Term
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Definition
| extensive deposition of collagen due to GFs and cytokines |
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Term
| What are the 2 mechanisms that stimulate cell proliferation? |
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Definition
1 shortening the cell cycle
2 forcing resting cells to enter cell cycle |
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Term
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Definition
| continuously dividing tissue |
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Term
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Definition
| normally have low levels of cell division but capable of rapid division in response to stimuli |
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Term
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Definition
| in every cell division, one cel retains the capacity to self-replicate and one cell differentiates into a mature, non-dividing cell |
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Term
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Definition
| the capacity to differentiate into any type of cell in the body |
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Term
| Where are pluripotent cells found in early development? |
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Definition
| Within the inner cell mass of blastocysts |
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Term
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Definition
| generate all of the blood cell lineages |
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Term
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Definition
MULTIPOTENT
migrate to injured tissues and generate stromal cells |
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Term
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Definition
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Term
| CDK1 is used for which transition? |
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Definition
| G2/M transition (other cyclins mostly used for G1/S transition) |
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Term
| Retinoblastoma susceptibility protein |
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Definition
normally prevents cells from replicating by forming a tight complex with transcription factor E2F
phphorylation of RB releases it from E2F and allows transcription |
|
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Term
| p53 response if DNA damage is too severe |
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Definition
| activated leading to increased expression of a CDK inhibitor ultimately leading to apoptosis |
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Term
| Via what type of receptors does VEGF work through? |
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Definition
| Tyrosine kinase receptors |
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Term
| Binding of tyrosine kinase receptor leads to what 2 downstream effects? |
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Definition
1. Phopholipase Cy which produces IP3 (increase in calcium) and DAG which activates protein kinase C which activates transcription factors.
2. PI-3 kinase, which activates kinase Akt (protein kinase B) which is involved in cell proliferation and inhibition of apoptosis. |
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Term
| What is the GRB-2 pathway? |
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Definition
GRB-2 binds to activated tyrosine kinase receptor
GRB-2 binds SOS which together act on RAS
RAS binds to raf which together act on MAP kinase cascade
Phophorylation of transcription factors FOS and JUN which promote growth |
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Term
| Receptors for cytokines without tyrosine kinase activity |
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Definition
| JAK-->STATS-->transcription! |
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Term
| What happens to liver to repair? |
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Definition
| "compensatory hyperplasia" replication of mature cells in liver |
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Term
| Do intrahepatic stem cells play a role in the compensatory growth of the liver? |
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Definition
|
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Term
| What are the two major adhesive glycoproteins? |
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Definition
|
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Term
| What is the most common protein in animals? |
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Definition
|
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Term
| What is important for the tensile strength of collagen? |
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Definition
Cross-linking
-vitamin C is required for the hydroxylation of procollagen |
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Term
| What are some examples of defects in collagen production (inherited syndromes)? |
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Definition
| Ehlers-Danlos and osteogenesis imperfecta |
|
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Term
| What types of collagen are fibrillar (the most common type)? |
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Definition
|
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Term
| What types of collagen are nonfibrillar? |
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Definition
| Type 4; forms sheets; main component of the basement membrane along with laminin. |
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Term
| What acts as a scaffolding for elastin deposition? |
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Definition
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Term
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Definition
| inherited defect of fibrillin resulting in abnormal elastic fibers |
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Term
|
Definition
transmembrane protein that link the cell surface with the intracellular cytoskeleton
zonula adherens (cadherin-cadherin)
desmosoms (spot welds) |
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Term
|
Definition
bind actin (subunit of cadherin) and involved in cell-cytoskelteon interactions that allow for cell motility and differentiation
cell-cell contact inhibition |
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Term
|
Definition
| binding of fibronectin and laminin |
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Term
|
Definition
| bind many molecules (collagen, fibrin, proteoclycans, surface receptors) |
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Term
|
Definition
most abundant protein in the basement membrane
binds tightly to type 4 collagen |
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Term
|
Definition
| long repeating polymers of specific disaccharides |
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Term
|
Definition
GAGs linked to a core protein
heparan sulfate, chondroitin, keratan sulfate, and hyaluronan for example |
|
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Term
| What do fragments of hyaluronan do? |
|
Definition
| help recruit leukocytes to site of inflammation and stimulates production of inflammatory cytokines |
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Term
| What are the 5 steps of healing? (in order) |
|
Definition
inflammation
angiogenesis
migration and proliferation of fibroblasts
scar formation
connective tissue remodeling |
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Term
|
Definition
| proteolytic degradation of the basement membrane for angiogenesis |
|
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Term
| where do endothelial progenitor cells come from? |
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Definition
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Term
|
Definition
help destabilize cell-matrix interactions thus promoting angiogenesis (compare to metalloproteinases)
a "matricellular protein" |
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Term
| What is the order of cutaneous wound healing? |
|
Definition
1. Inflammation and formation of blood clot
2. Proliferation
-formation of granulation tissue
-proliferatin and migration of connective tissue cells
-re-epithelization
3. Maturation
-ECM deposition
-Tissue remodeling
-Wound contraction |
|
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Term
| First intention (primary union) |
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Definition
clean uninfected incision
death of limited amount of cells
re-epitheliazation occurs with formation of a thin scar |
|
|
Term
| second intention or secondary union |
|
Definition
large skin defects
-more intense inflammation
-intense granulation tissue formation
-extensive collagen deposition
-significant scarring which usually contracts by myofibroblasts |
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Term
|
Definition
within 24-72 hours
proliferation of fibroblasts and endothelial cells
hallmark of tissue repair
angiogenesis occurs
amount formed depends on the size of the tissue deficit |
|
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Term
| Timeline of cutaneous healing |
|
Definition
24-48 HOURS: epithelial cells move from the wounded edge depositing basement membrane component as they move
DAY 3: neutrophils replaced by macrophages, granulation tissue invades space, vertical collagen fibers, epithelial cell proliferation continues
DAY 5: neovascularization is maximal, epidermis returns to normal thickness, collagen fibrils begin to bridge gaps
SECOND WEEK: Continued accumulation of collagen and proliferation of fibroblasts, WBCs, edema and increased vascularity are gone
END OF FIRST MONTH: scar is composed of cellular connective tissue, dermal appendages permanently lost, tensile strength continues for months |
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|
Term
| What is the most important fibrogenic agent, released by macrophages? |
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Definition
|
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Term
| What are some of the keys to scar formation, emigration and proliferation of fibroblasts stage 1? |
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Definition
| VEGF responsible for increase in vascular permeability, which allows fibrinogen and fibronectin to endter the ECM. TGF-B most important to enable fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM by metalloproteinases |
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Term
| What are the 3 steps to scar formation? |
|
Definition
1.Emigration and proliferation of fibroblasts
2.ECM deposition and scar formation.
3. Tissue remodeling |
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Term
| What are some of the keys to scar formation, ECM deposition and scar formation stage 2? |
|
Definition
fibrillar collagens form a major portion of the connective tissue in repair sites
as the scar matures, vascular regression contiues resulting in a pale, avascular scar
eventually granulation tissue is converted into a scar |
|
|
Term
| What is the composition of a scar? |
|
Definition
| spindled fibroblasts, dense collagen, fragments of elastic tissue, other ECM components |
|
|
Term
| What are some of the keys to scar formation, tissue remodeling phase 3? |
|
Definition
| Remodeling is done by matrix metalloproteinases (collagenases, gelatinases, stromelysins) |
|
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Term
|
Definition
| degrade amorphous collagen and fibronectin |
|
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Term
|
Definition
| breakdown proteoglycans, laminin, fibronectin |
|
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Term
| After 1 week, what is the strength of a wounded site? After 3 months? |
|
Definition
|
|
Term
| What accounts for strength of a wound in first two months? Second two months? |
|
Definition
collagen synthesis
cross-linking collagen and increase collagen fibril size |
|
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Term
|
Definition
|
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Term
|
Definition
| due to inadequate vascularization, in areas with no sensation |
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Term
|
Definition
| excessive amounts of collagen producing a raised scar |
|
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Term
|
Definition
| scar tissue grows beyond the boundaries of the original wound and DOES NOT REGRESS |
|
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Term
|
Definition
| excess granulation tissue that protrudes above level of surround skin |
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Term
|
Definition
| aggressive fibromatosis (exuberant proliferation of fibroblasts and can fall between a benign proliferation and a low-grade malignant tumor |
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Term
|
Definition
| exaggerated process resulting in deformities of the wound and surrounding tissue (palms, soles, anterior chest, serious burns) |
|
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Term
|
Definition
excessive deposition of collagen and other ECM components in tissue
usually indicates the deposition of collagen in chronic disease
leads to chronic inflammation |
|
|
Term
| examples of fibrotic disorders |
|
Definition
liver cirrhosis
fibrosing diseases of the lung
chronic pancreatititis
constrictive pericarditis |
|
|
Term
| Phosphorylation of RB______from E2F |
|
Definition
|
|
Term
| if p53 is activated, it will lead to an increased expression of what? |
|
Definition
|
|
Term
| most abundant glycoprotein in the basement membrane |
|
Definition
|
|
Term
| what do integrins bind to? |
|
Definition
|
|
Term
| what molecule do cadherins utilize for cell mobility? |
|
Definition
|
|
Term
| what does laminin bind tightly to? |
|
Definition
|
|
Term
| hyaluronan falls under what category of proteins? |
|
Definition
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