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122 Cards in this Set
- Front
- Back
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Asymmetric division
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When one cell receives all the old DNA (the stem cell) and the sister cell receives all the new DNA that may be defective
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Mitogen
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Something that causes cell division
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Motogen
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Something that causes cell migration or scattering
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Morphogen
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Something that causes morphological cell change
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TGF-Alpha and TGF- Beta - Act on what cells?
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Mostly epithelial and mesenchymal. Also can act on liver cells
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VEGF - Act on what cells? Uses what receptor
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Act on endothelial cells
VEGF-R2 |
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HGF - Act on what cells? Uses what receptor?
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Liver cells
c-met is the receptor |
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EGF - Act on what cells? Uses what receptor?
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Epithelium
c-erbB1 is the receptor |
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FGF - What cell type does it act on?
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Endothelium and fibroblasts
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Prolactin - Acts on what cells?
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Breast epithelium during pregnancy
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Hyperplasia
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Increase in the number of cells
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Hypertrophy
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Increase in cell or organ size
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Atrophy
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Reduction in cell size - decrease in organelles and cytoplasm
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Hypoplasia
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Reduction in cell number
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Metaplasia
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Change in cell type - change in differentiated state
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Squamous metaplasia
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Transformation of a less resistance mucinous or glandular epithelium to a more resistant stratified squamous type
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Gladular metaplasia
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Change from squamous epithelium to glandular epithelium
Barrett's Esophagus |
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Dysplasia
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Loss of architectural organization of cells
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Neoplasia
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Autonomy and uncontrolled cell growth
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Coagulative necrosis - common sites
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heart, kidne, spleen, brain
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Intrinsic apoptosis - trigger, important activating caspase?
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Release of cyt c from mitochondria due to cell stress
Caspase 9 activates other caspases |
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Extrinsic apoptosis - Trigger? Receptor? Caspases activated?
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TNF - binds CD95 (FASl) and TNFR
Activates caspase 7 and 8 |
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Locus heterogeneity
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Different loci disruptions causing the same phenotye
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Allelic heterogeneity
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Same locus causing two different phenotypes
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Hurler and Scheie syndromes - locus or allelic?
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Allelic
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Sanfilippo A and B - locus or allelic?
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Locus
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von Gierke's disease - enzyme deficency of what? What are the consequences?
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Lack of Glu-6-phosphatase
Cannot generate Glu from Glu-6-P Hypoglcyemia |
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Propionic acidemia - accumulation or lack of product? What enzyme is deficient?
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Accumulation of propionyl-coA
Propionyl-coA carboxylases is deficient |
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Early onset multiple carboxylase defiency - What enzyme is deficient?
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Holocarboxylase synthetase
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Late onset - multiple carboxylase deficiency - What enzyme is deficient?
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Biotinidase to reclaim biotin
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Galactosemia - What enzyme deficency? What toxin?
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Gal-1-P uridyl transferase
Gal-1-P is toxic |
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Osteogenesis Imperfecta - defect?
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Normally defect of Type I collagen
Pro-alpha1 or Pro-alpha2 |
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Balanced translocation - What is it? Consequences for somatic cells? For gametes?
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Break of a homologous chromosome reattached to a NON-homologous chromosome
No consequences for somatic cells generally High likelihood of gametic consequence |
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Robertsonian translocation - What is it? What chromosomes affected?
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Translocation results in a large chromosome and a very small one
Acrocentric chromosomes - 13-15, 21, 22 |
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Down syndrome - What chromosomal abnormality? What increases risk?
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Trisomy 21 - 95%
Robertsonian 13 or 14 - 5% Maternal age increases risk NOT paternal |
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Fragile X syndrome - What gene? What repeat causes it?
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FMR-1 Gene
Increased CGG repeats (over 230) Leads to overmethylation of CpG island and reduced transcription |
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Expansion of Fragile X site - when does it occur
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During meioses of female carriers
During meiosis and mitosis of affected individuals |
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Myotonic dystrophy - What concept does it illustrate? What happens in congenital cases?
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Illustrates anticipation - gets progressively worse with each generation
Congenital - muscular Hypotonia and only born to affected mothers |
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SBMA vs. androgen insensitivity - Difference and symptoms?
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SBMA - repeat- leads to gain of function causing neuro problems
Androgen insensitivity - point mutation - leads to inactive receptor |
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Huntington disease - What type of inheritance?
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True dominance - heterozygote and homozygote have exact same phenotype
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All-or-none period - When is it?
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0-2 weeks after fertilization
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Critical period?
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Time when a teratogen can affect organ development
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Fetal warfarin syndrome - What disease does it resemble? What common pathway do they affect?
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Chondrodysplasia punctata
Both affect arysulfatase E - leads to malformations |
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Major anomaly
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Alterations that compromise survival, create significant functional impairment, or result in serious deformity
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Minor anomaly
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Alteration of no functional significance
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Malformation
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Morphologic defect of an organ
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Deformation
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Abnormal position or form of a body part from mechanical forces
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Disruption
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Morphologic defect resulting from break down with normal development processes
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Sequence
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Condition in which several abnormalities arise as secondary consequences of a single underlying problem
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Spatial colinearity - What is the spatial colinearity for HOX genes?
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Order of genes map an axis in the developing embryo
HOX genes map anterior to posterior (head to toe) |
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Temporal colinearity - How are genes temporally arranged for HOX genes?
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Order of genes is mapped to reflect temporal expression during development
3' genes are expressed earlier than 5' genes (therefore head is expressed first) |
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Organizing centers for Sonic Hedgehog
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Notocord
ZPA |
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SHH induces formation of what structures?
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Floor plate
Motor neuron differentation (Ventral structures) Sclerotome - vertebral bodies and ribs |
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What limb axis does ZPA encode for? What is its signalling molecule? Where is it most concentrated?
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Defines anterior-posterior axis of limb (difference b/e thumb and pinky)
SHh Proximal, posterior limb bud |
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What limb axis does AER encode for? What is its signalling molecule? Where is it most concentrated?
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Encodes proximal-distal axis
(difference b/e hand and shoulder) FGF Distal edge of limb bud |
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What limb axis does dorsal ectoderm encode for? What is its signalling molecule? Where is it most concentrated?
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Encodes dorsal-ventral axis
(difference between palm and back of hand) Wnt-7a Dorsal aspect |
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Loss of sonic hedgehog - affects on Ptc and GLI
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Loss of sonic hedgehog leads to Ptc activation and GLI inhibition - no transcription
Holoprosencephaly |
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Loss of Ptc - affects on GLI and overall consequence
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Loss of inhibition of GLI - more transcription
Increase in cancer |
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Inverse agonist definition
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Negative antagonists - negative intrinsic activity - reduce the resting level of activity of a receptor
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Potency
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Concentration of a drug required to reach it's maximum effect
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Efficacy
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The response produced by a certain drug
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Dose-response relationships - Graded versus quantal - difference
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Graded - individual - sees continuous repsponse dependent on dose
Quantal - population - binary outcome - dependent on dose |
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Therapeutic index
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Concentration of undersired effects to desired effects - Higher is better
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Non-competitive antagonist
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Antagonist that antagonizes at an allosteric site
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Monod-Wyman Changeux model - Receptor model?
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Receptors exist in two conformational states
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Koshland-Nemethy-Filmer model - Receptor model?
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Receptors have multiple conformations based on antagonists, agonists etc.
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Aquaglyceroporins - What are they? What can they transport?
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Transport water and glycerol - also allow low MW drugs (under 150 Da)
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P-pg and MRP1 - What are they?
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Glycoprotein modulating drug permability and Multidrug Resistance Protein - Drug pumps that allow brain cells to pump out drugs
Utilized by cancer cells against chemotherapy |
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Vectorial transport - Definition? Which directions can SLC transporters go? Which can ABC transporters go?
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Transferring solutes across epithelial or endothelial cells
SLC - Efflux or uptake ABC - ONLY on direction |
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Cytosis - Definition? Size of drugs?
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Vectorial drug transport that involves vesicle formation and movement
Large MW drugs - 100,000 Da |
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Paracellular transport - Definition? Drug size?
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Formed by minute intercellular space around interendothelial junctions
Allows diffusion of molecules smaller than 3 nm |
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Henderson Hassebalch equation
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pH=pKa+log([unprotonated]/[protonated])
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Most important organ for drug excretion?
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Kidney
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First-pass effect - Definition
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Metabolism of drug by gut and liver before gaining access to systemic circulation
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Benefit of rectal administration
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Bypasses first-pass metabolism - still not absorbed as efficiently
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Bioavailability
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Amount of administered drug that reaches the systemic circulation
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Intrmauscular injection - mechanism of transport
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Simple diffusion to plasma along concentration gradient (paracellular) - more hydrophilic move more quickly
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Factors for drug entry to brain - Directly proportional to what to properties of a chemical?
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Lipid solubility
Concentration gradient |
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Volume of distribution - Vd
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Plasma volume over which a drug is distributed
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Clearance
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Part of the volume of distribution from which a substance is irreversibly removed per unit time
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Ubiquitination - Definition? Pathway?
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Adding of ubiquitin to proteins destined for degradation
Degradated by 26S proteasome |
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Lipofuscin
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Dark pigment
Result of lipid oxidation from aging free radicals |
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Melanin
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Black pigment derived from tyrosine
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Hemosiderin
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Hemoglobin derived brown pigment in which iron is stored
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What process leads to uric acid buildup?
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Purine metabolism
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Anthracosis
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Increasing of carbon particles in airway epithelium - fibrogenesis from SILICA
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Dystrophic calcification - Definition
Serum calcium levels? |
Depoisition of calcium in dead tissue
Normal Ca levels |
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Metastatic calcification - Definition
Serum calcium levels? |
Deposition of calcium in normal tissues
Associated with increased Ca and PO4 in serum |
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Hayflick limit
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After 50 rounds of cell division most cells stop or dramatically slow cell cycle progression
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Cell crises
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After Hayflick limit - cells either die or become malignant
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Anaplasia
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Lack of differentiation in cell culture - malignant tumors are anaplastic
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Barrett's esophagus
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Replacement of stratified squamous with glandular epithelium in lower third of the esophagus
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Carcinoma
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Malignant tumor of epithellium
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Adenocarcinoma
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Malignant tumor of glandular epithelium
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Sarcoma
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Malignant tumor of mesenchymal origin
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Leukemia
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Uncontrolled proliferation of expansion of hematopoietic stem cells that are not completely differentiated
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Lymphoma
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Arise in lymphoid organs - proliferation of lympoid cells (T or B cell)
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PCNA
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Proliferating cell nuclear antigen - measures growth rate (needs high concentration for DNA replication)
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E-cadherin
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Integrin that allows for cell adhesion - mutations cause detachment and metastasis
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Beta-catenin
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Attaches E-cadherin to cellular cytoskeleton - mutations can cause detachment and metastasis of cell
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MMP - Which are important for BM destruction?
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MMP-2 and MMP-9 - degrade basement membrane
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TIMP
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Tissue Inhibitor of Metalloproteinases - keep MMP's in check - in cancer get overwhelmed by MMP
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Which types of cancer commonly spread hematogenously?
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Renal
Hepatocellular |
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Alpha-Fetoprotein (AFP) - What type of cancer
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Hepatocellular carcinoma
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Carcinoembryonic antigen (CEA) - What types of cancer?
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Colonic adenocarcinoma
Pancreatic adenocarcinoma Pulmonary tumors |
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Prostate Specific Antigen (PSA) - What types of cancer?
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Prostate (also elevated with BPH)
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Human chorionic gonadotropin (HcG) - What type of cancer?
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Testicular
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What type of translocation causes CML?
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Translocation 22 to 9
Creates Philadelphia chromosome |
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What type of translocation causes Burkitt's lymphoma?
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Translocation 8,14
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Oncogene activation - dominant or recessive?
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Dominant - only need one misfunctioning protein to lead to overproliferation
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Tumor supressor gene - dominant or recessive?
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Recessive - need both supressor genes inactivated in order to have cancer
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Significance APC gene
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Can lead to autosomal dominant inheritance of Familial adenomatous polyposis
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Promotion of tumor growth by promoters
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Promote but DO NOT alter genome
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UV-A or UV-B radiation - which leads to melnoma and carcinoma?
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UV-B
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UV-B radiation - mechanism for DNA damage
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Cause pyrimidine dimer formation
Mutate p53 tumors |
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Most malignant forms of HPV
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16 and 18
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E7 - function
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HPV gene that binds tumor suppressor gene
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E6 function
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Binds p53
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P21 - Activated by what? Function?
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Activated by p53
Cyclin dependent kinase inhibitor |
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GADD45 - Activated by what? Function?
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Activated by p53
DNA Repair enzyme |
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Difference between myxedema and edema?
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Myxedema is non-pitting due to mucopolysaccharides in CT
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CD-14 - Importance in sepsis?
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Binding site for LPS-LPB complex which stimulates TLR
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