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45 Cards in this Set
- Front
- Back
Transmissible Spongiform Encephalopathies cause problems due to
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failure to clear a protein (prion) leads to neuronal death
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what is the major distinguishing key of prion diseases
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transmissibility of a protein can lead to dz in other ppl
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what structure of prion is damaging to a host? what is importance about this form?
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B-sheet (aberrant form)
Aberrant forms are resistant to degradation, and are non-immunogenic to host |
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common pathogenesis of Creutzfeld-Jacob Disease (CJD)
another important way? |
spontaneous conversion from alpha to beta prions
passed by person to person (reusing surgical tools, eating mad cow beef) |
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man hunts a deer and wants to take it home and eat it. If he is in CO, WV or a few other places what dz does he have to worry about?
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Chronic wasting disease (CWD, deer and elk)
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all ppl who had nvCJD had changes where
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homozygous methionine at codon 129
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Rapidly progressive dementia and myoclonus. Death within year of onset. Due to an infective protein
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Creutzfeld-Jakob Disease
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what 2 ways can you distinguish mad cow (nvCJD) from sporadic CJD?
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ncCJD: “florid” plaque
other finding is “Pulvinar sign” in MRI |
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what are prion proteins?
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small proteins, expressed primarily in neurons, and inserted into neuronal cell membranes
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what chromosome are prion proteins encoded on?
What is the gene and how many copies of the gene are there? |
1. Encoded on chromosome 20
2. CPRNP gene (single copy) |
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describe the pathogenesis of prion dz (i.e., the protein conformational change that occurs)
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conversion of normal prion structure to abnormal:
alpha helix ---> beta sheet |
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list the 3 causes that can lead to the development of abnormal prion protein and thus disease
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1. genetic (inherited or spontaneous mutation: point mutation, insertion, deletion)
2. incorrect post-translational modification 3. "spontaneous" conversion |
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describe:
1. normal degradation of a prion protein 2. what occurs with degradation of mutated prion protein 3. what occurs from an infection of a prion protein |
1. Normal (PrP^sen) --> proteolysis --> degradation
2. Mutated (PrP^res) --> incomplete proteolysis --> amyloid 3. Infection: mutated + normal protein --> (2) mutated proteins --> amyloid |
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1. Creutzfield-Jacob Disease (CJD) can be caused by what 2 types of mutations?
2. CJD due to infection are associated with what 3 things? 3. CJD causes what type of neurologic disorder |
1. Inherited or somatic mutation
2. Infection a) Surgical instruments b) Dura mater grafts c) Human Growth hormone 3. Pre-senile dementia |
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New variant CJD (nvCJD) results via?
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infection via prion-contaminated beef
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1. Gerstmann-Straussler Scheinker Disease (GSS) is caused by what type of mutation?
2. What neurologic problems does it cause? |
1. Inherited mutation
2. Progressive ataxia/dementia |
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1. Fatal Familial Insomnia (FFI) is caused by what type of mutation?
2. Which part of the brain are the abnormal proteins found? 3. What neurological problems does it cause? |
1. Inherited mutation; rare somatic mutations, spontaneous conversions.
2. Thalamus 3. Intractable insomnia, dementia. ***Rare somatic mutations, spontaneous conversions |
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Kuru results due to what?
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Ritualistic cannibalism
***(Fore’ people, New Guinea) |
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what is the pathogenesis of Scrapie (sheep)
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sheep --> sheep infection via blood, placenta
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Bovine spongiform encephalopathy (BSE) results from what?
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Infection via sheep/cattle meat and bone meal
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Transmissible mink encephalopathy (TME) is found in what type of animals
What is the pathogenesis of this disease? |
1. Captive animals.
2. Infection via sheep/cattle meat |
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Chronic wasting disease (CWD, deer and elk) is spread to humans via what?
how is CWD initially spread to deer and elk? |
1. Current mechanism of spread unknown
2. Initial infection via sheep (blood) contaminated grasses |
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CJD can result in slightly different diseases due to what?
Also describe what is different |
1. Mutations (point, insertion, deletion) at **different locations** in the prion gene (250 codons, chromosome 20)
2. results in different: a) Location b) Onset c) Symptomatology d) Duration |
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flip to see the where the different prion diseases affect the brain
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mutation for Sporadic CJD (85%) occurs at what codon?
what does this lead to? |
1. Codon 129
(*normal*, Met/Val) |
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mutation for Familial CJD (5%) occurs at what codon(s)?
what does this lead to? |
Codon 200 (178, 208, 210)
(Glu --> Lys) |
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mutation for GSS occurs at what codon(s)?
what does this lead to? |
Codon 102 (105, 117, 145, 198)
(Pro --> Leu) |
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mutation for FFI occurs at what codon(s)?
what does this lead to? |
Codon 178
(Asp --> Asn) |
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mutation for nvCJD (infection with bovine prion) occurs at what codon(s)?
what does this lead to? |
Codon 129
***determine susceptibility...... in all cases, homozygous mehtionine |
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mutation for nvCJD protection (Japanese) occurs at what codon(s)?
what does this lead to? |
Codon 219
(Glu --> Lys) |
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What is the age of onset for CJD? What is seen on microscopy? What is seen clinically? What is the worldwide frequency?
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1. onset 60-65 yrs
2. microscopy: Progressive vaculoation, degenteration of brain 3. Rapidly progressive dementia and myoclonus (death within year of onset) 4. Occurs in low frequency worldwide (1/million, 15/million over age 60) *** Familial, sporadic (85%) and acquired forms (brain biopsies, corneal transplants, pituitary growth hormone, dura mater grafts, ingestion of contaminated meat). |
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in England/UK how is nvCJD passed to human?
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Passed to human by ingesting beef from cattle w/ bovine spongiform encephalopathy (damn Brits)
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describe what is seen on post mortem histopath of nvCJD pts
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"florid" plaque of nvCJD
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what protein is detectable in the CSF in sporadic CJD?
what protein is found to be elevated in nvCJD |
1. 14-3-3 protein (less/later on in nvCJD)
2. INC CSF tau protein |
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(nvCJD) - after a tonsillar biopsy is done what lab test preformed to look for the BSE prion?
What is seen on MRI |
1.Western Blot assay (humans and animals)
***New blood test developed (2011), not yet available 2. "Pulvinar sign" on MRI |
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classic CJD vs. nvCJD:
median age of death |
cCJD - 68 yo
nvCJD - 28 yo |
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classic CJD vs. nvCJD:
median duration of illness |
cCJD: 4-5 months
nvCJD: 13-14 months |
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classic CJD vs. nvCJD:
signs and symptoms |
cCJD - dementia; early neurologic signs
nvCJD - a) prominent psychiatric/behavioral sym. b) abnormal physical sensations c) delayed neurologic signs |
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classic CJD vs. nvCJD:
periodic spharp waves on electroencephologram |
cCJD: often present
nvCJD: absent |
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classic CJD vs. nvCJD:
agent in lymphoid tissue |
cCJD: not readily defected
nvCJD: readily detected |
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classic CJD vs. nvCJD:
immunohistochemical analysis of brain tissue |
cCJD: variable accumulation
nvCJD: marked accumulation of protease resistant prion protein |
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classic CJD vs. nvCJD:
florid plaques |
cCJD: rare or absent
nvCJD: large number |
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classic CJD vs. nvCJD:
Pulvinar sign on MRI |
cCJD: not reported
nvCJD: present >75% of cases |
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classic CJD vs. nvCJD:
INC glycoform ration on immunoblot analysis of protease-resistant prion protein |
cCJD: not reported
nvCJD: marked accumulation of protease-resistant prion protein |
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classic CJD vs. nvCJD:
treatment |
none currently
non-specific for pain, myoclonus, other symptoms |