SEARCH · PubMed Health

Results for “Cell 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 199 records · Page 11Linked to original sources

PubMed1994

Contrasting roles for integrin beta 1 and beta 5 cytoplasmic domains in subcellular localization, cell proliferation, and cell migration.

To carry out a detailed comparison of the roles of integrin beta 1 and beta 5 cytoplasmic domains, we expressed both wild type beta 1 and chimeric beta 1/5 constructs in CHO cells. In the latter, the cytoplasmic domain of beta 1 was replaced with that of beta 5. The human beta 1 and beta 1/5 constructs appeared at similar levels at the cell surface (mostly as alpha 5 beta 1 heterodimers) and contributed equally to CHO cell adhesion to fibronectin. However, beta 1 but not beta 1/5 localized to focal adhesion-like structures when CHO cells were spread on fibronectin. Furthermore, only the beta 1-CHO cells showed increased proliferation in response to fibronectin plus an integrin-activating anti-beta 1 antibody, and showed increased appearance of 32P-labeled protein (p90) that correlated with proliferation. In sharp contrast, the beta 1/5-CHO cells were notably more migratory than beta 1-CHO cells in a transwell haptotactic migration assay. These results indicate that the beta 1 and beta 5 integrin subunit cytoplasmic domains can translate similar adhesive information into highly contrasting subsequent events. Thus, we have established that "inside-out" and "outside-in" integrin signaling pathways are regulated by fundamentally distinct mechanisms. In addition, we suggest that the same properties of the beta 1 cytoplasmic domain that promote recruitment to visible focal adhesion-like structures may also be conductive to cell proliferation. Conversely, the properties of the beta 5 tail that make it less likely to localize into focal adhesion-like structures may contribute to enhanced cell migration.

Amino Acid Sequence↗

PubMed1995

p53 expression and cell proliferation in squamous cell carcinomas of the head and neck.

BACKGROUND: In squamous cell carcinoma of the head and neck (SCCHN), overexpression of the p53 protein has been found in 34-80% of the tumors studied. No data are available regarding p53 expression versus tumor cell proliferation and prognosis for this tumor type. METHODS: p53 protein levels were studied by immunohistochemical staining of 33 primary SCCHN using 3 antibodies (DO7, PAb 1801, and CM1) that react with different epitopes of the p53 protein. The cellular expression of p53 was compared with in vivo incorporation of the thymidine analog iododeoxyuridine (IdUrd) and expression of proliferating cell nuclear antigen (PCNA). RESULTS: Twenty-one tumors (64%) had a positive nuclear staining for p53 with the monoclonal antibody DO7, which reacts with a denaturation-resistant epitope in wild-type and mutant p53. PAb 1801 and CM1 reacted with 19 and 20 tumors, respectively, all of which were DO7-positive. No correlation was found between incorporation of IdUrd and p53 expression or between PCNA and p53 expression. The data indicate that intracellular accumulation of the p53 protein was related to tumor stage and localization of the tumor. No indication of a clinical or prognostic significance of p53 expression in SCCHN was found. CONCLUSIONS: No association between p53 deregulation and tumor cell proliferation was found.

Carcinoma, Squamous Cell↗

PubMed1998

Progesterone and estrogen regulation of rat decidual cell expression of proliferating cell nuclear antigen.

This study was an examination of the role of progesterone (P4) and estradiol-17beta (E2) as stromal cell mitogens in the decidua basalis (DB) of the rat during pregnancy. Pregnant rats were ovariectomized (Ovx) on Days 8 and 12 of pregnancy, treated with P4, E2, or both, and killed on Days 10 and 14, which correspond to times of stromal cell proliferation and regression, respectively. In some experiments, rats received pellets of the anti-progestin RU-486 on Day 9 and were killed 6, 12, and 24 h later. The mitotic index (MI) and in situ image analysis of expression of proliferating cell nuclear antigen (PCNA) were used to assess cell cycle progression. Highest expression of PCNA occurred on Days 8-12 of pregnancy, and MI was maximum; MI became zero and PCNA expression decreased dramatically thereafter (i.e., Days 14, 17, 21). Percentage of cells expressing intense PCNA on Day 10 (40%) declined to 5% after Ovx and Ovx + E2 (p < 0.05), whereas Ovx + P4 maintained PCNA. By Day 14, only 1% of stromal cells expressed intense PCNA, which was not significantly altered by Ovx, Ovx + E2, or Ovx + P4 but increased after Ovx + P4 and E2 (p < 0.05). By 6 h of RU-486, MI declined 3-fold, and intense PCNA expression was essentially lost. These changes preceded loss of histological integrity of the DB. Cells with undetectable PCNA steadily increased from 8% at 6 h to 28% by 24 h (p < 0.05). Thus RU-486 appeared to block cell cycle progression and enhanced PCNA turnover. P4 was essential for stromal cell proliferation during early pregnancy (Days 8-10), but this action was lost by Day 14.

Animals↗

PubMedDate not supplied

Correlation between microvessel density and tumor cell proliferation with clinical factors in breast carcinomas.

Fifty-nine methacarn-fixed, paraffin-embedded human breast carcinomas were immunostained by QB-END/10 (an antibody to CD34 antigen) to observe microvessels and by PC10 (an antibody to proliferating cell nuclear antigen; PCNA) to determine tumor cell proliferation; 9 normal human breast tissue specimens were also immunostained by QB-END/10. The number of microvessels in the periphery of the breast carcinoma was significantly greater than both that in the center of the breast carcinoma and that in the normal breast. There was also a significant relationship between the number of microvessels in the periphery of breast carcinomas and the histological tumor size and lymph node status. However, there was no significant relationship between the tumor cell proliferation activity (PCNA positive cell ratio) and any clinical or histopathological variables. The number of microvessels and the tumor cell proliferation activity showed a weak negative correlation.

Adult↗

PubMed1993

Cell proliferation as a prognostic indicator in conjunctival malignant melanoma.

Expression of proliferating cell nuclear antigen, a DNA polymerase delta auxiliary protein, was studied in 20 specimens from 20 patients with conjunctival malignant melanoma by means of the total number of cells that showed immunoreactivity per square millimeter. The countings were shown to be reproducible with minimal intraobserver variability. In a multifactor analysis of variance (ANOVA) that adjusted for possible confounders, patients who subsequently died of metastatic disease had significantly higher counts of cells that were positive for proliferating cell nuclear antigen per square millimeter (P = .0011) than patients with a minimum survival of five years without clinical signs of metastatic disease. A multivariate Cox regression model confirmed the independent prognostic value (P = .048) of the cell counts. Individual hazard ratios were estimated in a final Cox model and two groups of patients with low and high hazard ratios were formed. Five-year cumulated survival proportions of the two groups were 90% and 60%, respectively. The total count of cells displaying immunoreactivity for proliferating cell nuclear antigen per square millimeter may be used as a prognostic indicator in patients with conjunctival melanoma.

Analysis of Variance↗

PubMed2005

Proliferating-cell nuclear antigen (PCNA) as an independent prognostic marker in patients after prostatectomy: a comparison of PCNA and Ki-67.

OBJECTIVE: To investigate the prognostic value of prostatic tumour cell proliferation, as measured by Ki-67 and proliferating cell nuclear antigen (PCNA), and to compare these measures in men at low and high risk for progression of tumour. PATIENTS AND METHODS: Two groups of patients with prostate cancer, i.e. 'metastatic' (M, 22) who had pT3b-4aN0M0 and pTanyN1M0, and 'nonmetastatic' (NM, 18), who had < or =pT3aN0M0 disease, were selected from a well-examined and mapped group of 114 treated by radical prostatectomy. Patients in the NM group were selected by the criteria of having a Gleason score of < or = 7. To assess proliferation, 1000 cells were counted at x 400 magnification by two observers and the percentage of tumour cells positively stained with Ki-67 and PCNA defined as the Ki-67 and PCNA labelling index (LI), respectively. The two LI were compared in the NM and M groups, and the correlation of the LIs with pathological stage, progression and prostate-specific antigen (PSA)-free survival evaluated. Prognostic values of the LI were analysed using multivariate analysis. RESULTS: The mean (range) follow-up was 33 (4-78) months. The mean LIs were higher in the M than the NM group for both PCNA and Ki-67 (P = 0.02 and 0.019, respectively). Both LIs were markedly different between the groups when stratified by progression, with both significantly higher in men with progression in the NM group. Both LIs had a significant association with Gleason score, pathological stage, progression and PSA-free survival. In multivariate analysis the PCNA LI, surgical margin status and pathological stage were independent factors for progression. CONCLUSION: Tumour cell proliferation as assessed by Ki-67 or PCNA correlate significantly with progression. The PCNA LI was an independent predictor of progression, especially in patients with a low risk of progression according to predefined criteria.

Aged↗

PubMed1997

Hepatic microsomal enzyme induction, beta-oxidation, and cell proliferation following administration of clofibrate, gemfibrozil, or bezafibrate in the CD rat.

Male and female CD rats were administered one of two dose levels of clofibrate, gemfibrozil, or bezafibrate daily by oral gavage for a period of 14 days in order to establish an empirical data base using the Charles River CD rat with a single class of drugs against which the potency of novel proprietary compounds could be compared. Subsequent gross examination of the liver indicated significant and dose-related increases in relative and absolute liver weights in males following clofibrate and gemfibrozil. In females, absolute and relative liver weights were significantly elevated to a similar degree with either dose of gemfibrozil, and absolute liver weights were higher in clofibrate-dosed animals. Bezafibrate had no effect on female liver weights. Clofibrate and gemfibrozil increased hepatic palmitoyl CoA beta-oxidation in both sexes; however, clofibrate had the greater effect in males and gemfibrozil had the least effect in females. Bezafibrate treatment resulted in a very pronounced elevation of palmitoyl CoA beta-oxidation in the males but had no similar effect in the females. Concurrent ELISA analysis for cytochrome CYP4A revealed very good correspondence between beta-oxidation and cytochrome induction for each of the three compounds in males, but other cytochromes were not greatly affected, except CYP1A1 which was elevated in bezafibrate-dosed females. For males, further analysis for markers of cellular proliferation, namely cyclin-dependent kinases (CDK) and proliferating cell nuclear antigen (PCNA), indicated dose-related increases for both with clofibrate, increases at the high dose for gemfibrozil, and, for PCNA, a dose-related increase for bezafibrate. In females, both markers for cell proliferation showed either slight or no increases following any of the three drug treatments. These results demonstrate clear sex-dependent differences in terms of relative potency in the hepatic response of the Sprague-Dawley-derived rat to these peroxisome proliferators. Bezafibrate is most potent and gemfibrozil is least potent in stimulating peroxisome-associated beta-oxidation and cytochrome P450 4A induction in the males. Even though gemfibrozil significantly increased liver weights, beta-oxidation and cytochrome P450 4A in the females increased only after clofibrate treatment, although to a lesser degree than in the males administered the same dose. Similar sex-related differences were observed for cell proliferation. In conclusion, sex-related differences were noted in the potency to stimulate acyl Co-A oxidation, its association with hepatomegaly, and the stimulation of cell proliferation, but CYP4A induction always accompanied any substantial drug-dependent increases in beta-oxidation.

Animals↗

PubMed1999

Protein kinase C-theta (PKCtheta) distribution analysis in hematopoietic cells: proliferating T cells exhibit high proportions of PKCtheta in the particulate fraction.

A comparative analysis of protein kinase C-theta (PKCtheta) protein expression was performed in various mouse organs and tissues, freshly isolated populations of mouse and human hematopoietic cells, primary leukemias, and established cell lines of different histological origins. Results demonstrated a predominant expression of PKCtheta in lymphoid tissues and skeletal muscle. Expression levels of PKCtheta, as well as PKCalpha, delta, epsilon, zeta, and eta in the thymus, were not markedly changed during postnatal development. High levels of expression were observed in CD4(+) and CD8(+) single-positive T cells and CD4(+)CD8(+) double-positive thymocytes, while B cells were completely devoid of PKCtheta. PKCtheta was found also in platelets, but relatively low levels or no detection of PKCtheta expression were observed in neutrophils, monocytes, and macrophages. Highly proliferating leukemic T cells of established lines or primary tumors, but not freshly isolated resting peripheral blood T cells, exhibited high levels of membrane-bound PKCtheta. Increased proportions of PKCtheta in the particulate fraction was not restricted to malignant cells but correlated with the extent of proliferation of the T cells. Thus, human peripheral blood T cells that were induced to proliferate by exposure to mitogen and IL-2 expressed increased levels of PKCtheta in the particulate fraction. Significantly lower proportions of membrane-bound PKC were observed for five other isoenzymes expressed in T cells. The occurrence of PKCtheta in T, but not B, cells and its subcellular distribution in proliferating cells implicate PKCtheta in cellular mechanisms regulating the sustained proliferation of T cells.

Adult↗

PubMed2005

Galectin-3 and proliferating cell nuclear antigen (PCNA) expression in papillary thyroid carcinoma.

BACKGROUND AND AIM: To examine the relationship between galectin-3 and cell proliferation in thyroid tumor tissue. Galectin-3, a beta-galactoside binding protein, has recently been recognized as a promising molecular marker of thyroid malignancy, due to its high expression in thyroid carcinomas and absence from normal or benign thyroid tissue. However, its exact role in thyroid tumor biology is still unknown. PATIENTS AND METHODS: We examined the relationship between galectin-3 and cell proliferation by comparative immunostaining for galectin-3 and proliferating cell nuclear antigen (PCNA) in paraffin-embedded tissues from 126 cases of papillary thyroid carcinoma. RESULTS: Positive cytoplasmic immunostaining for galectin-3 was found in 115 (91.3%) cases. Nuclear staining for PCNA was detectable in 93 (74.4%) cases. A low level of PCNA staining (less than 10% positive cells) was found in 36 (28.6%) cases, moderate staining for PCNA (more than 10% but less than 30% positive cells) in 35 cases (27.8%), while highly increased PCNA expression (more than 30% positive cells) was found in 32 (25.4%) cases. Moderate or strong galectin-3 expression, found in 99 cases, was associated with highly increased PCNA staining in 28.3% of them but with no detectable PCNA expression in 24.3% of them. CONCLUSION: These results suggest that overexpression of galectin-3 is not clearly related to proliferative activity of papillary thyroid carcinoma cells as assessed by PCNA immunostaining.

Biomarkers, Tumor↗

PubMed1993

[Cell proliferation and maturation of ectopic submucosal glands of the stomach].

Stomachs with multiple submucosal glands keep our attention because of their high risk for having gastric carcinomas, but little is known about the relationship between submucosal glands and occurring cancers. So we investigated the structure of submucosal glands including location of proliferating cells. We labeled proliferating cells of three stomachs with cancerous lesions by circulating artificial blood through the isolated organs with bromodeoxyuridine (BrdU). Serial sections of submucosal glands were stained with hematoxylin eosin, periodic acid Schiff, Alcian blue, high iron diamine-Alcian blue, concanavalin A paradox, galactose oxidase Schiff as well as anti-BrdU immunohistochemically. Results showed that most of submucosal glands were composed of functionally matured cells and these cells made regular structure just like those of mucosal layer. Labeling index of BrdU of these submucosal glands were low (0.2%-0.7%). Two atypical glands were seen, and labeling index were 2.6% and 22.2% respectively. In conclusion, submucosal glands of the stomachs were thought to be made by moving proliferating cells from mucosal layer to submucosal layer. So we saw these submucosal glands paracancerous lesions rather than precancerous ones. But we couldn't deny the possibility to occur cancerous lesions from atypical glands in submucosal glands.

Aged↗

PubMed2001

Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism.

To determine whether exposure to fox odor alters granule neuron production, we examined proliferating cells and their progeny in the dentate gyrus of adult male rats exposed to trimethyl thiazoline, a component of fox feces. Additionally, to determine whether this effect is adrenal hormone-mediated, we examined animals exposed to fox odor after bilateral adrenalectomy and replacement with low levels of the endogenous glucocorticoid corticosterone. Stereologic analyses of the number of 5-bromo-2'deoxyuridine (BrdU) -labeled cells revealed that exposure to fox odor but not other, nonthreatening, odors (mint or orange) rapidly decreased the number of proliferating cells in the dentate gyrus. This effect is dependent on a stress-induced rise in adrenal hormones; exposure to fox odor resulted in an increase in circulating corticosterone levels and prevention of this increase (by means of adrenalectomy plus low-dose corticosterone replacement) eliminated the suppression of cell proliferation. Examination at longer survival times revealed that the decrease in the number of new granule cells in fox odor-exposed animals was transient; a difference was still detectable at 1 week after BrdU labeling but not at 3 weeks. In both fox and sham odor-exposed animals, many new cells acquired morphologic and biochemical characteristics of mature granule neurons. The majority of these cells expressed a marker of immature granule neurons (TuJ1) by 1 week after BrdU labeling and markers of mature granule neurons (calbindin, NeuN) by 3 weeks after labeling. These findings suggest that stressful experiences rapidly diminish cell proliferation by increasing adrenal hormone levels, resulting in a transient decrease in the number of adult-generated immature granule neurons.

Administration, Inhalation↗

PubMed2001

Relationship between cell proliferation, cell-cycle phase, and retroviral vector production in FLYRD18 human packaging cells.

The relatively low concentrations of retroviral vectors produced by most packaging cells requires the optimization and intensification of their production to make a commercially viable product for gene therapy. While a number of reports exist concerning target cell-cycle effects on retroviral vector infection efficiency, no studies have been reported on the effects of packaging cell cycle on vector production. We have studied the effect of proliferation of the human packaging cell line, FLYRD18, on vector production. In addition, the titer levels of vector produced by cells in each phase of the cell cycle were compared. Numerous studies suggested progression of the cells through the cell cycle to be essential for vector production. However, vector release was found not to be predominant in any particular phase of the cell cycle. These findings indicate that packaging cell proliferation is important for optimal virus production and that arrest of the cells in any particular phase of the cell cycle affords no benefits in retroviral vector production. In contrast to previous reports (using other cell lines), we observed no temporary inhibition of cell cycle progression after detachment of cells from their substratum and that virus production occurred immediately after re-plating of the cells. The findings in this report are important for determining the optimal culture conditions for vector production by packaging cells in vitro.

Cell Count↗

PubMed2006

Effect of advanced glycation end-products on cell proliferation and cell death.

The effect of advanced glycation end products (AGE-s) was studied on the proliferation and cell death of human skin fibroblasts in culture. Several AGE-products were prepared from proteins, a peptide and amino acids, using Glucose or Fructose, with or without Fe2+. The AGE preparations increased cell death at the 7th day, after only 72 hours of incubation. Some of these glycation products modified also proliferation. This effect of AGE-s was even maintained without these products in fresh medium for a second period of incubation up to 10 days from the start of the experiment. In order to explore the role of AGE-receptors, especially of AGE-receptor and of growth factor receptors (fibroblast and epidermal growth factors receptors), antibodies to these receptors were added to cell cultures and their effect on both cell death and proliferation were determined as for the AGE-s. These anti-receptor antibodies imitated to some extent the results obtained with AGE-s, producing increase of cell death and proliferation, followed above a certain concentration of antibodies by a decrease and a new increase or plateau. This might correspond to the internalization of the receptors followed by a re-expression on the cell membrane. The role of receptor-mediated Reactive Oxygen Species-production was also explored using scavengers: N-acetyl-cysteine (NAC), L-Carnosine, superoxide dismutase (SOD) and Catalase. Several of these scavengers decreased cell death, suggesting that Reactive Oxygen Species-production is partially involved in the observed phenomena.

Antibody Formation↗

PubMed1986

Differential human interferon alpha receptor expression on proliferating and non-proliferating cells.

The expression of interferon-alpha (IFN-alpha) receptors was studied on a variety of human cells, using monoiodinated IFN-alpha 2 probes. Steady-state binding at 4 degrees C revealed a single class of non-interacting IFN receptor on peripheral blood lymphocytes, and tonsillar B lymphocytes, which are both known to be G0/G1 resting cell populations. The binding affinity of this class of receptor was found to be on the order of 5 X 10(-10) M, expressed as an apparent dissociation constant (Kd). However, cells proliferating either in culture or in vivo were found to express a heterogeneity in IFN-alpha 2 binding. Such binding could be objectively resolved (by a version of the LIGAND program of P. Munson) into a two-site receptor model. Hill plots of binding to proliferating cells indicated a negative cooperativity in the interaction of IFN and receptor. The high-affinity component, expressed on proliferating cells, typically exhibits a Kd of (1-10) X 10(-11) M, while the lower-affinity component indicates a Kd of (1-10) X 10(-9) M. Furthermore, the low-affinity component is apparently expressed on the order of 10-200 times the copy number, per cell, of the high-affinity site. Affinity-labeling experiments revealed that, in addition to the 140-160-kDa IFN-binding complex reported by others, both the proliferating and non-proliferating cell populations possess a novel IFN-binding component of 60 kDa.

Affinity Labels↗

PubMed1984

A zonal pattern of cell proliferation and differentiation in the rhesus endometrium during the estrogen surge.

The cellular and tissue basis of endometrial renewal in the rhesus monkey is being investigated by radioautographic localization of proliferating cell populations. Here we report our findings on epithelial cell proliferation during the midcycle estrogen surge. Endometrial biopsies were obtained by hysterotomy at approximately 1 h after a single intravascular injection of [3H] thymidine ([3H]T). Light and electron microscopic radioautography was performed on 7 specimens obtained from 4 monkeys in relation to the serum estradiol (E2) peak as follows: -2, -1, 0, +1, +2, and +3 days (+/- 1 day). Cell proliferation and differentiation were analyzed according to the 4 horizontal histologic endometrial zones (Bartelmez et al., 1951). Epithelial labeling indices were higher in the functionalis (Zone I, luminal epithelium, 9-12%; Zone II, uppermost gland segments, 7-14%) than in the basalis (Zone III, middle gland segments, 5-7%; and Zone IV, basal gland segments, 1-7%). Despite the large and rapid serum E2 fluctuations during the surge from -2 days to +3 days E2 peak, proliferating epithelial populations within Zones I, II and III remained quite uniform in size. In the basalis, the proliferative patterns of Zones III and IV were dissimilar. The labeling index of Zone III remained quite uniform (5-7%), whereas in Zone IV, it increased progressively from 1% (-2 days) to 7% (+3 days). These data establish the bipartite nature of the basalis. Radioautographic evidence indicates that endometrial cell proliferation is tightly coupled to progressive cell differentiation in the functionalis and basalis. Thus intrinsic positional differences exist in the responsiveness of the primate endometrium to common hormonal stimulation during the E2 surge and the initial postovulatory rise of progesterone.

Animals↗

PubMedDate not supplied

A new monoclonal antibody against DNA ligase I is a suitable marker of cell proliferation in cultured cell and tissue section samples.

The extensive characterization of the replicative human DNA ligase I (LigI) undertaken in the last decade demonstrated that the level of this protein strongly correlates with the rate of cell proliferation. This may allow to expand the repertoire of clinical biomarkers for the analysis of cell proliferation. We have produced a new monoclonal antibody (5H5) against LigI and exploited it as cell proliferation marker in Western blotting and immunofluorescence as well as in immunohistochemistry on paraffin tissue sections. The Western blot analysis showed that the LigI level detected by 5H5 antibody is high in all proliferating cells. On the contrary the protein is down regulated in resting human fibroblast and peripheral blood lymphocytes. Immunofluorescence analysis on cultured HeLa cells showed that 5H5 antibody labels all proliferating cells and displays the same staining pattern of BrdU in S-phase nuclei. Finally the analysis of serial sections of inflamed tonsils and NHL lymph nodes (either frozen or paraffin embedded) demonstrated that 5H5 marks the same population of cells as the Ki-67 antibody. Our results demonstrate that 5H5 antibody is a valuable tool for labeling proliferating cells that can be conveniently used in Western blotting, immunocytochemistry and immunohistochemistry.

Antibodies, Monoclonal↗

PubMed1994

Physeal distraction and cell proliferation in the growth plate.

We studied the cellular response to physeal distraction in the growth plates of skeletally immature rabbits. We used a new method of labelling and detection of proliferating cells with bromodeoxyuridine (BUdR) and an anti-BUdR antibody. The application of an external fixator but no distraction force produced no changes in the growth plates. After five days of distraction at a maximum force of 20 N, the growth plate became thicker, mainly because of an increase in the number of hypertrophic chondrocytes, but there was no evidence of increased cell proliferation. Recent fractures were seen at the junction of growth plate and metaphysis but the increase in bone length was insignificant. After ten days of distraction at the same maximum force, the chondrocyte columns had become disorganised and cell proliferation was significantly decreased. There was an increase in bone length due to distraction of the fracture gap. In this model, physeal distraction did not stimulate cell proliferation, but actually inhibited it. The apparent increase in growth-plate thickness produced by distraction is not due to increased cell production, but results from inhibition of endochondral ossification and the consequent accumulation of hypertrophic chondrocytes. Any growth after distraction depends on the ability of growth-plate chondrocytes to divide. The decrease in proliferative activity which we found after ten days of distraction suggests the need for caution in the use of such procedures in young children.

Animals↗

PubMed2004

Marked species and age-dependent differences in cell proliferation and neurogenesis in the hippocampus of wild-living rodents.

Variations in the extent of adult neurogenesis and natural and experimental factors controlling it have been described in laboratory animals. The wide range of variation seen even within a species, the mouse, raises the question as to which rates of neurogenesis can be expected in natural populations. Answering this question is important to evaluate the functional significance of adult neurogenesis under natural conditions and to define the factors controlling it. To address this issue, we investigated four species of wild-living rodents and outbred laboratory mice using markers for proliferating cells, Ki-67, and developing neurons, doublecortin and NeuroD. We found about four times as many Ki-67-positive cells per mm3 granule cell layer in two wood mouse species (Muridae; Apodemus spp.) than in bank and pine voles (Arvicolidae; Clethrionomys glareolus and Microtus subterraneus). Laboratory mice show proliferation rates between wood mice and voles. Markers for developing neurons, NeuroD and doublecortin, reflect the findings of proliferation activity. Hippocampal cell proliferation decreases dramatically with age in wild-living species. The onset of the downregulation varies among species. It occurs late in the life span of the yellow-necked wood mouse. In aged animals, the number of proliferating cells per mm3 granule cell layer is reduced to 19% of the adult value. Downregulation occurs early in pine voles, in which cell proliferation in adult animals is reduced to 33% of juvenile values. Proliferation and age-dependent changes along the deep border of the alveus and angular bundle follow those of the dentate gyrus. We conclude that cell proliferation and neurogenesis in the dentate gyrus vary significantly among wild-living rodents, and that they are downregulated with age, but at species-specific time points.

Aging↗