bluuebunny/crossref_metadata_2025_split huggingface dataset:
A COMPARISON OF IN VIVO AND IN VITRO STATHMOKINETIC METHODS FOR THE STUDY OF CELL PROLIFERATION IN HAMSTER ORAL EPITHELIA
Authors: Scragg Margaret A. , Johnson N. W. 
Published: May 2008

ABSTRACTMitotic indices (MI) expressed as numbers of metaphase figures per 100 basal cells in the cheek pouch and palatal epithelium of the Syrian hamster following metaphase arrest with vinblastine sulphate (VLB) were compared using in vivo and in vitro techniques. The MI in vivo 4 1/2 hr after intraperitoneal injection of 4 mg VLB/kg body weight was 2·69 ± 0·37 for cheek pouch and 12·08 ± 1·09 for palate. MI in vitro was measured using small tissue explants cultured for 4 hr in medium supplemented with VLB at concentrations ranging from 6‐600 μg/ml. The maximum MI for cheek pouch epithelium in vitro (2·7) did not differ significantly from that observed in vivo (P > 0·50) and was obtained in the presence of 12–30 μg VLB/ml, a concentration comparable with that used in vivo. In contrast, the maximum MI for palate epithelium in culture (5·6) was significantly lower than that in vivo (P < 0·001) and was only achieved in the presence of extremely high concentrations of VLB. Possible reasons are discussed for the discrepancy between the MI for palatal epithelium in vivo and in vitro.
FEEDBACK INHIBITION OF HEPATIC DNA SYNTHESIS
Authors: Schulte‐Hermann R. , Schmitz E. 
Published: May 2008

ABSTRACTα‐Hexachlorocyclohexane (α‐HCH) and some other xenobiotic inducers were used to elicit adaptive increases in mono‐oxygenase activity, size and DNA content of rat liver. After elimination of the inducers, organ size and mono‐oxygenase activity returned to normal whereas the DNA content of the liver remained increased. Upon renewed treatment with an inducer the adaptive responses uncoupled. While mono‐oxygenase induction and liver enlargement did occur, DNA replication was largely suppressed. These findings show that in the hyperplastic state the liver is resistant to stimulation of DNA synthesis by the inducers. It is concluded that the DNA content of the liver (or the number of liver cells) is controlled by a feedback system which monitors an excess of DNA (cells) and suppresses cell replication if the content of DNA exceeds the normal level. Organ mass has little, if any, effect on the operation of this feedback system.
CELL LOSS AND INFLUX OF LABELED HOST CELLS IN THREE TRANSPLANTABLE MOUSE TUMORS USING [125I]UdR RELEASE
Authors: Franko A. J. , Kallman R. F. 
Published: May 2008

ABSTRACTThe [125I]UdR loss technique was used to estimate cell loss from RIF‐1, EMT6 and KHJJ tumors in order to determine the length of the delay between labeling and the beginning of the loss of labeled cells, and also to calculate a value for ø, the cell loss factor. To determine the importance of reutilization of label released from the gut and/or the influx of labeled host cells, the blood flow to some tumors was occluded during and for 30 min after injection of the label. Relatively small amounts of radioactivity entered occluded RIF‐1 tumors during 9 days after injection of [125I]UdR, indicating that reutilization of systemic label and influx of labeled host cells are not significant in this system. In contrast, substantial amounts of radioactivity entered occluded EMT6 and KHJJ tumors, reaching 40% of the total activity in non‐occluded tumors during 6 days following injection. After corrections were made for this influx of label, the [125I]UdR loss curves from RIF‐1 and EMT6 tumors were essentially exponential from the first day following injection of label. This was interpreted as indicating the loss of proliferating as well as non‐proliferating cells from both tumors. The cell loss factor derived from the [125I]UdR loss curves corrected for influx appeared to agree well with published values derived from analysis of percent labeled mitoses curves. In contrast, the corrected [125I]UdR loss curves from KHJJ tumors showed that loss of activity began three days after injection of label, indicating that primarily nonproliferating cells are lost from this tumor.
I. THEORETICAL OUTLINE OF A NEW METHOD TO ANALYZE TIME SEQUENCES OF DNA HISTOGRAMS
Authors: Zietz S. 
Published: May 2008

ABSTRACTA new mathematical method is presented to analyze a time sequence of DNA distributions taken from perturbed cell populations. The method, called FPi analysis, consists of plotting the time variation of the fraction of cells in selected DNA contents ‘windows’ of the histogram. It is shown that kinetic information about the flow of cells through the cycle after the perturbation can be estimated from the FPi curves. An analysis of the method reveals that the method yields accurate results for the instrumental and cytochemical variations obtainable by present technology. The value of the method lies in the fact that the information needed can be obtained directly from the measured DNA distribution, thus bypassing the problems with other methods which estimate the fraction of cells in a given phase directly from a single histogram.
II. USE OF THE METHOD TO MONITOR THE IN VIVO KINETICS OF CELL POPULATIONS PERTURBED BY HYDROXYUREA
Authors: Zietz S. , Lessin S. , Grattarola M. , Desaive C. , Nicolini C. 
Published: May 2008

ABSTRACTIn a previous report, we described a new method called FPi analysis to analyze time sequences of DNA histograms taken from a perturbed population of cells. In this paper we utilize the method to analyze the in vivo kinetic response of bone marrow and of lung metastases of the B16 tumor to various chemotherapeutic agents. We show that the technique allows useful kinetic data to be obtained with minimal processing of the raw histograms, thus allowing fast analysis of the data. We also show that, in order to monitor the kinetic response of living tissues, it is essential to collect multiparameter distributions; to monitor only the one dimensional fluorescence histogram can give rise to misleading results. Using these multiparameter histograms, we are also able to monitor the growth fraction of the lung metastases during treatment, allowing discrimination between cell synchrony and cell recruitment from the resting compartment.
A RANDOM WALK MODEL FOR THE ANALYSIS OF THE ISOPRENALINE‐STIMULATED PROLIFERATIVE RESPONSE OF THE RAT SUBMAXILLARY GLAND
Authors: Hopper J. L. , Radley J. M. , Hodgson G. S. 
Published: May 2008

ABSTRACTIn a series of papers, Hodgson, Radley and Koschel have studied the proliferative response of the rat submaxillary gland to the drug isoprenaline. They found that whereas the mitotic activity of the gland is normally very low, a single injection of isoprenaline will stimulate a wave of DNA synthesis and repeated administration at daily intervals, or longer, results in further waves of DNA synthesis. An explanation of these observations was proposed by Radley, Hodgson & Koschel (1976) who introduced the concept that administration of isoprenaline resulted in a period of enhanced ‘biochemical activity’ of the cells.In this paper we present a stochastic model, based on a random walk model introduced by Hopper & Brockwell (1978), to represent quantitatively the concept of ‘biochemical activity'. It is shown that the parameters of this model can be adjusted to fit the observed data. It is noted that the simpler Smith & Martin model (1973), which is a special case of our random walk model, can also be fitted to the data. However, there is experimental evidence that contradicts an assumption of the Smith & Martin model, but agrees with the predictions of our model.The random walk model also reveals that the different responses of the cell population to different injection schedules cannot be fully explained by changes in the cell population's biochemical activity distribution.
SELF‐MAINTENANCE ABILITY AND KINETICS OF HAEMOPOIETIC STROMA PRECURSORS
Authors: Chertkov J. L. , Gurevitch Olga A. 
Published: May 2008

ABSTRACTThe use of repeated femoral curettages and repeated passages of ectopic haemopoietic foci has demonstrated the capacity of stromal precursor cells for repeated formation of haemopoietic microenvironment. During this process the stromal precursors undergo no less than ten to twelve mitoses. Precursors of bone marrow stroma proliferating slowly, if at all, in normal mice are triggered into cell cycle, as revealed by suicide methods, during formation of the ectopic haemopoietic focus.
A COMPREHENSIVE MATHEMATICAL MODEL OF STEM CELL PROLIFERATION WHICH REPRODUCES MOST OF THE PUBLISHED EXPERIMENTAL RESULTS
Authors: Loeffler M. , Wichmann H. E. 
Published: May 2008

ABSTRACTOn the basis of experimental knowledge about haemopoietic stem cells a catalogue of fundamental statements is formulated. From this a simple mathematical model of haemopoietic regulation mechanisms is developed. The functional net effects of regulatory processes which are still unknown or unmeasurable are estimated using evolution arguments. The model is developed in three steps. It allows description of the self‐replication of stem cells after direct destruction as well as their reaction to increased or reduced needs in the erythropoietic system. The most important experimental data about changes in CFUe, BFUe and CFUe after acute or chronic irradiation, anaemia, hypoxia, hypertransfusion or direct erythropoietic stimulation can be reproduced within the model. The model allows us to understand most of the results of experimental stem cell research. Furthermore, it can be applied for a more precise analysis of the existing data. Predictions about the results of certain experiments can be made.
NEW METHODS OF CELL CYCLE ANALYSIS BASED ON THE SELECTIVE TAGGING OF CELLS EITHER AT THE BEGINNING OR END OF S PHASE
Authors: Kurz J. B. , Friedman D. L. 
Published: May 2008

ABSTRACTNew techniques for cell cycle analysis are presented. Using HeLa cells, methods are described for the selection of a narrow window or cohort of lightly [3H]‐labeled cells located either at the very beginning or the very end of S phase. The cohort cells are tagged by a labeling procedure which entails alternating pulses of high and low levels of [3H]thymidine and are identified autoradiographically. Additional methods are described for following the progress of cohort cells through the cell cycle.Theoretically, with the methods described, it should be possible to follow the ‘early S cohort’ cells as they exit from S phase, as they enter and exit M and as they enter the subsequent S phase. This would allow a determination of S, S + G2, S + G2+ M and T. It should theoretically be possible to follow ‘late S cohort’ cells in a similar manner, allowing a determination of G2, G2+ M and G2+ M + G1.To test these predictions, several experiments are presented in which the progress of the two cohorts is monitored. The best data were obtained from the mitotic curves of cohort cells. For each of the cohorts, values were obtained for the time required for peak concentration of cells in mitosis, the coefficients of variation and of skew. The curve of cohort cells passing through mitosis is shown to fit a log‐normal curve better than a normal curve. In addition, the mitotic curves are used to estimate the length of M and to estimate the loss of cohort synchrony. Other uses of these methods are discussed.
THE CELL POPULATION KINETICS AND RESPONSE TO AN S‐PHASE SPECIFIC AGENT OF THREE TRANSPLANTABLE COLON TUMOR LINES
Authors: Simpson‐Herren Linda , Corbett T. H. , Griswold D. P. 
Published: May 2008

ABSTRACTThe relative cell population kinetics of three transplantable murine colon tumor lines (Colon 26, 36 and 38) with different histological and metastatic characteristics were studied in relation to the response of each line to an S‐phase specific agent. The mean doubling times for the three lines between 0·1 and 1·0 g are similar (4·2 days) but marked differences are apparent in times to tumor appearance (0·1 g) and in median days to death. The length of the cell cycle is about one day and the length of the S‐phase 10–11 hr for Colon 36 and 38. The length of the cell cycle in Colon 26 is difficult to estimate by conventional methods but probably exceeds 24 hr and the S‐phase is 10–11 hr; [3H]TdR pulse labeling indices for Colon 36 and 38 decrease with time and tumor size from about 0·45 in 0·1 to 0·2 g tumors to about 0·33 at 3 g. The decrease in the [3H]TdR labeling index for Colon 26 is more pronounced (from about 0·38 at 0·1 g to 0·21 at 1·0 g). The shapes of the PLM curves and the [3H]TdR labeling index data are consistent with the observed sensitivity to an S‐phase specific agent (Palmo‐AraC, NSC 135962) in Colon 36 and the minimal response observed in Colon 26. Colon 38 is intermediate between Colon 36 and Colon 26 in kinetic properties and in response to the S‐phase agent.
Proliferation Inhibition of Murine Pluripotent Haemopoietic Stem Cells By Interferon Or Poly I:C
Authors: Gidáli Julia , Fehér I. , Tálas Margerita 
Published: May 2008

ABSTRACTThe effect of mouse serum interferon (IF) in vitro and an inducer in vivo on the proliferation of a pluripotent stem cell population with high turnover rate was studied. Proliferation rate was characterized by the number of CFUs in the S phase of the cell cycle. Increased proliferation of bone marrow stem cell populations was produced either by irradiating the donor mice with 3·36 Gy (336 rad) 60Co‐gamma rays 7 days before the experiment or by incubating normal bone marrow cells with 10–11 M concentration of isoproterenol. IF considerably reduced the number of CFUs in S phase in both cases without reducing the CFUs content of the samples. Injection of IF inducer (4 mg/kg poly I:C) into regenerating mice also inhibited the proliferation of CFUs without decreasing the femoral CFUs level. Regeneration kinetics of CFUs from irradiated poly I:C‐treated mice ran parallel with that of irradiated untreated animals but showed a characteristic delay corresponding to approximately one CFUs doubling. A transient, non‐cytotoxic proliferation inhibitory effect of IF or IF inducer is, therefore, proposed.
Epidermis Extracts (Chalone) Inhibit Cell Flux At the G1‐S, S‐G2 and G2‐M Transitions In Mouse Epidermis
Authors: Elgjo K. , Clausen O. P. F. , Thorud E. 
Published: May 2008

ABSTRACTEpidermal cell flux at the G1‐S, S‐G2 and G2‐M transition was examined during the first 4 hr after injection of epidermis extract. the flux parameters were estimated by a combination of several methods. the G1‐S and S‐G2 transit rates were calculated on the basis of a double labelling technique with [3H]TdR, the G2‐M flux by means of colcemid and the relative proportion of cells in the S or G2 phase by means of flow cytometry. All experiments were performed both in early morning and late evening, corresponding to maximum and minimum rates of epidermal cell proliferation in the hairless mouse. the epidermis extract inhibited the S‐G and G2‐M transit rates to the same degree, while the inhibition of cell flux at the G1‐S transit was consistently stronger. In general, the inhibition of cell flux at the different transitions was most pronounced when the rate of cell proliferation was low and vice versa.
A Rapid Automated Stathmokinetic Method For Determination of In Vitro Cell Cycle Transit Times
Authors: Dosik G. M. , Barlogie B. , White R. Allen , Göhde W. , Drewinko B. 
Published: May 2008

ABSTRACTTo provide a rapid method for examining cell cycle dynamics, we utilized continuous exposure of Chinese hamster ovary cells and human colon cancer cells to colcemid to block cycling cells in metaphase, suppressing re‐entry into G1. Changes in cell cycle compartment distribution were monitored by DNA flow cytometry. Analysis of the rate of G2+ M compartment accumulation after addition of colcemid permitted calculation of all cycle transit parameters. These compared favorably with data in the same cell lines determined by the fraction of labeled mitoses technique. Serial assessment of DNA flow cytometry after addition of colcemid permits rapid quantitation of cycle traverse rates.
A Critique of the Practice of Comparing Control Data Obtained At A Single Time Point to Experimental Data Obtained At Multiple Time Points
Authors: Burns E. R. 
Published: May 2008

ABSTRACTThe normal circadian rhythm in DNA synthetic activity (DNA‐SA) in the tip of the mouse tongue is presented. When this rhythm, obtained from mice which were not treated (NT) or handled, was compared to the rhythms obtained from mice treated with saline (SAL) or 25 mg/kg isoproterenol (IPR), no alteration in the rhythm was observed after either treatment. the conclusion from this chronobiological, experimental design was that IPR had no effect on DNA‐SA in the tip of the tongue. However, when three single time points (08.00, 11.00 or 14.00) are selected from the SAL‐treated, control rhythm and compared to the multiple time point data from the IPR‐treated mice, three very different, statistically supported conclusions were reached.The common practice of obtaining data at only one time point in control animals and comparing these data to data obtained from drug‐treated animals at multiple time points is an example of poor experimental design which results in erroneous conclusions and unnecessary confusion in the literature on in vivo research.
Alterations In Gastrointestinal Steady‐State Kinetics Associated With the Growth of Experimental Tumours
Authors: Kovacs C. J. , Evans M. J. , Schenken L. L. , Burholt D. R. 
Published: May 2008

ABSTRACTChanges in the growth kinetics of the intestinal epithelium were observed in mice bearing the Lewis lung carcinoma and the T1699 mammary adenocarcinoma and in rats bearing the H‐4‐II‐E2 hepatoma. Proliferative activity in the jejunal tissue was markedly depressed with increasing tumour burden. Simultaneously, a significant reduction in total crypt cellularity occurred, followed by a reduction in villus height. While the total number of proliferative cells per crypt decreased, the relative proliferative compartment within the shrinking crypt increased. the rate of mucosal DNA synthesis remained constant during the initial cytokinetic changes, falling only after proliferative activity of the intestine was reduced to less than 50% of control levels. No general correlation could be drawn from the three tumour models studied between the level of gastrointestinal proliferation and tumour size, tumour growth rate or loss of weight by the tumour‐bearing animals. However, intestinal proliferation was reduced by 50% when the tumour burden for each of the three tumours reached 6–8% of the host animal weight.
A Flow Cytometric In Vivo Chalone Assay Using Retransplanted Old Murine Jb‐1 Ascites Tumour Cells
Authors: Barfod N. M. 
Published: May 2008

ABSTRACTA flow cytometric in vivo chalone assay is described. Transplantation of old JB‐1 ascites tumour cells to new hosts induced an influx of tumour cells, with G1 DNA content, to the S phase. This induction could be reversibly and specifically blocked by injections of an ultrafiltrate of old JB‐1 ascites fluid.The method described is superior to a previously published in vivo chalone assay using regenerating ascites tumours. Owing to a reduced variability in time of onset of DNA synthesis, a smaller scatter of observations is achieved and thus the number of mice per group may be reduced using the new method. In contrast to the older technique, the present one does not necessitate killing of mice during the observation period.
EFFECTS OF CHRONIC STEROID INGESTION ON GASTRODUODENAL EPITHELIAL RENEWAL IN THE RAT
Authors: Eastwood G. L. , Quimby G. Forrest , Laferriere J. R. 
Published: May 2008

ABSTRACTSteroids may predispose to peptic ulcer formation. One possible mechanism could be via alteration of normal epithelial renewal. to study the effects of steroids on gastroduodenal epithelial renewal, rats received hydrocortisone sodium succinate in the drinking water to deliver a dose of 10 mg/kg per day. Control rats received plain water. After 4 weeks, the rats were injected intraperitoneally with tritiated thymidine, to label proliferating cells, and killed 1 hr later, to determine measurements of epithelial proliferation, or 24 hr later to determine measurements of epithelial migration. Sections of fundus, antrum and post‐pyloric duodenum were processed for light microscopy and autoradiography. In fundic and antral mucosa, steroid treatment resulted in a reduction in the number of labelled cells and in the size of the proliferative zone and, in the fundus, the mucosal thickness was reduced. In the duodenum, although the number of labelled cells remained unchanged, steroid treatment did decrease the number of cells in the proliferative zone; further, crypt depth was reduced in steroid‐treated rats, but villous height was increased, resulting in an overall increase in mucosal thickness. Epithelial migration was also depressed in fundic and antral mucosa, but appeared to be accelerated in the duodenum of steroid‐treated rats. These studies indicate that although, in the duodenum, the effects of steroids on epithelial renewal are complex, in the stomach chronic steroid ingestion depresses epithelial renewal both in fundic and antral mucosa. This inhibition of epithelial renewal in the stomach may contribute to the ulcerogenic action of steroids by either rendering the mucosa susceptible to the effects of other ulcerogens or by retarding the healing of existing mucosal lesions.
Conditions Required For the Inhibition of In Vitro Growth of A Mouse Myeloma Cell Line By Adherent Bone‐Marrow Cells
Authors: Zipori D. 
Published: May 2008

ABSTRACTThe in vitro growth of the MPC‐11 myeloma cell line was inhibited when these cells were co‐cultured with adherent cells from mouse bone marrow. This growth inhibition involved prolongation of the specific population doubling time of the MPC‐11 cell line. Control cultures of MPC‐11 cells exhibited an average doubling time of 14–15 hr, whereas in the presence of adherent layers the length of the doubling time was up to 28 hr. This prolongation in the doubling time did not depend on the duration of incubation, but on the relative proportions of tumour cells and adherent cells employed. MPC‐11 cells seeded in relatively high starting cell concentrations partially overcame the growth inhibition. the inhibitory activity of adherent cells from the bone marrow did not appear to be due to production of soluble factor(s), since media conditioned by adherent cells did not affect cell growth. Moreover, in modified co‐cultures in which MPC‐11 cells grew physically separated from the adherent layers, only marginal growth inhibition activity was observed. the possibility that cell‐to‐cell interactions lead to the inhibition of growth of MPC‐11 cells by adherent cells from the bone marrow, and the implications of these findings to the control of cell growth by the haemopoietic microenvironment, are discussed.
Circadian Rhythms In the Epithelial Cells and the Pericryptal Fibroblast Sheath In Three Different Sites In the Murine Intestinal Tract
Authors: Neal J. Valerie , Potten C. S. 
Published: May 2008

ABSTRACTVariations in percentage labelling (LI) and mitotic activity (mitoses per crypt) have been studied over a 24‐hr period in the epithelial cells and pericryptal fibroblast sheath (PCFS) of the small intestine, caecum, and colon of the mouse. All three tissues displayed clear, synchronized circadian rhythms in DNA‐synthetic activity in both the epithelial cells and PCFS. Peak values were coincident within a tissue, but staggered between tissues. In the epithelial cells, peak mitotic values were found between 3 and 6 hr after the peak LI values. the low level of mitotic activity in the PCFS appeared to be synchronized with the rhythms in the adjacent epithelia. the epithelial cells of the lowest crypt third displayed the clearest circadian rhythms. However, the PCFS cells at all levels produced similar curves. A craniocaudal wave of proliferative activity is proposed.