In prion and Alzheimer's diseases, the roles played by amyloid versus nonamyloid deposits in brain damage remain unresolved. scrapie-infected transgenic mice expressing protein (PrP) lacking glycosylphosphatidylinositol (GPI) membrane anchor, abnormal protease-resistant PrPres was deposited as plaques, rather than usual form of PrPres. Although plaques induced reminiscent disease, clinical manifestations were minimal. contrast, combined expression anchorless wild-type PrP produced...

A better understanding of the infectious process in scrapie was sought by studying temporal distribution virus naturally infected Suffolk sheep. Virus detected (by mouse inoculation) first lymphatic tissues and intestine clinically normal lambs (age, 10-14 months). Titers were generally low. Infection central nervous system a 25-month-old sheep whose nonneural had moderate amounts virus. In affected with scrapie, similar accompanied high concentrations system, notably sites severest...

Scrapie and related transmissible spongiform encephalopathies result in the accumulation of a protease-resistant form an endogenous brain protein called PrP. As approach to understanding scrapie-associated modification PrP, we have studied processing sedimentation properties PrP (PrP-res) scrapie-infected mouse neuroblastoma cells. Like brain-derived PrP-res, cell PrP-res aggregated detergent lysates, providing evidence that tendency aggregate is intrinsic property not merely secondary...

Numerous studies have indicated that a modified proteinase K-resistant form of an endogenous brain protein, prion protein (PrP), is associated with scrapie infection in animals. This scrapie-associated PrP modification appears to occur posttranslationally brain, but its molecular nature not known. To learn about the normal biosynthesis and whether it altered by vitro, we did metabolic labeling experiments uninfected scrapie-infected mouse neuroblastoma tissue culture cells. Pulse-chase that,...

With the rationale that neuropathological similarities between scrapie and Alzheimer's disease reflect convergent pathological mechanisms involving altered gene expression, we set out to identify molecular events involved in both processes, using as a model study time course of these changes. We differentially screened cDNA library constructed from scrapie-infected mice mRNAs increase or decrease during discovered this way two are increased disease. These were subsequently shown by sequence...

Abstract: Transmissible spongiform encephalopathies (prion diseases), Alzheimer's disease, and other amyloidoses result in the accumulation of certain abnormally stable proteins that are thought by many to play central roles disease pathogenesis. Using serapieinfected neuroblastoma cells as a model system, we found Congo red, an amyloid‐binding dye, potently inhibits scrapie‐associated, protease‐resistant isoform protein PrP without affecting metabolism normal isoform. Growth with...

ABSTRACT The therapeutic efficacy of direct drug infusion into the brain, target organ transmissible spongiform encephalopathies, was assessed in transgenic mice intracerebrally infected with 263K scrapie agent. Pentosan polysulfate (PPS) gave most dramatic prolongation incubation period, and amphotericin B had intermediate effects, but antimalarial drugs such as quinacrine no significant prolongation. Treatment highest dose PPS at an early or late stage infection prolonged time by 2.4 1.7...

A mouse neuroblastoma cell line was successfully infected with scrapie agent. Agent derived from brain or spleen cultures. However, agent hamsters did not infect cultures, suggesting that species specificity influenced the infection process in vitro. Positive cultures supported replication for as many 47 passages shown to be cell-associated and between 631 7943 unselected culture cells constituted 1 LD50. fluctuation analysis indicated only one of 144 actually infected. Thus, confined a...

Probable transmission of bovine spongiform encephalopathy to humans has focused intense interest on all the transmissible encephalopathies (TSEs) and how they spread. In TSEs, an abnormal disease-associated, proteinase K—resistant protein referred as PrP-res or PrPSc accumulates in brain. some species, other tissues well. Sheep placenta, brain, spleen, lymph node were analyzed detail for infectivity. Both detected brain spleen samples placenta nodes 80% scrapie-infected sheep. A perfect...

The prion protein (PrP) is a scrapie-associated fibril that accumulates in the brains of hamsters and mice infected with scrapie agent, also persons affected kuru or Creutzfeldt-Jakob disease. It has been previously proposed PrP could be either primary transmissible agent secondary component involved pathogenesis scrapie. At present, second possibility seems more likely, for PrP-specific mRNA present both uninfected brains. We have isolated sequenced complete cDNA from mouse Comparison...

Abstract Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. Human susceptibility to CWD remains unproven despite likely exposure CWD-infected cervids. We used 2 nonhuman primate species, cynomolgus macaques squirrel monkeys, as human models for susceptibility. was inoculated into these species by intracerebral oral routes. After inoculation of 7 8 isolates induced clinical syndrome within 33–53 months. The monkeys'...

Prion diseases are fatal neurodegenerative of humans and animals characterized by gray matter spongiosis accumulation aggregated, misfolded, protease-resistant prion protein (PrPres). PrPres can be deposited in brain an amyloid-form and/or non-amyloid form, is derived from host-encoded protease-sensitive PrP (PrPsen), a normally anchored to the plasma membrane glycosylphosphatidylinositol (GPI). Previously, using heterozygous transgenic mice expressing only anchorless PrP, we found that...

Cattle infected with bovine spongiform encephalopathy (BSE) appear to be a reservoir for transmission of variant Creutzfeldt-Jakob disease (vCJD) humans. Although just over 100 people have developed clinical vCJD, millions probably been exposed the infectivity by consumption BSE-infected beef. It is currently not known whether some these individuals will develop themselves or act as asymptomatic carriers which might infect others in future. We studied agent persistence and adaptation after...

ABSTRACT Naturally occurring transmissible spongiform encephalopathy (TSE) diseases such as bovine in cattle are probably transmitted by oral or other peripheral routes of infection. While prion protein (PrP) is required for susceptibility, the mechanism spread infection to brain not clear. Two prominent possibilities include hematogenous leukocytes and neural axonal transport. In present experiments, following intraperitoneal transgenic mice with hamster scrapie strain 263K, PrP expression...

Mutations within a host cellular protein, PrP, have been associated with disease in the transmissible spongiform encephalopathies. Murine neuroblastoma cells persistently infected mouse scrapie accumulate protease-resistant PrP (PrP-res), abnormal form of These provide controlled system which to study molecular interactions are important formation PrP-res. We expressed recombinant molecules scrapie-infected murine and assayed effect these heterologous genes on accumulation The results...

We characterized a strain of Aleutian disease virus adapted to growth in Crandall feline kidney cells at 31.8 degrees C. When purified from infected cells, had density CsCl 1.42 1.44 g/ml and was 24 26 nm diameter. [3H]thymidine could be incorporated into the viral genome, DNA then studied. In alkaline sucrose gradients, single species that cosedimented 15.5S with single-stranded adeno-associated virus. analyzed on neutral again observed, which sedimented 21S clearly distinct 16S duplex DNA....

Congo red inhibits the accumulation of protease-resistant PrP in scrapie-infected mouse neuroblastoma cells. Here we show that also replication scrapie infectivity these This observation is consistent with idea a vital component agent or depends on presence cell.

Virologic and neurohistologic findings in three dairy goats that became affected with scrapie while living naturally infected Suffolk sheep were essentially like those sheep. Virus, detected by mouse inoculation, was widespread non-neural sites, particularly lymphatic tissues intestine. Im most titers of virus ranged from 3.0 to 3.5 log10 intracerebral LD50/30 mg tissue. Virus nervous tissue much higher titer. Ranging 5.1 5.8 log10, the highest mean diencephalon, midbrain, medulla oblongata...

Previous studies have indicated that scrapie infection results in the accumulation of a proteinase K-resistant form an endogenous brain protein generally referred to as prion (PrP). The molecular nature scrapie-associated modification PrP accounting for K resistance is not known. As approach understanding cellular events associated with tissue, we sought identify (PrP-res) scrapie-infected neuroblastoma cells vitro and compare properties PrP-res those its normal K-sensitive homolog, PrP-sen....

Scrapie, a spongiform encephalopathy of sheep and goats, is caused by poorly understood transmissible agent in which no nucleic acid has been conclusively identified. Biochemical characterization derived from animal tissues not precise because the tenacious association with tissue components. As an approach toward obtaining homogeneous preparations generated vitro, we cloned scrapie-infected neuroblastoma cells. By frequency analysis, nearly every cell expanded cultures contained scrapie...

In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed and elk were inoculated intracerebrally into various rodent species assess rodents' susceptibility develop new models of CWD. The Syrian golden, Djungarian, Chinese, Siberian, Armenian hamsters, transgenic mice expressing golden hamster protein, RML Swiss C57BL10 wild-type mice. hamsters...