Mp Ch3

Front 1

What are the two organs that undergo any sort of regeneration? What type of regeneration is it?

Back 1

1. Liver and kidney
2. Compensatory hypertrophy

Front 2

Healing is usually a tissue response to what three things?

Back 2

1. Wound
2. Inflammation in an internal organ
3. Cell necrosis in organs that cannot regerate

Front 3

Healing can be broken down into what two phases?

Back 3

1. Regeneration
2. Scar formation

Front 4

Inflammation of the lining of internal organs usually heals in what way?

Back 4

Scarring

Front 5

What is the replacesment of inflammatory infiltrates with granulation tissue called?

Back 5

Organization

Front 6

Scarring occurs when the tissue that is damaged lacks an intact _______ .

Back 6

ECM scaffold

Front 7

In adult tissues, what three factors determine the population size?

Back 7

1. Proliferation rate
2. Differentiation
3. Apoptosis

Front 8

What type of cell can replace some terminally differentiated cells?

Back 8

Stem cells

Front 9

What is an example of physiologic cell proliferation becomes pathologic?

Back 9

Benign Prostatic Hyperplasia

Front 10

What is the number one factor involved with proliferation of tissues?

Back 10

Activation of quiescent cells

Front 11

What are the three categories of tissues in terms of their division rates?

Back 11

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

Front 12

What are two properties of stem cells that make them unique?

Back 12

1. Prolonged self-renewal
2. Asymmetric replication

Front 13

How would you describe an embryonic stem cell (ESC) and where can you isolate them?

Back 13

1. Pluripotent
2. Blastocyst

Front 14

What can you attribute a ESCs pluripotentcy to?

Back 14

That activation of certain trascription factors like Nanog and Wnt-Beta-Catnin.

Front 15

What type of cells have limited division capacity and are lineage specific?

Back 15

Adult stem cells

Front 16

What are stem cells outside the bone marrow called?

Back 16

Tissue stem cells

Front 17

What is the name of the location where one can fine stem cells?

Back 17

Niches

Front 18

What type of cells regenerate/generate all types of blood cells and reconstitute bone marrow after irridation?

Back 18

Hematopoietic Stem Cells

Front 19

What are three ways to collect HSC?

Back 19

1. Tapping Marrow
2. From the umbilical cord
3. From circulation after treatment with the cytokine GMCSF

Front 20

What type of cells do bone marrow stromal cells give rise to(5)?

Back 20

1. Chondrocytes
2. Osteoblasts
3. Adipocytes
4. Myoblasts
5. Endotheilial cell precursors

Front 21

A change in a stem cell differentiation from one cell type to another is called?

Back 21

Transdifferentiation

Front 22

A cell that can differentiate into multiple cell lines is said to have _______ .

Back 22

Developmental Plasticity

Front 23

What are the heterogeneous group of stem cells that have broad differentiation capabilities that are adult bone marrow called?

Back 23

Multipotent Adult Progentitor Cells

Front 24

Where do liver stem cells reside? What type of cells do they differentiate into? What do those cells turn into?

Back 24

1. Canals of Hering
2. Oval cells
3. Hepatocytes and biliary cells

Front 25

When is the only time when liver stem cells are used?

Back 25

When normal liver cell proliferation is blocked.

Front 26

Where are neural stem cells located in the brain and what was used as the marker to locate them?

Back 26

1. Dentate gyrus and olfactory bulb
2. Nestin

Front 27

In the renewal of epithelial tissue, cell numbers are increased by what methods?

Back 27

1. Increasing the number of dividing stem cells
2. Increasing the number of replications in the amplification compartment
3. Shortening the replication time

Front 28

Growth factors have effects on what five areas?

Back 28

1. Proliferation
2. Locomotion
3. Contractibility
4. Differentiation
5. Angiogenesis

Front 29

What two growth factors share the same receptor? What are their basic functions? How does their receptor work? What is their main receptor?

Back 29

1. TGF-Alpha - proliferation of epithelial tissue
2. EGF - Mitogenic for a variety of different cells
3. Tyrosine Kinase activity
4. EGFR1

Front 30

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?

Back 30

1. Hepatocyte Growth Factor (HGF)
2. Scatter factor
3. c-MET

Front 31

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?

Back 31

1. Angiogenesis and Vasculogenesis
2. Tyrosine kinase receptors
3. VEGFR-2
4. VEGF-A

Front 32

Which VEGF receptor can be used in the mobilization of stem cells and inflammation? What type of VEGF binds to this receptor?

Back 32

1. VEGFR-1
2. VEGF-B

Front 33

Which receptors and VEGF are used for the production of lymphatics?

Back 33

1. VEGFR-3 with VEGF-C and VEGF-D

Front 34

What does platelet derived growth factor do? What is the main cell that releases PDGF? PDGF can be responsible for what condition and why?

Back 34

1. Causes the migration and proliferation of fibroblasts, smooth muscle and monocytes
2. Platelets upon activation
3. Liver fibrosis by activating stellate cell proliferation

Front 35

PDGF is made up of how many chains? How many surface receptors does PDGF have?

Back 35

1. Two; A and B (AA BB AB)
2. Two alpha and beta

Front 36

What are four functions of Fibroblast Growth Factor?

Back 36

1. Angiogenesis: FGF-2
2. Wound repair
3. Development - skelatal muscle and lung development for example
4. Hematopoesis

Front 37

Which FGF is a monocyet differentiation blocker?

Back 37

FGF-6

Front 38

How many isoforms are there of TGF-Beta? Which isoform is the most widespread? Is TGF-B active when secreted?

Back 38

1. Three TGF-B(1-3)
2. TGF-B1
3. No

Front 39

Describe what happens when TGF-B binds to its receptor?

Back 39

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

Front 40

Does TGF have many funtions?

Back 40

Yes it is considered pleiotropic with a vengence

Front 41

Does TGF-B promote or inhibit epithelial and leukocyte growth? If you lose TGF-B recptors you can develop what?

Back 41

1. Inhibit - inhibits Cip/Kip and INK/ARF
2. Cancer

Front 42

What effect does TGF-B have on fibroblasts and smooth muscle?

Back 42

Increases their proliferation - it is a potent fibrogenic agent

Front 43

Is TGF-B pro or anti inflammatory?

Back 43

Anti-inflammatory

Front 44

In basic terms, growth factors do two things. What are they?

Back 44

1. Up-regulate transcription
2. Allow the cell to move into the next step in the cell cycle

Front 45

What type of cell signalling is typically used in tissue repair of wounds? It is also used in hepatocyte replication.

Back 45

Paracrine

Front 46

What type of cell signalling is occuring when a molecule is anchored in the cell membrane for signalling purposes?

Back 46

Juxtacrine signalling

Front 47

True or false: most signal transduction pathways involve the dimer or trimerization of receptors?

Back 47

True

Front 48

What type of receptor do all of the growth factors use along with insulin?

Back 48

Tyrosine-Kinase

Front 49

Basically what happens when a Tyrosine-Kinase receptor is activated?

Back 49

Dimerization which allows cross P which acivates the kinase activity.

Front 50

What are three other molecules/enzymes used in tyrosine-kinase signalling?

Back 50

1. Phospholipase C
2. PI3K - activates Kinase-Akt
3. GRB-2 and SOS

Front 51

The activation of Kinase Akt results in what two things? What else is it used in?

Back 51

1. Increased cell proliferation and decreased apoptosis
2. Insulin signalling

Front 52

GRB-2 and SOS end up activating what? Then that molecule makes what?

Back 52

1. MAP-Kinase
2. TFs FOS and JUN

Front 53

Cytokines, interferons, erythropoientin, GSCF, GH and prolactin signal through what system? In this system, what is produced?

Back 53

1. JAK/STATs
2. STATS act as TFs

Front 54

Where do breast cancer steroid receptors bind?

Back 54

In the cytoplasm of the cell instead of the nucleus.

Front 55

When a rapid response is needed, are new TFs made? What happens?

Back 55

1. No existing ones are used
2. They are modified

Front 56

What type of genes are directly related to the proliferation of cells?

Back 56

Proto-onco genes

Front 57

What two things generally stimulate a cell to replicate?

Back 57

1. Growth factors
2. Signalling of ECM components through integrins

Front 58

What point in the cell cycle is known as the rate limiting restriction point? What regulates this step

Back 58

1. G1/S point
2. CDK that bind cyclins and end up P proteins needed for the transcription

Front 59

What is the role of Rb in replication?

Back 59

When activated, it P EF2 so that it no longer works. When P by the CDK/cyclin complex, Rb no longer can P EF2

Front 60

If there are mistakes in the replication of cell DNA, what initates apoptosis?

Back 60

p53

Front 61

Most tissue regeneration is what? What does it end up restoring?

Back 61

1. Compensatory hypertrophy or hyperplasia
2. Function not anatomy

Front 62

What is attributed to the lack of true regeneration in human tissues?

Back 62

Rapid scarring

Front 63

What five organs are the only ones with regenerative capabilities?

Back 63

1. Kideny
2. Liver
3. Adrenal gland
4. Thyroid
5. Pancreas

Front 64

In liver regeneration, hepatocytes move from what stage in the cell cyle to what stage in the cell cycle?

Back 64

1. G0 to G1

Front 65

What is special about the wave of proliferation of the hepatocytes and non-parenchymal cells?

Back 65

It is synchronized.

Front 66

What is hepatocyte replication dependent on?

Back 66

Paracrine effects of growth factors and cytokines released by non-parenchymal cells

Front 67

What are the two major cell cyle restriction points in liver regeneration and what cytokines/GF are associted with each?

Back 67

1. G0/G1: IL-1 and TNF
2. G1/S: HGF TGF-Alpha

Front 68

What CDK-Cyclin complexes helps move the cell at the G1/S point?

Back 68

1. CyclinD-CDK4: P of Rb
2. CyclinE-CDK2

Front 69

What is the primer for replication in liver regeneration? What does it cause the release of for the G1/S phase?

Back 69

1. TNF
2. HGF release and TGF-Alpha activation

Front 70

What are the three macromolecules that constitute ECM?

Back 70

1. Fibrous structural proteins
2. Adhesive glycoproteins
3. Proteoglycans and hyaluronic acid

Front 71

What is the amino acid sequence that makes collagen unique?

Back 71

Gly-X-Y

Front 72

What type of collagen is amorphous and where is it seen?

Back 72

1. Type IV
2. Basement membrane

Front 73

What other compound is seen in the basement membrane with Type IV collagen?

Back 73

Laminin

Front 74

What enzyme crosslinks collagen? What substance is required for cross-linking? What disorder is a result of a lack of this substance?

Back 74

1. Lysyl Oxidase
2. Vitamin C
3. Scurvy

Front 75

What are three disorders that involve collagen? Which collagens do they involve?

Back 75

1. Scurvy - Vit C def.
2. Ehlers Danlos - Type I, III and IV collagens
3. Osteogenesis imperfecta - Type I collagen

Front 76

What type of fibers allow for tissue recoil?

Back 76

Elastic fibers

Front 77

What syndrome is marked by a mutation in elastic fibers?

Back 77

Marfan Syndrome

Front 78

What are the four familes of CAM that can act as a receptor or protein?

Back 78

1. Integrin
2. Selectin
3. Immunoglobin
4. Cadherins

Front 79

What are two examples of ECM proteins that integrins bind to?

Back 79

1. Fibronectin
2. Laminin

Front 80

What is tissue fibronectin used in? What is plasma fibronectin used in?

Back 80

1. Wound healing
2. Clotting

Front 81

What is the most abundant ECM protein in the basement membrane? What does it bind to?

Back 81

1. Laminin
2. Type IV collagen

Front 82

What allows the transmission of enviromental signals to the cell for the releasal of growth factors?

Back 82

Integrins binding with actin and intermediate filaments

Front 83

What is the name for the area where clusters of receptors for certain ligand localize? What are some cytoskeletal proteins that localize here?

Back 83

1. Focal adhesion complexes
2. Talin, vinculin and paxillin

Front 84

What class of molecules link cadherins with actin?

Back 84

Catenins

Front 85

What molecule can be a regulator of nuclear transcription and is involved with cancer?

Back 85

Free B-Catenin

Front 86

What does SPARC/Osteonectin and Thrombospondins do?

Back 86

Angiogenesis inhibitor

Front 87

What does osteopontin do?

Back 87

Regulates calcification

Front 88

What does tanacin do?

Back 88

Regulates morphogensis and cell adhesion

Front 89

What is a proteoglycan? What are the most common? What do they do?

Back 89

1. Protein + GAG
2. Heparan sulfate, chondriotin sulfate and dermatin sulfate
3. Regulate tissue structure/permeability and modulate cell growth and differentiation

Front 90

What is the main function of hyaluronic acid. What is another function? What surface glycoprotein on leukocytes binds HA?

Back 90

1. Binds lots of H2O and becomes a viscous gel for joint (cartilage)
2. Prevents migrating cells from binding to other cells
3. CD44

Front 91

What two processes are going on at once during fibrosis?

Back 91

1. Wound healing and wound damage

Front 92

What is a hallmark for healing? When is its production begun? What are its key features?

Back 92

1. Granulation tissue
2. 24h after insult
3. Angiogenesis and proliferation of fibroblasts

Front 93

Can angiogenesis occur from the recruitment of endothelial progenitor cells?

Back 93

Yes

Front 94

What is the common precursor cell in HSC and Angioblasts?

Back 94

Hemangioblast

Front 95

What do angioblasts form?

Back 95

1. New vessels, pericytes and smooth muscle from the vessel

Front 96

It is now known that what angioblast-like cells are stored in bone marrow and called upon when needed?

Back 96

Endothelial Progentitor Cells

Front 97

Which VEGFR is the most important in angiogenesis and what does it bind?

Back 97

1. VEGFR-2
2. VEGF-A

Front 98

What happens in the basic model of angiogenesis? What is a second option?

Back 98

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

Front 99

What must new vessels be supported by?

Back 99

1. Pericytes
2. Smooth muscle
3. ECM

Front 100

What are four stabilizing factors of new vessels and their function?

Back 100

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

Front 101

What can cause venous malformations?

Back 101

Abscence of Tie2

Front 102

In fibroblast migration and proliferation, what causes the increased vascular permeability that allows proteins like fibrinogen and fibronectin to enter the area?

Back 102

VEGF

Front 103

What cytokines are active in the migration and proliferation of fibroblasts in scar formation?

Back 103

1. IL-1
2. TNF

Front 104

What is the most important growth factor in inflammatory fibrosis? Why?

Back 104

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

Front 105

What is the main component of the formation of the actual scar? When does the laying of collagen begin?

Back 105

1. Fibrillar Collagen
2. 3-5 days after insult

Front 106

The balance between ECM synthesis and degradation is referred to as ________.

Back 106

Remodeling

Front 107

ECM degradation is achieved by what enzymes? They are dependent on what metal?

Back 107

1. MMP
2. Zinc

Front 108

How are MMPs synthesized?

Back 108

1. Propeptides which means they need to be activated

Front 109

What inhibits MMP secretion? What also inhibits the actions of collagenases?

Back 109

1. TGF-B
2. Tissue Inhibitors of MMPs

Front 110

What are the actions of ADAM enzymes? What defiency leads to embryonic death by pulmonary hypolasia?

Back 110

1. They cleave the membrane bound forms of GFs allowing to be become free.
2. ADAM-17

Front 111

Why do fetal cutaneous wounds heal with no scarring and little inflammation?

Back 111

They have a different isoform of TGF-B.

Front 112

What is hallmark of healing by second intention?

Back 112

Wound contracture

Front 113

What is the maximal strength of a wound after healing?

Back 113

About 70% of normal strength

Front 114

Steroids can activate what recepor that is important in the cellular differentiation of adipocytes?

Back 114

Peroxisome Proliferator Activated Receptors

Front 115

White is a primer for cellular replication in liver damage? What does it do?

Back 115

1. TNF
2. Upregulates everything needed for replication
3. Causes the release of HGF and the activation of TNF-Alpha

Front 116

What is a key ECM protein that mediates angiogenesis?

Back 116

1. Alpha v Beta 3
2. Interacts with MMP-2, regulates VEGFR-2, mediates adhesion to ECM components such as fibronectin, thrombospondin and osteopontin

Front 117

Fibroblast Migration and Proliferation is triggered by what six factors?

Back 117

1. TGF-B
2. IL-1
3. TNF
4. PDGF
5. FGF
6. EGF

Front 118

Ulceration is usually due to what?

Back 118

Inadequate vascularization

Front 119

What deficiency causes great contracture in mice?

Back 119

MMP3 (Stromelysin-1)