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119 Cards in this Set
- Front
- Back
What are the two organs that undergo any sort of regeneration? What type of regeneration is it?
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1. Liver and kidney
2. Compensatory hypertrophy |
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Healing is usually a tissue response to what three things?
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1. Wound
2. Inflammation in an internal organ 3. Cell necrosis in organs that cannot regerate |
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Healing can be broken down into what two phases?
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1. Regeneration
2. Scar formation |
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Inflammation of the lining of internal organs usually heals in what way?
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Scarring
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What is the replacesment of inflammatory infiltrates with granulation tissue called?
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Organization
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Scarring occurs when the tissue that is damaged lacks an intact _______ .
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ECM scaffold
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In adult tissues, what three factors determine the population size?
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1. Proliferation rate
2. Differentiation 3. Apoptosis |
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What type of cell can replace some terminally differentiated cells?
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Stem cells
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What is an example of physiologic cell proliferation becomes pathologic?
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Benign Prostatic Hyperplasia
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What is the number one factor involved with proliferation of tissues?
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Activation of quiescent cells
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What are the three categories of tissues in terms of their division rates?
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1. Quiescent tissues - low levels of replication
2. Continuosly dividing tissues - surface epithelia and bone marrow; most cells derived from stem cells 3. Non-dividing tissues - cells in these tissues have left the cell cycle; skeletal, cardiac or neurons |
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What are two properties of stem cells that make them unique?
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1. Prolonged self-renewal
2. Asymmetric replication |
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How would you describe an embryonic stem cell (ESC) and where can you isolate them?
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1. Pluripotent
2. Blastocyst |
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What can you attribute a ESCs pluripotentcy to?
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That activation of certain trascription factors like Nanog and Wnt-Beta-Catnin.
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What type of cells have limited division capacity and are lineage specific?
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Adult stem cells
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What are stem cells outside the bone marrow called?
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Tissue stem cells
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What is the name of the location where one can fine stem cells?
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Niches
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What type of cells regenerate/generate all types of blood cells and reconstitute bone marrow after irridation?
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Hematopoietic Stem Cells
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What are three ways to collect HSC?
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1. Tapping Marrow
2. From the umbilical cord 3. From circulation after treatment with the cytokine GMCSF |
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What type of cells do bone marrow stromal cells give rise to(5)?
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1. Chondrocytes
2. Osteoblasts 3. Adipocytes 4. Myoblasts 5. Endotheilial cell precursors |
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A change in a stem cell differentiation from one cell type to another is called?
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Transdifferentiation
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A cell that can differentiate into multiple cell lines is said to have _______ .
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Developmental Plasticity
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What are the heterogeneous group of stem cells that have broad differentiation capabilities that are adult bone marrow called?
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Multipotent Adult Progentitor Cells
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Where do liver stem cells reside? What type of cells do they differentiate into? What do those cells turn into?
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1. Canals of Hering
2. Oval cells 3. Hepatocytes and biliary cells |
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When is the only time when liver stem cells are used?
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When normal liver cell proliferation is blocked.
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Where are neural stem cells located in the brain and what was used as the marker to locate them?
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1. Dentate gyrus and olfactory bulb
2. Nestin |
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In the renewal of epithelial tissue, cell numbers are increased by what methods?
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1. Increasing the number of dividing stem cells
2. Increasing the number of replications in the amplification compartment 3. Shortening the replication time |
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Growth factors have effects on what five areas?
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1. Proliferation
2. Locomotion 3. Contractibility 4. Differentiation 5. Angiogenesis |
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What two growth factors share the same receptor? What are their basic functions? How does their receptor work? What is their main receptor?
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1. TGF-Alpha - proliferation of epithelial tissue
2. EGF - Mitogenic for a variety of different cells 3. Tyrosine Kinase activity 4. EGFR1 |
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What growth factor acts as a morphogen in embyronic development that causes cell scattering and migration? 2. What is another name for the GF? Its receptor is a product of what protoonco gene?
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1. Hepatocyte Growth Factor (HGF)
2. Scatter factor 3. c-MET |
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What two processes is VEGF protent in stimulating? What action do its receptors signal through? What is the main receptor? Which VEGF binds to it?
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1. Angiogenesis and Vasculogenesis
2. Tyrosine kinase receptors 3. VEGFR-2 4. VEGF-A |
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Which VEGF receptor can be used in the mobilization of stem cells and inflammation? What type of VEGF binds to this receptor?
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1. VEGFR-1
2. VEGF-B |
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Which receptors and VEGF are used for the production of lymphatics?
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1. VEGFR-3 with VEGF-C and VEGF-D
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What does platelet derived growth factor do? What is the main cell that releases PDGF? PDGF can be responsible for what condition and why?
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1. Causes the migration and proliferation of fibroblasts, smooth muscle and monocytes
2. Platelets upon activation 3. Liver fibrosis by activating stellate cell proliferation |
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PDGF is made up of how many chains? How many surface receptors does PDGF have?
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1. Two; A and B (AA BB AB)
2. Two alpha and beta |
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What are four functions of Fibroblast Growth Factor?
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1. Angiogenesis: FGF-2
2. Wound repair 3. Development - skelatal muscle and lung development for example 4. Hematopoesis |
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Which FGF is a monocyet differentiation blocker?
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FGF-6
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How many isoforms are there of TGF-Beta? Which isoform is the most widespread? Is TGF-B active when secreted?
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1. Three TGF-B(1-3)
2. TGF-B1 3. No |
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Describe what happens when TGF-B binds to its receptor?
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1. TGF-B binds to a type II receptor which binds to a type I receptor (serine/threonine)
2. This leads to the P of smad2 and smad 3. 3. They form dimers with smad 4 and become TFs |
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Does TGF have many funtions?
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Yes it is considered pleiotropic with a vengence
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Does TGF-B promote or inhibit epithelial and leukocyte growth? If you lose TGF-B recptors you can develop what?
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1. Inhibit - inhibits Cip/Kip and INK/ARF
2. Cancer |
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What effect does TGF-B have on fibroblasts and smooth muscle?
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Increases their proliferation - it is a potent fibrogenic agent
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Is TGF-B pro or anti inflammatory?
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Anti-inflammatory
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In basic terms, growth factors do two things. What are they?
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1. Up-regulate transcription
2. Allow the cell to move into the next step in the cell cycle |
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What type of cell signalling is typically used in tissue repair of wounds? It is also used in hepatocyte replication.
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Paracrine
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What type of cell signalling is occuring when a molecule is anchored in the cell membrane for signalling purposes?
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Juxtacrine signalling
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True or false: most signal transduction pathways involve the dimer or trimerization of receptors?
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True
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What type of receptor do all of the growth factors use along with insulin?
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Tyrosine-Kinase
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Basically what happens when a Tyrosine-Kinase receptor is activated?
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Dimerization which allows cross P which acivates the kinase activity.
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What are three other molecules/enzymes used in tyrosine-kinase signalling?
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1. Phospholipase C
2. PI3K - activates Kinase-Akt 3. GRB-2 and SOS |
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The activation of Kinase Akt results in what two things? What else is it used in?
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1. Increased cell proliferation and decreased apoptosis
2. Insulin signalling |
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GRB-2 and SOS end up activating what? Then that molecule makes what?
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1. MAP-Kinase
2. TFs FOS and JUN |
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Cytokines, interferons, erythropoientin, GSCF, GH and prolactin signal through what system? In this system, what is produced?
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1. JAK/STATs
2. STATS act as TFs |
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Where do breast cancer steroid receptors bind?
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In the cytoplasm of the cell instead of the nucleus.
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When a rapid response is needed, are new TFs made? What happens?
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1. No existing ones are used
2. They are modified |
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What type of genes are directly related to the proliferation of cells?
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Proto-onco genes
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What two things generally stimulate a cell to replicate?
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1. Growth factors
2. Signalling of ECM components through integrins |
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What point in the cell cycle is known as the rate limiting restriction point? What regulates this step
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1. G1/S point
2. CDK that bind cyclins and end up P proteins needed for the transcription |
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What is the role of Rb in replication?
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When activated, it P EF2 so that it no longer works. When P by the CDK/cyclin complex, Rb no longer can P EF2
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If there are mistakes in the replication of cell DNA, what initates apoptosis?
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p53
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Most tissue regeneration is what? What does it end up restoring?
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1. Compensatory hypertrophy or hyperplasia
2. Function not anatomy |
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What is attributed to the lack of true regeneration in human tissues?
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Rapid scarring
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What five organs are the only ones with regenerative capabilities?
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1. Kideny
2. Liver 3. Adrenal gland 4. Thyroid 5. Pancreas |
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In liver regeneration, hepatocytes move from what stage in the cell cyle to what stage in the cell cycle?
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1. G0 to G1
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What is special about the wave of proliferation of the hepatocytes and non-parenchymal cells?
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It is synchronized.
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What is hepatocyte replication dependent on?
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Paracrine effects of growth factors and cytokines released by non-parenchymal cells
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What are the two major cell cyle restriction points in liver regeneration and what cytokines/GF are associted with each?
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1. G0/G1: IL-1 and TNF
2. G1/S: HGF TGF-Alpha |
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What CDK-Cyclin complexes helps move the cell at the G1/S point?
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1. CyclinD-CDK4: P of Rb
2. CyclinE-CDK2 |
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What is the primer for replication in liver regeneration? What does it cause the release of for the G1/S phase?
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1. TNF
2. HGF release and TGF-Alpha activation |
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What are the three macromolecules that constitute ECM?
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1. Fibrous structural proteins
2. Adhesive glycoproteins 3. Proteoglycans and hyaluronic acid |
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What is the amino acid sequence that makes collagen unique?
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Gly-X-Y
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What type of collagen is amorphous and where is it seen?
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1. Type IV
2. Basement membrane |
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What other compound is seen in the basement membrane with Type IV collagen?
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Laminin
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What enzyme crosslinks collagen? What substance is required for cross-linking? What disorder is a result of a lack of this substance?
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1. Lysyl Oxidase
2. Vitamin C 3. Scurvy |
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What are three disorders that involve collagen? Which collagens do they involve?
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1. Scurvy - Vit C def.
2. Ehlers Danlos - Type I, III and IV collagens 3. Osteogenesis imperfecta - Type I collagen |
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What type of fibers allow for tissue recoil?
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Elastic fibers
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What syndrome is marked by a mutation in elastic fibers?
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Marfan Syndrome
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What are the four familes of CAM that can act as a receptor or protein?
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1. Integrin
2. Selectin 3. Immunoglobin 4. Cadherins |
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What are two examples of ECM proteins that integrins bind to?
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1. Fibronectin
2. Laminin |
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What is tissue fibronectin used in? What is plasma fibronectin used in?
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1. Wound healing
2. Clotting |
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What is the most abundant ECM protein in the basement membrane? What does it bind to?
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1. Laminin
2. Type IV collagen |
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What allows the transmission of enviromental signals to the cell for the releasal of growth factors?
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Integrins binding with actin and intermediate filaments
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What is the name for the area where clusters of receptors for certain ligand localize? What are some cytoskeletal proteins that localize here?
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1. Focal adhesion complexes
2. Talin, vinculin and paxillin |
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What class of molecules link cadherins with actin?
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Catenins
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What molecule can be a regulator of nuclear transcription and is involved with cancer?
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Free B-Catenin
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What does SPARC/Osteonectin and Thrombospondins do?
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Angiogenesis inhibitor
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What does osteopontin do?
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Regulates calcification
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What does tanacin do?
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Regulates morphogensis and cell adhesion
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What is a proteoglycan? What are the most common? What do they do?
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1. Protein + GAG
2. Heparan sulfate, chondriotin sulfate and dermatin sulfate 3. Regulate tissue structure/permeability and modulate cell growth and differentiation |
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What is the main function of hyaluronic acid. What is another function? What surface glycoprotein on leukocytes binds HA?
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1. Binds lots of H2O and becomes a viscous gel for joint (cartilage)
2. Prevents migrating cells from binding to other cells 3. CD44 |
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What two processes are going on at once during fibrosis?
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1. Wound healing and wound damage
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What is a hallmark for healing? When is its production begun? What are its key features?
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1. Granulation tissue
2. 24h after insult 3. Angiogenesis and proliferation of fibroblasts |
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Can angiogenesis occur from the recruitment of endothelial progenitor cells?
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Yes
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What is the common precursor cell in HSC and Angioblasts?
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Hemangioblast
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What do angioblasts form?
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1. New vessels, pericytes and smooth muscle from the vessel
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It is now known that what angioblast-like cells are stored in bone marrow and called upon when needed?
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Endothelial Progentitor Cells
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Which VEGFR is the most important in angiogenesis and what does it bind?
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1. VEGFR-2
2. VEGF-A |
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What happens in the basic model of angiogenesis? What is a second option?
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1. VEGF stimulates the migration of EPCs from bone marrow to the site. These cells form a capillary plexus that matures into mature vessels.
2. VEGF can cause the mobilization of endothelial cells from existing vessels to form new ones |
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What must new vessels be supported by?
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1. Pericytes
2. Smooth muscle 3. ECM |
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What are four stabilizing factors of new vessels and their function?
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1. Ang1 - interacts with Tie2 to recruit pericytes
2. Ang2 - interacts with Tie2 to loosen vessels to be more reactive with VEGF 3. PDGF - recruits smooth muscle cells 4. TGF-B - recruits ECM proteins |
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What can cause venous malformations?
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Abscence of Tie2
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In fibroblast migration and proliferation, what causes the increased vascular permeability that allows proteins like fibrinogen and fibronectin to enter the area?
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VEGF
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What cytokines are active in the migration and proliferation of fibroblasts in scar formation?
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1. IL-1
2. TNF |
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What is the most important growth factor in inflammatory fibrosis? Why?
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1. TGF-B
2. Because it big in the recruitment of cells needed for fibrosis and it also is a chemotactic for monocytes and causes angiogenesis |
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What is the main component of the formation of the actual scar? When does the laying of collagen begin?
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1. Fibrillar Collagen
2. 3-5 days after insult |
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The balance between ECM synthesis and degradation is referred to as ________.
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Remodeling
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ECM degradation is achieved by what enzymes? They are dependent on what metal?
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1. MMP
2. Zinc |
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How are MMPs synthesized?
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1. Propeptides which means they need to be activated
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What inhibits MMP secretion? What also inhibits the actions of collagenases?
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1. TGF-B
2. Tissue Inhibitors of MMPs |
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What are the actions of ADAM enzymes? What defiency leads to embryonic death by pulmonary hypolasia?
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1. They cleave the membrane bound forms of GFs allowing to be become free.
2. ADAM-17 |
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Why do fetal cutaneous wounds heal with no scarring and little inflammation?
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They have a different isoform of TGF-B.
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What is hallmark of healing by second intention?
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Wound contracture
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What is the maximal strength of a wound after healing?
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About 70% of normal strength
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Steroids can activate what recepor that is important in the cellular differentiation of adipocytes?
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Peroxisome Proliferator Activated Receptors
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White is a primer for cellular replication in liver damage? What does it do?
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1. TNF
2. Upregulates everything needed for replication 3. Causes the release of HGF and the activation of TNF-Alpha |
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What is a key ECM protein that mediates angiogenesis?
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1. Alpha v Beta 3
2. Interacts with MMP-2, regulates VEGFR-2, mediates adhesion to ECM components such as fibronectin, thrombospondin and osteopontin |
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Fibroblast Migration and Proliferation is triggered by what six factors?
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1. TGF-B
2. IL-1 3. TNF 4. PDGF 5. FGF 6. EGF |
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Ulceration is usually due to what?
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Inadequate vascularization
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What deficiency causes great contracture in mice?
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MMP3 (Stromelysin-1)
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