UMLS:C0027819 - FACTA Search

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

The techniques of somatic cell hybridization allow a genetic analysis of differentiated functions of mammalian cells in vitro. Clonal lines of mouse neuroblastoma cells expressing a variety of differentiated neuroectodermal functions have been fused to L cells not expressing these functions. The resulting NL hybirds, on a clonal basis, express a variety of parental and non-parental phenotypes. Some hybrid clones inherit the ability to synthesize the neurotransmitter acetylcholine (Ach) (expression of high levels of choline acetyltransferase, CAT) while others do not. The ability to synthesize Ach and the ability to degrade this neurotransmitter (high levels of acetylcholinesterase activity, AChE) appear to segregate independently in NL hybrid progeny.--When a a variety of clonal cell lines replicating in culture are fused to cells freshly derived from the embryonic nervous system, interesting phenotypes result in the hybrid progeny. Neuroblastoma x rodent nervous tissue hybrids express AChE and in a few instances have developed the ability to synthesize CAT. Transformed human fibroblasts fused to normal rodent nervous tissue yield hybrid progeny that retain human and segregate mouse chromosomes and isozymes. No expression of differentiated functions has yet been found in these latter hybrids but they are useful for mapping mouse genes.
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PMID:Expression of phenotypes in hybrid somatic cells derived from the nervous system. 115 88

Presentation of a series of 14 cases of neural crest derived tumours located in the retroperitoneal space in adult patients (five pheochromocytoma, six paraganglioma, two ganglioneuroma, and one neuroblastoma), and review and update of the diagnostic and therapeutic aspects. All pheochromocytoma cases presented high BP and the classic triad of sudation, tachycardia and headaches, as well as high levels of blood and urine catecholamines and/or their metabolites. CAT, ultrasound scanning and 123MIBG were the main diagnostic techniques used. All four paraganglioma were functioning and generally located surrounding both kidneys (one case was paired). No malignancy was found in any of the 11 tumours while controls remain with normal BP and normal levels of urine catecholamine metabolites. None of the two ganglioneuromas showed specific signs and symptoms but were diagnosed accidentally. The one neuroblastoma was juxtavesical showing a highly unfavourable evolution in spite of radical surgery, radiotherapy and multiple chemotherapy and the patient died within 16 months with local recurrence and haematogenous dissemination to bones and lungs.
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PMID:[Neural crest derived retroperitoneal tumors. General review]. 131 88

The 5'-flanking DNA of the mouse RII beta subunit of the cAMP-dependent protein kinase gene was characterized by transient transfection of RII beta-CAT constructs into mouse neuroblastoma cells (NB2a) and Chinese hamster ovary (CHO) cells and by gel mobility shift and footprinting assays. The minimal promoter of the RII beta gene was composed of two adjacent functional elements. A 3'-element which supported enhanced CAT activity was located between base pairs (bp) -267/-168 from the translation initiation start site. CAT plasmids containing these RII beta sequences showed 12- and 16-fold increased CAT activity in the NB2a and CHO cells, respectively, compared to the basic CAT vector. Plasmids containing 20 additional bp 5' to the -267/-168 fragment showed 2-fold more CAT activity than the shorter fragment in NB2a cells, while CAT activity in CHO cells was nearly the same for both constructs. CAT plasmids containing only this 20-bp fragment showed 9- and 13-fold increased CAT activity in NB2a and CHO cells, respectively. The core promoter of the RII beta gene lacked classical TATA and CAT sequences, but contained 3 copies of the Sp1 core consensus sequence. Gel mobility shift assays using 32P-labeled 5'-flanking DNA containing bp -291/-49 and nuclear extracts from NB2a and CHO cells displayed several retarded bands in the gels suggesting complex formation with nuclear DNA-binding factors. Unlabeled DNA containing bp -291/-49 blocked the appearance of all retarded bands. Competition using an oligonucleotide corresponding to the Sp1 DNA-binding site effectively blocked the appearance of the two more slowly migrating bands but did not affect the major rapidly migrating bands. DNase I footprinting analysis using purified Sp1 protein confirmed that Sp1 could bind to the Sp1 sites. Methylation interference and mutational analysis showed that one of the faster migrating bands was the result of factor binding to the DNA sequence adjacent to the Sp1 sites. Additional tissue-specific nuclear-binding factor sequences were detected upstream of the core promoter. Our data suggest that the core promoter of the RII beta gene can initiate transcription from the DNA around the Sp1 sites but that there are tissue-specific nuclear factor-binding sites located distal to the Sp1 sites.
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PMID:Characterization of a minimal promoter element required for transcription of the mouse type II beta regulatory subunit (RII beta) of cAMP-dependent protein kinase. 133 64

The human neuroblastoma cell line IMR-32 exhibits both cholinergic and adrenergic properties. We have used IMR-32 cells to study the effects of CDF (CAT development factor) and bFGF (basic fibroblast growth factor) on the development of neurotransmitter properties. CDF treatment increases CAT activity in a dose-dependent manner, independent of cell density. Time course studies show that there is a threefold increase in the specific CAT activity in IMR-32 cells treated with CDF for 6 d. CDF does not, however, affect the level of tyrosine hydroxylase (TH) activity, or the rate of cell proliferation. bFGF, on the other hand, induces TH activity and decreases CAT activity in a dose-dependent manner. bFGF's effect on TH is enhanced by increasing cell density, while its reduction of specific CAT activity is independent of cell density. Time course studies show a 30-fold increase in TH activity per cell and a threefold decrease in CAT activity per cell, after treatment with bFGF for 6 d. In contrast to the effects of CDF, bFGF enhances cell proliferation in IMR-32 cells. Double-labeled immunofluorescence studies showed that 95% of the cells stain for CAT and 65% stain for TH following treatment with CDF and bFGF, respectively. When these factors are combined, approximately 75% of the cells express both CAT and TH, demonstrating that IMR-32 cells are bipotential with regard to neurotransmitter-associated enzyme expression. We also show that insulin-like growth factor I and NGF selectively induce CAT activity and cell proliferation, respectively, whereas epidermal growth factor has no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of neurotrophic factors on neurotransmitter development in the IMR-32 human neuroblastoma cell line. 134 44

To investigate the regulatory processes involved in the expression of the D2 dopamine receptor gene, a rat genomic clone was isolated using a 21-mer oligonucleotide probe made of exon 1 sequences. A 1.3-kb region including all of exon 1, its 5'-flanking region, and part of intron 1 was sequenced. S1 nuclease analysis indicated three consecutive nucleotides as the main transcription start sites; several weaker sites were also noted between 321 and 363 nucleotides upstream from the 3' end of exon 1. The promoter region lacks TATA and CAAT boxes and is rich in G+C content with several putative Sp1 binding sites. Transient expression assays using chimeric constructs of D2 promoter deletion mutants-chloramphenicol acetyl-transferase gene in the neuroblastoma cell line NB41A3 which expresses D2 binding sites indicated strong transcription enhancing activity between nucleotides -75 and -30 and silencing activity between nucleotides -217 and -76. DNase I footprinting studies using nuclear extract from NB41A3 suggested Sp1 binding to its consensus sequence at nucleotide -48 but inhibition of Sp1 binding at nucleotide -86 by the extract. The D2 promoter could not induce transcription of the heterologous CAT gene in C6 glioma, embryonal NIH 3T3, or hepatic Hep G2 cells. It is concluded that the rat D2 gene shares with the human D1A dopamine receptor gene several features typical of "housekeeping" genes but they are both tissue-specific, regulated genes. Unlike the D1A gene, however, the D2 gene has a strong preference for transcription initiation to three consecutive nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of the promoter region of the rat D2 dopamine receptor gene. 139 Jun 23

Genomic and cDNA clones encoding the rat D1 receptor were isolated and sequenced. Comparison of the D1 receptor cDNA and genomic sequences revealed that the rat D1 receptor gene is organized into two exons separated by a small intron in the 5' untranslated region of its mRNA. The transcription start site is located 864 bp upstream from the translational initiation site. The 5'-flanking sequences of the D1 receptor gene do not contain TATA and CAAT canonical sequences, but have a high G+C content, potential cyclic AMP and glucocorticoid response element sequences, and binding sites for transcription factors such as Sp1, Ap1, and Ap2. Transfection studies using the D1 5'-flanking sequence and CAT gene fusion constructs have demonstrated that (1) the D1 promoter is active in D1-expressing neuroblastoma NS20Y cells, but inactive in D1-deficient glioma C6 and kidney 293 cells, (2) the information contained within 735 bp of 5'-flanking sequence of the D1 gene appears to be sufficient to confer its cell-specific expression, and (3) the D1 gene promoter responds to cyclic AMP induction, suggesting the existence of an auto-regulation mechanism by which the stimulation of D1 receptor exerts a positive feedback on its own gene expression.
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PMID:Characterization of gene organization and promoter region of the rat dopamine D1 receptor gene. 140 30

Brain-derived neurotrophic factor (BDNF) has recently been shown to enhance the survival of dopamine neurons in cultures derived from the embryonic rat mesencephalon. We now extend this study by demonstrating that, in addition to the effect of sustaining survival of dopaminergic neurons, BDNF also confers protection against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenylpyridinium ion (MPP+). Exposure of mesencephalic cultures to either 6-OHDA or MPP+ resulted in a loss of 70-80% of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunocytochemistry. In BDNF-treated cultures, loss of TH-positive cells after exposure to either toxin was reduced to only 30%. To facilitate biochemical measurements, we studied SH-SY5Y dopaminergic neuroblastoma cells. BDNF was found to protect these cells from the dopaminergic neurotoxins, 6-OHDA and MPP+. Indicative of oxidative stress, treatment of SH-SY5Y cells with 10 microM 6-OHDA for 24 h caused a fivefold increase in the levels of oxidized glutathione (GSSG). Pretreatment with BDNF for 24 h completely prevented the rise in GSSG. Further examination revealed that BDNF increased the activity of the protective enzyme, glutathione reductase, by 100%. In contrast, BDNF had no effect on the activity of catalase. These results add further impetus to exploring the therapeutic potential of BDNF in animal models of Parkinson's disease.
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PMID:Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenylpyridinium ion toxicity: involvement of the glutathione system. 845 44

This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase.
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PMID:N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells. 167 45

The cytotoxicity of dopamine (DA) and 6-hydroxydopamine (6-OHDA) on living cells, in vitro, has been previously deeply investigated in neuroblastoma cells. This study was designed to explore the possibility to use bacteria as targets for studying DA and 6-HODA cytotoxicity. Both DA and 6-HODA oxidize when added to bacteriological media. The rate of autoxidation of 6-HODA was greater than DA within the first hours. The oxidation-dependent cytotoxicity caused bacterial growth-inhibition and killing at concentration of 10(-4)M. All the bacterial strains tested were slightly more susceptible to DA than to 6-HODA. Antioxidants (sodium metabisulfite, cysteine) prevented the oxidation and abolished the growth-inhibitory activity. The addition of exogenous catalase protected the cells against the effect of the oxidation of both the catecholamines up to the concentration of 5 mM, while the addition of exogenous superoxide dismutase protected the cells only at the minimal inhibitory concentrations. Taking into account that some of the results obtained are similar to those previously reported using neuroblastoma cells as targets, the use of bacteria for studying oxygen toxicity from these catecholamines seems to be a potentially useful model system.
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PMID:An in vitro bacterial model of cytotoxicity to living cells caused by dopamine and 6-hydroxydopamine oxidation at physiological pH. 190 28

We have isolated a rat cDNA, named FE65, hybridizing to an mRNA of about 2,300 nucleotides present in rat brain, undetectable in rat liver and very poorly represented in other tissues. An mRNA of the same size is present in human neuroblastoma cells and is absent from other human cell lines. The FE65 cDNA contains an open reading frame (ORF) coding for a polypeptide of 499 amino acids in which 143 residues can be aligned with the DNA binding domain of the integrases encoded by mammalian immunodeficiency viruses. The remaining part of the FE65 ORF is not homologous with the correspondent regions of the integrases; the first 206 residues of the FE65 ORF show numerous negative charges and a short sequence not dispensable for the function of the transactivating acidic domain of the jun family transcriptional factors. A plasmid which expresses FE65 amino acids 1-232 fused to the yeast GAL4 DNA binding domain was co-transfected with a plasmid containing five GAL4 binding sites upstream of a minimal Adenovirus promoter controlling the expression of the CAT gene. This experiment showed that the fused protein GAL4-FE65 is able to obtain a 30-40 fold increase of the CAT gene expression compared to the expression observed in the presence of the GAL4 DNA binding domain alone. Two types of FE65 mRNA are present in rat brain, differing only for six nucleotides. We demonstrate that this is the consequence of a neuron-specific alternative splicing of a six-nucleotide miniexon, which is also present in the human genome, in an intron/exon context very similar to that of the rat FE65 gene.
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PMID:A rat brain mRNA encoding a transcriptional activator homologous to the DNA binding domain of retroviral integrases. 192 10

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