3/18 Flashcards
How does huntingtin mutation in Hungtinton cause disease?
Transcriptional repression through histone deacetylation
Does hypermethylation of the promoter region increase or decrease transcription?
Decrease
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)
Do acetylated histones bind more or less tightly to DNA?
Less
What is the triad of Huntington manifestation?
BCD: behavioral abnormality, chorea, dementia
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
What is pleiotropy?
One gene mutation that leads to multiple phenotypic abnormalities
What function do snRNPs serve?
Spliceosomes for removing introns
What are the components of a nucelosome?
dsDNA wrapped around a histone protein core
How is isoniazid activated by mycobacteria?
Processing by catalase–peroxidase, allowing it to inhibit mycolic acid synthesis
Mechanism of mycobacterial resistance to Isoniazid?
Non-expression of catalase-peroxidase enzyme OR
modification of isoniazid’s mycolic acid synthesis enzyme binding site
Mechanism of mycobacterial resistance to Rifampin?
Mutation in gene for DNA-dependent RNA polymerase
Mechanism of mycobacterial resistance to Ethambutol?
Increased production of arabinosyl transferase
What class is streptomycin? Mechanism of resistance?
Aminoglycoside that disables 30S ribosomal subunit. Resistance through modification of binding site.
Mechanism of mycobacterial resistance to Pyrazinamide?
Modification of pyrazinamidase, which is necessary to activate it
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.
Prevention of acute transplant rejection? Treatment of active acute rejection?
Prevention: calcineurin inhibitors (cyclosporine, tacrolimus)
Tx: corticosteroids +calcineurin inhibitors
What are the calcineurin inhibitors?
Cyclosporine, tacrolimus
Mechanism for hyperacute transplant rejection?
Preformed anti-ABO ab causing immediate rejection through acute thrombosis of vascular supply.
Timeline for chronic transplant rejection? Mechanism?
Timeline: years post-transplant
Mechanism: Host T and B cell sensitization against graft MHC
MOA of calcineurin inhibitors?
Inhibit activation and proliferation of Th cells by inhibiting calcineurin and subsequent cytokine synthesis
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
Rapidly progressive dementia and myoclonic jerks are suggestive of what disease?
Creutzfeldt-Jakob disease
How do you calculate renal PLASMA flow (RPF) using PAH clearance?
RPF = PAH clearance
PAH clearance = (urine PAH x urine flow rate)/plasma PAH
How does RBF relate to RPF?
RBF = RPF/(1-hematocrit)
Markers for small cell carcinomas?
Neuron-specific enolase
Chromogranin
Synaptophysin
Neurofilaments
What is vimentin useful for diagnosing?
Sarcomas
What are cold agglutinins?
Ab against erythrocytes caused by Mycoplasma pneumoniae, EBV, or hematologic malignancy; that lead to agglutination at low temps
Mechanism of penicillin resistance? What do you give?
Penicillinase (beta-lactamas)
Can give beta-lactamase resistance drugs: oxacillin, nafcillin, methicillin
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
Resistance to what drugs is conferred by active efflux?
Tetracycline and sulfonamides
Resistance to what drugs is conferred by mutation in DNA gyrase?
Fluoroquinolones
Resistance to what drug is conferred by mutation in RNA polymerase?
Rifampin
What is the first line, disease modifying drug for RA?
Methotrexate
What disease-modifying drugs can be added to methotrexate for RA?
Leflunomide and TNF-a inhibitors (etanercept, infliximab, adalimumab)
What are the TNF-a inhibitors?
Etanercept, infliximab, adalimumab
Methotrexate MOA?
inhibit dihydrofolate reductase, blocking folinic acid synthesis
What is the serum inhibitor of extracellular elastase?
alpha1-antitrypsin
What would you likely find in the lungs and liver of a patient with a1-AT deficiency?
Lungs: PANacinar emphysema
Liver: cirrhosis
What is the best drug for treating a woman with osteoporosis who has HTN/CHF?
HCTZ
What is the proposed reason for effectiveness of spironolactone in CHF patients?
Inhibition of aldosterone effects, not so much the diuresis
Why is activation of the RAAS system bad in CHF patients?
Aldosterone can cause ventricular remodeling, leading to cardiac fibrosis
What to give for Alzheimers?
Donepezil (cholinesterase inhibitor), vit E (alpha tocopherol), or Memantine (NMDA-R antagonist)
What is a type 2 error (beta)?
Probability of wrongly ACCEPTING null hypothesis
What is a type 1 error (alpha)?
Probability of wrongly REJECTING null hypothesis
Basically the p-value
What is statistical power the “opposite” of?
type 2 (beta) error Power = 1 - beta
Chronic lymphedema is a risk factor for what?
Cutaneous angiosarcoma
Axillary lymph node dissection due to what procedure is a risk factor for chronic lymphedema?
Radical mastectomy
What is the most potent stimulator for neutrophil chemotaxis?
LTB4
Leukotrienes are produced from arachidonic acid by what enzyme?
5-lipoxygenase
Demyelination of axons in MS is due to depletion of what cells?
Oligodendrocytes
These sx should remind you of what: neuropsych sx incl. Parkinsonian tremor, rigidity, ataxia, slurred speech, drooling, personality changes, depression, paranoia, catatonia
Wilson disease
What is the risk of metastasis in a horizontally growing malignant melanoma?
None
What is the best prognostic indicator for malignant melanoma?
Depth of invasion (Breslow thickness)
What is suggested with bilateral hilar adenopathy and elevated serum calcium and ACE levels?
Sarcoidosis
