bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferation of mature and immature subpopulations of bronchoalveolar monocytes/macrophages and peripheral blood monocytes
Authors: Van Hal P. Th. W. , Wijkhuijs J. M. , Mulder P. G. H. , Hoogsteden H. C. 
Published: May 2008

AbstractA continuous influx of peripheral blood monocytes (PBM) to the lung is thought to maintain the local population of alveolar macrophages (AM). However, local proliferation of a small subpopulation of AM has been demonstrated in animal studies and in humans. AM exhibit a great heterogeneity with regard to their morphology (cell size, shape of nucleus), immunophenotype (expression of CD14 and RFD9 antigen), and function. Part of this heterogeneity may be explained by the presence of different maturation stages of AM, ranging from small immature, CD14+ RFD9− PBM‐like cells to large, CD14− RFD9+ mature AM. These findings prompted us to study whether proliferation of PBM and AM is related to their stage of maturation.The expression of the proliferation marker Ki‐67 was studied in AM from both healthy volunteers and patients suffering from sarcoidosis. Using double immunofluorescence staining, we studied proliferation of immature, CD14+ AM, and mature, RFD9+ AM in sarcoidosis, and we compared this with PBM. A significantly larger percentage of AM in general expressed Ki‐67 antigen in sarcoidosis (3.0 (median); range 1.1–5.5) as compared with healthy volunteers (0.8; 0.2‐1.3). In sarcoidosis, proliferation was observed in both the immature and the mature subpopulation of AM. Proliferating PBM were rarely observed [less than 0.2% of the CD14+ mononuclear cells (MNC)] both in healthy volunteers and sarcoidosis patients. A small subpopulation of PBM showed a weak expression of RFD9 antigen (less than 1% of MNC). Interestingly, proliferation of PBM was concentrated in this subpopulation (15% of the RFD9+ MNC).These data show that even mature AM, which are generally thought to be terminally differentiated cells with little capacity to replicate, are able to proliferate, whereas a relatively very low percentage of their precursors in the blood circulation proliferates. Furthermore, the findings suggest that lung tissue in sarcoidosis creates an environment which promotes proliferation of monocytic cells.
Purine suppression of proliferation of Sertoli‐like TM4 cells in culture
Authors: Shaban M. , Smith R. A. , Stone T. W. 
Published: May 2008

AbstractThe effect of adenosine and related compounds on the proliferation of cultured TM4 cells, a Sertoli‐like cell line, has been examined. Adenosine, as well as A1 and A2 adenosine receptor agonists (cyclohexyladenosine and N6‐[2‐(3,5‐dimethoxyphenyl)‐2‐(2‐methylphenyl)ethyl]adenosine) inhibited cell proliferation. These effects were prevented by 8‐cyclopentyl theophylline, 1,3‐dimethyl‐propargylxanthine and caffeine, antagonists at the A1, A2 and both receptors, respectively. The xanthines had no effect by themselves and, consistent with this, the bathing medium was found not to contain detectable levels of adenosine. It is concluded that TM4 cell proliferation can be regulated by receptors for adenosine.
Cell cycle analysis by the relative movement approach: effect of variability across S‐phase of DNA synthesis rate
Authors: Bertuzzi A. , Grosso N. Del , Gandolfi A. , Sinisgalli C. , Starace G. 
Published: May 2008

AbstractCell populations pulse‐labelled with BrdUrd, and sampled at increasing times after the pulse, yield DNA‐BrdUrd distributions from which the relative movement (RM) and the depletion function (DF) of labelled, undivided cells can be calculated. In this paper we present an extension of the equation for the time course of RM, given by White and Meistrich (Cytometry 1986, 7, 486–490), to the case in which the rate of DNA synthesis changes across S‐phase. Some modalities of cell loss were also considered. Computer simulations showed that different patterns of DNA synthesis rate across S‐phase can result in appreciably different RM curves. An analytical expression of the RM curve, in which the variability across S‐phase of the rate of DNA synthesis is accounted for by only one parameter, was proposed. This expression was used for the simultaneous fitting of time sequences of RM and DF data of U937 cells, in order to estimate the phase transit times TS and TG2+M, and the potential doubling time Tpot. The use of the extended model gave better results than those obtained under the assumption of constant rate of DNA synthesis across S‐phase.
The effect of extracellular calcium on colonocytes: evidence for differential responsiveness based upon degree of cell differentiation
Authors: Buras R. R. , Shabahang M. , Davoodi F. , Schumaker L. M. , Cullen K. J. , Byers S. , Nauta R. J. , Evans S. R. T. 
Published: May 2008

AbstractCalcium supplementation decreases the incidence of colon cancer in animal models and may prevent colon cancer in man. Potential mechanisms include binding of mitogens and direct effects of calcium on colonic epithelial cells. In this study, the effects of extracellular calcium on epithelial cell growth and differentiation were studied in three colon carcinoma and two colonic adenoma cell lines. The characteristics studied included morphology, cell cycle kinetics, [Ca2+]IC (intracellular calcium concentration), proliferation, and expression of differentiation markers such as carcinoembryonic antigen (CEA) and alkaline phosphatase (AP). Sodium butyrate (NaB) and 1,25‐dihydroxyvitamin D3 were used as controls in the latter three assays as these two agents are known differentiating agents. Alteration of [Ca+2]EC (extracellular calcium concentration) did not affect carcinoembryonic antigen (CEA) or alkaline phosphatase (AP) expression. NaB enhanced the expression of AP three‐fold and CEA five‐fold. This effect was augmented by increasing [Ca2+]EC. The exposure of cells to 1,25‐(OH)2‐Vitamin D3 increased CEA but not AP. [Ca2+]IC increased in response to 1,25‐(OH)2‐vitamin D3 and NaB but not with variation in [Ca2+]EC. Increased [Ca2+]EC inhibited proliferation of well‐differentiated cells, but had no effect on poorly‐differentiated cells. Morphological studies showed that extracellular calcium was necessary for normal cell—cell interactions.These studies have demonstrated direct effects of calcium on colonic epithelial cells which may contribute to the protective effects of dietary calcium against colon cancer. Loss of responsivess to the antiprotective effects of [Ca2+]EC with de‐differentiation suggests that calcium supplementation may be most beneficial prior to the development of neoplastic changes in colonic epithelium.
Nucleolin and fibrillarin expression in stimulated lymphocytes and differentiating HL‐60 cells. A flow cytometric assay
Authors: Méhes G. , Pajor L. 
Published: May 2008

AbstractNucleolin and fibrillarin are two histone‐like major proteins in the nucleolus that were found to be overexpressed in proliferating cells. Using specific antibodies to either nucleolin or fibrillarin flow cytometric, measurements were carried out to demonstrate quantitative changes of these proteins during lymphocyte mitogenic activation and differentiation of HL‐60 promyelocytic leukaemia cells. The expression of nucleolin increased during lymphocyte stimulation and decreased slowly but constantly in the course of differentiation of HL‐60 cells. Expression of fibrillarin reached a maximum in the first cell cycle and then dropped to a basic level in stimulated lymphocytes. Compared to nucleolin, the level of fibrillarin decreased more rapidly and more extensively in differentiating HL‐60 cells. The data support other observations that nucleolin is a stabile structural protein at the ribosomal genes while fibrillarin may have a more specific functional role in nucleologenesis and ribosome production.
Secretion rates and levels of vascular endothelial growth factor in clone A or HCT‐8 human colon tumour cells as a function of oxygen concentration
Authors: Leith J. T. , Michelson S. 
Published: May 2008

AbstractMolecular and in situ hybridization studies have shown, in a number of cell types, that under hypoxic conditions, vascular endothelial growth factor (VEGF) mRNA expression is up‐regulated and VEGF protein is concomitantly increased. To establish a quantitative relationship between VEGF protein levels and oxygenation, we exposed exponentially growing clone A or HCT‐8 human colon tumour cells in vitro (22 h at 37°C) to oxygen concentrations from 21% (air mixture) to 0.01%. Protein levels in cells and medium were then assayed using an enzyme‐linked immunoabsorbent assay (ELISA). Intracellular levels of VEGF in clone A or HCT‐8 cells exposed to either air (21% O2) or the 0.01% O2 mixture respectively increased from about 73 to 1270, and 1.5 to 1180 pg/106 cells (about 17‐ and 80‐fold increases). The shapes of the response curves (log of the intracellular VEGF concentrations v. log oxygen concentration) for both cell types were sigmoidal. However, intracellular VEGF levels in HCT‐8 cells were always less than that of clone A cells until levels of about 0.3 to 0.1% O2 were reached. Levels of VEGF in the supernatant were also increased after the 22 h hypoxic exposures. Because cell proliferation and clonogenicity were also measured, it was possible to estimate the secretion rates of VEGF for both cell lines as a function of oxygen percentage. For clone A cells, the secretion rate (pg/106 cells/h) in 21% O2 was 62.5. This rate increased to 428.8 pg/106 cells/h at 0.01% O2, a 7‐fold increase. For HCT‐8 cells, levels in the medium at 21% O2 were too low to be measured by ELISA. However, between 10% and 0.01% O2, secretion rates increased from 5.0 to 376.0 pg/106 cells/h, a 75‐fold increase. Therefore, at very low O2 levels, VEGF secretion rates were similar in the two cell lines. We propose that the different VEGF responses of clone A and HCT‐8 colon tumour cells to hypoxic stress in vitro are related to the in vivo observation that the respective hypoxic percentages of solid neoplasms originating from these cell lines are markedly different (i.e. about 3 versus 80%) at equivalent volumes of 750 mm3.
Inhibitory effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on rat hepatocyte proliferation induced by 2/3 partial hepatectomy
Authors: Bauman J. W. , Goldsworthy T. L. , Dunn C. S. , Fox T. R. 
Published: May 2008

AbstractTo better understand the mode of action of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) induced alterations in hepatic cell proliferation and the potential link to tumour‐promoting activity, we investigated the effects of TCDD on the expression of certain key genes involved in liver cell growth and the effects of TCDD on induced hepatocyte cell proliferation. Gene expression analysis was conducted, by Northern blot hybridization, using RNA isolated from female Sprague‐Dawley rat livers collected at various times during a 14‐day dosing period with TCDD known to produce alterations in cell proliferation. No major changes were observed in the expression of the transforming growth factors TGF‐α and TGF‐β or in oncogenes ras, src and myc. However, the expression of the transcription factors C/EBP, HNF‐1 α and HNF‐4 decreased after 14 days of TCDD treatment. To investigate how TCDD affects hepatic growth, cell proliferation analysis was conducted in rats stimulated to undergo hepatocyte proliferation following either 2/3 partial hepatectomy or lead nitrate treatment. Cell proliferation was quantified by means of immunocytochemical detection of Proliferating Cell Nuclear Antigen (PCNA). Fourteen days of pretreatment with TCDD caused an overall inhibiton of hepatocytes in the growth fraction (G1, S, G2 and M) from 61 ± 3% in the control‐partial hepatectomy group to 41 ± 3% in the TCDD‐partial hepatectomy group. A periportal pattern of cell proliferation was observed in the TCDD‐partial hepatectomy group as compared to the panlobular pattern of cell proliferation in the control‐partial hepatectomy group. TCDD pretreatment also produced an inhibition of cell proliferation induced by the liver mitogen lead nitrate. TCDD‐induced inhibition of hepatocyte proliferation could play a role in TCDD tumour promotion and hepatocarcinogenesis through the creation of a environment whereby preneoplastic cells continue to expand while normal hepatocyte proliferation is inhibited.
Regulation of NIH‐3T3 cell G1 phase transit by serum during exponential growth
Authors: DiSalvo C. V. , Zhang D. , Jacobberger J. W. 
Published: May 2008

AbstractThe proliferation rate of mammalian cells is regulated normally in the G1 phase of the cell cycle. During this phase, it is convenient to assign positive and negative roles to the molecular programs that regulate the duration of G1 and the phase transition from G1 to S phase. Density‐dependent inhibition of cellular proliferation results in an increase in the duration of G1. This form of regulation is due to both secreted factors and cell—cell contact. Serum is mitogenic to a variety of mammalian cell types. Because quiescent cells enter S phase as a result of serum addition to culture media, serum is usually regarded as a source of positive regulatory growth factors. We have measured the length of the G1, S and G2+ M phases of NIH 3T3 cells during exponential growth as a function of cell density and serum concentration. The G1 length increases during exponential growth as a function of density while S and G2+ M are relatively constant. Further, this increase in G1 phase time, or density mediated negative regulation, is inhibited by increasing serum concentration. This phenotype is saturable between 10% to 20% serum. Serum concentrations above 2.5% are able to increase the rate of cell cycling (decrease the G1 phase time) by inhibiting density dependent negative regulation of NIH 3T3.
E2F transcription factor action, regulation and possible role in human cancer
Authors: Sladek T. L. 
Published: May 2008

AbstractE2F transcription factors regulate expression of a panel of cellular genes that control cellular DNA synthesis and proliferation, either by activating or repressing their transcription, largely in a cell cycle‐dependent manner. The ability of E2F proteins to regulate expression of these target genes is, in turn, regulated by other cellular proteins that are important for normal control of cell cycle progression. Together, E2F proteins, their target genes, and the proteins that regulate E2F activity comprise a genetic pathway that is probably the most frequently altered pathway in human cancer. This review examines this genetic pathway and focuses on the role of E2F proteins in its function. Specifically, the target genes regulated by E2F, the likely mechanisms by which activation and repression of target gene transcription is achieved, and the regulation of E2F activity by other proteins in the cell, are discussed.
Prolactin receptor expression by splenocytes from rats in various hormonal states
Authors: Güneş H. , Zawilla S. , Mastro A. M. 
Published: May 2008

AbstractProlactin (PRL) is mitogenic for lymphocytes in vitro, but the responsiveness of lymphocytes depends on the in vivo hormonal status of the rats from which the cells were obtained. Lymphocytes from ovariectomized (OVX) rats, but not from rats in oestrus or from male rats, respond to prolactin; administration of oestradiol to OVX rats diminishes the response. In order to determine if a correlation exists between lymphocyte responsiveness to prolactin and levels of cell surface prolactin receptors (PRL‐R) expression, the percentage of splenocytes and each splenocyte subpopulation expressing surface PRL‐R from rats of various hormonal states (OVX, oestradiol‐injected OVX, oestrus and male) was analysed by single‐colour and dual‐colour flow cytometric analysis. We found that approximately 20% of splenocytes expressed surface PRL‐R regardless of hormonal states (n= 16). The majority (85%) of PRL‐R positive splenocytes were B lymphocytes whereas 11.1% and 4.8% of splenocytes expressing the PRL‐R were CD4 positive T‐helper (TH) and CD8 positive T‐cytotoxic (Tc) lymphocytes, respectively. B lymphocytes also stained more brightly than T lymphocytes. This distribution of PRL‐R expression did not show significant alterations on total splenocytes or TH and Tc lymphocytes during various hormonal stages. However, the percentage of PRL‐R‐positive B lymphocytes increased markedly in OVX rats (twofold), compared to rats at oestrus. In summary, no correlation was found between the responsiveness to prolactin as a mitogen and levels of PRL‐R expression by lymphocytes from rats at different hormonal states. This result suggests that sex steroid hormones may control prolactin responsiveness of lymphocytes by affecting the signal transduction pathway through PRL‐R rather than by altering the level of the cell surface receptor expression.
WR‐1065, an active metabolite of the cytoprotector amifostine, affects phosphorylation of topoisomerase IIα leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells
Authors: Murley J. S. , Constantinou A. , Kamath N. S. , Grdina D. J. 
Published: May 2008

AbstractThe effects of WR‐1065 (2‐((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) IIα activity, and topo IIα phosphorylation in Chinese hamster ovary (CHO) cells have been investigated. Exposure of CHO cells to 0.4 μm of WR‐1065 for 30 min did not effect cell cycle progression nor topo IIaL activity and phosphorylation status. However, concentrations ranging from 4 μm to 4 mm were equally effective in significantly altering these three end points. Cell cycle progression was analysed by flow cytometry. Following a 30 min exposure to this range of concentrations, cells redistributed throughout the cell cycle with the most prominent changes being an accumulation of cells in G2. Topo IIα activity was measured using a kinetoplast DNA (kDNA) decatenation assay. Enzyme activity was reduced by 50% relative to control levels throughout the 4 μm to 4 mm dose range tested. Likewise, topo IIα phosphorylation levels, analysed using an immuno‐precipitation assay and an antibody specific to the 170 kDa band of topo II, decreased between 42% to 48% of control levels. Inhibition of topo IIα activity in cells exposed to WR‐1065 is consistent with the associated observation of WR‐1065 mediated cell cycle progression delay and build‐up of cells in the G2 phase of the cell cycle.
Engagement of DNA polymerases during apoptosis
Authors: Miscia S. , Di Baldassarre A. , Rana R. Alba , Di Pietro R. , Cataldi A. 
Published: May 2008

AbstractDNA replicative and repair machinery was investigated by means of different techniques, including in vitro nuclear enzymatic assays, immunoelectron microscopy and confocal microscopy, in apoptotic cell lines such as HL‐60 treated with methotrexate, P815 and K562 exposed to low temperatures and Friend cells exposed to ionizing radiation. The results showed a shift of DNA polymerase α and β activities. DNA polymerase α, which in controls was found to be the principal replicative enzyme driving DNA synthesis, underwent, upon apoptosis, a large decrease of its activity being replaced by DNA polymerase β which is believed to be associated with DNA repair. Such a modulation was concomitant with a topographical redistribution of both DNA polymerase α and the incorporation of BrdUrd throughout the nucleus. Taken together, these results indicate the occurrence of a dramatic response of the DNA machinery, through a possible common or at least similar behaviour when different cell lines are triggered to apoptosis. Although this possibility requires further investigation, these findings suggest an extreme attempt of the cell undergoing apoptosis to preserve its nuclear environment by switching on a repair/defence mechanism during fragmentation and chromatin margination.
Gompertzian growth curves in parathyroid tumours: further evidence for the set‐point hypothesis
Authors: Parfitt A. M. , Fyhrie D. P. 
Published: May 2008

Abstract Background: Clinical and cell kinetic data in parathyroid tumours show that their rate of growth slows down progressively and that tumour size approaches an asymptotic value. The Gompertz equation has been widely used in oncology to model growth retardation in malignant tumours; we describe its first aplication to a benign tumour. Methods: In 41 patients with radiation associated hyperparathyroidism, individual solutions were derived for the Gompertz equation: Nt= Exp[A/a(1–Exp–at)], where A is the rate constant (years‐1) for initial exponential growth and a is the rate constant (years‐1) for exponential decline in A. Input data comprised three estimates of tumour age at surgery, 100%, 75% and 50% of the time since irradiation, cell number estimated from tumour weight, and current tumour growth rate, representing the difference between current cell birth rate, estimated from the prevalence of mitotic figures, and an assumed mean rate of cell loss of 5%. Results: With 100% tumour age, geometric mean values were 2.76 for A, 0.134 for a, and 0.87 g for the growth asymptote. As assumed tumour age decreased, the rate constants increased and the growth asymptotes declined from 22% to 9% greater than the geometric mean tumour weight. Depending on assumed tumour age, the rate constants were about 15–45 times smaller than in myeloma and in testicular tumours, and the growth asymptotes about 2500 and about 60 times smaller, respectively. A and a were highly correlated (r2= 0.993), with a slope of 20.9 and no significant intercept. Depending on assumed tumour age, the geometric mean time from the initial mutation to the first cell division ranged from 39 to 92 days, much longer than in malignant tumours. Conclusions: (1) The Gompertz modelling demonstrates that both the nonprogressive clinical course and the slow growth of parathyroid tumours can be accounted for by a single mutation. (2) The extremely low values for A and a, and consequent very long delay before the first cell division, support the notion that the initial mutation does not affect a growth regulatory gene, but increases growth indirectly via an increase in secretory set‐point, the clone of mutant cells behaving as if they were in a hypocalcaemic environment until the plasma calcium rises to the new set‐point. (3) The clinical characteristics of radiation‐induced parathyroid tumours are modelled more closely if there is a substantial delay between time of irradiation and onset of tumour growth. (4) The rate constants A and a are highly correlated because the variability