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)

The mouse neuroblastoma cell line N2a was persistently infected with the Chandler strain of the mouse scrapie agent. Although the infection did not spread to infect > 1% of the cells, clones were established that had from 50 to 100% infected cells. These clones expressed the abnormal protease-resistant form of prion protein (PrP), which is believed to mediate brain degeneration in animals with scrapie and bovine spongiform encephalopathy and in humans with kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome. With this in vitro system, Congo red and several sulfated polysaccharides, including heparin and pentosan polysulfate, were found to inhibit accumulation of protease-resistant PrP. These results and additional data confirming PrP binding to heparin suggested a possible role for sulfated glycosaminoglycans in the generation of protease-resistant PrP during scrapie infection. Accumulation of protease-resistant PrP was also blocked in vitro by expression of foreign PrP molecules, indicating that PrP from different species might compete for common substrates in this process. These results using scrapie-infected cell lines provide new opportunities for development of drugs capable of blocking the brain degeneration caused by scrapie and other transmissible spongiform encephalopathies.
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PMID:Prion protein and the scrapie agent: in vitro studies in infected neuroblastoma cells. 781 55

Although familial prion disorders are a direct consequence of mutations in the prion protein gene, the underlying mechanisms leading to neurodegeneration remain unclear. Potential pathogenic mechanisms include abnormal cellular metabolism of the mutant prion protein (PrP(M)), or destabilization of PrP(M) structure inducing a change in its conformation to the pathogenic PrP-scrapie (PrP(Sc)) form. To further clarify these mechanisms, we investigated the biogenesis of mutant PrP V203I and E211Q associated with Creutzfeldt-Jakob disease, and PrP Q212P associated with Gerstmann-Straussler-Scheinker syndrome in neuroblastoma cells. We report that all three PrP(M) forms accumulate similarly in the cytosol in response to proteasomal inhibition, and finally assemble as classical aggresomes. Since the three PrP(M) forms tested in this report are distinct, we propose that sequestration of misfolded PrP(M) into aggresomes is likely a general response of the cellular quality control that is not specific to a particular mutation in PrP. Moreover, since PrP has the remarkable ability to refold into PrP(Sc) that can subsequently replicate, PrP(M) sequestered in aggresomes may cause neurotoxicity by both direct and indirect pathways; directly through PrP(Sc) aggregates, and indirectly by depleting normal PrP, through induction of a cellular stress response, or by other undefined pathways. On the other hand, sequestered PrP(M) may be relatively inert, and cellular toxicity may be mediated by early intermediates in aggresome formation. Taken together, these observations demonstrate the role of proteasomes in the pathogenesis of familial prion disorders, and argue for further explanation of its mechanistic details.
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PMID:Aggresome formation by mutant prion proteins: the unfolding role of proteasomes in familial prion disorders. 1259 Jan 62

A microwave digestion technique using a mixture of HF + HNO(3) + HCl + H(3)BO(3) was found to be effective for the rapid dissolution of various silicate rock and sediment reference samples. From the solutions thus prepared, it was possible to determine quantitatively trace and ultratrace amounts of yttrium, thorium, uranium and the lanthanides by inductively coupled plasma-mass spectrometry (ICP-MS) without any separation of matrix elements or preconcentration. In the ICP-MS determinations, oxide and non-spectral interferences on individual masses of the rare earth element ions were corrected by the method of algebraic approach of elimination and dilution, respectively, and measurement drift was controlled by ruthenium and rhenium internal standards. The method yielded excellent results comparable with "recommended", "consensus" and "working" values of the literature for the specified elements on various well-known international reference materials such as andesite (AGV-1), basalts (BCR-1, BHVO-1, BIR-1 and BE-N), granites (G-2 and NIM-G), syenite (SY-2), gabbro (MRG-1), diabase (W-2 and DNC-1), marine mud (MAG-1), river sediment (NBS 1645), lake sediments (LKSD-1-LKSD-4) and stream sediment (GSD-1, GSD-5, GSD-6 and STSD-1-STSD-4)). New values for Er, Gd, Ho, Pr and Tm in LKSD-1-LKSD-4 and STSD-1-STSD-4, and Er, Ho, Lu, Nd, Pr, Tb, Tm and Yb in NBS 1645 are first reported in this work.
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PMID:Direct ICP-MS determination of trace and ultratrace elements in geological materials after decomposition in a microwave oven. I. Quantitation of Y, Th, U and the lanthanides. 1896 93