Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prion protein (PrP), which is involved in the pathogenesis of scrapie, occurs in 2 forms. The form extracted from scrapie brain is protease resistant (PrP-res), whereas PrP from normal brain is protease sensitive (PrP-sen). This study examined whether PrP-res could be detected in brains of sheep with scrapie by immunohistochemistry (IHC). A suitable IHC procedure was developed using brain tissue from hamsters that had been inoculated with the transmissible mink encephalopathy agent. Tissue samples were fixed in PLP (periodate, lysine, paraformaldehyde) that contained paraformaldehyde at a concentration of 0.125%. Before application of the IHC technique, tissue sections were deparaffinized and treated with formic acid to simultaneously enhance PrP-res immunoreactivity and degrade PrP-sen. Primary antibody was obtained from a rabbit immunized to PrP-res extracted from brains of mice with experimentally induced scrapie. Brain from 21 sheep with histopathologically confirmed scrapie were examined by IHC. In all 21 brains, PrP-res was widely distributed throughout the brain stem. Staining was particularly intense in neuronal cell bodies and around blood vessels. The IHC technique successfully detected PrP-res in brain samples that had been frozen or that were severely autolyzed before fixation in PLP. Brains from 11 scrapie-suspect sheep that were not considered histologically positive were also examined by IHC. PrP-res was found in 4 of these brains. Sections of brains from 14 clinically normal sheep did not have detectable PrP-res. Results of this study indicate that IHC detection of PrP-res is equivalent, and perhaps superior, to histopathology for the diagnosis of scrapie in sheep. Furthermore, IHC is applicable to tissues that have autolytic changes or processing artifacts that prevent satisfactory histopathologic evaluation for lesions of scrapie.
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PMID:Immunohistochemical detection of prion protein in sheep with scrapie. 810 39

It is proposed that exposure of the bovine embryo to specific high-dose lipophilic formulations of organophosphate insecticide (containing phthalimide) applied exclusively in the UK during the 1980s/early 1990s was the primary trigger that initiated the UK's bovine spongioform encephalopathy epidemic. Multi-site binding organophosphate toxic metabolites penetrate the fetus, covalently binding with, phosphorylating and ageing serine, tyrosine or histidine active sites on fetal central nervous system prion protein. An abnormal negative charge corrupts prion protein molecular surface, which blocks both proteases and chaperones from accessing their cleavage/bonding sites. This impairs normal degradation and folding of prion protein respectively. Once the abnormally phosphorylated abnormal prion protein isoform agent is initiated, any stress event ensuing in adult life induces a nerve growth factor-mediated synthesis of normal cellular prion protein isoform that aggregates to abnormally phosphorylated abnormal prion protein isoform, thereby becoming 'infected'/transformed into the same; due to the vicious circle of positive feedback invoked by the blocking of a prion protein-specific kinase. Prion protein could therefore serve as a hitherto unrecognized critical link in a chain of delayed neuroexcitotoxic proteins that are triggered off by chronic exposure to specific classes of chemical/metal that 'hit and run' during the vulnerable in utero period, producing spongioform encephalopathy disease years later.
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PMID:The UK epidemic of BSE: slow virus or chronic pesticide-initiated modification of the prion protein? Part 1: Mechanisms for a chemically induced pathogenesis/transmissibility. 873 81