bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIURNAL VARIATION IN THE LABELING INDEX OF MOUSE EPIDERMIS: A DOUBLE ISOTOPE AUTORADIOGRAPHIC DEMONSTRATION OF CHANGING FLOW RATES
Authors: Crube D. D. , Auerbach H. , Brues A. M. 
Published: May 2008

ABSTRACTA diurnal rhythmicity in the labeling index was observed in the epidermis of hairless mice, injected with either 14C‐ or 3H‐thymidine, at different times during a 24 hr period.A modified autoradiographic technique, using 14C‐ and 3H‐thymidine and two overlying emulsion layers, makes it possible to clearly differentiate synthesizing cells which are singly labeled with either carbon‐14 or tritium, and cells labeled with both isotopes. At various times during a 24 hr period, hairless mice were injected with thymidine‐2‐14C and colcemid, followed at 2 or 3 hr by a second injection of 3H‐thymidine. The labeling indices were calculated for the 14C‐ and 3H‐thymidine injection times. These labeling indices were consistent with the control, single isotope, labeling indices and exhibited the same diurnal rhythm.Cells singly labeled with 3H‐ or 14C‐thymidine have either started or completed DNA synthesis during the interval between the two injections. Flow rates into and out of DNA synthesis, throughout the 24 hr period, can be calculated from these singly labeled cells. The flow rates varied rhythmically throughout the day and paralleled changes in the labeling indices. The influx and efflux flow rates, at all times measured, were not equal. The influx flow rate was reflected in the efflux rate at a time later equal to the duration of S.By means of these flow rates, the per cent of cells in DNA synthesis was calculated for each hour during a 24 hr period. The resulting labeling index curve matches the observed 24 hr diurnal rhythm in labeling indices. By extension of these flow rates through mitosis, the resulting mitotic index curve is comparable to the reported 24 hr diurnal rhythm in mitotic indices.
THE EFFECT OF POLYCYTHAEMIC SERUM ON THE PROLIFERATION OF RAT BONE MARROW CELLS IN VITRO
Authors: Kivilaakso E. , Rytömaa T. 
Published: May 2008

ABSTRACTThe effect of experimental polycythaemia on the rate of proliferation of erythrocytic precursor cells was investigated by means of an in vitro technique. The serum obtained from polycythaemic rats was found to inhibit significantly 3H‐thymidine incorporation in normal rat bone marrow cells in vitro, as compared with normal serum. Autoradiographic analysis revealed that this inhibition resulted from a reduction in the number of labelled bone marrow cells. The inhibition proved to be specific to the erythrocyte precursor cells; the labelling index was reduced in the erythrocytic cell population by 21–50% (P < 0.001) at different incubation times, while the effect on the granulocytic cell population was negligible. It is deduced that an inhibitor substance responsible for the effects observed is present in polycythaemic serum. It is proposed that this factor is the ‘erythrocytic chalone'. The results support the general view that triggering of stem cells is not the only mode of regulation of erythropoiesis, but that the rate of proliferation of the precursor cells in the erythron is also regulated.
THE DEVELOPMENT OF FIBROBLAST COLONIES IN MONOLAYER CULTURES OF GUINEA‐PIG BONE MARROW AND SPLEEN CELLS
Authors: Friedenstein A. J. , Chailakhjan R. K. , Lalykina K. S. 
Published: May 2008

ABSTRACTIn monolayer cultures of guinea‐pig bone marrow and spleen the development of discrete fibroblast colonies takes place on days 9–12. The linear increase in the number of colonies with increasing numbers of explanted cells and the distribution of male and female cells in mixed cultures support the view that fibroblast colonies are clones. The concentration of colony‐forming cells in bone marrow and spleen is approximately 10‐5. Bone marrow culture (but not spleen culture) fibroblasts are capable of spontaneous bone formation in diffusion chambers. Fibroblasts from both bone marrow and spleen cultures are inducible to osteogenesis in diffusion chambers in the presence of transitional epithelium.
CELL CYCLE PROPERTIES OF DIFFERENTIATING SPERMATOGONIA IN ADULT SPRAGUE‐DAWLEY RATS
Authors: Huckins Claire 
Published: May 2008

ABSTRACTThe duration of the mitotic cycle and of its components was analysed for each of the six successive generations of differentiating spermatogonia (A1, A2, A3, A4, intermediate and B), using radioautographed whole mounts of seminiferous tubules from testes of adult Sprague‐Dawley rats. Cell cycles were determined from two successive waves of per cent labeled metaphases obtained during the period of 81 hr after a single dose of 3H‐thymidine. Except for the A1 spermatogonia, all spermatogonial types (A2 to B) had similar cell cycle durations of 41‐42.5 hr and comparable pre‐DNA synthesis phases (G1) of 11‐13 hr. Although the combined duration of DNA synthesis (S) and the post‐synthesis phase (G2) remained identical for all the cell types including A1, there was a progressive lengthening of the S period at the expense of G2 during the process of spermatogonial maturation. This change was most marked during the transition from A1 to A3 spermatogonia when the S period increased from 14 hr to 21 hr, and the G2 phase shortened from 13 hr to 7.5 hr. This feature seems to be unique to germ cells and may be associated with an increasing amount of heterochromatin in the nucleus. Excluding the development of type A1 cells, the entire process of spermatogonial maturation lasted for 208 hr. Combined data on cell cycle times indicated that every 313 hr or 13 days, a new sequence of spermatogonial differentiation was initiated by the A1 cells. This was equivalent to the duration of one ‘cycle’ of the seminiferous epithelium as measured by other techniques.
THE SPERMATOGONIAL STEM CELL POPULATION IN ADULT RATS
Authors: Huckins Claire 
Published: May 2008

ABSTRACTRadioautographed whole mounted seminiferous tubules from adult rat testes were used to analyse undifferentiated type A spermatogonia at various intervals up to 81 hr following a single injection of 3H‐TdR. the data obtained led to the identification of the spermatogonial stem cell and to the formulation of a new model for spermatogonial renewal and differentiation.Undifferentiated type A cells were morphologically alike, but were topographically classified as (1) isolated or (2) paired and aligned. Although labeled isolated A cells were scattered over most stages of the seminiferous epithelium, their proliferative activity varied with the stage; their labeling index was 20‐30% in stages I and II, but less than 1% in stages VII and VIII. By tracing the labeled divisions of isolated A spermatogonia in time, it was seen that some daughter cells became separated from one another to form two new isolated cells, while others remained together as paired A spermatogonia. Analysis of two successive waves of labeled mitoses revealed that most paired A spermatogonia continued to proliferate forming four aligned A cells, many of which divided again to produce a chain of eight and so on. the greatest incidence of labeling among paired and aligned A spermatogonia occurred in stages XIII‐III. In stage I, where the labeling index was 50%, the calculated proliferative fraction was 1 for these spermatogonia. Between stages II and V, they began to leave mitotic cycle, and during stage V this entire cohort morphologically transformed into A1 spermatogonia. Labeled metaphase curves for undifferentiated A spermatogonia were distinct from any of the curves previously constructed for the six classes of differentiating spermatogonia, especially because of particularly long S and G2 phases in the former. the cell cycle time of paired and aligned A cells was 55 hr, compared to an average of 42 hr for differentiating types A2 to B.
MECHANISM OF EOSINOPHILIA
Authors: Spry Christopher J. F. 
Published: May 2008

ABSTRACTEosinophil leucocyte production was studied in the bone marrow of normal rats and rats given single injections of Trichinella spiralis larvae which stimulated eosinopoiesis. the development sequence of eosinophils in the bone marrow was based on morphological criteria combined with studies of the extent of eosinophil labelling after injections of tritiated thymidine. the proliferative compartment contained at least three recognizable steps in eosinophil development which were defined.There was a delay of 23 hr after injection of larvae before the proportion of eosinophils in the bone marrow increased and it had doubled by 49 hr. the mitotic index increased by a factor of 3 after stimulation. Estimates of the cell cycle parameters were made for marrow eosinophils 1‐3 days after stimulation, using the technique of analysing labelled mitoses. the results were compared with a similar group of normal rats, and were processed by using a computer program. Marrow eosinophil cell cycle time was 30 hr in normal rats and 9 hr in stimulated rats, and this acceleration was associated with a reduced spread of cell cycle times. the number of eosinophil cell divisions and the transit times for each compartment in normal and stimulated rats were estimated. This showed that the stimulus may have resulted in five or six additional divisions among the youngest eosinophils in the dividing compartment. From these figures an outline of eosinopoiesis in the marrow of normal and stimulated rats is proposed.
INCORPORATION OF TRITIATED THYMIDINE INTO THE SKIN AND HAIR FOLLICLES
Authors: Potten Christopher S. , Jessup Barbara A. , Croxson Mary B. 
Published: May 2008

ABSTRACTDiurnal fluctuations in incorporation of tritiated uridine and tritiated thymidine are reported for full thickness skin and its two proliferative populations, the epidermal basal layer and the hair follicle germ or matrix. Recently developed techniques whereby these two populations can be studied independently were utilized. Resting (unplucked) skin and skin in the middle of the hair growth cycle (10 days after plucking) was studied. the diurnal fluctuations differed at these two stages of the hair cycle. Generally a single minimum level of activity was observed shortly after the beginning of the dark period of the day, i.e. after 18.00 hours.
THE ROLE OF BONE MARROW OF X‐IRRADIATED MICE IN THYMIC RECOVERY
Authors: Blomgren Henric 
Published: May 2008

ABSTRACTThe influence of the bone marrow on the repopulation of the thymus in X‐irradiated mice has been investigated.It was observed that the thymus and a certain population of bone marrow lymphocytic cells were repopulated in parallel in a cyclic fashion. This occurred either after a single exposure of mice to 400 R or after serial weekly X‐ray treatments with 170 R. Lethally irradiated recipients which were grafted with bone marrow cells obtained 12‐24 days after four weekly irradiations of donor mice with 170 R also exhibited a cyclic repopulation of both the thymus and the bone marrow lymphocytic population. In contrast, mice which were transplanted with bone marrow cells from unirradiated donors, containing an equal number of stem cells (CFU), exhibited a continuous rather than a cyclic recovery of both cell populations. the bone marrow stem cells of mice recovering from X‐irradiation were found to have a decreased proliferative activity, since they produced significantly smaller spleen colonies in lethally irradiated recipients than marrow cells from unirradiated mice.The results were interpreted as indicating that the bone marrow lymphocytic cells may act as thymic precursor cells and that thymic lymphopoiesis is dependent on the presence of such cells. Evidently, the production of lymphocytic cells will decrease when the stimulus for granulocyte production increases due to the limited proliferative activity of the surviving bone marrow stem cells after irradiation. This may result in a cyclic variation of the production of bone marrow lymphocytic cells and it follows that thymic lymphopoiesis will run parallel.
COLONY FORMATION IN AGAR: IN VITRO ASSAY FOR HAEMOPOIETIC STEM CELLS
Authors: Dicke K. A. , Platenburg M. G. C. , van Bekkum D. W. 
Published: May 2008

ABSTRACTUsing a method in which embryo fibroblasts were used as feeder layers, the colony forming capacity in agar of a variety of mouse haemopoietic suspensions was compared with their CFUs content. A striking parallelism between the results of the two assays was found. In addition, under certain conditions higher numbers of CFUs could be retrieved from 5‐day‐old agar colonies than were originally plated, indicating that the CFCa (Colony Forming Cell agar) may fulfil the requirements of pluripotency as well as of self‐renewal, both prerequisites for any haemopoietic stem cell candidate. Although our data by no means provide direct proof that the CFCs and the CFCa are identical, they certainly support such a concept. the contradictory findings by others that CFUs and CFUc (Colony Forming Unit culture) can be separated on a velocity gradient is attributed to different culture conditions, in other words, that their CFUcè are not identical with our CFUa.Our findings also indicate that for mouse cells our soft agar colony assay meets the criteria of a quantitative assay for haemopoietic stem cells and that extension of this technique to bone marrow of primates including humans seems to be justified.
SELF‐RENEWAL OF COLONY FORMING UNITS (CFU) IN SERIAL BONE MARROW TRANSPLANTATION EXPERIMENTS
Authors: Vos O. , Dolmans M. J. A. S. 
Published: May 2008

The capacity of stem cells (CFU) for self‐renewal was tested by transplanting normal bone marrow (primary transplantation) and bone marrow which had been subjected to one or two earlier transplantations (secondary and tertiary transplantation) into lethally irradiated syngeneic recipients. It was found that the capacity for self‐renewal is diminished within the first weeks after one or more previous transplantations. This ability of stem cells recovered after a longer interval after the previous transplantation. The time required for this recovery depended upon the number of previous transplantations and amounted to more than 1 or 2 months after one or two transplantations respectively. Shortly after transplantation the CFU/nucleated cell ratio in bone marrow was below normal and its decrease was more pronounced when the bone marrow had been transplanted more often. An increase of the ratio towards normal values was observed in the course of one month after the last transplantation. Measurements of the spleen colony size after transplantation of normal and re‐transplanted bone marrow indicated that CFUs from re‐transplanted marrow gave slightly smaller spleen colonies than those of normal marrow.It is concluded that the decreased self‐renewal of stem cells shortly after previous transplantations is probably not due to a limitation in the number of normal mitoses they can perform, but to a loss of stem cells by transfer to the compartment of differentiating cells.
THE EFFECT OF CHEMOTHERAPY ON THE GROWTH OF LEUKEMIA L1210 II. PERSISTENCE OF A NITROSOUREA‐INDUCED CHANGE IN THE GROWTH CHARACTERISTICS OF TRANSPLANT GENERATIONS
Authors: DeVita Vincent T. , Bray David A. , Bostick Frieda , Bagley Charles M. 
Published: May 2008

A strain of murine leukemia L1210 was treated with subcurative doses of 1,3 bis‐(2‐chloroethyl)‐1‐nitrosourea. When the leukemia cells repopulated the abdominal cavity, aliquots were transplanted to other animals and the growth characteristics measured.A PLM curve obtained twenty‐one generations later had a different configuration than the control line with a prolongation of Ts and Tc. The configuration suggested that treatment with BCNU may have led to the selective growth of a population of cells with a longer Tc and less variation about the mean Tc. Permanent actual alteration of Tc could not be excluded. Measurements of TD also appeared to be affected by the number of tumor cells present on the day of the study. Although Tc was prolonged in drug‐exposed transplanted cell lines, cell loss, which may be influenced by many factors, appears to be the major factor that must be considered in alterations of doubling times in this model tumor system.
FOETAL ERYTHROPOIESIS IN GENETICALLY ANAEMIC, FLEXED‐TAILED (f/f) MICE
Authors: Tarbutt R. G. , Cole R. J. 
Published: May 2008

This paper presents measurements of foetal weights, haemoglobin concentrations, red cell counts, blood volumes, erythroblast thymidine labelling indices and cell cycle parameters in genetically anaemic, flexed‐tailed (f/f) and haematologically normal (f/+) foetuses.The production of red blood cells from the livers of (f/f) foetal mice lags behind that of heterozygote (f/+) foetuses, and the cells that are produced are small and poorly haemoglobinized. The anaemia is not due to an abnormal cell cycle in f/f erythroblasts, which appear to be capable of responding to the anaemia by a small increase in their rates of proliferation. The number of red cells in the foetal circulation can be calculated from the cell cycle time and number of hepatic erythroblasts; the calculated number agrees quite well with the measured number in both f/f and f/+ foetuses. Many characteristics of the anaemia of the f/f foetus can be accounted for if it is assumed that there is a deficiency in the production or activity of an enzyme involved early in the haem synthetic pathway.
AUTORADIOGRAPHIC INVESTIGATION ON THE CELL KINETICS OF CRYPT EPITHELIA IN THE JEJUNUM OF THE MOUSE °CONFIRMATION OF STEADY STATE GROWTH WITH CONSTANT FREQUENCY DISTRIBUTION OF CELLS THROUGHOUT THE CYCLE
Authors: Schultze B. , Haack V. , Schmeer A. C. , Maurer W. 
Published: May 2008

Cell kinetic parameters of cells in the crypt of the jejunum of the mouse were obtained autoradiographically. A number of different methods used in cell proliferation studies were applied to the same animal strain kept under constant conditions. In order to avoid effects of geometrical factors, squashes of isolated crypts were used.The generation time was determined by the per cent labelled mitoses method of Quastler, modified by double labelling with 3H‐ and 14C‐TdR. This modified method permits a more exact determination of the generation time. The duration of the cycle was 14 hr.Double labelling experiments in which an injection of 3H‐TdR was followed by an injection of 14C‐TdR after 1 hr showed that the cell flux was 7.0%/hr at the beginning of the S‐phase and 7.68%/hr at the end. Assuming steady state growth a constant cell flux of 7.15%/hr within the whole cycle can be derived from the measured generation time of 14 hr. These results clearly show that the crypt epithelia constitute a steady state system with constant frequency distribution of the cells throughout the cycle.The per cent labelled mitoses method after a single injection of 3H‐TdR as well as double labelling experiments with 3H‐ and 14C‐TdR give an estimate of the S‐phase of 8.0 or 7.4 hr respectively. Double determinations lead to a value of 0.54 or 0.52 hr respectively for the duration of mitosis and to values of 77% and 72%
THE PROLIFERATIVE CAPACITY OF HAEMOPOIETIC COLONY FORMING UNITS IN THE RAT
Authors: Dunn C. D. R. 
Published: May 2008

ABSTRACTAfter transplantation into rats lethally treated with cytotoxic chemicals both bone marrow and spleen CFU in the spleen and spleen derived CFU in the bone marrow expand with doubling times (Td) of approximately 18 hr. However, bone marrow derived CFU in the bone marrow have a Td of 36 hr. Evidence obtained using tritiated thymidine in vitro and methotrexate in vivo show that the proliferation rate of bone marrow derived CFU is similar in both the bone marrow and spleen and calculations suggest that the different Td between these two sites is due to the higher loss of CFU through differentiation in the bone marrow compared to the spleen. These findings further support the hypothesis of an environment in the spleen which favours CFU self‐maintenance over differentiation with the opposite situation occurring in the bone marrow.
AN ESTIMATION OF PROLIFERATIVE POPULATION SIZE IN STOMACH, JEJUNUM AND COLON OF DBA‐2 MICE
Authors: Kovacs Laszlo , Potten Christopher S. 
Published: May 2008

ABSTRACTLiquid scintillation and autoradiographic techniques have been used to provide quantitative data on the proliferative units, the crypts, of stomach, jejunum and colon of DBA‐2 mice. A slight modification of the crypt squash technique has provided data suggesting that about 50% of the cells of the jejunal crypt are at any given time in the proliferative state. This value is lower in the colon while in the stomach glands only 20% of the cells are involved in cell production. The data provide estimates for cell cycle times of 26·3, 16·0 and 23·2 hr for stomach, jejunum and colon respectively.The size and number of proliferative units have been determined for three regions of the gastrointestinal tract of mice. A review of the literature suggests that considerable strain differences may exist.
PROPERTIES OF HAEMOPOIETIC STEM CELLS IN PHENYLHYDRAZINE TREATED MICE
Authors: Hodgson G. S. 
Published: May 2008

ABSTRACTRecovery of erythropoiesis was fast in Balb/c mice irradiated 700 R 5 days after initiation of phenylhydrazine treatment and took place predominantly in the spleen, which showed numerous large frequently confluent endogenous colonies. Post irradiation phenylhydrazine induced anaemia did not accelerate recovery of erythropoiesis; it did, however, produce a slight but significant rise in endogenous colony formation.Radiosensitivity of spleen CFU‐S from phenylhydrazine treated mice was similar to that of CFU‐S in normal mouse spleen.Spleen CFU‐S in mice 5 days after initiation of phenylhydrazine treatment were sensitive to the lethal action of Hydroxyurea, while bone marrow CFU‐S were not.The self‐renewal capacity of CFU‐S in the endogenously repopulated spleen of phenylhydrazine pretreated 700 R X‐irradiated mice was low when compared to that of spleen exogenously repopulated by cells from normal mouse bone marrow, normal and phenylhydrazine treated mouse spleen. CFU circulating in blood of phenylhydrazine treated mice had a low self‐renewal capacity.The marked strain differences in self‐renewal capacity of spleen CFU‐S, and of the capacity of spleen CFU‐S to increase by proliferation are discussed.
CONTROL OF EPITHELIAL CELL PROLIFERATION IN THE SMALL INTESTINAL CRYPT
Authors: Tutton P. J. M. 
Published: May 2008

ABSTRACTA heat labile factor which has been shown to inhibit proliferative activity in crypt epithelium both in rat jejunum in vivo and in explants of rat jejunum maintained in organ culture has been prepared from the soluble fraction of homogenized epithelial cells isolated from rat small intestinal crypts. The factor appears to have tissue specificity, for it has no influence on epithelial cell proliferation in colonic crypts, oesophagus or skin. Extracts of rat intestinal villous cells prepared using identical techniques were without effect on proliferative activity of small intestinal crypt epithelium.Isoprenalin, which was also found to suppress cell proliferation, did not potentiate the effect of the factor and its effects were evanescent.
IN VITRO AND IN VIVO LABELLING OF ANIMAL TUMOURS WITH TRITIATED THYMIDINE
Authors: Denekamp Juliana , Kallman R. F. 
Published: May 2008

ABSTRACTThe labelling indices obtained by incubating tumour specimens with tritiated thymidine in vitro under hyperbaric oxygen have been compared with those obtained by labelling a matched tumour in vivo. The correspondence between these individual labelling indices is sometimes very poor; however, the average labelling index derived from groups of tumours labelled in the two ways does not differ significantly. There was a large variation from field to field within any tumour, and considerable variation from one tumour to another within each tumour type. The mitotic index was also compared in the matched tumour preparations; the mitotic index in vitro was almost always considerably lower than the values observed in vivo.