Resp 2 - Froberg Cf

Front 1

What gene pattern is the CFTR gene?
Most common lethal genetic disease in what population?
When does CF present?

Back 1

Autosomal recessive pattern
Caucasians
newborn-young child

Front 2

Which 3 systems does CF effect? Variable spectrum and severity

Back 2

Respiratory
GI
Reproductive

Front 3

What is the primary manifestation of CF Clinical GI? Name some others...

Back 3

Pancreatic insufficiency (90%)
Meconium ileus ~10%
Biliary disease ~20%
Cirrhosis ~5%
Diabetes Mellitus ~20%
Idiopathic pancreatitis

Front 4

What is the primary manifestation of CF in Reproductive?

Back 4

Obstructive azoospermia - 90%

Front 5

What is the most frequent pathogen of CF patients?
What is the most common pathological manifestation in the resp system of CF patients?

Back 5

Pseudomonas (80-90%)

COPD (90%) - also bronciectasis

Front 6

The CFTR gene is on which chromosome? q31-32 and specficially found on what cells? What does it do in a normal lung?

Back 6

Chr 7
apical epithelial cells
cAMP regulated chloride channel expressed on the cells

Front 7

In a CF lung - there is a block of _____ leaving the cell which leads to an increase of _____ influx that results in a viscouse mucus which is dehydrated and hard to get rid of.

Back 7

chloride
sodium

leads to a build up and salty sweat

Front 8

What is the 1st and most common mutation in CF?
What is lost from NBD1 as a result?
Not glycosylated, causes folding defect, accelerated degradation in the ER

Back 8

deltaF508

phenylalanine

Front 9

CF Mutation class II: Abnormal trafficking so degraded before reaching membrane - caused by what mutation?

Back 9

DeltaF508

Front 10

If there is a decrease in mannose-binding lectin (MBL) what happens to CF pts?
CF patients have a decrease of __ in airways

Back 10

Decreased survival

NO

Front 11

Increased TNF-alpha, TGF-beta, IL-23 does what in CF?
Polymorphisms in TGF-beta does what?

Back 11

Increased inflammation so more rapid decline in resp function
Increase disease severity

Front 12

What tests Dx CF?

Back 12

Sweat chloride test - inject pilocarpine and then take sweat and test content
+ = > 80 mmol/L in adults. > 60 mmol/L in children

but SOME can have normal sweat chloride, not definitive

Front 13

Mutant CFTR leads to decreased internalization of what bug?
Wild type CFTR binds ___ , internalizes and clears bacteria

Back 13

Pseudomonas

LPS

Front 14

GI and reproductive damage are secondary to what pathophysiology of CF?

Back 14

Plugging of ducts by dehydrated airways surface liquid causing mucus plugs

Front 15

Pulmonary Rx:
Chest physiotherapy
___lytics
DNAse
_______ saline

Back 15

mucolytics
hypertonic

Front 16

Rx Inflammation of CF:
Ibuprofen
inhaled _______
______ antibiotics

Back 16

corticosteroids
macrolide

Front 17

Which type of vector works best for gene therapy?

Back 17

Viral vectors

Front 18

Why don't adenoviral vectors work for gene therapy?

Back 18

Local inflammation leading to immunologic response by neutralizing antibodies.
No improvement in lung, brief improvement in some noses

Front 19

Adeno-associated viral vectors are useful because they don't cause what effects that adenoviral vectors caused?

Back 19

acute inflammatory response
Also transgene expression can be sustained for months (adeno was for hours)

However, small vector doesn't have enough room for robust promoter - working on this

Front 20

Lentivirus integrating vectors are good because they integrate permanently and can transfect what kind of cells?
Disadvantages - safety!

Back 20

non-dividing

Front 21

___ ____ gene transfer agents are safe, but don't really work

Back 21

Non viral

Front 22

Barriers to gene transfer _____ in CF lungs:
Mucin
Edema
Cell and inflammatory debris in airways and alveolar spaces
Protease digestion of vectors
Increased immune surveillance
Also have normal lung ones... alveolar mos, tight jcns, etc

Back 22

Increase!