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3/18 Flashcards

1
Q

How does huntingtin mutation in Hungtinton cause disease?

A

Transcriptional repression through histone deacetylation

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2
Q

Does hypermethylation of the promoter region increase or decrease transcription?

A

Decrease

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3
Q

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

A

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

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4
Q

Do acetylated histones bind more or less tightly to DNA?

A

Less

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5
Q

What is the triad of Huntington manifestation?

A

BCD: behavioral abnormality, chorea, dementia

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6
Q

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

A

Anticipation

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7
Q

What is pleiotropy?

A

One gene mutation that leads to multiple phenotypic abnormalities

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8
Q

What function do snRNPs serve?

A

Spliceosomes for removing introns

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9
Q

What are the components of a nucelosome?

A

dsDNA wrapped around a histone protein core

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10
Q

How is isoniazid activated by mycobacteria?

A

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

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11
Q

Mechanism of mycobacterial resistance to Isoniazid?

A

Non-expression of catalase-peroxidase enzyme OR

modification of isoniazid’s mycolic acid synthesis enzyme binding site

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12
Q

Mechanism of mycobacterial resistance to Rifampin?

A

Mutation in gene for DNA-dependent RNA polymerase

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13
Q

Mechanism of mycobacterial resistance to Ethambutol?

A

Increased production of arabinosyl transferase

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14
Q

What class is streptomycin? Mechanism of resistance?

A

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

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15
Q

Mechanism of mycobacterial resistance to Pyrazinamide?

A

Modification of pyrazinamidase, which is necessary to activate it

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16
Q

What is the timeframe for acute transplant rejection? Mechanism?

A

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

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17
Q

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

A

Prevention: calcineurin inhibitors (cyclosporine, tacrolimus)

Tx: corticosteroids +calcineurin inhibitors

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18
Q

What are the calcineurin inhibitors?

A

Cyclosporine, tacrolimus

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19
Q

Mechanism for hyperacute transplant rejection?

A

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

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20
Q

Timeline for chronic transplant rejection? Mechanism?

A

Timeline: years post-transplant

Mechanism: Host T and B cell sensitization against graft MHC

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21
Q

MOA of calcineurin inhibitors?

A

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

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22
Q

What is the typical brain morphology of prion diseases?

A

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

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23
Q

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

A

Creutzfeldt-Jakob disease

24
Q

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

A

RPF = PAH clearance

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

25
Q

How does RBF relate to RPF?

A

RBF = RPF/(1-hematocrit)

26
Q

Markers for small cell carcinomas?

A

Neuron-specific enolase
Chromogranin
Synaptophysin
Neurofilaments

27
Q

What is vimentin useful for diagnosing?

A

Sarcomas

28
Q

What are cold agglutinins?

A

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

29
Q

Mechanism of penicillin resistance? What do you give?

A

Penicillinase (beta-lactamas)

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

30
Q

Mechanism of methicillin resistance? Other drugs also resistant?

A

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

31
Q

Resistance to what drugs is conferred by active efflux?

A

Tetracycline and sulfonamides

32
Q

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

A

Fluoroquinolones

33
Q

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

A

Rifampin

34
Q

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

A

Methotrexate

35
Q

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

A

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

36
Q

What are the TNF-a inhibitors?

A

Etanercept, infliximab, adalimumab

37
Q

Methotrexate MOA?

A

inhibit dihydrofolate reductase, blocking folinic acid synthesis

38
Q

What is the serum inhibitor of extracellular elastase?

A

alpha1-antitrypsin

39
Q

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

A

Lungs: PANacinar emphysema
Liver: cirrhosis

40
Q

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

A

HCTZ

41
Q

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

A

Inhibition of aldosterone effects, not so much the diuresis

42
Q

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

A

Aldosterone can cause ventricular remodeling, leading to cardiac fibrosis

43
Q

What to give for Alzheimers?

A

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

44
Q

What is a type 2 error (beta)?

A

Probability of wrongly ACCEPTING null hypothesis

45
Q

What is a type 1 error (alpha)?

A

Probability of wrongly REJECTING null hypothesis

Basically the p-value

46
Q

What is statistical power the “opposite” of?

A 
type 2 (beta) error
Power = 1 - beta
47
Q

Chronic lymphedema is a risk factor for what?

A

Cutaneous angiosarcoma

48
Q

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

A

Radical mastectomy

49
Q

What is the most potent stimulator for neutrophil chemotaxis?

A

LTB4

50
Q

Leukotrienes are produced from arachidonic acid by what enzyme?

A

5-lipoxygenase

51
Q

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

A

Oligodendrocytes

52
Q

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

A

Wilson disease

53
Q

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

A

None

54
Q

What is the best prognostic indicator for malignant melanoma?

A

Depth of invasion (Breslow thickness)

55
Q

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

A

Sarcoidosis

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