bluuebunny/crossref_metadata_2025 huggingface dataset:
CONTROL OF GRANULOCYTE PRODUCTION: SEPARATION AND CHEMICAL IDENTIFICATION OF A SPECIFIC INHIBITOR (CHALONE)
Authors: Paukovits W. R.
Published: May 2008

Abstract. It has previously been shown by others that blood serum contains inhibitors of blood cell production acting on the proliferation of granulocy tic and erythrocytic precursor cells in the bone marrow. It is now shown that the active extract from calf blood serum can be further subfractionated into six different components, all of them exhibiting inhibitory effects on the proliferation of rat bone marrow cells in vitro. Ascitic fluid from rats treated intraperitoneally with polyvinylpyrrolidone contains inhibitors which apparently are the same as those found in calf serum.

It was further possible to demonstrate that only one of these inhibitors is contained in mature granulocytes where it is actively synthesized from amino acids and subsequently released into the surrounding medium. By chromatography on Sephadex G‐25 of this conditioned medium the inhibiting substance could be obtained in relatively pure form being contaminated only by low amounts of two ninyhdrin‐positive substances. the experiments allow the granulocytic inhibitor to be identified as a polypeptide with a molecular weight below 5000. the results suggest that this substance is the granulocytic chalone.
Human Lymphocyte Proliferation: Dna Synthesis Time
Authors: Schiffer L. M.
Published: May 2008

Abstract. The DNA synthesis time (Ts) of lymphocytes from spleens and lymph nodes of patients with Hodgkin's disease was determined by the double labeling method. 3H‐TdR was administered in vivo and removed tissues minced in 14C‐TdR in vitro. Lymphocytes from patients with lymphosarcoma and reticulum cell sarcoma were studied in a similar manner. Lymphocytes were divided into A cells, small with non‐basophilic cytoplasm, B cells, small with basophilic cytoplasm, C cells, large with non‐basophilic cytoplasm, and D cells, large with basophilic cytoplasm.

The Ts of splenic lymphocytes, in four samples not containing Reed‐Sternberg cells, in hours, was: B 11.3; C, 7.9; D, 8.4; combined, 8.8. the Ts of B lymphocytes was significantly longer than that of C and D lymphocytes. A lymphocytes did not label sufficiently to measure Ts. C and D lymph node lymphocytes and lymphocytes in tissues containing Reed‐Sternberg cells had a longer Ts than splenic C and D cells. the former was: B, 12.7; C, 11.7; D, 11.0; combined, 11.8. the latter was: B, 12.2; C, 11.3; D, 11.2; combined, 11.6. the Ts of Reed‐Sternberg cells in one specimen of a splenic Hodgkin's tumor was 13.1 hr. Macrophage Ts was 10.7 and 15.1 hr. Lymphosarcoma cell Ts was 14.2 and 14.6 hr. Reticulum cell sarcoma cell Ts was 7.5 and 7.7 hr.

The following minimum times were calculated from observation of 3H‐TdR only labeled mitotic figures: S to prophase, 71 min; S to metaphase, 75 min; S to telophase, 100 min.
THE DISTRIBUTION OF MONOCYTES IN THE RAT
Authors: Whitelaw D. M. , Batho H. F.
Published: May 2008

In the rat, labeled transfused monocytes initially leave the circulation with a halftime of 0.2 hr. They first collect on the walls of small vessels then migrate outward until equilibrium is established between the circulating pool and a large extravascular pool which contains about twenty‐five times as many monocytes as the circulating blood. From this pool they leave randomly and irreversibly with a halftime of 14 hr. The spleen and lungs make up a large part of the pool and splenectomy reduces the size of the extravascular compartment and slows the rate of sequestration.
LOCATION OF THE G0‐PHASE IN THE CELL CYCLE OF THE MOUSE HAEMOPOIETIC SPLEEN COLONY FORMING CELLS
Authors: Lahiri S. K. , Van Putten L. M.
Published: May 2008

Experiments in mice on the fraction of haemopoietic stem cells in S‐phase after irradiation indicated that a large fraction of the cells resting in G0 will enter S‐phase after a very short interval of time.

After excluding alternative explanations it must be concluded that cells in G0 have completed all preparations for going into S‐phase or, in other words, that the localization of these G0 cells in relation to other phases of the cell cycle must be between G1 and S‐phase.
CELL KINETICS OF GROWTH CARTILAGE IN THE RAT TIBIA I. MEASUREMENTS IN YOUNG MALE RATS
Authors: Walker K. V. R. , Kember N. F.
Published: May 2008

Cell kinetic parameters for the proximal growth plate of the tibia have been measured in young rats. Analysis of a pulse labelled mitosis study gave values of 55 ± 40 hr for the cycle time and 6.5 ± 0.3 hr for the synthesis time in 6‐week‐old rats. The results of a simulated continuous labelling experiment agreed with this data and provided further information on the size and proliferation rate of the stem cell zone. Diurnal variations in mitotic index and labelling index in the tissue have been investigated.
INFLUENCE OF AGE AND ANTIGENIC STIMULATION ON GRANULOCYTE AND MACROPHAGE PROGENITOR CELLS IN THE MOUSE SPLEEN
Authors: Metcalf D. , Stevens S.
Published: May 2008

The frequency and proliferative activity of granulocytic and macrophage progenitor cells were determined in the spleens of C57BL, BALD/c, NZB and CBA mice. These cells were detected by their capacity to form granulocytic and/or macrophage colonies (in vitro colony‐forming cells, CFC) in agar culture. In vitro CFCs were low in frequency in the adult spleen (4–28/105 cells) compared with the bone marrow (180–280/105 cells). However, the neonatal spleen, both in germfree and conventional mice, contained high levels of in vitro CFCs. From the low suiciding index with tritiated thymidine and the small numbers of cluster‐forming cells in relation to colony numbers, many in vitro CFCs in the adult C57BL spleen appear to be in a non‐cycling state. The level and activity of in vitro CFCs were extremely low in the spleen of adult germfree CBA mice but were greatly increased in conventional mice following the injection of a bacterial antigen.
EFFECT OF ERYTHROPOIETIN ON PROLIFERATION OF ERYTHROPOIETIN‐RESPONSIVE CELLS
Authors: Reissmann K. R. , Udupa K. B.
Published: May 2008

A single dose of Myleran suppressed CFU in polycythemic mice to around 1% of normal for a period of 2 weeks and permitted the study of effects of erythropoietin on unipotential, erythroid stem cells (erythropoietin‐responsive cells, ERC) in the absence of cell inflow from the CFU compartment. Without erythropoietin no ERC were detectable for 12 days after Myleran. Injections of erythropoietin had no effect on CFU but restored ERC populations in proportion to the dose of erythropoietin. Hydroxyurea given after erythropoietin markedly inhibited ERC repopulation and the latter is attributed to a stimulation of ERC proliferation by erythropoietin. Evidence in support of an age structure in the ERC population is presented. Daily erythropoietin injection resulted in stable ERC populations, indicating that ERC loss through differentiation and ERC self‐replication were in balance.
CELL DIFFERENTIATION AND CARCINOGENESIS: A CRITICAL REVIEW*
Authors: Dustin P.
Published: May 2008

Many resemblances exist between cell differentiation and neoplastic change: the importance of cytoplasmic factors is particularly evident, as the genotype appears to remain unmodified in the nuclei of differentiated as in malignant cells.

There is no opposition between malignancy and differentiation, highly malignant cells retaining in many cases a differentiation very close to normal. Loss of differentiation in malignancy is only an epiphenomenon.

While differentiation appears to be partially reversible, and in some models totally reversible, neoplastic changes are, with a very small number of exceptions, irreversible. Differentiation involves the gradual change of a group or a population of cells, malignancy of a single cell.

Further work on the molecular basis of differentiation would help to understand the nature of neoplasia, and vice versa.
DNA TURNOVER IN ADRENAL MEDULLARY CELLS OF DIFFERENT STRAINS OF RATS AND ITS ENHANCEMENT AFTER INTERMITTENT EXPOSURE TO COLD
Authors: Malvaldi G. , Viola‐Magni Maria Pia
Published: May 2008

In Italico and Wistar rats maintained at room temperature 1% of nuclei of cells in the adrenal medulla incorporate 3H‐thymidine. Following intermittent exposure to cold, the numbers incorporating increase to 10% and 7% in Italico and Wistar strains respectively. Only in the Wistar strain does the increase occur during actual exposure.

Assuming S to be 6–8 hr the labelling indices actually determined indicate a turnover time of DNA of 21–29 days. Since mitotic indices in experimental and control animals were found to be 0.004% without colchicine treatment and 0.009% after 3 hr of colchicine treatment, the turnover times of cells were calculated to be 1388–3125 days. To correlate mitotic indices and labelling indices, an S period of 400 hr would have to be assumed. It is concluded therefore that: (i) most of the observed labelling of DNA is due to metabolic turnover of DNA and only a small proportion represents pre‐mitotic synthesis, (ii) differences in the rates of DNA synthesis found during exposure to cold in Italico and Wistar rats respectively are sufficient to account for the differences in reduction of DNA previously found between the two strains under these experimental conditions.
HEMOPOIETIC STEM CELL PROLIFERATION AND MIGRATION FOLLOWING BORDETELLA PERTUSSIS VACCINE
Authors: Monette Francis C. , Morse Bernard S. , Howard Donald , Niskanen Eero , Stohlman Frederick
Published: May 2008

The ability of a single injection of killed, intact bacteria to effect an increase in the proliferative rate of hemopoietic stem cells was studied. The total numbers of colony forming units in bone marrow, spleen and peripheral blood as well as the proportion of CFU in cycle was assessed. Splenic CFU were observed to rise exponentially due initially to in situ proliferation and later to proliferation in bone marrow with migration via the blood to the spleen. The results are discussed in the light of current concepts of stem cell regulation.
CELL PROLIFERATION IN HAEMATOPOIETIC SPLEEN COLONIES OF MICE: DIFFERENCE BETWEEN COLONIES DERIVED FROM INJECTED ADULT BONE MARROW AND FOETAL LIVER CELLS
Authors: Micklem H. S.
Published: May 2008

Cell proliferation in mouse spleen colonies, derived from injected foetal liver and young adult bone marrow, was studied by measuring incorporation of radio‐iodine‐labelled 5‐iodo‐2′‐deoxyuridine (IUdR). Foetal liver‐derived colonies incorporated significantly more IUdR than marrow‐derived colonies on the 8th and 12th days after cell injection. The data are consistent with the view that foetal haematopoietic stem cells are capable, on average, of producing larger descendant populations than are stem cells from young adults.
COLONY FORMING CELLS IN THE LIVERS OF PRENATAL FLEXED (f/f) ANAEMIC MICE
Authors: Bateman A. E. , Cole R. J.
Published: May 2008

The colony forming unit (c.f.u.) content of foetal livers of f/f and f/+ genotypes has been investigated. Although proportions of c.f.u. to nucleated liver cells do not vary with genotype, the total number of c.f.u. and erythroid cells per foetus is reduced in f/f embryos from 11 to 16 days of gestation. The differentiative capacity of f/f stem cells, measured by 59Fe uptake into blood 7 days after transplantation of cells, was less than that of f/+ stem cells. An initially low growth rate of c.f.u. in early foetal liver and in young spleen colonies can explain several characteristics of flexed erythropoiesis.
TEMPORARY LOCALIZED DEPRESSION OF TRITIATED THYMIDINE INCORPORATION IN MOUSE TISSUES AFTER PULSE LABELLING
Authors: Potten Christopher S. , Hagemann Ronald F. , Reiland Jean M.
Published: May 2008

Approximately two to six in every 100 mice injected with 3H‐TdR appear not to incorporate the labelled precursor into the DNA. The tritium activity appears to be distributed throughout these poor utilizers of thymidine. The lack of incorporation of the precursor is not always general to the whole animal but may be restricted to a given tissue. The effect does not appear to be permanent but varies with time.
AUTORADIOGRAPHIC DETECTION OF DNA POLYMERASE CONTAINING NUCLEI IN SARCOMA 180 ASCITES CELLS
Authors: Nelson Janet S. R. , Schiffer Lewis M.
Published: May 2008

A technique has been developed allowing the autoradiographic detection of incorporation of 3H‐thymidine‐5′‐triphosphate (3H‐TTP) into nuclear DNA of smears of Sarcoma‐180 (S‐180) mouse ascites tumors under the direction of the cell's own nuclear DNA polymerase. Dried smears are dipped into an agar solution, which strips cytoplasm from the nuclei, and are then air dried and incubated with a buffered mixture containing four nucleotide triphosphates (one labeled), Mg++, and Ficoll, with the cell's own DNA acting as primer. The incorporation of 3H‐TTP into the nuclei, like the cell free DNA polymerase assay, is largely dependent on the presence of all four nucleotide triphosphates and Mg++ and produces a product which is DNase sensitive and RNase resistant.

DNA polymerase activity, as studied in a cell free assay, decreases with tumor age. This correlates well with a decreasing 3H‐TTP labeling index in autoradiographs of aging tumors. The 3H‐TTP labeling index has also been shown to exceed but parallel the in vivo3H‐thymidine (3H‐TdR) pulse labeling index for all tumor ages examined.

In at least some cell systems DNA polymerase seems characteristic of cells in cycle. The autoradiographic detection of nuclei containing the enzyme offers a new tool for the study of tumor cytokinetics.
COMPUTER SIMULATION OF GROWING CELL POPULATIONS
Authors: Valleron A.‐J. , Frindel E.
Published: May 2008

A new technique of computer simulation of growing population of cells is presented. This method can be used to study various biological problems the examples of which are discussed in this paper.
THE CELL SPECIFIC EFFECT OF THE GRANULOCYTE CHALONE DEMONSTRATED WITH THE DIFFUSION CHAMBER TECHNIQUE
Authors: Benestad H. B. , Rytömaa T. , Kiviniemi Kyllikki
Published: May 2008

The granulocytic chalone is secreted by mature granulocytes and inhibits 3H‐thymidine incorporation of proliferating granulocytes in vitro. The effect and the cell line specificity of this chalone was assessed with the in vivo diffusion chamber culture technique. Tests were carried out on cultures from normal mouse bone marrow cells and mouse and rat blood leucocytes. The majority of the DNA synthesizing cells in marrow cultures were proliferating granulocytes. Macrophages and immunoblasts proliferated in rat leucocyte cultures, when the chambers had been carried for 5 days in host mice. Repeated chalone or control injections were given i.p. to the host mice during 6–7 hr prior to 3H‐thymidine injection. Isotope uptake of proliferative granulocytes was reduced by the chalone treatment. No such effect was found on the rat immunoblasts and macrophages. The viability of cultured cells was apparently not affected by the chalone treatment.
CELL PROLIFERATION IN THE CASTRATE MOUSE SEMINAL VESICLE IN RESPONSE TO TESTOSTERONE PROPIONATE
Authors: Appleton David , Morley Adrian R. , Wright Nicholas A.
Published: May 2008

The cell cycle kinetics of a conditional renewal system which has been stimulated by a continuing supply of hormone were investigated by means of a model, basic to which is the concept of decycling probability. The integral equations of the system were formulated and solved numerically in an environment of interaction with the computer. Graphical output on a visual display screen was used to facilitate the extraction of information from the model, and its consistency with experimental data was demonstrated.
CYTOLOGICAL CHARACTERISTICS OF NORMAL HUMAN PERIPHERAL BLOOD CELLS IN CULTURE BEFORE ESTABLISHMENT INTO LYMPHOCYTOID CELL LINES*
Authors: v. Heyden H. W. , Heyden Dorit v.
Published: May 2008

Human peripheral blood cells were observed in culture. Attached cells and those floating in the supernatant fluid were classified as macrophages, lymphoid and fibroblastoid cells. Peroxidase positive granules were demonstrated in macrophages and fibroblastoid cells. It is concluded that (a) appearance of macrophages is dependent on the formation of a monolayer, (b) a gradient relationship between the attached and supernatant cells exists, (c) some fibroblastoid cells are derived from macrophages, and (d) lymphocytes alone are not able to form a monolayer.
SPERMATOGONIAL STEM CELL RENEWAL IN THE MOUSE: II AFTER CELL LOSS
Authors: van Keulen C. J. G. , de Rooij D. G.
Published: May 2008

The repair of the mouse seminiferous epithelium after cell loss has been studied in seminiferous tubules mounted in toto. Cell loss was inflicted by injection of Myleran in a dose of 10 mg/kg body weight. In stages 7–8, in which we mainly counted, the numbers of Aisolated (Ais), Apaired (Apr), Aaligned (Aal) and A1 spermatogonia and resting primary spermatocytes decreased after injection. After about 24 days normal numbers of A1 spermatogonia were found again. Thereafter a substantial overshoot in the number of A1 spermatogonia was found.

While normally most of the Apr and Aal cells differentiate into A1 spermatogonia in stages 3 and 4 and do not divide until stage 9, during repair they pass through one more division during stages 6 and 7. Normally, during these stages divisions of these spermatogonia are rare. Owing to this extra division the transformation of Apr and Aal into A1 spermatogonia is delayed from stage 3 or 4 to stage 8, i.e. still before stage 9, in which A1 spermatogonia divide. From 16 days after the injection onwards the extra division takes place less generally and more and more cells transform into A1 spermatogonia at the normal time.
ON THE RESTING STAGES OF THE JB‐1 ASCITES TUMOUR
Authors: Bichel P. , Dombernowsky P.
Published: May 2008

Cytophotometric determination of single‐cell DNA after repeated 3H‐thymidine labelling of the JB‐1 ascites tumour in the plateau phase of growth showed a massive accumulation of unlabelled cells with both G1 and G2 content. Autoradiography combined with cytophotometry or colcemid block demonstrated that some of these unlabelled cells were rapidly triggered into the cell cycle when plateau tumours were transferred to new hosts. This indicated that tumour cells may be held up in non‐cycling stages corresponding to both the G1 and the G2 phase of the cell cycle.
KINETICS OF NEUTROPHILIC GRANULOCYTES IN THE BLOOD OF RATS
Authors: Gerecke D. , Schultze B. , Maurer W.
Published: May 2008

The kinetics of neutrophilic granulocytes in the blood of rats were investigated using in vivo3H‐TdR labelling and autoradiography. The radioactive precursor was administered by single injection, repeated injections at 5 hr intervals and continuous infusion. The appearance of labelled granulocytes in the blood and in the sputum was recorded up to 120 hr after tracer application. In contrast to results after a single injection of 3H‐TdR, complete labelling of the blood granulocyte pool was achieved when the DNA precursor was given by continuous infusion or four repeated injections at 5 hr intervals. In the latter experiments, an exponential replacement of unlabelled blood granulocytes by labelled granulocytes could be demonstrated, the mean intravascular half‐life being 5·7 hr. This figure is in good agreement with values obtained by isotopic techniques in other mammalian species.
COMPUTER OPTIMIZATION OF THE FRACTION OF LABELLED MITOSES ANALYSIS USING THE FAST FOURIER TRANSFORM
Authors: Ashihara Tsukasa
Published: May 2008

This paper provides a numerical technique for the solution of the fraction of labelled mitoses curve. The essence of the method is to facilitate convolutions of phase time distributions using the FFT. This FFT method, in conjunction with the optimization technique, is found to be an efficient, general procedure.
RESPONSE OF MOUSE BONE MARROW COLONY FORMING UNITS IN DIFFERENT STAGES OF THE CELL CYCLE TO IN VITRO INCUBATION WITH MITOMYCIN‐C
Authors: Lahiri S. K.
Published: May 2008

A short‐term in vitro method was employed to study the Mitomycin‐C sensitivity of normal mouse bone marrow CFU without triggering the G0‐phase cells into the proliferative cycle. Comparison was made of the toxicities of the drug against cells in different phases of the cell cycle including G0. Mitomycin‐c killed CFU both in and out of the S‐phase. No significant difference could be found between its toxicities against normal and proliferating CFU; along the exponential part of the survival curve 1·6 μg/ml concentration of the drug reduced survival to 10%. Although in the normal bone marrow only a few CFU are in the S‐phase and are killed by the agent, presence of the sensitive G0 cells produce a significant amount of non‐S‐phase mortality. Among the proliferating CFU population the non‐S‐phase lethality is less due to the absence of G0 cells. About 75% of the S‐phase cells are killed after incubation with 1 μg/ml drug; outside the S‐phase, the lethality is about 40–50%. The studies indicate that the G0 cells which are situated near the G1‐S boundary are almost as sensitive to the drug as other non‐S‐phase cells like G1 cells. The clinical significance of the findings is discussed.
A NOTE CONCERNING NON‐UNIFORM POOL LABELING
Authors: Prothero John W. , Tyler Ruth
Published: May 2008

An analytical relation is suggested, which in certain cases may permit the labeling pattern of a cellular compartment to be computed from the labeling pattern of cells in a precursor compartment.
DOUBLE PULSE LABELLING WITH 3H‐THYMIDINE: A METHOD FOR CALCULATING CELL POPULATIO KINETICS
Authors: Sharav Y. , Brin‐Erb I. , Sciaky I.
Published: May 2008

A method was developed for calculating cell population kinetics with the aid of double pulse labelling with 3H‐TdR. The labelling index was measured from auto‐radiographs of the oral epithelium of two groups of 30‐day‐old rats. One group was injected once with 3H‐TdR the other twice, with a time interval of 90 min between injections. DNA synthesis time was calculated from the equation:

where Ts= synthesis time; LI1= labelling index in the single‐injected group; LI2= labelling index in the double‐injected group; and Ti= time interval between injections. Synthesis time in the palate was 4.8 hr and 7.6 hr in the tongue. Generation time was calculated from the equation: Tg= (Ts/LI1) × 100, where Tg= generation time. Generation time in the palate was 46.1 hr and 75.8 hr in the tongue
PERIODIC THERMAL STRESS: OPTIMAL SPACING PREDICTED BY A SIMPLE SET‐BACK MODEL OF CELL DIVISION SYNCHRONIZATION
Authors: Rooney David W. , Kovac Anthony L.
Published: May 2008

Digital computer simulations have been used to make quantitative predictions based on a simple set‐back model of cell division synchronization. According to the model appropriate thermal stress reverses progress within a segment of the division cycle called the set‐back interval. In the simulations normally distributed cell‐to‐cell variations in division cycling rate between periodic thermal shocks were produced with the Monte Carlo method.

The simulations have shown that reasonably good synchronization with the single shock per division strategy requires a relatively long set‐back interval and small cell‐to‐cell variations in rate of progress through the division cycle. The simulations have shown that the degree of synchrony produced by such periodic shocks is highly dependent on the time interval between shocks—with a series of as many as seven shocks inappropriately spaced producing less synchrony than a single shock! The optimal time interval between successive thermal shocks was found approximately equal to the mode division cycle time at synchrony equilibrium multiplied by 1 plus half the fraction of the division cycle occupied by the set‐back interval. Position of the set‐back interval within the division cycle had little effect on synchrony at the end of the final shock.
IN VITRO PRODUCTION OF COLONY‐STIMULATING ACTIVITY. I. EXPOSURE OF MOUSE PERITONEAL CELLS TO ENDOTOXIN
Authors: Eaves A. C. , Bruce W. R.
Published: May 2008

Cell suspensions, obtained from bone marrow, spleen, thymus, lung, liver, and from peritoneal washings, were incubated in vitro with low concentrations of endo‐toxin and the supernatant media assayed for colony‐stimulating activity (CSA). Peritoneal cells were markedly responsive. The kinetics of CSA production in vitro by peritoneal cells were not remarkably different from that seen in vivo following intravenous administration of endotoxin. The activities of CSA prepared from peritoneal cells and serum were compared following serial dilution; both gave a similar linear relationship when plotted as a function of log‐concentration. The bulk of the CSA was produced by adherent peritoneal cells. Separation of peritoneal cells by velocity sedimentation showed that the CSA‐producing cell had a sedimentation velocity of 7 mm/hr. Cells with this sedimentation velocity were found to be large mononuclear cells which demonstrated adherence and phagocytosis.
CFU‐C YIELDS FROM THE HAEMOPOIETIC TISSUES OF NORMAL AND LEUKAEMIC RFM MICE
Authors: Gordon Myrtle Y. , Coggle J. E.
Published: May 2008

Spleen and bone marrow cells from normal and leukaemic RFM mice have been assayed for numbers of colony forming cells in soft agar (CFU‐C). The fluctuations in CFU‐C yield observed during the development of myeloid leukaemia are similar to the results from in vitro experiments set up to test a model, and are not incompatible with the idea that interaction between normal and leukaemic cells may modify the yield of CFU‐C under the present conditions of culture. Colonies grown from leukaemic spleen and bone marrow cells appear to be derived from the residual population of normal haemopoietic cells within the leukaemic mouse.
THE EPIDERMAL PROLIFERATIVE UNIT: THE POSSIBLE ROLE OF THE CENTRAL BASAL CELL
Authors: Potten Christopher S.
Published: May 2008

A model is suggested for the organization of the epidermis based on the ordered structure of the differentiating layers, as demonstrated by published work. This ordered structure enables one to look through the epidermis at the basal cell nuclei and to see their arrangement beneath the differentiating column of cells. In dorsal skin from male DBA‐2 mice there are 10.6 basal nuclei beneath a column of cells. The central nucleus of the group responds slightly earlier and more effectively than the rest to stimulation, is cycling more slowly than the majority of the basal nuclei and may spend significant periods of time out of cycle.

The skin appears to contain a series of fairly independent proliferative units, each of which contain ten or eleven basal nuclei and eight to ten superficial cells of which only the youngest one or two retain their nuclei. At the centre of each group of basal nuclei is a cell that behaves differently from the rest and which is present in the skin in numbers compatible with the number of clonogenic cells. It is suggested that this represents the basic stem cell of the unit.
ADAPTATION OF HEMOPOIETIC TISSUE RESULTING FROM ESTRONE‐INDUCED OSTEOSCLEROSIS IN MICE
Authors: Morse Bernard S. , Giuliani Dennis , Soremekun Maurice , DiFino Santo , Giuliani E. Regina
Published: May 2008

The redistribution of hemopoietic tissue resulting from estrone‐induced osteosclerosis in the mouse was studied. As the marrow was gradually replaced by bone, extramedullary hematopoiesis in the spleen increased at a rate sufficient to maintain hemopoietic homeostasis.

The total numbers of colony forming units (CFU) in the tibia and spleen as well as the proportion of CFU in cycle was assessed. After five injections of estrone, tibial CFUs decreased to 2% of control values whereas splenic CFUs increased approximately nine‐fold. The proliferative capacity of the splenic CFU was also increased in the estrone‐treated animals. The increased numbers of splenic CFUs as well as the increased proliferative capacity of this compartment are probably related to the ability of extramedullary hematopoiesis in the spleen to compensate for a marrow that has been replaced by bone.
KINETICS OF DEVELOPMENT OF EMBRYONIC ERYTHROID CELLS
Authors: Wheldon T. E. , Kirk J. , Orr J. S. , Paul J. , Conkie D.
Published: May 2008

Embryonic erythropoiesis is an intrinsically non‐steady‐state process. A method of non‐steady‐state analysis is employed to approximately determine the kinetics of maturation of embryonic erythroid cells during the hepatic phase of erythropoiesis in the mouse.

It appears from this analysis that embryonic erythroid cells have significantly shorter maturation times than their adult counterparts. In the embryo, there is insufficient time for more than three divisions between the proerythroblast and the orthochromatic erythroblast.
AN AUTOMATIC SYNCHRONIZER FOR SUSPENSION CULTURE OF L5178Y CELLS
Authors: Okada S. , Shinohara K.
Published: May 2008

The excess thymidine‐colcemid synchronization method for mouse leukemia L5178Y was automated by deleting the removal of excess thymidine. The synchronizer adds thymidine and colcemid at predetermined times and makes the population accumulated at mitosis available at a designated time. The apparatus is inexpensive to build, easily operated and applicable to large volumes of a static suspension culture.
THYMIDINE SUICIDE IN VIVO AND IN VITRO OF SPLEEN COLONY FORMING AND AGAR COLONY FORMING CELLS OF MOUSE BONE MARROW
Authors: Blackett N. M. , Millard R. E. , Belcher H. M.
Published: May 2008

The ‘thymidine suicide’technique for indicating differences in the proliferation rate of early haemopoietic progenitor cells (spleen colony forming and agar colony forming cells) in C57BL mice has been evaluated. Special care was taken to use the same bone marrow cell suspension for the two progenitor cell assays. Both the in vivo and the in vitro techniques were employed.

Following 3H‐TdR in vivo, about 20% of both types of progenitor cell are killed in normal mice; however, after incubation in vitro with 3H‐TdR, 35% of agar colony forming cells but only 4% of spleen colony forming cells are killed. Reasons for the difference between the in vivo and the in vitro results are discussed. With bone marrow from continuously irradiated animals, the thymidine suicide for both agar colony forming and spleen colony forming cells is in the range 42–50%, and there is no difference between in vivo and in vitro suicide.

The in vivo results support the conclusion, based on the effect of proliferation dependent cytotoxic agents, that in C57BL mice agar colony forming and spleen colony forming cells are proliferating at the same rate in normal animals, and are speeded up to the same extent by continuous γ‐irradiation. It is considered that in normal C57BL mice the in vitro method does not give a correct estimate of the proliferation rate of these progenitor cells.

It would seem that the similarity in the proliferation rate of agar colony forming and spleen colony forming cells in C57BL mice is not true for other strains of mice: indeed using normal CBA and in vivo suicide, we have shown a significantly greater thymidine suicide for agar colony forming cells compared to spleen colony forming cells.
SENSITIVITY OF EARLY EMBRYONIC THYMIC LYMPHOID DEVELOPMENT TO 3H‐THYMIDINE OF HIGH SPECIFIC ACTIVITY
Authors: Juhlin Roger , Alm Gunnar V.
Published: May 2008

The pulse technique, using high specific activity 3H‐TdR to selectively kill cells in cell cycle, was applied to the thymic anlagen of chick embryos. With optimal specific and total 3H‐TdR activities and pulse times of 2–4 hr the subsequent lymphoid development in organ culture of the thymic anlagen of 10‐day‐old chick embryos could be almost completely inhibited.

The most important effect of the 3H‐TdR was on the lymphoid precursor cells of the anlagen. The thymic epithelium appeared more resistant to 3H‐TdR and allowed a lymphoid development of pulsed anlagen grafted to the chorioallantoic membrane of chick embryos when new lymphoid precursor cells were provided. The lymphoid precursor cells of the thymic anlagen of 10‐day‐old chick embryos therefore appeared to be in cell cycle with short generation time.

The thymic anlagen of 8‐, 9‐ and 10‐day‐old but not 7‐day‐old embryos showed a lymphoid development in organ culture. They did not differ with respect to the sensitivity to hot pulses of 3H‐TdR. Thus no evidence of a lag in the onset of lymphoid precursor cell proliferation during the development of the early embryonic chick thymus was noted.
CELL POPULATION KINETICS OF TRANSPLANTED AND METASTATIC LEWIS LUNG CARCINOMA
Authors: Simpson‐Herren L. , Sanford A. H. , Holmquist J. P.
Published: May 2008

The growth rate of Lewis lung carcinoma, either as primary subcutaneous tumors or as spontaneous lung metastases, decreases with increasing age or mass. The length of the median cell cycle of the primary tumors increased from 17.6 hr at Day 5 to 25.9 hr at Day 21 with a concomitant increase in experimental doubling time from 2.5 to 9.6 days. The length of the median cell cycle of the metastatic lung nodules was 15.2 hr in the mice bearing 21‐day primary tumors. Two mathematical models were used to analyse the per cent labeled mitoses data and the results are given for comparison.

The labeling index of the primary tumors decreased in a nearly linear manner with time postimplant and the percentage of cells labeled in the metastatic nodules was higher than in the primary tumors when measured in the same hosts.
DELAYED RESPONSE TO ERYTHROPOIETIN IN POLYCYTHAEMIC ANIMALS TREATED WITH CYTOTOXIC AGENTS
Authors: Millar J. L. , Constable T. B. , Blackett N. M.
Published: May 2008

This communication deals with the phenomenon of delayed response to erythropoietin and provides many examples of this phenomenon with a variety of cytotoxic agents. Explanations for the delayed response presented by other authors have been examined in the light of the available experimental evidence. These explanations, generally involving restoration of the depleted ERC compartment before differentiation into proerythroblasts, have been shown to be unlikely. An alternative explanation for the delayed response involving continuous maturation of a committed stem cell to ERC and sensitization of cells in this maturation pathway to erythropoietin after treatment with cytotoxic agents, is presented.
THE EFFECT OF FETUIN AND OF SPLEEN EXTRACTS ON HEMATOPOIETIC PRECURSORS AND ON DIFFERENTIATED HEMATOPOIETIC CELLS IN IRRADIATED MICE
Authors: Dons Robert , Knospe William H. , Trobaugh Frank E. , Fried Walter
Published: May 2008

Injection of extracts from normal mouse spleen tissue into irradiated mice enhance the rate of regeneration of colony forming units (CFU‐S) in the femoral marrow. This effect was most pronounced when spleen extract was injected between 24 hr before and 24 hr after the time of irradiation, and was observed only during the first week after a single injection of extract. Another result of injecting spleen extract was an immediate and transient decrease in the marrow cellularity and particularly in the number of mature myeloid cells in the marrow. Fetuin produced comparable effects on the rate of regeneration of CFU‐S and on the numbers of mature myeloid cells in the marrow.

On the basis of these results it is tempting to speculate that injection of spleen extracts and of fetuin primarily cause a rapid depletion of the marrow's granulocyte reserve. This in turn releases the precursor cell compartment from the inhibitory effects of cell–cell interaction and results in an acceleration of the rate of CFU‐S regeneration.

It is equally plausible that factors present in spleen extract and in fetuin cause a depletion of the marrow granulocyte reserve and, by an unrelated mechanism, directly accelerate the rate of regeneration of CFU‐S.
CELL POPULATION GROWTH IN THE CASTRATE MOUSE PROSTATE COMPLEX: EXPERIMENTAL VERIFICATION OF COMPUTER SIMULATION
Authors: Alison Malcolm R. , Appleton David R. , Morley Adrian R. , Wright Nicholas A.
Published: May 2008

The stimulatory action of androgen on cell proliferation in the castrate mouse seminal vesicle and coagulating gland has been studied by DNA measurements in mice 14 days after castration. 100 hr after continuous androgen treatment the level of DNA had increased 2.5‐fold in the seminal vesicle and coagulating gland compared with 14 days castrated controls. A mathematical model predicted this new experimental data when the parameters employed in the simulation were constrained by the results of previous experiments.
DIFFERENT ACTION OF SUICIDAL DOSES OF TRITIATED THYMIDINE AND HYDROXYUREA ON MURINE HAEMOPOIETIC CELLS
Authors: Schreml W. , Bock O. , Bock E. , Heit W. , Kubanek B.
Published: May 2008

In order to gather information on the factors that cause the different action of suicidal doses of tritiated thymidine (3H‐TdR) and of hydroxyurea on murine stem cells, the incorporation of 3H‐TdR into DNA of bone marrow and spleen cells has been studied. Continuous death of labelled cells after suicidal 3H‐TdR is indicated by a more pronounced decline of total DNA‐bound radioactivity in bone marrow and spleen cells compared to that in control animals which had received tracer doses of 3H‐TdR. Extensive and rapid loss of DNA‐bound radioactivity occurred in 3H‐TdR labelled animals after hydroxyurea treatment indicating an instantaneous and highly effective killing of labelled cells. After double labelling of DNA with 3H‐TdR and 125iodo‐deoxyuridine (125I‐UdR), the decline of the ratio of DNA‐bound 125I to DNA‐bound 3H after suicidal 3H‐TdR indicates prolonged tritium reutilization. Following hydroxyurea, reutilization was completed within the first 12 hr after drug administration. These findings explain in part the slow recovery of different stem cell compartments after suicidal 3H‐TdR on the basis of protracted tritium reutilization as compared to the fast recovery which follows the rapid action of hydroxyurea.
EFFECT OF VILLUS LENGTH ON CELL PROLIFERATION AND MIGRATION IN SMALL INTESTINAL EPITHELIUM
Authors: Rijke R. P. C. , Meer‐Fieggen W. van der , Galjaard H.
Published: May 2008

For the interpretation of data supporting the hypothesis of a feedback regulation of proliferative activity in intestinal crypts by the functional villus cell compartment the life span and migration rate of epithelial cells on villi of experimentally reduced length should be known. Autoradiographic studies and scintillation counting of isolated villi at different time intervals after 3H‐thymidine labelling were carried out 36, 48 and 60 hr intervals after X‐irradiation. The results showed that the life span of epithelial cells in rat small intestine (36–48 hr) is independent of the villus length. In villi of reduced length the migration rate of the epithelial cells was found to be decreased compared with controls. Changes in the migration rate in turn seem to be dependent on the production of epithelial cells in the crypt. Comparative studies on the recovery of crypt and villus epithelium after various doses (300 and 700 R) of X‐radiation support the hypothesis that increased proliferative activity in the crypt cell compartment is related to a reduction of the number of functional villus cells below a critical villus length. The importance of these findings in the interpretation of data on (micro) biochemical analyses of certain cell differentiation characteristics during increased proliferative activity is discussed.
3H‐5‐IODO‐2′‐DEOXYURIDINE TOXICITY PROBLEMS IN CELL PROLIFERATION STUDIES
Authors: Dethlefsen Lyle A.
Published: May 2008

The toxicity of 3H‐5‐iodo‐2′‐deoxyuridine (3H‐IUdR) was evaluated by injecting tumor‐bearing C3H mice with different concentrations of ethanol (the solvent), different doses of tritium tagged onto either IUdR or thymidine and different chemical doses of IUdR, and then measuring the 3H‐IUdR incorporation into duodenal and mammary tumor DNA as well as the cellular kinetics of duodenal crypt cells. Ethanol (37% or less, 0.2 ml/mouse) does not significantly inhibit IUdR incorporation into DNA, and the incorporation after a tritium dose of 75 μCi 3H‐IUdR/mouse (about 3 μCi/g body weight) is not less than the incorporation following an injection of 25 μCi 3H‐IUdR/mouse when the IUdR dose is below 0.005 μmole per mouse. The toxic effects are primarily due to chemical toxicity from IUdR per se. IUdR, at doses of 0.2 μmoles per mouse does inhibit IUdR incorporation into duodenal and tumor DNA, and the duodenal labeling index and the fraction of labeled mitoses are significantly reduced when 0.013 μmole IUdR per mouse is injected. Also some of the duodenal cells containing IUdR apparently undergo only one post‐labeling division and the generation time (Tc) of the cells containing IUdR (25 μCi 3H‐IUdR/mouse) is 15.3 hr as compared to 13.3 hr for cells labeled with 3H‐T (75 μCi/mouse). This increase in Tc is probably not statistically significant; nevertheless, these results do indicate that one must be exceedingly cautious when using 3H‐IUdR as a radiotracer for studies concerned with in vivo cellular kinetics and, at least for C3H mice, the dose should be less than 0.01 μmole per 25 g mouse.
VARIATIONS OF MITOSIS‐INHIBITING CHALONE ACTIVITY IN EPIDERMIS AND DERMIS AFTER CARCINOGEN TREATMENT
Authors: Rohrbach R. , Laerum O. D.
Published: May 2008

During regeneration and hyperplasia following a single application of a carcinogen to mouse epidermis, the rate of epidermal cell proliferation varied inversely with the content of mitosis‐inhibiting activity (chalone). The main inhibitory activity was present within the epidermal cells, but a lesser activity was also found in the corresponding extracts of dermis. This supports the concept that chalones act as physiological regulators of cellular proliferation under pathological as well as normal conditions. The possibility that the dermis also takes an active part in this regulation is discussed.
CYTOKINETIC STABILITY OF AN EHRLICH ASCITES TUMOR
Authors: Schiffer Lewis M. , Markoe Arnold M.
Published: May 2008

An Ehrlich ascites tumor has maintained much of its cytokinetic stability through multiple passages which included a change in host.
THE KINETICS OF 51,Cr RELEASE FROM TARGET CELLS IN CELL MEDIATED CYTOTOXICITY AND THE RELATIONSHIP TO THE KINETICS OF KILLING
Authors: Sanderson Colin J. , Taylor Geoffrey A.
Published: May 2008

The kinetics of T‐cell mediated cytotoxicity (CMC) have been re‐examined. It is clear that per cent 51Cr release is linearly related to effector cell number and not to its log as often suggested. Data are presented showing that killing can occur within 1 min of lymphocyte‐target cell contact and that 51Cr is released rapidly from killed cells. Inactivation experiments aimed to stop ongoing cytolysis indicate that all target cells are brought into contact with effector lymphocytes within 45 min. At a ratio of 50:1 the kinetics of contact resemble saturation kinetics, indicating a number of effector cells similar to or in excess of the number of target cells (that is, at least 2 % of total lymphocytes). Although CMC is causally related to cell contact, it is chronometrically unrelated and occurs as a random reaction (that is it can occur immediately or up to hours later than contact). The mean time depends on the number of effector cells.

The killing reaction is temperature dependent and proportional to the number of effector cells but does not depend on the intact effector cell. An intact effector cell is only required to bring about contact. It is suggested that this final cytolytic event is brought about by the target cell itself, perhaps as a result of attempts to free itself from the attached lymphocyte.
RECOVERY OF PROLIFERATING HAEMOPOIETIC PROGENITOR CELLS AFTER KILLING BY HYDROXYUREA
Authors: Hodgson G. S. , Bradley T. R. , Martin R. F. , Sumner M. , Fry P.
Published: May 2008

Two doses of 1 mg/g of hydroxyurea (HU), injected 7 hr apart into irradiated mice in which CFU‐S were proliferating during marrow regeneration, killed about 90% of CFU‐S. This same dose regime injected into normal female mice, with non‐proliferating CFU‐S killed 92 % of CFU‐C, 99 % of ESC and only 30 % of CFU‐S. One day after the treatment CFU‐S had decreased to 50 % and remained at about this level for a further day then returned to normal values. In spleen the increase in CFU‐S was delayed by a day and showed a marked overshoot. During the period that CFU‐S were decreased in number they were actively proliferating. Marrow CFU‐C recovered in an exponential manner with a doubling time of 16 hr. Spleen CFU‐C recovered 1 day later than marrow and showed a pronounced overshoot. ESC recovered very rapidly with doubling time of 5 hr. The changes in 59Fe incorporation into RBC, and the peripheral blood picture, were a delayed reflection of the changes in ESC and CFU‐C.
DURATION OF MITOSIS AND SEPARATE MITOTIC PHASES COMPARED TO NUCLEAR DNA CONTENT IN ERYTHROBLASTS OF FOUR VERTEBRATES
Authors: Grosset Lise , Odartchenko Nicolas
Published: May 2008

The passage of a wave of tritiated. thymidine‐labelled cells through each of the phases of mitosis is analysed in erythroblasts of four vertebrates species, selected because of their widely differing diploid DNA content. Mitotic time (tm) and relative durations of separate mitotic phases as well as that of the G2 period are thus accurately determined. Mean duration of tm appears to vary according to the species specific DNA amount. This relation is approximately the same as for S, for G1 and for the generation time, which have been previously determined.
FISSION OF CRYPTS IN THE SMALL INTESTINE OF THE IRRADIATED MOUSE
Authors: Cairnie A. B. , Millen B. H.
Published: May 2008

Following 1600 R of X‐rays there was a reduction in the number of crypts in the small intestine of the mouse by 77% as measured 5 days later. However, by 21 days the number had increased steadily to levels approaching normal. The number of villi did not change following irradiation. The mechanism of increase in crypt number was by budding and fission of repopulated crypts which had become larger than normal. Some aspects of crypt organization are discussed.
NEURAL STIMULATION OF MITOTIC ACTIVITY IN THE CRYPTS OF LIEBERKÜHN IN RAT JEJUNUM
Authors: Tutton P. J. M.
Published: May 2008

The influence of nerve stimulation and sham‐stimulation on the mitotic rate in epithelial cells lining the crypts of Lieberkühn in the jejunum of anaesthetized rats was studied.

Administration of the anaesthetic and opening the abdominal cavity was without significant effect on the crypt cell mitotic rate. However, externalizing a loop of jejunum and applying sham‐stimuli to its mesenteric nerves resulted in a significant decrease in the crypt cell mitotic rate in that loop. Application of electrical stimuli to the mesenteric nerves of another externalized jejunal loop resulted in a significant increase in the mitotic rate in the crypt cells of that segment. Similar acceleration of crypt cell proliferation by electrical stimuli applied to mesenteric nerves was also seen in chemically sympathectomized rats.
AN AUTORADIOGRAPHIC AND MORPHOLOGICAL STUDY OF MOUSE BONE MARROW LITTORAL CELLS DURING AND AFTER TREATMENT WITH URETHANE
Authors: Langdon HerbertL. , Berman Irwin
Published: May 2008

This study demonstrates that the labeling index of mouse marrow littoral cells can be markedly altered as a result of treatment with ethyl carbamate (urethane). Young C57/BL mice were given daily intraperitoneal urethane injections for periods up to 6 days. Following treatment each day, as well as daily over a 10 day recovery period, a group of animals was administered tritiated thymidine every 3 hr over a 24 hr period and sacrificed ½ hr after the last injection. Marrow was embedded in epon and 0·5 μm sections cut for autoradiographic and light microscopic analysis. A thirty‐five‐fold increase in the percentage labeled littoral cells was observed after three injections of urethane. The labeling index of littoral cells fluctuated during the treatment period and during the 10 day recovery period. The labeling data are discussed in relation to the possible effects of urethane on the cell cycle of mouse marrow littoral cells; the morphological sequela to urethane treatment and the nossibilitv that littoral cells mav act as stem cells.