Mad Cow Disease and Englishmen: Dementia of Humans—Prions: Folding Protein Transmissible Diseases

Protein Supplement ◽

Infected Cattle ◽

The United Kingdom ◽

Disease Pattern ◽

Jakob Disease ◽

Mad Cow Disease ◽

Cattle Feeds

This chapter studies mad cow disease. In 1985–1986, bovine spongiform encephalopathy (BSE), or mad cow disease, was first identified in cattle of southern England, and within two years, over 1,000 instances of infected cattle surfaced in more than 200 herds. Epidemiologic investigations indicated that the addition of meat and bone meal as a protein supplement to cattle feeds was the likely source of that infection. By 1993, cases of mad cow disease peaked at over 1,000 per week. In addition to controlling the BSE epidemic in cattle, procedures were established to gauge whether this disease was a human health problem and to safeguard the population from the potential risk of BSE transmission. As a defense measure, in 1990, a national Creutzfeldt-Jakob disease (CJD) surveillance unit was established in the United Kingdom to monitor changes in the disease pattern of CJD that might indicate transmission of BSE to humans. Although CJD is the most common form of transmissible spongiform encephalopathies in humans, it is a rare disease with a uniform world incidence of about 1 case in 1 to 2 million persons per year.

How to Limit the Spread of Creutzfeldt-Jakob Disease

Infection Control and Hospital Epidemiology ◽

10.1017/s0195941700004720 ◽

1996 ◽

Vol 17 (8) ◽

pp. 521-528

Author(s):

Dominique Dormont

Keyword(s):

Blood Donation ◽

Transmissible Spongiform Encephalopathy ◽

Infected Individual ◽

Experimental Models ◽

Corneal Grafting ◽

Jakob Disease ◽

Spleen And Lymph Nodes

AbstractTransmissible spongiform encephalopathies are rare lethal diseases induced in humans and animals by unconventional agents called transmissible spongiform encephalopathy agents (TSEAs), virions, or prions. Several cases of iatrogenic Creutzfeldt-Jakob disease (CJD) have been reported in the literature after neuro-surgery, treatment with pituitary-derived hormones, corneal grafting, and use of dura mater lyophilisates. In a given infected individual, TSEA-associated infectiousness depends on the nature of the organ: the central nervous system has the highest infectiousness, spleen and lymph nodes a medium infectiousness, and organs such as bone, skin, or skeletal muscles do not harbor any detectable infectiousness in experimental models. Transmissible spongiform encephalopathy/prions have unconventional properties; in particular, they resist almost all the chemical and physical processes that inactivate conventional viruses. Therefore, prevention of CJD agent transmission must be taken into account in daily hospital practice. Efficient sterilization procedures should be determined. In tissue and blood donation, donors with a neurologic history must be excluded, and patients treated with pituitary-derived hormones should be considered potentially infected with TSEA and excluded.

Sympathetic Prions

The Scientific World JOURNAL ◽

10.1100/tsw.2001.258 ◽

2001 ◽

Vol 1 ◽

pp. 555-556 ◽

Cited By ~ 4

Author(s):

Markus Glatzel

Keyword(s):

Gastrointestinal Tract ◽

Injection Site ◽

Peripheral Nerves ◽

Infectious Agent ◽

Membrane Glycoprotein ◽

Jakob Disease ◽

The Brain

Transmissible spongiform encephalopathies are a group of invariably fatal neurodegenerative diseases. The infectious agent is termed prion and is thought to be composed of a modified protein (PrPSc or PrPRES), a protease-resistant conformer of the normal host-encoded membrane glycoprotein, PrPC[1]. Bovine spongiform encephalopathy, scrapie of sheep, and Creutzfeldt-Jakob disease are among the most notable transmissible spongiform encephalopathies. Prions are most efficiently propagated trough intracerebral inoculation, yet the entry point of the infectious agent is often through peripheral sites like the gastrointestinal tract[2,3]. The process by which prions invade the brain is termed neuroinvasion[4]. We and others have speculated that, depending on the amount of infectious agent injected, the injection site, and the strain of prions employed, neuroinvasion can occur either directly via peripheral nerves or first through the lymphoreticular system and then via peripheral nerves[5].

Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein

Journal of General Virology ◽

10.1099/vir.0.042507-0 ◽

2012 ◽

Vol 93 (7) ◽

pp. 1624-1629 ◽

Cited By ~ 52

Author(s):

Rona Wilson ◽

Chris Plinston ◽

Nora Hunter ◽

Cristina Casalone ◽

Cristiano Corona ◽

...

Keyword(s):

Prion Protein ◽

Chronic Wasting Disease ◽

Wild Type ◽

Wasting Disease ◽

Jakob Disease ◽

Human Prion Protein

The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

Use of 14-3-3 in the diagnosis of Creutzfeldt-Jakob disease

Biochemical Society Transactions ◽

10.1042/bst0300382 ◽

2002 ◽

Vol 30 (4) ◽

pp. 382-386 ◽

Cited By ~ 20

Author(s):

A. J. E. Green

Keyword(s):

Cerebrospinal Fluid ◽

Diagnostic Tests ◽

Human Diseases ◽

Animal Diseases ◽

Jakob Disease ◽

Sporadic Cjd

The transmissible spongiform encephalopathies include human diseases such as Creutzfeldt-Jakob disease (CJD) and kuru as well as animal diseases such as scrapie and bovine spongiform encephalopathy (BSE). The emergence of variant CJD, which is causally related to BSE, has generated much interest in the development of rapid and sensitive diagnostic tests for the pre-mortem diagnosis of CJD. In 1986 two proteins were detected in the cerebrospinal fluid (CSF) of patients with sporadic CJD. These proteins were later demonstrated to be members of the 14-3-3 family, and tests for the detection of CSF 14-3-3 were developed. A number of studies have shown that the detection of CSF 14-3-3 is an accurate test for sporadic CJD, although the results with variant CJD are less promising.

Autoantibodies to Brain Components and Antibodies to Acinetobacter calcoaceticus Are Present in Bovine Spongiform Encephalopathy

Infection and Immunity ◽

10.1128/iai.67.12.6591-6595.1999 ◽

1999 ◽

Vol 67 (12) ◽

pp. 6591-6595 ◽

Cited By ~ 15

Author(s):

Harmale Tiwana ◽

Clyde Wilson ◽

John Pirt ◽

William Cartmell ◽

Alan Ebringer

Keyword(s):

Escherichia Coli ◽

Immunoglobulin A ◽

Acinetobacter Calcoaceticus ◽

Allergic Encephalomyelitis ◽

Jakob Disease ◽

Experimental Allergic

ABSTRACT Bovine spongiform encephalopathy (BSE) is a neurological disorder, predominantly of British cattle, which belongs to the group of transmissible spongiform encephalopathies together with Creutzfeldt-Jakob disease (CJD), kuru, and scrapie. Autoantibodies to brain neurofilaments have been previously described in patients with CJD and kuru and in sheep affected by scrapie. Spongiform-like changes have also been observed in chronic experimental allergic encephalomyelitis, at least in rabbits and guinea pigs, and in these conditions autoantibodies to myelin occur. We report here that animals with BSE have elevated levels of immunoglobulin A autoantibodies to brain components, i.e., neurofilaments (P < 0.001) and myelin (P < 0.001), as well as toAcinetobacter calcoaceticus (P < 0.001), saprophytic microbes found in soil which have sequences cross-reacting with bovine neurofilaments and myelin, but there were no antibody elevations against Agrobacterium tumefaciens orEscherichia coli. The relevance of such mucosal autoantibodies or antibacterial antibodies to the pathology of BSE and its possible link to prions requires further evaluation.

Prion disease: advances in diagnosis and treatment

Morecambe Bay Medical Journal ◽

10.48037/mbmj.v4i10.877 ◽

2005 ◽

Vol 4 (10) ◽

pp. 273-278

Author(s):

Steve Dealler

Keyword(s):

Prion Disease ◽

The Political ◽

Potential Treatment ◽

Current State ◽

Jakob Disease ◽

Pentosan Polysulphate

Steve Dealler is a medical microbiologist with Morecambe Bay Hospitals NHS Trust. His work on on the diagnosis, epidemiology and potential treatment of transmissible spongiform encephalopathies has brought him inter-national recognition. He has been at the forefront of work on the epidemiology of human food containing the vector for bovine spongiform encephalopathy (BSE), and the development of prophylaxis against variant Creutzfeldt-Jakob disease (vCJD). He is currently working on a potential treatment, pentosan polysulphate. Here he describes the current state of knowledge in the battle against this devastating disease and the political inertia that frustrated earlier attempts to prevent the epidemic.

Human Prion Diseases

Escourolle and Poirier's Manual of Basic Neuropathology ◽

10.1093/med/9780199929054.003.0006 ◽

2013 ◽

pp. 149-160

Author(s):

James W. Ironside ◽

Matthew P. Frosch ◽

Bernardino Ghetti

Keyword(s):

Prion Diseases ◽

Neuronal Loss ◽

Pituitary Hormone ◽

Human Pituitary ◽

Jakob Disease ◽

Prnp Codon ◽

Codon 129

This chapter describes and illustrates the neuropathology of prion diseases, also known as transmissible spongiform encephalopathies. These diseases are characterized pathologically by varying combinations of spongiform change, neuronal loss, reactive gliosis, and prion protein (PrP) deposition. The morphologic pattern depends on the etiology of the disease and the genotype of the patient. Different clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (CJD) have been described depending on the PRNP codon 129 genotype and the PrP isotype. A novel form known as variably protease-sensitive prionopathy has been recently identified. Familial prion diseases include familial CJD, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Over 40 different PRNP mutations have been identified. Acquired prion diseases include Kuru; iatrogenic CJD, particularly in recipients of contaminated human pituitary hormone, and variant CJD, which seems closely related to bovine spongiform encephalopathy.

Detection and Analysis of Animal Materials in Food and Feed

Journal of Food Protection ◽

10.4315/0362-028x-63.11.1602 ◽

2000 ◽

Vol 63 (11) ◽

pp. 1602-1609 ◽

Cited By ~ 42

Author(s):

DRAGAN MOMCILOVIC ◽

AVRAHAM RASOOLY

Keyword(s):

Animal Feed ◽

Neurological Diseases ◽

Variant Form ◽

Food And Feed ◽

Ruminant Animals ◽

Jakob Disease ◽

Animal Material

Bovine spongiform encephalopathy (BSE) belongs to a group of progressively degenerative neurological diseases known as transmissible spongiform encephalopathies (TSEs) associated with a variant form of Creutzfeldt-Jakob disease in humans. TSEs are fatal diseases caused by prions (proteinaceous infectious particle) and are characterized by an incubation period that may range from several months to several years, depending on the host. Because BSE is spread through animal feed, the main strategy for preventing the establishment and spread of BSE is to prohibit the use of proteins derived from mammalian tissue in feed for ruminant animals. Enforcement of these regulations relies on the ability to identify the presence of prohibited proteins in ruminant feed. The methods to detect bovine products in rendered and cooked materials are based on analyses of DNA, bone, or protein. In this article, we discuss the current methodology as well as other potentially useful methods of analysis of animal material in food. While methods are generally useful, none specifically distinguish between prohibited bovine material and allowable bovine products, such as milk or blood. Furthermore, all these methods are hampered by the fact that the rendering process involves heat treatment that denatures and degrades proteins and DNA. There is a need for improving existing methods and developing new methods to overcome these two limitations.

Transmissible spongiform encephalopathies: the relationship between Creutzfeldt-Jakob disease and bovine spongiform encephalopathy

Current Opinion in Infectious Diseases ◽

10.1097/00001432-199702000-00001 ◽

1997 ◽

Vol 10 (1) ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

James W. Ironside

Keyword(s):

Jakob Disease ◽

The Relationship

Prion protein as a target for therapeutic interventions

Pure and Applied Chemistry ◽

10.1351/pac200476050915 ◽

2004 ◽

Vol 76 (5) ◽

pp. 915-920 ◽

Cited By ~ 4

Author(s):

P. P. Liberski

Keyword(s):

Prion Protein ◽

Phenotypic Expression ◽

Therapeutic Interventions ◽

Public Health Perspective ◽

Mad Cow Disease

Transmissible spongiform encephalopathies (TSEs), currently known as prion diseases, are neurodegenerative disorders of the central nervous system (CNS) caused by an elusive infectious agent called “prion” (proteinaceous infectious particle). These dis orders include: kuru, Creutzfeldt –Jakob disease (CJD) and its variant (vCJD), Gerstmann–Sträussler–Scheinker (GSS) disease and fatal familial insomnia (FFI) in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, and chronic wasting disease (CWD) in cervids. According to the widely accepted “prion hypothesis”, prion is an aggregate of the abnormal isoform of prion protein (PrPSc). Prion protein is a cell-derived glycoprotein (this normal isoform is called PrPc) encoded by a gene on chromosome 20 in humans (PRNP). In familial forms of TSEs, mutations within the ORF of PRNP are linked to the phenotypic expression of the disease. TSEs are important from public health perspective, and “mad cow disease has created the greatest threat to the safety of human food supply in modern times. vCJD threatens the safety of the blood supply worldwide”. Thus, to search for effective therapy is more than an urgent task. In TSEs, aggregates of PrPSc accumulate in the brain in a form of plaques, or synaptic deposits. The conversion of PrPc into PrPSc and subsequent deposits of PrPSc are targets for therapeutic interventions. These include: tricyclic compounds—acridine and phenothiazine derivatives; quinacrine; anti-PrPSc antibodies; dendrimers; polyethylene antibiotics (amphotericin B, MS-8209); pentosan polysulfate; and dextran sulfate. All these compounds are active in many in vitro and in vivo assays, but not proved definitely active in humans. Thus, albeit interesting and promising, the chemotherapy of TSEs is still in the infant phase.