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 829 records · Page 46Linked to original sources

Nicotinic environment affects the differentiation and functional maturation of monocytes derived dendritic cells (DCs).

Differentiation of tissue monocytes into DCs is a critical phase in the development of a competent immune system. We show that in a nicotinic environment, while human monocytes differentiate into DCs (henceforth called nicDCs) with a typical morphology, they display unique phenotype and cytokine profile that adversely affect their function. Despite an increased capacity for receptor-dependent antigen uptake, nicDCs do not express CD1a and fail to fully up-regulate MHCs, molecules essential for their antigen-presenting function. Additionally, in response to bacterial antigen LPS, maturing nicDCs hardly express the chemotactic cytokine receptor 7 required for their entry into lymphatic vessels. Furthermore, in parallel with their differential expression of costimulatory molecules CD80 and CD86 and lack of IL-12, nicDCs display profoundly reduced Th1 promoting capacity. These findings thus indicate that nicotine impedes the development of cell-mediated immunity by skewing DC differentiation. These effects of nicotinic environment on DC differentiation may contribute to the increased risks of respiratory tract infection and various cancers in smokers.

Animals↗

The effect of steroids on differentiation and function of cultured, mononuclear cells.

When monocytes had differentiated to macrophages during 8 days of culture in vitro without being exposed to steroids, neither the engulfement nor the digestion step of phagocytosis was found to be influenced by cortisol or the other steroids tested. This indicates that cortisol has no direct effect on the phagocytic function of macrophages in doses below 10(-1) mg/ml. Continuous exposure to cortisol during the period of differentiation resulted in a dose dependent inhibition of the differentiation of monocytes to macrophages. Testosterone, deoxycorticosterone and tetrahydrocortisol in concentration of 10(-1) mg/ml, tested in the same way were found to be toxic to the cells. In lower concentrations, however, these steroids were found to have no effect on the cultured cells. The impaired differentiation of monocytes is suggested as an additional explanation of the reduced number of macrophages appearing at the site of inflammation during cortisol treatment.

Cell Differentiation↗

Islet cell antigens. Initial studies of their biology and function.

Differentiation antigens expressed by pancreatic islet cells presumably play important roles in islet physiology and pathophysiology. We have developed a series of monoclonal antibody probes directed towards islet endocrine cells. Utilizing these antibodies we have identified and biochemically characterized several glycoprotein and glycolipid islet cell antigens. Many islet cell antibodies appear to react with unique carbohydrate residues on their antigen molecules. Islet cells share several monoclonal antibody-defined antigens and antigenic determinants with other neuroendocrine and related cell types. The detailed molecular structure, ontogeny, function and pathogenetic relevance of these islet antigens are being investigated.

Antibodies, Monoclonal↗

Regulation of osteoclast differentiation and function by the CaMK-CREB pathway.

Calcium (Ca(2+)) signaling is essential for a variety of cellular responses and higher biological functions. Ca(2+)/calmodulin-dependent kinases (CaMKs) and the phosphatase calcineurin activate distinct downstream pathways that are mediated by the transcription factors cAMP response element (CRE)-binding protein (CREB) and nuclear factor of activated T cells (NFAT), respectively. The importance of the calcineurin-NFAT pathway in bone metabolism has been demonstrated in osteoclasts, osteoblasts and chondrocytes. However, the contribution of the CaMK-CREB pathway is poorly understood, partly because of the difficulty of dissecting the functions of homologous family members. Here we show that the CaMKIV-CREB pathway is crucial for osteoclast differentiation and function. Pharmacological inhibition of CaMKs as well as the genetic ablation of Camk4 reduced CREB phosphorylation and downregulated the expression of c-Fos, which is required for the induction of NFATc1 (the master transcription factor for osteoclastogenesis) that is activated by receptor activator of NF-kappaB ligand (RANKL). Furthermore, CREB together with NFATc1 induced the expression of specific genes expressed by differentiated osteoclasts. Thus, the CaMK-CREB pathway biphasically functions to regulate the transcriptional program of osteoclastic bone resorption, by not only enhancing induction of NFATc1 but also facilitating NFATc1-dependent gene regulation once its expression is induced. This provides a molecular basis for a new therapeutic strategy for bone diseases.

Animals↗

Regulation of CFTR expression and function during differentiation of intestinal epithelial cells.

CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco-2 and HT-29) show a lower level of CFTR mRNA, while a 10-fold increase is seen in differentiated cells. These differences correlate well with those of other intestinal-specific genes, including sucrase-isomaltase, villin and alpha 1-antitrypsin, indicating that the regulation is cell specific. In Caco-2 cells the increase in CFTR mRNA cannot be accounted for by increased transcription of the gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present in differentiated cells. The higher levels of CFTR mRNA in differentiated cells are accompanied by decreased protein levels, indicating, as well, involvement of translational control in the regulation of CFTR in these cells. Finally, fully differentiated cells show lowered levels of cyclic AMP-activated C1- transport, the characteristic function of CFTR. Thus, CFTR function in differentiated cells is modulated by a complex interaction of regulatory elements. Caco-2 and HT-29 cells provide a suitable in vitro system in which to study the mechanism of regulation of CFTR.

Blotting, Western↗

Differential item functioning (DIF) and the Mini-Mental State Examination (MMSE). Overview, sample, and issues of translation.

BACKGROUND: Various forms of differential item functioning (DIF) in the Mini-Mental State Examination (MMSE) have been identified. Items have been found to perform differently for individuals of different educational levels, racial/ethnic groups, and/or of groups whose first language is not English. The articles in this section illustrate the use of different methods to examine DIF in relation to English and Spanish language administration of the MMSE. OBJECTIVES: The aim of this article is to provide a context for interpretation of the findings contained in the following set of papers examining DIF in the MMSE. METHODS: The performance of the MMSE, when administered in English and Spanish, was reviewed. "Translation" has been discussed in the context of measurement bias, illustrating the variability in Spanish translations. Presented are the readability of the MMSE, description of the translation method, the study design and sample for the data set used, together with treatment of missing data, and model assumptions related to the analyses described in the accompanying set of papers examining DIF. CONCLUSIONS: The examination of item bias in cognitive impairment assessment instruments has practical and theoretical implications in the context of health disparities. Considerable DIF has been identified in the MMSE. A critical factor that may contribute to measurement bias is language translation and conversion. Once DIF has been established consistently in a measure, decisions regarding adjustments proceed. Perhaps the development of guidelines for appropriate adjustments for DIF correction in self-reported measures represents the next challenge in addressing measurement equivalence in crosscultural research.

Aged↗

Differential leg function in a sprawled-posture quadrupedal trotter.

Legs of sprawled-posture, quadrupedal trotting geckos (Hemidactylus garnotii) each functioned differently during constant average-speed locomotion. The center of mass decelerated in the first half of a step and accelerated in the second half, as if geckos were bouncing in fore-aft and side-to-side directions. Forelegs decelerated the center of mass only in the fore-aft direction. Hindlegs provided all the acceleration in the latter half of the step. Lateral ground reaction forces were always directed toward the midline and exceeded the magnitude of fore-aft forces. The differential leg function of sprawled-posture geckos resembled sprawled-posture hexapods more than upright-posture quadrupeds. The pattern of leg ground reaction forces observed may provide passive, dynamic stability while minimizing joint moments, yet allow high maneuverability. Integrating limb dynamics with whole body dynamics is required to resolve the trade-offs, if any, that result from stable sprawled-posture running with differential leg function.

Analysis of Variance↗

The distinction between perceiving and memorizing in the presence of category cues.

The study proposed and tested 2 hypotheses to account for the claim by Appel, Cooper, Knight, McCarrell, Yussen, and Flavell (1972) that "memorizing and perceiving are functionally undifferentiated for the young child" by presenting preschool, second-, and fifth-grade children a "memory" and a "look" problem under several treatments in which semantic category cues were present. Surprisingly, preschoolers showed functional differentiation even in the absence of semantic cues--a finding interpreted as evidence for a functional differentiation in the young child's deployment of attention. Second and fifth graders also exhibited functional differentiation in the absence of semantic cues, and there were age changes in the facilitating effects of input and retrieval cues on children's memory.

Age Factors↗

Mammary organoids from immature virgin rats undergo ductal and alveolar morphogenesis when grown within a reconstituted basement membrane.

We have recently described a primary culture system which allows for extensive proliferation and functional differentiation of immature mammary epithelial cells. Herein, these findings are extended to demonstrate that a distinct pattern of ductal and alveolar morphogenesis can be induced within the mammary organoids isolated from virgin female rats and cultured within an Engelbreth-Holm-Swarm sarcoma-derived reconstituted basement membrane under defined serum-free conditions. The lobular and multilobular organoids that emerged resemble the alveoli of the mammary gland in gross form, multicellular architecture, and cytologic and functional differentiation, while the ductal organoids expressed characteristics typical of mammary gland ducts in vivo. The epithelial cells within the alveolar- and duct-like organoids displayed the capability of secreting two morphologically distinct milk products, casein and lipid, into the luminal compartment. The expression of histiotypic morphogenesis and mammary-specific functional differentiation by the cultured mammary organoids proceeded in the absence of a morphologically distinct basal lamina. We illustrate that development highly reminiscent of that which naturally occurs in the mammary gland in vivo can be induced and supported in vitro under defined serum-free conditions. In addition, the methodologies are available to simultaneously monitor mammary organoid morphogenesis, growth, and functional differentiation. This system should serve as a unique model in which the regulation of branching morphogenesis, development, gene expression, and transformation can be examined.

Animals↗

Macrophages that have phagocytosed particles are capable of differentiating into functional osteoclasts.

The aim of the current study was to determine whether human macrophages that have phagocytosed particles are capable of differentiating into osteoclastic bone-resorbing cells. Macrophages isolated from human peripheral blood were cultured with latex particles in the presence of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) on dentine slices and coverslips. After 24 h incubation, particles that had not yet been phagocytosed were removed by washing the slices. Histochemistry and immunohistochemistry was used to determine expression of macrophage and osteoclast markers and lacunae resorption, scanning electron microscopy, and transmission electron microscopy were used to examine cells with phagocytosed particles. Isolated macrophages on dentine slices were noted to contain a large number of particles inside, and no particles were identified outside of culture cells after washing. After 14 days of incubation, numerous tartrate-resistant acid phosphatase-positive multinucleated cells that contained particles in their cytoplasm, capable of extensive lacunae bone resorption, formed in these cultures. Our results clearly indicated that macrophages that have phagocytosed particles were still capable of differentiating into osteoclastic bone-resorbing cells. Macrophages that have phagocytosed wear particles in the pseudomembrane surrounding an implant not only produce cytokines but also may differentiate into functional osteoclasts, and influence bone resorption and loosening of a prosthesis.

Journal Article↗

Clinical impact of differential renal function to indicate and assess pyeloplasty and the significance of coexisting vesicoureteral reflux.

PURPOSE: In patients with ureteropelvic junction obstruction (JPJO) who are conservatively treated, 5% to 10% of them show a deterioration of renal function without recovery after delayed pyeloplasty. Should surgery be indicated based on observed deterioration of differential renal function (DRF)? Can we expect improvement of the DRF after pyeloplasty? What other influencing parameters may affect DRF? MATERIALS AND METHODS: In this study, the authors examined 85 ureterorenal junctions that had undergone the Anderson-Hynes technique for surgical correction of UPJO. Based on the values obtained from the preoperative DRF (Tc-99m mercaptoacetyltriglycine), the cases were separated into three categories: group I had poor DRF (less than 11% of total renal function [TRF]), group II had moderate DRF (11% to 33% of TRF), and group III had adequate DRF (more than 33% of TRF). Twelve months after surgery, renal function was reassessed. The results were correlated with age at surgery, symptoms, coexisting vesicoureteral reflux, and drainage. RESULTS: Seven ureterorenal junctions (8%) comprised group I, 15 (18%) comprised group II, and 63 (74%) comprised group III. After UPJO repair, 13% showed marked improvement in DRF, 86% remained stable, and 1% exhibited diminished function. In 50% of the renal cases with preoperative DRF less than 33%, postoperative improvement was seen. In follow-up renal scans, 30 cases (35%) revealed nonobstructive drainage, whereas the remaining 53 junctions (62%) showed moderate delayed drainage. Both the moderate delayed group (57%) and the nonobstructive group (50%) showed similar DRF improvement. Sixty-six percent of the patients with impaired DRF improved after pyeloplasty performed within the first 3 months of life, compared with 42.8% of patients in whom surgery was performed after 5 years of age. Vesicoureteral reflux was evident in 27.2% of the patients with preoperative impaired DRF compared with 11% with normal DRF. Forty-five percent of the patients with impaired DRF and no improvement after surgery had coexisting vesicoureteral reflux, compared with 9% of those with postoperative improvement. CONCLUSIONS: Sustained renal impairment after pyeloplasty is likely as a result of preexisting renal dysplasia with vesicoureteral reflux. Moderate delayed drainage after surgery does not affect DRF. Surgery for UPJO should be indicated independent of a DRF follow-up (except very low DRF) or the age at the time of diagnosis.

Child↗

Overexpression of a potassium channel gene perturbs neural differentiation.

Functional regulation of potassium currents in developing neurons is pivotal for changes in excitability and action potential waveform. Here, we test whether an excess of potassium channel transcripts is sufficient to drive functional expression of potassium current and shortening of the duration of the action potential. Injection of Shaker-like potassium channel transcripts into two-cell stage embryos achieves increases in RNA levels. The elevated levels of potassium channel RNA produce larger delayed-rectifier currents. Action potential durations are briefer, indicating that larger potassium currents are not compensated by changes in inward currents. Strikingly, overexpression of potassium current RNA leads to a reduction in the number of morphologically differentiated neurons in culture. We suggest that, by prematurely reducing the duration of the impulse, early overexpression of potassium channel activity suppresses normal developmental cues.

Action Potentials↗

Differential item functioning by sex and race in the Hogan Personality Inventory.

The authors examined measurement bias in the Hogan Personality Inventory by investigating differential item functioning (DIF) across sex and two racial groups (Caucasian and Black). The sample consisted of 1,579 Caucasians (1,023 men, 556 women) and 523 Blacks (321 men, 202 women) who were applying for entry-level, unskilled jobs in factories. Although the group mean differences were trivial, more than a third of the items showed DIF by sex (38.4%) and by race (37.3%). A content analysis of potentially biased items indicated that the themes of items displaying DIF were slightly more cohesive for sex than for race. The authors discuss possible explanations for differing clustering tendencies of items displaying DIF and some practical and theoretical implications of DIF in the development and interpretation of personality inventories.

Adult↗

Defective osteoclast differentiation and function in the osteopetrotic (os) rabbit.

We tested the ability of normal osteoclast progenitors found in neonatal liver and bone marrow to develop into functional osteoclasts when co-cultured with metatarsals from newborn osteopetrotic rabbits; the latter inherit an osteoclast incompetence resistant to cure by bone marrow transplantation. This system, developed by Burger and colleagues, has been shown to produce normal, functional osteoclasts when used with normal metatarsals. Our study tested the competence of the mutant skeletal microenvironment for differentiation of normal osteoclasts. Mutant and normal metatarsals were cultured alone or with normal liver, spleen, or bone marrow for up to 14 days. All normal cultures possessed a marrow cavity and contained numerous osteoclasts with cytochemical characteristics (tartrate-resistant acid phosphatase) of active cells. Mutant metatarsals co-cultured with normal spleen, liver, or bone marrow failed to develop a marrow cavity (evidence in itself of reduced bone resorption) and had osteoclasts reduced in both numbers and cytochemically detectable activity. Similar metatarsal cultures of an osteopetrotic rat mutation (incisors--absent) curable by bone-marrow transplantation exhibited marrow cavity development in mutant metatarsals co-cultured with normal spleen. These data suggest that the skeletal environment of osteopetrotic rabbits contains an inhibitor or lacks a promoter of osteoclast differentiation and function.

Acid Phosphatase↗

Modern psychometric methods for detection of differential item functioning: application to cognitive assessment measures.

Cognitive screening tests and items have been found to perform differently across groups that differ in terms of education, ethnicity and race. Despite the profound implications that such bias holds for studies in the epidemiology of dementia, little research has been conducted in this area. Using the methods of modern psychometric theory (in addition to those of classical test theory), we examined the performance of the Attention subscale of the Mattis Dementia Rating Scale. Several item response theory models, including the two- and three-parameter dichotomous response logistic model, as well as a polytomous response model were compared. (Log-likelihood ratio tests showed that the three-parameter model was not an improvement over the two-parameter model.) Data were collected as part of the ten-study National Institute on Aging Collaborative investigation of special dementia care in institutional settings. The subscale KR-20 estimate for this sample was 0.92. IRT model-based reliability estimates, provided at several points along the latent attribute, ranged from 0.65 to 0.97; the measure was least precise at the less disabled tail of the distribution. Most items performed in similar fashion across education groups; the item characteristic curves were almost identical, indicating little or no differential item functioning (DIF). However, four items were problematic. One item (digit span backwards) demonstrated a large error term in the confirmatory factor analysis; item-fit chi-square statistics developed using BIMAIN confirm this result for the IRT models. Further, the discrimination parameter for that item was low for all education subgroups. Generally, persons with the highest education had a greater probability of passing the item for most levels of theta. Model-based tests of DIF using MULTILOG identified three other items with significant, albeit small, DIF. One item, for example, showed non-uniform DIF in that at the impaired tail of the latent distribution, persons with higher education had a higher probability of correctly responding to the item than did lower education groups, but at less impaired levels, they had a lower probability of a correct response than did lower education groups. Another method of detection identified this item as having DIF (unsigned area statistic=3.05, p<0.01, and 2.96, p<0.01). On average, across the entire score range, the lower education group's probability of answering the item correctly was 0.11 higher than the higher education group's probability. A cross-validation with larger subgroups confirmed the overall result of little DIF for this measure. The methods used for detecting differential item functioning (which may, in turn, be indicative of bias) were applied to a neuropsychological subtest. These methods have been used previously to examine bias in screening measures across education and ethnic and racial subgroups. In addition to the important epidemiological applications of ensuring that screening measures and neuropsychological tests used in diagnoses are free of bias so that more culture-fair classifications will result, these methods are also useful for the examination of site differences in large multi-site clinical trials. It is recommended that these methods receive wider attention in the medical statistical literature.

Aged↗

Basic helix-loop-helix proteins can act at the E-box within the serum response element of the c-fos promoter to influence hormone-induced promoter activation in Sertoli cells.

The Sertoli cell is a terminally differentiated testicular cell in the adult required to maintain the process of spermatogenesis. Previously basic helix-loop-helix (bHLH) factors and c-fos have been shown to influence Sertoli cell-differentiated functions. The induction of Sertoli cell differentiation appears to involve the serum response element (SRE) of the c-fos promoter to activate c-fos and intermediate bHLH factor(s) that regulate down-stream Sertoli cell-differentiated genes (e.g. transferrin expression). The SRE of the c-fos promoter is influenced through the serum response factor (SRF). Interestingly, an E-box nucleotide sequence is present within the SRE. bHLH proteins act through E-box elements, and the current study investigates the possibility that bHLH proteins may directly influence the SRE of the c-fos promoter. The activation of the c-fos promoter in Sertoli cells was found to be inhibited with the overexpression of the inhibitory HLH protein Id. Analysis of major response elements within the c-fos promoter demonstrated that the expression of Id specifically inhibited the activation of SRE in Sertoli cells and no other elements tested. Mutations in the E-box of the SRE also inhibited the activation of SRE, suggesting the direct role of bHLH proteins in regulating SRE activity in Sertoli cells. In contrast, the activation of SRE containing a mutated E-box was comparable to wild-type SRE in control stromal cells. Analysis of SRE oligonucleotide gel mobility shift assays with nuclear extracts from Sertoli cells demonstrated the presence of both the SRF and the ubiquitously expressed bHLH protein E12/E47. In contrast, no E12/E47 was detected in the SRE oligonucleotide gel shift using control stromal cell nuclear extracts. Observations suggest the binding of E12/E47 to SRE may be a cell-specific event. The SRF and bHLH proteins appear to bind to the SRE and activate the c-fos promoter in Sertoli cells. Observations provide evidence that a bHLH protein can interact with the SRE of the c-fos promoter to influence hormone-induced promoter activation. Cross-talk between these nuclear transcription factors appears to be instrumental in the control of Sertoli cell-differentiated functions.

Animals↗

Transcription factors in islet development and physiology: role of PDX-1 in beta-cell function.

Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a cascade of gene activation events controlled by various transcription factors. The first molecular marker identified that specifies the early pancreatic epithelium is the homeodomain-containing transcription factor PDX-1. Its absence in mice and humans during development leads to agenesis of the pancreas. Later, it becomes restricted primarily to beta cells where it regulates the expression of beta cell-specific genes, and, most importantly, mediates the glucose effect on insulin gene transcription. Although exposure of beta cells to high glucose concentrations for relatively short periods stimulates insulin gene expression, chronic exposure has adverse effects on many beta-cell functions, including insulin gene transcription. These events appear to correlate with pdx-1 gene expression and its ability to bind the insulin gene. We consider that loss of PDX-1 function or altered pdx-1 gene expression due to mutations or functional impairment of transcription factors controlling its expression can lead to diabetes.

Animals↗

Assessment of endometrial differentiation and function.

The failure to produce an endometrium which is receptive and able to support implantation may underlie some cases of infertility and represent a contributory factor preventing higher pregnancy rates in IVF. This is of direct relevance to ovarian hyperstimulation protocols which may affect the pattern of endometrial differentiation and function and to patients possessing intrinsic defects in their endometrial response. It is apparent that markers of endometrial differentiation are required, particularly those defining the ability of the tissue to support implantation. The common method of assessing endometrial differentiation by histological evaluation, which has been substantially improved by techniques of morphometric analysis, depend upon alterations in endometrial structure. However, the production of monoclonal antibodies to proteins and epitope-bearing mucins which exhibit specific patterns of expression during the luteal phase now also enables immunohistological assessment of endometrial differentiation. Whether these proteins mediate essential functions is not known but as they represent end-points of hormone action this would suggest that their measurement may form the basis of tests of endometrial function and supplement morphometric analyses.

Embryo Implantation↗