bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation Between the Rhythms of Blood Insulin Levels and the Stimulation of Spleen Lymphocytes By Concanavalin‐A In Mice
Authors: Prunet J. , Panijel J. 
Published: May 2008

AbstractAn ultradian rhythm of DNA synthesis and an in‐vitro response to Concanavalin‐A (Con‐A) stimulation has been found in splenocytes of DBA/2 male mice, living under conditions standardized for light‐synchronized periodicity. It was characterized by two peaks during the nycthemeral cycle. One of them was very sharp.In spite of a constant mode of synchronization of the animals, there were seasonal variations of the rhythm. Such variations did not, however, affect the position of the sharp peak, which occurred always at the same hour.The rhythm of incorporation of [3H]‐thymidine by splenocytes, whether or not stimulated by Con‐A, seemed correlated with that of blood insulin levels in mice. the possible effect of the physiological increase in blood insulin during the circadian cycle has been confirmed experimentally. Thus it seems probable that insulin would be one of the internal synchronizers.
Pluripotent Stem Cells Do Not Completely Maintain Normal Human Steady‐State Haemopoiesis
Authors: Dörmer P. , Ucci G. 
Published: May 2008

AbstractSince the classical work on the regulation of canine erythropoiesis by Alpen & Cranmore (1959), it has been generally accepted that recognizable bone‐marrow cells are continuously replaced from sources of unrecognizable precursors. Although many features of pluripotent stem cells (PSC) and committed haemopoietic precursors have been determined, direct demonstration of a continuous influx, under normal steady‐state conditions, from PSC into the recognizable bone‐marrow cell compartments is still lacking. There is abundant evidence that PSC, in a number of species, including primates, resemble atypical or immature (‘transitional’) lumphocytes. By utilizing the technique of quantitative 14C‐autoradiography, we have measured the activities of DNA and protein synthesis in individual bone‐marrow cells of two healthy humans. A positive relationship was established between the protein synthesis rate and rate of movement through the cell cycle in all proliferative compartments. Lymphoid cells, considered to contain the fraction of PSC, were found in the lower range of this relationship. These low metabolic rates exclude fast growth as well as short cell‐cycle times. In view of the low frequency of the potential PSC in the human bone marrow, amounting to less than 2%, these cells cannot be considered to represent a source continuously supplying the pool of rapidly proliferating, recognizable blast cells in the bone marrow under steady‐state conditions. Some self‐maintenance of a subcompartment within the pool of recognizable normal bone‐marrow blast cells is therefore suggested.
Regulation of haemopoietic stem‐cell proliferation in mice carrying the Slj allele
Authors: Ploemacher R. E. , Nikkels P. G. J. , Molendijk W. J. , Brons N. H. C. , Brockbank K. G. M. 
Published: May 2008

AbstractWe investigated a haemopoietic stromal defect, in mice heterozygous for the Slj allele, during haemopoietic stress induced by treatment with bacterial lipopolysaccharides (LPS) or lethal total body irradiation (TBI) and bone‐marrow cell (BMC) reconstitution. Both treatments resulted in a comparable haemopoietic stem cell (CFU‐s) proliferation in Slj/+ and +/+ haemopoietic organs. There was no difference in committed haemopoietic progenitor cell (BFU‐e and CFU‐G/M) kinetics after TBI and +/+ bone‐marrow transplantation in Slj/+ and +/+ mice. the Slj/+ mice were deficient in their ability to support macroscopic spleen colony formation (65% of +/+ controls) as measured at 7 and 10 days after BMC transplantation. However, the Slj/+ spleen colonies contained the same number of BFU‐E and CFU‐G/M as colonies from +/+ spleens, while their CFU‐s content was increased. On day 10 post‐transplantation, the macroscopic ‘missing’ colonies could be detected at the microscopic level. These small colonies contained far fewer CFU‐s than the macroscopic detectable colonies. Analysis of CFU‐s proliferation‐inducing activities in control and post‐LPS sera revealed that Slj/+ mice are normal in their ability to produce and to respond to humoral stem‐cell regulators.We postulate that Slj/+ mice have a normal number of splenic stromal ‘niches’ for colony formation. However, 35% of these niches is defective in its proliferative support.
Kinetic Differences Between Fed and Starved Chinese Hamster Ovary Cells
Authors: Nelson John M. , Todd Paul , Metting Noelle F. 
Published: May 2008

AbstractWhen Chinese hamster (CHO‐K1) cells are grown as monolayer cultures, they eventually reach a population‐density plateau after which no net increase in cell numbers occurs. the kinetics of aged cells in nutritionally deprived (starved) or density‐inhibited (fed) late plateau‐phase cultures were studied by four methods: (i) Reproductive integrity and cell viability were monitored daily by clonogenic‐cell assay and erythrosin‐b dye‐exclusion techniques. (ii) Mitotic frequencies of cells from 18 day old cultures were determined during regrowth by analysing time‐lapse video microscope records of dividing cells. (iii) Tritiated‐thymidine ([3H]TdR) auto‐radiography was used to determine the fractions of DNA‐synthesizing cells in cultures entering plateau phase and during regrowth after harvest. (iv) the rate of labelled nucleoside uptake and incorporation into DNA was measured using liquid scintillation or sodium iodide crystal counters after labelling with [3H]TdR or [125]UdR.Non‐cycling cells in starved cultures accumulate primarily as G1, phase cells. Most cells not in G1 phase had stopped in G2, phase. Very few cells (< 2%) were found in S phase. In contrast, about half of the cells in periodically fed cultures were found to be in DNA‐synthetic phase, and the percentage of these S phase cells fluctuated in a manner reflecting the frequency of medium replacement. Populations of both types of plateau‐phase cultures demonstrate extremely coherent cyclic patterns of DNA synthesis upon harvest and reculturing. They retain this high degree of synchrony for more than three generations after the resumption of growth. From these data it is concluded that nutritionally deprived (starved) late plateau‐phase cells generally stop in either G1, or G2, phase, whereas periodically fed late plateau‐phase cultures contain a very large fraction of cycling cells. Populations of cells from these two types of non‐expanding cultures are kinetically dissimilar, and should not be expected to respond to extracellular stimuli in the same manner.
Different Epidermal Cell Kinetic Effects of Hydroxyurea When Injected At Two Different Times of the Day
Authors: Thorud E. , Clausen O. P. F. , Kauffman S. L. 
Published: May 2008

AbstractCircadian rhythms in epidermal basal cell‐cycle progression in hairless mouse skin have been repeatedly demonstrated. A dose of 10 mg/animal hydroxyurea (HU), given to inhibit DNA synthesis was injected intraperitoneally to two groups of hairless mice. One group was injected at 10.00 hours MET, when the cell‐cycle progression and cell division rate are relatively high, and another group was injected at 20.00 hours, when the same variables are at minimum values. Various cell kinetic methods—[3H]TdR autoradiography, DNA flow cytometry and the stathmokinetic method (Colcemid)—were used to study HU‐induced alterations in cell kinetics.Hydroxyurea (HU) immediately reduced the labelling index (LI) to less than 10% of controls when injected at both times of the day, and higher then normal values were observed 8 hr later. A subsequent decrease towards normal values was steeper in the 20.00 hours injected group. the proportion of cells with S‐phase DNA content was transiently reduced in both series, but the reduction was less pronounced and control values were reached earlier in the series injected at 10.00 hours. the observed alterations in LI and fraction of cells in S phase were followed by comparable alterations in the fraction of cells in G2 and in the mitotic rate. Hence the changes in G2 and mitotic rate are easily explained as consequences of the previous perturbations in the S phase.The time‐dependent differences in the cell kinetic perturbations caused by HU in the S phase may be explained by a circadian‐phase‐dependent action of HU on the influx and efflux of cells to and from the S phase, respectively. At 10.00 hours the efflux of cells from S is most heavily inhibited; at 20.00 hours the influx is predominantly blocked. Hence, when physiological flux is high HU mainly blocks the efflux from S, but when flux normally is low, HU mainly blocks the entrance to S.Within 20 hours after the HU injection, the cell kinetic variables had approached the unperturbed circadian pattern.
Alkalinization Stimulates Ca2+‐Dependent Spreading During the Activation of Resting Lens Epithelial Cells In Primary Culture
Authors: Glaesser Dietmar , Iwig Martin , Ngoli Dominique , Udelnow Christa 
Published: May 2008

AbstractLens epithelium, when attached to its natural substratum, the lens capsule, can be maintained in culture for more than 2 weeks in a simple HEPES‐ and EDTA‐buffered salt solution (HBS). In HBS, the epithelium shows the same characteristic phenomena of locomotion, initial retraction and respreading which in MEM plus serum precedes the inception of DNA synthesis. These phenomena have been shown to be dependent on extracellular Ca2+. 0·05 mM Ca2+ is necessary for maintaining cell‐to‐cell contacts of the in vivo epithelium. Higher concentrations of Ca2+ cause the epithelium to retract initially. In contrast, Mg2+ greatly favours cell‐substratum interactions leading to the formation of lamellopodia and an initial spreading of the epithelium. After some hours in culture the epithelium changes markedly in response to extracellular Ca2+ and Mg2+; it respreads and flattens in the presence of Ca2+, while Mg2+ becomes less effective in maintaining cell‐to‐substratum contacts. Mg2+‐dependent initial spreading is promoted at pH values near 7·0 but the Ca2+‐dependent respreading requires an alkalinization of the salt solution.
Two‐Step Cell‐Death Kinetics In Vitro During Cis‐Platinum, Hydroxyurea and Mitomycin Incubation
Authors: Böhmer Ralph‐M. 
Published: May 2008

AbstractA human leukaemic cell line (REH) growing in suspension was incubated with cis‐platinum, hydroxyurea and mitomycin C at various concentrations causing complete cell‐cycle arrest. At different times the cell suspensions were harvested, diluted 1:1 with a buffer solution, stained without further treatment with a mixture of acridine orange (AO) and ethidium bromide (EB) and analysed with a biparametrical flow cytometer. Fluorescent plastic beads were introduced into the suspensions to provide an internal numerical reference for the control of cell loss.The fluorescence distributions showed three groups of cells: vital cells (V) which were only stained with AO; dead cells in which EB stained cytoplasmic components but not the nuclear DNA (D1), and dead cells which allowed EB to stain both cytoplasm and nuclear DNA (D2). the kinetics of cells entering D1 depended on drug concentration and showed equal characteristics for cis‐platinum and mitomycin, but were different for hydroxyurea. the subsequent entry into D2 occurred about 15 hr later and showed no pronounced dependence on drug concentration. Parallel trypan‐blue (TB) exclusion tests revealed that TB only stained D2 cells and therefore is not useful for investigating cell‐death kinetics during exposure to cell‐killing agents.
Effects of [3H]Udr On the Cell‐Cycle Progression of L1210 Cells
Authors: Darzynkiewicz Z. , Carter Sally , Kimmel M. 
Published: May 2008

AbstractTritium‐labelled uridine ([3H]UdR) perturbs progression of L1210 cells through the mitotic cycle. the main effect manifests as a slowdown or arrest of a portion of cells in G2 and is already observed 2 hr after addition of 0.5–5.0 μCi/ml of [3H]UdR into cultures. At 2.5–5.0 μCi/ml of [3H]UdR a slowdown of cell progression through S is also apparent. Additionally, there is an increase in the number of cells with DNA values higher than 4C in cultures growing in the presence of [3H]UdR for 8–24 hr. A pulse of [3H]UdR of 2 hr duration labels predominantly (95%) cellular RNA. the first cell‐cycle effects (G2 slowdown) are observed when the amount of the incorporated [3H]UdR is such that, on average there are fewer than thirty‐six [3H] decays per cell which corresponds to approximately 12–19 rads of radiation. the S‐phase slowdown is seen at a dose of incorporated [3H]UdR twice as high as that inducing G2 effects. the specific localization of [3H]UdR in nucleoli, peripheral nucleoplasm and in cytoplasm, as well as differences in the kinetics of the incorporation in relation to phases of the cell cycle are discussed in the light of the differences between the effects of [3H]UdR and [3H]thymidine. Mathematical modelling of the cell‐cycle effects of [3H]UdR is provided.
Kinetic Analysis of Drug‐Induced G2 Block In Vitro
Authors: Kimmel Marek , Traganos Frank 
Published: May 2008

AbstractThe data on cell‐cycle effects of two prospective antitumour agents, (+)‐1,2,‐bis(3,5‐dioxopiperazine‐l‐yl)propane (soluble ICRF; NSC 169780) and 1,4‐bis(2′chloroethyl)‐1,4‐diazabicyclo [2.2.1] heptane diperchlorate (CBH; NSC 57198) were used to determine whether a modified stathmokinetic experiment could predict the effects of continuous, long‐term (0–48 hr) drug exposure in an in vitro L1210 murine leukaemia cell system. Generally, continuous drug exposure of exponentially growing cells does not provide sufficient quantitative information concerning cell‐cycle‐phase‐specific mechanisms of drug action. Alternatively, stathmokinetic experiments, which are usually limited to some fraction of one cell doubling time, provide little information about long‐term drug effects. By using mathematical models constructed for this purpose, however, stathmokinetic data can predict the overall proportion of cells affected by a drug though failing to discern between various kinds of drug action (e.g. reversible v. irreversible block, blocking v. killing action, etc.), especially when it occurs in G2 phase. In addition, it can be shown that for at least one of the drugs (soluble ICRF) the stathmokinetic experiment fails to predict ‘after‐effects’ of drug treatment which extend into the following cell cycle(s). It also becomes clear that the degradation of exponential growth characteristics of quickly dividing cells during long‐term, continuous drug exposure makes prediction of cell‐cycle kinetic perturbations uncertain when derived from short‐duration stathmokinetic experiments. However, with care, the joint application of ‘short term’ (e.g. stathmokinesis) and ‘long term’ (e.g. continuous exposure) techniques allow adequate quantitative insight into drug‐perturbed cell‐cycle kinetics. the applicability of modelling techniques is discussed: in the present instance it is limited to lower drug concentrations. For higher drug concentrations, effects like increased ploidy, ineffective division, etc., make it impossible in the present study to obtain a clear picture of the kinetics.
Determination of [3H]Tdr‐Labelling Indices of Cultured Cells Grown On Detachable Chamber Slides
Authors: Simpson William G. , Ballou Rick J. , Tseng Michael T. 
Published: May 2008

AbstractThe in vitro effects of xenobiotic agents on the incorporation of DNA precursors was determined using a detachable chamber slide assembly. the technique presented allows for the comparative assessment of several agents, even when a limited number of cells is available. the use of a glass slide also potentiates the use of higher magnifications with a greater resultant resolution than that achievable with past methods.
Haemopoietic modulation in tumour‐bearing animals: enhanced progenitor‐cell production in femoral marrow
Authors: Kovacs C. J. , Emma D. A. , Evans M. J. , Johnke R. M. , Scarantino C. W. 
Published: May 2008

AbstractAltered haematopoiesis in the femoral marrow was observed in mice bearing the Lewis lung carcinoma (LLca). During tumour growth, a marked reduction was observed in the myeloperoxidase‐positive cells (granulocytes) of the marrow 7 days after inoculation of the LLca tumour reaching a nadir (17% of control) by day 28. Accompanying this suppression of mature white cells was a gradual expansion of the CFUc‐GM compartment followed by an increase in the number of femoral CFUs. Humoral‐stimulating activity (HSA) increased through day 14 in the serum of these animals; then returned to control levels by day 28. During this same interval, the more primitive erythroid progenitor (BFUe) compartment expanded to 168% of control, while the more differentiated (CFUe) compartment was reduced (45% of control at day 28). Reductions in both 59Fe‐incorporation and erythroblasts/femur confirmed the suppression of erythroid differentiation in marrow during tumour growth. Similar results were observed following the daily injection (188 mg equivalent dose; q 24 hr × 10) of the supernatant prepared from LLca tissue. Marked differences were observed between the response of the spleen and the marrow to the supernatant. the data suggest that the growth of the LLca tumour results in a dissociation of the normal continuity of haematopoietic steady‐state differentiation in the marrow of tumour‐bearing animals.
Crypt fission and crypt number in the small and large bowel of postnatal rats*
Authors: St. Clair W. H. , Osborne J. W. 
Published: May 2008

AbstractThe aim of this investigation was to study crypt fission, a process which may be instrumental in regulating crypt number in the intestine. Young Holtzman rats were killed at various times after parturition and samples of the small intestine and colon were removed and processed. A microdissection technique was used to separate crypts from other structures. Crypts were scored as normal or fissioning. the percentage of crypts in fission (PCF) reached peak values of 25% and 52% in the small bowel and colon, respectively, at 21 days post‐parturition. From this time onward, the PCF dropped until the adult value of approximately 7% was reached in each site. During this same period, the number of crypts increased from 1.9 × 106 to 3.3 × 106 in the small bowel and 2.2 × 105 to 6.5 × 105 in the colon. Thus an inverse relationship between the percentage of crypts in fission and crypt number was found. Distribution of fissure heights in fissioning crypts did not change as the animal aged. the majority of the fissures were found in the lower 1/4 of the fissioning crypts. This suggests that as soon as the fissure extends beyond the stem cell zone, division into two crypts soon occurs.
Quasi‐Exponential Generation Time Distributions From A Limit Cycle Oscillator
Authors: Klevecz R. R. , Shymko R. M. 
Published: May 2008

AbstractIn spite of the apparently random behaviour and the often exponential distribution of generation times expressed in cell populations, there is evidence for rather precise timekeeping in the cell cycle. In experiments using time‐lapse video‐tape microscopy, we have noted that cell generation times are often not distributed smoothly but in many cases seem to cluster at roughly 4 hr intervals. Phase shift responses following application of heat shock, ionizing radiation or serum pulses in each case show a pattern which is repeated twice in cells with an 8–9 hr modal generation time. We describe here a cell cycle model with an independent cellular clock controlling cell cycle events which accounts for the phase response data, while also reconciling the stochastic and periodic behaviour characteristic of animal cells.
Vindesine As A Stathmokinetic Agent In Human Rectal Tumours In Organ Culture
Authors: Pritchett C. J. , Senior P. V. , Sunter J. P. , Watson A. J. , Appleton D. R. , Wilson R. G. 
Published: May 2008

AbstractOrgan culture, using human colorectal mucosa and tumours, is a good system in which to test a new stathmokinetic agent such as vindesine. Using this system we have found that vindesine has similar metaphase‐arresting properties to vincristine, including at least a 6‐fold dose response difference in its ability to arrest mitosis in mucosa and tumour, mucosa being the more sensitive. Vindesine is a satisfactory stathmokinetic agent, but in view of its greater cost offers no particular advantages over vincristine.
Cyclic Amp Response to Various Haemopoietic Regulators
Authors: Wdzieczak‐Bakala J. , Pines M. , Guigon M. , Lenfant M. 
Published: May 2008

AbstractDiffusible inhibitors and stimulators are involved in the regulation of bone marrow pluripotent stem cell (CFU‐S) proliferation. We have previously shown the existence of CFU‐S inhibitors in foetal calf marrow and liver and have started their purification. the lack of a simple and time‐saving test to determine the kinetic state of CFU‐S and the activity of the inhibitors led us to explore the possibility of a biochemical proliferation marker that could be used for screening purpose. Since it was shown that cyclic AMP was implicated in the regulation of CFU‐S proliferation, it was of interest to study the variations in cAMP levels after stimulation and inhibition of CFU‐S entry into cycle. the results of in vitro experiments showed that the increase in cAMP levels observed in bone marrow cells after incubation with different haemopoietic stimulators was specific neither for bone marrow cells nor for the various haematopoietic regulators. In the in vivo experiments, an increased cAMP level was observed 8 hr after one injection of Ara‐C at the time when CFU‐S are recruited into S phase. However, no modification of cAMP levels has been observed after injection of CFU‐S inhibitors in the Ara C‐treated mice. Although cAMP does not seem to be a suitable marker for testing the activity of inhibitory fractions during the purification process, this work has contributed to the study of CFU‐S stimulators.
Metaphase‐Arrest Technique Applied to Human Cervical Epithelium. Ii. Cell Production Rates In Normal and Pathological Cervical Epithelium
Authors: Ireland David 
Published: May 2008

AbstractAn application of the metaphase‐arrest technique to human cervical epithelium, in vivo, was utilized to obtain cell birth rate data for seventy‐six patients with normal and pathological cervical epithelium. Mean cell production rates for basal and parabasal layers of normal epithelium were 0.91 and 0.92 cells/1000 cells/hr respectively. Histologically normal epithelium adjacent to CIN (cervical intra‐epithelial neoplasia) had a significantly higher rate for the parabasal layer compared to the ‘normal’ group (P < 0.05). Values for the lower two‐thirds of CIN III were 8–10 times higher than for normal epithelium, with microinvasive carcinoma having the highest rates of all. Values for wart‐affected cervical epithelium (NCWVI) were intermediate between normal and CIN, but there was activity in the superficial layer, possibly reflecting activity of the papilloma virus. Large variation in birth rates between individuals in the same histological category was noted for each group, this being particularly the case in six patients with early invasive carcinoma.The data is used to attempt to elucidate some of the uncertainties surrounding the aetiology and biological behaviour of cancer of the cervix and its precursors. Sources of inaccuracy are emphasized and practical difficulties discussed.