bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIFFERENTIAL LETHAL EFFECTS OF BOTH CYTOSINE ARABINOSIDE AND HYDROXYUREA ON JEJUNAL CRYPT CELLS AND TESTOSTERONE‐STIMULATED ACCESSORY SEX GLANDS
Authors: Alison M. R. , Wright N. A. 
Published: May 2008

ABSTRACTDNA‐synthesizing cells from mouse jejunal crypts and accessory sex glands respond differently to the DNA synthesis inhibitors cytosine arabinoside and hydroxyurea. A single injection of either agent brought about a rapid inhibition of thymidine labelling in both the tissues. Whilst both agents had a lethal effect upon the majority of S‐phase cells in the crypts, only a minority of S‐phase cells in the accessory sex glands showed evidence of necrosis. These differences are considered in the context of possible physiological differences between continually dividing cells and putative G0 cells. The accessory sex glands are normally quiescent proliferative tissues. They were stimulated to undergo DNA synthesis and later mitosis by testosterone propionate injections, commencing three days after castration. Cytosine arabinoside was the more effective cytocidal agent in the accessory sex glands, and when two injections were scheduled so as to affect a large number of DNA‐synthesizing cells, a compensatory hyperplasia was evoked. In the coagulating gland, this compensatory response involved the proliferation of many cells which, in the absence of cytotoxic perturbation, would be non‐proliferative (Q cells).
INDUCTION OF ERYTHROPOIETIN RESPONSIVENESS IN VITRO BY A DISTINCT POPULATION OF BONE MARROW CELLS
Authors: Wagemaker G. , Peters M. F. , Bol S. J. L. 
Published: May 2008

ABSTRACTBone marrow contains a small population of primitive erythroid progenitor cells which can be detected by their capacity to form large numbers of erythroid progeny in viscous cultures containing erythropoietin (EP). These cells have been termed erythroid ‘burst‐forming units’(BFUe). The present study demonstrates that expression of the erythroid differentiation potential of BFUe requires the presence of an activity additional to EP. This activity has been designated as BFA (burst feeder activity). It is shown that the number of BFUe detected and their apparent sensitivity to EP are directly related to the BFA concentration of the cultures.BFA was found to be associated with a population of bone marrow cells of high buoyant density and small volume, which are sensitive to irradiation. The radiation dose‐effect curve provided strong evidence that bone marrow BFA is independent of cell proliferation; this was supported by showing that BFA is unaffected by in vivo treatment with hydroxyurea.The findings are compatible with a two‐step regulation model for erythroid differentiation in which BFA‐induced progeny of BFUe acquire sensitivity to EP.
PARTICLE‐INDUCED ERYTHROPOIETIN‐INDEPENDENT EFFECTS ON ERYTHROID PRECURSOR CELLS IN MURINE BONE MARROW
Authors: Ploemacher R. E. , van Soest P. L. , Wagemaker G. , van't Hull E. 
Published: May 2008

ABSTRACTA possible regulatory action of phagocytic cells on erythropoiesis was investigated by infusion of inert polystyrene latex particles (LAT). LAT appeared to induce changes in the femoral content of erythroid progenitor cells. These changes were most pronounced in primitive erythroid progenitor cells (BFUe) and appeared to be gradually damped in more differentiated populations (CFUe and erythroblasts). LAT did not influence granulocyte/macrophage progenitor cells (CFUc). The effects of LAT could not be attributed to changes in the systemic erythropoietin (EP) concentration. Administration of dexamethason nullified the effect of low doses of LAT, suggesting that phagocytosis of the particles is essential to the observed effects.Erythroid burst formation was previously found to be dependent on a bone marrow associated activity, termed BFA (burst feeder activity). BFA acts as an in vitro inducer of EP‐responsiveness in BFUe. In this study it was found that LAT‐induced changes in femoral erythroid progenitor cell content were characteristically preceded by corresponding changes in BFA. It was concluded that BFA‐associated cells probably play a role in vivo in the early differentiation of erythroid progenitor cells.The present data are interpreted as direct in vivo evidence supporting a two‐step regulatory model operating in erythropoiesis and provide evidence that phagocytic cells are a component of the erythroid haemopoietic inductive micro‐environment.
A MATHEMATICAL MODEL OF THROMBOPOIESIS IN RATS
Authors: Wichmann H.‐E. , Gerhardts M. D. , Spechtmeyer H. , Gross R. 
Published: May 2008

ABSTRACTA mathematical model of thrombopoiesis in rats is presented. This has four compartments; stem cells, megakaryocytes, thrombocytes and thrombopoietin. A high thrombopoietin concentration influences bone marrow proliferation in three ways. Firstly the stem cells are stimulated and a slow increase in megakaryocyte number follows. Secondly there are additional endomitoses in the (early) megakaryocytes resulting in an increase in megakaryocyte volume. Thirdly the megakaryocyte maturation time is shortened. The parameters of the model are determined from experimental values for the normal, maximum and minimum proliferation rates, maturation times and destruction rates. The model is tested by comparing simulated results for acute and chronic thrombocytopenia and thrombocytosis with experimental curves from the literature. The model and data agree within the limits of experimental error. Not all of the thrombopoietic regulatory system is known yet, so some important alternative hypotheses are investigated and compared with the model. Several hypotheses have been excluded in this way.
BUOYANT DENSITY ANALYSIS OF MYELOID COLONY‐FORMING CELLS IN GERMFREE AND CONVENTIONAL MICE
Authors: Byrne P. V. , Heit Hildegard , Heit W. 
Published: May 2008

ABSTRACTGranulocyte‐macrophage colony‐forming cells (CFUc), in the bone marrow of germfree and conventional CBA mice, were compared quantitatively and qualitatively. Cells were separated on the basis of their buoyant density by equilibrium centrifugation in continuous albumin density gradients. CFUc in the density subpopulations were detected by culture in agar containing three different types of colony stimulating factor (CSF). The sources of the CSF were post‐endotoxin mouse serum (CSFES), mouse lung conditioned medium (CSFMLCM) and human urine (CSFHU). Mice were removed from the germfree environment and the buoyant density status of their CFUc was examined 1, 4 and 8 weeks later.No difference was found between germfree and conventional mice in the number of nucleated cells per femur or in their modal density. Neither was the number of CFUc per femur different. The cell cycle status of CFUc, as determined by the thymidine suicide technique was not significantly different.Functional heterogeneity was found among the density subpopulations for both groups of mice. This depended on the type of CSF.The density distribution of CFUc was significantly different in germfree mice. There were proportionately more low density CFUc. The mean modal density of CFUc under CSFES stimulation was less by 0.0045 g/cm3 in germfree mice.The removal of mice from the germfree environment resulted in a shift of the distribution to higher densities. The trend was towards the conventional situation. The significance of the buoyant density status of CFUc is discussed.
THE PROLIFERATIVE STATE OF GRANULOCYTIC PROGENITOR CELLS IN HUMAN BLOOD AND MARROW
Authors: Standen G. , Philip M. A. , Fletcher J. 
Published: May 2008

ABSTRACTA double layer agar technique was used to investigate the proliferative state of granulocytic progenitor cells (Colony Forming Units in Culture; CFUc) in human peripheral blood and bone marrow. The sensitivity of the progenitor cells to the S‐phase specific agent, hydroxyurea, was used as an index of the proportion of cells engaged in DNA synthesis. In the presence of low concentrations of colony stimulating factor (CSF) the CFUc were found to be virtually insensitive to the drug. However, when cultured in the presence of increasing concentrations of CSF the proportion of CFUc apparently killed by hydroxyurea increased to a maximum of 23% for those cells in the blood and 39% for those in the marrow. The results indicate that CFUc which are slowly proliferating are sensitive to low concentrations of CSF. In contrast, those CFUc which are proliferating more rapidly require high concentrations of CSF before they will form colonies in culture. A model has been devised which suggests that as CFUc mature, their cell cycle time shortens and their sensitivity to CSF decreases.
MATRIX ALGEBRAIC SIMULATION OF MITOTIC CELL SELECTION EXPERIMENTS
Authors: Tomasovic S. P. , Roti J. L. Roti , Dethlefsen L. A. 
Published: May 2008

ABSTRACTMitotic cell selection experiments are frequently utilized in investigations on the effects of various metabolic inhibitors and/or X‐irradiation on cell‐cycle progression of mammalian cells in tissue culture. This study describes a method for matrix algebraic simulation of these experiments which involves the sequential multiplication of cell‐population matrices, growth matrices, and mitotic cell‐selection matrices. Simulations are shown for progression in control cultures and cultures perturbed either by X‐rays or 2‐mercapto‐1(β‐4‐pyridethyl) benzimidazole. Application of this model will enhance the planning of these investigations and allow more rigorous testing of alternate hypotheses concerning the mechanisms of action of perturbing agents.
IN VITRO PROLIFERATION OF MOUSE LYMPHOBLASTOID CELL LINES: GROWTH MODULATION BY VARIOUS POPULATIONS OF ADHERENT CELLS
Authors: Zipori D. 
Published: May 2008

ABSTRACTThe in vitro growth pattern of a number of mouse lymphoblastoid tumour cell lines was modified in the presence of adherent cell layers from various sources. The AVRij‐1 and ST‐4b cell lines exhibited a concentration—dependent growth pattern, i.e., they would only grow well when seeded at high starting cell concentrations. Better growth of these cells from low cell concentrations was observed in the presence of adherent cell layers from syngeneic or allogeneic bone marrow. Adherent cell layers derived from mouse spleen and pleural or peritoneal cavity could also promote the growth of the above tumour cells, but in a narrower range of cell concentrations and to a lower extent. Moreover, confluent adherent layers from the pleural and peritoneal cavities completely inhibited the growth of AVRij‐1 and ST‐4b cells, while adherent cell layers from the bone marrow did not inhibit growth at any cell concentration tested. The in vitro growth of concentration—independent cell lines was also affected by the presence of adherent cells from the bone marrow. Under syngeneic conditions, a slight increase in the growth of the ‘null’ or pre‐B lymphoma cell line ABLS‐8.1 was observed. On the other hand, the growth of tumour cells expressing more differentiated properties, such as the thymus T lymphoma tumour cell line ST‐1.3 and the plasma cell tumour MPC‐11.45.6.2.4, was inhibited in the presence of syngeneic bone marrow derived adherent cell layers. This inhibition was more pronounced under allogeneic conditions. Growth inhibition was also observed when concentration—independent cell lines were co‐cultured with adherent cells from the pleural and peritoneal cavities. Thus, adherent cell layers from non‐haemopoietic sources inhibited the growth of all cell lines tested. On the other hand, adherent cells from the bone marrow had a differential effect on growth of lymphoblastoid tumour cell lines. This depended on the in vitro growth properties of each tumour cell line and on some additional specific tumour cell properties. The latter could relate to the differentiation stage characterizing each tumour cell line. The culture method described here may serve as a model system for studies on interaction of leukaemic cell and the haemopoietic microenvironment.
DIFFERENT LABELLING PATTERNS IN MOUSE LYMPHOID TISSUES WITH [3H]DEOXYCYTIDINE AND [3H]THYMIDINE
Authors: Hamatani K. , Amano M. 
Published: May 2008

ABSTRACTThe percentages of labelled lymphocytes in smear preparations of mouse thymus were higher than those in similar preparations of mesenteric lymph nodes with either generally labelled tritiated deoxycytidine, [3H]CdR, or tritiated thymidine, [3H]TdR. Lymphocytes in the thymus cortex and in germinal centres of mesenteric lymph nodes were intensely labelled with [3H]CdR, whereas with [3H]TdR lymphocytes in the peripheral region of thymus and medullary cords of mesenteric lymph nodes were heavily labelled. The majority of lymphocytes in thymic cortex and germinal centres of mesenteric lymph nodes were labelled weakly with [3H]TdR. Thus, labelling patterns with [3H]CdR differed from those with [3H]TdR in lymphoid tissues of the mouse.Mouse lymphocytes can utilize [3H]CdR as a precursor molecule for cytosine and thymine in DNA. The ratio of radioactivity of thymine to that of cytosine was measured biochemically in DNA extracted from lymphocytes labelled with [3H]CdR. This radioactivity ratio in thymus was higher than that in mesenteric lymph nodes. These results suggest that the metabolic activities of utilizing CdR for DNA synthesis differ within lymphocyte populations in various lymphoid tissues in the mouse.
DETERMINATION OF NON‐PROLIFERATING CELLS IN CULTURE BY COMBINING FLOW CYTOMETRY WITH STATHMOKINETICS
Authors: Böhmer R.‐M. 
Published: May 2008

ABSTRACTColcemid was added to the growth medium of L‐cells in monolayer culture. The proliferating cells continued their progression through the cycle up to metaphase, where they were arrested. At different times after Colcemid addition the cells were trypsinized. suspended immediately in a solution of the DNA‐specific fluorescent dye Hoechst 33258 and analysed with a flow cytometer. The histograms were evaluated to give the fraction of cells in the 2c peak as a function of time after Colcemid addition. The flux into the 2c compartment being interrupted, the peak content decreased until all proliferating (G1) cells had entered S‐phase. With increasing cell density or with increasing time after serum deprivation an increasing fraction of cells remained in the 2c peak at times greater than the normal G1 duration. The possibility of applying this method to the determination of non‐proliferating cells in a population is discussed.
CELL KINETICS OF IRRADIATED EXPERIMENTAL TUMORS: CELL TRANSITION FROM THE NON‐PROLIFERATING TO THE PROLIFERATING POOL
Authors: Potmesil M. , Goldfeder A. 
Published: May 2008

ABSTRACTParenchymal tumor cells of murine mammary carcinomas can be divided into two pools, using nucleoli as morphological ‘markers’. Cells with dense nucleoli traverse the cell cycle and divide, thus constituting the proliferating pool. Cells with trabeculate or ring‐shaped nucleoli either proceed slowly through G1 phase or are arrested in it. The role of these non‐proliferating, G1 phase‐confined cells in tumor regeneration was studied in vivo after a subcurative dose of X‐irradiation in two transplantable tumor lines. Tumor‐bearing mice were continuously injected with methyl[3H]thymidine before and after irradiation. Finally, the labeling was discontinued, mice injected with vincristine sulfate and cells arrested in metaphase were accumulated over a 10‐hr period. Two clearly delineated groups of vincristinearrested mitoses emerged in autoradiograms prepared from tumor tissue at the time of starting tumor regrowth: one group with the silver‐grain counts corresponding to the background level, the other with heavily labeled mitoses. As the only source of unlabeled mitoses was unlabeled G1 phase‐confined cells persisting in the tumor, this observation indicated cell transition from the non‐proliferating to the proliferating pool, which took place in the initial phase of the tumor regrowth. Unlabeled progenitors have apparently remained in G1 phase for at least 5–12 days after irradiation.
ANALYSIS OF THE PROLIFERATION KINETICS OF BURKITT'S LYMPHOMA CELLS
Authors: Woo K. B. , Funkhouser W. K. , Sullivan C. , Alabaster O. 
Published: May 2008

ABSTRACTThe in vitro proliferation kinetics of a cell line derived from a patient with American Burkitt's lymphoma were investigated at three different growth phases: lag (day 1), exponential (day 3) and plateau (day 5). The growth curve, labeling and mitotic indices, percentage labeled mitosis (PLM) curves and DNA content distributions were determined. The data obtained have been analysed by the previously developed discrete‐time kinetic (DTK) model by which a time course of DNA distributions during a 10‐day growth period was characterized in terms of other cell kinetic parameters. The mean cell cycle times, initially estimated from PLM curves on days 1, 3 and 5, were further analysed by the DTK model of DNA distributions and subsequently the mean cell cycle times with respect to DNA distributions during the entire growth period were determined. The doubling times were 39·6, 31·2 and 67·2 hr, respectively, at days 1, 3 and 5. The mean cell cycle time increased from 23·0 to 37·7 hr from day 3 to day 5 mainly due to an elongation of the G1 and G2 phases. A slight increase in the cell loss rate from 0·0077 to 0·0081 fraction/hr was accompanied by a decrease in the cell production rate from 0·0299 to 0·0184 fraction/hr. This calculated cell loss rate correlated significantly with the number of dead cells determined by trypan blue exclusion. Analysis of the number of dead cells in relation to the cell cycle stage revealed that a majority of cell death occurred in G1 (r= 0·908; P < 0·0001). There was a good correlation between the in vitro proliferation kinetics at plateau phase of this Burkitt's lymphoma derived cell line and the in vivo proliferation kinetics of African Burkitt's lymphoma (Iversen et al., 1974), suggesting the potential utility of information obtained by in vitro kinetic studies.
STUDIES ON THE KINETICS OF INITIAL CYCLE PROGRESSION IN VITRO OF ASCITES TUMOUR CELLS SUBSEQUENT TO ISOLATION FROM ASCITES FLUID
Authors: Olivotto M. , Paoletti F. 
Published: May 2008

ABSTRACTA method is described for determining the duration of cell cycle phases traversed by cells responding to release from proliferation restraint. Experiments have been performed with arrested Yoshida ascites hepatoma cells allowed to re‐enter the growing stage after transfer of cells from the late stage of ascites into an in vitro incubation system. Experimentally, this method requires information on the rate of incorporation of labelled thymidine and on the rate of increase in cell number. The rate of [14C]thymidine incorporation in vitro was shown to be directly proportional to the number of cells synthesizing DNA. This was shown by correlating data from measurements of the rate of thymidine incorporation with those from measurements of the labelling index of the cell population. Theoretically, the method is based on analysis of the region limited by two integral curves, one corresponding to the kinetics of cell entry into and the other to the kinetics of exit from the S‐phase. From data on the actual rate of increase in the total number of cells and data on the S‐phase duration it is possible to obtain information on the cytokinetics of growth resumption by the ascites cell population.
LOCAL MITOGENIC EFFECT OF TISSUE MAST CELL SECRETION
Authors: Franzén L. , Norrby K. 
Published: May 2008

ABSTRACTThe effect of drug‐induced mast cell secretion on proliferation was studied in fibroblast‐like and mesothelial‐like cells in organ‐cultured rat mesentery. Mast cell degranulation achieved by Compound 48/80 was followed by a marked mitogenic reaction in the surrounding tissue cells. The drug itself lacked mitogenic effect on cultured guinea‐pig mesentery, the mast cells of which are unresponsive to the drug, and on a human normal fibroblast‐like cell line. In contrast, histamine at about 10−10 M, a major mast cell component, induced marked mitogenesis in guinea‐pig mesentery without causing degranulation of mast cells.It is concluded that secreting rat‐tissue mast cells release a mitogenic factor or factors acting locally on nearby tissue cells.
Detailed Kinetic Analysis of Shay Chloroleukaemia Cell Population Propagated In Permanent Suspension Culture In Vitro
Authors: Toivonen H. , Foa P. , Paile W. , Rytömaa T. 
Published: May 2008

ABSTRACTDetailed kinetic analysis of a growing cell population is difficult, even when assay conditions are nearly ideal. Therefore, it is usually essential to perform several types of experiments and analyse all the results in terms of a mathematical model, the use of which is not limited a priori by a specified application.In the present study we investigated cell population kinetics using rat chloroleukaemia cells propagated in suspension culture in vitro. the parameters were measured: doubling time of the population, fraction of labelled mitoses, changes in labelling index with time after pulse labelling, continuous labelling and stathmokinetic index. Analysis of the results was based on a computer program CECAM, which is a stochastic model capable of simulating essentially all types of kinetic experiments based on presently known assay techniques.The results showed that precise and reliable information on cell population kinetics could not be obtained from the analysis of any single type of experimental data. In particular, the technique of labelled mitoses underestimated the duration of the G1 phase, owing to subtle label‐induced changes in population behaviour. These changes could not have been detected with any certainty without rigorous quantitative comparisons with other types of experimental data. As a whole, however, results obtained by the different techniques were in agreement and the kinetic behaviour of chloroleukaemia cells in vitro could be established in detail.In certain circumstances even minute changes in the kinetic parameters of the cells can modify population behaviour drastically. to study these cases adequately the experiments must be designed with utmost care, preferably with the aid of preceding simulations. This is because demonstration of small primary changes in population kinetics may be beyond the limit of detection of any single assay method.
DIFFERENTIATION OF MURINE MARROW MEGAKARYOCYTE PROGENITORS (CFUM): HUMORAL CONTROL IN VITRO
Authors: Freedman M. H. , McDonald T. P. , Saunders E. F. 
Published: May 2008

ABSTRACTDifferentiation of mouse marrow megakaryocyte progenitors (CFUm) was studied in vitro by a colony assay using a plasma clot system. Erythropoietin (EPO) from sheep plasma (6 units/mg protein) in doses from 1 to 5 units/ml induced a linear increase in CFUm to a maximum of 20 colonies/105 cells plated. Human urinary EPO also induced a dose‐responsive increase in CFUm, but the maximum was 9 colonies/105 with 2·0 units/ml of EPO and there was a decrease in colonies above that concentration. Thrombocytopoiesis‐stimulating factor (TSF) derived from human embryonic kidney culture supernatant fluids induced a dose‐responsive increase in CFUm in concentrations from 0·01 to 0·32 mg protein/ml in the absence of added EPO. TSF did not support the growth in vitro of erythroid colonies from mouse marrow (CFUe and BFUe) indicating an absence of EPO activity. In these studies sheep EPO appeared more effective in supporting CFUe growth than human EPO. TSF also had a stimulatory function in megakaryocyte differentiation at a precursor level. Multiple humoral factors play a role in megakaryocytopoiesis in vitro.