The synchronizing effect of cyclic 3',5'-adenosine monophosphate on the mitotic cycle of Ehrlich ascitic carcinoma cells]

A study was made of the number of mitoses and of the DNA-synthesizing cells in the ascitic Ehrlich carcinoma in the course of 24 hours after the injection of cyclic 3',5'-adenosinmonophosphate to mice. It was found that as the result of the preprrophase inhibition and, possibly, of stimulation of the cell entry into the S-phase, 8 hours after the action a great number of cells began to divide almost simultaneously. The effect of mitosis synchronization was assessed in the tumour cell population.     

Diurnal changes in the duration of mitosis in rats]

The colchicine method was applied to the study of the 24-hour changes in the duration of mitosis in 45-day rats. The average diurnal duration of mitosis in the pancreatic epithelium, the liver and the epidermis of adult animals was almost half of that in the 7-day-old rats. Diurnal variations of the mitotic index in the investigated tissues could be due both to the variation in the mitotic rate and to that of the duration of mitosis.     

Circardian rhythm of mitoses in the epithelium of the cornea after splenectomy]

In corneal epithelium of CBA mice the index of colchicine mitoses diminished after splenectomy in the day period characterized by rising mitotic activity in control animals. The duration of active phase of cell division rhythm shortened while the maximum of mitotic activity delayed in comparison with control animals. The total amount of cells entering mitosis during 24 hours diminished by 27.7% and the rate of physiological regeneration of corneal epithelium decreased.     

Duration of mitosis in the corneal epithelium and spleen cells of mice with leukemia La

Mitotic fluctuations during 24 hours and duration of motoses were studied in the corneal epithelium and in the leukemic-La spleen cells of mice. The existence of correlative changes between the mitotic index and the duration of mitosis in the course of 24 hours was revealed. It is supposed that a more rapid course of mitosis in the intensively proliferating tissues and a slower one in the tissues with a low proliferative capacity served as a reflection of general regularity.     

Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support

Background

Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor.

Methods

We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb> 50 mg/dL was used as a marker of severe hemolysis.

Results

154 patients received ECMO for cardiac (n= 115) or pulmonary (n=39) indications. Patients’ mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p=0.026), lower 24-hour lactic acid (p=0.023), shorter ECMO duration (P=0.01), fewer RBC transfusions on ECMO (p=0.008) and lower level of PFHb 24-hours post ECMO implantation (p=0.029). 24-hour PFHb> 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p=0.002. A Cox proportional hazard analysis identified PFHb> 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 – 8.8, p= 0.011).

Conclusion

PFHb> 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.     

Effect of colchamine on Ehrlich ascitic carcinoma cells showing synchronized cell division]

The author studied the 24-hour changes in the number of normal and colchamine mitoses in the cells of Ehrlich's ascites carcinoma in mice after the injection of colchamine argainst the background of partial synchronization of cell division, obtained as a result of preliminary injection of dibutyryl cyclic 3',5'-AMP, and also in mice after the injection of colchamine alone or dibutyryl cyclic 3',5'-AMP. As shown, synchronization of cell division in the tumour led to the 2,6-fold increase in the number of tumour cells blocked by colchamine and also to the accelerated arrest of colchamine mitoses.     

Growth dynamics of an amphibian tissue

By the “labeled mitoses” method of Quastler and Sherman and others, the cell cycle of the germinative zone cells of the bullfrog lens epithelium has been characterized. It has been shown that this cycle lasts approximately 83 days with the DNA synthetic phase enduring 100 hours and G₂, 11 hours. G₁ occupies over 90% of the total time. the duration of mitosis itself has not been precisely determined. the length of the synthetic phase was corroborated by double labeling with c¹⁴ and h³-thymidine. When the temperature is raised by 6°c, from 24° to 30° the cycle is compressed by 40%. When the nongerminative, central cells of bullfrog lens epithelium are activated (stimulated to undergo DNA synthesis and mitosis) by injury or through in vitro culture, the length of the cycle also appears to decrease. in the in vitro experiments the generation time, as judged by the period elapsing between two successive bursts of DNA synthesis involving the same cells, amounts to 177–190 hours at 24°c. by raising the temperature to 30°c the time from injury or isolation until the appearance of the first wave of mitosis is reduced by 20%.     

Effects of the plant steroidal hormone, 24-epibrassinolide, on the mitotic index and growth of onion (Allium cepa) root tips

The purpose of the present study was to determine the effects of the steroidal plant hormone, 24-epibrassinolide (BL), on the mitotic index and growth of onion (Allium cepa) root tips. The classical Allium test was used to gather and quantify data on the rate of root growth, the stages of mitosis, and the number of mitoses in control and BL-treated groups of onions. Low doses of BL (0.005 ppm) nearly doubled the mean root length and the number of mitoses over that of controls. Intermediate doses of BL (0.05 ppm) also produced mean root lengths and number of mitoses that were significantly greater than those of the controls. The highest dose of BL (0.5 ppm) produced mean root lengths and number of mitoses that were less than control values, but the differences were not statistically significant. Examination of longitudinally sectioned root tips produced relatively similar results. This study confirms the suppositions of previous authors who have claimed that exogenously applied BL can increase the number of mitoses in plants, but failed to show cytogenetic data. This is the first report detailing the effects of BL on chromosomes and the cell cycle.     

THE EFFECT OF ACUTE RENAL FAILURE ON MITOTIC DURATION OF MOUSE ILEAL EPITHELIUM

Previous percentage labelled mitoses studies in acutely uraemic mice have demonstrated a lengthening of the cell cycle and the DNA synthetic phase of ileal epithelium. The mitotic index was unaltered. Further studies have been performed to obtain an estimate of mitotic duration. Acute renal failure was produced by urinary outflow obstruction in male mice. Controls were subjected to sham operation. The mean number of cells per crypt cell column, number of mitoses present per crypt section and differential mitotic stage count were assessed 18 hr after operation for uraemic and control mice. The mean number of metaphases accumulated per crypt section over a 2 hr interval following colchicine injection was obtained in other groups of mice and the mitotic duration calculated. The mean number of mitoses per crypt section was 1.30 ± 0.46 for the controls and 1.48 ± 0.66 for the uraemic group. No evidence for a block in mitosis was indicated by the differential mitotic stage count. After applying Tannock's correction factor the mitotic duration was estimated to be 0.91 ± 0.18 hr for the control group and 2.81 ± 0.89 hr for the uraemic group. The difference in duration between the groups, 1.90 ± 0.91 hr, was significant (P≤0.05). Reduction in cell proliferation may explain the development of uraemic lesions in the gastrointestinal tract.     

Diurnal variations in the duration of mitosis in the mouse esophageal epithelium]

Considerable differences were found in the morning and the evening mitotic indices of the epithelium in the oesophagus of C57BL/6J mice. By the colchamin method it was shown that the duration of mitosis was the same in the morning and the evening hours and was equal to 34--49 minutes. The results varied and depended on the dose of colchamin and duration of its action. Thus, the diurnal differences in mitotic index of the epithelium in the oesophagus depended on the differences in mitotic activity, the number of mitoses per time unit. It is emphasized that colchamin method should be used with great caution to obtain reliable results.     

Effect of thyroxine on the diurnal rhythm of the mitotic activity and parameters of the life cycle of cells of the liver and esophagus]

The duration of the cellular cycle and the diurnal rhythm of the amount of mitosis were studied in young rats in normality and under the influence of thyroxin. The parenchymal and connective-tissue cells of the liver and cells of the liver and the cells of the oesophagus epithelium basal layer were studied. It was found that under the influence of thyroxin there occured a shortening of the periods of the cellular cycle and a 3--6 h shift to the left of the diurnal rhythm curve of the amount of mitoses. In thyroxinized animals the 21--95% increase of the amount of mitoses in the period of maximum values of the mitotic index during a day was observed as compared with control animals. A conclusion is made about the diurnal rhythm of sensitivity of G0-phase cells to the synchronizing factor, suggesting the decisive significance of the state of the cell population in the interaction of the tissue and hormone cells. The data obatained in the work show that the thyroid hormones regulate the cellular reproduction in the organism by stimulating the cells in the division cycle, synchronization of greater amount of cells by the moment of beginning of the mitotic cycle at a definite time of day and by shortening the period of the cell mitotic cycle.     

Cardiovascular Magnetic Resonance Imaging of Scar Development Following Pulmonary Vein Isolation: A Prospective Study

Aims

Cardiovascular magnetic resonance (MR) provides non-invasive assessment of early (24-hour) edema and injury following pulmonary vein isolation (by ablation) and subsequent scar formation. We hypothesize that 24-hours after ablation, cardiovascular MR would demonstrate a pattern of edema and injury due to ablation and the severity would correlate with subsequent scar.

Methods

Fifteen atrial fibrillation patients underwent cardiovascular MR prior to pulmonary vein isolation, 24-hours post (N = 11) and 30-days post (N = 7) ablation, with T2-weighted (T2W) and late gadolinium enhancement (LGE) imaging. Left atrial wall thickness, edema enhancement ratio and LGE enhancement were assessed at each time point. Volumes of LGE and edema enhancement were measured, and the circumferential presence of injury was assessed at 24-hours, including comparison with LGE enhancement at 30 days.

Results

Left atrial wall thickness was increased 24-hours post-ablation (10.7±4.1 mm vs. 7.0±1.8 mm pre-PVI, p<0.05). T2W enhancement at 24-hours showed increased edema enhancement ratio (1.5±0.4 for post-ablation, vs. 0.9±0.2 pre-ablation, p<0.001). Edema and LGE volumes at 24-hours were correlated with 30-day LGE volume (R = 0.76, p = 0.04, and R = 0.74, p = 0.09, respectively). Using a 16 segment model for assessment, 24-hour T2W had sensitivity, specificity, and accuracy of 82%, 63%, and 79% respectively, for predicting 30-day LGE. 24-hour LGE had sensitivity, specificity, and accuracy of 91%, 47%, and 84%.

Conclusions

Increased left atrial wall thickening and edema were characterized on cardiovascular MR early post-ablation, and found to correlate with 30-day LGE scar.     

Proliferative activity of the epithelium of the rat large intestine during carcinogenesis]

Labelling index and mitotic regimen in the epithelium of the rat descending colon and the ileum was studied during the tumour induction with 1,2-dimethylhydrazine. One month after the beginning of the experiments there was a marked increase of abnormal mitoses (up to 51%) and a change in the proportion of the mitotic phases with the metaphase prevalence (up to 73%). Later, these parameters were unchanged. Beginning from the 3rd month of the experiment there was found an increase in the labelling index (especially, in the carcinoma in situ) and of the mitotic index. In the mucosa of the ileum (where the tumours never developed) no changes of the proliferative activity and of mitotic regimen were found.     

CYTOKINETIC STUDIES OF THE REGENERATIVE PHASE IN THE JB-1 ASCITES TUMOUR

The cell kinetics of recurrent growth of the murine JB-1 ascites tumour have been investigated 0 hr and 24 hr after aspiration of the main part of the tumour in the plateau phase of growth. The experimental data: growth curve, percentage of labelled mitoses curve and continuous labelling curves combined with cytophotometric determination of single-cell DNA content were analysed using two alternative mathematical models for the cell kinetics. Investigations 24 hr after aspiration showed that the doubling time had decreased to 70 hr as compared with 240 hr in the plateau tumour. This was due to a release of non-proliferating cells into the cell cycle, resulting in an increase in the growth fraction from 44% to 72%. The decrease in the doubling time was also due to a shortening of the mean cell cycle time from 41 to 20.5 hr. The analysis rendered it likely that the aspiration caused a shift in the mode of cell loss from an age-specific elimination of old non-cycling cells with post-mitotic DNA content in the plateau tumour to an elimination of younger cells immediately after mitosis. Investigations from 0 to 10 hr after aspiration verified the release of non-proliferating cells with both G₁ and G₂ DNA content into the cell cycle. The release was initiated from 3 to 6 hr after aspiration. 24 hr after aspiration the experimental data did not indicate any further transition.     

THE RELATIONSHIP BETWEEN DIURNAL VARIATION OF THE NUMBER OF CELLS IN MITOSIS AND OF THE NUMBER OF CELLS SYNTHESIZING DNA IN THE EPITHELIUM OF THE HAMSTER CHEEK POUCH

1. The numbers of cells in mitosis and in DNA synthesis in the epithelium of the hamster cheek pouch have been studied at different times of the day and night. 2. By accumulation of mitotic cells using colcemid, both the rate of entry of cells into mitosis and the duration of mitosis have been estimated at two different times of day. 3. A diurnal variation has been demonstrated in both the mitotic index and in the tritiated thymidine labelling index. Although these variations are of different amplitude and timing, the experimental data fit closely to the hypothesis that the diurnal mitotic variation is the result of a partially synchronous population moving through the DNA synthetic period. No direct action on the mitotic process need be postulated. 4. From the results of mitotic accumulation, it is clear that the rate of entry of cells into mitosis depends on the time of day at which this is studied. There is also the possibility that the duration of mitosis is slightly longer when the mitotic index is high. 5. It is concluded that, at least in the epithelium of the hamster cheek pouch, the diurnal rhythm in the number of mitoses present is a reflection of the diurnal variation in the number of cells synthesizing DNA at some time earlier. Small fluctuations in the mitotic pattern imposed by this partially synchronous population moving from S into mitosis, could be caused by slight variations in the duration of mitosis.     

Kinetics of cell replication in the uterine cervix. VII. Loci of mitotic basal cells during cervical carcinogenesis

The frequency and the topographic occurrence (i.e., loci) of vincristine-arrested mitosis in the basal-cell layer was studied during the process of cervical carcinogenesis in C57B1 mice. The total frequency of mitosis decreased (by comparison to controls) not only in cervical intraepithelial neoplasias of grades I, II and III and in invasive carcinomas, but also in the normal epithelium of carcinogen-treated animals. This confirms earlier results and suggests that the pace of replication of cells in contact with the stroma is decreased during carcinogenesis. On the other hand, the proportion of the number of mitotic basal cells occurring singly or in groups of 2, 3 or greater than or equal to 4, as well as the proportion of loci with 1, 2, 3 or greater than or equal to 4 mitoses, were similar during cervical carcinogenesis (when compared to controls). It would thus appear that the proliferation of the cervical epithelium during carcinogenesis is regulated by two factors: one that seems to diminish the total number of mitotic basal cells during carcinogenesis, and another that seems to maintain as constant the proportion of mitotic loci, both under normal conditions and throughout the development of intraepithelial neoplasias, in the uterine cervix.     

Computer simulations of mitosis and interdependencies between mitosis orientation, cell shape and epithelia reshaping

Finite element-based computer simulations are used to investigate mitosis and how mitosis, cell shape, and epithelium reshaping depend on each other. Frame- and cell-oriented patterns of mitosis with growing and non-growing daughter cells are considered. Previous simulations have shown that applied stresses or strains can reshape cells so that their long axes are aligned in the principal stretch direction. The simulations reported here show that this can produce global alignment of the mitosis cleavage planes. Other simulations reported here show that mitoses with suitably aligned cleavage planes can drive epithelium reshaping. Formulas that quantify these and other dependencies are derived. These formulas provide quantitative relationships against which current hypotheses regarding epithelia reshaping in real biological systems can be evaluated.     

The quantity of associated acrocentric chromosomes in human lymphocytes passing through 1st, 2d and 3d mitoses in culture

The reproductive ability of lymphocytes of peripheral blood with the usage of 5-bromine-deoxyuridine has been studied in 8 healthy children at the age of 5-6 years. Single second mitoses occurred in 48 hour cultures (6.5%), in 72 hour cultures the frequency of the first, second and third mitoses was equal, in 96 hour cultures the third mitoses dominated. Consequent divisions of lymphocytes were accompanied by a decrease in associative acrocentric chromosome, in average by 25%, within one mitotic cycle, while in mitoses of a given ordinal number the frequency of associations did not depend on the duration of cultivation. The fixation of the culture at the 48th hour of cultivation makes it possible to take into account the frequency of associations of acrocentric chromosomes without calculation of the ordinal number of mitosis because of an significant amount of second mitoses at this time, and of a sufficient value of the mitotic index (4.6 +/- 0.5%) necessary for cytogenetic analysis.     

Respiratory and immune response to maximal physical exertion following exposure to secondhand smoke in healthy adults

We assessed the cardiorespiratory and immune response to physical exertion following secondhand smoke (SHS) exposure through a randomized crossover experiment. Data were obtained from 16 (8 women) non-smoking adults during and following a maximal oxygen uptake cycling protocol administered at baseline and at 0-, 1-, and 3- hours following 1-hour of SHS set at bar/restaurant carbon monoxide levels. We found that SHS was associated with a 12% decrease in maximum power output, an 8.2% reduction in maximal oxygen consumption, a 6% increase in perceived exertion, and a 6.7% decrease in time to exhaustion (P<0.05). Moreover, at 0-hours almost all respiratory and immune variables measured were adversely affected (P<0.05). For instance, FEV(1) values at 0-hours dropped by 17.4%, while TNF-α increased by 90.1% (P<0.05). At 3-hours mean values of cotinine, perceived exertion and recovery systolic blood pressure in both sexes, IL4, TNF-α and IFN-γ in men, as well as FEV(1)/FVC, percent predicted FEV(1), respiratory rate, and tidal volume in women remained different compared to baseline (P<0.05). It is concluded that a 1-hour of SHS at bar/restaurant levels adversely affects the cardiorespiratory and immune response to maximal physical exertion in healthy nonsmokers for at least three hours following SHS.     

Effect of repeated cooling on the state of the adrenals and corneal epithelial proliferation in white rats]

The effect of repeated cooling on the adrenal glands, on the mitosis and the number of DNA-synthesising cells in the corneal epithelium of albino rats was studied. The animals were cooled by the contact method to 28 degrees C and were exposed to this temperature for an hour daily within 5 days. Strong activation of the suprarenal glands was observed: 2-fold increase in the suprarenal weight, 3-fold decrease in cholesterol content, 4-fold growth of 11-hydroxy-corticosteroid level in the blood and enhanced adrenaline excretion. The average number of mitoses in the corneal decreases 2-fold. Depression was not associated with the change in mitosis rate but with the inhibition of the cell entrance into mitosis in interphase. The level of pathological mitoses did not change. Chronic stress was not accompanied by the change in the number of DNA-synthesising cells or intensity of DNA-symthesis.