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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastomas often show amplification and high expression of the N-myc oncogene. N-myc expression could be explained as a consequence of gene amplification, but an alternative possibility is that expression primarily results from the inactivation or loss of some factor that normally represses the N-myc gene. To test this idea, we fused N-myc-overexpressing neuroblastoma cell lines with lines that do not express N-myc. In the resulting hybrids, N-myc expression turned out to be switched off, although amplified N-myc copies were still present. This suggests that N-myc overexpression in neuroblastomas results, at least in part, from the inactivation of a suppressor gene that is present in normal cells. In rat neuroblastomas, it has been found that N-myc can switch off class I major histocompatibility complex (MHC) expression. Therefore, we analyzed in our hybrid cells whether suppression of N-myc results in reexpression of human class I MHC genes. Because this was found to be the case, the picture emerges of a hierarchic pathway that connects a putative tumor-suppressor gene with the expression of N-myc and consequently of class I MHC, thus affecting the potential immunogenic properties of neuroblastomas.
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PMID:N-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells. 220 14

Studies of the development of the central nervous system would be greatly facilitated by the ability to immortalize neuronal tissue from a broad range of ages. We have previously used somatic cell fusion techniques to generate neuronal cell lines from embryonic mice. To immortalize older neuronal cells, a cell isolation technique was developed to obtain viable septal cells from postnatal day 21 mice. The septal cells were fused to N18TG2 neuroblastoma cells and then cultured in selective medium to isolate septum x neuroblastoma cell lines. The hybrid nature of the lines was verified by chromosome analysis and electrophoretic analysis of glucosephosphate isomerase isozymes. The lines express phenotypes typical of differentiated septal neurons. Many lines morphologically resemble neurons and express the high molecular weight neurofilament protein. Several lines express high levels of choline acetyltransferase activity; others synthesize nerve growth factor. These results demonstrate that young adult neuronal tissue can be immortalized and that hybrid cells express properties of the neuronal parent.
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PMID:Immortalized young adult neurons from the septal region: generation and characterization. 233 89

We have analyzed the modulation of amyloid beta-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human-recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reporter gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.
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PMID:Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. 250 93

In order to study whether cell fusion would modify the DNA copy number of an amplified oncogene, somatic cell hybrids were made between the human neuroepithelioma cell line MCIXC and HeLaCOT human adenocarcinoma cells. MCIXC contains approximately 21 copies of the c-myc oncogene and HeLaCOT contains approximately 5 copies relative to the control. All hybrid clones investigated displayed a marked decrease in the number of copies of c-myc DNA (an average of 5 copies), while the level of c-myc RNA in the hybrids was similar to that found in both parents. All eight hybrid clones were found to be completely nontumorigenic even though both parent cells formed tumors in 100% of the nude mice treated by injection. This loss of oncogene amplification in the hybrids was shown not to be due to either heterogeneity of c-myc amplification in the MCIXC parent or segregation of a copy of the chromosome 22 from the hybrids. This loss most likely resulted from the breakdown of a homogeneously staining region (containing the amplified gene copies) into double minutes, which were subsequently lost from the cells. The HeLaCOT cell line was also fused to the human neuroblastoma BE(2)C, which contains approximately 123 copies of the N-myc oncogene relative to control. Ten hybrid clones were found to contain an average of 47 copies of N-myc DNA, significantly less than the 91 copies predicted had no loss occurred. These BE(2)C x HeLaCOT hybrids expressed on average about 15% the N-myc RNA seen in the BE(2)C parent and, as with the MCIXC x HeLaCOT hybrids, were found to be completely nontumorigenic. However, upon passage in culture, one BE(2)C x HeLaCOT hybrid eventually became tumorigenic. This hybrid also displayed reduced copies of N-myc DNA in comparison to its parent hybrid but surprisingly showed a 2-fold increase in N-myc RNA. Thus, the expression of N-myc, but not the amplification state of either myc gene, appears to correlate with the tumorigenicity of the cells.
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PMID:Modification of myc gene amplification in human somatic cell hybrids. 256 70

Porcelain-fused-to-metal restorations are fixed several hundred degrees above the glass-transition temperature and cooled rapidly through the glass-transition temperature range. Thermal expansion data from room temperature to above the glass-transition temperature range are important for the thermal expansion of the porcelain to be matched to the alloy. The effect of heating rate during measurement of thermal expansion was determined for NBS SRM 710 glass and four commercial opaque and body porcelain products. Thermal expansion data were obtained at heating rates of from 3 to 30 degrees C/min after the porcelain was cooled at the same rate. By use of the Moynihan equation (where Tg systematically increases in temperature with an increase in cooling/heating rate), the glass-transition temperatures (Tg) derived from these data were shown to be related to the heating rate.
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PMID:The effect of thermal history on porcelain expansion behavior. 277 74

Hormonal regulation of Mg2+ influx was examined in the neuroblastoma X glioma hybrid cell line NG108-15 and the skeletal muscle cell line G8 using 28Mg2+. Both cell lines express multiple classes of hormone receptors; in addition, G8 cells can be induced to differentiate from a single myoblast-like cell into fused myotube-like cells. In NG108-15 cells, 2-Cl-adenosine, an adenosine receptor agonist, stimulated Mg2+ influx by about 60%. This effect was not mimicked by norepinephrine or PGE1, agonists at alpha 2-adrenergic and prostaglandin receptors which NG108-15 cells also express. Carbachol, acting through a muscarinic receptor, gave minimal and variable stimulation of Mg2+ influx. The effect of 2-Cl-adenosine was not blocked by theophylline, an adenosine receptor antagonist, and was not mimicked by adenosine analogs selective for either A1 or A2 adenosine receptors, suggesting that a nonclassical adenosine receptor mediates the effect on Mg2+ influx. Theophylline slightly stimulated Mg2+ influx as did the permeable cyclic AMP analog, 8-Br-cyclic AMP. These results indicate that cyclic AMP may influence Mg2+ influx in NG108-15 cells unlike previous results in murine S49 lymphoma cells [Maguire and Erdos, J. biol. Chem. 255: 1030-1035, 1980] where receptor modulation of Mg2+ influx was independent of cyclic AMP. In G8 cells, the nicotinic cholinergic receptor agonist carbachol stimulated Mg2+ influx at the myoblast cell stage but had no effect on Mg2+ influx after cells had formed myotubes. The beta-adrenergic agonist isoproterenol had the opposite effect, stimulating Mg2+ influx in the myotube stage but not in the myoblast stage. Taken together, these results demonstrate that only a subset of receptors expressed by a cell may be coupled to Mg2+ influx, that the regulation of Mg2+ influx differs from cell type to cell type, and finally, that modulation of Mg2+ influx by hormone receptors may change with differentiation.
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PMID:Hormonal regulation of magnesium uptake: differential coupling of membrane receptors to magnesium uptake. 282 11

A cultured line of neuroblastoma cells (NB) was found to contain double minute chromosomes (DMs) DMs have been reported to be acentric and, therefore, to be segregated randomly into daughter cells without separating their sister elements. When NB cells were fused with Chinese hamster metaphase cells, prematurely condensed chromosomes (PCCs) were induced. DMs seen together with G2 PCCs appeared to be closely paired, dot-like structures resembling DMs observable in metaphase cells. In contrast, DMs in G1 cells showed a tendency to become single as the stage progressed so that the majority of DMs in late G1 cells were actually no longer double. DMs in S-phase cells, however, again appeared double. These results clearly indicate why DMs are invariably double and never assume a quadruple configuration in metaphase cells in spite of their non-disjunctional segregation at anaphase. Such a characteristic mode of DM replication was further confirmed by a 5-bromo-2'-deoxyuridine (BrdUrd) labeling experiment: when NB cells were exposed to BrdUrd for two successive rounds of DNA replication prior to PCC induction, half of the resulting single G1 minutes as well as G1 PCCs stained dark and the other half stained light after staining for sister chromatid differentiation.
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PMID:Analysis of the replication mode of double minutes using the PCC technique combined with BrdUrd labeling. 321 16

In an attempt to immortalize the gene products of single neurons, somatic cell hybrids were produced by fusion of embryonic rat dorsal root ganglion (DRG) neurons with mouse neuroblastoma cells. Embryonic day 13 rat DRGs were fused with mouse neuroblastoma cells deficient in hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8). The hybrid cells were selected in medium with 100 microM hypoxanthine/1 microM aminopterin/12 microM thymidine to eliminate the neuroblastoma cells and with cis-hydroxyproline to retard fibroblast growth. Of the 17 lines derived, 4 manifested neuronal properties and were cloned. These lines retain both rat and mouse chromosomes and synthesize characteristic rat and mouse isoenzymes. Neuronal gangliosides, action potentials, and extensive neurite-like processes are exhibited by these hybrid cells, properties characteristic of DRG neurons but not of the neuroblastoma parent. Each line manifests a unique combination of action-potential properties and cell-surface markers, suggesting the selective expression of subsets of DRG neuronal genes. All of these neuronal properties are expressed constitutively, without the need for chemical induction or mitotic inhibition, and stably, without diminution after at least 5 months in culture. These lines may prove useful in the identification and isolation of gene products that characterize individual or small subsets of DRG neurons.
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PMID:Neuronal traits of clonal cell lines derived by fusion of dorsal root ganglia neurons with neuroblastoma cells. 385 35

Neuroblastoma cells with electrically excitable membranes were fused with electrically passive L cells having a hitherto undescribed electrical marker. Hybrid cells, examined 10-40 generations after fusion, were found to be electrically excitable. The results show that at least a part of the genetic information for neuron differentiation can be functionally expressed in N x L hybrid cells. Evidence for the regulation of action potential components was also found.
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PMID:Genes for neuronal properties expressed in neuroblastoma x L cell hybrids. 527 95

Ultrastructural features of cytodifferentiation in monolayer cultures of mouse neuroblastoma cells (clone neuro-2A) was further characterized by the presence of annulate lamellar arrays with up to 10 lamellae. The lamellae were made up of fused smooth surfaced cisternae forming pores or annuli and were surrounded by a dense filamentous to granular material. Stacks of nonfenestrated, parallel, regularly spaced cisternae, designated as lamellar bodies, also appeared in the cytoplasm in association with the endoplasmic reticulum and the nucleus. Such flattened cisternae were also seen to be formed from transformed endoplasmic reticulum. Furthermore a relatively large number of concentric whorled lamellar bodies were presented as well as dense whorled structures reminiscent of the cytoplasmic laminar bodies. All of these structures are derived from the rough endoplasmic reticulum, the tubules of which are coexistent with those of the latter. In addition there is a topographic relationship of these bodies with mitochondria and with the nucleus. There is a relative persistence of most of these organelles in old or atropic cells which show marked changes including loss of endoplasmic reticulum. The significance of all of these cytoplasmic inclusions is discussed.
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PMID:Specialized formations of the endoplasmic reticulum in cultures of murine neuroblastoma cells. 626 69


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