Kuru, Cannibalism, Prions, & Spongiform Encephalopathies

Question 1

meaning of Kuru

Answer 1

trembling from fear & cold

Question 2

(5) Symptoms of Kuru

Answer 2

prolonged headaches and minor loss of coordination
symptoms rapidly progressed & by 4 months victims were unable to walk
speech disturbed
victims can no longer swallow
death occurred within 1 year

Question 3

What approaches were tried to treat Kuru?

Answer 3

antibiotics
aspirin
vitamins
drugs to treat parasitic worms
tranquilizers

Question 4

Who was Kuru dominant in? Absent?

Answer 4

women and children

adult men

Question 5

Kuru was not caused by the following agents?

Answer 5

infectious agent
environmental factors
heredity
mass hysteria

Question 6

Components of Cannibalism in Fore Tribe

Answer 6

Practice not unusual to New Guinea that would provide an avenue for passage of infectious agent
Fore tribe ate tissues (especially the brain) of close relatives
A religious ceremony
But no infectious agent could be detected in laboratory studies

Question 7

Who was sent to diagnose Kuru

Answer 7

Gajdusek

Question 8

Results of the 12 brains observed by Gajdusek?

Answer 8

Brain tissue seemed normal (no signs of inflammation or infection)

Question 9

Results of the 12 brains observed by neuropathologist?

Answer 9

brain revealed abnormalities (Loss of neurons

activation of astrocytes)

Question 10

Loss of neurons?

Answer 10

spongiform encephalopathy

Question 11

(4) What is Creutzfeldt-Jakob Disease?

Answer 11

brain disease
rapid progressive global dementia & marked progressive motor dysfunction
normal blood & test results
occurs within 1 year of onset of symptoms

Question 12

Definitive diagnosis of CJD is based on

Answer 12

brain pathology at time of biopsy/autopsy

Question 13

Why was CJD termed spongiform encephalopathy?

Answer 13

Termed spongiform encephalopathy due to gaping holes where neurons had once been

Question 14

What is it the adult Fore women and children of both sexes are doing, but the adult men are not doing, nor are the people of the adjacent tribes?

Answer 14

Eating each other…cannibalism

Question 15

The Fore tribe believed they were under a sorcerer’s curse due to______, so_____

Answer 15

the amount of ppl dying
unmarried men forced to assume task usually done by females
organized meetings to stress friendship & unity (willing to change their traditions)

Question 16

Social Behavior of the men in the Fore Tribe

Answer 16

Adult men and adolescent boys lived largely separate lives living together in huts
Adult men and adolescent boys hunted in the forest, but kept meat for themselves, not sharing with the women

Question 17

Social Behavior of the women & children in the Fore Tribe

Answer 17

The women prepared the body of the deceased for the ceremony, women consumed body tissues
Women used bamboo blades to prepare the tissues and packed the brain in small bamboo tubes to be steamed over an open fire before consumption
Small children playing in the area also given pieces of brain tissue to consume

Question 18

What was revealed in the rhesus monkeys & chimps after being inoculated with fresh brain tissue taken from victims of Kuru?

Answer 18

Two chimpanzees ~20 months after inoculation developed clinical signs and symptoms of Kuru
Histopathologic analysis showed changes consistent with Kuru and Creutzfeldt-Jakob disease
Evidence that a transmissible agent is involved in the pathogenesis of Kuru

Question 19

What did Kuru have an impact on?

Answer 19

medicine, neurology, & infectious disease

Question 20

How did Kuru have an impact on medicine, neurology & infectious disease?

Answer 20

Opened new area of slow virus diseases
Opened new area of transmissible spongiform encephalopathies
Lead to identification of new infectious agent, the prion

Question 21

In the slow virus disease______

Answer 21

Years may separate the time of initial contact with infectious agent and appearance of clinical disease

Question 22

Conventional agents

Answer 22

viruses

Question 23

Unconventional agents

Answer 23

prions

Question 24

Subacute Sclerosing Panencephalitis

Answer 24

Caused by measles virus with defective matrix (M) protein
Incubation period usually 7 - 10 years
Progressive dementia, ataxia, myoclonus
Death usually occurs within 1 - 3 years

Question 25

Transmissible spongiform encephalopathies are rare, but always fatal, slow neurodegenerative diseases caused by an

Answer 25

unconventional infectious agents

Question 26

Unconventional agents of the slow virus disease can be found in ____ & _____

Answer 26

animals and humans

Question 27

Unconventional agents found in animals?

Answer 27

scrapie in sheep transmissible mink encephalopathy bovine spongiform encephalopathy

Question 28

Unconventional agents found in humans?

Answer 28

Creutzfeldt-Jakob disease Variant Creutzfeldt-Jakob disease (mad cow disease) (Kuru)

Question 29

(5) Details of transmissible spongiform

Answer 29

Dementia and/or ataxia; loss of brain function; death Prominent astrocytosis and neuronal loss Lack of inflammation Possible appearance of amyloid-like plaques or fibrils Etiologic agent traced to prion,a protease-resistant protein (PrP)

Question 30

The prion is ________

Answer 30

a small proteinacious infectious particle which is resistant to inactivation by most procedures that modify nucleic acids

Question 31

Purification of scrapie-infected tissue revealed a 27 - 30 kd protein identified by a procedure that used proteinases and various detergents____

Answer 31

known as PrP (proteinase-resistant protein)

Question 32

PrP is smaller in size than _______and have remarkable______

Answer 32

conventional viruses; hydrophobic properties

Question 33

PrP is resistant to? (4)

Answer 33

Resistant to ionizing radiation & UV light Resistant to formaldehyde, alcohols, nonionic detergents, proteinase K Resistant to conventional autoclaving (15 - 30 min at 121 F) Resistant to nucleases

Question 34

Sequencing of PrP followed by cloning its gene revealed that?

Answer 34

PrP is a protein found in normal hosts including humans (explains lack of immune response)

Question 35

PrP mRNA

Answer 35

found in highest levels in neurons

Question 36

PrP can be expressed in

Answer 36

brains of healthy animals | non-neuronal cells (T cells, B cells, and dendritic cells)

Question 37

What are the 2 isoforms of PrP?

Answer 37

PrPC is the cellular isoform of the prion protein | PrPSC (or PrPCJD) is the abnormal pathogenic isoform of the prion protein that causes illness

Question 38

PrPC vs. PrPSC

Answer 38

PrPC and PrPSC are encoded by same gene and share amino acid composition (immunological tolerance) PrPC is sensitive to proteinase K, whereas PrPSC is resistant PrPC is soluble in nondenaturing detergents, whereas PrPSC insoluble PrPSC (but not PrPC) aggregates and forms amyloid plaques in brains with TSE PrPC has an alpha-helix content of 42% and little beta-sheet, whereas PrPSC has an alpha-helix content of ~30% and 45% beta-sheet content

Question 39

After infection with PrPSC isoform, the PrPSC

Answer 39

causes the PrPC isoform to be converted into PrPSC

Question 40

PrP is a normal cellular protein

Answer 40

PrPc protease sensitive alpha helix conformation

Question 41

PrPc is converted to abnormal form

Answer 41

PrPsc protease resistant beta helix conformation

Question 42

What are the 4 forms of CJD?

Answer 42

Sporadic form Familial form Iatrogenic form Variant form of Creutzfeldt-Jakob disease (vCJD)

Question 43

Sporadic Form (4)

Answer 43

Accounts for ~85% of all cases of CJD Bulk of cases occur between ages 50 and 79 Presents as a presenile dementia characterized by rapidly progressive mental deterioration, myoclonic jerking, deterioration of motor functions, ataxia, Death within one year of onset of symptoms

Question 44

Familial Form (5)

Answer 44

Accounts for 5% to 15% of all cases of CJD A genetic disorder due to point mutations / Onset takes place at a younger age when compared with sporadic CJD Disease progression characterized by progressive insomnia, autonomic dysfunction, endocrine changes, decline in motor / cognitive functions, Death within one year of onset of symptoms

Question 45

Iatrogenic Form (5)

Answer 45

``` Accounts for ~1% of all cases of CJD Medical transmission of infectious agent Median incubation period of 13 years Disease progression similar to sporadic Kuru, an epidemic of iatrogenic form of CJD ```

Question 46

Variant form of Mad Cow Disease was first recognized?

Answer 46

1996 Great Britain as a form of CJD that differs from sporadic CJD

Question 47

What age do cases of Variant form of Mad Cow Disease occur?

Answer 47

younger age group...mean age 26 years

Question 48

Early Stage? Late? Variant Form Mad Cow Disease

Answer 48

early stages illness present w/ psychiatric symptoms | late have sensory symptoms develop that progress to ataxia, dementia, death usually 13 months after onset

Question 49

Origin of Variant Form Mad Cow Disease is unclear, but was identified

Answer 49

in pts who received blood transfusions from donors who late died of vCJD

Question 50

Prion Inactivation (5)

Answer 50

Incineration Treatment with mercaptoethanol, SDS Treatment with sodium hypochlorite (20,000 ppm) Immersion for 60 min in 2N sodium hydroxide Autoclaving for 90 min at 132 - 136 F