Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unusual ocular symptoms observed during intravenous treatment with anti-disialoganglioside antibody (Ab) in children suffering from neuroblastoma were analyzed and the results reported. Within the framework of the German Collaborative Neuroblastoma Study NB97, 85 children with high-risk neuroblastoma received anti-GD2 monoclonal antibody ch14.18 intravenously. Side effects were regularly reported to the study center. Ocular symptoms were recorded in clinical detail, duration and development over time. Symptoms of a parasympathetic deficit corresponding to internal ophthalmoplegia, i.e. mydriasis and accommodation deficit, were found in 10 patients. They were uni- or bilateral, began after the termination of Ab infusion and improved or disappeared in all surviving children. They did not reappear or worsen upon repeated Ab infusions. The pathophysiology of these disorders remains poorly understood. It is concluded that during systemic treatment with the anti-GD2 antibody ch14.18, reversible symptoms of parasympathetic denervation of the eye may occur which, however, do not warrant termination of this treatment.
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PMID:Ocular symptoms in children treated with human-mouse chimeric anti-GD2 mAb ch14.18 for neuroblastoma. 1190 35

Ataxin 1 (Atxn1) is a protein of unknown function associated with spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease of late onset with variable degrees of cerebellar ataxia, ophthalmoplegia and neuropathy. SCA1 is caused by the toxic effects triggered by an expanded polyglutamine (polyQ) within Atxn1 resulting in neurodegeneration in the cerebellum, brain stem and spinocerebellar tracts. To gain insights into Atxn1 function, we have analysed the cerebellar gene expression profiles by microarray analysis in Atxn1-null mice, and identified alterations in expression of genes regulated by Sp1-dependent transcription, including the dopamine receptor D2 (Drd2), retinoic acid/thyroid hormone and Wnt-signalling. Interestingly, Drd2 expression levels are reduced in both Atxn1-null and transgenic mice expressing a pathogenic human Atxn1 with an expanded polyglutamine in cerebellar Purkinje cells. Our co-transfection experiments in human neuroblastoma SH-SY5Y cells and luciferase assays provide evidence for transcriptional regulation of Drd2 by Atxn1 and its AXH module. We show that Atxn1 occupies at the Drd2 promoter in vivo, and interacts and functions synergistically with the zinc-finger transcription factor Sp1 to co-regulate Drd2 expression. The interaction and transcriptional effects are mediated by the AXH domain within Atxn1 and are abrogated by the expanded polyQ within Atxn1. Therefore, this study identifies novel molecular targets that are regulated by Atxn1 which might contribute to the motor deficits in SCA1, and provides new insights into the mechanisms by which Atxn1 co-regulates transcription.
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PMID:Down-regulation of the dopamine receptor D2 in mice lacking ataxin 1. 1759 52