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PubMed2000

Polyploidy induces centromere association.

Many species exhibit polyploidy. The presence of more than one diploid set of similar chromosomes in polyploids can affect the assortment of homologous chromosomes, resulting in unbalanced gametes. Therefore, a mechanism is required to ensure the correct assortment and segregation of chromosomes for gamete formation. Ploidy has been shown to affect gene expression. We present in this study an example of a major effect on a phenotype induced by ploidy within the Triticeae. We demonstrate that centromeres associate early during anther development in polyploid species. In contrast, centromeres in diploid species only associate at the onset of meiotic prophase. We propose that this mechanism provides a potential route by which chromosomes can start to be sorted before meiosis in polyploids. This explains previous reports indicating that meiotic prophase is shorter in polyploids than in their diploid progenitors. Even artificial polyploids exhibit this phenotype, suggesting that the mechanism must be present in diploids, but only expressed in the presence of more than one diploid set of chromosomes.

Centromere↗
PubMed1988

Changes in ploidy distributions in human liver carcinogenesis.

Cellular and nuclear DNA content was measured by flow cytometry and the fraction of binucleated cells by fluorescence microscopy in normal adult human livers, hepatocellular carcinomas, cirrhotic livers surrounding tumors, and in some benign liver conditions. In five normal livers about one-half of the hepatocytes were polyploid; the majority of these were binucleated tetraploids containing two diploid nuclei. Thus, polyploidization in human liver does not progress as far as, for example, in the rat, where 80%-90% of adult hepatocytes are polyploid, mostly with tetraploid or octoploid nuclei. In five human euploid hepatocellular carcinomas and one investigated case of focal nodular hyperplasia, the percentage of polyploid cells was significantly reduced. Four other carcinomas exhibited a prominent aneuploid (hypotetraploid) peak in addition to the diploid peak. An abnormally low fraction of binucleated cells was also indicated in these tumors. Liver tissue surrounding the tumors had a ploidy distribution similar to that of normal liver. The results suggest that, like in several models of experimental hepatocarcinogenesis, human hepatocellular tumor growth is associated with a decreased polyploidization tendency and a corresponding increase in diploid, divisional growth, which may give the tumors a growth advantage relative to the surrounding liver.

Adolescent↗
PubMed1988

Chemically induced aneuploidy in female germ cells.

Female mice were dosed with the spindle poisons colcemid (5 mg/kg) or colchicine (2 mg/kg) or with a dihydropyridazinone (ICI 109,081; 5 mg/kg; which inhibits oocyte maturation) or with saline, the vehicle control. The dosed females (whose ovulation was synchronized using exogenous gonadotrophins) were mated with undosed males, 12 or 3 h prior to ovulation, coresponding to MI or MII stages in preovulatory oocytes. First-cleavage embryos derived from these matings were then analysed for numerical chromosome aberrations. There were no numerical aberrations in the embryos derived from control matings. Polyploid embryos were isolated from females dosed with colchicine. When females were dosed 3 h prior to ovulation (PO) 26% of the first-cleavage embryos were polyploid; in those dosed 12 h PO it was 100%. Colcemid and ICI 109,081 induced both polyploid and aneuploid embryos; with colcemid these aberrations were only observed in the embryos derived from oocytes of females dosed 3 h PO. At this sample time 4% of the embryos were polyploid and 24% were aneuploid. In contrast, the majority of aberrations induced by ICI 109,081 were observed in females dosed 12 h PO where 10% of the embryos were polyploid and 3% were aneuploid.

Aneuploidy↗
PubMed1999

A high proportion of bovine blastocysts produced in vitro are mixoploid.

Fluorescence in situ hybridization with chromosome 6- and chromosome 7-specific probes was used to assess the extent of chromosome abnormalities in developing bovine blastocysts at 7-8 days after insemination in vivo or in vitro. Interphase nuclei (N = 10 946) were analyzed from 151 blastocysts produced in vitro and from 28 blastocysts recovered from superovulated animals. This revealed that 72% (109 of 151) of the in vitro-produced blastocysts were mixoploid, i.e., were a mixture of normal, diploid, and polyploid cells. However, only a small fraction of the total number of cells were chromosomally abnormal. Of the mixoploid blastocysts, 83% (91 of 109) contained less than 10% polyploid cells, 13% (14 of 109) contained 11-25% polyploid cells, and only 4% (4 of 109) of the blastocysts had more than 25% polyploid cells per blastocyst. In contrast, a significantly lower proportion (25%) of mixoploidy was found in 28 bovine blastocysts developed in vivo (p < 0.0001). All of the mixoploid blastocysts that had developed in vivo contained less than 10% polyploid cells. No entirely aneuploid blastocysts, i. e., blastocysts in which all cells had the same type of chromosome abnormality, were found in either of the groups. Taken together, the most common chromosome abnormalities observed were diploid-triploid mixoploidies and diploid-tetraploid mixoploidies. Thus, our results confirm earlier reports that morphologically normal bovine blastocysts developed in vivo are often mixoploids. We further show that in vitro-produced bovine blastocysts have a high rate of mixoploidy. Although the difference in mixoploidy rate detected in this study may not be general, it is an interesting phenomenon for further studies.

Animals↗
PubMed1994

Megakaryocyte growth in vitro predicts outcome in idiopathic thrombocytopenic purpura.

PURPOSE: The impact of megakaryocyte growth in vitro on clinical data, especially outcome, was studied in 25 consecutive children with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Twenty children with untreated de novo ITP and five children with pretreated ITP were evaluated. The number of megakaryocyte colonies (cloning efficiency), the mean cell number per colony (mitotic amplification) and the percentages of polyploid megakaryocytes after 7 and 12 days in culture (relative size of the endomitotic compartment) were determined in two separate clonal assays. The culture data were related to clinical findings and outcome of the thrombocytopenia. RESULTS: The mean cell number per megakaryocyte colony was significantly correlated with the observed increase in the platelet count 5 days after starting therapy (n = 23; r = 0.642), and a significant negative correlation was found between the relative size of the endomitotic compartment and the duration of thrombocytopenia after bone marrow culture analysis (n = 25; r = -0.503). If all 25 children with ITP (untreated de novo and pretreated ITP) were considered, a normal frequency of polyploid megakaryocytes was associated with a duration of ITP for < 6 months in 14 of 16 cases, whereas an impaired polyploidization predicted a persistence of ITP for > 6 months in 9 of 9 cases (p < 0.0005); if only children with untreated de novo ITP (n = 20) were considered, 13 of 15 children with a normal polyploidization had an acute course of their ITP and 5 of 5 children with an impaired polyploidization developed chronic ITP (p < 0.003). CONCLUSIONS: The results in this small group of patients suggest that the assessment of the relative size of the endomitotic compartment after 7 and 12 days in plasma clot culture actually appears to be the best method for predicting a chronic course in children with ITP.

Adolescent↗
PubMed1997

Expression of functional beta-adrenoceptors and polyploidy development in cultured vascular smooth muscle cells from spontaneously hypertensive rats.

The main objective of this study was to investigate the role of beta-adrenoceptor activation in the development of polyploidy in these cells. Smooth muscle cells (SMCs) were cultured from 3- to 4-, 10- to 12-, and 28- to 30-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Functional expression of beta-adrenoceptors was examined by treatment of cultured SMCs with a nonselective beta-adrenoceptor agonist, isoproterenol, or an adenylate cyclase activator, forskolin, or a membrane-permeable analog of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromo-cAMP, and the measurement of intracellular cAMP levels, using a radioimmunoassay. The effects of these treatments on polyploidy development were also studied by measuring the DNA content of SMCs, using scanning microdensitometry. Treatments with isoproterenol or forskolin increased intracellular cAMP levels in both strains of rats in all three age groups. Addition of the beta-adrenoceptor antagonist DL-propranolol inhibited the isoproterenol-stimulated response in SMCs from both SHR and WKY in all three age groups. The number of polyploid SMCs was significantly increased by treatments with isoproterenol, forskolin, or 8-bromo-cAMP in SMCs from 3- to 4-week-old WKY and SHR, but in the 10- to 12-week age group, an increase was found only in SMCs from WKY. Such treatments had no effect on the incidence of polyploid SMCs in the 28- to 30-week groups. We conclude that (i) beta-adrenoceptors expressed by the SMCs from WKY and SHR at all three ages are functional and are coupled via Gs proteins to the stimulation of adenylate cyclase, (ii) treatments that elevate intracellular cAMP levels (by activation of beta-adrenoceptors or of adenylate cyclase) lead to increased polyploid SMCs from WKY and SHR in the younger age group, confirming a role for the beta-adrenoceptor-adenylate cyclase pathway in the development of polyploidy in cultured SMCs from both of these strains of rats, and (iii) the absence of these treatment effects in the induction of polyploid SMCs in older age groups suggests that in these cells, other factors or processes may be involved in regulating the development of polyploid SMCs.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2006

Quantification of genetic relationships among A genomes of wheats.

The genetic relationships of A genomes of Triticum urartu (Au) and Triticum monococcum (Am) in polyploid wheats are explored and quantified by AFLP fingerprinting. Forty-one accessions of A-genome diploid wheats, 3 of AG-genome wheats, 19 of AB-genome wheats, 15 of ABD-genome wheats, and 1 of the D-genome donor Ae. tauschii have been analysed. Based on 7 AFLP primer combinations, 423 bands were identified as potentially A genome specific. The bands were reduced to 239 by eliminating those present in autoradiograms of Ae. tauschii, bands interpreted as common to all wheat genomes. Neighbour-joining analysis separates T. urartu from T. monococcum. Triticum urartu has the closest relationship to polyploid wheats. Triticum turgidum subsp. dicoccum and T. turgidum subsp. durum lines are included in tightly linked clusters. The hexaploid spelts occupy positions in the phylogenetic tree intermediate between bread wheats and T. turgidum. The AG-genome accessions cluster in a position quite distant from both diploid and other polyploid wheats. The estimates of similarity between A genomes of diploid and polyploid wheats indicate that, compared with Am, Au has around 20% higher similarity to the genomes of polyploid wheats. Triticum timo pheevii AG genome is molecularly equidistant from those of Au and Am wheats.

DNA Fingerprinting↗
PubMed1984

Chromosome segregation from cell hybrids. I. The effect of parent cell ploidy on segregation from mouse-Chinese hamster hybrids.

To determine whether the dosage of some parental factor influences the direction and extent of chromosome segregation, I have constructed hybrids between polyploid series of mouse and Chinese hamster lines. The input ratio of mouse:hamster chromosomes varied from 3.3 (in hybrids between diploid hamster and polyploid mouse cells) and 0.9 (in hybrids between polyploid hamster and near-diploid mouse cells). Mouse chromosomes were retained and hamster chromosomes were lost from all hybrids with input ratios greater than or equal to 1.3; the extent of hamster chromosome loss increased from 25 to 60% as the proportion of mouse chromosomes was increased. Reverse segregation was observed in hybrids in which the ratio was 0.9; hybrids between polyploid hamster and diploid mouse cells retained most hamster chromosomes and lost 52% of mouse chromosomes. I conclude that the direction and extent of chromosome segregation from these hybrids depends on the dosage of some factor contained in the parent cells; because the volumes of polyploid cells are proportional to chromosome number, this factor could be chromosomal, nuclear, or cytoplasmic. Dosage differences should therefore be considered when comparing chromosome segregation from hybrids with cells of the same species combination, but which might differ in chromosome number (e.g., diploid lines and established lines), or cell volume (e.g., cells from different tissues).

Animals↗
PubMed2001

Role of p21(Cip1/Waf1) in cell-cycle exit of endomitotic megakaryocytes.

The cyclin-dependent kinase inhibitor p21(Waf-1/Cip-1) is expressed at high level during megakaryocyte differentiation, but its precise function remains unknown. In this study, it is confirmed that p21 was expressed at a high level in hypoploid (2N and 4N) and polyploid (at least 8N) human megakaryocytes derived from CD34(+) cells. A high expression of p27(Kip1), p16, cyclin E, and cyclin D3 was also found in both populations associated with a hypophosphorylated form of retinoblastoma protein, suggesting that the majority of hypoploid and polyploid megakaryocytes are G(1)-arrested cells. As human megakaryocytes grown in vitro present a defect in their polyploidization, the study switched to the murine model. The modal ploidy of megakaryocytes derived from lineage-negative cells was 32N, and an elevated expression of p21 was found in high-ploidy megakaryocytes. In addition, p21 and p27 were coexpressed in the majority of mature polyploid megakaryocytes. The p21 was detected by immunofluorescence in megakaryocytes derived from p53(-/-) mice, demonstrating a p53-independent regulation during megakaryocyte differentiation. Megakaryocytopoiesis of p21(-/-) mice was subsequently studied. No marked abnormality in the ploidy of primary or cultured megakaryocytes was detected. Overexpression of p21 in p21(-/-) or normal murine megakaryocytes and in human megakaryocytes showed in all these cases a marked inhibition in megakaryocyte polyploidization. In conclusion, while a reciprocal relation is observed between p21 levels in megakaryocytes and the cycling state of the cells, p21 is not essential for the determination of the ploidy profile in normal megakaryocytes in vivo. However, high levels of its expression in cultured megakaryocytes arrest the endomitotic cell cycle.

Animals↗
PubMed1989

[Nuclear DNA cytofluorometry of normal human laryngeal epithelia and squamous cell carcinoma].

Normal human laryngeal epithelia and laryngeal squamous cell carcinoma were assayed by Feulgen DNA cytofluorometry using free cell nuclei isolated from carnoy-fixed, paraffin-embedded specimens. In all of the 12 normal specimens, the epithelium showed typical diploid cell clones with low proliferative activity. Polyploid cells were seen in only two specimens from subjects aged 61 and 69 years respectively, and the number of polyploid cells seen in these two specimens was only two. Fifteen cancer cases were divided into three groups: an untreated group (5 cases), a chemotherapy group (5 cases) and a group of cases with recurrence after radiation therapy (5 cases). Among these three groups the DNA ploidy patterns were compared. In the untreated group, all cases showed a two-peak diploid pattern and a high proliferative activity, and polyploid cells were present. In the chemotherapy group, a wide one-peak histogram extending from 2C to about 5C was noted in 4 cases, and an aneuploid pattern in one case. Thus, the DNA ploidy pattern in the chemotherapy group differed from that in the untreated group. Of the 5 cases with recurrence after radiation therapy, one had a tetraploid pattern, but the remaining 4, a two-peak diploid pattern similar to that seen in the untreated group. Polyploid cells were observed in all these cancer cases. However, because they were also seen in some normal subjects, the finding of polyploid cells is not considered to be conclusive of cancer diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Expression of CD34 and platelet glycoproteins during human megakaryocytic differentiation.

Megakaryocyte (MK) progenitors express the CD34 antigen, but the precise stage along the MK differentiation at which the CD34 is turned off is not known. Purified marrow CD34+ cells give rise within 4 days in culture to rare mature MK, suggesting that some MK precursors bear the CD34 antigen. By multiparameter flow cytometry, CD34+ cells bearing platelet glycoproteins (GP) could be detected, but at a low frequency (less than 2% of the marrow CD34+ cells). We used an in vitro liquid suspension culture to selectively amplify MK differentiation. CD34+ cells were isolated after 6 days before a wave of mature MK. These cells gave rise within another 4 days in culture to numerous MK (up to 50%), showing that these CD34+ cells were greatly enriched in MK precursors. This was confirmed by ultrastructural studies that showed the presence of typical promegakaryoblasts. By flow cytometry, three populations of small cell size could be defined: CD34+ GPIIIa-, CD34+ GPIIIa+, and CD34- GPIIIa+ cells. The two GPIIIa+ populations were almost pure immature blastic MK. alpha-Granules were rare in the CD34+ GPIIIa+ cells, whereas they were more developed in the CD34- GPIIIa+ cells, which also exhibited demarcation membranes. Approximately 45% of the two GPIIIa+ cell populations were capable of undergoing at least one cell division and of giving rise to a polyploid progeny. However, proliferation and polyploidization capacities were higher in the CD34+ GPIIIa+ than in the CD34- GPIIIa+ cells. A small fraction of GPIIIa+ cells (about 10%) were able to give rise to MK colonies containing a maximum of 16 cells for the double-positive cells. GPIb was expressed on about sixfold less cells than GPIIIa, but was detected on a few CD34+ cells. Most double-stained (CD34+ GPIb+) cells were polyploid. CD34- GP+ cells (more mature) contained less polyploid MK than the CD34+ GP+ fraction. Altogether, these findings show that CD34 is still expressed on a polyploid transitional immature MK and that GPIIIa is present on some MK progenitors with low proliferative capacities. They also suggest that the expression of CD34 is related to the ability of the MK precursors to accomplish DNA synthesis (either cell division or endomitosis). Such a characterization will facilitate the investigation of the role of the different cytokines on MK differentiation.

Adult↗
PubMed1976

[Analysis of DNA histograms by computer (author's transl)].

INTRODUCTION: Quantitative DNA cytophotometry, the study of morphology of chromosomes and cell kinetics are important approaches toward characterization of genetic information. Each approach has its own problems and limits. Difficulties with interpretation of DNA histograms arise from a lack of proper terminology, and from attempting to interpret them in terms of the existing terminologies for chromosomal analysis and cell kinetics. Aim of this research was to develop a computerized mathematical analysis of DNA histograms. MATERIALS AND METHODS: As a basis for the comparison of normal with those of tumor cell populations the DNA histograms of heart muscle cells were selected for the normal cell population from 14 normal hearts of adults, 16 hypertrophic hearts, 14 non-polyploidized hearts of children, and 14 hypertrophic hearts of children with congenital malformations. Normal diploid cell populations from 7 effusions were also included. The 24 populations of malignant cells consisted of primary tumors and metastatic effusions. DNA cytophotometry was performed on single nuclei in Feulgen stained preparations by means of the UMSP/XD 50 ZEISS. The approximation of the DNA histograms by linear combination of normal distributions was done according to spline-function and calculated by means of the IBM-375. RESULTS: The nuclear classes 2C, 4C, and 8C show no differences between the normal, left and right heart with respect to mean values (X), standard deviations (sx), variances (sX) and coefficients of variance (sx/X). However, coefficients of variance are smaller in hypertrophic (2.15 to 8.37%) than in normal hearts of adults (8.90 to 10.85%), and larger in hypertrophic heart of children (4.06 to 7.09%). The mean values of the DNA classes 2C, 4C, 8C, and 16C vary witin +/- 18.6% with a probability of 95.5%. Benign effusions contain only 2C and 4C nuclei with a variance of 4.00% and 8.75%, respectively. In DNA histograms of malignant cells, only one third has a first peak outside of 2C +/- 18.6%. In approximately one fifth of the histrograms the position of the second or third peaks deviates significantly from normal polyploid values. Since a large proportion of polyploid nuclei is limited to only a few normal tissues, pronounced polyploidy is suggestive of malignancy in all other tissues. If in the cases containing only two DNA classes, 2C and 4C, the populations are malignant, the proportion of 4C is more than 8% while in the corresponding benign populations the proportion of 4C atains only 2.97 +/- 2.5%. In some cases a few highly polyploidized nuclei not taken into a account by our computer program are suggestive of malignancy. In only one DNA histogram out of the 24 analysed, all of these criteria are negative. In six cases the computer analyses reveal two stemlines of tumor cells with corresponding polyploid values.

Adult↗
PubMed2004

[Polyploidy: significance for cardiomyocyte function and heart aerobic capacity].

Somatic polyploidy, defined as genome multiplication, was found in all differentiated mammalian tissues. The highest level of such a polyploidy was found in the myocardium. This phenomenon was shown to be associated with changes in the pattern of gene expression. Hence, polyploidization may create cells with new physiology. The effect of polyploidy on the heart function has never been studied. The aim of the present study was to investigate the effect of polyploidy on cardiomyocyte functioning and heart aerobic capacity. DNA and the total protein content, nucleolar activity reflecting the rate of rRNA synthesis and, consequently, ribosome biogenesis, were measured in ventricular myocytes isolated from the human and from 21 mammalian species by image cytometry and microscopic morphometry. The total protein content was estimated after staining slides with naphtol-yellow dye. For measurement of DNA and nucleolar area, staining with Hoechst and AgNO3 was applied. Cardiac aerobic capacity was evaluated by the heart mass to body mass ratio. A negative correlation between the heart index and the average cell ploidy was revealed (r = -0.79; P < 0.0001). The average genome number per myocyte was registered to be higher by approximately 35% in the sedentary mammals, with the heart index about 0.4% from body mass, than in the athletes with heart index about 0.6% of body mass. Polyploidization was shown to be associated with a sharp decrease in the protein/DNA ratio in cardiomyocytes. As a result, cardiomyocytes in the athletic mammals with poorly polyploid hearts have much higher protein content per genome than do cells in the sedentary species with highly polyploid hearts. Surprisingly, despite decreased protein/DNA ratio, the nucleolar area per genome significantly increased with polyploidization, indicating the imbalance between the cellular protein content and the rate of ribosome biogenesis. Such an imbalance should obviously impair cardiac function, because the additional genomes take some valuable space and biological resources from the cell, which could have been otherwise directed to the maintenance of cardiomyocyte contractile machinery. It is generally accepted that somatic polyploidy is associated with oxidative stress and energetic starvation. Thus, we suppose that additional genomes may serve for cardiomyocyte protection from oxidative damage in the hearts.

Animals↗
PubMed1992

[Analysis of the malignant potentiality in superficial esophageal carcinoma by cytofluorometry of nuclear DNA and cellular protein contents--in relation to histopathologic findings and prognosis].

Recently patients with superficial esophageal carcinoma have increased due to progress in endoscopy, but the results of surgical treatment are still not satisfactory. Cytofluorometric analysis of nuclear DNA and cellular protein contents, measurements of malignant potentiality, in superficial esophageal carcinoma were performed, and DNA ploidy patterns were compared statistically with histological findings and prognosis. Nuclear DNA and cellular protein contents were measured by the multiparametric cytofluorometry in 72 patients with squamous cell carcinoma (mucosal ca.: 14 cases, submucosal ca.: 58 cases). DNA ploidy patterns were classified into diploid (without polyploid), polyploid, and aneuploid according to the peaks of the DNA content histogram. In the current study, there were 22 cases (30%) of diploid, 17 cases (24%) of polyploid, and 33 cases (46%) of aneuploid. In patients with polyploid and aneuploid, there was high frequency of lymph vessel invasion, as compared with diploid (p less than 0.01). The overall five-year survival rates of patients with diploid, polyploid, aneuploid were 91%, 71%, 55%. The prognosis in patients with aneuploid was poorer than diploid (p less than 0.05). The recurrent cases of early esophageal carcinoma were aneuploid only. DNA ploidy patterns proved to be one of the major prognostic factors by multivariate analysis. The patients with higher DNA content had a high frequency of lymph node metastasis. In the patients with poor prognosis, cellular protein content showed higher. These results suggest that the analysis of nuclear DNA and cellular protein contents are useful for assessing the prognosis and planning postoperative combined therapy in patients with superficial esophageal carcinoma.

Adult↗
PubMed1990

[Nuclear DNA content in the cells of squamous cell carcinoma and Bowen's disease. I. Relationship between nuclear DNA content and grade of clinical and histological malignancy].

Nuclear DNA content of squamous cell carcinoma (SCC) was assayed by use of microfluorometry in an attempt to know the relationship between the content and grade of malignancy. As the results, we found that polyploid cell (greater than 4C) population tends to increase with advancing histological malignancy. However, the population of polyploid cells of grade 1, 2 and 3 SCC was almost the same. The number of polyploid cell of recurred lesion of SCC was increased than that of primary lesion. And polyploid cell (greater than GC) population in the primary lesion of the recurred case was higher than that in the tumor of non-recurred case. From these findings, it may be concluded that the polyploid cell population in SCC was proportional to clinical and histopathological malignancy in some extend.

Aged↗
PubMed1997

[Interconnection of parameters of the mitochondrial and myofibrillar apparatus of cardiomyocytes and ploidy and hypertrophy in certain mammalian species, differing in body mass].

Using cytophotometry and interferometry, ploidy levels and dry weights were determined in cardiac atrium and ventricle myocytes in various mammalian species. Besides, in the same species, using electron microscopy and image analysis, myofibril volume density (MFVD) and mitochondrial volume density (MTVD), as well as the total length of internal mitochondrial membranes (IMM) per cell area unit were measured. The total of 14 mammalian species were studied, with approximately 100,000-fold interspecies differences in the body weight. The dry weights of the left ventricle myocytes in different mammalian species have been shown to vary from 3660 +/- 127 to 8890 +/- 160 pg. Somewhat smaller were the right ventricle myocytes; their dry weight varied from 3598 +/- 134 to 8189 +/- 160 pg. The atrium myocytes were significantly smaller than the ventricle myocytes in all the mammalian species studied. The lowest dry weight of the left atrium myocytes was revealed in the mouse (2415 +/- 96 pg), while the largest weights of the left atrium myocytes were found in the pig (5530 +/- 138 pg). Myocytes of the right atrium, with their mean dry weights in different species varying from 2379 +/- 93 (in the mouse) to 5123 +/- 124 pg (in the pig), were the smallest among all cardiac chamber myocytes. The data obtained indicate that differences in size between the ventricles and atria in mammals are owing predominantly to differences in the number of cardiomyocytes in different parts of the heart rather than to the size of these cells. The dry weight ratio between the right and left ventricle myocytes in various mammalian species was, on average, 0.937 +/- 0.02, and between the right and left atrium myocytes 0.938 +/- 0.04. This ratio between the left atrium and left ventricle myocytes was 0.717 +/- 0.03 and that between the right atrium and right ventricle was 0.722 +/- 0.02. The data obtained indicate that the ratios of cardiomyocyte sizes in different heart parts are rather stable parameters in the mammalian evolution. The mean ploidy levels in myocytes in different parts of the heart corresponded to the mean sizes of the cells. In all the species studied in this work, the ploidy of myocytes of the right ventricle was lower, on average, by 7% compared to myocytes of the left ventricle. The atrial cardiomyocytes had a markedly lower ploidy than the ventricular cardiomyocytes, the myocyte ploidy levels in the left atrium being in all the species higher than in the right atrium. In spite of a higher ploidy level in the ventricular than in the atrial myocytes, this difference in ploidy was less pronounced than the corresponding difference in the myocyte sizes in the same heart parts. In the majority of mammalian species studied, myocyte polyploidization in different parts of the heart combined two ways promoting the increase in the number of genomes in the cells: (1) acytokinetic mitoses in binuclear and multinuclear cells, i. e. mitotic divisions of diploid nuclei without cytoplasm division; in this case no increase in the tissue cell number occurred, (2) alternation of acytokinetic mitoses in mononuclear cells and of bimitoses in binuclear cells; in this case tissue cells increased in number. The ratio of these two ways of polyploid cell formation differed in various species. The former way appeared to be the only in the nutria and horse, whereas the latter way was found in the shrew and arctic fox. In pigs, whose polyploid cardiomyocytes are also formed mainly through the increase in number of diploid cell nuclei, the multinuclear cardiomyocytes contained, apart from diploid nuclei, a small amount of polyploid 4c and 8c nuclei. The formation of such cells is due presumably to the two mechanisms: the asynchronous DNA synthesis in one of the nuclei in a multinuclear cell, and the subsequent incomplete polyploidizing mitosis. (ABSTRACT TRUNCATED)

Animals↗
PubMed1998

Enforced expression of human bcl-2 in CD4+ T cells enhances human herpesvirus 7 replication and induction of cytopathic effects.

The cytopathic effects (CPE) resulting from the infection of CD4+ T cells by human herpes-virus 7 (HHV-7) comprises two major mechanisms: generation of large polyploid cells, which eventually undergo necrotic lysis, and apoptosis, predominantly occurring in small mononucleated cells. To dissect the relative contribution of these two phenomena to the overall cytopathicity of HHV-7 in vitro, we have investigated the effect of acute HHV-7 infection on SupT1 CD4+ T cell lines stably transfected either with the bcl-2 anti-apoptotic gene or with the control vector. Overexpression of Bcl-2 protein by these cells was associated with a progressive decline of the total number of viable cells, and a relative increase of enlarged polyploid cell. Of note, the size of polyploid cells was significantly greater in SupT1 cells overexpressing bcl-2 than in cells transfected with the control vector. In addition, bcl-2 expression accelerated the kinetics of an acute spreading of HHV-7 infection, as determined by HHV-7-specific indirect immunostaining revealed by either fluorescence microscopy or flow cytometry. Our results indicate that inhibition of apoptosis in HHV-7-infected cultures greatly favors the process of polyploidization and represents a major mechanism to maximize viral transmission.

Antigens, Viral↗
PubMed1986

Cytofluorometric nuclear DNA determinations on the atrioventricular nodal cells in human hearts.

In the human heart, it is well known that the polyploidization of working heart-muscle cells increases in proportion to increases in heart weight, but there has been no investigation of the process of polyploidization in the specialized heart-muscle cells of the cardiac conduction system which have a nerve-like function. In order to investigate the process of polyploidization in these cells, the nuclear DNA content of atrioventricular nodal cells was measured using cytofluorometry. Tissue samples taken from autopsied hearts without arrhythmias were embedded in paraffin blocks after Carnoy fixation. Blocks containing the atrioventricular conduction system were cut according to the serial sectioning method of Lev et al. The compact atrioventricular nodes were removed from thick paraffin sections (150 micron) under a stereomicroscope. The cells were then isolated by enzyme digestion and ultrasonic treatment. Smears of the isolated cells were double stained with azocarmin-G and acriflavine-Feulgen. Cytofluorometric DNA determinations of the DNA content of atrioventricular nodal cells were performed. Atrioventricular nodes were found to be composed of a large number of diploid cells and a small number of tetraploid cells. No octaploid cells were found. These findings reveal that the process of polyploidization in atrioventricular nodal cells is different from that found in working heart-muscle cells.

Adult↗