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PubMed2004

Drosophila genetic variants that change cell size and rate of proliferation affect cell communication and hence patterning.

We explore in this paper the role of genetic variants that affect cell size and proliferation in the determination of organ size. We use genetic mosaics of loss or gain of function in six different loci, which promotes smaller or larger than normal cells, associated to either smaller or larger than normal territories. These variants have autonomous effects on patterning and growth in mutant territories. However, there is no correlation between cell size or rate of proliferation on the size of the mutant territory. In addition, these mosaics show non-autonomous effects on surrounding wildtype cells, consisting always in a reduction in number of non-mutant cells. In all mutant conditions the final size (and shape) of the wing is different than normal. The phenotypes of the same variants include higher density of chaetae in the notum. These autonomous and non-autonomous effects suggest that the control of size in the wing is the result of local cell communication defining canonic distances between cells in a positional-values landscape.

Animals↗
PubMed1971

Lipolytic response and adenyl cyclase activity of rat adipocytes as related to cell size.

The number of fat cells contained in the rat epididymal fat pad was found to increase rapidly as the rats grew to a weight of about 300 g. Additional increases in cell number above this weight were minimal. By contrast, cell size, as measured by the amount of triglyceride per cell, increased linearly until the rats reached about 600 g. Glycerol release per 10(6) cells in response to norepinephrine in vitro was observed to be independent of cell size. Basal release expressed in this manner showed a slight but significant positive correlation with increasing cell size. When the rate of lipolysis was based either on the amount of triglyceride in the incubation medium, as is the usual custom, or on the cell surface area, lipolysis was inversely related to cell size. In addition to these observations on lipolysis, it was also demonstrated that norepinephrine-activated adenyl cyclase activity expressed per 10(6) cells was unaffected by cell size. This leads to the suggestion that the number of adrenergic receptors in the fat cell is fixed and is independent of the size of the cell; as the cell enlarges, these receptors are merely distributed over a greater surface area.

Adenylyl Cyclases↗
PubMed1991

Cell cycle, cell size and mitochondrial activity of hybridoma cells during batch cultivation.

Cell cycle, cell size and rhodamine 123 fluorescence in cell populations of two batch cultures were analysed and quantified with a fluorescence-activated cell sorter (FACS). Two cultures derived from either exponential or stationary phase innocula were investigated in order to demonstrate the dependency of the subsequent cell growth on innoculum condition. The results demonstrated that the level of activity of cells in the innoculum culture could have a significant effect on cellular activity during the initial phase of the inoculated culture, as it advances through its growth cycle. Positive correlation was found between the cell size and mitochondrial activity (as measured by rhodamine 123 uptake) with S and G2 fractions as the cell progressed through the cell cycle. The enumeration of the fractions of cell cycle phases has helped in prediction of the changes in cell numbers following perturbation of the culture condition.

Animals↗
PubMed1995

Evaluation of image analysis and laser granulometry for microbial cell sizing.

A direct cell size measurement technique and an image analysis based sizing method were developed. The former consisted of a manual size measurement of the two-dimensional cell images on a video screen, with automatic data recording. This method was chosen as the reference. The latter, a semiautomatic method took advantage of a commercial computer program designed for image processing and particle morphology analysis. It gave average and median size values which were compatible with the manual method. However, the performance of these time consuming methods is limited. Hence, the laser granulometry technique, intrinsically far more powerful while capable of analysing millions of sample objects in a short time delay, was applied. The comparison revealed that this method gives too low size values, particularly in disagreement with the known dimensions of the bacterial (Zymomonas mobilis) cells. A size correction method was developed to realign the granulometry results of Z mobilis cell samples with those of the direct manual measurement method.

Bacteria↗
PubMedDate not supplied

[Polyethylene content and cell size of foreign body giant cells in aseptic hip prosthesis loosening--a histomorphometric study].

INTRODUCTION: In aseptic loosening of cementless hip arthroplasty polyethylene particles are phagocytized by macrophages and foreign-body giant cells. This initiates an osteolytic cascade. In this study, the authors investigated if there are correlations between the size of foreign-body giant cells and the polyethylene loading and number of intracellular particles as determined by light microscopy. MATERIAL AND METHOD: Histological specimens were processed from tissues retrieved during revision surgery of 7 cases of cementless hip arthroplasty which had become aseptically loose. The specimens were analyzed by histolomorphology and histomorphometry. The cell size, polyethylene loading and intracellular particle number of 111 foreign-body giant cells were determined. A regression analysis was performed to investigate if there was a correlation between these variables. RESULTS: The mean cell size was 1417 +/- 487 micron 2, the mean polyethylene loading was 49 +/- 42 micron 2 and the mean intracellular particle number was 10.4 +/- 5.4. The cell size correlated with both the intracellular particle number (r = 0.25) and the polyethylene loading (r = 0.39). CONCLUSIONS: In the cellular reaction to polyethylene particles in aseptic loosening of cementless total hip arthroplasty, the size of foreign-body giant cells correlates with intracellular polyethylene loading and intracellular polyethylene particle number as determined by light microscopy. The presence of large foreign body giant cells might be associated with a high particle load of the tissue and a high osteolytic activity.

Aged↗
PubMed2000

Relationships among Bacterial Cell Size, Productivity, and Genetic Diversity in Aquatic Environments using Cell Sorting and Flow Cytometry.

The study of relationships between cell size and productivity is of key importance in microbial ecology to understand which members of natural aquatic communities are responsible for the overall activity and/or productivity. Flow sorting of microorganisms from different environmental samples was used to analyze the activity of bacterial cells depending on their biovolume. Bacterial cells from five different natural samples taken along the Mediterranean coast including fresh- and seawaters were incubated with tritiated leucine, then stained with SYTO 13 and sorted by flow cytometry according to their average side-angle-scattered (SSC) light. In all samples, a bell-shaped relationship was found between cell biovolume and activity, whereas activity of a given cell-size class varied between samples. In contrast, an inverse relationship was found between biovolumes and abundances. These results suggest that medium-sized cells with highest growth rates are probably submitted to intense grazing. For one sample, bacteria within five different size classes were sorted and the genetic diversity of cells within each sorted size class and that of the whole community were analyzed by the denaturing gradient gel electrophoresis (DGGE) method. The genetic diversity, as determined at the community level was highly represented into the pool of small cells, whereas only few species were present into larger cell subpopulations. The results suggest that only a few genotypes may be dominant within the largest and most productive cells. Furthermore, cell size polymorphism as well as heterogeneous cellular activities were found within some species.

Journal Article↗
PubMed2004

CD1d1 displayed on cell size beads identifies and enriches an NK cell population negatively regulated by CD1d1.

NK cells destroy microbe-infected cells while sparing healthy cells, and are controlled, in part, by inhibitory receptors specific for class I Ag-presenting molecules. CD1d1, a beta(2)-microglobulin-associated class I-like molecule, binds glycolipids and stimulates NKT cells. We previously demonstrated that target cell lysis by IL-2-activated mouse NK cells is inhibited by target cell expression of CD1d1, suggesting that IL-2-activated NK cells may express a CD1d1-specific inhibitory receptor. We now report that a significant subset of mouse IL-2-activated NK cells specifically binds cell size beads displaying either naturally expressed or recombinant CD1d1. In contrast, although tetramers of soluble recombinant CD1d1 loaded with alpha-galactosylceramide identify NKT cells, binding of this reagent to resting or IL-2-activated NK cells was undetectable, even with activated NK cells sorted with CD1d1 beads. Cytotoxicity by the CD1d1 bead-separated NK subset was strongly inhibited by CD1d1, compared with the NK cell subset not bound to CD1d1 beads. An Ab that blocks NKT cell recognition of CD1d1 also reverses CD1d1 inhibition of NK lysis, suggesting that TCRs of NKT cells and NK inhibitory receptor(s) may interact with a similar site on CD1d1. These results provide direct evidence for a physical interaction of NK cells with CD1d1, mediated by a functional, CD1d1-specific low-affinity inhibitory NK receptor. Display of ligands on cell size beads to maximize multivalent interaction may offer an alternative approach to examine NK cell receptor-ligand interactions, particularly those of lower expression and/or lower affinity/avidity that may go undetected using tetrameric reagents.

Animals↗
PubMed2004

Quantitative analysis of cells in the ganglion cell layer of the chick retina: developmental changes in cell density and cell size.

Changes in cell density and size in the ganglion cell layer (GCL) of the retina were studied in chick embryos and post-hatching chicks. The total number of cells in the GCL increased from 3.64 million at embryonic day 8 (E8) to the maximal 7.85 million at E14. After E14, the number of cells decreased to 6.08 million at post-hatching day 1 (P1) and 4.87 million at P8. Cell density in the GCL decreased unevenly according to retinal regions; cell density in the presumptive central area (pCA) of P8-chicks decreased to approximately 45% of that in E8-embryos. Densities of the nasal peripheral retina (NP) and temporal peripheral retina (TP) of P8-chicks decreased to 23 and 18% of E8-embryos, respectively. Differentiation of the central (44,000 cells/mm(2) in pCA) - peripheral (28,000 cells/mm(2) in TP) gradient in cell density was formed by E8. The presumptive dorsal area (pDA) was shaped by E11, but became obscure with age. Although ganglion cell sizes were basically uniform at E8, differentiation occurred with the appearance of larger ganglion cells after E14. Mean size of retinal ganglion cells increased 2.8-fold in the pCA and 3.8-fold in the TP between E8 and P8, accompanying a similar scale of decreases in cell densities.

Animals↗
PubMed2002

Genomic scale mutant hunt identifies cell size homeostasis genes in S. cerevisiae.

BACKGROUND: In most eukaryotic cells, there is a relationship between cell size and proliferative capacity. For example, in order to commit to cell division, the yeast Saccharomyces cerevisiae must attain a "critical cell size." This mechanism coordinates growth with cell division to maintain cell size homeostasis. Because very few cell size control genes are known, the genetic pathways responsible for cell size homeostasis remain obscure. Furthermore, elucidation of the mechanism of cell size homeostasis has been recalcitrant to genetic analysis primarily due to the difficulty in cloning cell size control genes. RESULTS: To identify new size control genes, the effect of 5958 single gene deletions (4792 homozygous and 1166 heterozygous gene deletions) on cell size in yeast grown to saturation was systematically determined. From these data, 49 genes were identified that dramatically altered cell size. Of these, 34 are involved in transcription, signal transduction, or cell cycle control; 88% of these genes have putative human homologs. Sixteen genes regulate cell size in a dosage-dependent manner, and the majority of mutants identified fail to correctly exit the cell cycle. Many of these genes are components of Ccr4-Not transcriptional complexes or function in the PKC-MAP kinase pathway. These genes may modulate cell size by altering the expression or activity of G1-phase cyclins. CONCLUSIONS: These results illustrate how systematic genetic screens can be used to dissect intricate biological processes that are refractory to classic genetic approaches. This genomic-wide genetic screen yielded 46 new cell size mutants and systematically assessed the effect of 5958 single gene deletions on cell size as cells exited the cell cycle.

Cell Cycle↗
PubMed1988

Matrix-driven cell size change modulates aortic endothelial cell proliferation and sheet migration.

Current hypotheses suggest that the extracellular matrix modulates cellular function in physiologic homeostasis and during injury and repair and that selected cellular functions are cell and nuclear size dependent. For elucidation of the role of extracellular matrix-driven cell size changes in the modulation of endothelial cell proliferation and sheet migration an in vitro model system was used that allows for the culture of bovine aortic endothelial cells (BAEC) on various purified extracellular matrix components. BAEC exhibited distinct patterns in rates of attachment, spreading, migration, and proliferation when cultured on the selected extracellular matrix components laminin, types I and III collagen, type IV collagen, and fibronectin. In addition, there was a correlation between cell and nuclear size (on the various matrices tested) and rates of cell attachment and spreading. In contrast, an inverse correlation was noted between cell and nuclear size (on the various matrices tested) and proliferation and sheet migration. These data demonstrate that endothelial cells respond to matrix components in specific but complex fashions, mediated, in part, by changes in cell and nuclear size.

Animals↗
PubMed2007

Clinical predictors of metastatic disease to the brain from non-small cell lung carcinoma: primary tumor size, cell type, and lymph node metastases.

PURPOSE: To retrospectively assess possible clinical predictors of metastatic disease to the brain in patients with non-small cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Institutional review board approval was obtained, informed consent was waived, and data and other information were obtained prior to implementation of HIPAA. A review was performed of 264 patients (mean age, 65 years; 158 men and 106 women) with NSCLC who had undergone imaging studies of the chest and head. Hierarchical logistic regression was used to determine the predicted probability of metastatic disease to the brain as a function of patient age and sex and of size, cell type, peripheral versus central location, and lymph node stage of the primary NSCLC. RESULTS: Ninety-five (36%) patients had evidence of metastatic disease to the brain. Mean diameter of the primary tumors was 4.0 cm +/- 2.2 (standard deviation). Cell types included adenocarcinoma (136 [52%] patients), undifferentiated (68 [26%] patients), and squamous (47 [18%] patients), for which metastatic disease to the brain occurred in 43%, 41%, and 13% (P = .003) of patients, respectively. The predicted probability of metastatic disease to the brain correlated positively with size of the primary tumor (P < .001), cell type (adenocarcinoma and undifferentiated vs squamous, P = .001), and lymph node stage (P < .017) but did not correlate with age, sex, or primary tumor location. For primary adenocarcinoma without lymph node spread, the predicted probabilities of metastatic disease to the brain from 2- and 6-cm primary tumors were .14 (95% confidence interval: .06, .27) and .72 (95% confidence interval: .48, .88), respectively (P < .02). CONCLUSION: The probability of metastatic disease to the brain from primary NSCLC is correlated with size of the primary tumor, cell type, and intrathoracic lymph node stage.

Adult↗
PubMed2002

Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E.

The coordinated action of cell cycle progression and cell growth (an increase in cell size and cell mass) is critical for sustained cellular proliferation, yet the biochemical signals that control cell growth are poorly defined, particularly in mammalian systems. We find that cell growth and cell cycle progression are separable processes in mammalian cells and that growth to appropriate cell size requires mTOR- and PI3K-dependent signals. Expression of a rapamycin-resistant mutant of mTOR rescues the reduced cell size phenotype induced by rapamycin in a kinase-dependent manner, showing the evolutionarily conserved role of mTOR in control of cell growth. Expression of S6K1 mutants that possess partial rapamycin-resistant activity or overexpression of eIF4E individually and additively partially rescues the rapamycin-induced decrease in cell size. In the absence of rapamycin, overexpression of S6K1 or eIF4E increases cell size, and, when coexpressed, they cooperate to increase cell size further. Expression of a phosphorylation site-defective mutant of 4EBP1 that constitutively binds the eIF4E-Cap complex to inhibit translation initiation reduces cell size and blocks eIF4E effects on cell size. These data show that mTOR signals downstream to at least two independent targets, S6K1 and 4EBP1/eIF4E, that function in translational control to regulate mammalian cell size.

Adaptor Proteins, Signal Transducing↗
PubMed1978

Determinations of adipose cell size and number in suspensions of isolated rat and human adipose cells.

The osmic acid fixation-Coulter electronic counter method described for determining adipose cell size and number in intact adipose tissue fragments has been modified for use with suspensions of isolated rat and human adipose cells. Mean cell sizes in tissue fragments and isolated cell suspensions prepared from the same tissue are virtually identical in rats of various weights. No statistically significant difference in mean adipose cell size between tissue and isolated cell suspension was observed in human adipose tissue although the variability was much greater than in rat tissue. The distribution of cell sizes among replicate samples is more uniform in the isolated cell preparations, possibly reflecting the considerably larger quantities of tissue used in preparing isolated cells than in determining cell size and number directly from tissue fragments. An example of the utility of the modified method during routine metabolic studies with isolated rat epididymal adipose cells is described; isolated cells of increasing size can be obtained from rats of increasing body weight, or from the separated distal and proximal portions of the fat pads of rats of the same weight.

Adipose Tissue↗
PubMed2000

Genetic and molecular mechanisms of cell size control.

Since the discovery of the cell as the minimal indivisible living entity, scientists have tried to understand how all the various physiological aspects were assumed within this single functional unit. One fascinating question concerns the role of cell size and cell number in determining the overall size of an organism. During the past century, increasing knowledge in molecular genetics has allowed the characterization of a number of molecular events that influence the size of a cell. However, in spite of recent progress, precise molecular mechanisms governing cell size remain unclear. Although the existence of a master regulator is still possible, cell size may be primarily controlled by an interactive network linking gene expression with translational capacity and cell proliferation.

Animals↗
PubMed1978

Corticosteroid effect on epidermal cell size.

Changes in the epidermis following application of three corticosteroids, betamethasone 17-valerate, hydrocortisone 17-butyrate, and hydrocortisone have been studied histometrically in human volunteers. The reduction in epidermal thickness observed correlated significantly with a reduction in size of the viable epidermal cells. There was no significant reduction in the number of cells constituting the viable epidermis. These findings indicate that thinning of the epidermis is a function of cell size rather than cell number. The epidermal changes developed quickly and were rapidly reversible. It is suggested that measurement of cell size may be an early and sensitive index of atrophogenicity induced by topical corticosteroids. 0.1% Hydrocortisone 17-butyrate and 0.1% betamethasone 17-valerate showed equivalent potency in causing epidermal thinning and reduction in cell size. Reduction in cell size paralleled increasing concentrations of betamethasone 17-valerate, indicating a positive dose-effect relationship.

Adult↗
PubMed2005

Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification.

The transcription factor Myc (c-Myc) plays an important role in cell growth and cell death, yet its physiological function remains unclear. Ectopic activation of Myc has been recently suggested to regulate cell mass, and Drosophila dmyc controls cellular growth and size independently of cell division. By contrast, it has been proposed that in mammals Myc controls cell division and cell number. To gain insights into this debate we have specifically knocked out Myc in epidermis. Myc epidermal knockout mice are viable and their keratinocytes continue to cycle, but they display severe skin defects. The skin is tight and fragile, tears off in areas of mechanical friction and displays impaired wound healing. Steady-state epidermis is thinner, with loss of the proliferative compartment and premature differentiation. Remarkably, keratinocyte cell size, growth and endoreplication are reduced, and stem cell amplification is compromised. The results provide new and direct evidence for a role for endogenous Myc in cellular growth that is required for hyperproliferative cycles and tissue homeostasis.

Animals↗