bluuebunny/crossref_metadata_2025 huggingface dataset:
CELL KINETICS IN DIFFUSION CHAMBERS: SURVIVAL, RESUMPTION OF PROLIFERATION, AND MATURATION RATE OF MURINE HAEMOPOIETIC CELLS
Authors: Benestad Haakon B.
Published: May 2008

Bone marrow cells and blood leucocytes from mice have been cultured in vivo in diffusion chambers. Granulocytes and macrophages were formed in the chambers, whereas lymphocytes and mature end cells were gradually lost.

The proliferation, differentiation and death of cultured cells were quantified by total and differential cell counting, by scintillation counting and by radio‐autographic evaluation of 3H‐thymidine incorporation. Hydroxyurea and vinblastine were used as cytotoxic agents.

Ordinarily 40–60% of the cells inoculated could not be recovered after a few hours in culture. Proliferative cells resumed DNA synthesis shortly after implantation, and the rate of synthesis did not decline on further culturing. Steady‐state progenitor cells had a pre‐replicative lag period of about 18 hr, whereas regenerating progenitors started to synthesize DNA after about 14 hr. After 72 hr of culturing newly formed segmented granulocytes were detected. Maturation from the myelocyte to the segmented granulocyte stage lasted about 18 hr. Eosinophilic granulocytes had a long life span in the chambers, whilst the segmented neutrophils were rapidly eliminated after a life span estimated to be about 2 days.
MOBILIZATION OF HAEMOPOIETIC STEM CELLS (CFU) INTO THE PERIPHERAL BLOOD OF THE MOUSE; EFFECTS OF ENDOTOXIN AND OTHER COMPOUNDS
Authors: Vos O. , Buurman W. A. , Ploemacher R. E.
Published: May 2008

Factors affecting the circulation of haemopoietic stem cells (CFU) in the peripheral blood of mice were investigated. I.v. injection of sublethal doses of endotoxin, trypsin and proteinase appeared to raise the number of CFU per ml blood from about 30–40 to about 300–400 or more within 10 min. The effect was smaller when smaller doses of the substances were injected. After this initial rise the number of circulating cells returned to normal in a few hours. Following endotoxin there was a second rise which started 2–3 days after injection and attained a peak on the 6th–7th day. The first rise is explained as a mobilization of stem cells from their normal microenvironments into the blood stream; the second rise is considered to reflect proliferation of CFUs in the haemopoietic tissues. The spleen seems to be acting as an organ capturing CFUs from the blood and not as a source adding stem cells to the blood.

The early mobilization of CFU after endotoxin injection did not coincide with a mobilization of neutrophils. The number of circulating band cells was increased during the first hours.

The importance of ‘open sites’in the haemopoietic tissue for capturing CFUs was studied by emptying these sites through a lethal X‐irradiation and injecting normal bone marrow cells. When a greater number of syngeneic bone marrow cells was injected intravenously, the level of circulating CFU in irradiated mice was slightly lower than the level in unirradiated mice during the first hours.
INFLUENCE OF HAIR PLUCKING ON THE TURNOVER TIME OF THE EPIDERMAL BASAL LAYER
Authors: Hamilton Elizabeth , Potten C. S.
Published: May 2008

The epidermal cell kinetics of male DBA‐2 mice have been studied using tritiated thymidine. Liquid scintillation data from skin punches, taken after stimulation of hair growth by plucking, agree well with similar data from DBA‐1 mice. A technique has been devised for obtaining sheets of epidermal cells from haired mice. Labelling index values from these sheets show that epidermal proliferation increases after plucking and they agree well with values obtained from sections. Counts of cells per unit area of epidermis show that cells are removed by plucking.

Using an estimated value for the length of S, the turnover time of the basal layer was calculated. The growth fraction and proliferative cell cycle time have also been estimated.
TEMPERATURE AND DNA TURNOVER IN THE GOLDFISH
Authors: Nieto Manuel , Johnson Horton A.
Published: May 2008

Whole body DNA turnover in the goldfish, as measured by the rate of loss of incorporated 125I‐deoxyuridine, is remarkably invariant over a temperature range of 30 centigrade degrees. Apparently cell proliferation kinetics in this poikilotherm do not simply reflect chemical reaction rates but are under some sort of homeostatic control with respect to temperature. At the nearly lethal temperature of 37°C the rate of cell turnover increases and the absolute number of proliferating cells decreases.
HYDROXYUREA EFFECTS IN THE C3H MOUSE: I. DUODENAL CRYPT CELL KINETICS
Authors: Dethlefsen Lyle A. , Riley Reba M.
Published: May 2008

Duodenal crypt cell kinetics in C3H mice have been studied before and after the injection of a single dose (3 mg/g body weight) of hydroxyurea (HU). This was done by autoradiographic analysis of crypt cells which had been labeled with tritiated 5‐iodo‐2′‐deoxyuridine. This dose of HU kills the cells which are synthesizing DNA at the time of injection, inhibits DNA synthesis completely for 4–5 hr, and causes a partial synchronization of the cells when they recover from the inhibitory effects of HU. Duodenal crypt recovery is manifested by a decrease in the mean cell cycle time, an increase in the proliferating fraction, and a lengthening of the crypts. The acute cellular responses are apparently complete within 24–48 hr, but the length of the crypt has not returned to normal by 48 hr after HU administration.
COMPUTER SUBTRACTION OF BACKGROUND IN AUTORADIOGRAPHY WITH TRITIATED THYMIDINE
Authors: Benassi Marcello , Paoluzi Renato , Bresciani Francesco
Published: May 2008

An iterative method is suggested to estimate true labelling index even when background and experimental (background + true labelling) grain count distributions appear to be incompatible, generally a result of unavoidably insufficient counting in routine work. A computer program applying the iterative method has been written in Fortran IV for an IBM 1130 machine. This program, available on request, displays grain count distributions before as well as after correction and computes the labelling index and average grain count per labelled cell, with respective variance and standard errors.
STIMULATION OF DNA SYNTHESIS BY ISOPROTERENOL IN RAT SUBMANDIBULAR GLAND DURING POSTNATAL GROWTH
Authors: Barka Tibor , Chang William W. , Van der Noen Hendrika
Published: May 2008

The post‐natal growth of rat submandibular gland and the effect of isoproterenol on this process were studied. Between 2 and 42 days of age the DNA content of the gland increased linearly but the increase in RNA and protein content was more rapid after 29 days of age. The RNA: DNA and protein: DNA ratio increased linearly with age. The proliferative activity, measured by the incorporation of tritiated thymidine, was maximum in the gland of 7‐day‐old rats. It declined steadily to a low level in 42‐day‐old rats. A single injection of isoproterenol had no effect on thymidine incorporation in 2‐day‐old rats. The drug, however, stimulated DNA synthesis in older animals and the degree of stimulation was inversely correlated with the proliferative activity in control rats. Small doses of isoproterenol given to rats for 4 days between 2 and 5 days of age produced a hypertrophy of the submandibular gland. The same treatment between 7 and 10 days of age caused both hypertrophy and hyperplasia of the gland. It is concluded that both the regulation of growth and the regulation of induced cell proliferation are a function of cellular differentiation and that cell proliferation can be induced only in cells that reached a certain degree of differentiation.
EFFECT OF CYCLOPHOSPHAMIDE ON THE HEMATOPOIETIC MICROENVIRONMENTAL FACTORS WHICH INFLUENCE HEMATOPOIETIC STEM CELL PROLIFERATION
Authors: Fried W. , Husseini S. , Gregory S. , Knospe W. H. , Trobaugh F. E.
Published: May 2008

Transplanted hematopoietic stem cells (HSC) regenerate more rapidly in the femoral marrow of lethally irradiated hosts pretreated with cyclophosphamide (CY) 4 days prior to X‐irradiation than they do in that of uninjected irradiated hosts (control). On the other hand, regeneration of HSC transplanted into irradiated hosts given CY 7 days before X‐irradiation is slower than in controls.

The microenvironment in the femoral marrow was studied at various times after giving CY. Four days after injecting CY, the number of colony forming units (CFU), total nucleated hematopoietic cells, and mature myeloid and erythroid cells in the femoral marrow is markedly reduced. Seven days after injecting CY, the number of CFU in the femoral marrow is still reduced, the total nucleated cell count is back to normal, but the number of mature myeloid elements in the marrow are significantly increased. These observations suggest the conclusion that the rate of proliferation of HSC is modulated by the number of mature myeloid cells in the microenvironment.
CELL PROLIFERATION IN THE CASTRATE MOUSE SEMINAL VESICLE IN RESPONSE TO TESTOSTERONE PROPIONATE
Authors: Morley Adrian R. , Wright Nicholas A. , Appleton David
Published: May 2008

The cell proliferation kinetics following induced DNA synthesis in the mouse seminal vesicle were measured after treatment with testosterone propionate. Fraction labelled mitosis curves at 24, 48 and 72 hr after injection gave t2 values of 1·5, 2·0 and 1·8 hr respectively, and ts values of 10·5, 8·0 and 8·0 hr. Tc measured 48 hr after stimulation was 17·5 hr. Growth fraction rose from 0·14 at 24 hr to 0·64 at 48 hr, and fell to 0·32 by 72 hr. A simple model is proposed in which the rise and fall of mitotic index and labelled index is determined by the ‘cell distribution ratio’.
SPERMATOGONIAL STEM CELL RENEWAL IN THE MOUSE: I. NORMAL SITUATION
Authors: de Rooij D. G.
Published: May 2008

Spermatogenesis in the mouse has been investigated by counting the different kinds of spermatogonia throughout the cycle of the seminiferous epithelium. A description is given of the Aisolated (Ais), Apaired (Apr) and Aaligned (Aal) spermatogonia and the other A spermatogonia as they appear in tubules mounted in toto. This technique enabled Ais, Apr and Aal spermatogonia to be counted.

Our results complete the evidence for the concept of a population of morphologically undifferentiated A spermatogonia preceding the A1 spermatogonia in the line of spermatogenesis and that among these A spermatogonia, the Ais cells are to be regarded as the stem cells of spermatogenesis.

In population of Ais, Apr and Aal spermatogonia divisions take place during the life spans of A2, A4 and In spermatogonia and also rarely during the life span of B spermatogonia. During the life spans of In and B spermatogonia the Aal gradually differentiate into A1 spermatogonia. About 10% of the total number of A spermatogonia in stages 7–8, mainly Aisolated and some Apaired, do not differentiate but start a new multiplication cycle.
THE ALTERATION OF THE REGENERATIVE ACTIVITY AND THE CELL CYCLE OF PARTIALLY HEPATECTOMIZED RAT LIVER FOLLOWING ADMINISTRATION OF d‐GALACTOSAMINE
Authors: Lesch R. , Bachmann W. , Reutter W.
Published: May 2008

A single injection of d‐galactosamine given to rats at different times after partial hepatectomy (PH) changes the pattern of regenerative proliferation. When administered during the pre‐replicative phase of regeneration, the onset of DNA synthesis and the increase in labelling index after injection of 3H‐thymidine are delayed by about 12 hr. The injection of d‐galactosamine at 24 hr after PH inhibits the drop in DNA synthesis occurring normally during the following 12 hr period. This was detected by a high labelling index and by an increased specific activity of DNA. The findings indicate a lengthening of the S phase, while G2 and M remain normal. Two modes of action of d‐galactosamine on the cell cycle are discussed.
EFFECTS OF HYDROXYUREA AND RADIATION ON HAIR MATRIX CELLS
Authors: Malkinson F. D. , Griem M. L. , Marianovic R.
Published: May 2008

Investigations were undertaken in CF1 mice to study the effects of hydroxyurea (HU) on hair matrix cell kinetics, and to assess the effects of combined administration of HU and irradiation on induction of temporary alopecia. HU 100 mg/kg was administered intraperitoneally and each animal received tritiated thymidine 0·5 μCi/g 30 min before biopsy. Serial biopsies were taken up to 48 hr after drug administration. Autoradiographs of anagen follicle squashes revealed sharp reductions in mitotic and labeling indices within 30 min. Depressed mitotic indices of 0·6–0·9% at 1–4 hr returned to normal (2·3%) after 6 hr, followed by cyclic mitotic ‘overshoot’, and were preceded by parallel changes in the labeling indices. HU‐induced cellular damage was most marked 4 hr after HU injection, with almost complete recovery from injury observed at the 24 hr interval.

The effects of varying the time intervals from 1 to 12 hr between HU administration and irradiation (650 rads) after injection of HU 1200 mg/kg were examined. Hair loss was measured 7 days later by photomicroscopy. Cyclic maximum alopecia was found at the 1–5 and 8–12 hr intervals, with relative ‘protection’ occurring at the 6–7 hr time periods.
SYNCHRONIZATION OF BABY RAT HEPATOCYTES: A NEW TEST FOR THE DETECTION OF FACTORS CONTROLLING DNA SYNTHESIS IN RAT HEPATIC CELLS
Authors: Nadal C.
Published: May 2008

The subcutaneous injection of irritating substances to baby rats results in a very reproducible wave of synchronized S phase DNA synthesis in hepatic cell involving 20% of the total population. Use has been made of this reaction to detect factors affecting DNA synthesis in hepatic cells. It enables substances to be tested during precise periods of the cell cycle. Two activities which were detected in normal adult rat serum, could not be found in the serum of the baby rat or of the partially hepatectomized adult rat: an activity inhibiting the progression of hepatocytes through the cell cycle in the late G1 phase, and an activity inducing the production of binucleate hepatocytes, effective in the late G1 and in the S phase.
MALL LYMPHOCYTE POPULATIONS IN THE MOUSE BONE MARROW
Authors: Röpke C. , Everett N. B.
Published: May 2008

Autoradiography and scintillation counting have been used for evaluation of lymphocyte turnover and life span in the bone marrow, peripheral blood and thoracic duct lymph of BALB/C mice. It was shown that the bone marrow contained two populations of small lymphocytes. One population was labelled 100% after 3–4 days of intensive injections of 3H‐thymidine and constituted about 75% of the lymphocytes. The remaining 25% of the lymphocytes turned over at a much slower rate comparable to the rate of increase in labelled small lymphocytes of the thoracic duct. More than 10% of the small lymphocytes of the bone marrow were found to be unlabelled after 10 days of intensive injections of 3H‐thymidine. Nine weeks after giving 3H‐thymidine for 30 consecutive days, 8·6% of the small lymphocytes in the bone marrow remained labelled. The mean grain counts of cells in this population were comparable to those of thoracic duct lymphocytes at corresponding times. About 90% of the peripheral blood lymphocytes were found to have a slow turnover and a long life span.
FURTHER OBSERVATIONS ON THE LATE LABELLING ASSOCIATED WITH STIMULUS‐RESPONSIVE CELLS IN SKIN
Authors: Potten Christopher S.
Published: May 2008

The presence of a long‐lived DNA precursor pool which may show some specificity for stimulus‐responsive cells has been demonstrated. Autoradiography, biochemical analysis, hydroxyurea sensitivity, and the temporal response all suggest that the late incorporation is into DNA in cells in the basal layer of the skin that respond to stimulation. The effect is observed with various doses of tritiated thymidine and both methyl and 6 labelled material. 125Iododeoxyuridine also shows late labelling in skin. It is believed that the late labelling is readily distinguishable from reutilization and from possible slow utilization of catabolites into molecules other than DNA. Skin of the ear and dorsum shows similar degrees of late incorporation, while tail and foot skin apparently have smaller long‐lived pools. This may indicate smaller stimulus‐responsive cell populations. If tritiated thymidine is given to cells after stimulation there is still some slow or delayed uptake. The distribution of labelled cells in the autoradiographs suggests that the late labelling cells may be associated somehow with pre‐existing labelled cells (cells in S at the time of thymidine administration).
CELL POPULATION KINETICS AND DESQUAMATION SKIN REACTIONS IN PLUCKED AND UNPLUCKED MOUSE SKIN
Authors: Hegazy M. A. H. , Fowler J. F.
Published: May 2008

The kinetics of cellular proliferation in plucked and unplucked dorsal skin of mice after local X‐irradiation are described, in relation to the time course of the gross desquamation reaction in skin of the dorsum and of the foot.
THE EFFECT OF ACUTE RENAL FAILURE ON MITOTIC DURATION OF MOUSE ILEAL EPITHELIUM
Authors: McDermott F. T. , Dalton M. K. , Galbraith A. J.
Published: May 2008

Previous percentage labelled mitoses studies in acutely uraemic mice have demonstrated a lengthening of the cell cycle and the DNA synthetic phase of ileal epithelium. The mitotic index was unaltered. Further studies have been performed to obtain an estimate of mitotic duration.

Acute renal failure was produced by urinary outflow obstruction in male mice. Controls were subjected to sham operation. The mean number of cells per crypt cell column, number of mitoses present per crypt section and differential mitotic stage count were assessed 18 hr after operation for uraemic and control mice. The mean number of metaphases accumulated per crypt section over a 2 hr interval following colchicine injection was obtained in other groups of mice and the mitotic duration calculated.

The mean number of mitoses per crypt section was 1.30 ± 0.46 for the controls and 1.48 ± 0.66 for the uraemic group. No evidence for a block in mitosis was indicated by the differential mitotic stage count. After applying Tannock's correction factor the mitotic duration was estimated to be 0.91 ± 0.18 hr for the control group and 2.81 ± 0.89 hr for the uraemic group. The difference in duration between the groups, 1.90 ± 0.91 hr, was significant (P≤0.05).

Reduction in cell proliferation may explain the development of uraemic lesions in the gastrointestinal tract.
DISSECTING THE HEMATOPOIETIC MICROENVIRONMENT. I. STEM CELL LODGMENT AND COMMITMENT, AND THE PROLIFERATION AND DIFFERENTIATION OF ERYTHROPOIETIC DESCENDANTS IN THE Sl/Sld MOUSE
Authors: Wolf Norman S.
Published: May 2008

The anemic Sl/Sld mouse and its normal (+/+) congenic control were used to explore the possibility of stromal control over four phases of erythropoiesis: CFU lodgment, commitment of multipotent stem cells to the erythropoietic line, proliferation of stem cells and their descendants, and the differentiation of those descendants into successively more mature forms. Lodgment was found to be the same in the Sl/Sld as in the normal mouse, but commitment, although characteristically different for spleen compared to the bone marrow, was subnormal. The stimulus to proliferate, as measured by spleen colony size and cell type content, was even more reduced. It is suggested that the direct control of differentiation into more mature cells may not be under stromal control.
TURNOVER OF CELL‐RENEWING POPULATIONS UNDERGOING CIRCADIAN RHYTHMS IN CELL PROLIFERATION
Authors: Izquierdo Jorge N. , Gibbs S. Julian
Published: May 2008

Evidence is presented in support of the concept of partial synchrony of cells as the cause for circadian rhythms in DNA synthesis and mitotic activity. The nonuniform age distribution of cells in cycle indicated that equations based on total asynchrony were not applicable for calculation of cytokinetic parameters in cellrenewing populations undergoing circadian rhythms. The integration of the circadian mitotic curve is introduced as a simple and accurate method for determination of proliferation rate and turnover time. An approximately linear increase in the labeling index following repeated injections of 3H‐thymidine demonstrated that nearly 100% basal cells in hamster cheek pouch epithelia were in cycle during a turnover time. These experiments suggest that if there is a G2 phase in cellrenewing tissues, this is short with respect to turnover time and that it may be a specific compartment where the control of cell proliferation operates.
THE INFLUENCE OF ADRENORECEPTOR ACTIVITY ON CRYPT CELL PROLIFERATION IN THE RAT JEJUNUM
Authors: Tutton P. J. M. , Helme R. D.
Published: May 2008

The influence of adrenergic stimulation, adrenergic blockade and sympathectomy on crypt cell cycle time and mitotic time in rat jejunum was studied.

Alpha adrenergic stimulation by noradrenaline was found to shorten both cell cycle and mitotic times, whereas beta adrenergic stimulation by adrenaline or isoprenaline was found to prolong both cell cycle and mitotic times. Conversely, alpha adrenergic blockade by phentolamine prolonged cell cycle time and beta adrenergic blockade by propranolol or practolol shortened cell cycle time but not mitotic time.

Both chemical and surgical sympathectomy inhibited crypt cell proliferation. Chemically sympathectomized animals manifested supersensitivity to exogenous noradrenaline.
MIGRATION OF SMALL LYMPHOCYTES IN ADULT MICE DEMONSTRATED BY PARABIOSIS
Authors: Röpke C. , Everett N. B.
Published: May 2008

Parabiotic BALB/C mice were used to study the traffic of small lymphocytes in immunological mature but unchallenged mice.

By giving 3H‐thymidine (3H‐TdR) injections to only one member (A) of a pair by preventing the escape of the radioactive isotope to the other member (B), the kinetics of newly‐formed cells was followed.

Less than 10% labelled small lymphocytes were found in the peripheral lymphoid tissues of both A and B members, while the thymusses and bone marrows of A members showed labelling percentages up to 70% in this period. Hardly any labelled cells gained entrance into the thymus while a detectable number was found in the bone marrows of B members.

Results from pairs set up to follow migration of long‐lived lymphocytes revealed that labelled cells detected 4–5 weeks after injections were equilibrated between the peripheral tissues and the bone marrows of the partners. Very few labelled cells were seen in the thymic medulla and none were observed in the thymic cortex, germinal centres or medullary cords of lymph nodes from any B member.

It was concluded that short‐lived small lymphocytes are formed primarily in the thymus and bone marrow and the migration of these cells is limited in adult animals. Furthermore, the vast majority of long‐lived small lymphocytes are freely recirculating, and these cells gain entrance to and are normal residents in the bone marrow.
CLEARANCE RATE OF EXOGENOUS 3H‐THYMIDINE FROM THE PLASMA OF PREGNANT RHESUS MONKEYS
Authors: Nowakowski Richard S. , Rakic Pasko
Published: May 2008

The plasma clearance rate of 3H‐TdR was determined by thin‐layer chromatography of samples from pregnant rhesus monkeys who had received a single intravenous injection of 3H‐TdR. At 10 min after the injection the circulating levels of 3H‐TdR had fallen to less than 0.2% of the initial theoretical distribution of the label. In general the plasma clearance rate can be described by a ‘double exponential’curve with half‐lives of 1 min and 20 min. Thus, 3H‐TdR disappears from the circulation of the pregnant monkey more rapidly than it does from the bloodstream of rodents, which correlates with previously detected interspecies differences in autoradiographic labeling of neurons. This means (1) that higher doses of 3H‐TdR must be used for autoradiographic labeling of monkey tissues and (2) that the monkey may be useful for studying cell kinetics because it has a short pulse labeling of the DNA.
DAILY VARIATIONS OF MARROW AND SPLENIC ERYTHROPOIESIS, PINNA EPIDERMAL CELL MITOSIS AND PHYSICAL ACTIVITY IN C57Bl/6J MICE
Authors: Sharkis Saul J. , Palmer John D. , Goodenough Judith , LoBue Joseph , Gordon Albert S.
Published: May 2008

Regular daily fluctuations in spontaneous physical activity and in the mitotic indices of marrow and splenic erythroid elements and pinna cells, were observed. Both male and female C57Bl/6J mice showed these rhythms. Of particular interest was the finding that the spleen and the marrow mitotic activity showed a reciprocal relationship. The role of several hormones and the biological clock in control of these rhythms are discussed.
CELL KINETICS IN THE SEBACEOUS GLANDS OF THE MOUSE. I. THE GLANDS IN RESTING SKIN
Authors: Hamilton E.
Published: May 2008

Cell proliferation, differentiation and migration have been studied in the sebaceous glands of DBA‐2 mice in the resting (telogen) phase of hair growth. Cells labelled by a single injection of tritiated thymidine start to leave the glands of adult male mice 5 days later. About 80% of the proliferative cells in the basal layer have a cell cycle time of 40 hr or less. In 18% of the proliferative cells G1 is at least 4 days long and 16% have a G2 phase longer than 17 hr. The S phase is about 7.5 hr long and cells spend at least 21 hr in the basal layer before migrating into the differentiating cell region. The glands of mature female and immature mice are smaller than those of the mature male. They have fewer, smaller cells and a much lower labelling index.
QUANTITATIVE IN VITRO STUDIES ON STIMULATION OF MURINE HAEMOPOIETIC CELLS BY COLONY STIMULATING FACTOR
Authors: Van Den Engh Gerrit J.
Published: May 2008

A new standardization method for Colony Stimulating Factor (CSF) is described and criteria are introduced which enables stimulating activity to be assessed independent of absolute colony numbers. With this method CSF preparations from different sources are compared and evidence is presented that suggests an identical mechanism of action for these substances. Data are presented on the increase in colony numbers that is induced by the addition of erythrocyte lysates to the cultures. The relationship between colony forming cells that are stimulated by CSF alone and cells stimulated by the combined action of CSF and erythrocyte lysate is discussed.
ESTIMATION OF THE MEAN AND VARIANCE OF CYCLE TIMES IN CINEMICROGRAPHICALLY RECORDED CELL POPULATIONS DURING BALANCED EXPONENTIAL GROWTH
Authors: Jagers Peter , Norrby Klas
Published: May 2008

The mathematical and statistical problem of estimating the mean and variance of cell cycle times from cinemicrographically observed durations until mitosis (cytokinesis at late anaphase), disintegration, collision (cells superimposing each other) or emigration (moving out of the field of vision) of randomly chosen individual cells in a population in balanced exponential growth is treated. The resulting formulae are simple and considerably reduce the average cell observation time. They are applied to two normal human foetal cell lines and their SV40‐transformed counterparts. One result is that the latter seem to have longer cycle times in spite of their shorter doubling times. Another result is that the cell mobility seems somewhat increased in the transformed populations. This corroborates earlier findings, indicating that the extent of cell loss, rather than the length of cycle times, may play a decisive role for the (net) doubling time of cultivated cell populations.
CONTROL OF INTESTINAL EPITHELIAL REPLACEMENT: LACK OF EVIDENCE FOR A TISSUE‐SPECIFIC BLOOD‐BORNE FACTOR
Authors: Clarke Rufus M.
Published: May 2008

The small intestine of rats was cut across in two places, about 14 and 50% of the length of the small intestine from the pylorus, and continuity was re‐established by suturing the proximal and distal ends. The resulting sac of small intestine, averaging 36% of the total length of the small intestine, had its upper end closed off, and its lower end anastomosed, either to the intestine‐in‐continuity (an ‘intestine‐sac’), or to the skin of the abdominal wall (a ‘skin‐sac’).

On the ninth post‐operative day, the cell production rate in squashes of micro‐dissected whole crypts of Lieberkühn was measured by mitotic blockade with Colcemid. The rate of cell production in unoperated and sham‐operated rats was 30 cells/crypt/hr, throughout the length of the small intestine. In the intestine in continuity, the rate increased to an average of 46 cells/crypt/hr above the anastomosis, and to 54 cells/crypt/hr below it. At the lower end of the ‘intestine‐sac’, which drained into the intestine‐in‐continuity, the rate was 39 cells/crypt/hr, while in the lower end of the sac which drained to skin the rate of cell production was only 16 cells/crypt/hr. This significantly lower cell production rate in intestine which was not in contact with ingesta is taken to be evidence of the importance of local, rather than blood‐borne factors in the control of epithelial replacement.
SOME PROPERTIES OF A ‘Go’ MODEL OF THE CELL CYCLE
Authors: Maertelaer V. De , Galand P.
Published: May 2008

Some models describing the kinetics of cell proliferation present the major advantage of requiring a small set of parameters for the complete description of the kinetic behaviour of cell populations. Among such models, that proposed by Burns & Tannock (1970) offers the further advantage of allowing a generalized description of cell cycle that covers the ‘Go’ concept.

This model assumes that the cell life cycle consists of two phases: G‐phase and C‐phase. After division, the cells enter G‐phase and remain there for any length of time. They leave this phase at a constant rate (kG) to enter C‐phase where they divide. C‐phase has a constant duration: θ. Only the two parameters θ and kG are required for a complete kinetic description in the steady‐state case. This is also true for an exponentially growing population, provided cell loss is null or negligible.

We started from the equations relating kG, θ and NG/N (where NG is the number of cells in G‐phase and N the total cell numbers) associated with the following models:

(1) Burns & Tannock (1970) model based on the hypothesis that the cells may differentiate from any phase of the cell cycle.

(2) A variant of this model where only the cells in G‐phase may differentiate. We describe an original method allowing the determination of the parameters

of the model from published ‘labelled mitosis’ curves. We observe that the experimentally obtained values of those parameters constitute a non‐randomly limited part of the set of values that one may theoretically have. This suggests the necessity for further assumption(s) restricting the model.
ACTIVITY OF TUBULOSINE ON THE KINETICS OF ROOT MERISTEM CELL POPULATION
Authors: Pareyre Claude , Deysson Guy
Published: May 2008

The action of tubulosine on the mitotic cycle was studied using continuous labelling with tritiated thymidine. This alkaloid provokes a lengthening of the G1 and S phases and a blocking of G2 is totally reversible when the treatment is followed by recovery in normal medium.

At a dose of tubulosine which induces a reversible mitostasis in the shortest possible time the lengthening of the phases of the cell cycle was estimated by three different techniques: labelled mitoses for the determination of G2; labelling intensity for the determination of S; binucleate cells for the determination of T, and an original technique using labelling index of binucleate cells for the determination of G1.

The limits of the technique of labelled mitosis together with the interest of the technique aiming at the direct determination of G1 in the case of a perturbed cycle are then discussed.
LYMPHOCYTE POPULATIONS IN MOUSE BONE MARROW: QUANTITATIVE KINETIC STUDIES IN YOUNG, PUBERTAL AND ADULT C3H MICE
Authors: Miller S. C. , Osmond D. G.
Published: May 2008

Continuous 3H‐thymidine infusion was used to characterize two kinetic subpopula‐tions of small lymphocytes in mouse bone marrow during normal growth and development. Young (4 wk), pubertal (8 wk) and mature (16 wk) C3H mice were infused subcutaneously with 3H‐thymidine for periods up to 10 days. Femoral marrow was then examined in radioautographic smears. During the first 3 days the proportion of marrow small lymphocytes labelled by 3H‐thymidine showed a rapid exponential increase to 93%, 81% and 72% in 4 wk, 8 wk and 16 wk mice respectively. The rate of appearance of labelled small lymphocytes then declined markedly but remained higher in younger than in older animals. The labelling curves were found to represent the summation of two exponential curves from which the proportions and renewal rate of corresponding cell populations were calculated. Most marrow small lymphocytes comprised a rapidly renewing population but in mice of increasing age the relative incidence of these cells fell (93‐3% at 4 wk; 88‐0% at 8 wk; 78‐5% at 16 wk) and their half‐renewal time (T½) lengthened (14 hr at 4 wk; 18 hr at 8 wk; 24 hr at 16 wk). The remaining small lymphocytes were slowly renewing with mean T½ of 4, 7 and 14 days in 4, 8 and 16 wk mice, respectively. Some heavily labelled small lymphocytes persisted in the marrow up to 10 wk after fourteen daily 3H‐thymidine injections in 10–12 wk mice. The numbers of rapidly renewing cells decreased from 604 times 103 to 228 times 103 per mm3 of marrow from 4 wk to 16 wk, respectively, while slowly renewing cells increased from 44 times 103 to 61 times 103 per mm3. The total number of nucleated marrow cells per femur increased from 4 wk to 16 wk but the rapidly renewing small lymphocytes per femur fell in numbers by 36% and in renewal rate by 63%. The results demonstrate a selective change in bone marrow small lymphocytes with age; rapidly renewing cells decline in number and renewal rate while the number of slowly renewing cells increases. The concept of bone marrow as a primary lymphoid organ is discussed.
COLONY‐FORMING ABILITY OF BONE MARROW CELLS OF W ANAEMIC MICE ON MACROPHAGE LAYER FORMED IN PERITONEAL CAVITY OF MICE
Authors: Kitamura Y. , Kawata T. , Okano K. , Asayama S. , Seki M.
Published: May 2008

The colony‐forming ability of haematopoietic cells of W anaemic mice was examined on the macrophage layer formed in the peritoneal cavity of mice. Bone marrow cells of W anaemic mice formed a considerable number of colonies on the macrophage layer, notwithstanding they did not form any colonies in the spleen of the same recipients. As the colony‐forming ability of the bone marrow cells was not reduced by the incubation with 3H‐thymidine, most of the cells which formed colonies on the macrophage layer seemed to stay in G0 state. The interrelationship between the spleen colony‐forming cells, the macrophage‐layer colony‐forming cells, and in vitro colony‐forming cells was discussed.
EXISTENCE OF TWO CHALONE‐LIKE SUBSTANCES IN INTESTINAL EXTRACT FROM THE ADULT NEWT, INHIBITING EMBRYONIC INTESTINAL CELL PROLIFERATION
Authors: Brugal G. , Pelmont J.
Published: May 2008

The inhibiting effect of tissue extract from fully differentiated intestinal mucosa of adult animals on proliferation kinetics of exponentially growing embryonic epithelial gut cell populations was studied in the newt Pleurodeles waltlii. Crude extract was fractionated by G‐200 Sephadex chromatography and the effect of fractions on cell proliferation was studied using both mitotic index and 3H‐thymidine incorporation methods. The inhibitions we obtained were then displayed by means of cytophotometric study of age distribution of intestinal gut cells around the cell cycle, measuring the Feulgen‐DNA content. The results revealed the presence of two chalone‐like substances in the intestine of adults. One (factor 1) is characterized by a molecular weight of between 120,000 and 150,000 and inhibits the cell cycle at the end of the G1 phase, the other (factor 2) is characterized by a molecular weight lower than 2000 and inhibits the cell cycle in the course of the G2 phase. The cells delayed in the G2 phase escape from inhibition but the cells delayed in the G1 phase do not, although availability time of both factor 1 and factor 2 is about 12 hr. It is thus thought that cells prevented from dividing in G1 phase are indefinitely delayed in this phase and possibly differentiate.
KINETIC ANALYSIS OF CELL SIZE AND DNA CONTENT DISTRIBUTIONS DURING TUMOR CELL PROLIFERATION: EHRLICH ASCITES TUMOR STUDY
Authors: Kim M. , Woo Kwang B.
Published: May 2008

In order to study the growth dynamics of proliferating and non‐proliferating cells utilizing discrete‐time state equations, the cell cycle was divided into a finite number of age compartments. In analysing tumor growth, the kinetic parameters associated with a retardation in the growth rate of tumors were characterized by computer simulation in which the simulated results of the growth curve, the growth fraction, and the mean generation time were adjusted to fit the experimental data. The cell age distribution during the period of growth was obtained and by a linear transformation of the state transition matrices, was employed to specify the cell size and DNA content distributions. In an application of the model, the time‐course behavior of cell cycle parameters of Ehrlich ascites tumor is illustrated, and the parameters important for the transition of cells in the proliferating compartment to the non‐proliferating compartment are discussed, particularly in relation to the G1‐G0 and G2‐G0 transitions of non‐cycling cells as revealed by the variation of cell size distribution.
COMPARTMENTS AND CELL FLOWS WITHIN THE MOUSE HAEMOPOIETIC SYSTEM
Authors: Micklem H. S. , Ford C. E. , Evans E. P. , Ogden D. A.
Published: May 2008

Two chromosomally distinguishable haemopoietic cell populations were injected into lethally irradiated syngeneic recipients. The presence or absence of the T(14;15)6Ca reciprocal translocation (indicated by T6 marker chromosomes) did not affect the proliferation of a population. Wide disparities were found in the proportions of the two donor cell populations between animals and between the right and left femora of individual animals. This suggests (i) that there is, at most, a very limited interchange of proliferating cells and their precursors between the marrow of different bones; and (ii) that the number of clones proliferating in the bone marrow at any one time must be rather small; there was evidence that this number depended in part on the number of haemopoietic cells injected. Exchange between the mitotically active cell populations of spleen, thymus, lymph nodes and bone marrow was also limited, as shown by significant disparities in the proportions of the two donor populations proliferating in the different tissues of individual mice.
COMPARTMENTS AND CELL FLOWS WITHIN THE MOUSE HAEMOPOIETIC SYSTEM II. ESTIMATED RATES OF INTERCHANGE
Authors: Micklem H. S. , Ogden D. A. , Evans E. P. , Ford C. E. , Gray J. G.
Published: May 2008

Part‐body irradiated CBA mice were injected with CBA‐T6 bone marrow. In this way a predominantly donor population was established in the femora while the marrow of the humeri remained largely (average 94 %) of host origin. In animals examined cytologically up to 2 years later, no tendency was observed for the proportion of donor cells in the humeri to increase. Splenectomy had no effect on this. When femoral bone marrow from the experimental mice was injected into lethally (whole‐body) irradiated recipients, cells originating from the primary host repopulated the lymph nodes to a disproportionate extent. Equilibration between the cell populations of femora and humeri occurred after re‐exposure to 600 rad whole‐body irradiation, but not after 100 rad or 350 rad; thus, regeneration of damaged bone marrow involved a significant contribution from extrinsic stem cells only after the highest dose of radiation.

The data are compatible with an inflow of at most ten effective stem cells per humerus per day from the blood, and suggest a much lower figure. This means that few if any of the stem cells of peripheral blood enter the bone marrow and found haemopoietic clones. Evidence is adduced for the existence of a proliferating lymphoid sub‐population in the bone marrow, contributing some 5–10% of the observed mitoses.

The mitotic cells in the lymph nodes are replaced from marrow‐derived progenitors at an estimated rate of 4–5 %/day. The relevant data for the thymus are more variable, but suggest an average figure of 8–11 %/day. Earlier data from mouse parabionts suggest a lower rate of inflow to the thymus.
A STUDY OF THE KINETICS OF MICROSPOROGENESIS IN CAMPELIA ZANONIA (L.) H.B.K.
Authors: Wigglesworth D. J.
Published: May 2008

During maturation, microspores pass through a series of morphologically distinguishable stages or compartments. A study has been made of the systematic fluctuations in the frequency of microspores in these compartments, when plants are grown under rigidly controlled conditions.

A new approach to the construction of cumulative flux rate curves is described; these give the number of cells passing the compartment boundaries per unit time. The curves obtained indicate that simple models, which assume constant flux rates and compartment transit times, will not explain the observations. It is evident that not only do microspores mature at different rates, but that the maturation rate of individual microspores varies during the developmental sequence. The overall process may be controlled by the intimate relationship which exists between the microspores and the tapetal periplasmodium in the Tradescantiae.
CELL PROLIFERATION IN WALKER TUMOUR GROWING IN THE STOMACH WALL
Authors: Broyn Terje
Published: May 2008

Tumour cells from a Walker carcinosarcoma 256 were implanted in the gastric mucosa in rats. The tumour grew and infiltrated the lamina propria and the submucosal space after 7 days. It appeared to grow faster in the submucosal space than in the lamina propria. The cell proliferation was therefore studied separately in: (1) the tumour in the lamina propria, (2) the main tumour mass and (3) the tumour periphery, defined as the cells located within the outer 100–120 μm of the tumour. Mitoses arrested with vinblastine, cells labelled with tritiated thymidine and the grain count per labelled cell were studied at the three different sites. The rate of cell proliferation in the tumour was highest in the lamina propria, lower in the centre of the main tumour mass, and lowest at the periphery. Cell loss might explain the discrepancy between the rate of cell proliferation and the actual tumour growth. The factors that influence tumour cell proliferation in the different parts of the tumour are discussed.
KINETIC‐MICROARCHITECTURAL CORRELATIONS IN THE BONE MARROW OF THE MOUSE
Authors: Shackney S. E. , Ford S. S. , Wittig A. B.
Published: May 2008

Transverse histologic sections of bone marrow obtained from mice that were sacrificed by perfusion fixation at intervals following tritiated thymidine injection were studied by means of radioautography. A kinetic gradient was demonstrated across the marrow section, with the highest proliferative rate in the subendosteal region. Megakaryocytes were shown to originate from the rapidly proliferating subendosteal cells. The immediate proliferating precursors of mature granulocytes were slowly proliferating cells found predominantly in the central region of the marrow. It was concluded that in the steady state there must be a migration of cells from the subendosteal region to the central region with concomitant growth retardation of the migrating cells.
THE INDUCTION OF TRANSIENT INCREASES IN MITOTIC RATE IN MURINE TISSUES FOLLOWING PROLONGED INTRAVENOUS INFUSIONS OF HYDROXYUREA
Authors: Plager John
Published: May 2008

Intravenous infusions of hydroxyurea were established in mice and maintained for periods up to 48 hr. The influence of different rates of hydroxyurea infusion on the number of viable cells gathered in S phase was studied in eight different mouse tissues. An infusion rate which was sufficiently slow not to block thymidine incorporation completely, resulted in gathering of cells in S phase while offering some protection against hydroxyurea‐induced cell death. The duration of the period of DNA synthesis following release from hydroxyurea inhibition appeared to be shortened in some tissues. After the release of hydroxyurea blockades maintained for 12–24 hr, each of the tissues showed sharp increases in mitotic activity and peak mitotic index values were as much as twenty times greater than values found in tissues of control animals. An important finding was that the time of maximal mitotic activity for different tissues after release of blockade could differ by many hours.
THE PRESENCE OF A CSF ENHANCING ACTIVITY IN THE SERUM OF ENDOTOXIN‐TREATED MICE
Authors: Engh Ger van den , Bol Simon
Published: May 2008

Serum taken from mice a few hours after injection of endotoxin is a potent source of a stimulator of in vitro myelopoiesis. By means of dose‐response studies, the biological activity of this material was compared to that of a colony stimulating factor (CSF) from pregnant mouse uteri. Postendotoxin serum appears to contain two different activities: a stimulating activity which may be identical to CSF and an activity which augments the action of CSF. The separate nature of the two activities is demonstrated by differences in the rate at which they are diluted out and by differences in the time at which they are maximally present after endotoxin administration. It is therefore concluded that the colony‐stimulating properties of postendotoxin serum are not due solely to CSF present in the serum.
EVALUATION OF THE SPECIFICITY OF A LYMPHOID CHALONE
Authors: Garcia‐Giralt E. , Diaz‐Rubio E. , Rappaport H.
Published: May 2008

An extract from calf spleens, injected into mice, was found to inhibit their lymphocyte proliferative response to PHA‐M and PWM in vitro. Despite the ability of the spleen extract to inhibit the response of lymphocytes to stimuli in vitro, no effect was observed on the repopulation of lymphocytes in the peripheral blood of sublethally irradiated mice. The data suggest that the spleen extract acts as a specific inhibitor of the immune competent cells since neither the precursors of lymphocytes nor other haematopoietic cells were affected.
VARIATION OF CELL KINETIC PARAMETERS IN RELATION TO THE GROWTH RATE OF THE EHRLICH ASCITES TUMOR
Authors: Woo Kwang B. , Wiig Karl M. , Brenkus Larry M.
Published: May 2008

A multicompartmental model of the cell cycle and proliferation kinetics was used to analyse the time‐course behavior of the cell cycle time, the growth fraction, and the cell loss rate during Ehrlich ascites tumor growth. The growth rate of Ehrlich ascites tumor cells as the tumor aged was significantly influenced by change in the cell cycle time.