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Biomedical subjects

W Y Brodsky

Publications and source records attributed to W Y Brodsky.

6 recordsLinked to original sources

Mitotic-cyclic and cycle-independent growth of cardiomyocytes.

The number of myocytes in mouse heart ventricles increased by 25% to 30%, on average, mainly for 3 days after birth. The mean myocyte number was 1.87 +/- 0.04 X 10(6) in 3-week-old and older mice, while the individual values varied up to 25% in any age group. In newborn mice, up to 90% of the myocytes were diploid cells, then polyploidization occurred. The stable ratio of ploidy classes was observed from 3 weeks to 1 year of age. The main class was always binucleate 2c X 2, comprising approximately 80% of the entire population. Nor were many mononucleate tetraploids (4c) and octaploids of different types (8c, 4c X 2, 2c X 4, 2c + 2c + 4c) observed. An insignificant number of hexadecaploids (16c and 8c X 2) could be found in some animals. The mean protein content in myocytes was not always directly proportional to the weight of the ventricles. These data and a certain discrepancy between calculated wet and measured dry weights allowed us to assume that the water content and the non-muscle component of myocardium varied from heart to heart. In growing myocytes of different ploidy, the ratio of the myocyte masses did not correspond to the genome ratio 2: 4: 8: 16 being equal to 2: 3.3: 5.0: 6.3. Thus the growth of the cells outside mitotic cycle differs from that during polyploidization.

Animals

A cytophotometric and karyometric study of the cardiac muscle cells of young rats exposed to intermittent high altitude hypoxia.

Thirty-day-old rats were exposed to intermittent high altitude in barochamber (7000 m, 4 h per day, 4 exposures) and number of mono- and binucleated myocytes as well as DNA content per nucleus were determined in the right ventricular myocardium. The data indicate enhancement of mitotic division of mono- and binuclear diploid cells in hypoxic animals. Simultaneously, an increase in mononuclear and binuclear tetraploid cells occurred; the latter is probably due to DNA synthesis not followed by mitosis of some binuclear diploid cells.

Altitude

DNA synthesis in the Purkinje neurons.

(3H) Thymidine is incorporated into some cerebellar Purkinje cells of 6- to 30-day-old rats. The frequency of labelled neuronal nuclei was higher in the 12- to 30-day old rats than in the 6- to 10-day-old animals. The grain distribution pattern in autoradiographs was mostly nucleolar amounting to three to ten grains. Some other local labels were revealed, too. Only six Purkinje cells among 42,000 studied in 21 rats possessed heavy label (25 to 50 grains) distributed throughout the nucleus. Control estimations with deoxyribonuclease, hot perchloric acid and covering the autoradiographs again established that the Purkinje cells synthesize DNA perhaps for the purpose of DNA surplus accumulation and/or DNA repair in the neurons.

Age Factors

Mitotic polyploidization of mouse heart myocytes during the first postnatal week.

Polyploidization of myocytes in the cardiac ventricle of mice occurs predominantly during the first week of the postnatal life. Using isolated cells it was shown that about 70% of the cardiomyocytes become binuclear at this time (2c x 2), while 10% are mononuclear but contain 4c of DNA, where c was the haploid level of DNA. About 2% of the cell population were reprsented by 4c x 2 or 8c cells. Cytophotometry of Feulgen-stained DNA in 14C-thymidine-labeled nuclei has shown that the cells that enter the mitotic cycle are mainly diploid. After mitosis (30 h or more after thymidine application) the label was found predominantly in 2c x 2 and 4c cell types. Comparison of the curves presenting dynamics of labeled mitoses and the accumulation of labeled binuclear cells reveals that binuclear 2c x 2 cells are formed by acytokinetic mitosis. The formation of 4c mononuclear cells is accomplished via other types of mitotic arrest; this may be due, for example, to a block in the pro- or metaphase. Only very rare cases of cytotomy were detected and the number of newly formed 2c cells was very low. It is concluded that cell multiplication is practically arrested at this period of life, and growth of the ventricular mass is due to polyploidization of virtually all cycling cells, while their number remains unchanged. Mechanisms and functional significance cardiomyocyte polyploidization are discussed.

Animals

Kinetics of cellular proliferation in regenerating mouse liver pretreated with the alkylating drug dipin.

The effect of prior exposure to the alkylating drug 1,4-Bis[N,N'-di(ethylene)-phosphamide] piperazine (Dipin) on the cell cycle progression in a regenerating mouse liver is reported, using cytological, autoradiographical and DNA-cytophotometrical methods. In Dipin-treated animals 3H-TdR pulse labelled nuclei appeared 22 h after the partial hepatectomy, followed by a rapid rise in labelling index to a very high level between 43-54 h, and then by a gradual decline to 72 h. Four injections of 3H-thymidine at 16 h intervals resulted in 89% labelling of hepatocytes at 72 h. The DNA-synthesis time was assessed by DNA photometry combined with 3H-TdR autoradiography on the same nucleus. The DNA-content in Dipin-pretreated nuclei was doubled after 26 h, approximately three times longer than in the controls. Mitoses were completely absent during the first 2-4 days. They were observed subsequently for up to 2 months but with varying frequency. The frequency of binucleated hepatocytes remained constant during liver regeneration. Hence, pretreatment of resting liver with Dipin altered the kinetics of cell proliferation following partial hepatectomy. Delay in division resulted primarily from an increase in the DNA-synthesis time and a prolonged block of the transition from G2 to mitosis. No changes in the duration of the prereplicative period and in the size of the proliferative pool were noticed. The increase of the mitotic cycle time led to synchronization of the cell population. About a half of the hepatocytes were seen in the S phase by the end of the second day and by the end of the third day about 80% of the cells had passed into the G2 phase.

Alkylating Agents