bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF CELL CROWDING ON THE IN VITRO REACTIVITY OF NORMAL AND ABNORMAL HUMAN LYMPHOCYTES
Authors: Watkins Sylvia M. , Moorhead John F.
Published: May 2008

The effects of cell crowding on the blastogenic response to phytohaemagglutinin in in vitro cultures of lymphocytes from both normal subjects and from patients with lymphoproliferative disorders were studied. Moderate degrees of cell crowding resulted in enhancement of blast transformation; however, further increases in the degree of crowding produced relative or absolute inhibition of blast transformation, an effect which was more marked in the normal controls than in the lymphoproliferative group. The significance of these findings is discussed.
THE RATE OF DECAY OF THE DOSE EQUIVALENT OF RADIATION INDUCED SUB‐LETHAL DAMAGE
Authors: Liversage W. E.
Published: May 2008

Existing experimental data relating to the rate of recovery of the dose equivalent of sub‐lethal damage are analysed. A precise determination of the half‐life of the dose equivalent is found to be impossible, but all the evidence reviewed suggests that it is of the order of 1 or 2 hr for mammalian systems irradiated at normal body temperature and that, in such systems, little error is produced in dosage calculations by assuming a value of 1.5 hr to be applicable, as originally suggested by Lajtha & Oliver (1961).
HEPATOCYTIC PROLIFERATION IN NORMAL RATS AFTER MULTIPLE EXCHANGE TRANSFUSIONS WITH BLOOD FROM PARTIALLY HEPATECTOMIZED RATS
Authors: Grisham J. W.
Published: May 2008

Either three or four (but not one or two) consecutive exchange transfusions (75–85% washout of blood) of rats with intact livers, utilizing blood from donors partially hepatectomized 24 hr earlier, results in increased incorporation of 3H‐thymidine into hepatic DNA and hepatocytic nuclei 20 hr after the first transfusion. Exchange transfusion with blood from sham‐hepatectomized animals does not produce this effect.
DIFFERENTIATION OF DISEASED HUMAN MUSCLE IN CULTURE
Authors: Skeate Yvonne , Bishop Audrey , Dubowitz Victor
Published: May 2008

Diseased human muscle is capable of differentiation in culture in the same way as normal muscle.
A DELAY IN THE G2 PERIOD OF CULTURED HUMAN LEUCOCYTES AFTER TREATMENT WITH RUBIDOMYCIN (DAUNOMYCIN)
Authors: Brehaut Loreen A.
Published: May 2008

Human leucocytes were cultured for 3 days at 37°C, and during this time treated with rubidomycin (also known as daunomycin) for periods up to 48 hr. The effects of this treatment were studied by examining mitotic indices, uptake of 3H‐thymidine, and patterns of DNA content (measured by microdensitometry on Feulgen‐stained cells). A low concentration of rubidomycin (0.1 μg/ml) caused accumulation of cells in the G2 period, which in turn resulted in a decrease in the mitotic index. A secondary effect was a slight drop in 3H‐thymidine uptake after 12 hr. Higher doses (up to 10 μg rubidomycin per ml) caused an inhibition of DNA synthesis, with accumulation of unlabelled cells between G2 and G2. The probable mode of action of rubidomycin, as presented by earlier authors, is the intrusion of the drug molecule between DNA strands, forming a complex with DNA, and hindering its normal folding. This is discussed with respect to the present findings.
RADIOAUTOGRAPHIC STUDIES OF THE STEM CELL IN THE THYMUS OF THE IRRADIATED RAT
Authors: Everett N. B. , Tyler Ruth W.
Published: May 2008

Radioautographic evidence is presented which characterizes the marrow derived stem cell which promotes thymic recovery following irradiation in the rat. These immigrant cells are similar in morphology to blood monocytes and have been called monocytoid, meaning monocyte‐like in appearance. The typical cell had abundant pale staining cytoplasm and a nucleus with many invaginations and folds and a fine chromatin structure. There was no prominent nucleolus. The majority of these cells entered the thymus of the irradiated rat via the blood vessels into the septa and made their way through the connective tissue to the outer cortex. Three distinct morphological cell types appeared to be derived from the immigrant cells. These were fibrocyte‐like cells which were located within the septa, macrophages located mainly within the medulla and septa, and large blast cells within the cortex, which proliferated giving rise to large thymocytes. The blast cells were characterized as having abundant moderately basophilic (and pyroninophilic) cytoplasm with a distinct cytoplasmic boundary, a large nucleus which still had invaginations and folds, a loose chromatin structure and one or more very prominent nucleoli. They were located in groups primarily within the outer cortex and often adjacent to blood vessels. They were found to be highly susceptible to damage in smear preparations. In contrast, their progeny, the large thymocytes were not highly susceptible to damage in smear preparations but teased out as large round cells with a highly basophilic rim of cytoplasm. The large thymocytes were precursors to medium and small cells.

A radioautographic technique for 1 μ tissue sections is also described.
KINETIC PROPERTIES OF HAEMOPOIETIC STEM CELLS
Authors: Lajtha L. G. , Pozzi Laura v. , Schofield R. , Fox Margaret
Published: May 2008

A comparison of the exocolonizing and autorepopulating tests for haemopoietic stem‐cell assay indicate that the ‘overshoot’in splenic colony formation, observed 12–14 days after 150 rad total‐body radiation (TBR), only occurs with the auto‐repopulation assay. The explanation is that the priming dose of 150 rad increases the absolute seeding rate of stem cells from the marrow. A seeding rate significantly greater than normal can ‘take’only if the spleen is available—it can expand and accommodate stem cells while the bone marrow cannot. If, however, the absolute number of colony‐forming cells are decreased in the femur, a relative increase in seeding rate can take place even in the splenectomized animal. Evidence is presented concerning the different turnover states of exo‐ and autorepopulating stem cells (CFU) and those responsible for erythropoietic response (ERC), and the precursors of agar colony‐formers.
THE EFFECT OF X‐RAY INDUCED SYNCHRONY ON TWO‐DOSE CELL SURVIVAL EXPERIMENTS
Authors: Young Judith M. , Fowler John F.
Published: May 2008

Calculations were made based on experimental data of the variation in radiosensitivity and in cell cycle delay with age in Chinese hamster cells (Sinclair, 1967, 1968). The computed syntheses included: (a) single‐dose survival curves; (b) splitdose recovery curves, the pattern of survival; and (c) two‐dose survival curves, the shape of the second survival curve. It is clear that, after an initial dose, changes occur in the subsequent dose‐response curve which depend upon size of dose and time after irradiation. Following rapid and apparently complete repair of sublethal injury, these changes can be attributed to progression of a partially synchronized population through phases of varying radiosensitivity. These changes may be small in some systems, but important in others. The concept of equal dose‐increments after each of several dose fractions is an over‐simplification and must be used with care.
THE EFFECT OF HYDROCORTISONE ON HeLa CELL GROWTH
Authors: Kollmorgen G. M. , Griffin M J.
Published: May 2008

HeLa Chessen cells have a doubling time of 18 hr when grown in MEM containing 10% calf serum and antibiotics. When hydrocortisone (1.7 μg/ml) is added to exponentially distributed cells in log growth in this medium, a new pattern of growth begins to emerge after 10–12 hr. This pattern is characterized by a transitional state lasting for about 6 hr, and then a new doubling time of about 35 hr is maintained thereafter. Hydrocortisone removes about 5% of the cells from the proliferative pool and extends the generation time of proliferating cells to about 30 hr. The extension of the generation cycle appears to occur almost entirely in late G1.

Cells grown as clones (average 6 cells/clone) prior to the addition of hydrocortisone, undergo these changes with doses as low as 0.00017 μg/ml of medium. When the average clone size is 1.5 cells per clone, the drug concentration must be 0.017 μg/ml or higher to initiate this response.

The HeLa S3 strain continues to grow with an 18‐hr doubling time in the presence of hydrocortisone after a temporary delay in growth occurring between the 12th and 16th hour.
GRAFT SIZE CONSIDERATIONS IN THE KINETICS OF SPLEEN COLONY DEVELOPMENT
Authors: Schofield R. , Lajtha L. G.
Published: May 2008

The kinetics of spleen colony development has been studied after the injection of 106, 105 and 3 × 104 bone marrow cells. The results indicate that:

The CFU population growth rate is independent of cell dose until the logarithmic growth phase is passed. Slowing of growth was seen by day 12 after the highest dose, by day 15 after the median dose, but was not observed during the period of observation after the low dose.

The growth rate of CFU per colony is independent of cell dose, but the curves are not identical. The differences between the curves leads to the conclusion that there is a dose‐dependent delay in the commencement of CFU proliferation. The delay is roughly equal to one cell cycle time between the medium and high inoculum groups and also between the medium and low inoculum groups.

The number of cells per colony is graft size dependent, the doubling times, where these can be roughly assessed, being inversely related to the graft size. From the average number of cells per colony on day 6 it is calculated that the mean doubling time in the early stages of colony development is less than 7 hr.

The proportion CFU:colony cells is dose dependent with the highest inoculum having the highest proportion and the low inoculum group having the lowest proportion.
CYCLES OF REDUPLICATION IN MEGAKARYOCYTE NUCLEI
Authors: Goyanes‐Villaescusa Vicente
Published: May 2008

1. Estimates of the number of dividing megakaryocytes with mitotic apparatus have been obtained in intact and in phenylhydrazine‐papain treated rats.

2. In treated rats chromosome morphology was studied using colchicine and hypotonic treatment.

3. In bone marrow smears and in cultures two systems for nuclear reduplication were demonstrated: C‐mitosis, and multipolar mitosis without cytokinesis.

4. In phenylhydrazine‐papain treated rats, the mitotic index of each bone marrow cell series was greatly increased.
ANALYSIS OF THE KINETICS OF GRANULOSA CELL POPULATIONS IN THE MOUSE OVARY
Authors: Hartmann Niels Rudolph , Pedersen Torben
Published: May 2008

The kinetics of granulosa cell populations in two types of follicles in ovaries of 28‐day‐old Bagg mice are investigated. The analysis includes estimations of mean values and standard deviations of the transit times (TG1, TS, TG2 and TC), the doubling time TD, and the proliferative fraction p.

First the percentage of labelled mitosis curve (PLM‐curve) and the continuous labelling curve (CL‐curve) are estimated. Then a hypothesis concerning the cell kinetics of the granulosa cells in the two follicle types is set up. The normal distribution is chosen to simulate the probability density functions of the transit times. On the basis of the hypothesis mathematical expressions for the PLM‐ and CL‐curves are worked out. By fitting the calculated PLM‐curve to the experimental one it is possible to estimate mean values and standard deviations of TG1, TS>, and TG2. As a test of the hypothesis the CL‐curve is calculated by means of the estimated parameter values and compared to the experimental one. The calculated PLM‐ and CL‐curves are found to be in good agreement with the experimental data as far as both follicle types are concerned.

It is concluded that the method is a useful procedure. The choice of a normal distribution does not imply a significant limitation of the method in these investigations. Moreover it is concluded that the hypothesis is plausible. This means, e.g., that the proliferative fraction is unity in the two follicle types and that there is no cell loss from the cell systems.
RENEWAL OF GOBLET AND PANETH CELLS IN THE SMALL INTESTINE
Authors: Cairnie A. B.
Published: May 2008

Single and repeated injections of 3H‐thymidine were used to demonstrate that both Paneth and goblet cells in the small intestine of the rat undergo renewal but do not themselves proliferate. Goblet cells are renewed much faster than Paneth cells and probably migrate with the columnar cells from the crypts to the villi. Attempts were made to identify the proliferative precursors.
EFFECTS OF BACTERIAL ENDOTOXIN ON HEMOPOIETIC COLONY‐FORMING CELLS IN THE SPLEENS OF NORMAL MICE AND MICE OF GENOTYPE S1/S1
Authors: McCulloch E. A. , Thompson M. W. , Siminovitch L. , Till J. E.
Published: May 2008

Multiple doses of S. typhosa endotoxin caused an increase in the number of hemopoietic stem cells present in mouse marrow and spleen that could be detected using the spleen‐colony assay. This increase was inhibited by Colcemid, and by the genetically‐determined defect in hemopoiesis in mice of genotype S1/S1d. However, the defect in S1/S1d hosts did not prevent an endotoxin‐induced increase in the number of cells capable of forming colonies in cell culture. The results support the view that bacterial endotoxin acts, via a genetically‐controlled regulatory mechanism, to stimulate the proliferation of hemopoietic stem cells in the spleen.
ERYTHROPOIETIN SENSITIVITY OF RAT BONE MARROW CELLS SEPARATED BY VELOCITY SEDIMENTATION
Authors: McCool Dorothy , Miller R. J. , Painter R. H. , Bruce W. R.
Published: May 2008

Rat bone marrow cells have been separated on the basis of their sedimentation at unit gravity. The cell population most responsive to erythropoietin in vitro was found to have a sedimentation velocity of about 6.6 mm/hr. In the process of becoming hemoglobin‐synthesizing cells, it undergoes cell division and its sedimentation velocity decreases to 3.9 mm/hr and then to 2.1 mm/hr, the sedimentation velocity of mature red blood cells.
SOME COMPARISONS OF THE KINETIC PROPERTIES OF FEMORAL AND SPLENIC HAEMOPOIETIC STEM CELLS
Authors: Guzman E. , Lajtha L. G.
Published: May 2008

A slightly different radiosensitivity is confirmed between colony forming units (CFU) in the femur as opposed to those of the spleen. The recovery pattern of the CFU in the femur and in the spleen following sublethal doses of radiation can be markedly different, depending on the radiation dose, particularly concerning the postirradiation ‘dip’. The turnover state of splenic CFU appears to be greater in normal animals than that of the femoral CFU. Hypertransfusion doubles the splenic CFU by the fourth day, while only marginally affecting femoral CFU. Erythropoietin, while increasing the CFU turnover significantly in both femur and spleen of the polycythaemic animal, also increases femoral but not splenic CFU.
PROTEIN SYNTHESIS IN EHRLICH ASCITES CELLS
Authors: Frindel E. , Baserga R. , Brigham P.
Published: May 2008

Rapidly dividing Ehrlich ascites cells have a higher rate of protein synthesis than slowly‐growing cells. This is true whether protein synthesis is measured in vivo or in a cell‐free amino acid incorporating system. A lack of endogenous messenger RNA or a ribosomal defect in stationary cells is suggested as a likely cause of the decreased rate of protein synthesis.

The soluble proteins synthesized by rapidly‐dividing cells are qualitatively different from those synthesized by slowly‐growing cells. The latter also have a larger intracellular pool of several amino acids and a slower protein turnover than rapidly‐dividing cells.
KINETICS OF A DRUG SENSITIVE CLONE OF HeLa CELLS
Authors: Nias A. H. W. , Fox Margaret , Fox B. W.
Published: May 2008

Drug sensitive clones have been isolated from a population of HeLa cells after treatment with methyl methane sulphonate (MMS). One of these clones has now been studied in more detail and some possible mechanisms of drug sensitivity have been related to the proliferation kinetics of the cells of this clone. The cell cycle is elongated and labelling techniques show this elongation to be confined to the G1 phase. Synchronized cultures have shown that the G1 phase is more sensitive to MMS than the S phase. These observations provide some explanation for the drug sensitivity of this clone of cells.
ANTIBODY‐PRODUCING CELLS: ANALYSIS AND PURIFICATION BY VELOCITY SEDIMENTATION
Authors: Phillips R. A. , Miller R. G.
Published: May 2008

Velocity sedimentation cell separation is a simple and reproducible method for obtaining highly enriched populations of viable antibody‐producing cells. Using suspensions of spleen cells prepared from mice immunized with sheep erythrocytes, fractions containing up to 2% 19S‐PFC and 25% 7S‐PFC can be obtained. Granulocytes constitute almost all of the remaining cells in these fractions.

The sedimentation profile of 7S‐PFC is very broad in comparison with that of cell populations known to be homogeneous in size (e.g. mouse erythrocytes). Analysis of the profile of 7S‐PFC at different times after immunization suggests that the heterogeneity arises largely from the doubling in cell volume as a cell moves from one mitosis to the next. Early in the immune response, when the majority of the PFC are proliferating, the variation in sedimentation velocities is consistent with such a two‐fold variation in cell volume. Late in the response, when most PFC have stopped proliferating, the sedimentation profile is more homogeneous. This analysis suggests that the fractionation procedure is sensitive enough to separate PFC according to their position in the cell cycle.

Sedimentation velocities were also measured for several other classes of cells found in spleen. Comparison of these values shows that sedimentation velocity is a useful parameter for characterizing different types of cells.
THE USE OF 59Fe UPTAKE FOR THE EVALUATION OF CELL PROLIFERATION IN SPLEEN COLONIES
Authors: Siracusa G. , Silini G. , Bricanti G.
Published: May 2008

A technique of 59Fe uptake in the spleen of irradiated bone‐marrow‐transplanted mice has been applied to the study of some kinetic parameters of the erythroid spleen nodule cells. Measurements of the doubling time of this population have been obtained together with estimates of radioactivity disappearance from the spleen, owing to a release of nodule cells into the blood stream. The kinetics of expansion of the erythroid cell compartment is compared with the pattern of increase of the colony‐forming cells in the spleen. The expansion of the erythroid cell population seems to be the result of at least two processes: an increase in the number of differentiating cells and the release of mature cells into the blood stream. It is suggested that more refined attempts to evaluate kinetic parameters of the spleen nodule cell population should allow for these factors.
CELL CYCLE CHARACTERISTICS OF HUMAN SOLID TUMORS IN VIVO
Authors: Young Robert C. , DeVita Vincent T.
Published: May 2008

The duration of the DNA synthetic phase of solid tumors in six patients was determined in vivo by local injections of tritiated thymidine into tumor nodules on the skin and serial biopsies of the lesions. Labeled mitosis curves constructed from the data obtained revealed a distinct wave of labeled mitoses but no evidence of a second wave of DNA synthesis in all six patients. The duration of S phase was 24, 22 and 24 hr in the three patients with malignant melanomas and 19, 22 and 24 hr in the three patients with breast cancer. The method is relatively simple and requires much lower doses of tritiated thymidine; reproducible data are obtainable in patients with solid tumors in a much shorter period of time than with previous experiments.
STUDIES ON LYMPHOCYTES
Authors: Ruchti C. , Cottier H. , Cronkite E. P. , Jansen C. R. , Rai Kanti R.
Published: May 2008

Continuous extracorporeal irradiation of the circulating blood (ECIB) of from 3 to 501/2 hr duration was used to study in the calf the differential depletion of lymphocytes from spleen, lymph nodes and thymus as compared to blood and thoracic duct lymph. The cell content of tissues was measured by planimetry and/or test point analysis. Lymphocyte depletion by ECIB from various lymphoreticular organs, and from different areas within a given organ, was less than in the circulating blood or the thoracic duct lymph and varied from one site of a lymphoreticular organ to another. The degree of depletion with time followed an exponential function with at least two components. The first component corresponded to a relatively rapid fall and the second to a very slow reduction in lymphocyte content. The former is related to the elimination of an easily mobilizable pool of lymphocytes while the latter corresponds to a more sessile mass of lymphocytes which exchange with blood lymphocytes very slowly. Elimination of the easily mobilizable pool of lymphocytes by ECIB from all tissues studied was observed within 10–15 hr, indicating that the rate of exchange with blood is similar for this group of cells in various lymphoreticular tissues. The size, however, of the easily mobilizable vs the more sessile pools of lymphocytes may vary considerably, the best estimates for the former being as follows (in per cent of total lymphocyte mass): lymph node medulla, less than 10%; lymph node cortex plus paracortical zone, 18% (depletion mainly paracortical); red pulp of the spleen, 37%; densely populated white pulp of the spleen, 55%; and loosely populated white pulp of the spleen, 60%. In comparison, the approximate fractions of lymphocytes originating fromthe easily mobilizable pools in various lymphoreticular tissues plus the cells already circulating a t the onset of EClB correspond to 64% for the thoracic duct lymph and 78% for the circulating blood respectively. These findings are discussed in relation to production, recirculation and life span of lymphocytes, and immune reactions.
OPTIMIZED PARAMETERS FOR THE MITOTIC CYCLE
Authors: Barrett John C.
Published: May 2008

A method is described for the maximum likelihood estimation of the six parameters representing the means and standard deviations of the phases G1, S and G2 of the mitotic cycle. The likelihood is not explicitly formulated but is computed by the Monte Carlo program which evaluates the percentage of mitotic cells labelled with 3H‐thymidine. The method is applied to data obtained from an experiment performed with transplanted Marshall rat mammary tumours.
PROLIFERATION KINETICS IN EPITHELIUM OF GUINEA‐PIG COLON
Authors: Sawicki W. , Rowinaski J.
Published: May 2008

Autoradiographs of crypts of guinea‐pig colon labelled with 3H‐thymidine were quantitatively analysed. The analysis involved: (a) comparison of proliferation parameters in crypts situated in two well‐defined regions of colonic folds, i.e. in the top and the basal parts of the fold, and (b) comparison of proliferation parameters in the lower and in the upper parts of an individual crypt. The results provide evidence that: (1) Crypts situated in the top region of folds are significantly longer than those situated in the basal region. (2) The duration of cell cycle and its phases is similar in the crypts of the two regions examined. (3) The rate of 3H‐thymidine uptake is higher in the middle than in the initial and final parts of the S phase, and its pattern is the same for the crypts of the two regions of the fold as well as for the parts of the individual crypt. (4) The proliferating pool size is larger in crypts situated in the top than in the basal region of the fold. (5) The proliferating pool size is larger in the lower parts of crypts from each region than in the upper parts.

Control of cellular proliferation in the crypt epithelium is considered to operate separately at the level of the individual crypt and at the level of a group of crypts situated in a given region of the colonic wall.
CYTOKINETIC ANALYSIS of SLOWLY PROLIFERATING BONE MARROW CELLS DURING RECOVERY FROM RADIATION INJURY
Authors: Haas R. J. , Bohne F. , Fliedner T. M.
Published: May 2008

A continuous administration of tritiated thymidine (3H‐TdR) into pregnant rats results in a complete labelling of the offspring. Further injections with 3H‐TdR for 26 days maintained the 100% labelling. Four weeks after discontinuation of 3H‐TdR application, distinct classes of cytokinetically resting labelled bone marrow cells were detected. These animals received X‐irradiation of the body with 750 R with one leg shielded, or X‐irradiation of one leg with 750 R, or X‐irradiation of one leg with 1500 R. In none of the experiments did the reticular and endothelial cells show indications of destruction or stimulation.

In all X‐irradiated parts the small bone marrow lymphocytes decreased their labelling intensity. the same behaviour was seen in the marrow of the shielded leg. After 1500 R to one leg, a subsequent rise of mean grain count was detected after 3 days. No change of the labelling pattern of lymphocytes of other organs could be observed.

The behaviour of labelled bone marrow lymphocytes during recovery from radiation injury suggests that these cells play a role in the regenerative process of bone marrow. There may be a migration from shielded areas into X‐irradiated parts if the dose is high enough to prevent efficient endogenous regeneration.
A STUDY ON INEFFECTIVE ERYTHROPOIESIS IN THE DOG
Authors: Odartchenko Nicolas , Cottier Hans , Bond Victor P.
Published: May 2008

Erythrocytic cell kinetics were studied in normal dog bone marrow, at the transition between younger cells that are able to synthesize DNA, and more mature nucleated normoblasts which have lost this ability. the rate of progression out of the first group was compared to that into the second, after necessary adjustments of group sizes. No significant discrepancy was detected within the limits of resolution of autoradiographic cytokinetic analysis.

It is concluded that ‘ineffective’ red cell production in the normal dog, if it occurs at all, can only be very small in quantity.
THE DISTRIBUTION OF CELL GENERATION TIMES
Authors: Kubitschek H. E.
Published: May 2008

Two different distributions of generation times, log‐normal and reciprocal normal, were compared by fitting them to experimental generation time distributions for bacteria, yeast, protozoa, and mammalian cells. In every case, the reciprocal normal distribution gave better agreement, whether the original frequency distributions or their cumulatives were compared. the log‐normal distribution failed to give significant agreement for three of the original distributions. It is concluded that the reciprocal normal distribution of generation times, or more precisely, the truncated normal distribution of generation rates, is consistent with the published data for steady state populations of all kinds of cells that divide by regular binary fission. A model is suggested for this distribution of generation times, associating it with control of transport of materials into the cell, and with linear cell growth.
AN EVALUATION OF RADIOIODINE‐LABELED 5‐IODO‐2′‐DEOXYURIDINE AS A TRACER FOR MEASURING CELL LOSS FROM SOLID TUMORS*
Authors: Dethlefsen Lyle A.
Published: May 2008

Radioiodine‐labeled 5‐iodo‐2′‐deoxyuridine (IUdR) has been evaluated as a tracer for measuring cell loss from C3H mouse mammary tumors. This has been accomplished by considering the problems of label specificity, chemical and radiation toxicity, and reutilization; and by comparing the estimate for cell loss, as obtained here, to another independent estimate previously reported for tumors from the same slow‐growing line.

125I‐IUdR is the current tracer of choice for measuring cell loss from undisturbed solid tumors, and this method is simpler and more direct than the combined techniques of autoradiography and volumetric‐growth‐curve analyses. However, the following limitations apply: (1) the tumor DNA must be extracted prior to counting the radioactivity in the DNA, (2) one must be especially concerned with the chemical and radiation toxicity and they should be evaluated in each new situation, and (3) one must realize the potential for low levels of IUdR reutilization even in the undisturbed tumor. In perturbed situations (i.e. chemical or radiation induced killing) this problem may become severe.
THE KINETICS OF GRANULOSA CELLS IN DEVELOPING FOLLICLES IN THE MOUSE OVARY
Authors: Pedersen Torben , Hartmann Niels Rudolph
Published: May 2008

This investigation describes the kinetics of the granulosa cells in medium‐sized follicles type 3b, 4 and 5a in ovaries of 28‐day‐old Bagg mice. the method of labelling with 3H‐thymidine followed by high resolution autoradiography is used in the experimental work, which consist of determining percentage labelled mitosis (PLM‐) and continuous labelling (CL‐) curves. In order to analyse the data by computer two alternative hypotheses A and B are set up. Both include the assumptions of no cell loss, exponential growth and a resting compartment Q. In hypothesis A cells from Q re‐enter the mitotic cycle via the normal DNA‐synthesis compartment Sp. Hypothesis B includes beside compartment Sp a special DNA‐synthesis compartment Sq where only cells from Q are synthesizing DNA, and these cells re‐enter the mitotic cycle via the G2 compartment. the mean transit time in Sq is considered to be longer than the mean transit time in Sq. On the basis of the hypothesis mathematical expressions for the PLM‐ and CL‐curves are obtained, and by means of a computer the theoretical curves are fitted to the experimental values: thereby all relevant cell kinetical parameters are estimated. Hypothesis B seems to give the best fit between the theoretical and experimental curves. the estimated parameters are: mean cycle times, μc= (56.1 hr, 56.1 hr and 22.3 hr for type 3b, 4 and 5a respectively), doubling times, TD= (96.4 hr, 118.6 hr and 59.1 hr) and the proportion of cells in Q, pQ= (0.60, 0.71 and 0.69).
MEDIUM DEPLETION AND CONTACT INHIBITION OF REPLICATION: ABSENCE OF A SPECIFIC INHIBITOR
Authors: Smets L. A.
Published: May 2008

The role of medium exhaustion in the regulation of contact inhibition of growth was studied in 3T3 cells and various other mammalian cell lines. the concept of a diffusable inhibitor which sustains contact inhibition was not supported by the experimental results. Used medium could be restored by dialysis against a fresh one and also by the addition of nutritional constituents of low molecular weight.

The growth properties of several mammalian cell lines were studied. the results revealed an inverse correlation between the sensitivity to contact phenomena and the efficiency to utilize nutrients from the medium for replication.
RESPONSE OF THE PREOSTEOBLAST AND STEM CELL OF RAT BONE MARROW TO A LETHAL DOSE OF X‐IRRADIATION OR CYCLOPHOSPHAMIDE
Authors: Amsel Sheldon , Dell Elisabeth S.
Published: May 2008

Following syngeneic or autotransplantation of hemopoietic tissue to a heterotopic location, bone formation has been observed to occur in the implanted tissue. the characteristics of the cell residing in hemopoietic tissue with bone forming potential (preosteoblast) are unknown. to define some properties of this cell, its response to X‐irradiation and cyclophosphamide (CTX) was compared to the response of the hemopoietic stem cell. Adult, male rats were exposed to 900 R whole body X‐irradiation or 220 mg/kg of intraperitoneal CTX. With either treatment the dose was sufficient to kill the animals by bone marrow failure. At intervals following the X‐irradiation or CTX, hemopoietic tissue was examined for the presence of viable hemopoietic stem cells and preosteoblasts. Following X‐irradiation, viable hemopoietic stem cells and preosteoblasts could not be detected. Following CTX these cells could be detected. It is suggested that in the rat CTX at 220 mg/kg, although causing death by bone marrow failure, does not reduce the population of the preosteoblast or hemopoietic stem cell as effectively as 900 R X‐irradiation.
A COMPARISON OF METAPHASE ARRESTING AGENTS AND TRITIATED THYMIDINE AUTORADIOGRAPHY IN MEASUREMENT OF THE RATE OF ENTRY OF CELLS INTO MITOSIS IN THE CRYPTS OF LIEBERKÜHN OF THE RAT
Authors: Clarke Rufus M.
Published: May 2008

Three methods of estimating cell production rate were used: the rate of accumulation of metaphases blocked by Colcemid, or by vinblastine, and the rate of increase of labelled nuclei after administration of tritiated thymidine. These rates were determined for three sites in the small intestine by counts made on whole micro‐dissected crypts, fixed at various times after the administration of the agents.

Within the limits of error of the methods, the cell production rate per crypt was the same when measured by each method (35/hr), and showed a slight fall from the proximal to the distal end of the small intestine (36/hr to 33/hr). the advantages and limitations of each method are discussed.
STUDIES ON LIVER REGENERATION: I. 131IODODEOXYURIDINE AS A PRECURSOR of DNA IN NORMAL and REGENERATING RAT LIVER
Authors: Bürki K. , SCHAER J. C. , Grieder A. , Schindler R. , Cottier H.
Published: May 2008

Abstract. 131Iododeoxyuridine (131IDU) was injected into normal and partially hepatectomized rats, and the specificity of incorporation of this thymidine analogue into liver DNA was determined 2, 24 and 48 hr following intramuscular injection. At 2 and 24 hr after 131DU injection, a major proportion of radioactivity in the liver was in the acid‐soluble fraction, whereas 48 hr after injection the label in the acid‐soluble fraction had decreased considerably. In liver obtained 2 hr after injection of 131IDU, only 1.8–16.6% of the total radioactivity were in DNA. If, however, the tissue was subjected to formalin fixation, the acid‐soluble label was extracted selectively, and of the remaining radioactivity 64–88% was in DNA. Therefore, the radioactivity that is not extracted by formalin may be used as a measure of DNA synthesis at the time of injection of 131IDU, thus obviating time‐consuming biochemical fractionation procedures.
The Effect of Radiation Upon Lymphocyte Response to Pha
Authors: RICKINSON A. B. , ILBERY P. L. T.
Published: May 2008

Abstract. The proliferative response of lymphocytes to phytohaemagglutinin has been studied following incremental doses of 60Co gamma radiation delivered at the beginning of culture. A dose‐dependent inhibition of 3H‐thymidine uptake is apparent in 48 hr and 72 hr cultures throughout the 250–2000 rad range, and the effect appears more marked at the later labelling time. Parallel autoradiographic studies have revealed changes in the cell cycle kinetics of irradiated cultures which underlie the effects observed at the whole‐culture level. Irradiation reduces the number of cells reaching the first period of DNA synthesis and causes dose‐dependent delays at specific points in the cycle of proliferating cells.
Direct Measurement of the G1 Phase In Meristematic Cells At Two Different Temperatures
Authors: Giménez‐Martín G. , González‐Fernández A. , De La Torre C.
Published: May 2008

Abstract. The duration of the G1 period in meristematic cells has been measured directly at two different temperatures by using a synchronous cell population ‘labelled’ as binucleate by treatment with caffeine. By studying the uptake of a radioactive DNA‐precursor, it proved possible to determine the duration of the G1 period in relation to the total interphase duration, at two temperatures tested, and to demonstrate that the relationship remained constant.
The Effect of Thermal Shock On the Division Cycle of Meristematic Cells
Authors: De La Torre C. , González‐Fernández A. , Giménez‐Martín G. , Léópez‐Sáez J. F.
Published: May 2008

Abstract. The dynamic adaptation of a meristem to a thermal change from 15 to 35°C has been studied. A gradual drop occurs in the mitotic index during the first 6 hr after the change, while the percentage of prophases drops less steeply. At the same time the phenomenon of nucleolar segregation is observed.

By making use of a cell population morphologically differentiated as binucleate (by ‘labelling’ with caffeine), it was possible (a) to prove that prophase is specifically prolonged and (b) to locate a highly thermosensitive segment of interphase, situated in the middle of the S period, and apparently coinciding with the sub‐period S2, described in the same material as characterized by a decrease in the rate of DNA synthesis.

The lengthening of prophase and nucleolar segregation resemble the effects produced by drugs which inhibit RNA synthesis.

Intermittent thermal shocks are suggested as a possible means for synchronizing the division cycle of plant cells.
CELL CYCLE COMPARTMENT ANALYSIS OF CHINESE HAMSTER CELLS IN STATIONARY PHASE CULTURES
Authors: Ross D. W. , Sinclair W. K.
Published: May 2008

The distribution of Chinese hamster cells with respect to the compartments of the cell generation cycle was studied in cultures in the stationary phase of growth in two different media. A measure of the state of depletion of the nutrient medium was formulated by defining a quantity termed the nutritive capacity of the medium. This quantity was used to verify that the cessation of cell proliferation is due to nutrient deficiencies and not to density dependent growth inhibition. Cell cultures in stationary phase were diluted into fresh medium and as growth resumed, mitotic index, cumulative mitotic index, label index and viability were measured as a function of time. The distribution of cells with respect to compartments of the cell generation cycle in stationary phase populations was reconstructed from these data. Stationary phase populations of Chinese hamster cells that retained the capacity for renewed growth when diluted into fresh medium were found to be arrested in the G1 and G2 portions of the cycle; the relative proportion of these cells in G1 increased with time in the stationary phase, but the sequence differs in the two media. In early stationary phase, in the less rich medium, more cells are in G2 than in G1. Also in this medium a fraction of the population was observed to be synthesizing DNA during stationary phase, but this fraction was not stimulated to renewed growth by dilution into fresh medium.
EFFECTS OF ACTINOMYCIN D AND PUROMYCIN ON THE CELL PROGRESS FROM M TO G1 AND S STAGES IN CULTURED MOUSE LEUKEMIA L5178Y CELLS
Authors: Doida Y. , Okada S.
Published: May 2008

Actinomycin D (0.5 μg/ml) did not prevent M stage cells from entering G1 stage, but blocked their progress from G1 to S stage. The position of the block was approximately 1.4 hr before S stage or just after the beginning of G1 stage. Actinomycin D in this concentration also significantly depressed uridine‐3H uptake into G1 stage cells, but did not suppress leucine‐3H uptake by M and G1 cells. This suggests that some proteins may be synthesized in M and G1 stage cells by messenger RNA left over from the previous cell cycle. However, entry of G1 cells into S stage would require synthesis of new messenger RNA near the beginning of G1 stage. Puromycin (10 μg/ml) did not prevent M cells from entering G1 stage, but blocked their progress from G1 to S stage. The site of blockage was about 0.7 hr before S stage or in the first two‐third of G1 stage. This might be the site where the cells synthesize new G1 proteins necessary for entry to S stage.

Comparison of sensitivities of G1 and G2 stages to the two antibiotics reveals that the puromycin sensitivity of G1 cells was similar to that of G2 cells, but the actinomycin D sensitivity of G1 was greater than that of G2 cells.
AN ANALYSIS OF BONE MARROW ERYTHROPOIESIS IN THE MOUSE
Authors: Covelli V. , Briganti G. , Silini G.
Published: May 2008

Following the model of the erythropoietic system developed in the rat by Tarbutt and Blackett, the authors have carried out a kinetic analysis of bone marrow erythropoiesis in the mouse.

Using 59Fe labelling techniques the size of the recognizable precursor cells and of the functional cell compartments have been estimated, while the flow‐rate from the unrecognized precursor cells to the recognizable cells and from the latter compartment to the circulating erythrocytes have been evaluated by 55Fe autoradiography.

Differences in the kinetic parameters of the erythropoietic mouse bone marrow compared with the rat bone marrow are reported, whose interpretation has required a more detailed analysis of the original model.
DNA‐SYNTHESIS TIME OF BONE MARROW CELLS IN HEALTHY AND ASCITES TUMOR‐BEARING MICE
Authors: Lala P. K.
Published: May 2008

DNA‐synthesis (S) times of myelocytes and nucleated erythroid cells in the bone marrow of healthy mice as well as mice bearing advanced Ehrlich ascites tumors were measured with the aid of a combined in vivo‐in vitro double isotope labeling technique. Neither the S‐period nor the rate of proliferation of these cells were influenced by the presence of the tumor in these hosts. This finding discounts the possibility that the marked retardation of DNA‐synthesis and proliferation rate observed in the tumor cells themselves with advancing tumor‐age is a nonspecific effect of the nutritional deterioration in the host.
THE CELL CYCLE IN TUMOURS: AN EXAMINATION OF DATA GAINED BY THE TECHNIQUE OF LABELLED MITOSES
Authors: Steel G. Gordon
Published: May 2008

Published data from a large series of investigations by the technique of labelled mitoses have been analysed using a process of computer simulation. The results of the analyses of tumour data are discussed, first from the point of view of the quality of simulation that can be achieved and secondly as a review of the extent of our knowledge of the intermitotic time of cells in tumours. Particularly in primary tumors the data are often consistent with a broad distribution of intermitotic times within a tumour and the use of the term ‘cell cycle time’may be misleading.
THE DISTRIBUTION AND DIFFERENTIATION OF LYMPH‐BORNE IMMUNOBLASTS AFTER INTRAVENOUS INJECTION INTO SYNGENEIC RECIPIENTS
Authors: Hall J. G. , Parry Dilys M. , Smith Marilyn E.
Published: May 2008

Thoracic duct lymph from inbred, hooded rats was collected 3–5 days after antigenic stimulation of the caudal lymph nodes. During this period the lymph contained 10–15% of large, basophilic lymphoid blast cells (immunoblasts). By incubating the lymph cells at 38.C with radioactive DNA precursors, either 3H‐thymidine or 125I‐deoxyuridine, the immunoblasts became labelled but the small lymphocytes did not. The lymph cells were then washed and injected intravenously into syngeneic recipients which were killed after various intervals up to 24 hr so that the radioactivity of their organs could be assayed by scintillation counting and autoradiography.

The main finding was that in animals killed after 4 or more hours the small gut always contained most of the recoverable activity and autoradiographs showed that this was because the injected cells had infiltrated the lamina propria in large numbers. Earlier, many of the injected cells were retained temporarily in the lungs, liver and spleen but many of them soon left those organs and entered the lamina propria of the small gut.

An electron microscope study of autoradiographs showed that 24 hr after injection the cells which entered the lamina propria of the gut had differentiated into plasma cells so that they displayed abundant, lamellar endoplasmic reticulum.
HAEMOPOIETIC STEM CELLS IN EXPERIMENTAL HAEMOLYTIC ANAEMIA
Authors: Hodgson G. S. , Bradley T. R. , Telfer P. A.
Published: May 2008

Phenylhydrazine treatment produced an expansion of spleen CFU (10 x N) and an even greater expansion of spleen ACFU (40 x N). Blood CFU and ACFU levels also increased. While marrow CFU did not change marrow ACFU showed a pronounced drop. The ratio of ACFU/CFU varied between tissues, it was highest in marrow and lowest in peripheral blood. The changes in CFU, ACFU and blood granulocytes are discussed in relation to the radioprotective action of phenylhydrazine pretreatment of mice.
THE CELL POPULATION KINETICS OF NEUTROPHILIC CELLS
Authors: Constable T. B. , Blackett N. M.
Published: May 2008

Autoradiographic data for the entry of tritiated thymidine labelled cells into the post‐proliferative neutrophilic cell compartments following a single injection of isotope have been analysed in terms of two cell kinetic models which differ in the assumed relationships between cell maturation and division. Comparisons with the experimental data were made in an attempt to assess the validities of the models, and kinetic parameters for the compartments of recognizable neutrophilic cells were estimated. Control mechanisms which have been proposed for the granulocyte system are discussed in terms of the kinetic models which were chosen in their determination. Although it was not possible to make a clear choice between the proposed models, preference was established for a random model which did not involve cell loss.
RELATIONSHIP OF BONE MARROW CELLULARITY AND PROLIFERATIVE ACTIVITY: A LOCAL REGULATORY MECHANISM
Authors: Patt Harvey M. , Maloney Mary A.
Published: May 2008

An analysis has been made of tritiated thymidine (3H‐TdR) uptake and cellularity in normal and regenerating marrow. Comparison of right and left femoral marrow in ninety normal rabbits has revealed a significant negative correlation (−0.75) between thymidine uptake per presumptive proliferative cell and the concentration of such cells. Locally irradiated marrow follows the normal marrow regression down to about 40% relative cellularity and then shows an upward displacement. The regenerating mechanically depopulated marrow manifests a similar displacement over the entire cellularity range studied which suggests that recovery was not yet complete as in the case of some of the irradiated marrow samples. The negative regression of 3H‐TdR uptake on cellularity is not a consequence of altered thymidine availability, but rather of‐a changing DNA synthesis rate and/or a changing fraction of proliferative cells. Since 3H‐TdR uptake per presumptive proliferative cell reflects cell production, it follows that cell production is geared to the cellularity of a discrete marrow area. This provides a local self‐regulating mechanism.
CELL PROLIFERATION KINETICS IN GOLDFISH ACCLIMATED TO VARIOUS TEMPERATURES
Authors: Garcia M. Nieto , Johnson H. A.
Published: May 2008

Cell proliferation has been studied in goldfish which have been acclimated to temperatures of 6, 10, 15, 20, 30 and 37°C. Hemopoietic tissue and intestinal epithelium show similar temperature effects, but they are seen more clearly in the latter. The fraction of intestinal epithelial cells labeled by a single injection of tritiated thymidine decreases as the temperature increases above 20°C. The total tissue incorporation of DNA precursor also decreases with increasing temperature. On the other hand, the grain counts per nucleus tend to increase slightly with increasing temperature. The mean generation time as indicated by the rate of DNA turnover (loss of 125I‐DNA) shows little if any change as the temperature increases above 20°C. These observations imply that in the rapidly proliferating cells of the goldfish the mitotic cycle is remarkably insensitive to temperature change, except for the DNA synthesis phase, which has a temperature dependence (Q10= 2.6) characteristic of enzyme‐mediated chemical reactions.
VARIATION IN THE DURATION OF MITOSIS IN THE CRYPTS OF LIEBERKUHN OF THE RAT; A CYTOKINETIC STUDY USING VINCRISTINE
Authors: Wright Nicholas , Morley Adrian , Appleton David
Published: May 2008

The variation in the duration of mitosis (tm) with cell position in the small intestinal crypts of the adult rat has been measured by a stathmokinetic technique using vincristine. The value for the whole crypt column was 0.43 hr, or 26 min. At the bottom of the crypt tm was in excess of 1 hr, but rapidly decreased and throughout the greater part of the proliferative compartment was between 0.40 and 0.50 hr. At the top of the proliferative compartment an increase in tm was demonstrated.

If the value of 0.43 hr for the whole crypt column is correct, then one argument for postulating the formation of metabolic DNA during differentiation in the small bowel epithelium of the rat becomes invalid. Variations in tm within the crypt have been shown to increase the values of cell velocity obtained from cumulative birth rate diagrams. Finally further evidence has been presented for the existence of a slowly dividing subpopulation of cells at the base of the crypt. These cells may be important in crypt repopulation after damage with phase specific anti‐tumour drugs.