SEARCH · PubMed Health

Results for “Proliferation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed1975

Autoradiographic investigations of glial proliferation in the brain of adult mice. II. Cycle time and mode of proliferation of neuroglia and endothelial cells.

The cycle time of the proliferating glial cells outside the subependymal layer of the lateral ventricle as well as that of endothelial cells was studied autoradiographically in the brains of adult and untreated mice. To determine the mean cycle time two independent methods were used. A mean cycle time of about 20 hours was obtained for glial and endothelial cells from the decrease of the mean grain number/nucleus as a function of time after tritiated thymidine (3H-TdR) injection. Another group of experiments utilized the "method of labeled S phases". With this method the passage of labeled cells through successive S phases is observed. Passing through S phase following 3H-TdR injection the 3H-labeled cells are double labeled by an additional 14C-TdR injection. This method again resulted in a cycle time of 20 hours for glial and endothelial cells. From the present work and a former study (Korr et al., '73) the following cell cycle parameters were derived: Cycle time 20 hours; S phase 9.4 hours; G2 less than three hours; (G2+M) five hours; G1 five hours. The growth fraction of glial cells related to all glial cells is only 0.004. Furthermore, the present experiments show that in the case of glial cells 17% of the daughter cells after mitosis become pyknotic and are eliminated from the glial cell population. Apart from this cell loss, after mitosis about one-fourth of the daughter cells do not enter the next S phase. These cells leave the growth fraction and are replaced by a corresponding number of non-proliferating glial cells. There is a relatively extensive permanent exchange of cells between the growth fraction and non-growth fraction of glial cell.

Animals↗

PubMed1986

Regulation of thymocyte proliferation and survival by deoxynucleosides. Deoxycytidine produced by thymic accessory cells protects thymocytes from deoxyguanosine toxicity and stimulates their spontaneous proliferation.

Deoxyguanosine (dGuo) inhibits thymic blast DNA synthesis and then induces thymocyte cell death. The dGuo inhibitory action, measured with four different assays (spontaneous thymidine incorporation, immunofluorescent detection of 5-bromodeoxyuridine incorporation, dye exclusion, tetrazolium salt cleavage), was suppressed in the presence of supernatants from cultures containing phagocytic cells. In particular, we studied the anti-dGuo activity in supernatants from thymic reticulum cultures (TRS) and in those from phagocytic cells isolated from TR cultures (P-TR). The anti-dGuo substance was identified as deoxycytidine (dCyd) by high performance liquid chromatography and other physicochemical studies. Secretion of dCyd by P-TR is accompanied by thymidine but not by purine nucleoside secretion. A dual mechanism of thymocyte rescue by dCyd was demonstrated by a study of the dose-dependencies of dCyd-mediated prevention and reversal, respectively, of the dGuo inhibition. In addition to this exogenously added anti-dGuo action, dCyd and dCyd-containing TRS induced significant stimulation of spontaneous thymic blast proliferation, and the kinetics of both effects were identical. These findings might suggest that a major role of thymic phagocytic cells is the supply of pyrimidine nucleosides to thymocytes resulting in the maintenance of proliferation and protection of at least some thymic blasts from the toxic effects of dGTP accumulation. The role of this system in the intrathymic selection process is discussed.

Animals↗

PubMed1990

Differential effects of anti-CD45 monoclonal antibody on human B cell proliferation: a monoclonal antibody recognizing a neuraminidase-sensitive epitope of the T200 molecule enhances anti-immunoglobulin-induced proliferation.

We have generated seven monoclonal antibodies (mAb) that recognize the T200 molecule. These mAb have been classified by competitive binding assay in flow cytometry into three groups each reacting with a different epitope of the T200 molecule: (a) 136-4B5, that shows a sialic acid nature, (b) 135-4H9, 135-4C5, 144-2, 155-2 and (c) 72-5D3, 124-2H12b. A heterogeneous effect was observed when they were tested on an anti-immunoglobulin-induced B cell proliferation. Whereas 72-5D3 and 135-4H9 mAb inhibited the proliferative response of B cells, 136-4B5 mAb greatly enhanced it, both effects being dose dependent. We can conclude that anti-CD45 mAb have a different and contrary functional behavior on anti-Ig-induced B cell proliferation, depending on the epitope recognized. The basis for such a difference could reside in the glucidic nature of the epitope recognized by the 136-4B5 mAb.

Antibodies, Anti-Idiotypic↗

PubMed1993

Modulation of T cell proliferation by stimulation of the beta-adrenergic receptor: lack of correlation between inhibition of T cell proliferation and cAMP accumulation.

The presence of beta-adrenergic receptors on T cells suggests the potential for modulating T cell function upon binding of an appropriate agonist. Utilizing highly purified human T cells we assessed the proliferative capacity of T cells upon stimulation with immobilized anti-CD3 monoclonal antibody (mAb) in the presence of the beta-adrenergic agonist isoproterenol (ISO). The proliferative response of T cells and their CD4+, CD8+, or CD45RO+ subsets to anti-CD3 mAb was inhibited in a dose-dependent manner by ISO. In parallel experiments, various concentrations of prostaglandin E2 (PGE2) were added to anti-CD3 mAb-stimulated T cells and their subsets. Similar dose-dependent effects were observed with the important exception that PGE2 was considerably more immunosuppressive than ISO. The results also showed that PGE2 was a much more effective inhibitor of anti-CD3 mAb-induced interleukin 2 synthesis by T cells than was ISO. Because both the beta-adrenergic and PGE2 receptors are linked to adenylyl cyclase, the magnitude and kinetics of cAMP accumulation in T cells and their subsets were determined after stimulation with ISO or PGE2. The results show that PGE2 induced a greater and more sustained accumulation of cAMP than ISO. Moreover, these differences could not be ascribed to differential modulation of cAMP phosphodiesterase activity. Correlation of the degree of inhibition of anti-CD3 mAb-induced T cell proliferation by PGE2 or ISO with the level of accumulation of cAMP in these stimulated T cells indicate that, on an equimolar basis, cAMP elicited by PGE2 is more immunosuppressive than that induced by ISO. These results suggest that qualitative differences in cAMP accumulation in T cells have an important role in the subsequent modulation of anti-CD3 mAb-induced T cell proliferation.

CD3 Complex↗

PubMed1994

House dust mite-responsive human T cells require both interleukin 2 (IL2) and interleukin 4 for optimal proliferation, whereas IL2 alone is sufficient for proliferation of tetanus toxoid-responsive T cells.

Production of interleukin 4 (IL4) and response to IL4 may be a key determinant of the atopic immune response. Proliferation requirements of allergen-specific T cells derived from atopics and nonatopics were determined. Peripheral blood lymphocytes were cultured with either house dust mite (HDM) or tetanus toxoid under limiting dilution conditions with interleukin 2 (IL2) alone or IL2+IL4. The relative proportion of antigen-specific T cells responding under each of these conditions was determined by proliferation. The combination of IL2+IL4 resulted in the highest proportion of responding HDM-specific T cells. Similar results were obtained with HDM-specific T cells from both atopic and nonatopic donors. These HDM and Der pI responsive cells were found to be CD4+CD8-. In contrast, tetanus toxoid-responsive T cells from both atopic and nonatopic donors grew preferentially in response to IL2 alone.

Adult↗

PubMed1993

Intracellular growth factor metabolism in proliferation of a brain tumor cell line. Intracellular growth factors and brain tumor proliferation.

Brain tumor cells secrete platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta), and through local production of these growth factors, brain tumor cells may stimulate their own proliferation. Previously we have shown that several different clones of canine glioma cells secrete varying amounts of PDGF and TGF-beta which correlate with in vitro cloning efficiency and in vivo tumorigenicity. In this study, intracellular trafficking of PDGF and TGF-beta was assessed by treatment of each clone with agents preventing vesicular degradation and secretion of growth factors. Clone 2 was more sensitive to these agents (chloroquine and monensin) than clone 5, resulting in retention of intracellular 125I-PDGF and 125I-TGF-beta. Furthermore, exogenous TGF-beta inhibited DNA-synthesis dramatically in clone 2 (compared with clone 5), presumably by interfering with intracellular growth factor receptor availability. This is supported by the fact that exogenous TGF-beta increased the number of its receptors on clone 2 cells, whereas surface receptors decreased on clone 5 cells treated with TGF-beta. These results illustrate the potential for autocrine growth factors to interact with their receptors intracellularly during neoplastic cell proliferation.

Animals↗

PubMed1975

Glial cell proliferation in retinal detachment (massive periretinal proliferation).

In experimental retinal detachment of the owl monkey we observed the formation of preretinal and subretinal membranes which had cellular connections to the retina proper. Based on light microscopic findings we concluded that retinal cells grow out of the retina and build up the preretinal and subretinal tissue. Electron microscopically these cells are identified as astrocytes which grow out through focal interruptions in the internal or external limiting membrane. In the immediate area of outgrowth Muller cell processes praticipate in the formation of the preretinal or subretinal tissue. These glial membranes can cause wrinkling of the internal limiting membrane and the nerve fiber layer or full-thickness folding of the retina. Glial proliferation plays an important role in the development of a complication in retinal detachment which we suggest calling "massive periretinal proliferation" (MPP).

Animals↗

PubMed1992

Studies of the relationship between cell proliferation and cell death. II. Early gene expression during concanavalin A-induced proliferation or dexamethasone-induced apoptosis of rat thymocytes.

Several data in the literature suggest that an intriguing relationship exists between cell proliferation and cell death. Accordingly, we studied the early expression of different genes in the same cells, i.e. rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment. We showed that an early accumulation of c-fos, c-jun and c-myc mRNA occurred in both phenomena but with different kinetics. It can be speculated that the early induction of nuclear oncogenes is necessary to allow the later induction of other genes probably regulated at the transcriptional level by the AP-1 complex and/or by Myc protein. The accumulation of the transcript for another gene, i.e. poly(ADP-ribose)polymerase, an enzyme responsible for posttranslational modifications of several nuclear proteins, could instead be related to chromatin modifications occurring in both processes.

Animals↗

PubMed1986

Cell-mediated inhibition of proliferation and activation of alloreactive cytotoxic lymphocytes: maintenance of response potential of precursors and dissociation between proliferation and effector function of activated cytotoxic lymphocytes.

Adherent layers of macrophages (M phi-c) generated in vitro from splenic precursors inhibit lymphoproliferative responses to mitogen and to alloantigen without inhibiting the production of interleukin-2 (IL-2). Analysis of spleen cells stimulated for 48 hr in the presence of M phi-c indicated that both blastogenesis (increased cell mass) and expression of IL-2 receptors (7D4 determinants) were reduced. Analysis of BrdU incorporation (frequency of S-phase cells) and total cellular DNA revealed that the M phi-c inhibited the progression from G1 to S phase of cell cycle. The M phi-c not only inhibited the proliferative response to alloantigen but also prevented the generation of alloreactive cytotoxic T cells. The M phi-c were shown not to inhibit CTL responses by eliminating the stimulators or by inactivating precursors or inducing suppressors. The M phi-c were affecting the induction of CTL activity since the M phi-c did not affect the expression of cytolytic activity by activated CTL. The M phi-c did inhibit the proliferation of the activated CTL, suggesting that although cytolytic activity can be expressed in G1 phase of cell cycle, the activation of cytolytic activity in CTL-P may require a G1 to S phase transition. The cells recovered from 5-day MLC incubated in the presence of M phi-c were fully capable of generating a subsequent CTL response. This is in contrast to cells recovered from unstimulated cultures (no M phi-c) which have lost the ability to generate CTL responses. The M phi-c therefore prevent the generation of CTL responses in a totally reversible fashion, so as to allow activation and proliferation of CTL-P which have been removed from the influence of the M phi-c. These observations are discussed in the context of the currently hypothesized role of tissue macrophages in microenvironmental regulation.

Animals↗

PubMed1992

Distribution patterns and frequency of proliferating cells in cutaneous keratinocytic neoplasms. Immunohistochemical study with a monoclonal antibody (TOB7) used against proliferating cell nuclear antigen.

BACKGROUND: Almost all markers for proliferating cells need freshly frozen tissues for evaluation; therefore retrospective study is impossible. OBJECTIVE: In the present study, a murine monoclonal antibody (TOB7) against the proliferating cell nuclear antigen (PCNA) was used for the analysis of cell kinetics of cutaneous keratinocytic neoplasms. The antibody is applicable to formalin-fixed, paraffin-embedded tissues. METHODS: The frequency of PCNA-positive cells and their distribution patterns were immunohistochemically investigated in various cutaneous keratinocytic neoplasms. RESULTS: Squamous cell carcinoma and Bowen's disease showed significantly increased numbers of PCNA-positive cells when compared with other keratinocytic neoplasms. A characteristic marginal or random distribution pattern of PCNA-positive cells was observed in the lesions of each disease category. CONCLUSION: Important information on the growth dynamics of keratinocytic neoplasms was obtained in this retrospective immunohistochemical study.

Antibodies, Monoclonal↗

PubMed1990

In vitro effect of doxorubicin on non-proliferating and proliferating epithelial cells.

In vitro cultured mouse kidney epithelial cells were exposed for 2 hr to 0.5 microgram/ml of Doxorubicin. The proliferative activity of the cells was determined by combined DNA and total nuclear protein measurements. The sensitivity of the cells to the drug was higher in proliferating cells as compared to non-proliferating ones, that is, those exhibiting low amounts of total nuclear protein per unit DNA.

Animals↗

PubMed1982

The role of cellular proliferation in an experimental model of massive periretinal proliferation.

Transplantation of from 10,000 to 750,000 autologous and homologous dermal fibroblasts into the vitreous cavity of rabbit eyes resulted in identical clinical findings leading to massive periretinal proliferation. A dose-response relationship between the number of cells injected and the extent of retinal traction that developed was established. The second phase of the experiment evaluated the effects of formalin and cobalt irradiation on the fibroblasts' ability to cause traction retinal detachment. Cell proliferation or the attainment of a critical mass of living cells was necessary for the development of traction retinal detachment.

Animals↗

PubMed2001

Improving the in vitro antigen specific T cell proliferation assay: the use of interferon-alpha to elicit antigen specific stimulation and decrease bystander proliferation.

The measurement of the proliferative response of primed T cells to an antigenic stimulus (lymphocyte transformation assay: LTT) is commonly used for determining T cell immune responsiveness. However, the ratio between the spontaneous and the antigen-triggered response (stimulation index) is frequently quite low (<3-5) making the interpretation difficult. We modified the assay by the addition of interferon-alpha and the use of fresh autologous serum instead of human AB pool serum. These measures significantly enhanced the stimulation index following stimulation with tetanus toxoid, Candida albicans and tick-borne encephalitis (TBE) viral antigen in studies of sensitized patients. There was no concomitant increase in false positive results. Kinetic studies showed a reduced nonspecific background proliferation of non-stimulated cultures particularly between days 4 and 6 of culture. Furthermore, the positive effect of interferon-alpha were confirmed in studies of patients with contact allergy to nickel and gold. We conclude that this modified form of proliferation assay significantly increases the signal to noise ratio which can be attained. This may be of particular value when looking at T cell responses in immunocompromised patients or in diagnostic attempts to detect very low frequencies of antigen-specific T cells.

Adult↗

PubMed1984

About the effect of risk factors on the structure and the proliferation of arterial wall cells. Part 1: Changes in structure and proliferation of cultivated aortic smooth muscle cells from hypertensive-diabetic rats.

In cultivated aortic smooth muscle cells (SMC) from normal or hypertensive-diabetic rats respectively, two types of cells, small SMC and large ones, were observed. The differences between the surface areas, form factors and nucleus-plasma relations of the small and the large cells, measured by morphometric methods are evident. The ratio of small to large cells originating from the normal group was 87%: 13%, and of those originating from the hypertensive-diabetic group 76%: 24%. The percentages of polynuclear cells from the normal group were 3.9% and from the hypertensive-diabetic group 6.1%. The small cells from hypertensive-diabetic rats proliferated faster (3H-thymidine labeling index 23.7%) than those from the control rats (3H-thymidine labeling index 12.9%). Their large cells showed on the contrary a trend to slower proliferation.

Animals↗

PubMed2003

Peroxisome proliferator-activated receptor alpha induces rat sterol carrier protein x promoter activity through two peroxisome proliferator-response elements.

Sterol carrier protein x (SCPx) plays a critical role in the peroxisomal oxidation of fatty acids. It has been previously demonstrated in streptozotocin-induced diabetic rats that SCPx expression is induced in association with an elevation in serum fatty acid and triglyceride levels. To elucidate the mechanisms underlying the expression of this gene during diabetes, the rat SCPx promoter was cloned and analyzed for regulatory motifs. Sequence analysis of this TATA-less promoter revealed two putative peroxisomal-proliferator-response element (PPRE) binding motifs at positions -134 and -869 relative to the translation start site. To examine peroxisomal-proliferator-activated receptor alpha (PPARalpha) effects on this gene, 935 bp of the SCPx promoter containing both PPRE motifs was cloned in front of the chloramphenicol acetyl-transferase gene or the luciferase gene and co-transfected into HTB-9 cells with vectors that encoded for PPARalpha and retinoid X receptor (RXR). The results indicate that PPARalpha was able to induce SCPx promoter activity in both cases, an effect that was enhanced by RXR and clofibrate. In addition, mutational analysis studies demonstrated that both PPREs contributed to the PPARalpha/RXRalpha-dependent activation of the SCPx promoter. Mobility shift assays and supershift analysis showed that nuclear extracts containing PPARalpha bound to the two PPRE motifs. This investigation indicates that similar to other genes involved in beta-oxidation, SCPx transcription may be controlled by fatty acid levels via PPARalpha.

Acetyl-CoA C-Acetyltransferase↗

PubMed2001

Simulated shortening of proliferation-restricting telomeres during clonal proliferation and senescence of human cells.

In the absence of telomerase or other mechanisms to maintain their length, telomeres in human cells shorten at each round of cell division. This has been suggested to ultimately cause cell cycle exit when a critical telomere length is reached, leading to replicative senescence of the cell. At present, it is not clear whether the division potential of human cells is limited by the overall shortening of telomeres at all chromosomes or the shortening of specific telomeres on certain particular chromosomes. By computer simulations, my previous work has suggested that if the telomere theory is correct, the shortening of only a few, most likely two, telomeres might be preferentially involved in restricting the division of human cells. In this work, the length dynamics of individual telomeres in simulated cell clones were examined over their life span. It is shown that if the shortening of only two telomeres is responsible for restricting the proliferation of a cell, these two specific telomeres will shorten at different rates and have different length distributions from those of the rest telomeres. The unique pattern of length dynamics associated with the proliferation-restricting telomeres (PRT) provides a possibility of experimentally identifying these particular telomeres in human cells.

Cell Division↗

PubMed2000

Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.

Adult↗

PubMed2003

Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element.

The expression of several genes involved in fatty acid metabolism is regulated by peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of carnitine palmitoyltransferase (CPT) gene expression, we examined the transcriptional regulation of the human CPT II gene. We show that the 5'-flanking region of this gene is transcriptionally active and binds PPARalpha in vivo in a chromatin immunoprecipitation assay. In addition, we characterized the peroxisome proliferator-responsive element (PPRE) in the proximal promoter of the CPT II gene, which appears to be a novel PPRE. The sequence of this PPRE contains one half-site which is a perfect consensus sequence (TGACCT) but no clearly recognizable second half-site (CAGCAC); this part of the sequence contains only one match to the consensus, which seems to be irrelevant for the binding of PPARalpha. As expected, other members of the nuclear receptor superfamily also bind to this element and repress the activation mediated by PPARalpha, thus showing that the interplay between several nuclear receptors may regulate the entry of fatty acids into the mitochondria, a crucial step in their metabolism.

Base Sequence↗