bluuebunny/crossref_metadata_2025 huggingface dataset:
PREFERENTIAL LABELING OF RAT LYMPHOCYTES WITH A RAPID RATE OF TURNOVER BY TRITIATED DEOXYCYTIDINE
Authors: Amano M. , Everett N. B.
Published: May 2008

Lymphocytes in thymic cortex and germinal centers of lymphoid tissues are labeled intensely with generally labeled tritiated deoxycytidine [G‐3H]dCyd whereas they are weakly labeled with methyl tritiated deoxythymidine [methyl‐3H]dThd of the same specific activity, not only by single injection but also by an intensive injection schedule. [G‐3H]dCyd can be used to label short‐lived lymphocytes strongly, although not specifically. The distribution patterns of labeled lymphocytes were different depending on the injection schedules of [G‐3H]dCyd. [G‐3H]dCyd can be used as a precursor molecule for cytosine and also thymine found in DNA. The ratios of radioactive thymine to cytosine measured biochemically on DNA extracted from radioactive lymphocytes labeled by the various schedules indicate strongly that short‐ and long‐lived lymphocyte populations have different abilities to utilize pyrimidine nucleosides for DNA synthesis.
THE RODENT INCISOR TOOTH PROLIFERON
Authors: Zajicek G.
Published: May 2008

The rodent incisor tooth is the site of five cell populations proliferating in harmony: amelocytes, odontocytes, pulp cells, endothelial cells and the periodontal ligament. Their proliferating regions are located in the apex tip, where the various cells originate. Cells displaced from the tooth origin at the apex toward the periphery, mature to perform their specified function. The proliferative events in the tooth are summarized in a conceptual model of the incisor proliferon. The proliferon is an oriented structure with an origin and periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibres, all interacting continuously. All four are indispensable in the definition of the proliferon.
CHANGES IN LIVER CELLS PLOIDY OF YOUNG RATS FOLLOWING ISOPRENALINE TREATMENT
Authors: Gerzeli G. , Barni S.
Published: May 2008

Cell proliferation induced by isoprenaline (IPR) stimulation in very high doses was assayed in the liver of young rats, and the formation of polyploid cells was studied from the 15th to the 70th day of life.

A general stimulatory effect on a complex process of cellular multiplication, leading to a population of tetraploid cells, was found to be accelerated; the earlier appearance of binucleate cells and the subsequent significant variations in their incidence confirmed the role of this cell type as an intermediate step in the process of polyploidization. Evidence was found of concomitant size changes of the hepato‐cytes, which might be partially independent of the effect on DNA content.

The stimulation was no longer evident 20–30 days from the end of treatment, by when the cells which had come into contact with IPR should have completed the whole sequence of events leading to the formation of tetraploid mononucleate cells.
THE ROLE OF THE SPLEEN IN THE REPOPULATION OF THE HAEMOPOIETIC SYSTEM OF HEAVILY‐IRRADIATED MICE
Authors: Silini G. , Andreozzi U. , Pozzi L. V.
Published: May 2008

The respective role of the spleen or of the bone marrow in the regeneration of the haemopoietic progenitor compartment of heavily‐irradiated mice has been investigated. Splenectomy was used to this end in animals injected with exogenous isogenic cells or regenerating from endogenous spleen or marrow cells. Analysis of the data as a function of time shows that the presence of the spleen affects marrow CFU repopulation only at the early post‐irradiation stages. The expansion of the marrow progenitor pool proceeds, however, rather independently of the spleen and marrow CFU remain eventually as the main source of haemopoietic cells in the surviving mice. Thus the reaction of the spleen may be envisaged as a fast, important but transient contribution to the overall haemopoietic function of heavily‐irradiated animals.
A FAST AND ACCURATE METHOD FOR CALCULATING ENGELBERG'S SYNCHRONIZATION INDEX
Authors: Bakke O. , Pettersen E. O.
Published: May 2008

A method is described which makes a fast and accurate calculation of Engelberg's synchronization index possible. The calculation is only based on the growth curve for the synchronous and the corresponding asynchronous population, and makes it unnecessary to calculate the curve for the normalized rate of cell division.
THE ‘TRANSITION PROBABILITY MODEL’ AND THE REGULATION OF PROLIFERATION OF HUMAN DIPLOID CELL CULTURES DURING AGING
Authors: Grove GAry L. , Cristofalo Vincent J.
Published: May 2008

Genealogies derived from time‐lapse cinemicrophotographic studies of aging human diploid cell cultures were analysed in terms of the ‘transition probability’ model. It was found that the distribution of intermitotic times obtained from middle passage cells deviated only slightly from that predicted by the model. In contrast, the plot for late passage cultures did not fit the predicted pattern and appeared to be composed of multiple curves. These changes are discussed in reference to cellular senescence as expressed by normal human diploid cells in vitro.
EFFECT OF MECHANICAL STIMULATION ON CELL PROLIFERATION IN MOUSE EPIDERMIS AND ON GROWTH REGULATION BY ENDOGENOUS FACTORS (CHALONES)
Authors: Bertsch Stefan , Csontos Katharina , Schweizer Jurgen , Marks Friedrich
Published: May 2008

Mechanical stimulation of dorsal mouse skin by skin massage or removal of the horny layer results in a mutually comparable increase in DNA‐labelling and mitotic activity. However, only after injury such as removal of the horny layer hyperplasia develops. This phenomenon, called ‘hyperplastic transformation’ is characterized by a transient abolition of the epidermal G1 chalone responsiveness. There is some indication that the susceptibility to a heat labile factor, probably the epidermal G2 chalone, is not affected. Skin massage neither interferes with the responsiveness to epidermal G1 chalone nor induces ‘hyperplastic transformation’. Mouse tail epidermis shows a ‘functional hyperplasia’ and responds to the G1 chalone. To explain these observations, it is assumed that the epidermal stem cell population is heterogeneous consisting of G1 chalone‐sensitive and G1 chalone‐insensitive cells.
STUDIES ON THE MECHANISM OF DIURNAL VARIATION OF PROLIFERATIVE INDICES IN THE SMALL BOWEL MUCOSA OF THE RAT
Authors: Al‐Dewachi Hutaifa S. , Wright Nicholas A. , Appleton David R. , Watson Alexander J.
Published: May 2008

In the rat small bowel mucosa significant variation was found in both the labelling and the mitotic indices with time of day. The zenith and the nadir of labelling and mitotic activity coincided at 15.00 and 02.00 hours respectively. Small changes were found in the ‘cut‐off’ position, but this variation in proliferative compartment size was insufficient to account for the comparatively wider fluctuations in proliferative indices. Measurements of the rate of entry into mitosis, using metaphase arrest with vincristine at three widely separated times during the day, showed no significant change.

Changes in the growth fraction or in the birth rate as measured cannot account for diurnal variation in the proliferative activity of the small bowel mucosa. We propose a hypothesis which involves diurnal fluctuations in the transit times through G1 and through G2.
PROLIFERATION RATE OF HAEMOPOIETIC STEM CELLS AFTER DAMAGE BY SEVERAL CYTOSTATIC AGENTS
Authors: Nečas E. , Neuwirt J.
Published: May 2008

The haemopoietic tissue of mice was damaged by different cell‐cycle‐stage specific and cell‐cycle‐stage non‐specific cytostatic agents. The proliferation rate among the surviving pluripotential stem cells, i.e. those cells forming colonies in spleens of lethally irradiated mice (CFUs), was then investigated.

The results suggest that, at least in the CFUs population, the cells which synthesize DNA in the S phase of the cell cycle inhibit the entry of the non‐proliferating G0 cells into cell cycle. This evidence was based on the ability of three cytostatic agents, hydroxyurea, cytosine arabinoside and methotrexate, which are toxic specifically to the S phase cells to increase the proliferation in the CFUs population. This increase was quite out of proportion to the small amount of damage they caused to the population. Colchicine, which kills cells in mitosis, and ionizing irradiation, damaging cells in all stages, proved to be much weaker stimulators of proliferation.

It has been suggested that a mechanism for the control of cellular proliferation might be based on the negative feedback in the cell cycle. In this feedback control loop the cells which are preparing for cell division in the S phase of the cell cycle inhibit the entry of the non‐proliferating G0 cells into cell cycle.
CALCIUM AND IONOPHORE A‐23187 AS INITIATORS OF DNA REPLICATION IN THE PLURIPOTENT HAEMOPOIETIC STEM CELL
Authors: Gallien‐Lartigue O.
Published: May 2008

The proliferation rate of the haemopoietic stem cells of the mouse bone marrow can be stimulated by an increase in calcium influx. This key event may be brought about by raising the external calcium concentration or, at lower calcium levels, by use of A‐23187 as calcium carrier, within definite dose ranges depending on the Mg2+: Ca2+ molar ratio in the incubation medium. The hypothesis is postulated of an accelerated influx of Ca+ as the possible common mediator of the effects of the various types of agents known to control the CFU cell cycle.
REGENERATION OF CFUs IN THE MARROW OF MICE EXPOSED TO 300 RADS AFTER HAVING RECOVERED FROM 950 RADS
Authors: KEDO A. , BARONE JUDITH , FRIED W.
Published: May 2008

Exposure to 950 rads 60Co radiation has been reported to cause long‐lasting damage to the hematopoietic stroma (HS), although the size of the CFUs population recovers to pre‐irradiation levels. In these studies HS damage was detected only after subcutaneously implanting the femurs of the irradiated mice into syngeneic hosts. To exclude the possibility that what was considered to be HS damage was merely caused by artifacts due to the process of implantation in a new host, we compared the rate of regeneration of CFUs in mice which had recovered from 950 rads prior to receiving 300 rads 60Co radiation (950 + 300 rads group) with that of mice which received only 300 rads (0 + 300 rads group).

The CFUs population in the 950 + 300 rads group grew exponentially for 2 weeks at a rate which did not differ significantly from that of CFUs in the 0 + 300 rads group. However, the rate of CFUs growth reached a plateau before full recovery was achieved in contrast to that in the 0 + 300 rads mice.

We therefore conclude that the incomplete regeneration of CFUs in the marrows of 950 + 300 rads mice was most likely caused by X‐irradiation‐induced damage to the HS rather than damage to the inherent repopulating potential of the CFUs per se.
EHRLICH ASCITES TUMOR (EAT) CHALONE EFFECTS ON NASCENT DNA SYNTHESIS AND DNA POLYMERASE ALPHA AND BETA
Authors: Nakai George S.
Published: May 2008

EAT chalone effects on nascent DNA synthesis and DNA polymerase were examined. Concentration related inhibition of 3H‐thymidine (3H‐TdR) incorporation into EAT cell DNA was noted over a chalone range of 50–200 μg/ml. RNA synthesis was not affected, but protein synthesis decreased an average of 82% during 3 hr. Nascent DNA pulse‐labeled for 2 min was normally incorporated into bulk DNA in the presence of chalone, but crude α and β‐polymerase activities were inhibited. Crude DNA polymerase from C3H mouse kidney and spleen was also partially inhibited by EAT chalone, suggesting non‐specific inhibition of DNA polymerase. Preincubation studies of chalone with crude EAT DNA polymerase or ‘gapped’ DNA primer had no effect on chalone activity. Chalone may control mitotic activity by inhibiting α‐ and β‐polymerase activity, thereby decreasing nascent DNA synthesis. Nascent DNA is incorporated normally into bulk DNA in the presence of chalone, indicating that DNA ligase is not inhibited.
A DEFICIENCY OF HEMATOPOIETIC STEM CELLS IN STEEL MICE
Authors: McCarthy K. F. , Ledney G. D. , Mitchell R.
Published: May 2008

In the present study, population sizes of high self‐renewal potential stem cells, i.e. colony forming units (CFU), and low self‐renewal potential stem cells, i.e. transient endogenous colony forming units (TE‐CFU) in Sl/Sld mice and their normal congenic littermates were measured and compared. By correcting for differences in the seeding efficiency ‘f’, it was possible to demonstrate that Sl/Sld mice suffer a deficiency of both stem cell populations. Therefore, it is concluded that the defective stromal tissue of the Sl/Sld mouse does not support normal size stem cell populations. However, as noted in the discussion, it remains an open question as to whether the defective stromal tissue supports normal erythroid differentiation at the stem cell level.
REGULATION OF BONE MARROW CELL GROWTH IN DIFFUSION CHAMBERS: THE EFFECT OF GRANULOCYTE EXTRACTS
Authors: Løvhaug Dagfinn , Bøyum Arne
Published: May 2008

Hypotonic lysis of mature human blood granulocytes yielded an extract which reduced granulopoiesis and enhanced macrophage formation of mouse bone marrow cells cultured for 7 days in diffusion chambers (DC). The low molecular weight fraction (MW < 15,000–25,000 Daltons) obtained by Amicon filtration of the extract, reduced granulopoiesis without affecting macrophage formation. The high molecular weight fraction (MW > 15,000–25,000 Daltons) reduced the number of granulocytes and increased the number macrophages. Erythrocyte extract increased the macrophage formation in DC but did not alter the number of granulocytes. The spleen colony assay showed that the granulocyte extract increased the number of CFU‐S in DC. It is suggested that the granulocyte extract contain an inhibitor of stem cell differentiation to myeloid cells thereby reducing the number of proliferative granulocytes in DC 7 days later. The inhibitor of differentiation may lead to an increased self renewal of the stem cell in the DC system.
THE EFFECT OF VINCRISTINE ON MOUSE JEJUNAL CRYPT CELLS OF DIFFERING CELL AGE: DOUBLE LABELLING AUTORADIOGRAPHIC STUDIES USING 3H‐ AND 14C‐TdR
Authors: Jellinghaus W. , Schultze B. , Maurer W.
Published: May 2008

The mechanism of action of the alkaloid vincristine (VCR) has been investigated in vitro on HeLa cells in culture and in vivo on jejunal crypt cells of the mouse. The in vitro experiments with HeLa cells show that VCR affects not only mitotic but also interphase cells. The VCR‐affected cells first continue their passage through the cell cycle undisturbed but after reaching mitosis they are arrested in metaphase. This agrees well with the results obtained by Madoc‐Jones & Mauro (1968) and Madoc‐Jones (1973) on synchronized cell cultures.

Until now there has been no investigation of the mechanism of action of VCR in vivo. This is due to the absence of a suitable technique for synchronization in vivo. The present study is based on a method which permits the assessment of the VCR sensitivity as a function of the cell age without synchronization in the usual sense.

The jejunal crypt epithelium of the normal mouse was double labelled with 3H‐ and 14C‐thymidine (TdR) in such a way as to produce a narrow subpopulation of crypt cells with a maximum age difference of 1 hr. On autoradiographs these cells can be distinguished by their characteristic labelling from other cells. As this ‘pseudo’‐synchronized subpopulation passes through the cycle the effect of VCR can be studied, i.e. one can analyse the effect in well‐defined time intervals of the cycle. The results show that the effect of VCR is the same in vivo as in vitro. The crypt cells which are affected by VCR in interphase continue their passage through the cycle, but upon entering mitosis they are arrested in metaphase. VCR has, at the concentration used in the present study, no effect on the duration of the S and G2 phases. The necrotic cells seen after VCR application are formed from arrested metaphases.
GROWTH STIMULATION OF SPARSE, SERUM DEPRIVED AND OF CONFLUENT, CONTACT INHIBITED MAMMALIAN FIBROBLASTS BY A PREPARATION OF 3′:5′‐CYCLIC AMP PHOSPHODIESTERASE
Authors: Lawrence David A. , Dézelée Philippe , Jullien Pierre
Published: May 2008

Resting mammalian fibroblasts, either sparse and maintained in a serum‐free medium, or confluent and contact inhibited, are stimulated to divide by treatment with a preparation of 3′: 5′‐cyclic AMP phosphodiesterase. This enzyme preparation contained a low level of trypsin‐like and α‐chymotrypsin‐like activity, but its effect on cell growth could not be mimicked by pure, crystallized trypsin and α‐chymotrypsin at concentrations equivalent to their contamination in the above preparation. Preincubation of the 3′: 5′‐cyclic AMP phosphodiesterase preparation with the protease inhibitor, phenyl methane sulfonyl fluoride, did not affect, either, its stimulation of DNA synthesis in fibroblasts, or its enzymatic hydrolysis of cyclic AMP.
EFFECT OF PEPSIN PRETREATMENT ON PULSE‐CYTOPHOTOMETRIC DNA HISTOGRAMS
Authors: Beck H.‐P.
Published: May 2008

Samples of mitotic L‐cells were investigated after different preparation and staining procedures using the technique of pulse‐cytophotometry. It is shown that most mitotic cells which should appear in the second peak of the DNA histogram are disintegrated or separated into halves by pepsin pretreatment. Hence, the designation‘G2+ M’for the second peak is not correct for this preparative method. This should be taken into account in cell kinetic investigations performed after pepsin pretreatment.
STUDIES ON THE POPULATION KINETICS OF THE WALKER CARCINOMA BY AUTORADIOGRAPHY AND PULSE CYTOPHOTOMETRY
Authors: Erbe W. , Linden W. A. , Reddy S. B. , Zywietz F. , Baisch H.
Published: May 2008

The proliferation parameters of the Walker carcinoma were estimated from both in vivo and in vitro measurements. The transplantable Walker carcinoma 256 was grown in male inbred BD1 rats. During exponential growth, 5‐6 days after transplantation, a PLM curve was performed, yielding estimates of Tc ≅ 18.0 hr, Ts ≅ 6.4 hr, TG2+M≅ 4.1 hr. With the double labelling technique in vitro under 2.2 atm oxygen we obtained: Tc ≅ 18.2hr, Ts ≅ 8.2 hr, TG2+M≅ 2.0hr. From pulse cyto‐photometry DNA content histograms the fractions of cells in the cell cycle phases were calculated using a computer program: fG1≅ (47.6 ± 1.1)%, fs≅ (34.1 ± 1.0)%, fG2+M≅ (18.3 ± 1.5)%. These fractions remained constant between the fifth and the twelfth day after transplantation. At that time the tumour growth had already slowed down appreciably. The growth fraction determined by repetitive labelling was 0.96 on the fifth and 0.93 on the seventh and eleventh day. The cell loss factor was φ≅ 17% during exponential tumor growth and increased to about 100% between the tenth and twelfth day. The agreement of the cell kinetic data determined by autoradiography from solid tumours in vivo (PLM, continuous labelling) and autoradiography as well as pulse cytophotometry from in vitro experiments (excised material) was satisfactory.
POST‐MITOTIC AGE OF MONONUCLEAR CELLS MIGRATING INTO TA‐3(St) SOLID TUMORS
Authors: Kaizer L. , Lala P. K.
Published: May 2008

Subcutaneous transplantation of 5 × 106 TA‐3(St) mammary carcinoma cells into A/J mice produced rapidly growing tumors that showed a substantial accumulation of lymphocytes, monocytes and macrophages. This must have resulted primarily from an influx of circulating cells, since none of the cell types exhibited any significant local proliferation as indicated by 1 hr 3H‐TdR uptake. The post mitotic age of the various leukocyte types in circulation of normal and tumor bearing animals, and those appearing within the tumors, was evaluated by a repeated 3H‐TdR labeling protocol designed to label newly formed leukocytes. Tumor transplantation (or injection of an equivalent volume of saline in control animals) was preceded by thirteen 3H‐TdR injections (12.5 μCi every 8 hr) and followed by eight more injections at equivalent intervals. Animals were serially sacrificed at 5‐14 days after tumor transplantation or saline injection. Total lymphocyte labeling in the blood during these intervals was higher in tumor bearing mice (approximately 25% between 5 and 12 days) than in the saline injected controls (approximately 20%), indicating that tumor transplantation resulted in an increase in the proportion of young lymphocytes in circulation. More significantly, a much higher labeling (57‐60% at 5‐12 days) was exhibited by lymphocytes isolated from the tumors, indicating selective migration (and/or retention) of newly formed lymphocytes within the tumor. This finding applied to lymphocytes in all size categories. Although blood monocyte labeling in the control and experimental animals was similar (e.g. 83% at day 5 and 52% at day 14), significantly higher labeling (e.g. 93% and 70% at the respective intervals) was exhibited by monocytes isolated from tumors. This suggested a preferential accumulation of young monocytes at the tumor site. An identical macrophage labeling pattern compared to that shown by monocytes within the tumor indicated a rapid monocyte‐macrophage transition. Since these findings in the present strain‐specific solid tumor are similar to those previously obtained in this laboratory in the strain‐nonspecific Ehrlich ascites tumor, the phenomenon of selective localization of newly formed mono‐nuclear leukocytes appears to be a general occurrence in transplanted murine tumors.
MODULATION OF IN VITRO ERYTHROPOIESIS: ENHANCEMENT OF ERYTHROID COLONY GROWTH BY CYCLIC NUCLEOTIDES
Authors: Brown James E. , Adamson John W.
Published: May 2008

Mammalian erythropoiesis, as assayed by erythroid colony formation in vitro, is enhanced by cyclic adenosine nucleotides and agents which are capable of raising intracellular cyclic AMP (cAMP) levels. With canine marrow cells as target, this enhancement was shown to be specific for cAMP and its mono‐ and dibutyryl derivatives. Adenosine and its derivatives, such as AMP, ADP and ATP, and other cyclic nucleotides, such as cGMP, dibutyryl‐cGMP, cCMP and cIMP and sodium butyrate were inactive. The phosphodiesterase inhibitor, RO‐20‐1724, and the adenyl cyclase stimulator, cholera enterotoxin, both markedly increased colony numbers. Studies with tritiated thymidine showed that about 50% of the cells responding to either erythropoietin (ESF) or dibutyryl cAMP (db‐cAMP) were in DNA synthesis. However, by unit gravity sedimentation velocity analysis, the peak of ESF‐responsive colony forming cells sedimented more rapidly (8.7 ± 0.2 mm/hr) than the peak of db‐cAMP‐responsive cells (7.5 ± 0 mm/hr). These results demonstrate that adenyl cyclase‐linked mechanisms influence in vitro erythropoietic proliferation and suggest that other hormones and simple molecules might interact with surface receptors and thus modulate the action of ESF at the cellular level.
HYPERSENSITIVITY REACTIONS IN THE SMALL INTESTINE
Authors: MacDonald T. T. , Ferguson Anne
Published: May 2008

Allograft rejection of fetal intestine and graft‐versus‐host (GvH) disease have been used to study the effects of cell‐mediated immune reactions on epithelial cell kinetics in mouse small intestine. In heterotopically transplanted isografts the cell production rate per crypt was similar to that in normally sited small intestine of the same age. However there was a six‐fold increase in the rate of cell production per crypt during allograft rejection and a three‐fold increase during GvH disease. Furthermore animals with GvH disease developed villous atrophy and had fewer crypts per villus than littermate controls. At the age of 19 days cell production per villus per hour was 97.5 in animals with GvH disease compared with 54.6 in controls.

These results indicate that the pathological entity of ‘partial villous atrophy’evolves in two distinct phases. Phase 1, a state of increased cell turnover with crypt hyperplasia but villi of normal length precedes the development of Phase 2, true villous atrophy.
ALTERATION OF CELLULAR PROLIFERATION IN THE ILEAL EPITHELIUM OF SUCKLING AND WEANED RATS: THE EFFECTS OF ISOPROTERENOL
Authors: Klein Robert M.
Published: May 2008

The purpose of this study was to analyse cell proliferation in the ileum before and after neonatal closure to macromolecules and to determine the effects of the sympathomimetic amine, isoproterenol (IPR), on cell cycle parameters. 8‐ and 28‐day‐old rats were employed in this study representing the neonatal periods of pre‐ and post‐closure ileum respectively. The duration of the cell cycle phases was determined by the percentage of labeled metaphases technique (PLM) with computerized analysis of the curves. The generation cycle time was longer in 8‐day‐old suckling rats (18.63 hr) as compared to the older weaned rats (11.85 hr), and most of this 6.78 hr difference was in the G1‐period (4.5 hr). Other proliferative indices were also lower in the suckling rats—mitotic index (1.9 ± 0.4% as compared to 6.7 ± 0.9%), labelling index (26.8 ± 2.5% versus 44.2 ± 2.6%) and migration rate measured as per cent labeled villus cells (8.9 ± 3.1% versus 45.2 ± 3.4%). IPR was found to inhibit cellular proliferation in the ileal epithelium of both age groups. The cell cycle of the ileal epithelium of 8‐day‐old rats was lengthened from 18.63 to 21.07 hr and 28‐day‐old rats from 11.85 to 13.98 hr. IPR produced a decrease in mitotic index from 1.9 ± 0.4% to 1.6 ± 0.4% in pre‐closure ileum and from 6.7 ± 0.9% to 5.1 ± 0.6% in post‐closure ileum. Labeling index decreased from 26.8 ± 2.5% to 20.0 ± 2.0% in 8‐day‐old rats and from 44.2 ± 2.6% to 31.1 ± 3.0% in 28‐day‐old rats after IPR administration. There were also significant differences in growth fraction between age groups and a significant decrease in growth fraction after IPR‐treatment. From the results of this study it appears that β‐adrenergic stimulation has an inhibitory effect on neonatal ileal epithelium.
KINETICS OF ERYTHROPOIETIN STIMULATED PROLIFERATION OF ERYTHROID PROGENITORS IN THE SPLEEN
Authors: Hasthorpe S. , Hodgson G.
Published: May 2008

The effect of RBC transfusion and erythropoietin (EPO) on the proliferation of immature erythrocyte progenitors was studied in the spleens of RBC transfused, lethally irradiated mice injected with bone marrow. Transfusion decreased expansion of the progenitors and slowed their proliferation: the mean cycle time as measured by per cent labelled mitosis (PLM) on the third day after injection of bone marrow was 10.7 hr in transfused as compared to 5.6 hr in non‐transfused mice. One injection of five units of erythropoietin on day 2 decreased the mean cycle time to 7.3 hr in transfused mice and increased expansion of the progenitor cells. The effects of erythropoietin on cell proliferation were prompt: a significant increase of incorporation of 3H‐TdR into DNA occurred within 2 hr of injection.

Erythroblasts were absent from the spleens of transfused, irradiated bone marrow injected mice; however, erythroblasts appeared by 72 hr and 48 hr following EPO injection either 2 days or 5 days after transplantation respectively. Increased uptake of radioactive iron in spleen after erythropoietin injection preceded the appearance of erythroblasts by 2 and 1 days when erythropoietin was injected either 2 or 5 days after marrow transplantation respectively.

The increase in cellular proliferation induced by erythropoietin in transfused irradiated mice injected with bone marrow equivalent to 0.35 femoral shaft was manifested as an increase of the total DNA content in the spleen by 119 μg (11.9 × 106 cells) within 48 hr of injection. The cellular increment produced by EPO injection on day 5 to mice given 0.05 femoral shaft consisted mainly of undifferentiated mononuclear cells, most of which were labelled, with erythroblasts comprising only one quarter of the increment. Erythropoietin inactivated by mild acid hydrolysis failed to increase cellular proliferation.
MOBILIZATION OF B AND T LYMPHOCYTES AND HAEMOPOIETIC STEM CELLS BY POLYMETHACRYLIC ACID AND DEXTRAN SULPHATE
Authors: Ham A. C. van der , Benner R. , Vos O.
Published: May 2008

The leucocytosis which can be evoked by the polyanions dextran sulphate (DS), polymethacrylic acid (PMAA) and the copolymer of PMAA and styrene (PMAA—STYR) was studied in mice. After intravenous administration of these polyanions peak numbers of leucocytes were found in the peripheral blood 3 hr after injection. All three types of polyanions increased the number of lymphocytes, granulocytes and monocytes. Dose—response studies revealed that the nature of the polyanion determined the degree of leucocyte mobilization. The most potent mobilizer was found to be DS. This polyanion could evoke a six‐fold increase of the number of peripheral blood leucocytes.

By means of the membrane fluorescence technique it could be demonstrated that optimal doses of DS, PMAA and PMAA—STYR mobilized both B and T lymphocytes. The ratio between the number of B and T cells mobilized was greater for DS than for the other two polyanions.

Intravenous injection of DS, PMAA and PMAA—STYR also increased the number of circulating haemopoietic stem cells (CFU‐S). The most potent stem cell mobilizer appeared to be PMAA—STYR. This polyanion evoked a twenty‐five‐fold increase in the number of CFU‐S.
ESTIMATION OF THE MIGRATION OF THORACIC DUCT LYMPHOCYTES TO NON‐LYMPHOID TISSUES
Authors: Rannie G. H. , Donald K. J.
Published: May 2008

The distribution of radioisotopes in tissues was measured following i.v. injection of labelled thoracic duct lymphocytes into syngeneic rats. The rate of elution of an isotope from the labelled cells and the subsequent fate of the eluted isotope were shown to be the most important factors limiting the usefulness of such isotopes for measuring cell localization particularly in non‐lymphoid tissues. Comparison of labelling procedures using [3H] and [14C]uridine, [3H] and [14C]leucine, [75Se]‐L‐selenomethionine, [99mTc]sodium pertechnetate and [51Cr]sodium chromate in vitro and [3H]thymidine in vivo showed that 51Cr had the fewest disadvantages in the present context. Using 5ICr‐labelled cells, the radioactivity was measured in a wide range of non‐lymphoid tissues, and estimates of cell traffic were obtained. In skin, for example, the results indicate a cell flux in the range of 104‐105 lymphocytes/gm/hr. Evidence is presented which suggests that the early substantial localization of labelled cells in the lung is not an artefact due to sequestration or embolization of traumatized cells but probably reflects a slow intravascular transit time through this capillary bed. The primary lymphoid organs, thymus and bone marrow were shown to include a subpopulation of lymphocytes which belong to the recirculating pool. The thymus always contained a greater concentration of radioactivity at 24 hr than all non‐lymphoid tissues except liver and kidney (approx. 0‐1% of the recirculating lymphocyte pool) and the bone marrow was capable of temporarily accepting a substantial proportion (approx. 25%) of the injected cells.
THE EFFECT OF INTESTINAL RESECTION ON THIRY‐VELLA FISTULAE OF JEJUNAL AND ILEAL ORIGIN IN THE RAT: EVIDENCE FOR A SYSTEMIC CONTROL MECHANISM OF CELL RENEWAL
Authors: Hanson W. R. , Rijke R. P. C. , Plaisier H. M. , Ewijk W. Van , Osborne J. W.
Published: May 2008

Local and systemic control mechanisms have been postulated to explain the maintenance of steady state cell renewal in intestinal epithelium. Permanent alterations of cell renewal resulting in a new steady state imply alterations in control. Intestinal resection appears to cause such alterations resulting in hyper‐plasia of the residual intestine. To test the hypothesis of a systemic control, the effect of 60% mid‐intestinal resection on Thiry‐Vella fistulae of both jejunal and ileal origin was observed in rats. Results showed that hypoplasia occurred in fistulae without resection of the remaining intestine in continuity. Cell counts of crypt and villus columns and tritiated thymidine uptake in isolated whole crypts were reduced. Scanning electron microscopy showed marked hypoplastic alterations in villi. However, when 60% of the intestine in continuity was resected, hyperplasia occurred not only in the residual intestine but in the fistulae of both jejunal and ileal origin. Cell counts of villus and crypt columns were increased along with increased tritiated thymidine uptake per crypt. Neutral cc‐glucosidase and non‐specific esterase activities did not change as a result of resection but the activities of both enzymes were greater in ileal fistulae than in ileum in situ. Observations on the different resection response of the jejunal versus ileal fistulae lead to a distinction between inherent and induced differences within the small intestine. This study suggests a systemic control of cell renewal. A possible mechanism involving intestinal vascular physiology is discussed.
PREDICTION OF THE COMPLETE GROWTH PATTERN OF HUMAN MULTIPLE MYELOMA FROM RESTRICTED INITIAL MEASUREMENTS
Authors: Brunton G. F. , Wheldon T. E.
Published: May 2008

A method is presented for predicting the complete growth pattern of human IgG multiple myeloma from a few initial measurements of tumour cell number. This permits identification of patterns of undisturbed neoplastic growth in individual patients whose therapy cannot ethically be withheld for long periods. Since the unperturbed growth pattern is a necessary part of the information required for the prediction of individual patient response to alternative treatment schedules, the prospects for improved treatment of human multiple myeloma by optimal scheduling of drug administration are greatly increased.
AN AUTORADIOGRAPHIC STUDY OF THE 3H‐URIDINE AND 3H‐THYMIDINE INCORPORATION IN THE REGENERATING MOUSE LIVER
Authors: Lorup Christina
Published: May 2008

An autoradiographic study was made of the 3H‐uridine incorporation into RNA and DNA in nucleus and cytoplasm of parenchymal cells in the regenerating liver of the mouse after a pulse time of 2 hr.

After a decreased uptake of precursor into the parenchymal nucleus during the first 6 hr compared with the normal value, incorporation increased and was maximal at 36 hr; normal values were restored at 72 hr. The cytoplasmic labelling, after an initial small decrease, reached a maximum at 12 hr; this changed to normal 48 hr after hepatectomy. RNase‐digestion of the liver sections left a small incorporation in both nucleus and cytoplasm: presumably DNA. This incorporation is maximal at 12 hr over the nucleus and at 24 hr over the cytoplasm.

After a 2 hr pulse of 3H‐thymidine, there was a marked uptake of the precursor into DNA about 24 hr after hepatectomy. This was maximal at 48 hr and reached normal values at 72 hr. A small amount of incorporation of 3H‐thymidine into DNA was seen immediately after the operation, and this population of weakly labelled nuclei was still rather large 72 hr later.
RESPONSIVENESS TO HUMORAL FACTORS OF MOUSE MARROW COLONY FORMING CELLS AFTER TREATMENT WITH CYCLOPHOSPHAMIDE
Authors: Gordon M. Y.
Published: May 2008

Humoral factors affecting granulopoiesis have been detected by culturing bone marrow cells in intraperitoneal diffusion chambers. This study investigated the possibility that treatment with drugs alters the ability of cells to respond to these factors.

Three days after treatment with 200 mg kg‐1 cyclophosphamide, donor marrow cells were more responsive than normal cells to the factors produced in cyclophosphamide pretreated hosts. The optimum timing of host pretreatment for maximum colony stimulation also differed for cells from cyclophosphamide treated and untreated donors and these effects were found to depend on the dose of drug given to the animals.
Effect of Myleran On Murine Hemopoiesis
Authors: Delmonte L.
Published: May 2008

Time‐ and dose‐dependent patterns of depletion and regeneration of hemopoietic progenitor cells in mouse femora and spleens following treatment with the antileukemic agent Myleran (Busulphan, MY) were studied using the murine spleen colony system and the agar gel in vitro colony system. MY was found to depress granulopoiesis selectively, as manifested by the development of marked prolonged neutropenia, hypoplasia of the bone marrow and (to a lesser degree) of the spleen, reduction of the incidence of multipotential hemopoietic progenitor cells (CFU‐S) and of granulocytic progenitor cells (CFU‐C) in both femora and spleens, and impairment of the capacity of CFU‐S from either tissue to generate granulocytic colonies in the spleens of irradiated hosts. the severity and duration was greatest at high dose levels of MY (800 μ). the action of MY on CFU‐S was more pronounced than that on CFU‐C, suggesting that MY is a cycle‐independent agent. Repopulation of the CFU‐C pool preceded that of the CFU‐S pool. Development of neutropenia and maximal marrow hypoplasia followed the onset of depression of CFU‐S and CFU‐C incidence, while recovery of normal nucleated cellularity in the blood, femur and spleen preceded repopulation of the CFU‐S and CFU‐C pools. MY treatment resulted in transitory stimulation of colony stimulating factor (CSF) generation by the femur but had no effect on serum CSF levels. the peak of femoral CSF generation coincided with the nadir of CFU‐C depression. These findings indicated that the prolonged neutropenia following MY treatment was secondary to depletion of the progenitor cell pools, that during recovery granulopoietic repopulation took precedence over self‐maintenance of the hemopoietic progenitor cell pools, and that increased generation of CSF may play a role in the early phase of granulopoietic recovery.
Effect of Myleran On Murine Hemopoiesis
Authors: Delmonte L.
Published: May 2008

The direct and host‐mediated effects of the antileukemia agent Myleran (Busulphan, MY) on murine hemopoietic progenitor cells was assessed in vivo in the differential spleen colony system and in vitro in the agar gel granulocytic colony system. MY destroyed both spleen colony forming cells (CFU‐S) and agar gel colony forming cells (CFU‐C), the effect on CFU‐S being ten‐fold more severe than that on CFU‐C. Moreover, MY indirectly enhanced the seeding efficiency of CFU‐S and directly impaired their capacity to self‐replicate. MY also acted both directly and indirectly to impair the capacity of CFU‐S to generate granulocytic spleen colonies. Both the direct and indirect effect of MY on the CFU‐S' differential spleen colony forming bias was maintained following their retransplantation into lethally irradiated hosts that had not been exposed to MY. Finally, MY acted indirectly to impair the capacity of CFU‐S to differentiate to CFU‐C. the phenomenon appeared to be humorally mediated, since it was induced by exposure of CFU‐S to the MY‐treated host environment but not by their exposure to the MY‐damaged splenic stroma. an effect on the CFU‐S themselves does not appear to have been involved, since impairment of CFU‐C generation could be reversed by retransplantation of the CFU‐S into lethally irradiated hosts that had not been exposed to MY. the findings were compatible with the concept that MY (a) affects the membrane permeability of CFU‐S to modulating agents such as hemopoietins, and/or (b) selectively enhances survival of a subpopulation of erythrocytically committed CFU‐S, and/or (c) selectively abrogates survival of a subpopulation of cells capable of inhibiting commitment to the erythroid cell line.
Comparison of the Effects of Epidermal Chalone In Young and Aging Mice
Authors: Leith J. T.
Published: May 2008

The ability of epidermal chalones to produce inhibition of epidermal mitotic and DNA synthetic activities was investigated in young (2 month old) and old (27 month old) mice. Extracts of epidermal chalone were prepared from the skin of mice of these different ages, and these extracts were then tested for their inhibitory capacities against the same age group from which they were extracted, and also against the mice of the other age group. It was found that the ability of mouse skin to produce tissue‐specific agents with mitotic and DNA‐synthetic inhibitory capabilities did not change significantly with increasing age. There were however, decreases in both the labeling and mitotic indices with aging in untreated mice. These data suggest that chalone‐type inhibitory mechanisms are not primarily responsible for the increased cell cycle times seen to occur with aging in normal tissues.
Purification of Immunosuppressive Factors Extracted From Bovine Spleen (Lymphoid Chalone)
Authors: Lenfant Maryse , Garcia‐Giralt E. , Thomas M. , Di Giusto Laurette
Published: May 2008

A low molecular weight immunosuppressive factor FA which is able to reduce the blastic transformation capacity of lymphoid cells from treated mice has been characterized. It was prepared from a bovine spleen acetone powder and found to be associated partly with high molecular weight carriers in the form of an active complex characterized previously as part of a ‘lymphoid chalone’ fraction. FA may be obtained by selective ultrafiltration of F followed by P‐2 Biogel chromatography of the ultrafiltrate. Thymidine, deoxyinosine and deoxycytidine have been identified as the major constituents of FA by mass spectrometry, ultraviolet absorption data and thin layer chromatography. However, none of these nucleotides has the biological activity of FA.
Purification of Immunosuppressive Factors Extracted From Bovine Spleen (Lymphoid Chalone)
Authors: Garcia‐Giralt E. , Lenfant Maryse , de Garilhe M. Privat , MAYADOUX EVELYNE , MOTTA R.
Published: May 2008

A highly purified extract from bovine spleen (FA) possessing immunosuppressive capacity was studied. Its tissue specificity was analysed in vivo and in vitro and the main components of FA, the well‐known nucleosides deoxycytidine, deoxy‐inosine and thymidine, were tested in vivo.

It seems that the molecule responsible for the biological activity of FA is a new substance endowed with strong specific activity and that lymphoid tissue is highly sensitive to the inhibiting capacity of this purified fraction.
Effect of Hyperthyroidism On Haemopoietic Stem Cell Kinetics In Mice
Authors: Vacek A. , Rotkovská D. , BartoniČková A. , Pospísiil M.
Published: May 2008

Changes in the pool of haemopoietic colony‐forming units (CFUs) of bone marrow and spleen were studied in experiments with mice fed dried thyroid gland (TH) for 21 days, and during the 13 days that followed feeding. After HU treatment, the number of CFUs in DNA synthesis was estimated. As early as the second day of TH treatment, the pool of CFUs is gradually increased, leading to an increase in the total number of splenic and bone marrow CFUs persisting after TH treatment for the period examined. Simultaneously, the numbers of nucleated cells in the bone marrow and spleen are increased. During TH feeding and following its termination, the total number of erythrocytes and the haematocrit values did not change significantly, whereas an increased number of leucocytes was observed in the peripheral blood after TH treatment. Elevation of the proliferative activity of CFUs occurred early in the period of TH treatment, with the maximum attained by end of the first week of TH feeding. This suggests a rapid response of the haemopoietic stem cell compartment to the administration of TH hormones. the participation of humoral factors controlling CFUs compartments in the mechanism of the stimulatory effect of TH hormones on haemopoietic stem cells is discussed.
Enhanced Post‐Irradiation Recovery of the Haemopoietic System In Animals Pretreated With A Variety of Cytotoxic Agents
Authors: Millar J. L. , Blackett N. M. , Hudspith B. N.
Published: May 2008

It is known that pretreatment of mice with bacterial endotoxin and certain stathmokinetic agents between 1 and 3 days prior to exposure to ionizing radiation reduce radiation lethality. In this communication it is shown that pretreatment with cytosine arabinoside, methotrexate, nortestosterone and chlorambucil reduces radiation (1000 rad) induced lethality. This reduction can be ascribed to enhanced regeneration of the haemopoietic system in pretreated animals and not to increased survival of colony‐forming cells (CFU) in these animals. Regeneration of CFUs was underway within 24 hr after 900 rad in the pretreated mice but did not start until day 3 in mice treated with γ radiation only. Two agents, namely radiation itself (either 75 or 150 rad) and busulphan (10 mg/kg) did not reduce the lethal effects of subsequent γ irradiation nor enhance the regeneration of CFUs, even though radiation, like the protective cytosine arabinoside, induces early CFUs proliferation.

The administration of nucleoside precursors of DNA enhanced regrowth of haemopoietic stem cells to an extent comparable with that of the most effective pretreatment, cytosine arabinoside. It is postulated that drugs like cytosine arabinoside operate by causing cell death, providing a source of DNA that can enhance the regrowth of surviving stem cells in the bone marrow.
REGRESSION of the MOUSE PAROTID GLAND INDUCED WITH ISOPROTERENOL
Authors: Domon M. , Okano T. , Sasaki T. , Nakamura T.
Published: May 2008

Acinar cells in rodent salivary glands are induced into one cycle of cell proliferation by a single injection of isoproterenol (IPR) (Baserga, 1970). Repeated injections of animals with IPR lead these cells to a few cycles of cell proliferation and then hypertrophy, when IPR stimulated proliferative response is lost and enlargement of the glands occurs. Without further IPR injections the enlarged glands regress to a normal size (Barka, 1965; van den Brenk, Sparrow & Moore, 1970). the present communication concerns the regression, or disappearance and reappearance, of the acinar cells which respond to IPR treatment.

The parotid responds more readily to IPR in respect of cell proliferation and gland enlargement than the submaxillary gland (Baserga, 1970) and so was used in all studies. to produce full cell proliferation in the parotid, male SWR mice aged 3 months were given four injections at 48 hr intervals of DL‐isoproterenol‐HC1 (Sigma, St Louis, Missouri) at the dose of 7.5 mg per 30 g body weight. In the following description day zero refers to the date of fourth IPR injection. the parotid was then dissected out from animals at various days, and carefully freed of lymph nodes and fat tissues under a dissecting microscope. DNA content per gland (extracted by the method of Scott, Fraccastoro & Taft, 1956; Sasaki & Toda, 1972) increasea with the number of IPR injections, reaching a maximum after the fourth (Furuno, Iwasaki & Matsu‐daira, 1974), and then reverted to a control level in 15 days (Fig. 1). to follow the acinar cells induced into DNA synthesis, 20 hr after a second IPR treatment animals received single injections of methyl‐3H‐thymidine (The Radiochemical Centre, Arnersham, England) (3H‐TdR) by the amount of 20 μCi per 30 g body weight and then were killed at various intervals. Measurements were made on the amount of parotid DNA and its radioactivity in each animal, from which the specific activity of parotid DNA was calculated. the specific activity decreased about seven‐fold to a constant level in 15 days (Fig. 1). the DNA synthesis stimulated by a third and a fourth IPR treatment would account for the decrease in specific activity between day 3 and day 1. an autoradiographic study gave some estimate of cell turnover in the period day 1 to day 10. the IPR‐treated mice were given seventeen injections of 3H‐TdR at 12 hr intervals from 20.00 hours on day 2 to 20.00 hours on day 10 and then
Brief Communication Commercial Pha Preparations Contain Different Mitogenic Components
Authors: Smith C. J. , Allen J. C.
Published: May 2008

Three commercially available purified phytohaemagglutinin (PHA) preparations have been examined both chemically and biologically. Marked differences were observed in both composition and mitogenic effect on lymphocytes; the existence of at least two distinct mitogenic fractions in PHA was confirmed.

A number of commercial preparations of PHA have become available for use as mitogens in lymphocyte cultures. Since there is no cross‐standardization of biological activity between these preparations, workers have used their own discretion about which to use and whether further purification is desirable.

Three commercial purified PHA preparations have been examined, and marked biological and chemical differences have been found.