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Flashcards in 3/18 Deck (55):
1

How does huntingtin mutation in Hungtinton cause disease?

Transcriptional repression through histone deacetylation

2

Does hypermethylation of the promoter region increase or decrease transcription?

Decrease

3

Does the CAG repeat in Huntington cause a gain or loss of function of huntingtin protein?

deleterious (transcriptional repression) gain of function (increased histone deacetylation)

4

Do acetylated histones bind more or less tightly to DNA?

Less

5

What is the triad of Huntington manifestation?

BCD: behavioral abnormality, chorea, dementia

6

What is the term for the tendency for a disease to increase severity and/or start earlier in subsequent generations? (esp trinucleotide repeats diseases)

Anticipation

7

What is pleiotropy?

One gene mutation that leads to multiple phenotypic abnormalities

8

What function do snRNPs serve?

Spliceosomes for removing introns

9

What are the components of a nucelosome?

dsDNA wrapped around a histone protein core

10

How is isoniazid activated by mycobacteria?

Processing by catalase--peroxidase, allowing it to inhibit mycolic acid synthesis

11

Mechanism of mycobacterial resistance to Isoniazid?

Non-expression of catalase-peroxidase enzyme OR
modification of isoniazid's mycolic acid synthesis enzyme binding site

12

Mechanism of mycobacterial resistance to Rifampin?

Mutation in gene for DNA-dependent RNA polymerase

13

Mechanism of mycobacterial resistance to Ethambutol?

Increased production of arabinosyl transferase

14

What class is streptomycin? Mechanism of resistance?

Aminoglycoside that disables 30S ribosomal subunit. Resistance through modification of binding site.

15

Mechanism of mycobacterial resistance to Pyrazinamide?

Modification of pyrazinamidase, which is necessary to activate it

16

What is the timeframe for acute transplant rejection? Mechanism?

Acute is 1-4 weeks post-transplant. Mechanism is mediated by host T-lymphocyte sensitization against graft MHC.

17

Prevention of acute transplant rejection? Treatment of active acute rejection?

Prevention: calcineurin inhibitors (cyclosporine, tacrolimus)

Tx: corticosteroids +calcineurin inhibitors

18

What are the calcineurin inhibitors?

Cyclosporine, tacrolimus

19

Mechanism for hyperacute transplant rejection?

Preformed anti-ABO ab causing immediate rejection through acute thrombosis of vascular supply.

20

Timeline for chronic transplant rejection? Mechanism?

Timeline: years post-transplant

Mechanism: Host T and B cell sensitization against graft MHC

21

MOA of calcineurin inhibitors?

Inhibit activation and proliferation of Th cells by inhibiting calcineurin and subsequent cytokine synthesis

22

What is the typical brain morphology of prion diseases?

Spongiform encephalopathy, with vacuoles in the cytoplasm of neutrophils and neurons. These can transform to cysts. No inflammation

23

Rapidly progressive dementia and myoclonic jerks are suggestive of what disease?

Creutzfeldt-Jakob disease

24

How do you calculate renal PLASMA flow (RPF) using PAH clearance?

RPF = PAH clearance

PAH clearance = (urine PAH x urine flow rate)/plasma PAH

25

How does RBF relate to RPF?

RBF = RPF/(1-hematocrit)

26

Markers for small cell carcinomas?

Neuron-specific enolase
Chromogranin
Synaptophysin
Neurofilaments

27

What is vimentin useful for diagnosing?

Sarcomas

28

What are cold agglutinins?

Ab against erythrocytes caused by Mycoplasma pneumoniae, EBV, or hematologic malignancy; that lead to agglutination at low temps

29

Mechanism of penicillin resistance? What do you give?

Penicillinase (beta-lactamas)

Can give beta-lactamase resistance drugs: oxacillin, nafcillin, methicillin

30

Mechanism of methicillin resistance? Other drugs also resistant?

Alterations in penicillin-binding protein (PBP) structure. Resistant to all beta-lactam agents: oxacillin, nafcillin, methicillin, CEPHALOSPORINS, CARBAPENEMS, etc

31

Resistance to what drugs is conferred by active efflux?

Tetracycline and sulfonamides

32

Resistance to what drugs is conferred by mutation in DNA gyrase?

Fluoroquinolones

33

Resistance to what drug is conferred by mutation in RNA polymerase?

Rifampin

34

What is the first line, disease modifying drug for RA?

Methotrexate

35

What disease-modifying drugs can be added to methotrexate for RA?

Leflunomide and TNF-a inhibitors (etanercept, infliximab, adalimumab)

36

What are the TNF-a inhibitors?

Etanercept, infliximab, adalimumab

37

Methotrexate MOA?

inhibit dihydrofolate reductase, blocking folinic acid synthesis

38

What is the serum inhibitor of extracellular elastase?

alpha1-antitrypsin

39

What would you likely find in the lungs and liver of a patient with a1-AT deficiency?

Lungs: PANacinar emphysema
Liver: cirrhosis

40

What is the best drug for treating a woman with osteoporosis who has HTN/CHF?

HCTZ

41

What is the proposed reason for effectiveness of spironolactone in CHF patients?

Inhibition of aldosterone effects, not so much the diuresis

42

Why is activation of the RAAS system bad in CHF patients?

Aldosterone can cause ventricular remodeling, leading to cardiac fibrosis

43

What to give for Alzheimers?

Donepezil (cholinesterase inhibitor), vit E (alpha tocopherol), or Memantine (NMDA-R antagonist)

44

What is a type 2 error (beta)?

Probability of wrongly ACCEPTING null hypothesis

45

What is a type 1 error (alpha)?

Probability of wrongly REJECTING null hypothesis

Basically the p-value

46

What is statistical power the "opposite" of?

type 2 (beta) error
Power = 1 - beta

47

Chronic lymphedema is a risk factor for what?

Cutaneous angiosarcoma

48

Axillary lymph node dissection due to what procedure is a risk factor for chronic lymphedema?

Radical mastectomy

49

What is the most potent stimulator for neutrophil chemotaxis?

LTB4

50

Leukotrienes are produced from arachidonic acid by what enzyme?

5-lipoxygenase

51

Demyelination of axons in MS is due to depletion of what cells?

Oligodendrocytes

52

These sx should remind you of what: neuropsych sx incl. Parkinsonian tremor, rigidity, ataxia, slurred speech, drooling, personality changes, depression, paranoia, catatonia

Wilson disease

53

What is the risk of metastasis in a horizontally growing malignant melanoma?

None

54

What is the best prognostic indicator for malignant melanoma?

Depth of invasion (Breslow thickness)

55

What is suggested with bilateral hilar adenopathy and elevated serum calcium and ACE levels?

Sarcoidosis