bluuebunny/crossref_metadata_2025_split huggingface dataset:
The characterization of the monoclonal antibody Th‐10a, specific for a nuclear protein appearing in the S phase of the cell cycle in normal thymocytes and its unregulated expression in lymphoma cell lines
Authors: Muto M. , Utsuyama M. , Horiguchi T. , Kubo E. , Sado T. , Hirokawa K. 
Published: May 2008

AbstractA monoclonal antibody (Th‐10a) specific for the nuclear protein appearing in the S phase of the cell cycle in normal mouse thymocytes was derived by immunizing Wistar rats with a murine thymic lymphoma (TIGN), and its isotype was rat IgG2a and had κ light chain. Immunohistochemical staining of frozen sections of B10.Thy1.1 newborn thymus and embryonic intestine revealed that this monoclonal antibody reacted strongly with the nuclear proteins of subcortical thymocytes and the basal layer of the mucosa, where many cells were dividing, but not with that of the thymic medullary area. To evaluate the expression of the nuclear proteins during the cell cycle in detail, the results of an immunofluorescence analysis of the thymocytes from hydroxyurea‐treated B10 mice using Th‐10a monoclonal antibody were compared with those of DNA synthesis of these cells with the use of the FITC‐conjugated anti‐BrdUrd monoclonal antibody. The results indicated that the nuclear protein detected by Th‐10a monoclonal antibody was highly expressed in the S phase of normal thymocytes, while the cells in G1, G2 and M phases exhibited a low level of the expression. Moreover, the variations in expression of the nuclear proteins in the thymocytes at different times after hydroxyurea treatment were observed to correspond with the frequency of DNA synthesizing cells. In contrast, the high level and unregulated expression of the nuclear protein detected by Th‐10a monoclonal antibody was observed throughout the cell cycle of the mouse lymphoma cell lines examined. Since Th‐10a monoclonal antibody does not react with the nuclear proteins derived from human, hamster or rat proliferating cells, this antibody may recognize a murine specific epitope of the nuclear protein.To further characteize the nuclear proteins, we extracted them from normal thymocytes or thymic lymphomas, and analysed them by immunoblotting or***
Aspirin, age, and proximity to lymphoid nodules influence cell proliferation parameters in rat colonic crypts
Authors: Barnes C. J. , Lee M. , Hardman W. E. , Cameron I. L. 
Published: May 2008

AbstractRecent epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid) use and decrease risk for the development of fatal colorectal cancer. An increase in the size of the cell proliferation compartment in colorectal crypts has been correlated with an increased risk for the development of colon cancer in animals and in humans. To determine if acetylsalicylic acid acts to decrease the size of the cell proliferation compartment, young (3 month) and old (22 month) rats were treated intragastrically with: 1 the vehicle for acetylsalicylic acid delivery (0.25% wt/vol carboxymethylcellulose in 0.15 N HCI), 2 a single dose of acetylsalicylic acid (100 mg/kg), or 3 acetylsalicylic acid (30 mg/kg) given daily for 30 days. One day after the last treatment, colons were resected, fixed, sectioned and mounted on slides for immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen to assess cell proliferation parameters in the colonic crypts. The results were subjected to three way analysis of variance to assess the effects of: 1 rat age, 2 acute or chronic acetylsalicylic acid treatment, and 3 location of crypts over and away from aggregates of lymphoid nodules on the crypt proliferative parameters. Results demonstrated that: 1 acetylsalicylic acid treatment caused an overall decrease in the proliferative zone height, as measured in number of cells in the crypt column, 2 that crypts located over aggregates of lymphoid nodules had significantly higher proliferative activity than crypts located away from aggregates of lymphoid nodules, and 3 after chronic acetylsalicylic acid treatment there was a greater suppression of proliferative zone height in the crypts of old rats than in the crypts of young rats. In conclusion, acute and chronic intragastric delivery of acetylsalicylic acid caused an overall downward shift in the cell proliferation compartment of colonic crypts of young and of old rats. Whether or not acetylsalicylic acid administration will cause the same proliferative zone height response in carcinogen‐treated rats is not yet established.
Trophic effects of essential fatty acids on pig skin
Authors: Morris G. M. , Hopewell J. W. , Ross G. A. , Whitehouse E. , Wilding D. , Scott C. A. 
Published: May 2008

AbstractThe daily oral administration of 3 ml of two oils (So‐5407 and So‐1129) containing essential fatty acids (EFAs) for 16 weeks resulted in a transient increase in cell proliferative activity in the skin of female Large White pigs. The So‐5407 oil contained 7% gamma‐linolenic acid (GLA) whereas So‐1129 was an oil of similar composition, but with no GLA.Hyperplasia of the epidermis was observed after the administration of both oils, and this was characterized by an increase in the size of the rete pegs. The maximum effect occurred at 4 weeks after the start of oil administration, at which time the number of viable cell layers had increased by a factor of approximately 1.5, and mean epidermal thickness (excluding the stratum corneum) was approximately 40% greater than that of the epidermis prior to oil administration. There was a marked increase in the labelling index (LI) of the basal cell layer of the epidermis in pigs receiving So‐5407. Maximum LIs were quantified at 4 weeks after the start of administration and were 18.8 ± 1.3% and 13.1 ± 1.7% for pigs receiving So‐5407 and So‐1129, respectively. After this time the LI declined prgressively and had returned to values within normal limits (P>0.1) by 8 weeks after the start of administration of both oils. A similar pattern of change in the LI was seen in the follicular epithelium, although the peak values at 4 weeks after the start of oil administration of 12.2 ± 1.8% and 10.8 ± 0.9 for the groups receiving So‐5407 and So‐1129, respectively, were lower than in the epidermis. Labelled cells were also counted in the papillary dermis and maximum values were again seen at 4 weeks after the start of oil administration. Of the two oils, So‐1129 had the greatest effect, with the number of labelled cells in the papillary dermis being a factor of three to four‐fold higher than in skin prior to oil administration, between 2 and 12 weeks after the start of administration.
Regulation of thymosin β4 mRNA levels during cell proliferation
Authors: Zalvide J. B. , Alvarez C. V. , Vidal A. , Dieguez C. , Vega F. V. , Domínguez F. 
Published: May 2008

AbstractThe levels of thymosin β4 mRNA were studied throughout the cell cycle of NIH 3T3 cells. In serum deprived, quiescent cells, the levels of thymosin β4 were undetectable; after serum restoration, the cells were induced to proliferate and we found a pronounced increase in thymosin β4 mRNA levels at the G1/S transition. Thymosin β4 mRNA was induced even in the presence of cycloheximide. On the other hand, cycling cells that were synchronized at different stages of the cycle by means of mitotic shake‐off after nocodazole arrest or a double thymidine block did not show any variation in the levels of thymosin β4 mRNA when they progressed synchronously through the cycle. In conclusion, the present data indicate that the thymosin β4 gene is regulated by cell proliferation but it is not a cell cycle‐regulated gene. Finally, we studied thymosin β4 mRNA stability by inhibiting thymosin β4 gene transcription with actinomycin D. Our results suggest that thymosin β4 mRNA has a pronounced stability, a fact that might be relevant to account for the presence of thymosin β4 in enucleated cells like platelets.
A quantitative method for the analysis of mammalian cell proliferation in culture in terms of dividing and non‐dividing cells
Authors: Sherley J. L. , Stadler P. B. , Stadler J. Scott 
Published: May 2008

AbstractThe application of the exponential growth equation is the standard method employed in the quantitative analyses of mammalian cell proliferation in culture. This method is based on the implicit assumption that, within a cell population under study, all division events give rise to daughter cells that always divide. When a cell population does not adhere to this assumption, use of the exponential growth equation leads to errors in the determination of both population doubling time and cell generation time. We have derived a more general growth equation that defines cell growth in terms of the dividing fraction of daughter cells. This equation can account for population growth kinetics that derive from the generation of both dividing and non‐dividing cells. As such, it provides a sensitive method for detecting non‐exponential division dynamics. In addition, this equation can be used to determine when it is appropriate to use the standard exponential growth equation for the estimation of doubling time and generation time.
Streaming of labelled cells in the conjunctival epithelium
Authors: Zajicek G. , Perry A. , Pe'er J. 
Published: May 2008

AbstractThis study examines epithelial cell streaming and turnover in normal rat bulbar conjunctiva. Twenty seven male adult random‐bred Hebrew rats weighing between 250–300 g, were injected i.p. with [3H]‐thymidine. Three rats were killed at various times, thereafter from 1 h to 28 days. The enucleated eyes were fixed in formalin, cut into 5 μ thick sections, dipped into liquid emulsion, exposed for three weeks and stained with haematoxylin and eosin. Conjunctival epithelium was scanned from the limbus and outward, using an ocular micrometer grid with 10 x 10 divisions. In each consecutive field the grid was positioned along the basement membrane which was defined as the x‐axis. The y‐axis extended from the basement membrane outward. The x, y coordinate of each nucleus with three grains or more and its grain content were recorded along the entire epithelium.Conjunctival epithelium is divided into two cell kinetic compartments: a progenitor (P), along the basal and supra basal layer, in which cells proliferate, and a non proliferating Q‐compartment, in the layers above. One hour after labelling most of the labelled cells were in the basal and supra basal layers. From then onward labelled cells streamed along both axes. Their x‐velocity was 10·5±2·4 μ/day and the y‐velocity 9·3 ± 5·4 μ/day. Cells are eliminated at the epithelial surface which is the outer Q‐compartment boundary. Basal cell turnover was estimated from grain count dilution curves. The time it takes for the grains in a cell to reach half of their initial value was 8·3 days. It is closely related to the cell's generation time.The present study demonstrates that conjunctival epithelium in the rat streams along two axes, x, and y: 1 The x‐axis extends along the basal layer, from the limbus and outward. 2 The y‐axis extends from the basal layer into the layers above it. Cells first stream along the x‐direction and then turn y‐ward. Since cells are ultimately exfoliated from the conjunctival surface, and since the conjunctiva maintains steady state, we propose that stem cells located in the limbus generate transitional cells that stream along the two axes. Macroscopically the limbus is circular, and the stem cells are situated around the cornea. Each stem cell and its streaming progeny can be viewed as a conjunctival epithelial unit.We propose that conjunctival and corneal epithelium, are the descendants of an uncommitted stem cell that generates two differentiation pathways, a corneal and a conjunctival.
Levels of selected growth factors in viable and necrotic regions of xenografted HCT‐8 human colon tumours
Authors: Leith J. T. , Michelson S. 
Published: May 2008

AbstractXenografted tumours were produced in nude mice by injection of HCT‐8 human colon tumour cells. At average volumes of about 750 mm3, animals were injected with fast green vital dye, and 20 min later, tumours were excised and dissected into viable (stained) and necrotic portions (unstained). Viable and necrotic regions were then examined for cell yields, colony forming efficiencies, and levels of basic fibroblast growth factor (FGF‐2), transforming growth factors‐β1 and ‐α (TGF‐β1, TGF‐α), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) using enzyme‐linked immunoassay (ELISA) procedures. Levels in the viable and necrotic regions were compared to levels in unseparated tumours. The average extent of necrosis in HCT‐8 tumours of this size was 64%. The data for cell yields, colony forming efficiencies FGF‐2, VEGF, TGF‐β1 and TGF‐α indicated that values determined in the unseparated tumours could be understood on the basis of the weighted average between viable and necrotic tissue, with the higher values occurring in the viable tissue. Low levels of FGF‐2 and VEGF were found in the necrotic portions of the tumour while no measurable levels of TGF‐β1 and TGF‐α could be determined. PDGF levels were, however, equivalent in both the viable and necrotic regions indicating that necrotic tissue could be an important reservoir for this growth factor.
Evidence for quiescent S‐ and G2‐phase cells in human colorectal carcinomas: a flow cytometric study with the Ki‐67 antibody
Authors: Zölzer F. , Speer A. , Pelzer T. , Streffer C. 
Published: May 2008

AbstractThe expression of certain antigens specific for proliferating cells can be determined simultaneously with cell cycle distribution by means of two‐dimensional flow cytometry. In this way, a tumour's growth potential is characterized more precisely than with any one parameter alone. Here we describe such simultaneous measurements of DNA content and labelling with the Ki‐67 antibody that distinguishes between cycling and non‐cycling cells. Having overcome a number of technical problems we were able to analyse material from 29 biopsies of human colorectal tumours.In a number of cases, Ki‐67 negative cells were found with a DNA‐content of G0/1 only, whereas all cells with an S‐ or G2‐phase DNA‐content were Ki‐67 positive. There were other cases in which cells with an S‐ and G2‐phase DNA‐content had obviously become quiescent (Ki‐67 negative), sometimes even outnumbering the proliferating (Ki‐67 positive) cells in the respective compartments of the cycle. Generally, however, when Ki‐67 negative and positive subpopulations were analysed separately it was found that the former had a significantly lower (S + G2)‐phase fraction than the latter.There was evidence for a correlation between Ki‐67 index and (S + G2)‐phase fraction at least in the subgroup of aneuploid tumours. Neither of the two parameters was correlated with stage according to Duke's classification or tumour size. However, a positive correlation was found between the fraction of unlabelled S‐ and G2‐phase cells and tumour size as reflected in the T category.
Threshold expression of cyclin E but not D type cyclins characterizes normal and tumour cells entering S phase
Authors: Gong J. , Traganos F. , Darzynkiewicz Z. 
Published: May 2008

AbstractComplexes of cyclin‐dependent kinases (cdk) and their partner cyclins drive the cell through the cell cycle, each such complex phosphorylating a distinct set of proteins at a particular check‐point or phase of the cycle. Immunocytochemical detection of cyclins combined with measurement of cellular DNA content by flow cytometry makes it possible to relate expression of each of these proteins with the actual cell cycle position, without the necessity of cell synchronization. In the present study, we have investigated expression of E and D type cyclins in G1 cells and in cells entering S phase, in eight different human hematopoietic and solid tumour cell lines (two leukaemias, a lymphoma, three breast carcinomas, a colon carcinoma and a bladder transitional cell carcinoma) during their exponential phase of growth, as well as in normal mitogen stimulated lymphocytes. In all the cell types studied, the average level of D type cyclin expression was invariable throughout the cell cycle. A great intercellular variability, in particular of the G1 cell subpopulations, and the presence of a large fraction of G1, S and G2+ M cells that were cyclin D negative (20–40% in tumour cell lines and about 80% among lymphocytes), were other characteristic features of D type cyclin expression. In contrast to D type cyclins, the expression of cyclin E was discontinuous during the cycle, peaking at the time of cell entrance to S. Also, a well defined threshold in expression of cyclin E characterized cells that were entering S phase, and virtually no cyclin E negative cells were seen during the early portion of S phase. The data indicate that while cell entrance to S phase is unrelated to expression of D type cyclins (at the time of entrance), accumulation of cyclin E up to critical level is a prerequisite for initiation of DNA replication. The great intercellular variability in expression of D type cyclins and their invariant average level across the cell cycle suggest that these cyclins, in addition to their acknowledged function in promoting cell progression through mid‐ to late‐G1 may have other role(s), related or unrelated to the cell cycle progression. The presence of a large number of D type cyclin negative cells in all phases of the cycle suggests that during exponential growth the cells may not express this protein and yet may traverse the cycle, including G1 phase.
Regrowth resistance in cancer: why has it been largely ignored?
Authors: Preisler H. D. , Venugopal P. 
Published: May 2008

AbstractIn drug‐sensitive malignancies, treatment failure is a complex phenomenon resulting from both drug resistance and the rapid regrowth of malignant cells in between cycles of chemotherapy. This phenomenon has been referred to as regrowth resistance, and has been identified as a common impediment to the successful treatment of many neoplastic diseases. This phenomenon has received little attention in the past. The administration of maximally tolerated individual dosages of chemotherapeutic agents, combined with the use of biological response modifiers to slow the regrowth between courses of therapy, would be an effective approach to reduce the regrowth resistance. This also could reduce the emergence of drug resistant clones.
An analysis of the growth of the retinal cell population in embryonic chicks yielding proliferative ratios, numbers of proliferative and non‐proliferative cells and cell‐cycle times for successive generations of cell cycles
Authors: Morris V. B. , Cowan R. 
Published: May 2008

AbstractGrowth curves of the retinal cell population of embryonic chicks were fitted by a branching‐process model of cell population growth, thereby estimating the proliferative ratios and mean cell‐cycle times of the generations of cell cycles that underlie retinal growth. The proliferative ratio determines the proportion of cells that divides in the next generation, so the numbers of proliferative and non‐proliferative cells in each generation of cell cycles were obtained. The mean cell‐cycle times determine the times over which the generations are extant. Assuming growth starts from one cell in generation 0, the proliferative cells reach 3.6 × 106 and the non‐proliferative cells reach 1.1 × 106 by generation 23. The next four generations increase the proliferative cell numbers to 13.9 × 106 and produce 20.1 × 106 non‐proliferative cells. In the next five generations in the end phase of growth, non‐proliferative cells are produced in large numbers at an average of 13.9 × 106 cells per generation as the retinal lineages are completed. The retinal cell population reaches a maximum estimated here at 98.2 × 106 cells. The mean cell‐cycle time estimates range between 6.8 and 10.1 h in generations before the end phase of growth and between 10.6 and 17.2 h in generations in the end phase. The retinal cell population growth is limited by the depletion of the proliferative cell population that the production of non‐proliferative cells entails. The proliferative ratios and the cell‐cycle‐time distribution parameters are the likely determinants of retinal growth rates. The results are discussed in relation to other results of spatial and temporal patterns of the cessation of cell cycling in the embryonic chick retina.
In vivo labelling with halogenated pyrimidines of squamous cell carcinomas and adjacent non‐involved mucosa of head and neck region
Authors: Kotelnikov V. M. , Coon J. S. , Taylor S. , Hutchinson J. , Panje W. , Caldarelli D. D. , LaFollette S. , Preisler H. D. 
Published: May 2008

AbstractThe frequency and distribution of labelled cells were studied immunohistochemically in 37 squamous cell carcinomas (SCC) of head and neck after in vivo infusion of IdUrd and BrdUrd. Tumours were classified according to their labelling patterns. Low and moderate grade SCC consisted of tumour islands separated by interstitial tissue. In some tumours labelled cells only appeared near the basal layer while in others proliferative cells were evenly distributed within the neoplastic island. In anaplastic carcinomas labelled cells were distributed either randomly or around blood vessels (cord structures). While the basal layer in adjacent normal epithelium contained very few labelled cells (LI = 1.6 ± 0.2%), the LI of basal cells in tumour islands were much higher than the average LI of the tumour (47.2 ± 2.8% and 23.8 ± 1.6%, respectively). In patients who had received cytotoxic therapy up to two months before the biopsy, the LI in the basal layer of normal epithelium was 19.0 ± 3.5%. In sequential biopsies obtained 1–2 weeks after the infusion of IdUrd and BrdUrd some labelled tumour cells were found in necrotic foci and in pearl structures. Additionally, in six tumours, we found areas of cells labelled with IdUrd alone, even though the IdUrd infusion had been followed by a BrdUrd infusion 1 h later. This is in agreement with the phenomenon of intermittent tumour blood flow described earlier in experimental tumours.
Tissue kinetics in mouse tongue mucosa during daily fractionated radiotherapy
Authors: Dörr W. , Emmendörfer H. , Weber‐Frisch M. 
Published: May 2008

Abstract. The purpose of the present investigation was to quantify cell flux between the distinct layers of the epithelial lining of the ventral surface of mouse tongue during daily fractionated radiotherapy.A fraction of DNA‐synthesizing cells in control epithelium, or at various days through a course of daily fractionated radiotherapy with 3 or 4 Gy per day, was labelled with [3H]dT or BrdUrd, respectively. The labelling indices (LI) in the different epithelial layers were defined histologically after autoradiography, or immunohistochemistry, at intervals between 1 and 10 days after label administration.In tongue epithelium of untreated mice, the minimum residence time of cells in the germinal layer is 2–3 days. Migration through the functional layers requires an additional 2–3 days before labelled cells are observed in the most superficial layer of nucleated cells. A plateau in LI is observed for several days post‐labelling in control epithelium, indicating an equilibrium between loss and proliferation of labelled cells. During fractionated radiotherapy, the minimum time from division to occurrence of labelled cells in the stratum lucidum is less than 2 days, and hence significantly shorter than in control epithelium. In contrast to untreated epithelium, no plateau in the germinal layer LI is seen, indicating that frequently both labelled daughters from dividing labelled cells are being lost from this compartment.In conclusion, the present data support a recently described model of radiation‐induced accelerated repopulation in squamous epithelia, which postulates that the majority of damaged cells undergoes abortive’divisions resulting in two differentiating daughters.