bluuebunny/crossref_metadata_2025_split huggingface dataset:
THYMUS DERIVED INHIBITOR OF LYMPHOCYTE PROLIFERATION I. ISOLATION AND ASSESSMENT OF TISSUE SPECIFICITY
Authors: Rijke E. O. , Ballieux R. E. 
Published: May 2008

ABSTRACTPreparations from bovine thymus tissue were analyzed for their inhibitory effects during in vitro lymphocyte proliferation. The results indicate that these preparations strongly inhibit DNA synthesis in stimulated human peripheral lymphocytes, bone marrow cells, thymocytes and lymphoblastoid cells. This inhibition was dose‐dependent and not due to cytotoxicity of the preparations. No inhibition was found of the spontaneous proliferation of HeLa cells and human fibroblasts indicating that the inhibitory effect was specific for proliferating lymphocytes. Control preparations from bovine liver or kidney did not show any suppression in the test systems used.
GROWTH KINETICS OF A RAT MAMMARY TUMOUR TRANSPLANTED INTO IMMUNE‐SUPPRESSED MICE
Authors: Fu Karen K. , Steel G. G. 
Published: May 2008

ABSTRACTThe growth kinetics of a transplanted rat mammary tumour and its xenografts in immune‐suppressed mice were studied using the technique of labelled mitoses. Growth of the tumour in rats was regular and uniform but when transplanted into mice the growth of the implants was irregular and generally slower. The second passage tumours in mice showed rapid and regular growth with a volume doubling time approximately half that for the tumours in the rat. Values for the G1 phase duration, intermitotic time and growth fraction were greater for the tumours in the mouse although the data for the first passage in mice were difficult to interpret. The kinetic changes between the rat and mouse hosts primarily reflect a large and variable amount of cell loss from the first passage xenografts in the mouse, with adaptation by the second passage towards reduced cell loss.
CORRELATION BETWEEN CELL SIZE AND POSITION WITHIN THE DIVISION CYCLE IN SUSPENSION CULTURES OF CHANG LIVER CELLS
Authors: Skog S. , Eliasson E. , Eliasson Eva 
Published: May 2008

ABSTRACTChang liver cells from exponentially growing suspension cultures have been separated by sedimentation at unit gravity. Determinations of the protein content per cell showed that the fractionation procedure resulted in good separation of cells of different size. On the other hand, the DNA content of individual cells from the fractions, as determined cytofluorimetrically, indicated considerable heterogeneity in the size of cells from the same stage of the division cycle.On the basis of earlier results on intermitotic growth and the variation in the length of the cell cycle in homogeneous cell populations, a mathematical model has been constructed and tested using a computer program. The present results on the size distribution of cells from the different stages of the mitotic cycle are consistent with a regeneration of size heterogeneity in each cell generation, as a result of the dispersion of intermitotic times. The variation in cell cycle times may be related to a probabilistic event in the G1 period. In the mathematical model it was necessary to include a mechanism by which the regeneration of abnormally large cells is prevented. The experimental data are compatible with a gradually increasing inhibition of growth in cells larger than a certain size (circa 400 pg protein per cell).
MITOTIC INDEX, INFLUX AND MEAN TRANSIT TIME IN THE HAMSTER CHEEK POUCH EPITHELIUM, A PARTIALLY SYNCHRONIZED CELL SYSTEM*†
Authors: Møller U. , Hartmann N. R. , Faber M. 
Published: May 2008

ABSTRACTMitotic activity was followed in the epithelium of the hamster cheek pouch for about 12 hr in two experiments under different conditions of noise and light intensity.A mathematical model based on a non‐stationary probability density function for the transit time through mitosis was developed, making an analysis of this partially synchronized cell system possible.The most important result of the two experiments is the indication of a non‐stationary mean transit time for cells in mitosis. In the first experiment (70 db, 103 lux), which produced high mitotic indices (maximum 2.0%), the influx changed from 0 to 0.9%/hr (mean of 7‐hourly determinations: 0.4%/hr), and the mean transit time from 1.9 to 5.5 hr. In the second experiment (70 db, 265 lux), which had a lower level of MI (maximum 1.3%), the influx changed from 0 to 1.8%/hr (mean of 13‐hourly determinations: 0.4%/hr), and the mean transit time from 0.3 to 3.3 hr.It was difficult to say precisely whether the variation in influx or in mean transit time was the main factor in the increase and decrease of MI. The data could not be simulated with a stationary mean transit time. It is suggested that changes in MI due to different external circumstances are mainly the result of variation in the mean transit time.
IN VITRO INCORPORATION OF [3H]TdR IN HUMAN AND MURINE SOLID TUMOURS
Authors: Chavaudra N. , Malaise E. P. 
Published: May 2008

ABSTRACTABSTRACTUsing in vitro labelling with [3H]TdR, we measured the variation in mean grain count (MGC) with the distance from the periphery of the biopsy in twenty‐nine human solid tumours (seventeen squamous cell carcinomas of the oral cavity, seven mesenchymal sarcomas and five embryonal tumours). We found a decrease for two histological types of tumours (from 32 to 8 grains for squamous cell carcinomas and 19 to 9 grains for embryonal tumours, comparing the outer 0–40 μm zone to the inner 81–120 μm zone). The number of grains per cell was usually sufficient to provide a satisfactory estimation of the labelling index (LI) in the zone which is routinely studied (80 to 100 μm from the periphery). However, for squamous cell carcinomas for instance, we found the maximal LI between 21 and 40 μm (135% of the mean global LI) and only 77% in the region situated between 81 and 100 μm. Therefore, the probability of underestimating the LI in deeper regions should not be neglected (problems of penetration, metabolism or incorporation of [3H]TdR). This is why we have employed more sophisticated labelling methods to try to improve the results.In a murine mammary tumour (EMT6), we studied the influence of either hyperbaric oxygen (HPO) or 5‐FU or a combination of the two (5‐FU + HPO) on the change with depth in MGC and LI. In this murine tumour, as in the human tumours studied, MGC decreases slowly with increasing depth (MGC is 30 grains in 0–20 μm zone and 13 in 180–200 μm, and LI in the same zones, 29 and 16%). However, in neither case is the LI maximal at the periphery in spite of maximal MGC; this is probably due to local trauma. In two of the treated groups (5‐FU and 5‐FU + HPO), the MGC is significantly higher than controls (mean ratios: treated/control 1.3 and 1.4 respectively), whereas in the presence of hyperbaric oxygen alone no significant difference is observed. However, LI is greater in all three treated groups than in controls (mean ratios in presence of: HPO or 5‐FU or 5‐FU + HPO/conventional method 1.3, 1.3 and 1.2 respectively) and their change with depth follows a similar profile. In spite of the LI decrease with depth, if the area examined is chosen correctly, these improved techniques which preserve tissue integrity should provide a better LI estimation than conventional labelling methods.
QUANTITATION OF [3H]THYMIDINE UPTAKE BY STIMULATED HUMAN LYMPHOCYTES†
Authors: O'Leary J. J. , Mehta C. , Hall D. J. , Rosenberg A. 
Published: May 2008

ABSTRACTWe have investigated the relationship between cell numbers and the amount of tritiated thymidine ([3H]TdR) taken up by stimulated human peripheral lymphocytes, as a function both of labeling time and of the specific activity of the thymidine. Cells responding either to mitogens or to allogenic cells show simple first order kinetics for the uptake of thymidine. Fitting the data to a Michaelis‐Menten type of model, we observe for labeling times of 12 hr and longer, non‐competitive inhibition of thymidine uptake by increased specific activity of tritium label, regardless of the mode of stimulation. However, for an individual responder in MLC at any arbitrary but fixed specific activity, dose of [3H]TdR and labeling interval, we still observe a linear relationship between cell mass and incorporated label. In contrast, if specific responding combinations in mixed lymphocyte culture are compared, the inhibition by specific activity at longer time intervals becomes significant and influences the quantitative interpretation of results. Specific activities of less than 10 Ci/mmole and labeling times of 6 hr or less avoid inhibition and ensure a linear relationship between dividing cell number and CPM (counts per minute recorded) of incorporated label.
EFFECT OF EHRLICH ASCITES CELL CHALONE ON NASCENT DNA SYNTHESIS IN ISOLATED NUCLEI
Authors: Nakai G. S. , Gergely Hella 
Published: May 2008

ABSTRACTEhrlich Ascites Tumor (EAT) chalone has been shown to inhibit nascent DNA synthesis by inhibiting DNA polymerase α and β (Nakai, 1976), but one of the problems in studying eurkaryotic DNA replication has been the relative impermeability of the cell membrane to precursors and macromolecules; hence, to circumvent this restriction without sacrificing the integrity of the replication process, a broken cell system utilizing nuclei in aqueous media was investigated. Isolated nuclei appear to continue the process of DNA replication that was proceeding in vivo before their isolation and under optimal conditions are able to initiate new synthesis (Fraser & Huberman, 1977). The effects of partially purified EAT chalone on nascent DNA could be studied directly in this nuclear system, which excluded effects of the cell membrane, nucleotide pools and other cytosol elements. A concentration‐related inhibition of [3H]thymidine triphosphate ([3H]‐dTTP) incorporation was noted over a chalone range of 50–200 μg/ml. It appears that chalone can inhibit DNA polymerase α directly within the nucleus without an intermediate step such as a cell membrane receptor.
PROLIFERATION KINETICS OF THE MOUSE BLADDER AFTER IRRADIATION
Authors: Stewart Fiona A. , Denekamp Juliana , Hirst D. G. 
Published: May 2008

ABSTRACTThe proliferative response of the mouse bladder was investigated, using continuous labelling with tritiated thymidine, at various times after a single dose of radiation. Bladder epithelial and vascular endothelial cells were studied. The cell turnover rate in unirradiated epithelium and endothelium was found to be extremely slow (in excess of 1 year).Irradiation with a single dose of 25 Gy resulted in compensatory proliferation of the epithelium but the response was not initiated for many months. At 3 months after irradiation there was little difference from the control proliferation rate, but from 6 to 22 months after irradiation (the end of the study) there was a period of sustained rapid proliferation with the cell turnover time reduced to approximately 1 week. The increase in proliferative activity observed at 22 months was found to be dose—dependent.Endothelial cells in the blood vessels of the submucosa also showed an increased turnover rate after irradiation and the timing of this reponse was found to be similar to that of the epithelium. The onset of compensatory proliferation in both cell types was found to coincide with marked histological and functional changes in the bladder.In this slowly proliferating tissue, the onset of rapid compensatory proliferation after irradiation is delayed and occurs at the time that functional impairment is observed. This supports the postulate that proliferation is unlikely to contribute much to the sparing effect of prolonged fractionated radiotherapy in slowly dividing tissues.
THE PROLIFERATION KINETICS OF NHIK 1922 CELLS IN VITRO AND IN SOLID TUMOURS IN ATHYMIC MICE
Authors: Rofstad E. K. , Pettersen E. O. , Lindmo T. , Oftebro R. 
Published: May 2008

ABSTRACTThe proliferation kinetics of cells of the line NHIK 1922 grown in vitro and as solid tumours in the athymic mutant nude mouse has been studied. In vitro, growth curves were determined for exponentially growing populations and for populations synchronized by mitotic selection. The phase durations for these populations were determined by flow cytofluorometric measurements of DNA‐histograms and pulsed incorporation of [3H]TdR respectively. The generation time and the phase durations for synchronized populations were found to be about equal to those for exponentially growing populations. The duration of the phases G1, S and G2+ M was found to be 8·5–9·5, 11·0–12·0 and 6·0–6·5 hr respectively, i.e. the generation time was 26·5–27·0 hr. The proliferation kinetics in vivo were studied by flow cytofluorometry and by the technique of percentage labelled mitoses. The median duration of S‐phase and (G2+ M)‐phase in vivo was found to be approximately the same as that observed in vitro, while the median duration of G1‐phase was found to be approximately 5 hr longer in vivo than under the present in vitro growth conditions. The growth fraction in vivo was estimated to be approximately 50%. The non‐proliferative compartment of the tumour cells was found to consist mainly of cells with the DNA‐content of cells in G1‐phase. It is concluded that the reduced rate of proliferation of NHIK 1922 cells in vivo is correlated with alterations in the duration of G1‐phase and, hence, the proportion of cells in G1‐phase.
EVALUATION OF FLOW CYTOMETRIC DATA OF HUMAN TUMOURS
Authors: Beck H.‐P. 
Published: May 2008

ABSTRACTBackground signals and aggregation of cells affect flow cytometric DNA measurements to a great and mostly uncontrolled extent. These artefacts appear mainly in investigations of solid tumours leading to significant distortions in the results. Procedures are described that make possible quantitative corrections both of the background and of the cell aggregations
AN IN VIVO DOUBLE LABELLING STUDY OF THE SUBSEQUENT FATE OF CELLS ARRESTED IN METAPHASE BY VINCRISTINE IN THE JB‐1 MOUSE ASCITES TUMOUR
Authors: Camplejohn R. S. , Schultze B. , Maurer W. 
Published: May 2008

ABSTRACTThe fate of cells arrested by Vincristine (VCR) in metaphase is of interest because of the wide use of this substance in cancer chemotherapy and, particularly, in relation to its use in so‐called ‘synchronization’ therapy. The present study was designed to answer the question of whether cells blocked in metaphase by VCR subsequently proliferate further or whether they become infertile and die. By means of a double labelling technique with [3H] and [14C]thymidine (TdR) it was shown that all VCR‐arrested metaphases in the JB‐1 ascites tumour subsequently became necrotic. These cells did not re‐enter a viable G2 phase following arrest and thus could not take part in a wave of synchronous proliferation. In agreement with earlier studies, VCR was found to lead to arrest in metaphase, not only of cells in or shortly prior to mitosis at the time of VCR administration, but also of the majority of cells which had at this time been in the S and G2 phase.
ARRESTED GROWTH OF CHINESE HAMSTER OVARY (CHO) CELL COLONIES ON AGAR
Authors: Storrie B. , Konrad M. W. , Glaser D. A. 
Published: May 2008

ABSTRACTChinese hamster ovary (CHO) cells plated on agar form two classes of colonies; those which increase continuously in diameter and those which become arrested in outward growth. All colonies continue to increase in mass and thickness as demonstrated by computer‐assisted analysis of time sequence photographs of several thousand colonies and by examination of histological sections. Colonies which shift from a monolayer to a mounded morphology at fairly large colony diameter (≳1 mm) continue to increase in diameter. Colonies in which mounding occurs at smaller colony diameter (≲1 mm) cease to increase in diameter but continue to increase in thickness, as demonstrated by histological examination and by computer‐assisted analysis. Rapid cell division occurs at the edge of all colony classes, as shown by the distribution of mitotic figures. In arrested colonies these dividing cells must move toward the colony core to compensate for dying cells.Necrotic cells are found as a discrete zone at the air‐colony interface in all cases for CHO cell colonies growing on agar. As such, necrosis is probably due to limitations in nutrient diffusion upward from the agar rather than oxygen diffusion downward.
CELL PROLIFERATION IN EMT6 TUMOURS TREATED WITH SINGLE DOSES OF X‐RAYS OR HYDROXYUREA II. COMPUTER SIMULATIONS
Authors: Demeestere Michèle , Rockwell Sara , Valleron A.‐J. , Frindel Emilia , Tubiana M. 
Published: May 2008

ABSTRACTA computer simulation technique was used to analyse data on the proliferation of clonogenic cells in EMT6 tumours treated with 5 mg/mouse of hydroxyurea (HU) or 3·0 Gy (300 rads) X‐rays. This simulation technique is able to determine the respective roles of selective killing, blocks in cell progression and recruitment of the treated population.When the technique was applied to tumours treated with HU, it was possible to prove that both a G1/S block and recruitment occurred. These phenomena could not have been demonstrated quantitatively, or even qualitatively, without the use of the simulation. After irradiation, blocks in cell progression and differences in the proliferative patterns of the surviving clonogenic cells and the total tumour cell population were found.
QUANTITATIVE CHANGES IN THE CELLULARITY OF THE RAT SUBEPENDYMAL PLATE AFTER X‐IRRADIATION
Authors: Hubbard Bethan M. , Hopewell J. W. 
Published: May 2008

ABSTRACTThe brains of young adult rats were irradiated with a single dose of 8 Gy (800 rad) of 250 kVp X‐rays. Within 2 weeks of treatment the cell population of the subependymal plate was reduced by 30%. During this period the cell cycle time remained unchanged but the labelling index was reduced. The cell population subsequently returned to normal after 39‐52 weeks. Damage and subsequent recovery of the plate was due mainly to changes in the number of cells with small dark nuclei. Cells with small and large light nuclei were little affected.A model for the production and differentiation of cells in the subependymal region is proposed on the basis of age‐related changes in the total number and proportions of the various cell types in the subependymal plate of normal rats. This is discussed both in terms of the radiation response of cells in the plate and the manifestation of delayed white matter necrosis after higher doses.
PROTECTION OF CYCLING CFUs AGAINST HYDROXYUREA BY LOW DOSES OF ACTINOMYCIN D
Authors: Fehér I. , Gidali Julia 
Published: May 2008

ABSTRACTLow dose (80 μg/kg) Actinomycin D (AD) produced a significant but transient inhibition of proliferation of the haemopoietic stem cells (CFUs) in chimaeras or in mice regenerating after sublethal irradiation. The same dose of AD had no effect on the resting CFUs population. During the period of proliferation inhibition, CFUs proved to be insensitive to the killing effect of [3H]thymidine in vitro and hydroxyurea (HU) in vivo. In Ehrlich ascites tumour (EAT) bearing mice enhanced CFUs turnover rate was found. Eighty μg/kg AD produced a selective effect in these mice: it protected the proliferating CFUs population without diminishing the effect of hydroxyurea on the tumour cells.
CELL KINETIC ALTERATIONS IN NORMAL AND NEOPLASTIC CELL POPULATIONS IN VITRO AND IN VIVO FOLLOWING VINCRISTINE*. A REPLY TO DR CAMPLEJOHN'S REVIEW ARTICLE†
Authors: Klein H. O. 
Published: May 2008

ABSTRACTIt is shown that the lethal action of vincristine (VCR) is dose‐dependent and may occur at interphase and mitosis. In general, the VCR dose used to destroy cells must be approximately ten times higher than that used to arrest cells in mitosis at metaphase. There is strong evidence that cells can survive metaphase arrest by a sublethal dose of VCR either completing cytokinesis normally after metabolism of the drug or becoming polyploid because of an impaired mitotic spindle apparatus. These cells are not doomed to die, at least in some cell systems. Furthermore, there is strong evidence in three animal tumour systems (transplantable and autochthonous tumours) that VCR is able to induce in vivo partial synchronization of proliferating tumour cells and/or recruitment of resting cells into the proliferating compartment. Failures to induce partial synchrony in cell populations by VCR may be attributed to resistance to VCR or cytolysis or slow proliferation of cells in badly vascularized tumours. Chemotherapy after synchronization seems to be effective as shown by non‐randomized trials in bad‐risk patients with solid tumours and acute leukaemias. In a randomized co‐operative trial results of the two‐drug synchronization protocol in patients with non‐Hodgkin's lymphoma of high grade malignancy were statistically better than those of a four‐drug protocol (COPP) established empirically. The two‐drug protocol was equally effective as the four‐drug protocol in Hodgkin's disease. Side‐effects were less pronounced with the so‐called synchronization scheme.
VARIATIONS IN GROWTH AND CELL CYCLE TIME OF ARTERIAL SMOOTH MUSCLE CELLS CULTURED AT LOW DENSITY
Authors: Blaes N. , Bourdillon M. C. , Crouzet B. , Boissel J. P. 
Published: May 2008

ABSTRACTThe population kinetics of cultured rat arterial smooth muscle cells replated at various low densities were studied by direct counting and observation of the cells. Population doubling time decreases with increasing initial density of the culture. These variations in population doubling times depend on both the variation in the percentage of quiescent cells and on the variation of the mean cell cycle time of non‐quiescent cells.
THE STATHMOKINETIC METHOD IN VIVO TIME‐RESPONSE WITH SPECIAL REFERENCE TO CIRCADIAN VARIATIONS IN EPIDERMAL CELL PROLIFERATION IN THE HAIRLESS MOUSE
Authors: Thorud E. , Clausen O. P. F. , Bjerknes R. , Aarnæs E. 
Published: May 2008

ABSTRACTGroups of hairless mice were injected i.p. with a stathmokinetic dose of 0·15 mg colcemid at seven different times of the day and animals killed 0, 15 and 30 min, 1, 2, 3 and 4 hr after the injection. The proportion of cells in metaphase and ana/telophase was determined in histological sections.The results showed a transient accumulation of metaphases about 30 min after the injection, followed by an increase in metaphases from 1 to 4 hr. Therefore, no value before 1 hr after the colcemid injection should be used in calculations of the mitotic rate.The presence of circadian rhythms with high mitotic activity in the morning and low activity in the evening was confirmed. It is shown by regression analyses that the accumulation period of 4 hr is sufficiently short to reflect circadian variations in epidermal cell proliferation and that the 4‐hr accumulation value alone is sufficient to estimate the mitotic rate.
Thymus‐Derived Inhibitor of Lymphocyte Proliferation
Authors: Rijke E. O. , Lempers H. C. M. , Ballieux R. E. 
Published: May 2008

ABSTRACTA thymus crude factor (TCF) isolated from bovine thymus tissue has been tested for its effects on the proliferation of various murine cells. Specific inhibition in vitro has been found for DNA synthesis in murine T and B lymphocytes which appears not to be based on cytotoxicity. Moreover, TCF, when administered to mice, also interferes with the DNA synthesis in lymphoid tissue in vivo. Our data are suggestive for the presence in TCF of an endogenous ‘chalone‐like’ inhibitor of lymphoid cell proliferation in vitro and in vivo.