There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.
Bovine spongiform encephalopathy (BSE) and its human equivalent, variant Creutzfeldt±Jakob disease (vCJD), are caused by the same strain of infectious agent, which is similar to, but distinct from, >20 strains of their sheep scrapie homologue. A better understanding of the molecular strain determinants could be obtained from cells in monoculture than from whole animal studies where different cell targeting is commonly a strain-related feature. Although a few cell types can be infected with different strains, the phenotypes of the emergent strains have not been studied. We have cured the scrapie-infected, clonal SMB cell line with pentosan sulfate, stably re-infected it with a different strain of scrapie and shown that biological properties and prion protein pro®les characteristic of each original strain are propagated faithfully in this single non-neuronal cell type. These ®ndings attest to the fact that scrapie strain determinants are stable and host-independent in isolated cells.
Cell-mediated infection of target cells in this culture system is effective and requires significantly less PrP(Sc) than infection by a prion preparation. Several lines of evidence indicate that it depends on cell contact, in particular, the activity of aldehyde-fixed infected cells.
Transmissible spongiform encephalopathies (TSEs) are incurable, fatal diseases. The dye Congo Red (CR) can cure cells infected with agents of the sheep TSE, scrapie, but is not used as a therapeutic or prophylactic agent in vivo, as its effects are small, possibly due to low blood-brain barrier permeability, and complicated by its intrinsic carcinogenicity. In this paper, the development is described of a structure-activity profile for CR by testing a series of analogues of this dye for their ability to inhibit the formation of the protease-resistant prion protein, PrP-res, a molecular marker for the infectious agent, in the scrapie-infected, SMB cell line. It was found that the central benzidine unit in CR, which gives the molecule potential carcinogenicity, can be replaced by other, less toxic moieties and that the sulphonate groups on the core molecule can be replaced by carboxylic acids, which should improve the brain permeability of these compounds. However, detailed dose-response curves were generated for several derivatives and they revealed that, while some compounds showed inhibition of PrP-res accumulation at high concentrations, at low concentrations they actually stimulated levels of PrP-res above control values.
We have used a panel of monoclonal antibodies in a study of the expression of multiple tubulins in Physarum polycephalum. Three anti+tubulin monoclonal antibodies. DMlB, DM3B3 and KMX-1 all reacted with the fl,-tubulin isotypes expressed in both myxamoebae and plasmodia. However, these antibodies showed a spectrum of reduced reactivity with the plasmodial p,-tubulin isotype -the competence of recognition of this isotype was graded DM 1 B > KMX-1 > DM3B3. The anti-a-tubulin monoclonal antibody, YOL l/34 defined the full complement of Physarum a-tubulin isotypes, whilst the anti-a-tubulin monoclonal antibody, KMP-1 showed a remarkably high degree of isotype specificity. KMP-1 recognises all of the myxamoebal a,-tubulin isotypes but only recognises 3 out of the 4 a,-tubulin isotypes expressed in the plasmodium (which normally focus in the same 2D gel spot). KMP-1 does not recognise the plasmodial specific a,-tubulin isotype. This monoclonal antibody reveals a new level of complexity amongst the tubulin isotypes expressed in Physarum and suggests that monoclonal antibodies are valuable probes for individual members of multi-tubulin families. Monoclonal antibody Tub&nPhysarum
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