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)

Tourette's syndrome (TS) is a complex neurobehavioral disorder emerging in childhood and is characterized by motor and vocal tics of at least one year in duration. In a portion of patients with TS, environmental (non-genetic) factors may either have an etiologic role or act to modulate the phenotype. One possible environmental factor may be antibodies to central nervous system cells, as sera from several children diagnosed with either TS or Sydenham's chorea contained anti-neuronal antibodies. Using enriched membrane preparations isolated from HTB-10 neuroblastoma cells, a sensitive and specific assay was developed for the determination of human anti-neuronal antibodies associated with involuntary repetitive movement disorders. This assay exhibited between-run and within-run precision of 11.3 percent and 5.9 percent, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of this assay for the diagnosis of TS and TS or chorea are 79.1 percent, 61.2 percent, 61.6 percent, 78.8 percent, and 71.1 percent, 60.9 percent, 68.6 percent, and 63.6 percent, respectively. In addition, there was a significant difference (p < 0.0001) between the mean optical density in the patients with TS and children determined to be clinically "normal".
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PMID:An immunoassay for anti-neuronal antibodies associated with involuntary repetitive movement disorders. 914 76

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder similar to Huntington's disease, with clinical manifestations including chorea, incoordination, ataxia, and dementia. It is caused by an expansion of a CAG trinucleotide repeat encoding polyglutamine in the atrophin-1 gene. Both patients and DRPLA transgenic mice have nuclear accumulation of atrophin-1, especially an approximately 120-kDa fragment, which appears to represent a cleavage product. We now show that this is an N-terminal fragment that does not correspond to the previously described caspase-3 fragment, or any other known caspase cleavage product. The atrophin-1 sequence contains a putative nuclear localization signal in the N terminus of the protein and a putative nuclear export signal in the C terminus. We have tested the hypothesis that endogenous localization signals are functional in atrophin-1, and that nuclear localization and proteolytic cleavage contribute to atrophin-1 cell toxicity. In transient cell transfection experiments using a neuroblastoma cell line, full-length atrophin-1 with 26 (normal) or 65 (expanded) glutamines localized to both nucleus and cytoplasm, with no significant difference in toxicity between the normal and mutant proteins. A construct with 65 glutamine repeats encoding an N-terminal fragment (which removes an NES) of atrophin-1 similar in size to the truncation product in DRPLA patient tissue, showed increased nuclear labeling, and an increase in cellular toxicity, compared with a similar fragment with 26 glutamines. Full-length atrophin-1 with 65 polyglutamine repeats and mutations inactivating the NES also yielded increased nuclear localization and increased toxicity. These data suggest that truncation enhances cellular toxicity of the mutant protein, and that the NES is a relevant region deleted during truncation. Furthermore, mutating the NLS in the truncated protein shifted atrophin-1 more to the cytoplasm and eliminated the increased toxicity, consistent with the idea that nuclear localization enhances toxicity. In none of the experiments were inclusions visible in the nucleus or cytoplasm suggesting that inclusion formation is unrelated to cell death. These data indicate that truncation of atrophin-1 may alter its ability to shuttle between the nucleus and cytoplasm, leading to abnormal nuclear interactions and cell toxicity.
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PMID:Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicity. 1246 7

On the basis of some research evidence and consensus, identification of acute opsoclonus, ataxia, or myoclonus should prompt consideration of an underlying neuroblastoma. On the basis of some research evidence and consensus, surgical treatment options should be considered for children with dystonia, including secondary dystonias, such as those related to cerebral palsy, and include intrathecal baclofen pumps and deep brain stimulation. On the basis of some research evidence and clinical experience, tetrabenazine may be effective in treating chorea. On the basis of strong research evidence, although seldom inherently dangerous, tics may be uncomfortable for affected children and interfere with academic achievement and social development. On the basis of some research evidence and clinical experience, topiramate may be an effective treatment for tic disorders.
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PMID:Pediatric movement disorders. 2573 62