block 4 Flashcards
HIV protease serves to cleave the gag and pol gene products into their functional protein subunits
gag (p24) capsid protein
pol - reverse transcriptase, aspartate protease and integrase.
Cant cleave pol, no replication!
-point mutations in the viral protease region of HIV pol gene leads to resistance to protease inhibitors
protease inhibitors end in “navir” generally
examples:
ritonavir (inhibitor of cP450)
indinavir
navir never tease a protease\
side effects:
hyperglycemia, GI inoterlance, lipodystrophy
Kayser fleicher rings found in wilsons disease are brownish or gray green rings of fine granular copper deposits in?
The CORNEA
Neutrophil oxidative burst
- once phagocytosis has occured, NADPH oxidase is activated!!
- NADPH is a membrane protein on the phagosome and leads to superoxide
- superoxide can reaction with water to form H2O2
- fusion with azurophilic granules to the phagosome introduces proteases, defensinsa and myeloperoxidase.
- MPO with H2O2 produc HOCL and other oxidation products that lead to further oxidative mebrane damage of the offending organism
-defect in NADPH oxidase results in chronic granulomatous disease
superoxide dismutase
catalyzes the conversion of superoxide to H2O2 and O2
- it functions as a free radical scavenger to protect cells from oxidative damage
- glutathione peroxidase is ana antioxidant enzyme that converts H2O2 to water and reduces oxidation products in cell membrane lipids.
dysplastic nevus syndrome is assoc. with melanoma
mutations in CDKN2A gene on chromosome 9p21
encodes cyclin dependent kinase inhibitor 2A (p16)
this normally negatively regulates cell cycle progression at the checkpoint of G1 and S
The cerebellum is derived from the embyonic metencephalon which is a part of the primitive hindbrain called
rhombencephalon
Basic zipper proteins
- a short 30 amino acid alpha helical fragment with leucine residues in every seventh position is a part of leucine zipper dimerization domain found on transcription factors called basic zipper proteins
- two such helical fragments allow binding of DNA
- other DNA binding proteins include: helix loop helix and zinc finger motifs
Gq protein coupled receptor
Gq is a phosopholipase C which catalyzes the hydrolysis of phospholipids into inosityl triphosphate (IP3) and diacylglycerol (DAG).
- IP3 releases stored calcium from the smooth ER or SR.
- DAG activates protein kinase C which phosphorylates regulatory proteins and TF
Radiolabeled CO2 in de nova synthesis of pyrimidine and purine nucleotides
- the first reaction of de novo of pyrimides is in the cytosol.
- glutamine + CO2 + 2ATP make carbamoyl phosphate, this is catalyzed by carbamoyl phosphate synthetase II (CPSII).
- this is different than the first reaction of the urea cycle where NH3+ CO2 + 2ATP are converted to carbamoyl phosphate by carbamoyl phosphate synthetase I in the mitochondria
positive psoas test
psoas abscess, appendicitis
alocholic cardiomyapathy
dilated cardiomyopathy
wet beri beri
rifampin
inhibits bacterial DNA-dependent RNA polymerase
Isoniazid
blocks mycolic acid synthesis by binding acyl carrier protein and ketoacyl carrier protein synthase thereby resulting in mycobacterial cell death
stain mycobacteria use ziel-neelsen acid fast stain
acid fast organisms will retain the red color of carbolfuschin stain after washing with acid alcohol while other bacteria will not
isotretinoin
functions in acne to normalize epidermal differentiation, decrease sebum production and prevent obstruction of the follicular-sebaceous unit.
esophageal hiatus of the diaphragm
T10
-esophagus passes with the anterior and posterior vagal trunks
the aorta passes though the aortic hiatus at T12
-the IVC passes though the central dented known as the caval opening at T8
Glucokinase (Hexokinase of the liver and pancreas)
-defect –> MODY
recall) glycolysis, glucokinase makes G6P and eventually –> TCA and we get increased ATP. ATP:ADP ration leads to closure (inhibition) of the ATP-sensitive /K+ channels.
- closure of the K+ channels leads to cell depolarization and gared Ca release –> beta cell insulin excocytosis.
- no glucokinase, no glycolysis
note glucokinase has higher Km than hexokinase.
Von gierke disease
deect in glucose-6-phosphatease
glycogen storage disease type 1
provents g6p from going to glucose in gluconeogenesis and glycogenolysis
-patients will have severe fasting hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, hepatomegaly and renomegly
patients should avoid fructose and galactose as they cannot be converted to glucose due to a defect in gluconeogenesis
Pompe disease (glycogen storage disease type II) lysosomal enzyme alpha-1,4-glucosidase (acid maltase, acid alpha-glucosidase)
- degrades a small amount of glycogen
- cause glycogen accumulation within lysosome (PAS-positive granules)
- clinical findings in the HEART
- signs: hypotonia, macroglossia, massive hypertrophic cardiomyapathy
PAS stain
- glycogen storage diseases (pompe)
- adenocarcinoma (stains mucins)
- Pagets disease of the breast
- Whiple tophe whatever
- alpha 1-antitrypsin deficency
DIC labs
- low fibrinogen and platelets
- increase PT, PTT and fibrin degradation products
- some schisotcytes maybe
some inhibitors of CYP450 are cimetidine,metronidazole and quinidine
-inhibit p450, increase the amount of warfarin, leading to increased INR PT risk of bleeding
but if you induce p450, decrease warfarin, decrease PT INR and risk of embolus
Induces of p450
barbituates
cartilage/dermis/scelere with blueblack discoloration
- alkaptonuria
- autosomal recessive defect in homogentisic acid oxidase
- which is required for the degradation of phenylalanine and tyrosine.
- so homogentisic acid accumulates and deposits
rheumatoid factor
is an IgM autoantibody directed against a patients own IgG
Pontine hemorrhages
cause pinpoint pupils, loss of horizontal gaze, quadraperesis, decerebrate posturing and rapidly evolving coma culminating in death within hours. `
Neoplastic of inflammatory lesions of the CNS can promote vasogenci edema
-via compromised blood-brain barrier. Increase vascular leak into the interstititum of the CNS contributes to a rising ICP
Reiter syndrome (reactive), psoriatic athritis and ankylosing spondylitis and IBD are all HLA?
HLA B27 associated
Reactive arhtritis, reiter cant see, can’t pee cant climb a tree
-precipitated by urogentical infection such as clamydia but can also occur in relation to intestinal infections with salmonella, shigella, campy and yesinia
Amphotericin B is a polyene macrolide antifungal
- bind ergosterol, creating pores in the fungal cell membrane, that allow for electrolyte escape and disruption of cellular homeostasis
- side effects: nephrotoxicity, hypokalemia and hypo magnesia and renal tubule acidosis
Echinocandian agents such as caspofungin
-inhibit cell wall synthesis
Flucytosine is a pyrimidine analogue
its metabolites impair fungal DNA replication and RNA synthesis
Pasteurella multocida
typically causes human infections following a dog or cat bite
-the disease typically begins with redness, pain, swelling and possible ulceration at the bite site followed by lymphangeitis and regional lymphadenoapthy
water deprivation test, and urine doesnt concentrate but the serum becomes hyperosmolar
nephrogenic DI
-serum hyperosmolarity, dilute urine and increased serum vasopressin levels in the setting of dehydration
hypercalcemia can cause polyuria, polydipsisia and dilute urine
its path is similiar to Nephrogenic DI
it is not do to osmolar diueresis
GP IIb/III is a surface receptor on platelets that belong to a family of INTEGRIN receptors
- it binds fibrinogen (a type of integrin)
- inhibitors include:abciximab, eptifibatide and tirofiban.
epitifibatide is an analogue of the carboxy terminal of the delta chain of fibrinogen
Clopidogrel is an inactive produrg that must be activated by CP450!!
so inhibitors of Cp450 like omeprazole would decrease the amount of activated clopidogrel. Clopidogrel is an ADP receptor antagonist
