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Results for “Functional differentiation”

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At least 235 records · Page 13Linked to original sources
PubMed2000

Influence of vitamin D and retinoids on the induction of functional differentiation in vitro of canine osteosarcoma clonal cells.

The efficacy of 22-oxacalcitriol (OCT), calcitriol, cholecalciferol, all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) to differentiate in vitro four clonal cells of the canine osteosarcoma cell line POS into cells having properties of a functionally mature osteoblast bone cell were investigated. The induction of intracellular alkaline phosphatase (ALP) activity, osteocalcin (GLA-OC) and type I collagen (PIP) production after 72 h treatment were used as markers of differentiation. At a concentration of 10(-8)M, OCT and calcitriol significantly induced all markers, and ATRA only the ALP of osteoblast, chondroblast and undifferentiated clonal cells. At the same concentration, 9-cis RA and cholecalciferol induced ALP of chondroblast and osteoblast cells, respectively; ATRA, 9-cis RA and cholecalciferol induced PIP of chondroblast and undifferentiated cells. None of the drugs significantly differentiated fibroblast cells. The ability of these agents to differentiate osteosarcoma cells into cells that exhibit properties of functionally mature osteoblastic bone cells may promote normal osteogenesis and reverse the loss of control of their differentiation.

Alkaline Phosphatase↗
PubMed2003

Alcohol affects executive cognitive functioning differentially on the ascending versus descending limb of the blood alcohol concentration curve.

BACKGROUND: Executive cognitive functioning (ECF), a construct that includes cognitive abilities such as planning, abstract reasoning, and the capacity to govern self-directed behavior, has been recently researched as an antecedent to many forms of psychopathology and has been implicated in alcohol-related aggression. This study was designed to examine whether differential ECF impairments can be noted on the ascending versus the descending limbs of the blood alcohol concentration curve. METHODS: Forty-one male university students participated in this study. Twenty-one subjects were given 1.32 ml of 95% alcohol per kilogram of body weight, mixed with orange juice, and the remaining 20 were given a placebo. Participants were randomly assigned to either an ascending or descending blood alcohol group and were tested on six tests of ECF on their assigned limb. Subjective mood data were also collected. RESULTS: Intoxicated participants on both limbs demonstrated ECF impairment; the descending-limb group showed greater impairment than their ascending-limb counterparts. Intoxicated subjects were significantly more anxious at baseline than placebo subjects. The introduction of this covariate nullified any significant differences in subjective mood found on either limb of the blood alcohol concentration curve, but ECF impairments remained robust. CONCLUSIONS: Our results support the conclusion that alcohol negatively affects cognitive performance and has a differential effect on the descending versus the ascending limb of the blood alcohol concentration curve. The latter finding may have important ramifications relating to the detrimental consequences of alcohol intoxication.

Adult↗
PubMed1978

Functional differentiation of various types of cardiomyopathies by echocardiography.

Echocardiography was used to compare the left ventricular function in 35 cases of congestive cardiomyopathy (COCM), 16 cases of obstructive and 28 cases of non-obstructive asymmetric septal hypertrophy, 43 cases of scleroderma heart disease, 21 cases of ischaemic cardiomyopathy (ICM), 2 cases of restrictive cardiomyopathy, and one case of cardiac amyloidosis. COCM was characterized by left ventricular dilatation, decreased contractility and signs of elevated end-diastolic pressure. In asymmetric septal hypertrophy there was a decreased distensibility of the obstructed left ventricle, both in early and end-diastole, but the pump function remained normal. In scleroderma and amyloid heart disease both the contractility and distensibility of the small, stiff heart were reduced. In restrictive cardiomyopathy the only abnormality was the impaired end-diastolic distensibility. Reduced contractility confined primarily to the interventricular septum and impaired early diastolic distensibility are the characteristic features distinguishing ischaemic cardiomyopathy from COCM. However, echocardiography is not suitable for individual differentiation of ICM and COCM. The COCM can be differentiated from left ventricular aneurysm by M-mode sector scanning technique.

Adolescent↗
PubMed1998

Cytokine production by CD4+ and CD8+ T cells in mice following primary exposure to chemical allergens: evidence for functional differentiation of T lymphocytes in vivo.

It has been demonstrated previously that repeated exposure of mice to chemical allergens of different types results in the development of qualitatively divergent immune responses characterized by the production by draining lymph node cells (LNC) of distinct cytokine patterns. Chronic exposure of mice to contact allergens, such as 2,4-dinitrochlorobenzene (DNCB), resulted in the secretion by LNC of low or undetectable levels of interleukins 4 and 10 (IL-4 and IL-10), but comparatively high levels of interferon gamma (IFN-gamma); the latter cytokine being produced by both CD4+ and CD8+ cells. In contrast, chronic exposure of mice to trimellitic anhydride (TMA), a respiratory allergen associated in humans with occupational asthma, induced instead the production by LNC of relatively high concentrations of IL-4 and IL-10, but little IFN-gamma. The low levels of IFN-gamma secretion which were provoked by treatment with TMA were shown to derive from CD8+ cells exclusively. In the present investigations we have sought to determine whether the polarized responses observed following repeated exposure to these chemical allergens are reflected by cytokine secretion patterns provoked by primary exposure. To this end, mice of BALB/c strain were exposed epicutaneously daily for 3 consecutive days to concentrations of DNCB and TMA (1 and 10%, respectively), or to oxazolone, another contact allergen (0.25%), that resulted in substantial proliferative activity in draining lymph nodes. The production by draining LNC of IFN-gamma and of mitogen-inducible IL-4 was measured by enzyme-linked immunosorbent assay and the relative contribution of CD4+ and CD8+ cells to the patterns of cytokine secretion observed was analyzed using both positive and negative selection methods. It was found that primary exposure to DNCB, oxazolone and TMA each resulted in the production by LNC of both IFN-gamma and IL-4. Selective depletion of, or enrichment for, CD4+ and CD8+ cells revealed that only CD4+ cells elaborated mitogen-inducible IL-4. Depletion of neither CD4+ nor CD8+ cells compromised the production by TMA- or DNCB-activated LNC of IFN-gamma, although positively selected CD8+ cells were considerably less able than CD4+ cells to elaborate this cytokine, presumably secondary to a lack of appropriate accessory cells. Taken together the results demonstrate that early during immune responses to DNCB or oxazolone and TMA there is no evidence for the selectivity of cytokine secretion patterns that characterizes responses following more chronic exposure. Moreover, it is clear that exposure to TMA initially induces the production of IFN-gamma by both CD4+ and CD8+ cells, whereas after more chronic treatment the secretion of this cytokine is a function of CD8+ cells exclusively. Collectively, these results indicate that the polarized responses that develop in mice following chronic exposure to different classes of chemical allergen are not reflected by the characteristics of primary immune responses. As such the development of qualitatively divergent immune responses to chemical allergens provides a paradigm for the evolution of differentiated T cell function with time and/or with antigen exposure.

Allergens↗
PubMed1981

Functional differentiation in acute monoblastic leukemia.

Blasts from the bone marrow of a patient who had acute monoblastic leukemia were studied for functional maturity. Classification of the leukemia was based on cytochemical stains. The blasts were negative when stained with Sudan black B and did not have specific esterase activity. They were rich in alpha-naphthyl butyrate esterase, which was inhibited by fluoride. Functional assays included phagocytosis of Candida albicans, fungicidal activity measured by differential Giemsa staining of the ingested C. albicans, and locomotion using the agarose method to evaluate both random migration and chemotaxis. At a ratio of 20 yeast cells to one monoblast, 80% of the blasts could be stimulated to phagocytize an average of 4.4 organisms. These results compared favorably with the phagocytic potential of normal human monocytes. Candidacidal activity was present, but reduced. At high ratios of yeasts to monoblasts, only ten organisms were killed for every 100 phagocytic blasts. This correlates with the absence of myeloperoxidase activity demonstrated by negative Sudan black B staining. Neither chemotaxis nor random migration could be demonstrated, indicating that monoblasts lacked the apparatus necessary for locomotion. Extrapolation of these findings to normal monocyte maturation suggests that phagocytosis is acquired prior to microbicidal activity, which develops prior to locomotion.

Adult↗
PubMed2023

Genome-wide identification of transcriptional enhancers during human placental development and association with function, differentiation, and disease†.

The placenta is a dynamic organ that must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier protection. Proper placenta development and function are critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown. We hypothesized that mapping sites of transcriptional enhancer activity and associated changes in gene expression across gestation in human placenta tissue would identify genomic loci and predicted transcription factor activity related to critical placenta functions. We used a suite of genomic assays [i.e., RNA-sequencing (RNA-seq), Precision run-on-sequencing (PRO-seq), and Chromatin immunoprecipitation-sequencing (ChIP-seq)] and computational pipelines to identify a set of >20 000 enhancers that are active at various time points in gestation. Changes in the activity of these enhancers correlate with changes in gene expression. In addition, some of these enhancers encode risk for adverse pregnancy outcomes. We further show that integrating enhancer activity, transcription factor motif analysis, and transcription factor expression can identify distinct sets of transcription factors predicted to be more active either in early pregnancy or at term. Knockdown of selected identified transcription factors in a trophoblast stem cell culture model altered the expression of key placental marker genes. These observations provide a framework for future mechanistic studies of individual enhancer-transcription factor-target gene interactions and have the potential to inform genetic risk prediction for adverse pregnancy outcomes.

Humans↗
PubMed1972

Morphological correlates of functional differentiation of nodes of Ranvier along single fibers in the neurogenic electric organ of the knife fish Stern archus.

Electric organs in Sternarchidae are of neural origin, in contrast to electric organs in other fish, which are derived from muscle. The electric organ in Sternarchus is composed of modified axons of spinal neurons. Fibers comprising the electric organ were studied by dissection and by light- and electron microscopy of sectioned material. The spinal electrocytes descend to the electric organ where they run anteriorly for several segments, turn sharply, and run posteriorly to end blindly at approximately the level where they enter the organ. At the level of entry into the organ, and where they turn around, the axons are about 20 micro in diameter; the nodes of Ranvier have a typical appearance with a gap of approximately 1 micro in the myelin. Anteriorly and posteriorly running parts of the fibers dilate to a diameter of approximately 100 micro, and then taper again. In proximal and central regions of anteriorly and posteriorly running parts, nodal gaps measure approximately 1 micro along the axon. In distal regions of anteriorly and posteriorly running parts are three to five large nodes with gaps measuring more than 50 micro along the fiber axis. Nodes with narrow and with wide gaps are distinguishable ultrastructurally; the first type has a typical structure, whereas the second type represents a new nodal morphology. At the typical nodes a dense cytoplasmic material is associated with the axon membrane. At large nodes, the unmyelinated axon membrane is elaborated to form a closely packed layer of irregular polypoid processes without a dense cytoplasmic undercoating. Electrophysiological data indicate that typical nodes in proximal regions of anteriorly and posteriorly running segments actively generate spikes, whereas large distal nodes are inactive and act as a series capacity. Increased membrane surface area provides a morphological correlate for this capacity. This electric organ comprises a unique neural system in which axons have evolved so as to generate external signals, an adaptation involving a functionally significant structural differentiation of nodes of Ranvier along single nerve fibers.

Action Potentials↗
PubMed1992

Dependency of the in vitro stabilization of differentiated functions in liver parenchymal cells on the type of cell line used for co-culture.

The differentiation status in cultures of primary rat liver parenchymal cells was determined by measuring the activities of various xenobiotic metabolizing enzymes. Most enzyme activities dropped rather rapidly in monocultures of parenchymal cells. The protein content and the activities of cytosolic epoxide hydrolase, glutathione S-transferase, and alpha-naphthol UDP-glucuronosyl transferase were, however, well stabilized in 7-day-old co-cultures of parenchymal cells with two different lines of rat liver nonparenchymal epithelial cells (NEC1 and NEC2). Phenol sulfotransferase and microsomal epoxide hydrolase activity were reduced in this coculture system after 7 days to about 30 and 20% of the initial activity. Generally, higher enzyme activities were measured in co-cultures with one specific epithelial cell line (NEC2) as compared to those with the other line (NEC1). C3H 10T1/2 mouse embryo fibroblasts supported the parenchymal cells even better than the two epithelial lines, because the activity of microsomal epoxide hydrolase was also stabilized. Glutathione transferase activity was increased over time in this co-culture system. Our results show that the differentiation status of liver parenchymal cells was much better stabilized in co-cultures than in monocultures but that, depending on the type of cells used for co-culture, great quantitative differences existed. The entire pattern of xenobiotic metabolizing enzyme activities could not be stabilized at the kind of levels found in freshly isolated parenchymal cells.

Animals↗
PubMed2004

Expression analysis of ABC transporters reveals differential functions of tandemly duplicated genes in Caenorhabditis elegans.

We have previously identified 60 predicted ABC transporter genes in the Caenorhabditis elegans genome and classified them into eight groups. As an initial step towards understanding how these putative ABC genes work in worms, we generated promoter-fluorescent protein fusions for the entire family to address when and where these genes are turned on in vivo. Both Aequoria green fluorescent protein (GFP) and Discosoma red fluorescent protein (RFP) were used as reporters in our transgenic assay. Observable expression is more frequently seen from fusions to genes in subfamilies B, C, D and E than those in subfamilies A and G. Sixteen worm ABC genes are found in tandem duplications, forming two four-gene clusters and four two-gene clusters. Fifteen out of the 16 duplicated gene promoters drove different or partially overlapping expression patterns, suggesting active functions for these duplicated genes. Furthermore, our results suggest that an internal promoter can cause differential expression of genes within an operon. Finally, our observations suggest that it is possible for coding sequences to function as a regulatory region for a neighbouring gene.

ATP-Binding Cassette Transporters↗
PubMed2006

Adaptive functional differentiation of dendritic cells: integrating the network of extra- and intracellular signals.

Phenotypic maturation, cytokine secretion, and migration are distinct functional characteristics of dendritic cells (DCs). These functions are independently regulated by a number of extracellular variables, such as type, strength, and persistence of an array of soluble and membrane-bound mediators. Since the exact composition of these variables in response to infection may differ between individuals, the intracellular signaling pathways activated by these extracellular networks may more closely correlate with DC function and predict the course of adaptive immunity. We found that activation of p38 kinase (p38K), extracellular signal-related kinase 1/2 (ERK1/2), and phosphatidylcholine-specific phospholipase C (PC-PLC) enhanced cytokine secretion, whereas p38K, cyclic adenosine monophosphate (cAMP), and PC-PLC enhanced migration. In contrast, phosphatidylinositol 3-kinase (PI3K)/Akt-1 and cAMP inhibited cytokine secretion while ERK1/2 inhibited migration. Migration and cytokine secretion further differed in their sensitivity to inhibition over time. However, although DCs could be manipulated to express migration, cytokine secretion, or both, the level of activation or persistence of intracellular pathway signaling was not predictive. Our results suggest a modular organization of function. We hypothesize that the expression of specific DC functions integrates a large variety of activating and inhibitory variables, and is represented by the formation of a functional unit of molecular networks-the signal response module (SRM). The combined activities of these modules define the functional outcome of DC activation.

Cell Differentiation↗
PubMed1998

Functional differentiation along the anterior-posterior axis of the hippocampus in monkeys.

We tested whether the primate hippocampus was functionally heterogenous along its anterior-posterior axis. Two monkeys were trained on both a spatial and nonspatial memory task and the incidence of spatial and nonspatial delay activity in the anterior, middle, and posterior hippocampus was noted. Spatial delay activity (activity in the delay period after the sample stimulus on the spatial memory task) was more common in the posterior than the anterior hippocampus, whereas nonspatial delay activity (activity in the delay period after the sample stimulus on the nonspatial memory task) was evenly distributed throughout the hippocampus. Furthermore, delay neurons in the anterior hippocampus exhibited scalloping delay activity, whereas those in the middle and posterior hippocampus did not. These findings suggest that the hippocampus is functionally heterogeneous and that the posterior regions may be more important for processing spatial information, whereas the anterior regions may be more important for directing or coding movements to points in space.

Acoustic Stimulation↗
PubMed1993

The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins.

The major intrinsic protein (MIP) of the bovine lens fiber cell membrane was the first member of the MIP family of proteins to be sequenced and characterized. It is probably a homotetramer with transmembrane channel activity that plays a role in lens biogenesis or maintenance. The polypeptide chain of each subunit may span the membrane six times, and both the N- and C-termini face the cell cytoplasm. Eighteen sequenced or partially sequenced proteins from bacteria, yeast, plants, and animals have now been shown to be members of the MIP family. These proteins appear to function in (1) metazoan development and neurogenesis (MIP and BIB), (2) water transport across the human erythrocyte membrane (ChIP), (3) communication between host plant cells and symbiotic nitrogen-fixing bacteria (NOD), (4) transport across the tonoplast membrane during plant seed development (alpha-TIP), (5) water stress-induced resistance to desiccation in plants (Wsi-TIP), (6) suppression of a genetic growth defect on fermentable sugars in yeast (FPS1), and (7) transport of glycerol across bacterial cell membranes (GlpF). One other sequenced member of the MIP family (ORF1 of Lactococcus lactis) has no known physiological function. The biochemical functions of the eukaryotic proteins are not well established. Computer analyses have revealed that the first and second halves of all MIP family proteins probably arose by a tandem, intragenic, duplication event. Thus, the primary structure of putative transmembrane helices 1 to 3 is similar to that of putative transmembrane helices 4 to 6 even though they are of opposite orientation in the membrane. Among the most conserved residues in these two repeated halves are a membrane-embedded glutamate (E) in helices 1 and 4, an asparagine-proline-alanine (NPA) sequence in the loops between helices 2 and 3 (cytoplasmically localized) and helices 5 and 6 (extracellularly localized), and a glycine within helices 3 and 6. Statistical analyses suggest that the two halves of these proteins have evolved to serve distinct functions: the first half is more important for the generalized or common functions of these proteins, while the second half of these proteins is more differentiated to provide specific or dissimilar functions of the proteins. The apparent origin of MIP family proteins by duplication of a three-spanner precursor protein suggests an evolutionary origin distinct from other transport proteins with six transmembrane spanners.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1985

Functional differentiation of cell types of cortical collecting duct.

Interference-contrast and fluorescent microscopy were used to differentiate between the two cell types--principal cells (PC) and intercalated cells (IC)--of the isolated perfused cortical collecting duct of the rabbit. Using Hoffman Modulation Contrast optics, two types of cell outlines could be identified: "hexagonal" and "circular" profiles. To characterize the cell types further, the binding of fluorescein-labeled peanut lectin, which has been shown to be specific for the luminal cell membrane of the IC, was monitored with epifluorescent techniques. The lectin was observed to bind to the circular cell type only, confirming it as the IC. With use of the fluorescent nuclear probe acridine orange to quantitate the total number of cells per millimeter of tubule length, the fraction of ICs (lectin-binding cells) was estimated to average 29%, and the fraction of PCs (non-lectin-binding cells) to average 71% of all cells. The studies were extended to functionally separate between the two cell types by monitoring cell swelling when a lumen-to-bath current pulse was passed. Current-induced swelling was observed only in the PC and could be inhibited by the luminal addition of both the Na+ channel blocker amiloride, and the K+ channel blocker barium, thereby implicating the PC in the process of Na+ absorption and K+ secretion in this tissue. It is concluded that optical techniques can be applied to the cortical collecting duct perfused in vitro to differentiate between and study functional properties of the cell types.

Acridine Orange↗
PubMed2005

Differentiating functional constipation from constipation-predominant irritable bowel syndrome: management implications.

Symptoms of constipation are commonly seen in medical practice. Once other medical causes have been excluded, distinguishing patients who have constipation-predominant irritable bowel syndrome (IBS) from those with functional constipation has been considered useful in terms of planning management. However, the criteria used to distinguish IBS from functional constipation are arguably arbitrary, and the availability of new therapeutic approaches may render such distinctions of little practical relevance. In this article, the author presents a review of the management implications of differentiating constipation-predominant IBS from functional constipation.

Biofeedback, Psychology↗
PubMed1997

Restoration of the differentiated functions of serially passaged chondrocytes using staurosporine.

Among the various directions explored in order to have a large number of differentiated articular chondrocytes easily available, the restoration of the differentiated properties after cell multiplication in monolayer has been proposed. It has been clearly shown that the synthesis of cartilage proteoglycans and type II collagen synthesis is coincident with the presence of a faint microfibrillar architecture but is absent in chondrocytes showing well-defined actin cables. Staurosporin, mainly described as a protein kinase C inhibitor, has also been shown to rapidly induce the disruption of the actin microfilaments. The purpose of this paper was to investigate whether properties of differentiated chondrocytes were reinitiated upon staurosporin treatment of serially passaged chondrocytes. Results showed, after staurosporine treatment of cells at Passage two for 5 d, complete suppression of type I and type III collagen synthesis and induction of type II collagen synthesis and of Alcian blue stainable matrix. Additionally, we showed that staurosporin restored metabolic responses that chondrocytes in primary culture exhibit upon interleukin-1 beta treatment (decrease of Alcian blue- positive cells, induction of expression of the 92 kDa gelatinase, nitric oxide production). We conclude that staurosporin is a potent redifferentiating agent of articular chondrocytes that have been subcultured up to Passage two for multiplication. Taking into account that the cellularity of cartilage is very low, staurosporine-treated chondrocytes could be useful as an alternative cellular model to evaluate pharmacotoxicological effects of drugs.

Actins↗