Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies were raised against a cytoskeleton-associated, nonphosphorylated, 230,000-dalton bovine lens polypeptide (designated p230), and rendered monospecific by using a novel immunoaffinity technique. In immunofluorescence and electron microscopy of cultured fibroblasts, as well as of various other cells (endothelial, epithelial, lenticular, monocytes, neuroblastoma cells) and tissues (human kidney and liver), p230 was localized as a distinct subplasmalemmal layer in the peripheral cytoplasm of the cells. It constituted less than 0.3% of the total cellular protein in cultured fibroblasts and was not extractable with Triton X-100. In detergent-extracted cytoskeletal preparations of cultured fibroblasts, p230 remained as an elaborate peripheral network that showed a distribution distinctly different from that of the major cytoskeletal structures, stress fibers, cortical myosin, vinculin, and intermediate filaments (IF). The distribution was not dependent on the presence of intact stress fibers or microtubules, as shown by double-fluorescence microscopy of cells exposed to cytochalasin B or cultured in the presence of monensin and of cold-treated cells. Upon demecolcine-induced reorganization of intermediate filaments, however, the localization of p230 was rapidly altered to a dense plaque underneath the perinuclear aggregate of intermediate filaments. On the other hand, p230 seemed to colocalize with the detergent-resistant cell surface lamina, visualized in fluorescence microscopy with fluorochrome-coupled wheat germ agglutinin-lectin. The results suggest that p230 is part of a cell surface- and cytoskeleton-associated subplasmalemmal structure that may play an important role in cell surface-cytoskeleton interaction in various cells both in vitro and in vivo.
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PMID:Immunolocalization of a novel, cytoskeleton-associated polypeptide of Mr 230,000 daltons (p230). 633 21

A retrospective examination of the bone scans of 425 pediatric oncology patients was undertaken to determine the incidence of photon-deficient (cold) lesions in this population. Eight patients (1.8%) had cold lesions due to a wide variety of tumors. Of the tumor types, six had not been previously reported to give cold lesions on bone scan. The appearance of the radiograph at the site of the cold lesion was normal in five of the eight patients. All but one of the patients had "hot spots" as well as a cold lesion. Follow-up scans showed resolution of the cold lesions in two cases and a change from cold to hot in one case. A review of the literature revealed eight cases of cold lesions on bone scan due to tumor in pediatric patients. The previous reports included five patients with neuroblastoma and three with osteosarcoma.
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PMID:Cold lesions on bone scan in pediatric neoplasms. 670 10

[131I]metaiodobenzylguanidine ([131I]MIBG) is selectively taken up and stored by tumours derived from the neural crest, and is used for diagnosis and treatment of neuroblastoma (NB). The antitumoral effect of [131I]MIBG is closely related to the intracellular level of the radiopharmaceutical compound, which is dependent on uptake and storage/release mechanisms. While MIBG uptake is well characterised, storage and release mechanisms are still controversial. In order to better characterise [125I]MIBG release mechanisms, we studied the basal and stimulated efflux of [125I]MIBG in the human NB cell line, SH-SY5Y, preloaded with 0.1 microM [125I]MIBG for 1 h. We found that [125I]MIBG basal efflux is highly temperature-dependent, that [125I]MIBG release, induced by cell depolarisation with high potassium, is mainly calcium-independent, and induced by exchange with cold MIBG or noradrenaline, inversion of the sodium gradient across the cell membrane by veratridine by substitution of sodium chloride with equimolar concentration of lithium chloride. The exposure of NB cells to imipramine, an Uptake-1 inhibitor, also produces a net stimulatory effect on [125I]MIBG release. However, when used in association with other releasing stimuli, such as higher levels of intracellular sodium or external agonists, imipramine abolishes the consequent increase of [125I]MIBG release. Our findings suggest that stimulated [125I]MIBG release is mediated by a carrier, most probably the uptake carrier working in a reverse mode, while a minimal fraction of [125I]MIBG is released by an exocytotic mechanism.
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PMID:Release mechanisms of [125I]meta-iodobenzylguanidine in neuroblastoma cells: evidence of a carrier-mediated efflux. 757 75

1. [3H]-lifarizine bound saturably and reversibly to an apparently homogeneous class of high affinity sites in rat cerebrocortical membranes (Kd = 10.7 +/- 2.9 nM; Bmax = 5.10 +/- 1.43 pmol mg-1 protein). 2. The binding of [3H]-lifarizine was unaffected by sodium channel toxins binding to site 1 (tetrodotoxin), site 3 (alpha-scorpion venom) or site 5 (brevetoxin), Furthermore, lifarizine at concentrations up to 10 microM had no effect on [3H]-saxitoxin (STX) binding to toxin site 1. Lifarizine displaced [3H]-batrachotoxinin-A 20-alpha-benzoate (BTX) binding with moderate affinity (pIC50 7.31 +/- 0.24) indicating an interaction with toxin site 2. However, lifarizine accelerated the dissociation of [3H]-BTX and decreased both the affinity and density of sites labelled by [3H]-BTX, suggesting an allosteric interaction with toxin site 2. 3. The binding of [3H]-lifarizine was voltage-sensitive, binding to membranes with higher affinity than to synaptosomes (pIC50 for cold lifarizine = 7.99 +/- 0.09 in membranes and 6.68 +/- 0.14 in synaptosomes). Depolarization of synaptosomes with 130 mM KCl increased the affinity of lifarizine almost 10 fold (pIC50 = 7.86 +/- 0.25). This suggests that lifarizine binds selectively to inactivated sodium channels which predominate both in the membrane preparation and in the depolarized synaptosomal preparation. 4. There was negligible [3H]-lifarizine and [3H]-BTX binding to solubilized sodium channels, although [3H]-STX binding was retained under these conditions. 5. The potencies of a series of compounds in displacing [3H]-lifarizine from rat cerebrocortical membranes correlated well with their affinities for inactivated sodium channels estimated from whole-cell voltage clamp studies in the mouse neuroblastoma cell line, NIE-115 (r=0.96).6. These results show that [3H]-lifarizine is a high affinity ligand for neuronal sodium channels which potently and selectively labels a site, allosterically linked to toxin binding site 2, associated within activated sodium channels.
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PMID:[3H]-lifarizine, a high affinity probe for inactivated sodium channels. 758 9

Ten different mouse cell lines were examined for Japanese encephalitis virus (JEV) infection in vitro and then tested for their ability to generate virus specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro 2a (a neuroblastoma) was readily infected with JEV as examined by immunofluorescence and viral replication. Among other cells, P388D1, RAW 264.7 (Macrophage origin), Sp2/0 (B-cell Hybridoma), YAC-1 (T-cell lymphoma), and L929 (Fibroblast) were semipermissive to JEV infection. The cytopathic effects caused by progressive JEV infection varied from cell line to cell line. In the case of YAC-1 cells long-term viral antigen expression was observed without significant alterations in cell viability. Intermediate degrees of cytopathicity are seen in RAW 264.7 and L929 cells while infection of PS, Neuro 2a, P388D1 and Sp2/0 caused major viability losses. All infected cell lines were able to prime adult BALB/c (H-2d) mice for the generation of secondary JEV specific CTL. In contrast to YAC-1, the permissive neuroblastoma cell line Neuro 2a (H-2KkDd) was found to be least efficient in its ability to stimulate anti-viral CTL generation. Cold target competition studies demonstrated that both Neuro 2a and YAC-1 (H-2KkDd) cells expressed similar viral determinants that are recognised by CTL, suggesting that the reason for the lower ability of Neuro 2a to stimulate anti-viral CTL was not due to lack of viral CTL determinants. These findings demonstrate that a variety of mouse cell lines can be infected with Japanese encephalitis virus, and that these infected cells could be utilised to generate virus specific CTL in BALB/c mice.
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PMID:Japanese encephalitis virus infection of mouse cell lines: ability to prime mice for generation of virus specific cytotoxic T lymphocytes and differences in CTL recognisable viral determinants. 764 37

Several H-2 defined cell lines were examined for their ability to support infection and replication of Japanese encephalitis virus (JEV) before their use in in vitro and in vivo stimulation protocols for generating cytotoxic T lymphocytes (CTLs) against JEV. Among 11 different cell lines tested, two H-2d macrophage tumour lines (P388D1, RAW 264.7), an H-2d hybridoma (Sp2/0), an H-2KkDd neuroblastoma (Neuro 2a), and H-2k fibroblast cell line (L929) were found to support JEV infection and replication. These cell lines were used to generate anti-JEV CTLs by using in vivo immunization followed by in vitro stimulation of BALB/c mice. We observed that not only syngeneic and allogeneic infected cells but also JEV-infected xenogeneic cells could prime BALB/c mice for the generation of JEV-specific CTLs upon subsequent in vitro stimulation of splenocytes with JEV-infected syngeneic cells. Although infected xenogeneic cells were used for immunization, the anti-JEV effectors that were generated lysed infected syngeneic targets but not JEV-infected xenogeneic or allogeneic target cells in a 5 h 51Cr release assay. These anti-JEV effectors recognized syngeneic target cells infected with West Nile virus to a lesser extent and were shown to be Lyt-2.2+ T cells. The results of unlabelled cold target competition studies suggested alterations in the cell surface expression of viral antigenic determinants recognized by these CTLs. We further demonstrate that the JEV-specific CTLs generated could virtually block the release of infectious virus particles from infected P388D1 and Neuro 2a cells in vitro.
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PMID:Cytotoxic T lymphocytes raised against Japanese encephalitis virus: effector cell phenotype, target specificity and in vitro virus clearance. 815 Dec 96

1. Most neurotransmitters are inactivated by uptake into presynaptic nerve terminals and into glial cells. We recently provided evidence for uptake of amines in postsynaptic neurones. Uptake was evident at nanomolar concentrations of prazosin, but at concentrations of unlabelled prazosin greater than 10(-7) M, there was a further activation of uptake, manifested by a paradoxical increase in accumulation of the radioligand. We have now studied further characteristics of amine uptake in immortalised gonadotrophin-releasing hormone (GnRH) neurones. Control cells included SK-N-SH neuroblastoma cells (which possess presynaptic type amine transporters) and non-neuronal (COS-7) cells. 2. [3H]-prazosin bound to intact GnRH cells and was displaced by unlabelled prazosin in concentrations of 10(-9) to 10(-7) M. However, at higher concentrations of unlabelled prazosin, there was an increase in apparent [3H]-prazosin binding, as we had previously described. This paradoxical increase in accumulation of the radioligand was abolished by desipramine. 3. Desipramine had no effect on the association of prazosin with COS-7 cells. There was no paradoxical increase in accumulation of [3H]-prazosin in COS-7 cells, indicating that this effect requires the presence of a desipramine-blockable uptake process. 4. The increase in binding of the radioligand that was observed in the GnRH cells is not a general property of neuronal transporters; in SK-N-SH cells, there was no increase in accumulation of (-)-[3H]-noradrenaline in the presence of concentrations of unlabelled (-)-noradrenaline greater than 10(-7) M. 5. The uptake of prazosin and the increase in accumulation of [3H]-prazosin were abolished in the cold, indicating that this is an active, energy-requiring process. 6. Desipramine-sensitive uptake of prazosin was demonstrable in the GnRH cells in the absence of sodium. Further, the Na+/K(+)-ATPase inhibitor, vanadate, abolished noradrenaline uptake in SK-N-SH cells but had no effect on prazosin uptake in GnRH cells. Thus, the uptake of prazosin does not derive its energy from the sodium pump. 7. Prazosin uptake was inhibited by the V-ATPase inhibitor bafilomycin A1, the H+/Na+ ionophore, monensin and the organic base, chloroquine, indicating that uptake derives its energy from a proton pump. In contrast to other proton-dependent amine transporters, the uptake of prazosin was unaffected by reserpine. 8. Increasing extracellular pH did not increase the uptake of prazosin into GnRH cells, indicating that it is unlikely to be due to non-specific diffusion and concentration of a lysosomotropic drug into intracellular acidic particles. 9. The uptake of prazosin was unaffected by steroid hormones. 10. In COS-7 cells transfected with alpha 1-adrenoceptor cDNA, [3H]-prazosin was displaced by unlabelled prazosin without causing an increase in binding of the radioligand. This indicated that the increase in accumulation of the radioligand is unlikely to be due simply to some function of alpha 1-adrenoceptors. 11. Thus, peptidergic neurones possess an uptake process with properties that are distinguishable from known amine transporters.
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PMID:Functional properties of the uptake of amines in immortalised peptidergic neurones (transport-P). 882 51

There is growing evidence that cytoskeletal instability of neuronal cells is an important step towards tangle formation and subsequent functional disconnection in the AD brain. Sabeluzole, a new drug in clinical trials for Alzheimer's disease (AD), has been shown to slow down the clinical progression of the disease. In a search for the mechanism of action of this compound, the effect of sabeluzole on the neuronal cytoskeleton was investigated. Previous studies have shown that in human TR14 neuroblastoma cells and in rat hippocampal neurons a hyperstimulating medium of kinase activators leads to induction of aberrant tau phosphorylation followed by neurotoxicity. This report documents the attenuation of this neurotoxicity by sabeluzole. By selective permeabilization procedures and quantitative immunocytochemistry we show that the compound is found to preferentially increase the fraction of polymerized tubulin. Evidence is presented that the compound differentially modulates a nocodazole-induced depolymerization in contrast to a cold-induced depolymerization. In the mouse, N4 neuroblastoma cells sabeluzole decreases the spontaneous retraction frequency of neurites and lowers the lateral mobility of the cells. We, therefore, propose that sabeluzole exerts its neuroprotective effect by a stabilization of the neuronal cytoskeleton and that this mechanism provides a completely new approach for treatment in Alzheimer's disease.
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PMID:Sabeluzole stabilizes the neuronal cytoskeleton. 883 32

Results of transgenetic studies argue that the scrapie isoform of the prion protein (PrPSc) interacts with the substrate cellular PrP (PrPC) during conversion into nascent PrPSc. While PrPSc appears to accumulate primarily in lysosomes, caveolae-like domains (CLDs) have been suggested to be the site where PrPC is converted into PrPSc. We report herein that CLDs isolated from scrapie-infected neuroblastoma (ScN2a) cells contain PrPC and PrPSc. After lysis of ScN2a cells in ice-cold Triton X-100, both PrP isoforms and an N-terminally truncated form of PrPC (PrPC-II) were found concentrated in detergent-insoluble complexes resembling CLDs that were isolated by flotation in sucrose gradients. Similar results were obtained when CLDs were purified from plasma membranes by sonication and gradient centrifugation; with this procedure no detergents are used, which minimizes artifacts that might arise from redistribution of proteins among subcellular fractions. The caveolar markers ganglioside GM1 and H-ras were found concentrated in the CLD fractions. When plasma membrane proteins were labeled with the impermeant reagent sulfo-N-hydroxysuccinimide-biotin, both PrPC and PrPSc were found biotinylated in CLD fractions. Similar results on the colocalization of PrPC and PrPSc were obtained when CLDs were isolated from Syrian hamster brains. Our findings demonstrate that both PrPC and PrPSc are present in CLDs and, thus, support the hypothesis that the PrPSc formation occurs within this subcellular compartment.
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PMID:Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. 896 61

Neuronal hybrid cells established by somatic cell fusion are useful for studies of neuronal properties at the molecular level (Hammond, D.N., Lee, H.J., Tonsgard, J.H. and Wainer, B.H., Development and characterization of clonal cell lines derived from septal cholinergic neurons, Brain Res., 512 (1990) 190-200; Wainwright, M.S., Perry, B.D., Won, L.A., O'Malley, K.L., Wang, W.Y., Ehrlich, M.E. and Heller, A., Immortalized murine strial neuronal cell lines expressing dopamine receptors and cholinergic properties, J. Neurosci., 15 (1995) 676-688). The somatic cell fusion method requires a fusion partner which is unable to survive in the selection medium if it does not fuse with primary cells to isolate the hybrid cells. Hypoxanthine guanine phosphoribosyltransferase (HPRT)-deficient partner cells and hypoxanthine, aminopterin and thymidine (HAT) selection medium are commonly used for this procedure (Harlow, E. and Lane, D. (Eds.), Antibodies: a Laboratory Manual, Cold Spring Harbor Laboratory Publications, New York, 1988, pp. 139-243). The present method requires neither HPRT-deficient cells nor HAT medium. Primary neurons are fused with the C1300 neuroblastoma cells pretreated with emetine (Grollman, A.P., Inhibitors of protein biosynthesis, J. Biol. Chem., 243 (1968) 4089-4094), an inhibitor of ribosomes and actinomycin D (Perry, R.P., Selective effects of actinomycin D on the intracellular distribution of RNA synthesis in tissue culture cells, Exp. Cell Res., 29 (1963) 400-406), an inhibitor of ribosomal RNA (rRNA) synthesis, before fusion. By this treatment, we are able to isolate hybrid cells after fusion because non-fused C1300 cells die due to the loss of active ribosomes and protein synthesis, whereas C1300 cells fusing with primary cells survive due to the supply of intact ribosomes and rRNA from primary cells. This method produces neuronal hybrids at high efficiency.
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PMID:Method for production of neuronal hybridoma using emetine and actinomycin D. 938 57


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