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)

Serums from six patients with progressive idiopathic acute or chronic polyneuropathy possessed a cytolytic activity against transformed mouse cholinergic or noncholinergic neuroblasts but not against transformed rat astrocytes. This activity was not qualitatively nor quantitatively present in serums from normal controls or from patients with a variety of other motor system disorders and other neurologic disorders. Fluorescein conjugated goat antihuman IgG and IgM monospecific immunoglubulins were used to characterize further the cytotoxic activity from patient serums and these studies suggested the presence of immunoglobulin G (IgG) and immunoglobulin M (IgM) directed against a cell surface neuroblastoma antigen. Cold reactive immunoglobulins of the IgG and IgM type were present in the serums of all six patients. A bioassay is described that may be helpful in evaluating other patients with progressive idiopathic polyneuropathies.
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PMID:Idiopathic polyneuropathy associated with cytotoxic anti-neuroblastoma serum. IgG and IgM immunoglobulin studies. 123 54

On the 4th day of acyclovir treatment for Herpes simplex pneumonia, a 28 month-old girl who had received allogenic marrow transplant for stage IV neuroblastoma presented with severe neurologic disorders including coma and choreic movements. These symptoms disappeared 9 days after acyclovir was stopped. The disturbance in acyclovir kinetics because of acute renal failure and/or a cerebral cortex atrophy might explain the poor neurologic tolerance of acyclovir. This reversible neurologic involvement on a prone patient should be known as a differential diagnosis of Herpes simplex encephalitis.
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PMID:[Neurologic effects of acyclovir after an allogenic marrow graft]. 284 39

Mouse glial and neuroblastoma cells were infected with the mouse adapted strains C506 and 139A of scrapie agent. Lysates of the in vitro infected cells (from the 3rd to the 16th passage) intracerebrally inoculated into CD-1 mice, caused the development of a neurological disease, with characteristic signs of scrapie. Morphological changes in scrapie-infected neural cells were observed after about fifteen in vitro passages. In liquid medium, the cloning efficiency of these cells increased. They acquired the capacity to form large tridimensional colonies in agar. Heating the infectious brain extracts at 60 and 80 degrees C for 30 minutes did not inhibit these changes thus showing the involvement of the thermoresistant scrapie agent. Supernatants of scrapie-infected glial cells promoted colony formation in liquid medium with different types of normal cells. Analysis of supernatants of scrapie-infected mouse neuroblastoma cells showed a profound modification of neurotransmitter metabolism.
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PMID:Effects of in vitro infection of mouse glial and neuroblastoma cells with the scrapie agent. 392 69

Borna disease is a rare but severe neurological disease of horses and sheep. Borna disease virus (BDV) has not been fully characterized because cell-free virus has not been isolated. Homogenates of infected brain are infectious both for animals and for some cell lines in culture. We report here the partial purification and characterization of cell-free BDV from the tissue culture supernatant of infected human neuroblastoma SKNSH cells. A single negative strand 10-kb RNA was detected in purified virions. Immunoprecipitation analysis of the BDV proteins in purified virions shows the presence of the 60-, 38-, 24-, and 14-kDa proteins previously identified as BDV-specific proteins in infected cells.
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PMID:Partial purification and characterization of Borna disease virions released from infected neuroblastoma cells. 818 47

Calcium channel antagonists are drugs currently used in the treatment of neurological and cardiovascular disorders and occasionally produce parkinsonism and movement disorders as a side effect. We investigated the effects of calcium channel antagonists on the pharmacology of dopamine systems in vivo and in vitro. Flunarizine, cinnarizine, and diltiazem reduce the viability of dopamine-rich human neuroblastoma cells in vitro. These compounds plus verapamil, nifedipine, and nicardipine reduce 3H-spiperone binding to bovine striatal membranes, 3H-dopamine uptake, K(+)-induced 3H-dopamine release, and apomorphine-induced rotation, but not amphetamine-induced rotation, in 6-OH-dopamine-lesioned rats. Therefore, all calcium channel antagonists tested reduce dopamine neurotransmission in vitro and in vivo, whereas the evidence of toxicity for dopamine cells in vitro is restricted to flunarizine, cinnarizine, and diltiazem. The clinical relevance of these toxic effects may depend on several factors, including age, penetration across the blood-brain barrier, and types of calcium channels present in the different neuronal subtypes. On the other hand, the finding of dopamine-regulating properties not associated to neurotoxic effects in the dihydropyridines and verapamil provides new putative therapeutics tools for the treatment of neurologic disorders associated with dopamine hyperactivity.
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PMID:Effects of calcium antagonists on the dopamine system. 866 55

Serum neuron-specific enolase (NSE) levels were studied by an enzymo-immunoassay method in 2 groups of patients: a group of epileptic patients, and a group of patients with refractory major depression after electroconvulsive therapy (ECT). In patients without organic neurological disease (n = 274) the mean serum NSE level (+/- S.D.) was 8.4 +/- 3.4 micrograms/l. No correlation with sex or age was observed. No significant difference was observed between epileptic patients without seizure or major electroencephalogram (EEG) abnormality, and a reference group. Significant increases were observed in 32 samples collected from patients with interictal EEG without spikes and waves before the 7th day after a seizure, in whom mean NSE was 21.5 +/- 9.4 micrograms/l, and in 26 samples from 4 patients without seizures but with spikes and waves in the interictal EEG, whose mean NSE was 20.6 +/- 11.5 micrograms/l. The increases of serum NSE levels in epileptic patients seem therefore to be linked to seizures and/or to EEG abnormalities. The consequences of these observations for the survey of epileptic patients, and for the diagnosis of cerebral tumors (mainly neuroblastoma) or for monitoring treatment after surgical resection, are discussed. In only 1 patient out of 6, an increase in serum NSE levels was observed with a peak about 12 h after ECT. No significant correlation with the ECT features (length of seizures, one- or two-sided electrodes) was observed.
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PMID:Increased serum levels of neuron-specific enolase in epileptic patients and after electroconvulsive therapy--a preliminary report. 871 37

Cysteine (CYS) is a non-essential amino acid which elicits excitotoxic properties via the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. CYS levels are known to be elevated in association with neurological disease such as Alzheimers Disease (AD) and Parkinsons Disease (PD). We have previously reported studies investigating the toxicity of CYS and its major metabolite cysteinesulfinic acid (CSA) to human neuronal cell lines in vitro and in continuation of this we now report the toxicity of other compounds (Homocysteic Acid, HCA; Homocysteine, HCYS; and Cysteic Acid, CA) in the CYS metabolic pathway. Three cell lines, all of human origin and derived from separate discrete areas of the brain were used in the neurotoxicity assays. Lactate dehydrogenase (LDH) release was assayed as a measure of cell death. The cell lines investigated showed varying degrees of toxic responses which were the reverse of those seen when they were exposed to CYS or CSA. The SK.N.SH (Neuroblastoma) cell line, which exhibits a high toxic response to CYS and CSA, gave a low toxic response to HCA and CA while the TE 671 (Medulloblastoma) cell line, which exhibits a low toxic response to CYS and CSA, showed a high toxic response to HCYS, HCA and CA. However, the U-87 MG (Glioblastoma) cell line, which has a median toxic response to CYS and CSA, also has median response to HCYS, HCA and CA. These results show that toxic responses are cell-type specific for CYS and its metabolites and this may be reflected in the patterns of neurodegeneration observed in such diseases as AD and PD. HCYS is selectively toxic to medulloblastoma cells; this may explain why high HCYS levels result in neural tube defects in prenatal humans, where the same cell-type is involved.
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PMID:In vitro effect of the cysteine metabolites homocysteic acid, homocysteine and cysteic acid upon human neuronal cell lines. 974 17

Some patients with small cell lung cancer (SCLC) or neuroblastoma develop an immune response against HuD, a human homologue of the Drosophila protein, elav, which is expressed in the nucleus and to a lesser degree the cytoplasm of neurons and tumor cells. This immune response is characterized by antibodies (anti-Hu) that at high titers are associated with a disease called paraneoplastic encephalomyelitis/sensory neuronopathy, in which infiltrates of T cells are found in the tumor and nervous system. Although all SCLCs express HuD, anti-Hu antibodies are identified in only 17% of patients with SCLC, usually at low titers, and are associated with indolent tumor growth. To determine whether the anti-Hu immune response causes indolent tumor growth, we developed an animal model using HuD DNA immunization. We found that a plasmid coding for a secreted form of HuD induced a strong and specific anti-Hu response. Immunized animals were challenged by s.c. implantation of a neuroblastoma cell line that constitutively expresses HuD. When compared with controls, mice immunized with the secreted HuD showed significant tumor growth inhibition (51% reduction volume; P = 0.0012), and 14% of them had complete tumor rejection. Tumors from these animals showed three times more CD3+ lymphocytic infiltrates than those from control mice and had a higher CD8+:CD4+ ratio. None of the animals developed neurological deficits or neuropathological evidence of nervous system pathology. In this mouse model of neuroblastoma, DNA immunization with HuD resulted in tumor growth inhibition but did not induce neurological disease. This model closely mimics the clinical course of more indolent tumor growth seen in patients with the anti-Hu immune response.
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PMID:DNA vaccination with HuD inhibits growth of a neuroblastoma in mice. 982 48

Rat synaptotagmin IV (SYT IV) is a depolarization-inducible synaptic vesicle protein. SYT IV homozygous mutant mice are viable and have deficits in fine motor coordination and some forms of memory. In this study, we report the identification of a human SYT IV orthologue. The predicted amino acid sequence of the human SYT IV clone is nearly 90% identical to the rat and mouse SYT IV proteins. In addition, human SYT IV has a characteristic serine for aspartate substitution within the first C2 domain that is conserved among Drosophila, Caenorhabditis elegans, mouse, and rat SYT IV sequences. The human SYT IV gene maps to chromosome band 18q12.3, a region that defines a break point in the synteny with mouse chromosome 18 and has been implicated by associated markers in two human psychiatric disorders. In the human neuroblastoma cell line SK-N-SH, SYT IV is an immediate-early gene inducible by elevated intracellular calcium and by forskolin, an activator of adenylyl cyclase. Expression of human SYT IV mRNA is restricted to brain and is not detectable in non-neuronal tissues. Within brain, human SYT IV mRNA is most highly expressed in hippocampus, with lower levels present in amygdala and thalamus. These results suggest a role for SYT IV in human brain function and in human neurological disease.
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PMID:The human synaptotagmin IV gene defines an evolutionary break point between syntenic mouse and human chromosome regions but retains ligand inducibility and tissue specificity. 1093 84

The KCNQ family of K(+) channels has been implicated in several cardiac and neurological disease pathologies. KCNQ2 (Q2) is a brain-derived gene, which in association with KCNQ3 (Q3) has been shown to provide a molecular basis for the neuronal M current. We have cloned a long (Q2L) and a short (Q2S) splice variant of the human KCNQ2 gene; these variants differ in their C-terminal tail. Northern blot analysis reveals that Q2L is preferentially expressed in differentiated neurons, whereas the Q2S transcript is prominent in fetal brain, undifferentiated neuroblastoma cells, and brain tumors. Q2L, transfected into mammalian cells, produces a slowly activating, noninactivating voltage-gated K(+) current that is blocked potently by tetraethylammonium (TEA; IC(50), 0.14 mm). Q2S on the other hand produces no measurable potassium currents. Cotransfection of Q2S with either Q2L, Q3, or Q2L/Q3 heteromultimers results in attenuation of K(+) current, the suppression being most profound for Q3. Inclusion of Q2S in the heteromultimer also positively shifts the voltage dependence of current activation and alters affinity for the TEA block, suggesting that under these conditions, some Q2S subunits incorporate into functional channels on the plasma membrane. In view of the crucial role of M currents in modulating neuronal excitability, our findings provide important insight into the functional consequences of differential expression of KCNQ2 splice variants: dampened potassium conductances in the developing brain could shape firing repertoires to provide cues for proliferation rather than differentiation.
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PMID:Differential expression of kcnq2 splice variants: implications to m current function during neuronal development. 1116 Mar 79


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