Unit 2- prions

The mis-folded form of the prion protein has been implicated in a number of diseases in a variety of MAMMALS, including bovine spongiform encephalopathy (BSE, also known as ___ in CATTLE and Creutzfeldt-Jakob disease (CJD) in____.

"mad cow disease", humans

Sterilization: Immerse in a pan containing ___ NaOH and heat in a gravity-displacement autoclave at___ for 30 minutes; clean; rinse in water; and then perform routine sterilization processes

1N, 121°C

Varient CJD: Median age at death: __ Median duration of illness: __ Clinical signs & symptoms Periodic sharp waves on ELECTROENCEPHALOGRAM

28 yrs 13-14 months Prominent psychiatric/behavioral symptoms; painful dysesthesias; delayed neurologic signs Often absent

Classic CJD : Median age at death: __ Median duration of illness: __ Clinical signs and symptoms: Periodic sharp waves on ELECTROENCEPHALOGRAM:

68 yrs 4-5 months Dementia; early neurological signs Often present

Affected animal: Cattle Disease = ___

Bovine Spongiform Encephalopathy (BSE) a.k.a MAD COW DISEASE

The HUMAN prion disease variant Creutzfeldt-Jakob disease, however, is believed to be caused by a PRION which typically infects cattle, causing ____ and is transmitted through infected___.

Bovine spongiform encephalopathy , meat

Prions cause neurodegenerative disease by aggregating extracellularly within the ___ to form plaques known as ___, which disrupt the NORMAL TISSUE structure. This disruption is characterized by "holes" in the tissue with resultant spongy architecture due to the ____ formation in the neurons.

CNS, amyloid, vacuole

Affected animal: White tailed deer, elk, mule deer, moose Disease=

Chronic wasting disease (CWD)

Human disease: CJD, iCJD, vCJD, fCJD, sCJD, GSS, SFI

Creutzfeidt Jakob Disease, iatrogenic Creutzfeidt Jakob Disease, variant Creutzfeidt Jakob Disease, Familial Creutzfeidt Jakob Disease, sporadic Creutzfeidt Jakob Disease, Gerstmann-Sträussler Scheinker syndrome, Fatal familial insomnia/Kuru?

Affected animal: Cat Disease =

Feline Spongiform encephalopathy (FSE)

How can u get CJD?

Iatrogenic transmission-----the Medical Staff caused the infection

Animals born in captivity and those born in the wild have been affected with the disease CWD. Based on epidemiology, transmission of CWD is thought to be ___ (from animal to animal).

LATERAL

While the INCUBATION PERIOD for prion diseases is generally quite ___, once symptoms appear the disease progresses rapidly, leading to BRAIN DAMAGE and ___. Neurodegenerative symptoms can include convulsions, ___, ataxia (balance and coordination dysfunction), and behavioural or personality changes

LONG, death, dementia

How else can u get CJD?

Many cases in which transmission is not known

___ transmission may occur in CWD, although it appears to be relatively unimportant in maintaining epidemics

Maternal

The word prion is a portmanteau derived from the initial and final letters of the words ___ and ___.

PRoteinaceous and infectION. = PRION!

STANLEY ____ coined the word "prion" as a name for the _____. While the infectious agent was named a ___, the specific protein that the prion was composed of is also known as the ___, though this protein may occur both in ___ and ___forms.

Pruisner, infectious agent, prion, Prion Protein (PrP), infectious, non-infectious

Prusiner was awarded the Nobel Prize in Physiology or Medicine in 1997 for his research into ___

Prusiner, Prions

Affected animal: Sheep, Goat Disease = ___

Scrapie

Brain. The red box indicates the region of the obex, which is the portion of the brain that must be obtained for the diagnosis of __ and other spongiform encephalopathies such as ___ and ___.

TSE , scrapie, chronic wasting disease

Affected animal: Mink Disease = ___

Transmissible mink encephalopathy (TME)

Kuru: The preclinical or ___ phase, also called the incubation period, lasts longer, possibly ___ years following the initial exposure.

asymptomatic, FIVE-TWENTY YEARS (5-20 YRS)

Variant Creutzfeld-Jakob disease has occurred only where cases of ___, also have been found, leading researchers to theorize that eating beef from ___with BSE could spread the agent. In France and England whole herds of cattle have been put to death in an effort to prevent the spread of disease.

bovine spongiform encephalopathy , cattle

All known prion diseases affect the structure of the __ or other ___, and all are currently untreatable and are always fatal.

brain, neural tissue

vCJD: The human prion disease variant Creutzfeldt-Jakob disease, however, is believed to be caused by a prion which typically infects ___, causing Bovine spongiform encephalopathy and is transmitted through infected __.

cattle, meat

Creutzfeldt-Jakob disease or CJD (is a ___ disorder (brain disease) that is incurable and invariably fatal. It is the most ___ among the types of transmissible spongiform encephalopathy found in humans

degenerative neurological , common

Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions therefore involves the ___ of the protein to a state where the molecule is no longer able to induce the abnormal folding of normal proteins. Prions are generally quite resistant to____, heat, ___, and formalin treatments.

denaturation , proteases, radiation

Kuru transmission: The __ evident in the infection rates—kuru was ___ times more prevalent in women and children than in men at its peak—is because while the men of the village took the choice cuts, the women and children would eat the rest of the body including the __, where the ___ particles were particularly concentrated.

dysmorphism, 8-9x, brain, prion

Kuru transmission: It is believed by some that the disease spread easily and rapidly in the Fore people due to their ___ funeral practices, in which relatives consumed the deceased to return the "life force" of the deceased to his hamlet, a Fore societal subunit.

endocannibalistic

Although CJD is the MOST COMMON ___ prion disease, it is still ___, occurring in about one out of every one million people every year. It usually affects people aged 45-75, most commonly appearing in people between the ages of 60-65. The exception to this is the more recently-recognized 'variant' CJD (vCJD), which occurs in ___ people.

human , rare, younger

A prion is an ___ that is composed primarily of ____.

infectious agent, protein

To date, all such agents that have been discovered propagate by transmitting a ___ state; as with ___ the protein itself does not ____, rather it induces existing POLYPEPTIDES in the host organism to take on the rogue form.[

mis-folded protein , viruses, self-replicate,

How can u get CJD? People can also acquire CJD genetically through a ___ of the GENE that codes for the prion protein (PRNP). This only occurs in ___ of all CJD cases

mutation, 5-10%

Kuru is believed to be caused by ___ and is related to ___ . It is best known for the epidemic that occurred in ___ in the middle of the twentieth century, and earlier.

prions, Creutzfeldt-Jakob disease, Papua New Guinea

Research has recently shown that an infected DEER'S ___ is able to spread the CWD prions.

saliva

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very ___ in all mammals. Due to small differences in PrP between different species it is ___ for a prion disease to be transmitted from one ___ to another.

similar, unusual, species

All known prion diseases, collectively called __ (TSEs), are ___.

transmissible spongiform encephalopathies , UNTREATABLE & FATAL

Kuru: Trembling is present in almost all patients with ___.

transmissible spongiform encephalopathy

Although KURU is considered a ___ prion disease, there is some evidence that the origin of the outbreak was due to consumption of an individual ____ () with sporadic CJD, thus implying a common pathophysiology

transmissible, CANNIBALISM

The origin and mode of transmission of the prions causing CWD is ___, but recent research indicates that prions can be EXCRETED by ___,, and is TRANSMITTED by eating grass growing in ___ soil.

unknown, deer and elk, contaminated