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75 Cards in this Set
- Front
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What is the role of p53?
What other gene has this function? |
p53 and Rb both inhibit G1 to S (DNA Synthesis) phase progression.
Mutations in these genes result in unrestrained growth. |
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Role of cyclins.
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Activate cyclin-dependent kinases to proceed with cell cycle.
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How are Cyclin-CDK complexes inactivated?
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p21, p27, and p57 bind and inactivate cyclin-CDK complexes.
p53 controls activation of p21. |
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What is the role of cyclin D?
Downstream effects? |
Cyclin D binds/activates CDK4
CDK4 phosphorylates Rb protein Rb protein released from transcription factor E2F (elongation factor) Cell is now free to transcribe/synthesize components needed for progression through S phase (cyclin E, DNA pol, thymidine kinase, DHF reductase) (allows G1 to S) |
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What is the role of cyclin E?
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Cyclin E binds/activated CDK2-->cell progresses into S phase from G1
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What cyclins allow the progression from G2 to M phase?
How? |
Cyclin A-->CDK2-->mitotic phase
Cyclin B-->CDK1-->breakdown of nuclear envelope (nuclear lamin breakdown) and initiation of mitosis |
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Permanent vs Stable Cells:
General Examples |
Permanent cells remain in Go; ex: neurons, ekeletal, cardiac muscle, RBCs
Stable: Enter G1 from G0 when stimulated; ex: hepatocytes, lymphocytes |
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Labile vs Stable Cells:
General Examples |
Labile: Never go to G0; divide rapidly with short G1. Ex: BM, gut epithelium, hair follicles.
Stable: Enter G1 from G0 when stimulated; ex: hepatocytes, lymphocytes |
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rER vs sER:
General Which contain free ribosomes?--Function? |
rER: Site of synthesis of secretory (exported) proteins, ex: mucus
Contain free ribosomes: unattached to any membrane; site of synthesis of cytosolic and organellar porteins sER: steroid synthesis and detox; ex: liver hepatocytes and steroid hormone-producing ells of adrenal cortex |
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Label
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A: rER--stippled appearance (rough) due to ribosomes bound to membranes
B: Nucleolus-synthesis and assembly of ribosomal components (NOT membrane-bound) C: Nucleus--lighter region is euchromatin (DNA that has been unpackaged and is actively being transcribed) D-Mitochondria E-Exocrine secretory granule (contains exocrine enzymes and proteins packaged for secretion) |
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Describe the molecular structure of cilia.
Discuss dynein. |
9+2 arrangement of MTs
Axonemal dynein--ATPase that links peripheral 9 doublets and causes bending of cilium |
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What is Kartagener's syndrome?
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Immotile cilia due to dynein arm defect.
Results in male and female infertility (fallopian tubes can't move ovum along), bronchiectasis, and recurrent sinusitis; assocd w/situs inversus. |
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What drugs act on microtubules?
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Bendazoles (antihelminths)
Griseofulvin (antifungal) Vincristine/vinblastine (anti-cancer) Paclitaxel (anti-BrCa) Colchicine (anti-gout) |
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What is Chediak-Higashi syndrome?
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Microtubule polymerization defect resulting in dec'd phagocytosis
Results in recurrent pyogenic infections, partial albinism, peripheral neuropathy |
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Which amino acids are modified by the Golgi apparatus?
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Asparagine
Serine Threonine |
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I-cell Disease:
Pathophys Presentation |
(inclusion cell dz)
Inherited lyosomal storage disorder Failure of addition of mannose-6-phosphate to lysosome proteins (enzymes secreted outisde the cell instead of being targeted to lysosome) Results in coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes (often fatal in childhood) |
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What are the roles of the Golgi apparatus?
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Distribution center of proteins and lipids from ER to plasma membrane, lysosomes, secretory vesicles
Modifies oligosaccharides on asparagine Adds oligosaccharides to serine, threonine Adds mannose-6-phosphate to lysosomal proteins (targets protein to lysosome) Sulfation of |
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COPI vs COPII:
General |
These are both vesicular trafficking proteins
COPI (Co-protein I): retrograde--Golgi to ER COPII: anterograde: RER to cis-Golgi |
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Clathrin:
Role |
Vesicular trafficking protein--
Trans-Golgi-->lysosomes, plasma membrane-->endosomes (receptor-mediated endocytosis) |
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What protein is involved in transporting an endocytosed vesicle from the plasma membrane to the endosome?
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Clathrin
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What molecule targets proteins in the endoplasmic reticulum for lysosomes?
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Mannose-6-phosphate
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How is arachidonic acid formed?
What inhibits this? |
Membrane lipid (phosphatidylinositol)-->Arachidonic acid via Phospholipase A2
Corticosteroids inhibit Phospholipase A2 |
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Zileuton:
MOA |
Inhibits Arachidonic acid-->--->Leukotrienes via inhibiting LIPOXYGENASE
Lipoxygenase catalyzes Arachidonic acid-->Hydroperoxides(-->Leukotrienes) |
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Zafirlukast:
MOA |
Inhibit LTC4, LTD4, LTE4 and thus prevent bronchoconstriction
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Montelukast:
MOA |
Inhibit LTC4, LTD4, LTE4 and thus prevent bronchoconstriction
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NSAIDs:
MOA What other drugs share this MOA? |
Inhibit Cyclooxygenase which catalyzes:
Arachidonic acid-->Endoperoxides(-->Prostacyclin, Prostaglandins, Thromboxane) ASA, acetaminophen, COX-2 inhibitors |
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Prostacyclin:
Effects |
Dec'd PLT aggregation
Dec'd uterine tone Vasodilation |
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Prostaglandins:
Effects |
Dec'd vasc tone
Inc'd pain, uterine tone, temp |
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Thromboxane:
Effects |
Inc'd PLT agg (it's pro-THROMBOtic)
Vasoconstriction |
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Which hormones utilize the cAMP pathway?
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Think: Anterior Pituitary hormones, hormones that share alpha-subunit
So: FLAT CHAMP FSH LH ACTH TSH CRH hCG ADH (V2 receptor) MSH PTH Calcitonin, GHRH, glucagon |
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Which hormones utilize the cGMP pathway?
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Think: Vasodilators
So: ANP, NO |
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Which hormones utilize IP3?
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Think: Posterior pituitary
So: GOAT GnRH Oxytocin ADH (V1 receptor) TRH |
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Which hormones utilize cytosolic steroid receptors?
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VET CAP
Vit D Estrogen Testosterone Cortisol Aldosterone Progesterone |
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Which hormones utilize nuclear steroid receptors?
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T4/T3
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Which hormones utilize intrinsic tyrosine kinase pathways?
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Growth factors.
Insulin, IGF-1 FGF, PDGF |
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Describe the 4 types of cartilage.
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Be (So Totally) Cool, Read Books
Or A Strong Slippery Bloody BM I. (90%)--Bone, Skin, Tendon, fascia, late wound repair II--Cartilage (including hyaline), vitreous body III--Reticulun--skin, BVs, uterus, fetal tissue, granulation tissue IV--BM or basal lamina |
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Describe the synthesis of collagen.
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1. Synthesis in RER--translation of preprocollagen, usually Gly-X-Y
2. Hydroxylation in ER of specific proline and lysine residues; requires VITAMIN C 3. Glycosylation or pro-alpha-chain lysine residues to form procollagen 4. Exocytosis into extracell space 5. Proteolytic processing (cleaving of procollagen) to form tropocollagen 6. Cross-linking of tropocollagen to form fibrils |
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Ehlers-Danlos Syndrome:
Pathophys Presentation |
Faulty collagen synthesis causing hyperextensible skin, tendency to bleed (easy bruising), hypermobile joints
Collagen III (bloody collagen) most frequently affected |
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Osteogenesis Imperfecta:
Pathophys Presentation |
Abnormal Type I collagen causing multiple fractures with minimal trauma (may occur during birthing)
Blue sclerae Hearing Loss (abnl middle ear bones) Dental imperfections (lack of dentin) |
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Alport's Syndrome:
Pathophys Presentation |
Abnl type IV collagen-->progressive hereditary nephritis, deafness
Can't see, can't pee, can't hear |
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When is apoptosis initiated?
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Cells deprived of important cell signals such as GFs
Cell stress present DNA damage pressent and DNA repair process fails-->p53 triggers apoptosis Cytokines such as TNF trigger apoptosis Cytotoxic T cells insert granzyme into cells-->activation of caspases |
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Role of p53.
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Triggers apoptosis if DNA damage is present and repair mechanism fails.
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Caspase:
Role |
Protease that executes apoptosis and have Cysteine protease that cleaves ASPartic acid residues
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Apoptosis:
Extrinsic vs Intrinsic Pathways |
Extrinsic: via activation of cell surface death receptor
Type I TNF receptor I (TNFR1) Fas (CD95): Fas ligand binds Fas-->Fas-associated death domain (FADD) binds inactive caspase-8-->activates it -->apoptotic proteolytic cascade Intrinsic: INc'd mitochondrial permeability-->release of pro-apoptotic molecules into cytoplasm Bcl-2 proteins regulate (and prevent) apoptosis |
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Under what physiologically normal conditions is the intrinsic pathway of apoptosis utilized?
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Need intrinsic PW for:
Embryogenesis Menstruation Atrophy (endometrial linging during menopause) (also in response to radiation, toxins, hypoxia). This deals with mitochondrial perm and release of cytochrome c. |
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Role of CD31.
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Expressed by healthy cells to prevent phagocytosis.
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What are the histologic features of apoptosis?
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Cell shrinkage
Nuclear shrinkage Basophilia (pyknosis) Membrane blebbing Pyknotic nuclear fragmentation Nuclear fading (karolysis) |
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What is necrosis?
How does it differ histologically from apoptosis? |
Enzymatic degradation and protein denaturation of a cell resulting from exogenous injury.
Inflammatory process (unlike apoptosis. APOPTOSIS IS NOT AN INFLAMMATORY PROCESS) Necrosis = cell swelling, not shrinkage! |
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Where does coagulative necrosis occur?
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Heart, liver, kidney
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Where does liquefactive necrosis occur?
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Brain, bacterial abscesses, pleural effusion
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Where does caseous necrosis occur?
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TB, systemic fungi
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Where does fatty necrosis occur?
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Pancreas (saponification)
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Where does fibroid necrosis occur?
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BVs
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Where does gangrenous necrosis occur?
Wet vs Dry? |
Dry = ischemic coagulative
Wet = with bacteria Common in limbs, GI tract |
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Cell injury:
Reversible vs Irreversible changes--characteristics of cells |
Reversible (with O2):
Dec'd ATP synthesis Cell swelling (no ATP-->impaired Na/K pump) Nuclear chromatin clumping Dec'd glycogen Fatty change Ribosomal detachment (dec'd prot synth) Irreversible-- Nuclear pyknosis (basophilia) Karolysis (nuclear fading) Karyorrhexis (pyknotic nuclear fragmentation) Ca2+ influx-->caspase activation |
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Red vs Pale Infarction:
General |
Red: hemorrhagic; occurs in loose tissues with collaterals, such as liver, lungs, intestine or following reperfusion (due to free radicals)
Pale: occur in solid tissues with single blood supply, such as heart, kidney, and spleen; no reperfusion |
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Amyloid:
Stains |
Apple-green birefringence of Congo red stain under polarized light
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What drugs act on microtubules?
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-bendazoles
-taxels Griseofulvin Vincristine/Vinblastine Colchicine |
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What findings are a/w Ehlers-Danlos syndrome?
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Hyperextensible skin
Inc'd bleeding tendency Hypermobile joints Berry aneurysm |
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Which arachidonic acid product:
Increased bronchial tone |
Leukotrienes
Thromboxane |
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Which arachidonic acid product:
Decreased bronchial tone |
Prostacyclins
PG's |
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Which arachidonic acid product:
Increased platelet aggregation |
Thromboxane
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Which arachidonic acid product:
Decreased platelet aggregation |
Prostacyclin
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Which arachidonic acid product:
Increased uterine tone |
PG
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Which arachidonic acid product:
Decreased uterine tone |
Prostacyclin
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Which arachidonic acid product:
Increased vascular tone |
Thromboxane
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Which arachidonic acid product:
Decreased vascular tone |
PG, prostacyclin
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What are the two most abundant substances in plasma membranes?
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Cholesterol
Phospholipids |
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What provides the structural framework for DNA and the nuclear envelope?
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Lamins A, B, C
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What drugs act on the arachidonic acid product pathway?
What enzymes do they affect? |
Corticosteroids inhibit Phospholipase A2
Zileuton inhibits lipoxygenase Zafirlukast and Montelukast inhibit luekotriene receptors COX inhibited by NSAIDs, acetaminophen, ASA, COX-2 inhibitors |
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In trying to determine the genomic location of genes x, y, and z, you cut multiple copies of the gene with
a variety of different endonucleases. The following proteins are expressed x, xz, y, and z. What are the most likely relative locations of genes x, y and z? |
SOmetimes x and z expressed together, and y never expressed with them, so y must be far way from x and z.
so would be something like: y-----------------------x---z |
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Describe the process of leukocyte extravasation.
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Rolling mediated by selectins
TIght binding mediated by integrins Diapedesis mediated by PECAM Migration mediated by chemotactic factors (IL-8, LTB4, C5a, Kallikrein) |
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How are molecules transported into the nucleus?
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Nuclear localization signals rich in :
Lysine Arginine Proline |
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What histologic features are seen in apoptotic liver cells?
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Cell shrinkage
Nuclear shrinkage, basophilia (pyknosis) Membrane blebbing Formation of apoptotic bodies |
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What are the signaling pathway effects of activating Gq?
What are the effects of activating Gs? |
Gq is QC
Gq activates phospholipase C Phopholipase C makes IP3 IP3 increases intracell Ca2+ Phopholipase C makes DAG DAG activates Protein Kinase C-->more IP3 Activating Gs: Stimulates adenylyl cyclase to use ATP to make cAMP cAMP activates protein kinase A |
