Prion Disease, Infections and chronic diseases: Obesity, MS, Rheumatic fever, Depression, EBV and Mareks Disease Virus, Pathogens and Chronic Disease

Chronic disease cost ______ annual health care

$3.3 trillion

What to know about Scrapie?

- Pathological changes apparent on the macro and micro scale -wide spread neurodegeneration - Large single or multilocular soap bubble vacuoles -high degree of astrogliosis (star like) -Inflammatory cells from the immune system are absent

Jean Charcot

- father of neurology -linked pathology with clinical symptoms -identified the dz in living pts -described lesions around vessels and expansion of lesions from ventricles

Human prion disease

-Kuru -Sproadic Creutzfeldt Jakob disease (sCJD) -Iatrogenic -Genetic CJD -Variant CJD (vCJD)

Animal prion disease

-Scrapie -Bovine spongiform encephalopathy (BSE) -Chronic Wasting disease (CWD)

Kuru is characterized by

-ataxia -involuntary tremors -incoordination

Other symptoms of Kuru are

-decreased intelligence -marked emotionalism -loss of speech -inability to chew and swallow

Symptoms of Rheumatic fever

-fever -joint pain -carditis -skin manifestations -chorea

Prions are transmitted by 3 routes

-oral (Kuru) -transcutaneous -Aerosol (CWD)

Public control measures for vCJD

-surveillance -culling sick animals -banning specific risk materials -in the UK all animals >30 months of age excluded from human food and animal feed supplies

A vaccine is available for Hepatitis B/C but not B/C

B, not C

The interval between the most likely period for the initial extended exposure of the population to potentially is consistent with incubation periods

BSE-contaminated food (1984-1986) and the onset of initial variant CJD cases (1994-1996)

Tissue specific expression levels of PRNP in what tissue?

Brain

______is an aggressive type of non Hodgkins lymphoma

Burkitt's Lymphoma

Isolation of viruses from the ____ of MS patients

CNS

MS Epidemiological studies in

Faroe Islands

Cross epithelial barrier then go the lymphoid tissue (Prions)

GALT

Most highly expressed in brain tissue > ____

Neurons> astrocytes> oligodendrocytes

William J Hadlow

Noticed that Kuru is the human form of scrapie

Prion disease gene

PRNP (chromosome 20)

Prion disease protein name is

PrP

What to know about Kuru is similar to

Scrapie

MDV causes

T cell lymphoma

According to the CDC chronic disease is caused by (4)

Tobacco use and second hand smoke Poor nutrition Lack of physical activity Excessive alcohol use

HPV are DNA viruses that are grouped as ___, ____, and _____

alpha, beta or gamma

MDV is an

alphaherpesvirus

acute Rheumatic Fever is caused by an ______ to throat infection with

autoimmune response streptococcus pyogenes

MDV strategies (vx)

avirulent MDV turkey herpesvirus 1 (HVT)

Chronic Wasting disease (CWD) was first identified in _____ in Colorado ( )

captive deer 1967

High risk HPV types cause

carcinoma

KSHV associated with

castlemans disease

Scientific evidence shows a ______ association between BSE and vCJD

casual

Kuru is neurodegenerat, especially in the

cerebellum and extrapyramidal system

HPV cancers include cancers of the

cervix, vulva, vagina, penis, or anus as well as the back of the throat, including the base of the tongue and tonsils.

The first discovery that viral infections can cause cancer was made in

chickens

aa polymorphisms at ______ of PRNP are risk modifiers of prion disease

codon 129 and 219

Prion function is not understood, but probably important given that it is

conserved across species

Prions are very resistant to

degradation

Stanley B. Prusiner

discovered prions

D. Carleton Gajdusek

discovered the new mechanisms for the origin and dissemination of infectious diseases

BSE originated as a result of

feeding cattle meat and bone meal that contained BSE infected products

Kuru predominantly affects

females

J. Michael Bishop and Harold Varmus

found the DNA related to the transformation of avian sarcoma viruses present in normal DNA

HPV low risk types cause

genital warts

Alpha HPV infects the

genitals and oropharnygeal mucosa

PrP is a

glycosylphosphatidylinositol anchored cell surface glycoprotein

People with Hepatitis C often

have no symptoms

The finding that a single protein was was infectious was deemed

heretical

Mareks Disease was found to be a

herpesvirus

Cancer is ______ aggressive

highly

Kuru shows no sings of

inflammation or infection

MS Viral infection can cause

inflammatory demyelination

Kuru is/ is not transmittable?

is

Symptoms of Scrapie in sheep

itching hyper-excitability ataxia paralysis and death

CJD is very similar to ______ and ______ but most often occurs ______

kuru scrapies spontaneously

What does kuru laik i-kamp translate to?

kuru is about to begin

Prevelence of Kuru by

linguistic group

Hepatitis C is a leading cause of

liver cancer

Chronic diseases cause _______ of all deaths worldwide

more than half

_____ is a major problem in the U.S

obesity

EBV paved the way for uncovering other

oncogenic viruses

Majority of _____ cases have been exposed to EBV

pediatric

KSHV is the cause of

primary effusion lymphoma

Prions are resistant to

protease of the stomach

Kuru means to

shiver or be afraid

In 1982 Prusiner and his colleagues successfully produced a brain preparation that contained a single infectious agent which was a

single protein

Kuru was thought to be

sorcery-induced malady

Kuru was most prevalent in

the Fore group

First virus associated with cancer is s

y-herpes virus

Two prominent ways infection can trigger chronic disease

1. Inflammation triggered by infection can lead to chronic disease 2.Infection can predispose one to chronic illness

Infections cause cancer in _____ of cases

15-20%

Payton Rous won the nobel prize in

1966

Bovine Spongiform Encephalopathy (BSE) infections were identified in _____ causeing ______ deaths

1986 180,000

There have been ____ cases of vCJD

229

About _______ people in the US have chronic Hepatitis C

3.2 mill

Kuru occurs after what age?

4-5 years

Probability of cancer developing in AIDS patients is ___%

40

Roughly ______ % of the population becomes seropositive for EBV

90-95%

Stanley Prusiner began his work after one of his patients died of dementia resulting from

Creutzfeldt-Jakob disease (CJD)

Scrapie was identified as a transmissible agent by

Cuille and Chelle

_______ replicate prions and are needed for propagation to the brain

Dendritic Cells

Described the presence of ___ in brain tissue from MS patients

EBV

Proposed that ______ contributes to ____

EBV , MS

Burkitt's Lymphoma is caused by

Epstein-Barr virus

Oncogenic viruses (6)

Epstein-Barr virus (EBV) Human herpes virus 8 High-risk human papillomavirus (HPV), Hepatitis B virus (HBV) Hepatitis C virus (HCV) Merkel-cell polyomavirus.

What else could contribute to Kuru?

Exocannibalism- eating enemies Endocannibalism-eating relatives after death

(8) Chronic diseases include

Heart disease Stroke Cancer Chronic lung disease (COPD) Diabetes Stroke Chronic kidney disease Depression

Mareks Disease Virus was first described by

Jozsef Marek

Jean Charcot identified _____ in _____

MS ,1868