Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “functional differentiation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 793 records · Page 44Linked to original sources
PubMed2003

[Regulatory mechanism of bone resorption: roles of bone remodeling-regulatory cytokines 'osteokines' in osteoclast differentiation and function].

The recent discovery of receptor activator of NF-kappa B ligand(RANKL)-RANK interaction confirms the well-known hypothesis that osteoblasts play an essential role in osteoclast differentiation. Osteoblasts express RANKL, a tumor necrosis factor alpha (TNF-alpha) family member, as a membrane-associated factor. Osteoclast precursors that express RANK, a receptor for RANKL, recognize RANKL through the cell-cell interaction and differentiate into osteoclasts. Recent Studies have shown that lipopolysaccharide and inflammatory cytokines such as TNF-alpha and interleukin 1 directly regulate osteoclast differentiation and function through a mechanism independent of the RANKL-RANK interaction. Interferon-gamma and beta are also shown to be important negative regulators in osteoclastogenesis. These findings have opened new areas for exploring the regulatory mechanisms osteoclast differentiation and function by immune and inflammatory cells.

Bone Remodeling↗
PubMed1987

Role of laminin in maintenance of type II pneumocyte morphology and function.

Loss of differentiated function by type II pneumocytes plated on plastic surfaces was demonstrated by decreased lamellar body content, increased cellular protein, and rapid cellular flattening, changes that were retarded modestly by plating cells on laminin-coated surfaces. Laminin surfaces also inhibited [3H]thymidine (THM) incorporation into cellular DNA by 40% compared with plastic at 40 h, but did not alter an additional mitogenic effect of rat serum over fetal calf serum. In contrast, cells plated on the laminin-rich basement membrane-like gel formed from an extract of EHS mouse sarcoma, matrix gel (MG), maintained a high content of intracellular lipids in lamellar inclusions and retained a rounded morphology for at least 3 days. MG markedly inhibited THM incorporation and morphological changes when cells were cultured on this surface or when MG was formed over cells initially plated on plastic for various intervals. The importance of the laminin component of MG was demonstrated when these surfaces were pretreated with a highly specific antilaminin serum. Type II cells commenced flattening on the treated MG surface, and THM incorporation increased with the same time course as did control cells on plastic. The data suggest that short-term culture and study of differentiated type II pneumocytes may require a laminin-rich substratum. THM incorporation into type II cell DNA provides an important early and sensitive index of cell-basement membrane interaction and subsequent maintenance of function.

Animals↗
PubMed2003

Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory mechanism to clinical implication.

To investigate the regulatory effects of decoy receptor 3 (DcR3) on the differentiation and function of dendritic cells (DCs), bone marrow-derived DCs (BM-DCs) from nonobese diabetic (NOD) mice were cultured with recombinant DcR3.Fc protein. Their differentiating phenotypes and T cell-stimulating functions were then evaluated. Expression of CD11c, CD40, CD54, and major histocompatibility complex I-A(g7) was reduced in cells cultured with additional DcR3.Fc, compared with DCs incubated with granulocyte macrophage-colony stimulating factor and interleukin (IL)-4, indicating that DcR3 interferes with the differentiation and maturation of BM-DCs. One of the most striking effects of DcR3.Fc on the differentiation of DCs was the up-regulation of CD86 and down-regulation of CD80, suggesting a modulatory potential to skew the T cell response toward the T helper cell type 2 (Th2) phenotype. Consistent with this, the proliferation of CD4(+) T cells cocultured with DcR3.Fc-treated DCs was significantly reduced compared with that of T cells stimulated by normal DCs. Moreover, the secretion of interferon-gamma from T cells cocultured with DcR3.Fc-treated DCs was profoundly suppressed, indicating that DcR3 exerts a Th1-suppressing effect on differentiating DCs. Furthermore, adoptive transfer experiments revealed that NOD/severe combined immunodeficiency mice received DcR3.Fc-treated DCs, and subsequently, autoreactive T cells showed delayed onset of diabetes and a decrease in diabetic severity compared with mice that received normal DCs and T cells, suggesting a future therapeutic potential in autoimmune diabetes. Data from two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight analysis show an up-regulation of some proteins-such as mitogen-activated protein kinase p38 beta, cyclin-dependent kinase 6, and signal-induced proliferation-associated gene 1-and a down-regulation of the IL-17 precursor; tumor necrosis factor-related apoptosis-inducing ligand family member-associated nuclear factor-kappaB activator-binding kinase 1; and Golgi S-nitroso-N-acetylpenicillamine in cells treated with DcR3, further demonstrating its effect on DC differentiation and function.

Adjuvants, Immunologic↗
PubMed2000

Immunohistochemical demonstration of an enamel sheath protein, sheathlin, in odontogenic tumors.

Enamel proteins can be useful markers for assessment of the functional differentiation of neoplastic epithelium and the nature of extracellular matrices in odontogenic tumors. In the present study, we examined immunohistochemical localization of sheathlin, a recently cloned enamel sheath protein, in various odontogenic tumors to evaluate functional differentiation of tumor cells and the nature of hyalinous or calcified matrices in odontogenic neoplasms. Distinct immunolocalization of sheathlin was observed in the immature enamel of the tooth germ at the late bell stage. Secretory ameloblasts facing the enamel matrix also showed positive staining in their cytoplasm. Definite localization of sheathlin was demonstrated in the enamel matrix in odontogenic tumors with inductive dental hard tissue formation such as ameloblastic fibroodontomas and odontomas. Immunoexpression of sheathlin was, furthermore, demonstrated in eosinophilic droplets in solid nests of adenomatoid odontogenic tumor (AOT) and ghost cells in the epithelial lining of calcifying odontogenic cyst (COC). In AOT, cells facing the eosinophilic droplets also expressed the protein in their cytoplasm. There was neither intracellular staining for sheathlin in the tumor cells nor extracellular staining in the matrix of ameloblastomas and calcifying epithelial odontogenic tumors. Dentin, dysplastic dentin-like hyaline material and cementum in the tumors examined were negative for sheathlin. These results show that immunodetection of sheathlin is a useful marker for functional differentiation of secretory ameloblasts and enamel matrix, which is often hard to differentiate from other hard tissues in odontogenic tumors. Our findings from the view point of sheathlin expression support that the tumor cells of ameloblastomas do not attain full differentiation into functional ameloblasts. It is very interesting that epithelial cells in odontogenic tumors can differentiate into functional ameloblasts without induction by odontogenic mesenchyme, as shown by immunoexpression of sheathlin in eosinophilic droplets within solid epithelial sheets in AOT and ghost cells in the epithelial lining of COC where inductive participation of mesenchymal cells was most unlikely.

Ameloblastoma↗
PubMed2000

Matrix metalloprotease-9 release from monocytes increases as a function of differentiation: implications for neuroinflammation and neurodegeneration.

Naïve monocytes extravasate in response to monocyte chemoattractant-1 (MCP-1) and subsequently, following differentiation within tissue, carry out effector functions. Consistent with this concept, expression of the MCP-1 receptor CCR2 decreases with monocyte differentiation, as production of cytokines increases (Fantuzzi et al., 1999). Because matrix metalloproteases (MMPs) may also play an important role in the ability of monocytes to migrate into tissues and/or to promote pathogen clearance/tissue injury, we have examined production of matrix metalloprotease-9 as a function of both monocyte differentiation in vitro and expression of CCR2. Increased time in culture, which is linked to monocyte differentiation, resulted in enhanced production of MMP-9, assessed by gelatin substrate zymography. Further, CCR2-negative monocytes produced greater quantities of MMP-9 than did naïve CCR2-positive cells. Our results indicate that MMP-9 release increases during monocyte differentiation, consistent with a prominent role in effector functions. Because extracellular matrix proteins are important to cell structure and survival (Wee Yong et al., 1998), increased expression of MMP-9 could contribute to tissue damage following monocyte differentiation.

Cell Differentiation↗
PubMed2004

Recovery of renal retention function by differentiating the Patlak-Rutland plot.

INTRODUCTION: It has been suggested that renal retention function can be estimated by differentiation of the Patlak-Rutland plot. AIM: To evaluate the error resulting from this method. METHODS: A total of 5800 renograms were generated by convolving real input functions with artificial retention functions. Ten bi-exponential plasma disappearance curves of Tc mercaptoacetyltriglycine (Tc-MAG3) with varying renal clearances served as input functions and 580 retention functions with mean transit time between 3 and 60 min, and variable ratios of minimal to mean transit time served as original retention functions. The retention function was estimated by differentiation of the Patlak-Rutland plot of each renogram. A variant of this retention function was calculated by setting negative values to zero. RESULTS: Minimal transit time was estimated correctly in all cases but the recovered retention function systematically underestimated the original, and negative values were observed. Mean transit time was underestimated with a difference ranging from -22.05 to -0.06 min. By setting the negative values to zero, a less important underestimation was observed which ranged from -13.37 to 0.00 min. Maximal transit time was underestimated systematically with a difference ranging from -22.05 to 0.00 min. All differences were influenced by mean transit time, renal clearance and ratio of minimal to mean transit time. CONCLUSION: Estimation of the renal retention function by differentiation of the Patlak-Rutland plot results in systematic and sometimes important underestimations. By setting the negative values of the recovered retention function equal to zero, important but still partial improvement can be obtained.

Algorithms↗
PubMed1993

Differentiation of functional hepatocytes and biliary epithelial cells from immature hepatocytes of the fetal mouse in vitro.

Differentiation of functional hepatocytes and biliary epithelial cells from immature hepatocytes was analysed in vitro. When fetal mouse liver fragments containing immature hepatocytes but no bile ducts were cultured organotypically, the immature hepatocytes differentiated into large hepatocytes. Some of these expressed bile duct markers such as cytokeratin and Dolichos biflorus agglutinin-binding sites, though only to a small extent, and typical intrahepatic bile duct cells failed to differentiate. Dexamethasone stimulated immature hepatocytes to differentiate into both mature hepatocyte and biliary epithelial cell lineages. Especially in the liver fragments cultured on Matrigel, dexamethasone stimulated the expression of bile duct markers (such as cytokeratin and binding sites for two types of lectin) in the immature hepatocytes. These results support the idea that immature hepatocytes can differentiate into both mature hepatocytes and biliary epithelial cells during normal development of the mouse liver, and suggest that glucocorticoids stimulate both these differentiation pathways. It also seems that basal laminar components may play a role in bile duct differentiation.

Animals↗
PubMed1995

The differentiation and function of the touch receptor neurons of Caenorhabditis elegans.

We have identified several genes required for four aspects of the differentiation and function of a set of six touch receptor neurons in the nematode Caenorhabditis elegans: (1) the generation of appropriate cells; (2) the specification of those cells to differentiate as touch receptors; (3) the maintenance of the differentiated state; and (4) the expression of products need for the cell function. Three major conclusions about the development of the touch cells arise from the analysis of these genes. First, specification of cell fate is a combinatorial process. At least seven genes, none of which are expressed solely in these cells, are needed to restrict the expression of touch-cell features in the appropriate cells. Second, the differentiated state must also be maintained. Three genes appear necessary for this maintenance function. Third, regulation of development is not strictly linear; at least one gene is needed at more than one stage of differentiation. In addition to being interested in the factor that determine cell fate, we are also interested in understanding the molecular basis of mechanosensory transduction. The function class genes are particularly important in this regard, especially those that when mutant result in the loss of the touch response without producing any obvious morphological defects in the touch cells.

Animals↗
PubMed1989

Regulation of Sertoli cell function and differentiation through the actions of a testicular paracrine factor P-Mod-S.

The current study was designed to investigate the actions of the testicular paracrine factor P-Mod-S on Sertoli cell function and differentiation. Transferrin production by Sertoli cells was stimulated by P-Mod-S to a greater extent than any individual regulatory agent and in a manner similar to a combination of FSH, insulin, retinol, and testosterone (FIRT). P-Mod-S had an additive response in combination with FIRT. The increase in transferrin production with a combination of P-Mod-S and FIRT is the highest level of stimulation (up to 8-fold) observed. These profound effects of P-Mod-S on Sertoli cell function implied a potential unique mechanism of action for the paracrine factor. FSH and FIRT significantly stimulated cAMP levels with both 60-min and 72-h treatments. In contrast, P-Mod-S had no effect on cAMP levels with a 60-min treatment and only a small increase with a 72-h treatment. Interestingly, P-Mod-S stimulated cGMP levels that remained above basal levels up to 72 h of treatment. FSH had no effect on cGMP levels. P-Mod-S did not affect inositol phosphate hydrolysis with treatments between 15 and 60 min. The actions of P-Mod-S on cGMP levels influenced Sertoli cell function on a molecular level. Northern blot analysis indicated that P-Mod-S and FIRT both stimulated the apparent levels of the 2.6-kilobase transcript of transferrin and the 1.7-kilobase transcript of androgen-binding protein. A solution hybridization procedure was used to quantitate the influence of P-Mod-S on Sertoli cell gene expression. P-Mod-S stimulated steady state levels of both transferrin and androgen-binding protein message approximately 2-fold, similar to the effects of FIRT. Both forms of P-Mod-S had similar biological activities and mechanisms of action. P-Mod-S (A) and P-Mod-S (B) both stimulated cGMP, altered Sertoli cell gene expression, and had profound effects on transferrin production. Although slightly different biochemically, both forms of P-Mod-S appear to be functionally similar. Combined observations indicate that the paracrine factor produced by peritubular cells, P-Mod-S, acts on Sertoli cells in part through a cGMP-mediated response to influence the expression of specific genes which subsequently have profound effects on Sertoli cell function and differentiation.

Androgen-Binding Protein↗
PubMed2006

Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification.

Cartilage functions at a lower oxygen tension than most other tissues. To determine the role of oxygen tension in chondrocyte differentiation and function, we investigated the influence of oxygen tension in the pluripotent mesenchymal cell line C3H10T1/2 and 14.5E mice embryo forelimb organ culture. 10T1/2 cells and embryo forelimbs were cultured under normoxia (20% O2) or hypoxia (5% O2) in the presence of recombinant human bone morphogenetic protein 2. To elucidate the mechanism by which oxygen tension influences chondrocyte differentiation, the Smad pathway was examined using Smad6 overexpression adenovirus and Smad6 transgenic mice embryo forelimbs. The p38 MAPK pathway was examined using dominant-negative MKK3 and FR167653, a specific p38 MAPK inhibitor. The transcriptional activities of Sox9 and Runx2 were also investigated. Hypoxia promoted bone morphogenetic protein 2-induced glycosaminoglycan production and suppressed alkaline phosphatase activity and mineralization of C3H10T1/2. Thus, hypoxia promoted chondrocytic commitment rather than osteoblastic differentiation. In the mice embryo forelimb organ culture, hypoxia increased cartilaginous matrix synthesis. These effects were primarily mediated by p38 MAPK activation, independent of Sox9. Hypoxia inhibited Col10a1 (type X collagen alpha1) expression via down-regulation of Runx2 activity by Smad suppression and histone deacetylase 4 activation. In conclusion, hypoxia promotes chondrocytic differentiation and cartilage matrix synthesis and suppresses terminal chondrocyte differentiation. These hypoxia-induced phenomena may act on chondrocytes to enhance and preserve their phenotype and function during chondrocyte differentiation and endochondral ossification.

Animals↗
PubMed2001

Mechanical stretch promotes alveolar epithelial type II cell differentiation.

Functional maturation of pulmonary alveolar epithelial cells is crucial for extrauterine survival. Mechanical distension and mesenchymal-epithelial interactions play important roles in this process. We hypothesized that mechanical stretch simulating fetal breathing movements is an important regulator of pulmonary epithelial cell differentiation. Using a Flexercell Strain Unit, we analyzed effects of stretch on primary cultures of type II cells and cocultures of epithelial and mesenchymal cells isolated from fetal rat lungs during late development. Cyclic stretch of isolated type II cells increased surfactant protein (SP) C mRNA expression by 150 +/- 30% over controls (P < 0.02) on gestational day 18 and by 130 +/- 30% on day 19 (P < 0.03). Stretch of cocultures with fibroblasts increased SP-C expression on days 18 and 19 by 170 +/- 40 and 270 +/- 40%, respectively, compared with unstretched cocultures. On day 19, stretch of isolated type II cells increased SP-B mRNA expression by 50% (P < 0.003). Unlike SP-C, addition of fibroblasts did not produce significant additional effects on SP-B mRNA levels. Under these conditions, we observed only modest increases in cellular immunoreactive SP-B, but secreted saturated phosphatidylcholine rose by 40% (P < 0.002). These results indicate that cyclic stretch promotes developmentally timed differentiation of fetal type II cells, as a direct effect on epithelial cell function and via mesenchymal-epithelial interactions. Expression of the SP-C gene appears to be highly responsive to mechanical stimulation.

Animals↗
PubMed1997

Differential item functioning in the Mini-Mental State Examination in English- and Spanish-speaking older adults.

The purpose of this study was to determine if the Mini-Mental State Examination (MMS; M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975) demonstrates item bias with respect to measuring cognitive functioning of older Hispanics and non-Hispanics. Assessment of differential item functioning (DIF) of individual MMS items across 3 language/ethnicity groups (English test administration/non-Hispanic ethnicity, English test administration/Hispanic ethnicity, and Spanish test administration/Hispanic ethnicity) was performed by using a logistic regression procedure. Fifteen of the 26 MMS items were significantly related to total score and were shown to provide unbiased measurement across the 3 groups. Normative data are presented for older Hispanics (n = 365) and non-Hispanics (n = 388) on the raw MMS, a 15-item version in which items with significant DIF were eliminated, and a total score statistically adjusted for effects of education and age.

Aged↗
PubMed2006

Differential item functioning on the Mini-Mental State Examination. An application of the Mantel-Haenszel and standardization procedures.

Differential item functioning (DIF) attempts to identify items for which subpopulations of examinees exhibit performance differentials that are not consistent with the performance differentials seen among those subpopulations on a reliable measure of the construct of interest. DIF assessment requires a rule for scoring items and a matching variable on which different subpopulations can be viewed as comparable for purposes of assessing their performance on items. Typically, DIF is operationally defined as a difference in item performance between subpopulations, eg, Spanish-speakers and English-speakers, which exist after members of the different subpopulations have been matched on some one-dimensional matching variable such as total score. This work defines DIF, describes 2 standard procedures for measuring DIF, applies these DIF procedures to the Mini-Mental State Examination, and contrasts DIF with score equity analysis (SEA). The description of DIF assessment presented in this paper is applicable to any examination question that has responses that can be ordered, eg, with respect to correctness or severity.

Bias↗
PubMed2004

Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon beta in multiple sclerosis.

Interferon beta (IFN beta) has complex immune regulatory properties that contribute to its treatment effect on multiple sclerosis (MS). In this study, we investigated the role of IFN beta in differentiation and functional properties of monocytes and monocyte-derived dendritic cells that are critical to the inflammatory process in MS. The results revealed that IFN beta inhibited intracellular production of interleukin (IL)-1b (P<0.01) in both monocytes exposed to in vitro treatment of IFN beta and monocytes analysed ex vivo from MS patients treated with IFN beta. IFN beta was shown to modulate differentiation of monocytes into dendritic cells in the presence of IL-4 and GM-CSF, which resulted in a delayed differentiation process. Furthermore, it characteristically altered the phenotypic features of differentiated dendritic cells by inhibiting the expression of CD1a, CD11b, CD11c, CD123 and CD209 while upregulating costimulatory molecules, such as CD86. The selective regulatory properties of IFN beta appeared to render the function of differentiated dendritic cells to produce an increased amount (P<0.01) while their ability to secrete proinflammatory IL-12 and TGF beta was significantly reduced. The observed collective effects of IFN beta seemed to correlate with Th2 immune deviation. The study has provided new insights into the regulatory mechanisms of IFN beta in the treatment of MS.

Adjuvants, Immunologic↗
PubMed2007

Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle.

BACKGROUND: Mesenchymal stem cells (MSCs) play a crucial role in hematopoietic development and have been shown to exert a powerful immunosuppressive effect. In this study, we investigated the effect of bone marrow MSC on the differentiation and function of peripheral blood monocytes into dendritic cells (DCs). METHODS: Human MSCs, generated from normal bone marrow, were added to peripheral blood monocytes stimulated in vitro with granulocyte-macrophage colony stimulating factor and interleukin-4 to become DCs. Monocytes were then examined for the expression of markers characteristic of DCs and their ability to stimulate allogeneic T cells. In addition, the effect of MSCs on the cell cycle of monocyte-derived DCs and the expression of various cell cycle proteins were analyzed by cytometric analysis and Western blotting with specific antibodies. RESULTS: MSCs blocked the differentiation of monocytes into DCs and impaired their antigen-presenting ability. This resulted from a block of monocytes from entering the G1 phase of the cell cycle with a progressive number of cells accumulating in the G0 phase. Cyclin D2 was downregulated. However, differently from what was observed in T-cells stimulated in the presence of MSCs, the expression of p27 was found decreased, suggesting the involvement of similar but not identical pathways. CONCLUSIONS: We conclude that MSCs impair monocyte differentiation and function by interfering with the cell cycle. These findings imply that MSC-induced immunosuppression might be a side product of a more general antiproliferative effect.

Antigens, CD↗
PubMed2002

Race/ethnicity and depressive symptoms in community-dwelling young adults: a differential item functioning analysis.

To examine variations in the manifestation of depressive symptomatology across racial/ethnic groups, analyses of differential item functioning (DIF) on the Center for Epidemiologic Studies Depression Scale (CES-D) were separately conducted for representative samples of young adults in the following groups: African-Americans (n = 434), Hispanics born in the US (n = 493), and Hispanics born outside the US (n = 395). Non-Hispanic whites (n = 463) were employed as the reference group in all analyses. The effects of gender and age were controlled. DIF analyses indicated that: (1) about half of the CES-D items functioned differently among non-Hispanic whites compared to each of the other racial/ethnic groups; (2) the manifestation of symptoms seemed to be similar for both Hispanic groups, except for low positive affect; (3) African-Americans tended to favor somatic symptoms over affective (depressive) symptoms; (4) Immigrant Hispanics appeared to inhibit the expression of positive affect, and thus more high scorers on the total CES-D were observed within this subgroup. In contrast, no differences were observed when only negative items were considered. The use of positive affect items might artifactually induce spurious differences among people who were born outside the United States or North America.

Adult↗
PubMed1992

Can technetium-99m-mercaptoacetyltriglycine replace technetium-99m-dimercaptosuccinic acid in the exclusion of a focal renal defect?

The presence of focal renal damage dictates different management of a child with urinary tract infection (UTI) compared with children who have normal kidneys. Technetium-99m-dimercaptosuccinic (DMSA) has a high sensitivity in the detection of a focal defect, and allows estimation of differential function. The introduction of 99mTc-MAG3 with high renal extraction suggests that this may be useful in children with UTI but its role remains speculative. Fifty-nine children with previous UTI underwent both 99mTc-DMSA and MAG3 within 4 wk of each other. Differential function and assessment of the images were undertaken. There is close correlation (R2 = 0.97) between the differential function. Analysis of the 99mTc-DMSA and functional MAG3 images showed that the functional image had a specificity of 88% and a sensitivity of 88% in the detection of a focal parenchymal defect. Technetium-99m-MAG3 in the clinical setting of a child with UTl allows accurate assessment of differential function and a high probability of detecting a focal renal abnormality.

Adolescent↗