3/18 Flashcards

(55 cards)

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
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