were revealed to be significantly closer to each other than random. The chromosome pairs were identified by a trypsin-banding technique. The method used has been elaborated previously with the specific aim of determining associations in a manner that avoids all subjective criteria. The tendency for association between homologous chromosomes is in decreasing order: 21 and 13 greater than 1 greater than 14, 18 and 19 greater than 17. Among the nonhomologous acrocentric chromosomes the significant tendencies for associations are between D-D: 13-14 greater than 13-15 greater than 14-15; between D-G: 13-21 greater than 14-21 greater than 13-22 greater than 15-22. The implication of the different tendencies to associate are dicussed in terms of aetiology of numerical and structural chromosome abnormalities.

Adult↗

Stability of centromere-center distances in normal human metaphases.

Centromere-center distances were analyzed in 50 normal female and 100 normal male metaphases. Compared with the random distribution of all chromosomes, chromosome pair 6 had a significantly different distribution in both female and male metaphases. Moreover, a significant peripheral location of chromosome pairs 4 and 5 and a significant central location of chromosome pairs 13, 15, 21, and 22 were found in male metaphases. But no specific peripheral location could be assigned to the X or Y chromosomes. No inter- nor intraindividual differences or sex-dependent variation in centromere-center distances were observed. Variance analyses demonstrated consistent centromere-center distances in normal human metaphases obtained from individuals of the same age. The constancy of these chromosome distributions may correlate with chromosome duplication pattern, chromosome length, and chromosome structure.

Adult↗