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)

In adult mammalian CNS, axons mostly fail to regenerate after injury, while in the PNS they often succeed in reaching their previous targets. Crucial differences are present in the local tissue microenvironment of CNS and PNS. To investigate the substrate properties of nervous tissue for neuronal adhesion and fiber growth, we used frozen sections of rat CNS and PNS as culture substrates for neuroblastoma cells and for sympathetic and dorsal root ganglia. The results showed that CNS white matter from adult rat spinal cord, cerebellum, forebrain, or optic nerve did not allow cell adhesion and axonal elongation. In contrast, gray matter areas, sciatic nerve, and also trout CNS white and gray matter were permissive substrates. To delineate the tissue components of white matter involved in this nonpermissive substrate effect, newborn rats were injected for 13 d with the antimitotic agent 5-azacytidine. This treatment strongly reduced the oligodendrocyte population and the myelin content of the spinal cord. The immunoreactivity for specific oligodendrocyte and astrocyte markers confirmed the selective suppression of oligodendroglia in these rats. Neuroblastoma cells plated on spinal cord sections taken from these animals were no longer exclusively localized on the gray matter but were also found on regions normally rich in myelin. A significant reduction of the white matter nonpermissive substrate effect was also obtained by the monoclonal antibody IN-1 directed against 2 defined myelin proteins with inhibitory substrate properties (Caroni and Schwab, 1988b). Our results, therefore, show that, in the adult mammalian CNS, cell adhesion and axonal elongation are prevented by white matter components, which are, at least in part, associated with oligodendrocytes and myelin.
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PMID:Rat CNS white matter, but not gray matter, is nonpermissive for neuronal cell adhesion and fiber outgrowth. 246 69

We used immunoblot and immunocytochemical methodologies to characterize the appearance and intracellular localization of the high molecular weight neurofilament subunit (NF-H) within the Triton-insoluble cytoskeleton during the first 5 days of differentiation of mouse NB2a/d1 neuroblastoma cells. Hypophosphorylated and partially phosphorylated forms of NF-H were detected in cells before and throughout differentiation. By contrast, some extensively phosphorylated forms of NF-H were first detected on the third day of differentiation and at least one additional 200 kDa isoform was visualized in cytoskeletons only after five days of differentiation. Extensively phosphorylated forms of NF-H were restricted to axonal neurites; by contrast, hypophosphorylated and partially phosphorylated forms of NF-H were present throughout undifferentiated and differentiated cells.
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PMID:Appearance and localization of phosphorylated variants of the high molecular weight neurofilament protein in NB2a/d1 cytoskeletons during differentiation. 251 Sep 55

We have examined the regulation of plasma membrane proteolipid (PM-PLP) synthesis and steady-state levels in mouse NB2a/d1 neuroblastoma cells during differentiation with dibutyryl cyclic AMP (dbcAMP) and retinoic acid (RA), agents which have been previously shown to induce the elaboration of exclusively axonal or dendritic neurites, respectively. We report that a PM-PLP-immunoreactive species is expressed by this neuroblastoma cell line, and that its expression is regulated by specific states of differentiation. Differentiation of cells with dbcAMP was accompanied by an initial 2-fold increase in this PM-PLP immunoreactive species at 24 h after treatment, which returned to control levels by 96 h after treatment. By contrast, no significant increase in synthesis was detected when cells were treated with RA. Protein blot analysis of PM-PLP in dbcAMP-treated cells indicated that there was little change in its steady-state level until 96 h following treatment, at which time a reduction of 40% was observed. Throughout induced differentiation with dbcAMP, NB2a/d1 cells continued to express a PM-PLP-immunoreactive species which comigrated on immunoblot analysis with PM-PLP form characteristic of embryonic brain (14-16 kDa), and apparently did not express the PM-PLP form characteristic of adult brain (18 kDa).
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PMID:Expression of the plasma membrane proteolipid in mouse neuroblastoma cells: transient increase in synthesis during differentiation with N6,O2-dibutyryl adenosine 3',5'-cyclic monophosphate. 255 Feb 93

Glia-derived nexin (GDN), also known as protease nexin I, is a serine protease inhibitor of deduced relative molecular mass 41,700, identified in conditioned media of glioma cells by its neurite-promoting activity. GDN can promote neurite outgrowth in vitro from neuroblastoma cells, sympathetic neurons and hippocampal neurons (L. Farmer et al., manuscript in preparation). In vivo, GDN is constitutively expressed in all parts of the olfactory system, where axonal regeneration and neurogenesis occur continuously throughout life. This observation indicates that GDN could be important for axonal regeneration in vivo. To investigate this possibility, we have taken advantage of the fact that damage to nerves in the peripheral nervous system leads to their regeneration, whereas in the central nervous system no such regeneration can occur. Here we report that after lesion of the rat sciatic nerve there is a large transient increase in the amount of GDN messenger RNA and of released GDN. The cells showing GDN immunoreactivity are mainly localized distal to the lesion site. These results further support the suggestion that GDN is important for axonal regeneration in vivo, and indicate that protease inhibitors could have a role in Wallerian degeneration and peripheral nerve regeneration.
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PMID:Induction of glia-derived nexin after lesion of a peripheral nerve. 268 11

NB2a/dl neuroblastoma cells were exposed to aluminum chloride or aluminum lactate (0.1-1 mM) for 3 and 6 days. Additional cultures were exposed to aluminum salts as the cells were stimulated to elaborate axonal neurites by dibutyryl cyclic AMP. By phase-contrast microscopy, aluminum salts had no effect on the morphology of undifferentiated (NB2a(-] or differentiated (NB2a(+] cells, or on neuritic elaboration and maintenance. Silver straining by the Bielschowsky method, however, demonstrated argyrophilic accumulations in perikarya of many NB2a(-) and NB2a(+) cells treated with aluminum salts. At the ultrastructural level, whorls of intermediate filaments were the most prominent abnormalities in neuronal perikarya. Although phosphorylated high-molecular weight neurofilament subunits (NF-H) are normally detected by immunocytochemical analyses only within axonal neurites of NB2a/dl cells, aluminum salt treatment caused the detection of phosphorylated epitopes of NF-H within perikaryal of NB2a(-) and NB2a(+) cytoskeletons, suggesting that the argyrophilic filamentous accumulations are composed at least partly of phosphorylated NF-H.
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PMID:Aluminum salts induce the accumulation of neurofilaments in perikarya of NB2a/dl neuroblastoma. 275 11

We have characterized the effects of retinoic acid (RA) on the growth, morphology and biosynthesis of cytoskeletal proteins in NB2a mouse neuroblastoma cells. In addition, the morphological and biochemical changes were compared to those induced by dibutyryl cyclic AMP (db cAMP). Growth inhibition by RA was concentration-dependent and was first detected 24 h after addition of RA. The proliferation of RA-treated NB2a was more dependent on serum than was the proliferation of untreated cultures and RA decreased the saturation density of NB2a cells grown in serum. Morphological changes induced by RA include the formation of an elaborate network of branching neurites in NB2a cells. In contrast, neurites induced by db cAMP or serum deprivation were bipolar and unbranching. Ultrastructural observations of neurites induced by RA revealed dendritic characteristics such as polysomes, spines and absence of intermediate filaments, while neurites induced by db cAMP had axonal characteristics such as filament bundles, absence of ribosomes, and the formation of membrane densities when neurite endings contacted another cell body. These morphological differences were also reflected in a number of changes in the biosynthesis of cytoskeletal proteins. These results suggest that NB2a cells treated with RA and db cAMP are a model system for the study of distinct stages of differentiation.
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PMID:Effect of retinoic acid on growth and morphological differentiation of mouse NB2a neuroblastoma cells in culture. 299 50

This paper describes the immunohistochemical staining properties of four monoclonal antibodies (MAbs) (CF, EB, AD, and KB) which had been previously shown to be specific for purified neuron-specific enolase (NSE) by a solid-phase radioimmunoassay. In this study, the authors immunostained a spectrum of normal and neoplastic neuronal, "neuroendocrine," and nonneuronal tissues fixed in formalin and embedded in paraffin. Positivity was generally restricted to normal neuronal structures and neuronal tumors, including adrenal neuroblastoma, ganglioneuroblastoma, olfactory neuroblastoma, pheochromocytoma, carotid body paraganglioma, duodenal gangliocytic paraganglioma, and teratoma with neuroepithelial components. Three staining patterns of the normal or neoplastic neuronal structures were observed: two MAbs (CF and EB) stained predominantly the nerve fibers (axoplasm); one (AD) stained predominantly the cell bodies (perikaryon); and one (KB) stained both the axoplasm and the perikaryon. "Neuroendocrine" tumors such as pulmonary small cell carcinoma, pancreatic islet cell tumor, thyroid medullary carcinoma, and carcinoid tumors from various locations showed a variable staining pattern. Tumor cells undergoing mitotic division were usually positive regardless of type. Normal structures other than neuronal or "neuroendocrine," including normal glial cells, were negative. The authors also studied a range of glial cell tumors with MAbs CF and AD as well as with Dako polyclonal antiserum to NSE. The results showed that CF stained the axonal fibers in the normal white matter surrounding these tumors; it did not stain the tumor cells or the perikarya of neurons in the surrounding normal gray matter. AD stained the glioma cells as well as the perikarya and dendrites of neurons in the surrounding normal gray matter; it did not stain the axonal fibers in the surrounding normal white matter. By contrast, the polyclonal antiserum stained all of these structures. The high degree of staining specificity of the MAbs should prove them to be valuable in immunohistochemical diagnosis of tumors as well as in further understanding the role of NSE in neuronal differentiation.
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PMID:Immunohistochemical characterization of a set of monoclonal antibodies to human neuron-specific enolase. 328 44

We previously reported a positive correlation between the number of cold-stable microtubules (MTs) remaining after cold treatment of cat sympathetic nerve and the extent to which the original uniform polarity orientation of axonal MTs was recapitulated after rewarming (J cell biol 99 (1984) 1289). We interpreted these data to indicate that cold-stable fragments, part of larger, generally labile MTs, could act as seeds to organize MT assembly in axons. We report here a direct investigation of the form of cold-stable MTs in neurites of PC-12 cells using two-dimensional reconstruction of serial thin sections. Our data provides strong support for our previous interpretation. The number of MTs in cold-treated neurites was 2-3 times as great while the total length of polymer was approximately half that in control neurites. The average length of MTs in cold-treated neurites was 7-10 times lower than in control neurites. We observed that treatments that depolymerize axonal microtubules cause a marked increase in the number of membranous elements within the axoplasm. This may, however, be a non-specific result of an insult to the axon, since such changes have also been observed in severed, regenerating nerve fibres. We observed that neuroblastoma neurites respond to MT-depolymerization stimuli by developing lateral filopodia similar to those observed in chick dorsal root ganglion cells. Ultrastructural observation of detergent-lysed, whole mounted neuroblastoma (Neuro 2A) cells indicated that the cytoskeleton remaining after MT depolymerization splayed out perpendicular to the long axis of the neurite. That is, we were able to observe many more cytoskeletal 'ends' after MT depolymerization. The concomitant production of filopodia and the splaying of the cytoskeleton after MT depolymerization supports the hypothesis put forward by Wessels et al. (Exp cell res 117 (1978) 335) that the presence or absence of cytoskeletal ends regulates which region of the cell surface is involved in motile behaviour.
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PMID:The cytoskeleton of neurites after microtubule depolymerization. 394 62

Batrachotoxin has been reported to inhibit fast axonal transport. We have examined the effect of batrachotoxin on saltatory organelle movements in N115 neuroblastoma cells (a model of fast axonal transport) using time-lapse video intensification microscopy. Batrachotoxin (0.1-1.0 microM) inhibits saltatory organelle movement. Contrary to previously published hypotheses, this inhibition of intra-axonal movement depends upon the action of batrachotoxin on action potential Na+ channels. Evidence for this conclusion is: (1) the range of concentrations of batrachotoxin which inhibit saltatory organelle movement is consistent with the dose-response curve for the activation of action potential Na+ channels by batrachotoxin in N18 neuroblastoma cells; (2) tetrodotoxin, which blocks action potential Na+ channels, prevents the inhibition of organelle movements by batrachotoxin; (3) batrachotoxin has no effect on saltatory movement in cells, including some neuroblastoma cell lines, which lack action potential Na+ channels; and (4) in Na+-free or low Na+ media, batrachotoxin does not block organelle movement. We suggest that changes in internal ion concentrations which follow the influx of Na+ are responsible for the inhibition of fast axonal transport by batrachotoxin.
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PMID:Batrachotoxin blocks saltatory organelle movement in electrically excitable neuroblastoma cells. 626 81

A number of neural and nonneural tumor cell lines of rat and human origin were assayed for neuron-specific enolase (NSE) by radioimmunoassay. Most neural tumor cell lines had appreciably higher levels of NSE than did the nonneural tumor cell lines, the highest levels being found in two anaplastic rat glioma lines ( F98 and T24). These two lines contained more than twice the amount of NSE found in a rat pheochromocytoma line (PC12) and in neuroblastoma lines derived from rats ( B35 and B50 ) or humans (IMR-32 and SHSY - 5Y ). Several of the rat glioma and schwannoma lines were inoculated intracerebrally into syngeneic rats. In the resulting tumors, NSE was demonstrable by immunohistochemistry only in those from the F98 and T24 cell lines. A number of ethylnitrosourea-induced rat tumors were also examined immunohistochemically for NSE: NSE was demonstrated in three anaplastic gliomas; three astrocytomas; and two mixed gliomas. Reactive astrocytes were also positive. Fibroadenomas of apocrine and mammary glands in rats were weakly positive, but other extraneural tumors tested were negative. Since normal neuronal elements, axonal swellings, and amine precursor uptake and decarboxylation cells are strongly positive for NSE, whereas glia and most other normal cells are negative, we hypothesize that the elevated metabolic demands imposed on neoplastic and reactive glial cells and on some extraneural tumors necessitate the opening up of metabolic pathways that are normally operative only in neurons and neuroendocrine cells, therefore resulting in the synthesis of the more stable neuron-specific form of enolase.
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PMID:Immunoradiometric and immunohistochemical demonstration of neuron-specific enolase in experimental rat gliomas. 672 96


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