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Results for “Functional differentiation”

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At least 1,009 records · Page 56Linked to original sources
PubMed1990

Cytochrome c oxidase activity in preosteoclasts induced by experimental tooth movement.

Cytochrome c oxidase activity was detected in preosteoclasts induced by experimental tooth movement. Mitochondria with reaction products of the enzyme in the inner membrane and outer compartment, which we classified as type 1 mitochondria, were observed in preosteoclasts. The number of type 1 mitochondria in the preosteoclasts, however, was distinctly fewer as compared with those in active osteoclasts described in our previous studies. Also, some of preosteoclasts adjacent to the bone surface contained more type 1 mitochondria than preosteoclasts separated from the bone surface. These results suggest that cytochrome c oxidase activity is closely related to functional differentiation of preosteoclasts, and additionally can be used as an indicator of functional differentiation from preosteoclast to osteoclast.

Animals↗
PubMed1985

Folic acid uptake characteristics of a human colon carcinoma cell line, Caco-2. A newly-described cellular model for small intestinal epithelium.

To investigate a newly described model for differentiated small intestinal function, folic acid uptake characteristics were examined in the human colon carcinoma cell line, Caco-2. Monolayers of this cell line spontaneously exhibit structural and functional differentiation patterns characteristic of mature enterocytes, with the appearance of brush border microvilli and high activity levels of the enzymes associated with the brush border. Our results concur with other models of folic acid uptake that emphasize the importance of intraluminal factors on micronutrient absorption. Folate uptake declined rapidly between pH 5.8 and 7.5, and was dependent on the initial folate concentration in the media. A dual uptake process is suggested, with a high rate of uptake at folate concentrations below 20 nmol/ml and linear uptake characteristics at higher concentrations.

Cell Line↗
PubMedDate not supplied

[The effect of thymalin on biochemical and immunological indices of lymphocyte differentiation and functional activity].

Polypeptide preparation thymalin obtained from thymus was found to normalize the LDH isoenzyme spectrum and cyclase system in lymphocytes of patients. Thymalin contributed also to expression of differentiation antigens on T-lymphocytes surface. As a result of this functional activity of T-lymphocytes was restored, which correlated with improvement of the patients clinical state. Biochemical and immunological patterns of lymphocytes differentiation may be used both in diagnosis and control of treatment efficiency in patients with acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Cell differentiation and proliferation--simultaneous but independent?

Despite studies over many years, it is still not clear to what extent cellular controls on proliferation and on differentiation are interrelated. For example, the idea that exit from cell cycle into G1/G0 is a necessary-or at least frequent-prelude to differentiation developed partly from studies of haemopoietic cell maturation, often using cell lines as models. The responses of cells to treatment with differentiating agents suggested that exit from cell cycle into G1/G0 occurs quite quickly, with functional differentiated characteristics acquired later, and so promoted the notion that cyclin-dependent kinase inhibitors (CDKIs) might be important initiators of normal differentiation. However, recent work has made it clear that differentiation and cell proliferation are regulated simultaneously but independently, that cells often start differentiating long before they stop dividing, and that the launching of differentiation is not restricted to any particular segment of the cell cycle. This combination of attributes allows expansion of cell numbers and acquisition of differentiated function to occur in parallel, generating abundant effector cells. Given this dichotomy, future studies to develop a more exact picture of the events that initiate and drive differentiation might be simplified by studying differentiation under experimental conditions that divorce it from concerns about cell cycle control.

Animals↗
PubMed1979

Expression of fetal and neonatal hepatic functions by mouse hepatoma-rat hepatoma hybrids.

In order to analyze the mechanisms implicated in the expression of differentiated functions during development, we have studied ten hybrid clones arising from fusion of cells of a mouse hepatoma characterized by the expression of only fetal hepatic functions with those of a rat hepatoma which express, like adult hepatocytes, a set of neonatal as well as fetal hepatic functions. The cells of most hybrid clones contain one set of chromosomes of each parent and coexpress the hepatic functions common to both parents. Among the hepatic proteins characteristic of only one parental line, some continue to be expressed while others are extinguished. The three functions out of the eight examined which are subject to extinction are expressed uniquely by the rat parental cells and appear only near or at birth during normal liver development. These results suggest that regulatory mechanisms (whose final effect is negative) operate in fetal cells to inhibit the expression of differentiated functions limited to a later stage of development.

Animals↗
PubMed1996

Novel ipriflavone receptors coupled to calcium influx regulate osteoclast differentiation and function.

Ipriflavone (7-isopropoxyisoflavone) is an effective antiresorptive agent used to treat osteoporosis. However, the mechanism of its action on osteoclasts and their precursor cells is not well understood. To determine whether the mechanism involves direct effects on osteoclasts or their precursors, we examined the effects of ipriflavone on cytosolic free calcium ([Ca2+]i) in osteoclasts and their precursors and measured specific binding of 3H-labeled ipriflavone. Highly purified chicken osteoclast precursors, which spontaneously differentiate into multinucleated osteoclasts in 3-6 days, were loaded with fura-2, and the subcellular [Ca2+]i distribution was monitored by videoimaging. Ipriflavone induced a rapid increase in [Ca2+]i followed by a sustained elevation [EC50 = 5 x 10(-7) M, 263 +/- 74 nM (SE) (n = 8) above basal levels, by 10(-6) M ipriflavone, sustained phase]. The responses were the same in differentiated chicken osteoclasts and isolated rabbit osteoclasts. An influx of extracellular Ca2+ is likely to be responsible for the ipriflavone-induced change in [Ca2+]i because the response was abolished by 0.5 mM LaCl3, or by Ca-free medium containing EGTA. Moreover, high [Ca2+]i levels were detected adjacent to the cell membrane after ipriflavone addition. Ipriflavone induced Ca influx mainly through dihydropyridine-insensitive Ca2+ channels, because nicardipine (10(-7)M) and verapamil (10(-7)M) had no effects on ipriflavone-induced [Ca2+]i responses. [3H]Ipriflavone binding studies indicated the presence of specific ipriflavone binding sites (two classes), both in precursor cells [dissociation constant (Kd), 7.60 x 10(-8)M, 2.67 x 10(-6)M] and in mature osteoclasts (Kd, 4.98 x 10(-8)M, 3.70 x 10(-6)M). Specific ipriflavone binding was not displaced by various modulators of avian osteoclast function, such as estradiol (10(-8)M) or retinoic acid (10(-6)M), indicating that ipriflavone receptors differ from the receptors for these Ca-regulating hormones. The fusion of osteoclast precursor cells was significantly inhibited by ipriflavone, which led to dose-dependent inhibition of bone resorption and tartrate-resistant acid phosphatase activity. Novel specific ipriflavone receptors that are coupled to Ca2+ influx were demonstrated in osteoclasts and their precursor cells. These ipriflavone receptors may provide a mechanism to regulate osteoclast differentiation and function.

Acid Phosphatase↗
PubMed1994

Transformation of human granulosa cells with the E6 and E7 regions of human papillomavirus.

Ovarian granulosa cells are the primary site of estrogen and progesterone synthesis and play an essential role in the maturation of the developing ovum. Freshly isolated granulosa cells are often used to study the regulation of steroid and protein biosynthesis, but the small number of cells available for these cultures has proven inadequate for many detailed gene regulatory studies. The goal of this study was to develop human granulosa (HG) cell lines that maintain differentiated function. The E6 and E7 open reading frames of high risk strains of human papillomavirus have been used to produce immortalized cell lines. Primary cultures of human luteinized granulosa cells were infected with defective retroviruses containing the E6 and E7 regions of human papillomavirus 16 and with the neomycin phosphotransferase gene to confer G418 resistance. Three of eight clones that were isolated after selection in medium containing G418 were found to produce progesterone following treatment with forskolin or dibutyryl cAMP for 48 h. Forskolin caused these cells to retract in the characteristic rounding response, as described in primary HG cultures. One clone, HGL5, was used for a detailed characterization of differentiated function. HGL5 cells retained the ability to increase progesterone production and convert exogenously added androstenedione to estradiol in response to agonists of the protein kinase-A pathway (forskolin and dibutyryl cAMP), but were not responsive to FSH or LH treatment. A key enzyme in the production of estradiol, cytochrome P450 aromatase, has proven difficult to maintain in long term cultures of granulosa cells. For that reason, we examined the expression of aromatase in the transformed HGL5 clone by monitoring mRNA levels. Aromatase mRNA increased by 4- to 5-fold after forskolin treatment, as determined by Northern analysis. This human granulosa cell culture line maintains many of the functions of normal cells and should provide an important model to study the molecular events controlling granulosa cell differentiation and function.

Aromatase↗
PubMed2006

Calcitonin gene-related peptide stimulates human villous trophoblast cell differentiation in vitro.

Calcitonin gene-related peptide (CGRP) is a multifunctional peptide present in both maternal and fetal circulations in pregnancy. Its receptors have been identified on human trophoblast cells, but the role of CGRP in trophoblast differentiation remains unknown. This study was designed to determine the effect of CGRP on the differentiation of villous trophoblasts isolated from normal human term placentae. The morphological and functional differentiation of the trophoblast cells were assessed by desmosomal protein immunofluorescent staining and the quantification of hCG, estrogen and progesterone secretion. Results showed that (i) exposure of villous trophoblast cells to CGRP led to a dose-dependent increase in intracellular cyclic adenosine monophosphate (cAMP) accumulation; (ii) immunofluorescent staining with antidesmosomal antibody was identified at the boundaries between aggregated cytotrophoblast cells, and these stainings disappeared when cells fused to form syncytiotrophoblast cells; (iii) the formation of multinucleated syncytiums in primary cultured cytotrophoblasts was stimulated by CGRP as evidenced by the changes in antidesmosomal staining; (iv) CGRP increases trophoblast hCG secretion in a time- and dose-dependent manner, and this secretion was blocked by CGRP antagonist, CGRP(8-37), and (v) both 17beta-estradiol (E(2)) and progesterone concentrations in the culture medium were increased by CGRP, and these increases were dose dependent. These observations suggest that CGRP may be involved in the morphological and functional differentiation of trophoblast cells, and these actions might be attributed to CGRP-induced intracellular cAMP accumulation.

Calcitonin Gene-Related Peptide↗
PubMed2003

Participation of protein kinase C beta in osteoclast differentiation and function.

Protein kinase C (PKC) proteins have been shown to be involved in diverse cellular responses of various cell types. In experiments to identify genes regulated during osteoclast differentiation by a cDNA microarray approach, we found that the gene expression of PKC-betaII was upregulated in differentiated cells. Reverse transcription-polymerase chain reaction and Western blotting analyses also showed an increase in PKC-betaI as well as PKC-betaII during osteoclast formation in mouse bone marrow cell cultures in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL). Use of an antisense oligonucleotide to PKC-betaII resulted in a reduction in the RANKL-driven osteoclastogenesis. Pharmacological intervention with PKC-beta activity by the specific inhibitor CG53353 suppressed cellular differentiation and fusion processes during osteoclastogenesis and inhibited bone-resorbing function of mature osteoclasts. PKC-beta inhibition abolished the ERK and MEK activation by macrophage-colony stimulating factor and RANKL in osteoclast precursor cells whereas the cytokine-induced NF-kappaB activation was not hampered by the PKC-beta inhibition. Our findings indicate that PKC-beta has a role in regulation of osteoclast formation and function potentially by participating in the ERK signaling pathway of M-CSF and RANKL.

Animals↗
PubMed1995

Effects of hepatocyte growth factor on viability and biotransformation functions of hepatocytes in gel entrapped and monolayer culture.

OBJECTIVES: An extracorporeal bioartificial liver device must maintain viability and differentiated function of hepatocytes cultivated at high cell density. Growth factors, such as hepatocyte growth factor, found in high concentrations in the plasma of patients with fulminant hepatic failure, have the potential to promote hepatocyte dedifferentiation and thus, decrease function. We tested the hypothesis that hepatocyte growth factor would improve viable cell density and decrease biotransformation functions of liver cells in monolayer culture and in hepatocytes entrapped in collagen cylindrical gel "noodles" as found in the extracorporeal bioartificial liver. DESIGN: In vitro, controlled study. SETTING: University research laboratory. SUBJECTS: Adult Sprague Dawley Rats. INTERVENTIONS: Hepatocytes were harvested by a two-step collagenase technique. Harvested hepatocytes were plated onto type 1 collagen coated plates or entrapped in type 1 collagen cylindrical gels and cultured in different concentrations of hepatocyte growth factor. Interval measurements of 3H-thymidine incorporation, albumin synthesis, biotransformation functions, and viability were made. MEASUREMENTS AND MAIN RESULTS: In monolayer culture, the addition of hepatocyte growth factor caused a dramatic increase in 3H-thymidine incorporation. This increase was accompanied by a decrease in the appearance of the lidocaine metabolite, monoethyglycinexylidide. Albumin production was unchanged. In cylindrical gel entrapment cultures, hepatocyte growth factor caused a significant increase in 2-day viability but had no effect on the metabolite appearance of lidocaine or 4-methyl umbelliferone or albumin production. CONCLUSIONS: Hepatocyte growth factor induces dedifferentiation of hepatocytes in monolayer culture. Collagen matrix entrapment appears to abrogate this effect and improve liver cell viability. There may be reciprocal regulation of hepatocyte reproductive and differentiated functions, such as biotransformation, which can be influenced by the entrapment of hepatocytes in an extracellular type 1 collagen matrix.

Animals↗
PubMed2000

The osteoblast-specific transcription factor Cbfa1 contributes to the expression of osteoprotegerin, a potent inhibitor of osteoclast differentiation and function.

Bone formation and resorption are tightly coupled under normal conditions, and the interaction of osteoclast precursors with cells of the osteoblast lineage is a prerequisite for osteoclast formation. Cbfa1 is an osteoblast-specific transcription factor that is essential for osteoblast differentiation and bone formation. At present, it is not known whether Cbfa1 regulates any of the osteoblast-derived factors involved in the bone resorption pathway. Osteoprotegerin (OPG) is an osteoblast-secreted glycoprotein that functions as a potent inhibitor of osteoclast differentiation and bone resorption. Cloning and computer analysis of a 5.9-kilobase human OPG promoter sequence revealed the presence of 12 putative Cbfa1 binding elements (osteoblast-specific element 2 (OSE(2))), suggesting a possible regulation of OPG by Cbfa1. We cloned the promoter upstream of the beta-galactosidase reporter gene (pOPG5. 9betagal) and evaluated whether Cbfa1 could regulate its expression in transient transfection assays. The 5.9-kilobase promoter directed increased levels of reporter gene expression, reminiscent of OPG protein levels in osteoblastic cell lines (BALC and U2OS) as compared with the nonosteoblastic cell line COS1. Cotransfection of a Cbfa1 expression construct along with pOPG5.9betagal reporter construct led to 39-, 7-, and 16-fold increases in beta-galactosidase activity in COS1, BALC, and U2OS cells, respectively. Removal of all the putative OSE(2) elements led to an almost complete loss of transactivation. Mutational analysis demonstrated that the proximal OSE(2) element contributes to a majority of the effects of Cbfa1, and Cbfa1 bound to the proximal element in a sequence-specific manner. Further, overexpression of Cbfa1 led to a 54% increase in OPG protein levels in U2OS cells. These results indicate that Cbfa1 regulates the expression of OPG, thereby further contributing to a molecular link between bone formation and resorption.

Animals↗
PubMed2002

Doppler echocardiographic differentiation of functional from anatomical pulmonary atresia: analysis using quantitative parameters.

Functional pulmonary atresia must be distinguished from anatomical atresia, which has an intact ventricular septum, to avoid inappropriate treatment, but there is a paucity of data regarding the echocardiographic features that differentiate these conditions. Echocardiographic findings in 5 neonates with functional atresia were compared to those in 5 with anatomical atresia. The left and right ventricular end-diastolic dimensions (LVDd, RVDd), percent of normal predicted LVDd, RVDd/LVDd, tricuspid valve ring diameter (TVD), percent of normal predicted TVD, grade of tricuspid regurgitation (TR), peak TR velocity, pulmonary valve ring diameter (PVD), percent of normal predicted PVD, the minimum diameter of the ductus and the peak velocity through it (PDA velocity) were measured. In addition, systolic pulmonary (PAp) and right ventricular pressure (RVp) from either PDA velocity or TR velocity, and calculated PAp/RVp were also estimated. There were significant differences in RVDd/LVDd, %TVD, and peak TR velocity between the 2 groups. All functional patients showed RVDd/LVDd >0.6, %TVD >100%, estimated RVp <50mmHg, PAp/RVp >0.85, and peak TR velocity <4m/s, whereas the findings in anatomical atresia patients were completely the opposite. In conclusion, a large RVDd/LVDd, TVD, PAp/RVp, low RVp and small TR velocity all suggest functional rather than anatomical pulmonary atresia, although there may be some exceptions such as severe Ebstein anomaly.

Diagnosis, Differential↗