Exam 2

Question 1

What makes up the epimysium?

Answer 1

nerves and blood vessels in CT tissue (investing fascia)

Question 2

What does the perimysium do?

Answer 2

separates the muscle into fascicles

Question 3

What does the endomysium do and what is it made of?

Answer 3

separates individual muscle fibers, made up of reticular fibers and ECM

Question 4

What is considered the histological functional unit/cell of the muscle?

Answer 4

muscle fiber

Question 5

Define myofibrils.

Answer 5

parallel cylinders of contractile proteins and organelles

Question 6

Define myofilaments.

Answer 6

contractile, structural, and regulatory proteins

Question 7

What is the sarcolemma?

Answer 7

the plasma membrane of the muscle cell or fiber

Question 8

What is a syncyctium?

Answer 8

multinucleated with nuclei just under the sarcolemma

Question 9

Where can the mitochondria of a skeletal muscle cell be located?

Answer 9

nuclear pores and rows between myofibrils

Question 10

Where can the Golgi be found in a skeletal muscle cell?

Answer 10

perinuclear region

Question 11

What is the T-tubule system?

Answer 11

invagination of sarcolemma, contains voltage sensitive CA2+ channel connected to SR which opens with depolarization

Question 12

What makes up the triad in skeletal muscle cells?

Answer 12

the T-tubule and 2 adjoining terminal cisternae, located at the A-I junction (2 per sarcomere)

Question 13

What is the sarcoplasmic reticulum?

Answer 13

continuous system of membrane lined canaliculi, longitudinally organized over fiber

Question 14

what are fenestrated cisternae?

Answer 14

anastomosis over center of sarcmoere

Question 15

What are terminal cisternae?

Answer 15

large transverse channels located next to T tubles, conc CA2+, part of the SR

Question 16

What makes up the protein Actin? What type of muscle protein is it considered?

Answer 16

contractile, G actin binds head to tail which makes up f actin, 2 F actin form double helix

Question 17

What prevents the actin in muscles from being degraded?

Answer 17

Cap Z at + end where it attaches to the Z line, and tropomodulin on the - end

Question 18

What makes up the protein myosin and what type of muscle protein is it?

Answer 18

motor, 2 heavy chains with globular heads and 2 light chains form a helix, fixed together along the M line with globular heads projecting out away from m line and a portion on either side of the line bare of heads

Question 19

What type of muscle protein is tropomyosin and describe it?

Answer 19

regulatory, in groove formed by double helix of actin, it inhibits actin myosin interaction, when displaced by troponin it exposes binding site

Question 20

what type of muscle protein is troponin and describe it?

Answer 20

regulatory, at intervals along actin and tropomyosin, CA2+ sensitive,

Question 21

What are the three subunits of troponin and their functions?

Answer 21

TnT- binds tropomyosin
TnC- binds Ca2+
TnI- inhibits actomyosin Mg2+ ATPase and binding of myosin

Question 22

What proteins can be found in the z-disk matrix?

Answer 22

cap Z, filamin, amorphin, a-actin, actin binding protein

Question 23

What type of protein is a-actin in muscles and what does it do?

Answer 23

structural, dense amorphous region making up most of the z-disc contains actin binding protein holding actin filaments in a lattice structure

Question 24

What type of protein is Myomesin and what does it do?

Answer 24

structural, interconnects 6 myosin filaments and holds them in the center of A band at M line, also called M-protein

Question 25

What does C protein do in muscles?

Answer 25

myosin binding protein in strips parallel to M line

Question 26

What type of muscle protein is Titin and what does it do?

Answer 26

structural, elastic, largest, from z-disk to M-line, associated with myosin, contributes to assembly and resting tension acts as 2 springs in series, also called connectin

Question 27

What type of muscle protein is Nebulin and what does it do?

Answer 27

structural, inextensible filament from z disk along actin to regulate/stabilize length

Question 28

What type of muscle protein are Desmin and Vimentim and what do they do?

Answer 28

Intermediate filaments that link adjacent myofibrils at z-lines

Question 29

What type of muscle protein is Dystrophen and what does it do?

Answer 29

structural, cytoskeletal proteins that binds the ECM protein laminin 2, connects actin to sarcolemma to stabilize and reinforce sarcolemma during contraction

Question 30

Deficiency or lack of Dystrophin results in what condition? How?

Answer 30

Duchenne’s muscular dystrophy, tiny ruptures in the sarcolemma occur during contraction leading to cell death

Question 31

What 3 “structures” make up the A band? How are they arranged? What changes during contraction?

Answer 31

M-Line, dark line in center
L Lines, lighter on either side of M line
H band lighter band beyond L lines, changes in length during contraction

Question 32

What structure is in the I band? What changes during contraction?

Answer 32

the Z-line dark line in the center, gets smaller during contraction

Question 33

Explain sliding filament theory fo muscle contraction.

Answer 33

thick and thin filaments maintain length, Actin pulled toward center of A band narrowing and obliterating I band, Z disk drawn toward A band

Question 34

Explain the motor Protein and energy theory of muscle contraction.

Answer 34

myosin “walks” along actin filament in sequence repetitive binding and release, process powered by ATP hydrolysis

Question 35

What is located at the Myoneural junction?

Answer 35

motor end plate= termination of mortor nerve fiber, synaptic vesicles with Ach, receptors for Ach

Question 36

What causes Myasthemia Gravis?

Answer 36

autoimmune disorder, antibodies bind to Ach receptors and block contraction

Question 37

What are muscle spindles? Function?

Answer 37

proprioceptor sensory organs, signal length and rate of contraction

Question 38

What are intrafusal fibers? Function?

Answer 38

specialized muscle fibers, attached to endomyosin, sense contraction

Question 39

What are satellite cells in muscle?

Answer 39

inactive adult stem cells, divide after damage, spindle shaped just below basal lamina

Question 40

Describe Excitation contraction coupling.

Answer 40

AP, release Ach, Muscle AP, T-system transmission, release of Ca2+ from SR, activation of contractile proteins, Ca2+ reaccumulation into SR

Question 41

Name the differences between cardiac and skeletal muscle.

Answer 41

Cardica is uninucleated in center of cell, have branched fibers, myofibrils diverge around nucleus, intercalated discs connect cells end to end, spontaneous rhythmical contraction, fewer larger T-tubules lined with glycoprotein and located at Z line (1/sarcomere), SR smaller & simpler, Termial Cisternae form dyads, larger more numerous mitochondria, many glycogen granules

Question 42

What structures make up the intercalated discs?

Answer 42

maculae adherens, fascia adherens, nexus, and intercellular gap

Question 43

What is the maculae adherens in intercalated discs?

Answer 43

desmosome, thickening of inner layer of plasma membrane, condensation with intermediate filaments

Question 44

What is the fascia adherens?

Answer 44

part of intercalated disc, dense material subadjacent to membrane, termination of I band filaments, corresponds with Z line

Question 45

What is a Nexus in cardiac tissue?

Answer 45

gap junction in intercalated disc, low electrical resistance for spread of imulse

Question 46

What is the intercellular gap in cardiac tissue?

Answer 46

part of intercalated disc, unspecialized region of variable size.

Question 47

Where can smooth muscle be found?

Answer 47

GI tract wall, ducts of glands (GI, Resp, UG), blood vessels and lymph vessels, iris and ciliary body

Question 48

what makes smooth muscles different from skeletal?

Answer 48

long spindle shape, variable size, central elongated nucleus, not striated, staggered arrangement of cells, covered by a basement membrane, surrounded by reticular fibers, capable of active regeneration, dense bodies of a-actin desmin and vimentin inserting into dense bodies, Caveolae, myosin organized into thick filament at activation, actin always arranged

Question 49

What are calveolae?

Answer 49

micropinocytic vesicles act as primitive t-tubule system with a rudimentary SR

Question 50

How do the smooth muscle cells relate cell to cell?

Answer 50

basal lamina with collagen bundles, no desmosomes, mechanical force of contraction transmitted through CT, Nexus-limited areas of narrowed intercellular space-site of low electrical resistance opposing sarcolemma specialized

Question 51

Describe contraction of a smooth muscle cell?

Answer 51

Slow rate, sustained contracted state with little energy expenditure, activation by nerve impulse, Ca2+, calmodulin, cAMP, hormones, local changes and stretching

Question 52

what does Calmodulin do?

Answer 52

Ca2+ binding protein, activates MLCK

Question 53

What does MLCK stand for and what does it do?

Answer 53

myosin light chain kinase, phosphorylates myosin, causes myosin conformational change to expose actin binding site, triggers cross bridge cycling

Question 54

What is signal transduction?

Answer 54

process by which information sent by one cell is chemically converted into a response by another

Question 55

What is contact dependent signaling?

Answer 55

ligand fixed to signaling cell which binds to receptor on target cell, Juxtacrine signaling, very local

Question 56

What is paracrine signaling?

Answer 56

relay system, ligand from signal cell diffuses to local target cell

Question 57

What is synaptic signaling?

Answer 57

also neuronal, very short term, enzymes in synapse hydrolyze ligand rapidly, spike (seconds or less)

Question 58

What is endocrine signaling?

Answer 58

gland, ductless, like beta cell secreting insulin, ligand enters blood stream and acts on target cells through out the body, Wave (minutes to hours)

Question 59

what two signaling methods are important in cancer progression?

Answer 59

autocrine and intracrine

Question 60

What is autocrine signaling?

Answer 60

self signaling release a ligand that acts on cell, signal cell=target cell

Question 61

What is intracrine signaling?

Answer 61

signal never leaves the cell

Question 62

Name the three categories of signaling molecules?

Answer 62

Hormones (steroids, Peptides, amino acid derivatives), Local mediators (paracrine- polypeptides or gas NO), Neurotransmitters (often polypeptides)

Question 63

What is pleiotropy?

Answer 63

signal can cause different effects in a particular target cell or response may be distinct between two different cell types, response is based on target cell not ligand

Question 64

What is integration in cell signaling?

Answer 64

cell specific collection of different receptors leads to modulated response to a particular signal by presence of another, simultaneous signal, ie basal activity, proliferative signal, differentiation, or lack of signal leading to cell death (regional)

Question 65

what signal molecules use direct entry?

Answer 65

Amphipathic- steroid, retinoic acid, vitamin D, and thyroid (gene responses), or Nitric Oxide- dissolved gas from arginine, endothelial cells release NO to stimulate smooth muscle contraction and cause dilation of the vessels.

Question 66

What does NO bind to and describe it effect?

Answer 66

activates enzyme gaunylate cyclase turning GTP to cGMP, the PDE5 (phosphodiesterase) turns cGMP to GMP to make it inactive

Question 67

What are the functions of cell surface repceptors?

Answer 67

transfer signal, transform signal(transduce), amplify signal, distribute signal to parallel paths (pleiotopy), integrate signal in response with other signals

Question 68

What happens in the target cell to respond to signal?

Answer 68

ligand binding, conformational change in receptor, change in activity in cell ->->-> response

Question 69

what two things do different signaling cascades have in common?

Answer 69

G protein as a switch, reversible phosphorylation of proteins controlled by kinases and phosphatases to regulate activity of enzymes

Question 70

What in a signal cascade becomes phosphorylated? What is the result?

Answer 70

enzymes (metabolism up or down)
transcription factors (gene express up or down)
motility factors/cytoskeleton regulators
cell cycle regulators (proliferation/death)

Question 71

Describe the structure of the G Protein coupled receptors (GPCR).

Answer 71

7 pass transmembrane, heterotrimer (alpha, beta, gamma) subunits. Alpha is the speficic to ligand, beta gamma from common pool

Question 72

What is conformation in inactive state of GPCR?

Answer 72

alpha is bound to GDP, beta and gamma in close association

Question 73

What is the conformation in active state of GPCR?

Answer 73

exchange of GTP for GDP, with GTP binding, alpha unit dissociates from beta gamma complex

Question 74

What happens with Cholera toxin?

Answer 74

covalent modification of Gs protein alpha subunit, inhibits GTPase activity and Gs remains in the on state, stimulates transport of NaCl and H2O into the gut, catastrophic diarrhea and dehydration

Question 75

What happens with pertussis toxin?

Answer 75

causes ADP ribosylation of Gi protein that keeps it persistently off. leads to fluid imbalance, severe life threatening congestion of whooping cough

Question 76

What is involved in the G protein switching from binding GDP to GTP?

Answer 76

GEF or guanonucleotide exchange factor

Question 77

What is involved in the G protein switch from binding GTP to GDP?

Answer 77

GAP GTPase Activating Protein, GTPase intrinsic to alpha subunit

Question 78

What two enzymes are the main targets of G-protein in effecting change in the cell? What are their products?

Answer 78

Adenylate cyclase- synthesizes cAMP
Phospholipase C (PLC)- inositol 1,4,5-triphosphate (IP3) and sn-1,2-diacylglycerol (DAG)
Both are second messengers

Question 79

What does the enzyme cAMP phophodiesterase do? Name something that is a common inhibitor.

Answer 79

inactivates cAMP by hydrolysis to AMP, methyl xanthines (ex. caffeine)

Question 80

What protein mediates the effects of cAMP in the cell usually? (i.e. what does it bind to) how does it work?

Answer 80

Protein Kinase A or PKA, active catalytic subunits separate from regulatory units, catalytic units then phosphorylate cellular substrates (Ser or Thr),

Question 81

give an example of a fast response to cAMP and how it works.

Answer 81

glycogen breakdown in skeletal muscles, “fight or flight”, active a kinase phosphorylates inactive phosphorylase kinase thus activating it to phosphorylate inactive glycogen phosphorylase thus activating it to change glycogen to glucose-1-phosphate to enter glycolysis

Question 82

Give an example of a slow cAMP response and how it works

Answer 82

gene expression, active A protein phosphorylates CREB activating it to bind to CREB transcription factor then the complex binds to DNA at cAMP response element (CRE) the cis element on DNA. results in transcription

Question 83

How does integration work with G protein?

Answer 83

adenylate cyclase is nexus of integration, stimulator ligand binds receptor and Gs complex passes signal to AC, inhibitory ligand bind receptor and Gi complex passes signal to AC. AC signals via cAMP based on overall info input from Gs and Gi, whole pool of AC involved.

Question 84

Describe the first step in the Inositol phosphate pathway.

Answer 84

Start as inositol-4,5-bisphosphate (PIP2), split by phospholipase C-beta into diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3),

Question 85

What does IP3 do?

Answer 85

binds to calcium channels in ER release Ca2+ to cytoplasm

Question 86

What does DAG do?

Answer 86

binds and contributes to activation of protein kinase C (PKC)

Question 87

What three things are required to activate PKC? What does it do when activated?

Answer 87

DAG binding, Ca2+ binding and phosphatidyl serine binding. it phosphorylates cellular substrates to effect changes in enzyme activities and gene expression

Question 88

What are the ten properties that cancer is defined by?

Answer 88

sustain proliferative signaling, evade growth suppressors, resist apoptosis, enable replicative immortality(ignore senescence, ), genomic instability and mutation, activate invasion and metastasis, avoid immune destruction, induce angiogenesis, tumor-promoting inflammation, deregulate energetics

Question 89

What are the key characteristics of dominant somatic mutations?

Answer 89

also called gain of function, create oncogenes, activated, one bad allele=disease

Question 90

What are the key characteristics of recessive somatic mutations?

Answer 90

loss of function mutation delete or inactivate tumor suppressor genes, 2 bad alleles = diesease

Question 91

What is caner susceptibility syndrome?

Answer 91

heterozygous for inactivating mutation of a tumor suppressor gene may have increased susceptibility

Question 92

Describe the pathway for familial colon cancer

Answer 92

first loss of Apc, leads to hyperplastic epithelium, rapid proliferation to early adenoma, activation of K-Ras oncogene leads to intermediate adenoma still rapid proliferation phase, loss of Smad4 and other supressors leads to late adenoma first stage of cancer, then loss of p53 which leads to carcinoma primary cancer, genomic instability leads to invasion and metastasis secondary cancer

Question 93

What leads to genomic instability?

Answer 93

stress cell by shortening cell cycle not allowing time to fix errors

Question 94

What four things can lead to mutations in DNA from endogenous biochemical processes?

Answer 94

spontaneous depurination of guanine to form abasic site, deamination of cytosine to form uracil, deamination of deoxy-5-methyl-cytosine to form deoxythymidine glycol, leakage of ROS reactive oxidative species from the mitochondria into cytoplasm or even nucleus (from metabolism)

Question 95

What does it mean to have fixed changes in the DNA sequence?

Answer 95

a mutation didn’t change in the DNA sequence

Question 96

What damage does ionizing radiation cause?

Answer 96

breakage of the phosphodiester backbone, base modifications, abasic sites

Question 97

What damage does ultraviolet radiation cause?

Answer 97

causes cyclobutane structures between neighboring pyrimidines on the same strand, (T=T, C=C, or C=T) and several types of 6-4 photoproducts

Question 98

What does p53 do?

Answer 98

guardian of the genome, pause and check for errors, either repairs damage or if too expensive to repair signals apoptosis

Question 99

What happens if the cell is lacking p53 and undergoes ionizing radiation?

Answer 99

cell cycle doesn’t stop, division with damaged chromosome, leads to either tumor regression (massive mitotic failure and cell death) or cancer(continued mutation selection, and tumor evolution)

Question 100

What enzymes are involved with polycyclic aromatic hydrocarbons from incomplete combustion (cigarette smoke)? What is the final product?

Answer 100

after 2 oxidizing steps catalyzed by cytochrome p450, BPDE the ultimate carcinogen is formed which alters Guanine creating an adduct

Question 101

What damage can chemical carcinogens cause?

Answer 101

cause formation of DNA adducts, most common in cancer related mutations is guanyl causing G-T transversion

Question 102

What does aflotoxin B do? How is it potentially ingested?

Answer 102

metabolized by cytochrome p450 then either a gaunyl adduct or metabolized by epoxide hydrase or glutathione s-tranferase resulting in a detoxified product. found in aspergillus flavus which grows on peanuts, causes liver cancer with low exposure

Question 103

Explain how receptor tyrosine kinase works?

Answer 103

2 single pass transmembrane proteins, ligand binds to both, causes cross phosphorylation of the intracellular portion of the proteins, the phosphate becomes a docking site for signaling proteins effectors and adaptors, these proteins send a signal downstream

Question 104

What does Ras do?

Answer 104

it is a small GTPase, activated by Grb2 which binds to tyrosine kinase, Grb2 activates a Ras GEF called SOS this allows the GDP on the inactive membrane bound Ras protein to be exchanges for GTP activating the protein, this activates a kinase cascade

Question 105

How is the signal in a tyrosine kinase receptor shut off?

Answer 105

dephosphorylation by phosphatases

Question 106

Explain the ERK MAP kinase pathway.

Answer 106

active Ras stimulates RAF-1 phosphorylation specifically Ser/Thr, RAF-1 utilizing ATP phosphorylates Mek, then using another ATP Mek phosphorylates ERK, ERK using ATP phosphorylates either a protein to affect its activity or a gene regulatory protein to effect gene expression

Question 107

What does ERK MAP kinase effect?

Answer 107

cell proliferation, gene expression, and protein synthesis

Question 108

What does PI3 kinase/Akt/PKB pathway control?

Answer 108

survival, growth, and proliferation

Question 109

Of the following which is bad and which is good; oncogenes or proto-oncogenes?

Answer 109

oncogenes bad, proto-oncogenes good

Question 110

Tumor viruses can trigger neoplastic transformation in cells they infect how?

Answer 110

in retroviruses the RNA genomes copies then goes back to DNA then inserts itself into host genome

Question 111

What is inserted or mutated in Rous sarcoma virus? What is the result in the cell? What is this virus an example of?

Answer 111

c-src is replaced by v-src, produces a constituitively active tyrosine kinase, example of a tumor retrovirus

Question 112

What cancer is caused by the virus EBV?

Answer 112

Burkitt’s lymphoma

Question 113

What cancer is caused by the virus HTLV-1?

Answer 113

non-hodgkins lymphoma

Question 114

What cancer is caused by the virus HHV-8?

Answer 114

Kaposi’s sarcoma, body cavity lymphoma

Question 115

What cancer is caused by the virus HBV?

Answer 115

hepatocellular carcinoma

Question 116

What cancer is caused by the virus HCV?

Answer 116

hepatocellular carcinoma

Question 117

What cancer is caused by the virus HPV?

Answer 117

cervical carcinoma

Question 118

What cancer is caused by the virus JCV?

Answer 118

astrocytoma, glioblastoma

Question 119

What are some key cellular regulators of growth and development that proto-oncogenes encode?

Answer 119

growth factor receptors, protein tyrosine kinases (Src, Abl), Signaling molecules (Ras), Transcription factors (Myc, Fos)

Question 120

What is unregulated expression?

Answer 120

insertional mutagenesis, gene amplification, and abberant transcriptional control can cause overexpression of the proto-oncogene at inappropriate phases of the cell cycle

Question 121

what three mechanisms allow proto-oncogenes to be converted or activated to oncogenes?

Answer 121

mutation, unregulated expression, or chromosomal rearrangement

Question 122

What is chromosomal rearrangement?

Answer 122

can alter transcriptional control of the proto-oncogenes or create a fushion protein with altered activity compared with a normal protein

Question 123

What happens if there is a mutation of Ras at codons 12,13, or 61?

Answer 123

encode for amino acid substitutions that makes Ras insensitive to GTPase-activating function of RAS-GAP, GTP cannot be hydrolyzed to GDP so it remains active.

Question 124

ErbB gene is mutated how? What does the gene encode normally?

Answer 124

a critical valine in the membrane bound region is switched with a glutamine causing a polar distortion in NEW causing erbB next to it to be always on, normally encodes form of epidermal growth factor receptor

Question 125

What two methods cause overexpression or unregulated expression of normal growth regulators?

Answer 125

retoviruses that express viral verions of proteins in an unregulated or constitutive manner, transforming capabilities, or amplification by proviral insertional mutagenesis can also lead to unregulated expression of myc in several species, leads to mistiming which leads to cancer

Question 126

What protein inactivates Ras and induces GTP hydrolysis?

Answer 126

RAS-GAP

Question 127

The Philadelphia chromosome is an abnormality that occurs in myeloblastic precursor stem cells of granulocytic lineage leading to what? This is an example of activation by what?

Answer 127

chronic myelogenous leukemia (CML), chromosomal rearrangement

Question 128

What happens in the genetic exchange to cause the Philadelphia chromosome?

Answer 128

between chromosome 9 and 22, the 3’ portion of c-ABL gene encoding the cytoplasmic tyrosine kinase was fused with the 5’ end of the BCR gene, creating a chimeric Bcr-Abl fusion protein, a constitutively active tyrosine kinase

Question 129

What is Gleevec?

Answer 129

an competitive inhibitor of the Abl kinase activity of the Bcr-Abl oncoprotein, its very effective in treatment of CML

Question 130

How does Gleevec work?

Answer 130

it binds to the ATP binding site of the Bcr-Abl which prevents it from binding to and phosphorylate the substrate protein, stoping the signal for leukemia, not specific for Abl

Question 131

What is retinoblastoma?

Answer 131

a childhood neoplasm, Rb locus maps to chromosome 13

Question 132

Rb is hereditary or familial and is passed how?

Answer 132

heterozygotes have only one good copy of the Rb gene, the normal chromosome is lost or suffers a somatic mutation inactivating the good Rb gene.

Question 133

Explain the pathway that leads to phosphorylation of Rb.

Answer 133

mitogen binds to receptor starting a ERK/Mapk path, gene regulatory protein Fos enters nucleus causing immediate early gene expression, signal passes to Myc which causes delayed-response gene expression by activating cyclins, G1 CDK then phosphorylates active Rb (pocket) bound to inactivated E2F, Rb is now inactivated (lose pocket) and releases E2F which is now active

Question 134

What is the function of the Rb gene? What is it regulated by?

Answer 134

it encodes an inhibitor of the action of several proteins involved in DNA replication, cell cycle dependent phosphorylation mechanism (cell cycle clock)

Question 135

Explain what E2F protein does and the feedback loop on it.

Answer 135

E2F causes s-phase gene transcription, this positively feeds back on itself. S phase transcription leads to G1/S-cyclins which leads to active G1/s-CDK and Active S-CDK, G1/S-CDK feeds back to activation of E2F and forward to activation of S-CDK, S-CDK leads to DNA synthesis

Question 136

What is Li-Fraumeni syndrome?

Answer 136

people who inherit one functional copy of p53, predisposed to cancer, characterized by development of wide variety of tumors in different organs early in adulthood

Question 137

What does p53 do? (function)

Answer 137

homotetrameric transcription factor, controls expression of many geens to arrest cell growth or induce programmed cell death

Question 138

How does p53 induce cell cycle arrest?

Answer 138

after Double strand break, signal sent and p53 is phosphorylated activating it, p53 binds to DNA increasing expression of p21Cip1, creates p21 inhibitor protein which binds to G1/S-CDK and S-CDK inactivating them and blocking cell cycle, also increased expression of 14-3-3sigma which sequesters cell cycle kinase complex cyclin B-Cdc2 in inactive form in cytoplasm, or suppress expression of IGF-1 receptor (critical stimulator of mitogenesis)

Question 139

What are the two pathways for apoptosis signaling and how can they effect each other?

Answer 139

extrinsic and intrinsic, extrinsic can activate the intrinsic path to ensure apoptosis

Question 140

What happens intracellularly after the extracellular signal for apoptosis via receptor?

Answer 140

initiator procaspases (proteolytic enzymes) are activated to caspases, these activate executioner caspases by cleaving them, this mediates the death pathway

Question 141

what two ways can activate the Extrinsic path of apoptosis?

Answer 141

death ligand(many kinds) binding to its death receptor, cytotoxic cell attaching to membrane and releasing granzyme B into the cell

Question 142

Where and how is the intrinsic pathway of apoptosis initiated?

Answer 142

in the mitochondria, cytochrome C or metabolic enzyme leaks out of pores, once in the cytosol they bind to Apaf-1 and caspase 9 (intiator caspase) forming the apoptosome

Question 143

What are some things that lead to activation of the intrinsic pathway of apoptosis?

Answer 143

hypoxia, DNA damage, massive DNA methylation, Nitric oxide stress

Question 144

What is the role of the executioner or effector caspases in apoptosis?

Answer 144

cleave death substrates

Question 145

What happens when there is proteolysis of nuclear lamins? What pathway is this part of and what step?

Answer 145

leads to changes in nucleus like pyknosis (nuclear condensation) and disintegration of the nuclear envelope,cleavage of death substrate in apoptosis

Question 146

What is ICAD? What pathway is part of?

Answer 146

inhibitor of caspase activated DNase, apoptosis, if cleaved it relives inhibition on DNase leading to internucleosomal DNA fragmentation

Question 147

How are vimentin and actin involved in apoptosis?

Answer 147

both are an example of protein complements of the cell surface and cytoskeleton that are altered causing blebbing and increasing the phosphatidyl serine content of the outer leaflet attracting macrophages.

Question 148

How does high levels of p53 block survival signaling? (3 ways)

Answer 148

Upregulation of Fas (death receptor) promoting extrinsic pathway, upregulation of pericellular IGF binding protein 3 (IGFBP-3) sequesters growth/survival factors IGF I and II, and increase expression of BAX the pro-apoptotic pore protein (activates intrinsic pathway)

Question 149

Of the 15k distinct known mutations of p53, what percent are missense mutations?

Answer 149

> 90% (amino acid substitution)

Question 150

Most of the missense mutations of p53 are what kind? What does this mean for the cell?

Answer 150

inactivating or recessive, normal cellular p53 activity may be maintained

Question 151

What are the two main types of the Bcl2 family of proteins? What does each do?

Answer 151

pro-apoptotic-stimulate apoptosis, anti-apoptotic- inhibit apoptosis or promote cellular survival

Question 152

What are dominant-negative mutations? What does it mean if it occurs in p53?

Answer 152

poison protein response, bad protein inactivates the good in a complex, interfere with the function of normal p53 in tetramer

Question 153

What is the main anti-apoptotic Bcl2 protein? What functional domains does it have?

Answer 153

Bcl2, BH1, BH2, BH3, and BH4

Question 154

What are the pro-apoptotic Bcl2 proteins? What functional groups does each have?

Answer 154

Bax-BH1, BH2, and BH3

Bad- BH3

Question 155

How does Bcl2 work?

Answer 155

in absence of death stimulus, Bcl2 binds to BH123 proteins (Bax) on the outer mitochondrial membrane inhibiting their pore-forming activity

Question 156

If apoptotic signal is received what happens to Bcl2 proteins?

Answer 156

Bad (BH3), binds to Bcl2 forming inactive heterodimers, causing Bcl2 to release Bax, Bax proteins cluster together forming pores in mitochondrial membrane beginning the intrinsic path

Question 157

What are IAPs? Which are endogenous to humans?

Answer 157

Inhibitors of apoptosis, endogenous proteins that block cell death by interfering with caspase activity. XIAP(x-linked), cIAP (cellular)

Question 158

What two viruses are known to contain IAPs?

Answer 158

Cytomegalovirus and Epstein Barr virus

Question 159

In cancer cell what happens to IAPs? How is this clinically relevant?

Answer 159

IAPs are upregulated and therefore a drug target,

Question 160

What are some Anti-IAPs? How do they work?

Answer 160

Smac and Diablo, bind to and inhibit certain IAPs which re-activates apoptosis.

Question 161

What are the main proteins involved in the survival signal pathway?

Answer 161

PI-3 kinase, Akt, and PKB

Question 162

In the PI3K/Akt/PKB path, PI-3 kinase phosphorylates what and what does it then become?

Answer 162

PIP2 becomes PIP3 which forms a lipid based docking site on the membrane

Question 163

In the PI3K/Akt/PKB path, what binds to PIP3?

Answer 163

Akt/PKB or PDK1

Question 164

In the PI3K/Akt/PKB path, what activates PDK1?

Answer 164

once bound to PIP3 it is phosphorylated by Akt and mTOR in complex with rictor

Question 165

In the PI3K/Akt/PKB path, what does activated Akt do?

Answer 165

migrates thru cytoplasm phosphorylating substrates (which activates or inactivates them) that mediate cell survival by inhibiting apoptosis and stimulating the cell cycle

Question 166

What are Akt anti-apoptotic substrates? What are they normally? Are they inhibited or activated?

Answer 166

Bad- pro-apoptotic- inhibited

caspase 9 - pro-apoptotic- inhibited

Question 167

How does Akt activate cellular protein synthesis?

Answer 167

activation of the kinase mTOR in complex with Raptor phosphorylates several regulatory proteins

Question 168

What three examples were given that are phosphorylated by mTOR to increase protein synthesis? How does each effect protein synthesis?

Answer 168

S6kinase ribosome- enhances ribosomal activity, 4E-BP inhibits elF4E
Gene regulatory factors that increase ribosome synthesis

Question 169

Is elimination of p53 enough to cause cancer?

Answer 169

no, need multiple mutations

Question 170

What is needed to maintain tissue viability? What happens to it as we age? Why?

Answer 170

stem cells, decrease in numbers due to a decrease in proliferation

Question 171

What are the four Cellular and molecular events in normal Aging?

Answer 171

reduced signaling thru PI-3K/Akt path, impairment of DNA repair pathways, Elevated levels of cell cycle inhibitors and apoptosis effectors, and decreased mitochondrial activity

Question 172

What is cockayne syndrome?

Answer 172

premature aging disorder, due to mutations of encoding proteins in transcription-coupled DNA repair path

Question 173

What is xeroderma pigmentosum?

Answer 173

inherited disease characterized with extreme sensitivity to UV, cause by mutation of 1 of 8 genes that encode proteins in the NER pathway

Question 174

What is Werner syndrome?

Answer 174

also called adult progeria, due premature aging disorder, due to mutation of WRN which encodes a DNA helicase of BER path

Question 175

What two things lead to cell cycle arrest in normal aging? What state do the cell enter?

Answer 175

rise of cyclin inhibitors p16^Ink4a and p21^Cip1 and chronically elevated p53, replicative cell senescence

Question 176

What happens in the mitochondria during aging?

Answer 176

decrease in effectiveness of ETC, decrease ATP production and increase production of ROS

Question 177

What is the Haflick limit?

Answer 177

number of divisions allowable for normal (non-transformed) cells in culture

Question 178

How does telomerase activity change at differentiation?

Answer 178

high in stem cells and decreases after differentiation, lose 100-200 nucleotides from telomeres everytime the cell divides

Question 179

Erosion of the telomere leads to what?

Answer 179

crisis, increased risk of end to end fushion of sister chromatids while they are paired in G2 by repair enzymes

Question 180

What is the BFB cycle?

Answer 180

fushion of dicentric chromatids due to telomere erosion, breakage then results when sister chromatids separate, imbalance of genetic material and no telomeres, (cycle repeats with a new site on the chromosome effected

Question 181

Cancer cells re-express high levels of what to overcome normal aging? what is the incidence rate of this amongst pre-cancerous cells?

Answer 181

telomerase 85-90% increase in activity, hTERT, avoid mitotic crisis, utilize clonal expansion to do so. this is rare as 99.9% of pre-cancerous cells die

Question 182

What is a Kaplain Meier Survival Curve?

Answer 182

tracks survival rate vs time since diagnosis comparing low TA level or high TA level (Telomerase Activity)

Question 183

What are the phases of mitosis in order?

Answer 183

Prophase, Metaphase, Anaphase, Telophase, and Cytokinesis

Question 184

What are the phases of the cell cycle in order?

Answer 184

G1, S, G2, and M (mitosis)

Question 185

What is the G0 phase of the cell cyle?

Answer 185

resting or non-proliferative stage ( subset of G1), also called quiescence

Question 186

what is karyokinesis?

Answer 186

nuclear division

Question 187

What is cytokinesis?

Answer 187

cytoplasmic division

Question 188

Can karyokinesis occur without subsequent cytokinesis? examples if any.

Answer 188

yes, cardiac and liver cells can be binucleated

Question 189

what are the two types of cell division? What is the resulting cell called.

Answer 189

mitosis = diploid and meiosis = haploid

Question 190

Interphase includes which phases of the cell cycle?

Answer 190

G0, G1, S, and G2

Question 191

what are the features of prophase?

Answer 191

completion of chromosome condensation, tight attachment of sister chromatids to centromere surrounding centrioles, dissolution/disappearance of nuclear envelope and nucleoli, formation of mitotic spindle, appearance of centrosome

Question 192

Explain the assembly and disassembly of the nuclear envelope.

Answer 192

in interphase lamins A,B, and C associate w/ chromatin and inner membrane, at mitosis cyclin B activated Cdc2 phosphorylates lamins creating free lamin dimers A and C, vesicles of the nuclear envelope associate with the B lamins, after division vesicles fuse and free lamins are dephosphorylated and reform the network

Question 193

what are the features of prometaphase?

Answer 193

nuclear envelope breaks into cytoplasmic vesicles, movement of spindle microtubules into nuclear region, maturation of the kinetochore complex on centromere

Question 194

What are the main features of metaphase?

Answer 194

formation of kinetochore (protein DNA complex), attachment of kinetochore to microtubule, formation of polar and astral microtubules

Question 195

What are the key features of Anaphase?

Answer 195

chromosomes move towards the spindle, topoisomerase facilitates separation of sister chromatids, kinetochore microtubules shorten, poles move away from each other, polar microtubules lengthen

Question 196

What are the key features of telophase?

Answer 196

uncoiling of chromosomes, development of nucleoli at nuclear organizer site, spindle disassembly, formation of nuclear envelope, initiation of cytokinesis

Question 197

How is cleavage during cytokinesis achieved?

Answer 197

beltlike bundle of actin and myosin called the contractile ring form in the cell cortex just inside the membrane

Question 198

What are the stages of genetic recombination that occurs during meiosis I and mitosis?

Answer 198

pairing, synapsis, synaptonemal complex, and recombination

Question 199

What are the four stages of meiotic prophase I? What is significant about each?

Answer 199

Leptotene- condensation of chromosome, telomeres attach to inside of nuclear membrane, Zygotene-homologous pairs formed for synapsis and formation of synaptonemal complex early part of stage resembles bouquet, Pachytene- chromosomes shorter and thicker synaptonemal complex formed, and Diplotene- synaptonemal complex disintegrates and decondense but sisters remain close for recondensation soon

Question 200

In what stage are females eggs stored and how long can it last? What is active in the cell at this time?

Answer 200

diplotene, days to years, active in transcription as they store up materials for the first few embryonic divisions, lampbrush appearance with DNA in center and RNA and proteins are “bristles”

Question 201

Describe the steps of recombination.

Answer 201

between paired homologues not sister chromatids, double strand break initiated by enzyme Spo11p, resection of breaks on the 3’ end by exonuclease, next strand invasion of the homologous pair this produces the Holiday Junction where strands cross, DNA synthesis fills in the gap, resolvase cuts at the holiday junction if symmetrical no crossing over, if not there will be crossing over

Question 202

What is diakinesis?

Answer 202

occurs after diplotene in meiosis, homologous chromosomes recondense, and form synaptonemal complex

Question 203

What are the key features of Meiotic metaphase I?

Answer 203

bivalent chromosomes attached to spindle microtubule by kinetochore are lined upon the metaphase plate

Question 204

What are the key features of Meiotic metaphase I?

Answer 204

bivalents move toward opposite poles pulling the homologous chromosomes of each bivalent pair

Question 205

What are the key features of Meiotic telophase I?

Answer 205

movement of chromosomes to opposite poles complete, nuclear envelopes formed and cytoplasm splits to form two daughter cells

Question 206

What are the key features of Meiosis II?

Answer 206

phases similar to mitosis except chromosomes on metaphase plate are half in number

Question 207

What is the significance of meiosis?

Answer 207

preservation of chromosome number and generation of genetic diversity for sexually reproducing organisms

Question 208

What are the major regulation points in the cell cycle? when do they occur?

Answer 208

restriction point in G1, DNA damage checkpoints in G1,S and G2, DNA replication checkpoint (shares components with DNA damage plus stabilizes stalled replication fork and intiates repair), spindle assembly checkpoint during mitosis

Question 209

Cell divisions are controlled by what two things?

Answer 209

external stimuli and nutrient availability

Question 210

When might a cell withdraw from the cell cycle? What type of regulation is this?

Answer 210

if environmental conditions are not suitable, restriction point

Question 211

What are the key factors of the DNA damage checkpoints in cell cycle regulation?

Answer 211

CDKs are master regulators, active only when complexed with cyclin, cyclins are in abundance during cell cycle, CDK partners with different cyclins during different phases to phosphorylate key proteins

Question 212

Explain the process of activation of the CDK complex.

Answer 212

CAK phosphorylates the Thr 167 of CDK1 activating the CDK1/cyclin B, phosphorylation of the Thr 14 and Tyr 15 by Wee family kinases CDK1 complex inactive in G2, at transition into M phase phosphorylation by Wee 1is reversed by Cdc25 family phosphatases resulting in activated complex

Question 213

What are the two ways CDK is inhibited?

Answer 213

CDI (CDK inhibitor) binds to either CDK or CDK cyclin complex or during G2 nuclear export of cyclin B dominates resulting in separation of cyclin B from CDK 1, normally phosphorylation of key residues in cyclin B attenuates its export resulting in nuclear accumulation and accessibility of substrates

Question 214

How is CDK inactivated after mitosis?

Answer 214

proteolysis of cyclin B contributes to it

Question 215

DNA replication checkpoints take advantage of what factors?

Answer 215

replication requires ordered assembly of protein complexes, occurs at origins that may be deined by sequence position or spacing mechanisms, initiation only occurs at origins licensed to regulate, once used they cant be used again until the next cell cycle

Question 216

What drives the release of sister chromatid cohesion?

Answer 216

Ubiquitin-mediated proteolysis by separase

Question 217

How does CDK regulate the activity of separase?

Answer 217

CDK1 phosphorylates APC (anaphase promoting complex) which binds its activator Cdc20. APC and Cdc20 target its substrate securin for proteolysis which normally binds separase

Question 218

What happens with the spindle assembly checkpoint?

Answer 218

if defects in spindle microtubule attachment are found transition from metaphase to anaphase is halted

Question 219

What do proto-oncogenes do in terms of the cell cycle?

Answer 219

encode proteins that drive cells into the cell cycle

Question 220

Tumor suppressor genes do what in terms of the cell cycle?

Answer 220

encode proteins that restrain cell cycle events

Question 221

What is the basic structure of the membrane lipid cardiolipin?

Answer 221

two phospholipids joined by glycerol

Question 222

What are gycosphingolipids?

Answer 222

glycolipids, family based and ceramide and do not contain phosphate

Question 223

Neutral sphingolipids are synthesized via what enzyme primarily? basic structure?

Answer 223

ceramide plus one or many glucose and or galactose

Question 224

What is the basic structure of Acid sphingolipids? What family are most of them?

Answer 224

ceramideplus gal or glu plus N-acetylneuraminic acid (NANA) or a sufoxide group, those containing NANA are the gangliosides

Question 225

What are three main types of lipids found in membranes? What one stiffens the membrane?

Answer 225

phosphoglyceride, sphingolipid and cholesterol-stiffens

Question 226

What are lipid rafts and what is their importance?

Answer 226

clump of phospholipids grouped together, regulate the activity of cell membrane receptors activity of hormone receptors is dependent on their location within the membrane as well as the presence of the ligand

Question 227

What can happen to the body during extensive ketone body production? When does this occur?

Answer 227

ketoacidosis, lower blood pH, starvation, uncontrolled diabetes mellitus

Question 228

Describe the path of ketone body formation.

Answer 228

2 acetyl CoA thiolase kicks off CoA to get acetoacetyl CoA then HMG CoA synthase adds acetyl group to get HMG CoA HMG Coa lyase kicks off Acetyl CoA to get Acetoacetate (first keton body, form here it either spontaneously kicks off a CO2 to become acetate or 3-hydroxybutyrate dehydrogenase makes it 3-hydroxybutyrate

Question 229

How do the peripheral tissues utilize ketone bodies in metabolism?

Answer 229

acetoacetate is converted to Acetyl CoAs and enters TCA

Question 230

what are the three main ketone bodies? Which is not energy yielding?

Answer 230

acetoacetate, acetone and 3-hydroxybutyrate, acetone does not yield energy

Question 231

what two fuels does the brain utilize and when?

Answer 231

glucose in short term and ketone bodies in long term, some amount of ketone bodies are produced in a well fed state

Question 232

What cell in the body requires glucose? Why?

Answer 232

erythrocytes, no mitochondria only utilize glycolysis

Question 233

What portion of cholesterol is from diet and what portion is synthesized?

Answer 233

50/50

Question 234

What is the rate limiting step of Cholesterol biosynthesis? How is this clinically relevant?

Answer 234

HMG-CoA reductase, target of statin drugs

Question 235

what is the pathway of Cholesterol Biosynthesis?

Answer 235

Acetyl CoA to Acetoacetyl CoA to 3-hydroxy-3-methylglutaryl-coA to Mevalonanic acid to isopentanyl pyrophosphate to famesyl pyrophosphate to squalene to lanesterol to cholesterol

Question 236

What can be made from cholesterol?

Answer 236

Bile salts, Vitamin D, Cortisol, Aldosterone, Testosterone, and Estradiol,

Question 237

What percent of bile salts are recycled? How is this clinically significant?

Answer 237

95%, target for cholesterol lowering drugs prevents reuptake so body has to use more cholesterol to make more

Question 238

What supplement is sold to increase testosterone production? Why?

Answer 238

DHEA, becomes Androsterone or Androtenediol which then becomes testosterone

Question 239

What is the general path of synthesis of testosterone?

Answer 239

cholesterol to progesterone to 17-OH-progesterone to Androsterone to Testosterone

Question 240

What is the general path of Estradiol synthesis?

Answer 240

cholesterol to progesterone to 17-OH-progesterone to Androsterone to either testosterone or Estrone then aromatase makes Estradiol

Question 241

What drug is prescribed for prostate cancer and why?

Answer 241

Casodex, its an anti androgen

Question 242

What drugw is often given to post-op women with breast cancer? Why?

Answer 242

tamoxifen or raloxifene, inhibits growth of tumors because most are estrogen receptor positive, it is an estrogen antagonist

Question 243

How do hormones work in the body?

Answer 243

regulate gene expression through hormone receptors in cytoplasm and nucleus

Question 244

What are the four precursors for phsophatidic acid in the acyl glycerol biosynthesis?

Answer 244

Triacylglycerol, Diacylglycerol, Glycerol-3-Phsophate, and DHAP

Question 245

What else is synthesized along the sphingolipid path besides sphingolipids? What is the start? Where does it occur in the cell?

Answer 245

glycolipids, from palmitoyl CoA and Serine, in the lumen of the Golgi (near the cell membrane)

Question 246

What is Tay-Sachs? Characteristics? Cause?

Answer 246

Autosomal recessive neurological disorder, death by 3, first diagnosed by cherry red spot in retina, higher incidence in Ashkenazi Jews, results in accumulation of undigested lipids in lysosomes in nerve cells, Increase in Ganglioside GM2, problem is with B-Hexosaminidase A enzyme in the glycolipid degradation pathway

Question 247

How can carriers of Tay-Sachs be distingiuished?

Answer 247

reduction but not a loss in Hexosaminidase A activity in blood lymphocytes

Question 248

Is genetic screening feasible for Tay-Sachs?

Answer 248

No over 100 types of mutations

Question 249

How are fatty acids broken down?

Answer 249

B-oxidation, two step process releasing acetyl CoA to enter the TCA cycle

Question 250

For fatty acid breakdown to occur what must happen first? Give the pathway that achieves this. What is the rate limiting step?

Answer 250

fatty acids must enter the mitochondria, Acyl CoA Synthetase transport acetyl CoA from FA across the outer membrane, carnitine palmitoyl transferase I puts the Acyl group on carnitine releasing the CoA, Carnitine acylcarnitine translocase on the inner membrane switches a carnitine from inside the mitochondria with the acylcarnitine between the membranes, finally carnitine palmitoyl transferase II puts a CoA back on the Acyl group releasing carnitine to go back between the membranes via Carnitine acylcarnitine translocase, rate limting steps are the Carnitine palmitoyl transferase I and II

Question 251

What are some lipid oxidation disorders? effects and treatment of each?

Answer 251

CPTI and CPT II deficiencies: muscle weakness, hypoketotic hypoglycemia, cardiac malfunction and death, avoid fasting and long chain fatty acids; primary carnitine deficiency: impairment of B-oxidation, dietary supplementation of carnitine; secondary carnitine deficiency: elevated secretion of acylcarnitine derivatives; dietary carnitine helps with effects of depletion

Question 252

List the pathway of B-oxidation.

Answer 252

starts with fatty acyl CoA oxidation via Acyl-CoA dehydrogenase and FAD to trans-Enoyl-CoA which is hydrated by enoyl-CoA hydratase (cronotase) to L-B-hydroxyacyl-CoA which is oxidized by L-hydroxyacyl-CoA dehydrogenase and NAD to B-ketoacyl-CoA which is cleaved by Thiolase and the addition of a new CoA to the remaining shortened fatty acid

Question 253

What happens to the electrons removed by Acyl-CoA dehydrogenase?

Answer 253

enter ETC as reduced coQ yielding 1.5 ATP

Question 254

what are the different enzymes in the Acyl-CoA dehydrogenase family?

Answer 254

SCAD, MCAD, LCAD, and VLCAD for the different length fatty acids short, medium, long and very long

Question 255

How many ATP are yielded by the NADH produced in B-oxidation?

Answer 255

2.5 ATP

Question 256

What differs in the B-oxidation in peroxisomes?

Answer 256

require FAD-dependent acyl-CoA oxidase instead of Acyl-CoA dehydrogenase, the hydrogens attached to FAD are then transferred to O2 producing H2O2 instead of utilizing ETC, fewer ATP

Question 257

What type of fatty acids are oxidized in peroxisomes? How are they brought in and the products out?

Answer 257

VLFA chains, peroxisomal carnitine acyltransferase transports long chain acylcarnitine in, after oxidation acetyl-CoA and octanol-CoA are converted to acetyl-carnitine and octanol-carnitine exported from peroxisome into cytoplasm for entry into the mitochondria, NADH react with pyruvate to form lactate which shuttles electrons to cytoplasm

Question 258

What is the end yield of odd chain fatty acid oxidation? What does the body do with it?

Answer 258

propionyl-CoA, in three reactions it becomes succinyl-CoA and enters TCA cycle

Question 259

How are unsaturated fatty acids oxidized?

Answer 259

an additional enzyme is sometimes needed to rearrange the double bond position so it can continue along the path.

Question 260

What is w-oxidation? When is it important?

Answer 260

oxidation of methyl carbon to carboxyl in ER by cytochrome p450 the dicarboxylic acid product can then be transferred to mitochondria and metabolized by B-oxidation from both ends, normal minor pathway is seen more when there is a disorder in B-oxidation

Question 261

What is lipogenesis? Where does it take place mostly? What is the main source of carbon?

Answer 261

synthesis of fatty acids and their esterification to glycerol to form triglycerides, in the liver, dietary carbohydrate

Question 262

What are the differences between B-oxidation and lipogenesis?

Answer 262

intermediates of synthesis are linked to -SH groups of acyl carrier proteins (compared to the SH groups of CoA), synthesis is in the cytosol oxidation in mitochondria, enzymes of synthesis are one polypeptide fatty acid synthase (multiple rxn sites), biosynthesis uses NADPH/NADP+ breakdown uses NADH/NAD+

Question 263

How does the cytosol get more Acetyl-CoA and NADPH for synthesis?

Answer 263

citrate-malate-pyruvate shuttle

Question 264

How is chain elongation achieved in fatty acid synthesis?

Answer 264

addition of 2 carbon units derived from acetyl CoA, acetate units are activated by formation of malonyl-CoA (use ATP) by acetyl-CoA carboxylase, addition of 2 carbon units is driven by decarboxylation of malonyl-CoA, repeated until 16 carbon length achieved, other enzymes add double bonds and additional carbons

Question 265

What is the first committed step of lipogenesis?

Answer 265

carboxylation of acetyl-CoA by acetyl-CoA carboxylase to malonyl-CoA utilizing ATP, bicarbonate, and biotin, it is irreversible, this is the rate limiting step

Question 266

How is the activity of ACC controlled?

Answer 266

ACC is modulated by phosphorylation, the dephosphorylated form is activated by low citrate and inhibited only by high levels of fatty acyl-CoA, the phosphorylated form is activated by high levels of citrate and inhibited by low fatty acyl-CoA

Question 267

What hormone regulates fatty acid synthesis and break down? How?

Answer 267

glucagon binds to receptor, g protein activates AC which turns ATP to cAMP which activates protein kinase phosphorylating ACC and triacylglycerol Lipase inactivating it. insulin- binds receptor which activates phosphodiesterase turns cAMP to AMP ending glucagon signal

Question 268

How is FA synth. regulated?

Answer 268

malonyl-CoA blocks carnitine acyltransferase and inhibits B-oxidation, citrate activates ACC, fatty acyl-CoA inhibits ACC, hormones regulate ACC: glucagon activates lipases/inhibits ACC and insulin inhibits lipases/activates ACC

Question 269

What is MAT?

Answer 269

malonyl-CoA-acetyl-CoA-ACP transacylase transfers acyl of acetyl CoA to acyl carrier protein(ACP), also transfers malonyl of malonyl-CoA to ACP

Question 270

What two fatty acids are essential? Why? What are they used for in the body?

Answer 270

w-3: cardioprotective, anti-inflammatory, anticarcinogenic precursor of EPA and DHA
w-6: precursor of prostaglandins, thromboxanes, leukotrienes, and arachidonic acid, neither can be synthesized in the body

Question 271

What are the different body fluid compartments?

Answer 271

Intracellular, Extracellular (Interstitial and plasma), and Transcellular

Question 272

Describe the relative level of Na, K, Cl, and Protein in the intracellular compartment.

Answer 272

Na low, K high, Cl low, Protein high

Question 273

Describe the relative level of Na, K, Cl, and Protein in the interstitial compartment.

Answer 273

Na high, K low, Cl high, Protein 0

Question 274

Describe the relative level of Na, K, Cl, and Protein in the Plasma.

Answer 274

Na high, K low, Cl high, Protein low but some present

Question 275

Describe the relative level of Na, K, Cl, and Protein in the transcellular.

Answer 275

all variable, effected by hormones, concentration in the blood

Question 276

Explain Fick’s Law of simple diffusion.

Answer 276

net flux (J) is equal to permeability coefficient (P) times the surface area for diffusion times the concentration gradient (delta C)

Question 277

What is the equation for movement of an ion across a cell membrane? the measurements of each.

Answer 277

Current (I, amps) = conductance (g,siemens) x the electrochemical force (membrane potential [Vm] - gradient potential [E], volts)

Question 278

How do electrolytes move across a membrane?

Answer 278

selective ion channels

Question 279

What is the membrane potential?

Answer 279

an electrical field or separation of charges along the cell membrane, it effects the movement of electrolytes across it.

Question 280

What is the chemical potential? how do you convert it to be added to the electrical potential?

Answer 280

if there is a gradient based on the concentrations inside and outside of the cell that is the chemical force driving movement of the chemical E=(60z)mV log(Co/Ci) Co and Ci are concentration inside and out of the cell and z is the valence of the ion

Question 281

What are the three types of carrier mediated transport?

Answer 281

facilitated diffusion, active transport, secondary active transport

Question 282

Carrier mediated facilitated diffusion takes advantage of what? is there a limit?

Answer 282

driven by chemical gradient to transport passively, integral membrane proteins are specific to what they carry, there is a saturation point at Jmax

Question 283

what role does insulin play in facilitated diffusion of glucose?

Answer 283

enhances diffusion of glucose by adding more transporters, GLUT4 to help the GLUT1 transporters when they are overwhelmed

Question 284

What are the characteristics of primary active transport?

Answer 284

break a phosphate bond in ATP to transport against a gradient.

Question 285

Where are Na/K pumps usually located?

Answer 285

on the basolateral plasma membrane of all cells

Question 286

Besides Na/K pumps what are some other examples of primary active transport?

Answer 286

H/K/ATPase, H-ATPase, and Ca-ATPase

Question 287

What are the different kinds of secondary active transport? Define them.

Answer 287

symport-the chemical gradient for one is used to transport another chemical the same direction and antiport- the chemical gradient is used to transport something in the opposite direction against its own gradient

Question 288

What are some examples of symport?

Answer 288

Na+-glucose and Na+-amino acid

Question 289

What are some examples of antiport?

Answer 289

Na-H exchanger and Na-Ca exchanger

Question 290

What is osmosis?

Answer 290

the flow or displacement of volume across a barrier due to movements of matter in response to a concentration difference, dependent on random thermal motion, result is abolition of the chemical gradient, difference is that volume is displaced in osmosis

Question 291

what special channel does water use? What are the features of it?

Answer 291

aquaporin, a non-gated channel

Question 292

What is the equation for the movement of water across a membrane barrier?

Answer 292

rate at which water moves (Jv) is equal to hydraulic conductivity of the barrier (Kf) times the driving force in terms of total pressure (deltaPt)

Question 293

What are the two types of pressure on a biological membrane?

Answer 293

Hydrostatic (blood pressure), Osmotic (Interstitial fluid to plasma) Osmotic pressure (delta pi) - hydrostatic pressure (delta p)

Question 294

How do you calculate osmotic pressure?

Answer 294

19.3 mm Hg/mM times the concentration difference of the impermeable solute (delta C)

Question 295

What is the reflection coefficient?

Answer 295

sigma, used to factor the partial permeability of a solute, 1-(Cf/Ci) Cf being concentration final and Ci being concentration initial, zero is impermeable 1 is completely permeable

Question 296

How does cystic fibrosis effect Cl secretion in the lungs?

Answer 296

defect in the Cl channel prevents secretion of fluid which follows Cl into the lungs

Question 297

What is the embryological origin of fibroblasts and chondroblasts?

Answer 297

Mesenchyme

Question 298

What are some key characteristics of cartilage?

Answer 298

avascular so nutrients and waste diffuse to adjacent loos connective tissue, Fibers embedded in a gel provides viscoelastic properties of firmness and resilience, have lacuna with cell in them, classified by the matrix characteristic, contains cells

Question 299

Describe the cells in cartilage. Lineage, differences, etc.

Answer 299

have a well developed rER and Golgi, stem cells give rise to chondroblasts start flat and get round as they migrate inward form perichondrium once in a lacuna and separated from other cells it becomes a chondrocyte.

Question 300

What is the difference between territorial matrix and interterritorial matrix?

Answer 300

Territorial is immediately surrounding a cell and between cells sharing a lacuna darker staining, interterritorial is between lacuna lighter staining

Question 301

What makes up the matrix of cartilage?

Answer 301

Type II collagen, GAGs (hyaluronic acid, chondroitin sulfate, keratin sulfate, aggregan), and Proteoglycans (multiadhesive glycoproteins like fibronectin, chondronectin and anchorin)- 60% water

Question 302

What are the primary characteristics of Hyaline Cartilage? Common sites?

Answer 302

homologous, amorphous matrix, because Type II collagen and GAGs have similar refractive index compressible and flexible but not elastic, covered by perichondrium except where it lines joints, initial skeleton of fetus, synovial joints, large airways, ventral ends of ribs, epiphyseal plate

Question 303

What are the primary characteristics of Elastic Cartilage? Common sites?

Answer 303

matrix with elastic fibers and collagen type II, perichondrium, blends into hyaline, visualized with special staining to make out elastic fibers (resourcin-fuchsin), Ear, auditory tube, epiglottis

Question 304

What are the primary characteristics of Fibrocartilage? Common sites?

Answer 304

Intermediate btwn Dense CT and Hyaline cartilage, no perichondrium, Type I (coarse) and II (opaque) collagen, chondrocytes can occur singularly or aligned in rows btwn bundles of I collagen. Site: Intervertebral disc, pubic symphysis, menisci, tendon attachments

Question 305

What are the two types of growth in cartilage? Define them.

Answer 305

Interstitial-isogenic groups secreting matrix outward for each cell, Appositional-lay down new matrix on the outside heading inward.

Question 306

What is an isogenic group?

Answer 306

cells in a lacuna derived from a single cell

Question 307

what are some characteristics of cartilage growth?

Answer 307

constant remodeling with synthesis and breakdown, breakdown favored with aging, limited regenerative/healing bcuz avascular, nutrients must diffuse through matrix to supply cells, no contact between cells

Question 308

What degenerative changes can occur in cartilage and why? Treatments.

Answer 308

most commonly calcification of matrix- shuts off normal diffusion which leads to cell death and further degeneration, modest repair capacity, Rx: perichondral grafts, cell transplantation, artificial matrices or growth factors

Question 309

What are the different covering of bone? cells or fibers in each?

Answer 309

Periosteum- outer fibrous (fibroblasts) and inner cellular (osteoprogenitor cells/osteoblasts), sharpey’s fibers(collagen, penetrate bone at an angle to anchor tissue)
Endosteum- usually single layer (bone lining cells at rest, osteoblasts and osteoclasts can become active)

Question 310

What is a osteoprogenitor cell? function?

Answer 310

stem cell derived from mesenchyme, differentiates into osteoblasts

Question 311

What is an osteoblast? function?

Answer 311

active bone forming cells, prime funct. is synthesis and mineralization of organic matrix (type I collagen, proteoglycans, glycoproteins & non collagenous proteins), formsepithelial like layer on outside of bone

Question 312

what is an osteocyte? function?

Answer 312

terminally differentiated cell derived from osteoblasts when surrounded by matrix, cell body trapped in space btween lamellae in lacunae, cytoplasmic process with cell to cell and cell to BV contact trapped in Canaliculi, maintainence of matrix

Question 313

what is an osteoclast? function?

Answer 313

multinucleated, giant cell, motile, derived from monocyte-macrophage lineage, phagocytic monocytes, secrete acid, collagenase, proteolytic enzymes (bone remodeling)

Question 314

What is a cytoplasmic process? What cell has them?

Answer 314

contact with adjacent osteoblasts via gap junctions, osteoblasts retain when become osteocytes used to pass nutrient and waste through network of cells to get to nearest blood vessel

Question 315

What is a Howship’s Lacunae? Components and functions of them?

Answer 315

etched depression in matrix at site of osteoclast attachment, Ruffles border- active border with folds on side facing matrix, Clear zone- area on osteoclast free of organelles on either side of ruffle border creates a tight seal to prevent leakage of enzymes

Question 316

How are osteoclasts regulated?

Answer 316

Parathyroid hormone stimulates synthesis of M-CSF- transforms monocytes into macrophages and differentiation into osteoclasts, increases serum Ca2+, Calcitonin (thyroid gland) inhibits osteoclast activity and stimulates osteoblast activity which decreases serum Ca2+ levels

Question 317

What are the organic components of bone matrix? What percent of bone matrix is organic?

Answer 317

Type I collagen (90%), Proteoglycans (10%)-chondroitin sulfate, keratin sulfate, hyaluronic acid, non collagenous proteins, 35%

Question 318

What are the inorganic components of bone matrix? What percent of bone matrix is inorganic?

Answer 318

calcium, phosphorus, calcium as hydroxyapatite crystals, 65%, high levels of alkaline phosphatase secreted by osteoblasts in to blood during active bone formation

Question 319

What are the different parts of the long bone?

Answer 319

Epiphysis (bulbous end, spongy bone covered by compact), Diaphysis (shaft of compact bone), Metaphysis (tapering transitional junction, ends when marrow cavity begins), and Epiphyseal plate (growth plate in metaphysis)

Question 320

What are the different parts of the long bone?

Answer 320

Epiphysis (bulbous end, spongy bone covered by compact), Diaphysis (shaft of compact bone), Metaphysis (tapering transitional junction, ends when marrow cavity begins), and Epiphyseal plate (growth plate in metaphysis)

Question 321

When can primary bone be seen?

Answer 321

immature, embryonic, or repair

Question 322

Describe the process of intramembranous ossification.

Answer 322

mesenchyme differentiates into osteoblasts and secretes matrix, anastomosing trabeculae form spongy bone, depositing of Ca2+, osteoblasts and vessels trapped in matrix as osteocytes and hematopoiesis tissues, woven converted to lamellar

Question 323

what are the general features of endochondrial ossification?

Answer 323

within hyaline cartilage, bone collar produced by osteoprogenitor cells in perichondrium (periosteum), bone collar prevents diffusion of nutrients, hypertrophic chondrocytes secrete VEGF, calcification of apoptosis of chondrocytes, BV of osteogenic bud enter through openings by osteoclasts, spaces filled with osteoprogenitor cells differentiate into osteoblasts, deposition of matrix (eosinophilic) on calcified cartilage (basophilic). primary ossification center along diaphysis, then a secondary ossification center in epiphysis forms the came way.

Question 324

/how does the epiphyseal plate achieve bone lengthening?

Answer 324

chondrocytes divide and expand (hypertrophy) adding length zones: resting, proliferation, hypertrophy and calcification of matrix then apoptosis; then there is removal of calcified matrix by osteoclasts

Question 325

What are the zones of endochondral ossification?

Answer 325

resting, proliferation (chondrocytes dividing into columns, “run” away from ossification center, hypertrophic (large chondrocytes), Calcification of cartilage begins then cells die, ossification-endochondrial bone appears, blood vessels and osteoprogenitor cells invade chondrocyte spaces

Question 326

What is the functional unit in the bone? How is it made up?

Answer 326

osteon or haversian system, haversian canal in center with BV, nerves, and loose CT, lined with osteoprogenitor cells (osteoblasts)4-20 concentric lamellae surround it, parallel to long axis, canaliculi channels with cellular processes running between cells and connecting to haversian canal, continuous construction and rebuilding, small hole = more mature osteon

Question 327

What are the different lamellae and where can they be found?

Answer 327

Concentric- around single Haversian canal, Circumferential- outer (whole bone) and inner (whole bone) lamellae, Interstitial (intermediate)- btwn Haversian systems left behind during remodeling

Question 328

What is a Volkman’s canal?

Answer 328

cross connections between haversian canals, contain BV but no concentric lamellae

Question 329

What type of growth occurs in remodeling?

Answer 329

piezo electricity realigns new bone growth in direction of force, so it will withstand force in a new direction but does not change overall mass

Question 330

Describe the phases of fracture repair.

Answer 330

hematoma formed is converted by granulation tissue by invasion of cells (macrophages) and capillaries, soft callus formation by conversion from the deposited collagen and fibrocartilage, osteoblasts deposit temporary bony collar around fracture to unite broken pieces while ossification occurs, small fragments are removed by osteoclasts with osteoblasts depositing spongy bone and then converting it to compact bone

Question 331

What is a greenstick fracture?

Answer 331

abnormal bending in younger children, incomplete mineralization

Question 332

What is osteoporosis?

Answer 332

loss of bone mass leading to bone fragility and fractures, primarily estrogen deficiency, resorbed bone exceeds amount formed, due to increase in osteoclasts, reversed by estrogen therapy, Calcium, Vit D

Question 333

What is osteomalacia?

Answer 333

progressive softeneing and bending of bones, due to defect in mineralization of osteoid,due to lack of vit D or renal tubulardysfunction

Question 334

What is ricket’s?

Answer 334

juvenile osteomalacia, defect in mineralization of growth plate cartilage

Question 335

What is Paget’s disease?

Answer 335

uncontrolled osteoclast activity along with increased osteoblast activity in thicker but softer bones

Question 336

What is osteoarthritis?

Answer 336

most common joint disease, degeneration or loss of articular cartilaeg

Question 337

What is Rheumatoid arthritis?

Answer 337

autoimmune dx with damage to synovial memb. and cartilage, inflammation and thickening of synovial membrane, hypertrophy and replaced by CT

Question 338

What is marasmus?

Answer 338

a condtion caused by calorie deprivation, often deprivation of carbs and protein in infants

Question 339

What is kwashiorkor?

Answer 339

a condition resulting from protein deprivation, grossly distended belly, due to edema related to reduction in plasma proteins resulting in inability to maintain fluid distribution between blood and tissues

Question 340

What is the percent breakdown of calories from different sources?

Answer 340

Fat 20-35 (n-6 5-10, n-3 0.6-1.2), Carbohydrate 45-65 (no less than 130g/day and no more than 25% from added sugars, fiber M 38g, Women 25g) Protein 10-35

Question 341

What occurs in the mouth for digestion?

Answer 341

hydration and starch digestion by alpha-amylase, some sugar absorbed

Question 342

What occurs in the stomach for digestion? absorption?

Answer 342

protein denaturation, hydrolysis (pH 2, )proteases pepsin from pepsinogen and some lipase and amylase activity, alcohol and aspirin absorped

Question 343

What occurs in the duodenum for digestion?absorption?

Answer 343

pH 7 activation of trypsinogen to trypsin, contains enteropeptidases, activation of propeptidases, prophospholipases A2, intraluminal hydrolysis of starch, protein, and lipids, all absorbed a little

Question 344

What occurs in the jejunum for digestion? absorption?

Answer 344

surface hydrolysis of oligo- and disaccharides and oligopeptides, all absorbed a little

Question 345

What occurs in the ileum for digestion? absorption?

Answer 345

absorption of monosaccharides, free amino acids, di and tripeptides, free fatty acids, and monoacylglycerols, bile acids, NaCal and Water

Question 346

What occurs in the colon for digestion? absorption?

Answer 346

nothing that is used by body just further digestion and breakdown by bacteria, only absorb H20 and NaCl.

Question 347

Explain concept of lactose intolerance? Prevalence rates?

Answer 347

human milk has highest amount of lactose, need enzyme lactase to breakdown into glucose and galactose, enzyme typically in brushborder in SI, as much as 75% of human population loses this enzyme expression partial or complete resulting in lactose intolerance (gas, diarrhea, abdominal pain, and nausea. 90% of northern Europeans or those of northern European descent are tolerant

Question 348

What are the fat soluble vitamins? why is too much dangerous?

Answer 348

A,D,K, and E, deposit in membranes and are harder to excrete out excess

Question 349

What does vitamin A do?

Answer 349

precursor to visual receptor, retinol, and controls gene expression through interaction with nuclear receptors

Question 350

what condition results from deficiency in thiamine? What are the symptoms and contributing factors to deficiency?

Answer 350

beriberi: neuropathy, muscle weakness and wasting, cardiomegaly, edema, opthalmoplegia; alcholism

Question 351

what condition results from deficiency in Riboflavin? What are the symptoms and contributing factors to deficiency?

Answer 351

magenta tongue, angular stomatitis, seborrhea, cheilosis

Question 352

what condition results from deficiency in niacin? What are the symptoms and contributing factors to deficiency?

Answer 352

pellagra: pigmented rash of sun exposed areas, bright tongue, diarrhea, apathy, memory loss, disorientation; alcoholism, vit B6 deficiency, riboflavin deficiency

Question 353

what condition results from deficiency in B6? What are the symptoms and contributing factors to deficiency?

Answer 353

seborrhea, glossitis convulsions, neuropathy, depression, confusion; alcoholism, isoniazide treatment (TB)

Question 354

what condition results from deficiency in folate? What are the symptoms and contributing factors to deficiency?

Answer 354

megaloblastic anemia, atrophic glossitis, depression, homocysteine, embryonic development of spina bifida or anencephaly; alcoholism, sulfasalazine, pyrimethamine, triamterene

Question 355

what condition results from deficiency in B12? What are the symptoms and contributing factors to deficiency?

Answer 355

megaloblastic anemia, loss of vibratory and position so abnormal gait, dementia, impotence, loss of bladder and bowel control, increase in homocysteine and methylmalonic acid; gastric atrophy (pernicious anemia), terminal ileal disease, strict vegetarian

Question 356

what condition results from deficiency in vitamin C? What are the symptoms and contributing factors to deficiency?

Answer 356

scurvy: petechaie, ecchymosis, coiled hairs, inflamed bleeding gums, joint effusion, poor wound healing; smoking, alcoholism

Question 357

what condition results from deficiency in vitamin A? What are the symptoms and contributing factors to deficiency?

Answer 357

xerophthalmia, night blindness, BitA t spots, follicular hyperkarytosis, impaired embryonic development and dysfunction; fat malabsorption, infection, measles, alcoholism, protein energy malnutrition

Question 358

what condition results from deficiency in vitamin D? What are the symptoms and contributing factors to deficiency?

Answer 358

rickets: skeletal deformities, rachitic rosary, bowed legs, osteomalacia; aging, lack of sunlight exposure, fat malabsorption

Question 359

what condition results from deficiency in vitamin E? What are the symptoms and contributing factors to deficiency?

Answer 359

peripheral neuropathy, spinocerebellar ataxia, skeletal muscular atrophy, retinopathy; fat malabsorption, genetic abnormalities of Vit E metabolism/transport

Question 360

what condition results from deficiency in vitamin K? What are the symptoms and contributing factors to deficiency?

Answer 360

elevated prothrombin time, bleeding; fat malabsorption, liver disease, antibiotic use

Question 361

why does folic acid cause megaloblastic anemia?

Answer 361

involved in reactions in biosynthesis of amino acids, purines and DNA specific pyr, thiamine, impaired nucleotide synthesis is cause

Question 362

How does vitamin cause night blindness? What are some sources?

Answer 362

retinal in in visual pigment rhodopsin, deficiency of that causes night blindness; as retinoic acid in liver, kidney, dairy and egg yolks or cleaved from B-carotene in yellow and dark green veggies and fruit

Question 363

Why is vitamin C needed?

Answer 363

required for collagen hydroxylation, needed for cross-linking of collagen fibrils and in synthesis of carnitine. We lost ability to synthesize.

Question 364

Why is Vitamin E needed?

Answer 364

antioxidant, thought to help prevent lipid peroxidation and other damage caused by oxidative stress

Question 365

What is needed to absorb Vitamin B12? How long can boy go without?

Answer 365

binds in intestine to intrinsic factor, stores well so years

Question 366

Why is vitamin B6 needed?

Answer 366

precursor of pyridoxal phosphate which is coenzyme for number of transamination, deamination, decarboxylation, and condensation reactions

Question 367

Why is niacin needed? What happens if receive a high dose?

Answer 367

precursor of NAD and NADP, at high doses is a treatment for hyperlipidemia because it inhibits lipolysis in adipose tissue

Question 368

Why is vitamin D needed? synthesized? synthesis regulated?

Answer 368

it is a hormone, which binds to intracellular receptors increasing gene expression of Ca2+ binding protein resulting in increase in absorption, body can synthesize UV changes 7-dehydrocholesterol to cholecalciferol, liver changes that to 25-(OH)D3 then the kidney changes that to 1,25(OH)D3 active form (last step effected by low PO4 and PTH

Question 369

Why is vitamin K needed? How can vitamin k mechanism be used clinically?

Answer 369

blood coagulation, promotes gamma-carboxylation of glutamic acid in proteins esp. prothrombin, inhibiting action of K is a clinical treatment for hypercoagulation

Question 370

why is iodine needed? 2 sources?

Answer 370

needed in thyroid to make thyroxine, goiter will result as thyroid enlarges trying to overcome problem, sources: iodine rich soil or supplementation (salt in states)

Question 371

what condition results from Toxicity in Boron?

Answer 371

Developmental defects, male sterility, testicular atrophy

Question 372

what condition results from deficiency in Calcium? Toxicity?

Answer 372

reduced bone mass and osteoporosis; Renal insufficiency (milk-alkalai syndrome), nephrolithiasis, impaired iron absorption

Question 373

what condition results from deficiency in Copper? Toxicity?

Answer 373

Anemia, growth retardation, defective keratinization and pigmentation of hair, hypothermia, degenerative changes in aortic elastin, osteopenia, mental deterioration; Nausea, vomiting, diarrhea, hepatic failure, tremor, mental deterioration, hemolytic anemia, renal dysfunction

Question 374

what condition results from deficiency in Chromium? Toxicity?

Answer 374

Impaired glucose tolerance; Occupational: renal failure, dermatitis, pulmonary cancer

Question 375

what condition results from deficiency in flouride? Toxicity?

Answer 375

increased Dental caries;Dental and skeletal fluorosis, osteoscleroisis

Question 376

what condition results from deficiency in iodine? Toxicity?

Answer 376

Thyroid enlargement, decreased T4; Thyroid dysfunction, acne-like eruptions

Question 377

what condition results from deficiency in iron? Toxicity?

Answer 377

Muscle abnormalities, kilonychia, pica, anemia, work performance, impaired cognitive development, premature labor, perinatal maternal mortality; Gastrointestinal effects (nausea, vomiting, diarrhea, constipation), iron overload with organ damage, acute systemic toxicity

Question 378

what condition results from deficiency in manganese? Toxicity?

Answer 378

Impaired growth and skeletal development, reproduction, lipid and carbohydrate metabolism; upper body rash; General: Neurotoxicity, Parkinson-like symptoms Occupational: Encephalitis-like syndrome, Parkinson-like syndrome, psychosis, pneumoconiosis

Question 379

what condition results from deficiency in molybdenum? Toxicity?

Answer 379

severe neurological abnormalities; reproductive and fetal abnormalities

Question 380

what condition results from deficiency in selenium? Toxicity?

Answer 380

Cardiomyopathy, heart failure, striated muscle degeneration; striated muscle degeneration General: Alopecia, nausea, vomiting, abnormal nails, emotional lability, peripheral neuropathy, lassitude, garlic odor to breath, dermatitis Occupational: Lung and nasal carcinomas, liver necrosis, pulmonary inflammation

Question 381

what condition results from deficiency in phosphorus? Toxicity?

Answer 381

Rickets (osteomalacia), proximal muscle weakness, rhabdomyolysis, paresthesia, ataxia, seizure, confusion, heart failure, hemolysis, acidosis: hyperphosphatemia

Question 382

what condition results from deficiency in zinc? Toxicity?

Answer 382

Growth retardation, taste and smell, alopecia, dermatitis, diarrhea, immune dysfunction, failure to thrive, gonadal atrophy, congenital malformations; General: Reduced copper absorption, gastritis, sweating, fever, nausea, vomiting. Occupational: Respiratory distress, pulmonary fibrosis

Question 383

What are the different types of effects from mutation on protein function?

Answer 383

loss of protein function, gain of function, novel property, ectopic or heterochromic expression

Question 384

Which genes are responsible for HbF?

Answer 384

gamma G and A within the Beta globin gene cluster on chromosome 11

Question 385

What genes are responsible for alpha globin?

Answer 385

Alpha globin gene cluster on chromosome 16

Question 386

What genes are responsible for B-globin?

Answer 386

Beta Globin Gene Cluster Chromosome 11 delta region -> HbA2 and Bets -> HbA

Question 387

what is alpha thalassemia?

Answer 387

lowered production of alpha-globin, resulting form deletions of Alppha globin genes (4), Hb Barts (gamma 4) can remain in infancy to compenasate in adulthood (sometimes infancy if major) have formation of HbH to compensate. if all 4 are deleted = hydrops fetalis and in utero death

Question 388

How can two thal minor parents combine bad genes and get different results?

Answer 388

deletions can be 2 on one chromosome and an intact chromosome can lead to 4 deletions in child (common in Asian ancestry), or one parent can have a deletion on one chromosome each resulting in 3 deletions and thal major

Question 389

What is the cause of most B-thal cases?

Answer 389

single base changes leading to lowered production of B-globin from single B-globin gene on chr 11

Question 390

How genetically can B thal patients differ?

Answer 390

Minor- heterozygote with null and normal or heterozygote with mild and normal
Intermedia: 2 mild, very mild and normal
Major: 2 null or a null and a minor

Question 391

What are hemoglobin structural mutatnts?

Answer 391

point mutations in structural genes are most common (insertion, deletion, gene fusion and chain extension mutations exist), HbVar= hemoglobin variants, a variant can have multiple mutations

Question 392

What is sickle cell anemia?

Answer 392

a HbVar, 1st genetic disease from structural change in protein, Bs gene, autosomal recessive, HbS

Question 393

What is Hb Kempsey?

Answer 393

a:B interface is locked in relaxed oxygenated form, reduced ability to release O2 to tissue

Question 394

What is Hb Kansas?

Answer 394

a:B interface is permanently in taut non-oxygenated form, reduced oxygen affinity leading to cyanosis

Question 395

What is Hb constant spring?

Answer 395

mutation in stop codon of a-globin gene, 30 AA added then stop, result is unstable a-globin results in reduced synthesis of normal.

Question 396

What is significant with the distribution of hemoglobinopathies?

Answer 396

correlate to areas with malaria problems

Question 397

What is osteogenesis imperfect?

Answer 397

OI, disorder in a1 or a2 collagen genes, Type I is mild with bone fractures, Type IImay get progressively worse resultin in a still born, or intermediate with fractures and bonydeformities (type III and IV). Dominant disorder, can be caused by partial loss of a-1 (I) or mutation in coding region of a1 or a2 (I-IV)

Question 398

What is Ehlers-Danlos Syndrome?

Answer 398

vascular defects, stretchy skin, disorder in collagens I, II, III and IV as well as post-translational modification of collagen chains (6 types)

Question 399

What is marfan syndrome?

Answer 399

defect in collagen associated protein fibrillin; tall thin people, often athletes, aortic aneurysms, dislocated lens die to fibrillin gene involvement in attachment of lens to zonular ligaments

Question 400

In mendelian inheritance what does P stand for? F?

Answer 400

parent generation or first generation, filial generation (2nd filial is a cross between filial 1 generation)

Question 401

What of the law of segregation?

Answer 401

during gamete formation each member of allelic pair for a specific genetic trait separates from one another to form the genetic contribution to a gamete

Question 402

What is the law of independent assortment?

Answer 402

segregation of alleles of one allelic pair is independent of the segregation of alleles of another pair

Question 403

What does the frequency of independence tell us?

Answer 403

how far apart two alleles are

Question 404

What is codominance? example?

Answer 404

pattern observed with contributions of both alleles at a locus are expressed equally, A and B in blood types

Question 405

What is incomplete dominance? examples?

Answer 405

pattern that results where the contributions of both alleles are expressed in a phenotype that is between the parent organism, red and white snapdragon= pink

Question 406

What is polygenic inheritance? examples?

Answer 406

2 or more genes contribute to eventual phenotype, more genes = less each individual plays in phenotype, height and hair color, CVD

Question 407

What is pleiotropy? examples?

Answer 407

one gene influences multiple different phenotypic traits, PKU, lack of phenyalanine dehydrogenase causes MR, seizures, and decreased pigment

Question 408

What is epistasis? examples?

Answer 408

effects of one gene are modified by one or several other genes, very common throughout genome, patients with oculocutaneous albinism, inherit genes for skin, hair and eye pigmentation but cant express them

Question 409

what is penetrance?

Answer 409

binary description of whether a particular trait or disease is present or not

Question 410

What is expressivity?

Answer 410

qualitative description of degree or severity of trait or disease

Question 411

What are features of inheritance of autosomal recessive?

Answer 411

both parents must be carriers, most metabolic diseases are autosomal recessive

Question 412

What are features of autosomal dominant disease?

Answer 412

2 types= affected parent usually demonstrate high fitness, or new mutation = low fitness;

Question 413

What is haplosufficiency? example? mutation type?

Answer 413

autosomal dominant,50% reduction in normal gene amount causes disease. Type I OI, stop premature and degrade, nonsense mutation, mild deformity, all ok collagen just 50% less

Question 414

What is dominant negative? examples? mutation type?

Answer 414

autosomal dominant,mutant gene product interferes with function of normal gene product type II, III, and IV OI), missense mutation, nonfunctional incorporated in cause bad collagen formation

Question 415

What is cytotoxicity in term of genetics? example?

Answer 415

autosomal dominant, mutant gene product is toxic to normal tissues, huntingtons, variable expressivity due to length of repeat effects when/ if symptoms manifest

Question 416

What is first hit in genetics? examples?

Answer 416

autosomal dominant, many dominant hereditary cancer syndromes are mutations of oncogenes (RB, LFS) human stand point dominant, phenotype behaves as dominant due to a spontaneous mutation of good

Question 417

Describe the difference in incidence and inheritance in x-linked recessive and dominant. exmples

Answer 417

recessive- higher incidence in male than female, frequently a single copy of working gene is sufficient for normal function, mom is carrier, (hemophilia)
dominant- incidence is much higher in females due to frequent male lethality, muatation in one gene is sufficient to cause disease in female (incontinentia pigmenti)

Question 418

What do you look for in pedigree for autosomal recessive?

Answer 418

parents of affected child typically unaffected, both are obligate heterozygotes, family history may be negative for disease, consanguineous mating should be asked about, no sex preference observed

Question 419

What do you look for in pedigree for autosomal dominant?

Answer 419

one parent affected if child is affected, family history frequently positive, no sex preference, new dominant mutations frequently seen and difficult to separate from AR

Question 420

What do you look for in pedigree for x-linked recessive?

Answer 420

incidence is much higher in men than women, no male to male transmission, look for affected grandfather, unaffected daughter, affected child triangle

Question 421

What do you look for in pedigree for x-linked dominant?

Answer 421

males and females can both be affected, males tend to be more severe phenotype, often look like AD transmission, no male to male transmission, several XLD causes disease in female and death in male

Question 422

What do you look for in pedigree for mitochondrial?

Answer 422

passed directly from mother to child, will not see transmission from male to child, frequently wide variances in severity of disease

Question 423

What is Hardy-Weinberg principle?

Answer 423

allele and genotype frequencies remain constant in a population from generation to generation, useful in risk description

Question 424

What are exceptions to hardy-Weinberg?

Answer 424

non-random mating (inbreeding), small population size, new mutations, open group (migration in or out), selective pressure

Question 425

What are chromosomes crossovers?

Answer 425

necessary for chromosome maintenance and repairs, responsible for generating new haplotypes in each generation and add diversity to individual germ cells, source of CNV detected by DNA microarrays

Question 426

What is the holiday junction?

Answer 426

mobile junction between 4 DNA strands, in prophase of meiosis I duplicated homologous chromosomes pair and align, crossover can occur between aligned chromatids leading to exchange of homologous segments by homologous recombination

Question 427

What is the Lyon law?

Answer 427

in a female one X chromosome will become inactive, it condenses to form a Barr body attached to nuclear membrane, # of barr bodies equals the number of x chromosomes minus 1

Question 428

How is it “decided” which x is inactivated?

Answer 428

random but x with deletion or mutation is preferentially inactivated, occasionally the normal is preferentially inactivated

Question 429

What is skewed x-inactivation?

Answer 429

larger than average proportion of cells with a mutated gene on the active X-chromosome, may result in signs of disorder, “manifesting carrier”

Question 430

what is on the y chromosome?

Answer 430

sex determining region, handful of genes for testicular function and sperm formation, and pseudoautosomal region

Question 431

what is the pseudoautosomal region? How can this be a problem?

Answer 431

contains genes that are inherited like autosomal, males have 2 copies one on Y and one on X, these genes escape X inactivation

Question 432

How can the pseudoautosomal region lead to abnormal passing of fenes?

Answer 432

males can receive a gene that was on their fathers X chromosome, females can receive a gene that was originally on their fathers y chromorome

Question 433

What is somatic mosaicism?

Answer 433

mutations occur after conception, depending on timing can involve many, a few or just a single cell, phenotype depends on number of factors: type of abnormality, level of mosaicism (abnormal vs normal), tissue mosaic state is expressed

Question 434

What is germline mosaicism? example?

Answer 434

person may possess a mutation in gonads that is not necessarily expressed, person would not tend to show any phenotype, any gametes produced from affected gonadal tissue would transmit the mutation, Osteogenesis Imperfecta

Question 435

What is sex limited inheritance?

Answer 435

not x linked, autosomal inheritance but expression only in one sex, gender specific factors required for expression (ovarian cancer, prostatitis)

Question 436

What is sex influenced inheritance? examples

Answer 436

mainly expressed in one gender, alopecia androgenetica mostly men, BCRA2 mostly effects women

Question 437

What is uniparental disomy? Types?

Answer 437

two copies of particular chromosome from the same parent; isodisomy (same chromosome) or heterodisomy (different chromosome)

Question 438

What is monosomy rescue?

Answer 438

results from non-disjunction event in gamete causing nullisomy, duplication of remaining chromosome results in uniparental isodisomy for that chromosome

Question 439

What is trisomy rescue?

Answer 439

results from nondisjunction event in gamete causing disomy for that chromosome, one chromosome is lost restoring numerical balance, 2/3 of time results in normal biparental inheritance, 1/3 results in uniparental heterodisomy

Question 440

What is UPD and neonatal diabetes mellitus an example of in genetic inheritance?

Answer 440

uniparental disomy, and imprinting

Question 441

What is genomic imprinting?

Answer 441

differential expression of paternal versus maternal DNA, monoallelic expression, differential expression of chromosomal deletions, temporary alteration in function, involves only certain genes (locus specific), may occur as early as gamete formation and as late as early embryogenesis, achieved by methylation

Question 442

What are possible reasons for imprinting?

Answer 442

normal regulation of placenta, maintenance of sexual reproduction, flexibility during development, response to environmental factors

Question 443

What is Russel-Silver syndrome? Cause?

Answer 443

intrauterine growth retardation, triangle shape head, above eyes larger than below eyes; hypermethylation at location IC1 on paternal chromosome, causes decreased expression of IGF2 and increase expression of H19

Question 444

What is Beckwith-Wiedemann Syndrome?

Answer 444

macroglossia, macrosomia, omphalocele or umbilical hernia; one cause is hypermethylation at IC1 on maternal chromosome causes increased expression of IGF2 and decreased expression of H19

Question 445

What is Sherman paradox? example?

Answer 445

unusual pattern of inheritance in disorders which show anticipation, Fragile X syndrome, symptoms worsened with each generation

Question 446

How can trinucleotides repeats be normal? How can they be dangerous?

Answer 446

can just be a repeat for polymorphic variation with no clinical significance, a certain threshold of repeats is associated with a tendancy for further expansion without a clinical phenotype=permutation, at a certain point there is effected gene expression and phenotype.

Question 447

What is myotonic Dystrohpy?

Answer 447

muscle weakness, distal leg hand, face and neck, respiratory can be affected; caused by trinucleotide repeats

Question 448

How can trinucleotide repeats cause disease?

Answer 448

LOSS OF FUNCTION: disrupt gene transcription, translation due to hypermethylation (Fragile X)
GAIN OF FUNCTION: excess metabolite inhibit other enzymes and/or regulatory systems (direct toxicity), mechanism of disease in Huntington disease; DOMINANT NEGATIVE EFFECT: abnormal product interfereswith normal physiological function of product (myotonic dystrophy)

Question 449

How is mitochondrial DNA different?

Answer 449

circular, double stranded, no introns, UGA=Trp not stop, AGA and AGG stop rather than arginine, AUA AUU sometimes initiation , codes for 13 oxidative phosphorylation enzyme complex subunits, 2 ribosomal RNA and 22 tRNA

Question 450

What is the difference between mitochondria content in eggs and sperm

Answer 450

eggs- 100,000, sperm 100-1500

Question 451

What is semiautonomous inheritance?

Answer 451

mitochondrial DNA segregates in daughter cells independent of nuclear chromosomes; have to have cell replication for segregation

Question 452

What is maternal inheritance?

Answer 452

mtDNA transmission is exclusively maternal; mtDNA from spermatozoa actively degraded at 2-4 cell stage

Question 453

What is replicative segregation?

Answer 453

homoplasmy: single mtDNA sequence in a given cell; heteroplasmy: more than one mtDNA sequence in a cell; cytokinesis stage of heteroplasmic cells partitions different into daughter cells -> replicative drift

Question 454

What is the bottleneck phenomenom?

Answer 454

restriction and subsequent amplification creates a genetic bottleneck, leads to an overall reduction in diversity

Question 455

What are the characteristics of mitochondrial disease?

Answer 455

since mitochondria are responsible for energy production the organs most effected are those which require more energy; pigmentary retinopathy, ptosis, external ophthalmoplegia, proximal myopathy, diabete mellitus

Question 456

What is MELAS?

Answer 456

Mitochondrial Encephalopathy Lactic Acidosis Stroke-like-episodes; ragged red fibers on muscle biopsy, may have most but not all, early unexplained stroke

Question 457

What is MERRF

Answer 457

Myoclonic Epilepsy Ragged Red Fibers, hearing loss, short stature, optic atrophy, cardiomyopathy with WPW, some will have Pigmentary Retinopathy (mitochondrial)

Question 458

What is leigh syndrome?

Answer 458

progressive neurologic disease with motor and cognitive delay, can have lactic acidosis or increased lactate in CSF, may be maternal milder history

Question 459

What is kearns-sayre syndrome?

Answer 459

classic triad, onset before age 20, pigmentary retinopathy, progressive external ophthalmoplegia; atleast one of the following: cardiac conduction block, elevated CSF protein, cerebellar ataxia

Question 460

What is hereditary hemochromatosis?

Answer 460

two mutations in HFE1 are causative, C282Y more severe, majority caused by C282Y homozygotes but compound heterozygotes can be affected, carrier rate 19% in US and 53% in Ireland

Question 461

Alpha-1-antitrypsin deficiency causes what commonly?

Answer 461

COPD and Liver disease

Question 462

What is familial hypercholesterolemia?

Answer 462

one of most common monogenetic diseases, mutations in LDL receptor, heterozygotes total cholesterol between 275-500, homozygotes above 500mg/dl severe atherosclerosis by childhood or young adulthood

Question 463

What creates susceptibility to disease?

Answer 463

each gene can have small changes that subtly alter function and interaction with other genes,

Question 464

What is MODY? Causes?

Answer 464

Maturity Onset Diabetes of the Young, Type II DM Variant- no ketoacidosis problem, HNF1A mutation, GCK mutations

Question 465

What causes neonatal diabetes mellitus?

Answer 465

KNJ11 gene or UPD 6 mutation, responds well to sulfonylureas=increases the amount of insulin release in Beta islet cells

Question 466

What is GWAS? What was discovered or suggested?

Answer 466

comparison of genomes or exomes of patients w/ certain disease or trait; numerous SNPs are associated with an increase risk of type II DM, related to insulin production, growth factors for Beta islet cells and reduced glucose-stimulated insulin secretion; also found obesity-associated loci associated with obesity and insulin resistance, neurologic development plausible due to hypothalamic control

Question 467

What is high resolution karyotyping?

Answer 467

G-banding involves a trypsin treatment and staining, AT rich regions stain darkly, GC rich regions stain lightly, analyze under a microscope

Question 468

What are the clinical features of triploidy?

Answer 468

miscarriage, large placenta and late loss if paternal, small placenta and early loss if maternal, etiologies: dispermy, retention of polar body, diploid egg or sperm

Question 469

What is turner syndrome? cause?

Answer 469

primary amenorrhea/infertility, short stature, congenital lymphedema, webbing of the neck, cardiac/renal anomalies; paternal non-disjunction, 18% miscarriage rate

Question 470

What is Klinefelter syndrome? Cause?

Answer 470

XXY, tall thin male with long legs, underdeveloped secondary sex characteristics, small testicles, gynecomastia(50%), infertility in all (30-40% only have infertility) caused by non-disjunction

Question 471

What is XYY? features?

Answer 471

extra Y, tall stature, speech delays, behavioral or learning problems maybe, occasionally: large teeth, glabella, long arms/legs, bad acne;

Question 472

What is down syndrome?

Answer 472

flat facial profile, small nose, epicanthal folds, single palmar crease, sandal gap, brushfield spots, short fingers, hypotonicity, intellectual disability, non-disjunction 95%, translocation 4-5%, risk increases with maternal age

Question 473

What is Williams syndrome? cause?

Answer 473

elfin faces, short stature, suprvalvular aortic stenosis, outgoing personality, developmental delay, hoarse voice, hypercalcemia, deletion on 7q11.23

Question 474

What is CGH microarray?

Answer 474

comparative genomic hybridization, imbalance between patient and control DNA is either control signal deletion or patient duplication, not a sequence, detects subtle deletions and duplications but no rearrangements

Question 475

What is SNP microarray?

Answer 475

similar to oligonucleotide micro-arrays, difficulty in hybridizing unique SNP so lots of built in redundancy

Question 476

What is RFLP?

Answer 476

early and simple method of SNP analysis, restriction endonuclease digestion on genomic sample creates fragments of a certain length which can be ascertained on gel electrophoresis

Question 477

What is PCR?

Answer 477

primers complementary to DNA region of interest are added to target DNA with heat stable polymerase, thermal cycler used to heat and cool repeatedly, allows replicated DNA to serve as templates for successive cycles, end result larger amount of DNA of target region

Question 478

What is Sanger sequencing?

Answer 478

aka chain terminator sequencing, oligonucleotide primers complimentary to a template are used with each of four nucleotides, dna polymerase is used to extend sequence, chain terminating nucleotides are placed in low concentration as well (usually dideoxybase with fluorescent tag)

Question 479

What is next generation sequencing?

Answer 479

a group of high throughput sequencing techniques: reversible dye terminator, parallel pyrosequencing, ligation-based sequencing, ion semiconductor sequencing, and others

Question 480

What is exome sequencing? why is it important

Answer 480

sequencing of all coding regions of all genes, estimated that 85% of all mutations will be in exome

Question 481

What was the first human experiment with gene therapy?

Answer 481

1970 in Germany, shope rabit virus caused decreased arginine levels, gave it to two girls who had a defect in arginase enzyme which cause a build up of arginine, nothing happened

Question 482

When was recombinant DNA via bacterium first possible?

Answer 482

mid1970

Question 483

When was the first experiment of gene therapy using recombinant DNA?

Answer 483

1980, Dr. Cline, 2 patients, trying to treat beta thalassemia, not approved trial, no harm to patients but sanctioned and lost grants

Question 484

What was the first success in gene therapy?

Answer 484

1990s after animal trials and switching from marrow to WBC target for ADA deficiency treatment, still needed enzyme replacement but less after gene therapy

Question 485

What happened with the Gelsinger gene therapy that was notable?

Answer 485

given adenovirus with functional OTC gene to treat metabolic condition, reacted badly to virus and died, later discovered that lead researcher had a financial stake in adenovirus vector, and she did not meet research criteria, language in informed consent had been removed about animal death and illness, didn’t report two prior severe reactions, changed order of patients without asking (not random)

Question 486

What are the barriers to gene therapy?

Answer 486

half-life (many therapeutic targets are rapidly dividing cells, therapy must be administered frequently), Immunogenecity (viral vectors/ replacement protein can trigger immune response), unintended viral consequences (inflammation, incorrect targeting of virus to other tissues, causation of initial viral disease or malignancy), and poor efficacy (frequently even if targeted correctly not enough gene product is integrated)

Question 487

What are the challenges to gene therapy in OI?

Answer 487

Type ! is haplosufficiency so replacement of collagen should be curative; Type II, III, and IV are dominant negative effect so need to silence mutant allele to impact disease

Question 488

What is the limitation in stem cell therapy in OI?

Answer 488

poor engraftment (generally expression in below 5% and often below 1%) bone marrow transplant (assumption that myeloablative conditioning would be needed to prevent rejecton of graft, at best means trading one disorder for another

Question 489

How effective is gene therapy in OI?

Answer 489

tried a viral vector with healthy COL1A1 in vitro to disrupt mutant version but cause normal collagen production dominant neg went to haplosufficiency but still not able to work, also have tried overexpression of COL1A1 but not effective enough to outweigh risk

Question 490

How have stem cells been used to treat OI?

Answer 490

mesenchymal cells from patients with OI collected, mutant genes inactivated by adenovirus, induced pluripotent stem cells were derived, mesenchymal cells were then derived, stem cells differentiated into osteoblasts, normal type I collagen made, mineralized bone made, proliferated more than bone-derived multipotent cells

Question 491

What are some problems still present with stem cell treatment of OI?

Answer 491

poor efficiency- only 1% needs to be 10-20%, unclear how to target iPSC into bone to grow (interosseus injection or bone marrow lavage?)

Question 492

What is the future of gene therapy look like?

Answer 492

silica based vector (nanites), polymer and lipid complex as vector, gene transfer to brain following stroke, microRNA to influence expression

Question 493

What are the lymphoid cells? What is the pathway of their development?

Answer 493

NK cell, T cell, B cell; Hematopoietic stem cell to common lymphoid progenitor to pre B cell or pre T cell or pre NK cell, to B cell or T cell or NK cell respectively these are released to blood, B cell can further differentiate into a plasma cell in connective tissue

Question 494

What are the WB cells? What is the pathway of their development? Which one has an exception?

Answer 494

dendritic cell, Neutrophil, Mast cell, Eosinophil, Macrophage, Monocyte, and basophil; hematopoietic stem cell to common myeloid progenitor to granulocyte monocyte progenitor to prodendritic cell or neutrophil progenitor or basophil/mast cell progenitor or eosinophil progenitor cell or monocyte progenitor, then to dendritic cell(CT) or neutrophil (blood) or basophil (blood) or mast cell progenitor (CT) or eosinophil (blood), or monocyte (blood) respectively, mast cell progenitor becomes a mast cell in the CT and a monocyte can become a macrophage in the CT; exception is that a dendritic cell can come from the lymphoid path into the pro-dendritic cell level

Question 495

What is the pathway of development of RBCs?

Answer 495

hematopoietic stem cell, to common myeloid to megakaryocyte/erythrocyte progenitor, to erythrocyte progenitor to proerythroblast to orthochromatophillic erythroblast to erythroblast

Question 496

What Is the pathway of development of platelets?

Answer 496

hematopoietic stem cell to common myeloid to megakaryocyte/erythrocyte progenitor to megakaryocyte progenitor to megakaryoblast to megakaryocyte then cell apoptosis and release of platelets

Question 497

Where and at what age does hematopoiesis occur? Which hemoglobin types are made at each?

Answer 497

yolk sac 4-10wks gestation HbE, fetal liver 6 weeks to term HbF, spleen 10 weeks to 7 months gestation HbF, bone marrow 4 months gestation to death HbA (HbA2) eventually HbB

Question 498

What is the source, target and primary effect of Flt3-ligand?

Answer 498

ubiquitous; stem cells and progenitor cells; synergistic for proliferation of early stem cells

Question 499

What is the source, target and primary effect of Stem cell factor?

Answer 499

BM stroma; stem cells and early myeloid progenitors; proliferation of early stem cells in synergy with other cytokines

Question 500

What is the source, target and primary effect of IL-1?

Answer 500

macrophages and keratinocytes; myeloid stem cells and thymocytes and endothelium; induces early and committed stem cells to enter cycle, induces GM-CSF, G & M CSF and IL-3 production, releases neutrophils from BM

Question 501

What is the source, target and primary effect of IL-3?

Answer 501

t-cells and macrophages; stem cells and immature progenitors; proliferation of early and committed stem cells

Question 502

What is the source, target and primary effect of IL-6?

Answer 502

t-cells, macrophages, endothelium and fibroblasts; stem cells and early myeloid progenitors; induces early stem cell proliferation and induces megakaryoblast proliferation

Question 503

What is the source, target and primary effect of GM-CSF?

Answer 503

t-cells, macrophages, endothelium and fibroblasts; myeloid progenitors; induces proliferation of myeloid stem cells, proliferation and activation of macrophage and granulocyte progenitors

Question 504

What is the source, target and primary effect of M-CSF?

Answer 504

macrophages, endothelium and fibroblasts; committed macrophage progenitors; proliferation and activation of monocyte precursors

Question 505

What is the source, target and primary effect of G-CSF?

Answer 505

macrophages, endothelium and fibroblasts; committed neutrophil progenitors; proliferation and activation of neutrophil precursors

Question 506

What is the source, target and primary effect of IL-5?

Answer 506

t-cells; eosinophil progenitors; proliferation and activation of eosinophil precursors

Question 507

What is the source, target and primary effect of IL-4?

Answer 507

t-cells; basophil progenitors; proliferation and activation of basophil precursors

Question 508

What is the source, target and primary effect of erythropoietin?

Answer 508

kidney, liver connective tissue cells; immature erythroid and megakaryocyte progenitors; proliferation of erythroid and megakaryocyte progenitors

Question 509

What is the source, target and primary effect of thrombopoietin?

Answer 509

liver; committed megakaryocytes; proliferation of megakaryocyte progenitors

Question 510

What is the source, target and primary effect of IL-11?

Answer 510

none listed; committed megakaryocytes progenitors; proliferation of megakaryocyte progenitors

Question 511

What is the normal frequencies of WBC in the blood? Which ones are classified as granulocytes?

Answer 511

Neutrophils: 55-65%, Eosinophils: 3-5%, Basophils: 0-1.5%, Lymphocytes: 25-40%, and Monocytes 3-8%; Neutrophils, Eosinophils, and Basophils

Question 512

What tests make up a CBC? Define each one.

Answer 512

total WBC, RBC- mass concentration, shape and agglutination; hematocrit: space occupied by packed RBCs closely parallels with hemoglobin and RBC; hemoglobin, and MCV-mean corpuscular volume represents average volume of RBC in femtoliters (macrocytic and microcytic); sedimentation rate- distance RBCs fall in one hour; Plasma proteins: fibrinogen, alpha globins and others

Question 513

What are some identifying features of Neutrophils? Function?

Answer 513

multilobed nucleus, primary graunles lysosomes, secondary granules, tertiary granules; phagocytosis mostly bacteria viaH2O2, HOCl, MPO, O2 and PLA2 (respond to acute chemotaxis

Question 514

What are some identifying features of eosinophils? function?

Answer 514

bilobed nucleus, primary granules, secondary eosinophil specific membrane bound to granules with crystalline inclusions; migrate to site of allergic reaction, inflammatory reponse or parasitic worms, eosinophil derived neurotoxin damages nervous system of parasites

Question 515

What enzyme is missing in children that effects the function of their neutrophils leading to their susceptibility to repeated bacterial infectons?

Answer 515

deficiency in NADPH oxidase so neutrophils cant generate superoxide H2O2 during phagocytosis

Question 516

Elevation of corticosteroid levels in the blood does what to which WBC?

Answer 516

suppress the number of eosinophils in circulation

Question 517

What are some identifying features of basophils? function?

Answer 517

bi-lobed or tri-lobed nucleus, specific membrane bound basophilic granules; heparin anticoagulant, histamine-vasoactive, heparin sulfate-vasoactive, leukotrienes-trigger prolonged sustained constriction of smooth muscle cells in pulmonary airways, receptor for IgE-binds to IgE releasing histamine and other vasoactive mediators resulting in hypersensitivity reaction (Anaphylactic shock), becomes mast cell in CT

Question 518

What are some identifying features of lymphocytes? function?

Answer 518

no prominent granules, nucleus takes up most of cell, macrophages are more indented in the nucleus than lymphocytes; t-lymphocytes major role in cell mediated immune response, B lymphocyte, NK cells kill tumor cells and virally infected cells

Question 519

What are some identifying features of monocytes? function?

Answer 519

largest, more indented nucleus because they become macrophages- antigen presenting cells in immune system

Question 520

What are key features of platelets and what is their function?

Answer 520

biconvex until activated, life span of <10 days, granules that store serotonin, microtubule bundles and dense tubular system; cellular phase- platelet adherence and then thrombus=hemostatic plug, enzymatic phase-enzymes and phospholipids released by platelets and injured tissues=fibrin clot, contraction phase-platelets contract platelet derived substances constrict injured vessels

Question 521

What changes cellularly as the cell progresses from pluripotent stem cell to red blood cell?

Answer 521

decrease in size cell and nucleus, increasing heterochromatin, decreasing cytoplasmic basophillia increasing acidophilia (purple to pink), decreasing polyribosomes: increasing Hb, polychromatic cells are the last mitotic stage, regulation by erythropoietin (EPO)-produced by the kidney

Question 522

What changes in the cell in the formation of platelets?

Answer 522

increase of cell size and ploidy, increasing granularity and formation of platelet demarcation zones, gradual complete loss of cytoplasm to platelet production

Question 523

What changes in the cell in the formation of granulopoiesis?

Answer 523

initial increase then decrease in size, increase in heterochromatin, lobulation of the nucleus, myelocytes are the last mitotic stage, acquisition of primary lysosomal granule then specific granules

Question 524

What changes in the cell in the formation of monocytes and macrophages?

Answer 524

relatively small morphological changes with maturation, most monocytes/macrophages retain their ability to divide

Question 525

How does the thymus function in the immune system?

Answer 525

primary lymphoid organ, antigen independent proliferation, multipotent stem cells from bone marrow enter into the epithelial which develops into the thymus, the thymic cortes or parenchyma contains developing T lymphocytes (stains purple),

Question 526

What are the 6 types of cells in the thymus and where are they located?

Answer 526

Type I, II, III epithelioreticular cells in the cortex, Type Iv, V, and VI epithelioreticular cells in the medulla

Question 527

What makes up the blood epithelial barrier and what is its purpose?

Answer 527

endothelium is highly permeable to macromolecules in the perivascular connective tissue, macrophages in phagocytosing antigenic molecules that escape from capillary lumen, Type I epithelioreticular cells contain occluding junctions to protect developing T lymphocytes, it protects developing T-cells

Question 528

What are the two types of T-cell education and basic principle of each?

Answer 528

positive selection: selection for thymocytes that recognize self MHC molecules expressed on cortical epithelium
negative selection: selection against thymocytes that recognize self antigen in context of self MHC

Question 529

How is positive selection achieved?

Answer 529

entrance of lymphoid stem cells into thymic medulla via post capillary venule, expression of CD2, CD7, CD1 followed by TCRs CD3 and CD4 and CD8, presentation of developing T cells with self by type II and type III cells, if lymphocyte recognizes self MHC and self-antigen, it will survive the positive selection if not death of unselected cell

Question 530

How is negative selection achieved?

Answer 530

cells directed to self antigen displayed by self MHC are eliminated by negative selection, cells that survive that selection become either cytotoxic CD8+ T lymphocytes or Helper CD4 + T lymphocytes, these are immunocompetent cells leave thymus and enter blood circulation, regulatory cytokines secreted by type VI cells promote this process

Question 531

What are the thymic or Hassal’s corpuscles and what are they for?

Answer 531

derived from Type VI cells, concentrically arranged exhibiting flattened nuclei, contain keratohyalin granules which are bundles of intermediate filaments and lipid droplets, produce interleukins such as IL-4 and IL-7 that function in thymic differentiation and education of T-lymphocytes

Question 532

What is necessary for B cell differentiation and maturation?

Answer 532

need intimate contact with stromal cell for signaling by GF (Cytokines of interleukins), starts along the endosteal surface and moves inward to let B cells entering circulation

Question 533

What is the lymph nodes function?

Answer 533

filters lymph, main site which T and B lymphocytes undergo antigen-dependent proliferation and differentiation into effector cells and memory cells

Question 534

What is located in the medulla of the lymph node?

Answer 534

medullary cords and sinuses

Question 535

What is located in the cortex of the lymph node? What occurs here?

Answer 535

lymph nodules (aggregates of lymphocytes), in active lymph this is the site of B cell proliferation and differentiation in response to an antigen, contain lighter area known as germinal center

Question 536

What is the area between the medulla and the cortex? What can be found here?

Answer 536

deep cortex contains high endothelial venules made of cuboidal cells, has a dense population of lymphocytes especially T cells

Question 537

What is the flow of lymph through a lymph node?

Answer 537

vessels empty into subcapsular sinus, wall of sinuses allow lymph to freely percolate into superficial and deep cortex allowing lymphocytes to engage in immune surveillance, after entering tissue lymphocytes migrate back to sinuses and leave to medullary sinus then efferent lymph vessel

Question 538

What is the function of reticular cells in the lymph node?

Answer 538

synthesize and secrete type III collagen, and associated ground matrix, provide support, express molecules and produce substance that attracts T and B cells and dendritic cells

Question 539

What is the function of dendritic cells?

Answer 539

involved in antigen presentation, class MHCI and II

Question 540

What is the function of macrophages?

Answer 540

phagocytic and antigen presenting cells expressing MHC I and II and costimulatory molecules but less than a dendritic cell (antigen)

Question 541

What do we know about follicular dendritic cells?

Answer 541

interdigitate between B lymphocytes in germinal centers, not APC (antigen presenting cell) because they lack MHCII

Question 542

What is the function of high endothelial venules?

Answer 542

90% of lymphocytes enter here, signal lymphocyte to leave circulation and migrate into lymph nodes via receptor for antigen primed lymphocytes, T cell remain in deep cortex and B cells migrate to nodular cortex (regulated by HEV)

Question 543

What occurs in germinal centers?

Answer 543

clonal proliferation, Ig class-switching, somatic hyper mutation and selection by antigen

Question 544

What does the spleen do?

Answer 544

major repository for mononuclear phagocytic cells (25%) and 1/3 of platelets, spleen filters blood with morphologic and immunologic filtering functions and reacts immunologically to blood borne antigens

Question 545

What are characteristics of the white pulp? function?

Answer 545

rich in lymphocytes form periarteriolar lymphatic sheath (PALS) around branches of artery that penetrate pulp, PALS predominantly contain T lymphocytes and lymphoid nodules contain B lymphocytes

Question 546

What are characteristics of the red pulp? function?

Answer 546

splenic sinuses surrounded by splenic cords, large number of RBC due to filters and degrading= trapped by macrophage and breakdown RBC and hemoglobin and retrieve and store iron from heme for reutilization in formation of RBC in marrow, non-functional platelets also degraded

Question 547

How does blood enter the red pulp for filtration?

Answer 547

open system, penicillar arterioles empty directly into reticular meshwork, blood percolates in through the cords and is exposed to macrophages there

Question 548

what are the immune functions and hematopoietic functions of the spleen?

Answer 548

immune: antigen presentation, initiation of immune response, activation and proliferation of B and T cells, production of antibodies, and removal of macromolecular antigens from the blood; Hematopoietic functions: removal and destruction of senescent or damaged RBC and platelet, retrieval of iron from hemoglobin, formation of RBC during fetal life, storage of blood and RBC in some species

Question 549

What are characteristics of the tonsil and its function?

Answer 549

dips of epithelium into CT called crypts, lymphatic nodules in crypts, plasma cells differentiate from here and secrete IgA antibodies

Question 550

What is a peyer’s patch?

Answer 550

multiple lymphatic nodules with visible germinal centers typically found in ileum,

Question 551

What are the steps in synthesis of purines coming off the denovo path?

Answer 551

IMP to AMP and GMP phosphorylated to ADP, ATP, GDP and GTP, ADP and GDP are reduced by ribonucleotide reductase to dADP and dGDP they can then be phosphorylated to dATP and dGTP or dephosphorylated to dAMP and dGMP

Question 552

What are the ribonucleotides made in denovo synthesis of purines?

Answer 552

IMP, AMP, XMP, GMP, ADP, GDP, ATP and GTP

Question 553

How does the body get rid of extra ribonucleotides?

Answer 553

XMP to xanthosine to xanthine to uric acid or IMP to Inosine to hypoxanthine to xanthine to uric acid or GMP to gaunosine to guanine to xanthine to uric acid

Question 554

What are to carbon donators in denovo synthesis of purines?

Answer 554

aspartate, glutamine, glycine, CO2, and fromyl tetrahydrofolate

Question 555

What is the key intermediate for denovo synthesis of purines?

Answer 555

PRPP, 5-phopshoribosyl pyrophosphate, ribose source

Question 556

What is the pathway for denovo synthesis of purines?

Answer 556

ribose-5-phopshate takes two phosphates from ATP via PRPP Synthetase to make PRPP, amine group added via glutamine and H2O via PRPP amidotransferase giving of PPi and glutamate resulting in Phosphoribosylamine utilizing and ATP glycine adds CO, CH2 and NH3 then formy-THF adds CHO then glutamine adds amine and takes O from first carboxylic carbon lose a water to close the ring, CO2 added to ring then aspartate donates its side chain give off fumerate, formyl-THF donates CHO lose H20 and close ring for IMP

Question 557

What are the main points of regulation in purine synthesis?

Answer 557

formation of IMP, AMP and GMP

Question 558

At what steps and how is IMP synthesis regulated?

Answer 558

1st step formation of PRPP is inhibited by AMP and GMP, 2nd PRPP to phosphoribosylamine via PRPP amidotransferase is feedback inhibited by adenine and guanine and stimulated by PRPP

Question 559

What is Gout? Causes?

Answer 559

build up of uric acid in the body, urate crystals are not soluble and will collect in joints esp big toe, excess synthesis of purines, (overactive PRPP amidotransferase or mutation making it less sensitive to feedback or elevated levels of PRPP synthetase) inadequate salvage of purines (deficiency in HGPRT), or impaired uric acid excretion in kidneys

Question 560

How is synthesis of AMP and GMP regulated?

Answer 560

feedback inhibition by themselves, stimulation of GMP via ATP and AMP via GTP

Question 561

Nucleotide salvage pathway is best defined as converting ____ & ____ to ______. Not What?

Answer 561

nucleobase, nucleoside, nucleotide, not further modification (addition of phosphate groups) of nucleotide

Question 562

What is the source of nucleosides and nucleobases in salvage path?

Answer 562

intracellular degradation of RNA and DNA only a very small amount comes from diet (not absorped

Question 563

What is the most important enzyme in the purine salvage pathway? What disease is caused by its deficiency?

Answer 563

HGPRT or hypoxanthine-guanine phosphoribosyl transferase, partial loss leads to gout complete deficiency causes Lesch-Nyhan syndrome

Question 564

What drug can be used for gout treatment how does it work?

Answer 564

allopurinol inhibits xanthine oxidase thus reducing amount of uric acid made, or probenecid which increases renal secretion of uric acid, colchicine relieves gout pain and is an anti-inflammatory

Question 565

What is Lesch-Nyhan syndrome how is it passed? Characteristics?

Answer 565

complete absence of HGPRT enzyme, x-linked recessive, affects males; self mutilation, mental retardation and gouty arthritis, CNS involved because low capacity for denovo path so complete absence of salvage damages brain by depriving it of purine nucleotides

Question 566

What is combined immunodeficiency?

Answer 566

aka adenosine deaminase deficiency resulting in excess dATP, high levels inhibit ribonucleotide reductase activity which is needed for DNA synthesis, impossible for WBC rapid proliferation for immune response, dATP is toxic in cells but cannot cross membrane due to negative charge, not toxic outside cell

Question 567

How does acyclovir work in treating herpes? Side effects?

Answer 567

acyclovir is purine analog, viral thymidine kinase (but not the hosts) converts acyclovir into a nucleotide, acyclovir has no 3’hydroxyl group, elongation of DNA stops once incorporated, Acute renal failure (poor solubility), nausea, vomiting, abdominal pain, diarrhea, and neurotoxicity

Question 568

In the prymidine pathway what does ribonucleotide reductase do?

Answer 568

UDP to dUDP and CDP to dCDP

Question 569

How is CTP made from UMP

Answer 569

UMP to UDP to UTP to CTP

Question 570

In the pyrimidine pathway what does thymidylate synthase do?

Answer 570

dUMP to dTMP

Question 571

What does thymidine kinase do?

Answer 571

thymidine to dTMP

Question 572

What does uridine kinase do?

Answer 572

uridine to UMP

Question 573

In pyrimidine salvage what is salvaged at a higher frequency?

Answer 573

nucleosides more than pyrimidine bases

Question 574

What are the two products of pyrimidine degradation?

Answer 574

beta-aminoisobutyric acid and beta-alanine

Question 575

What are the molecules contributing to the denovo synthesis of pyrimidines?

Answer 575

aspartate, ribose-5-phosphate, glutamine and CO2

Question 576

Describe the steps for denovo synthesis of pyrimidines.

Answer 576

NH3 and CO2 with ATP form carbamoyl phosphate, aspartate donates CONH2 to make carbamoyl aspartate, lose water to form ring dihydroorotate rearrange to orotate (orotic acid), add PRPP lose PPi and form orotidine monophosphate (OMP), lose CO2 to make Uridine monophosphate (UMP)

Question 577

At what points and by what molecule is denovo synthesis of pyrimidines regulated? difference in mamals and bacteria?

Answer 577

bacteria formation of carbamoyl aspartate (2nd step) stimulated by ATP and inhibited by CTP, mammals same step but activated by PRPP and inhibited byUTP, conversion of UTP to CTP is stimulated by GTP and inhibited by CTP

Question 578

What is orotic aciduria? Cause?

Answer 578

rare genetically inherited disease, 2 enzymes are deficient causing build up of Orotic acid, but problem is lack of nucleotides, onset early infancy, failure to thrive, megaloblastic anemia, orotic acid crystals in urine, regarded physical and mental development, weakness and fatigue, treat with Uridine which Uridine kinase changes to UMP

Question 579

Describe the detailed mechanism of thymidylate synthase.

Answer 579

takes methylene tetrahydrofolate and dUMP and produces dTMP and then regenerates the hydrogens lost on folate by dihydrofolate reductase and NADPH as donor then serine donates the lost methyl group and becomes glycine resulting in another methylene tetrahydrofolate

Question 580

What enzyme involved in dUMP to dTMP is a drug target? give an example and purpose.

Answer 580

dihydrofolate reductase, methotrexate, inhibits dTMP so DNA synthesis is blocked, important in treating cancer

Question 581

What does 5-Fluorouracil do? When is it used?

Answer 581

inhibits thymidylate synthase, breast and colon cancer it is an inactive precursor for FdUMP

Question 582

What is hydroxyurea?

Answer 582

a drug used fo treating leukemia, inhibits ribonucleotide reductase

Question 583

What regulates and where the synthesis of deoxyribonucleotides?

Answer 583

excess dATP caused by adenosine deaminase deficiency inhibits ribonucleotide reductase (immunodeficiency)

Question 584

What is the baseline/background risk for congenital anomaly?

Answer 584

3%, general population risk, cant make it go away

Question 585

What is a teratogen?

Answer 585

any environment agent such as drug, chemical, infection, or pollutant which potentially harms the developing fetus

Question 586

What is karnofsky’s law?

Answer 586

anything at the right time of pregnancy and the right does in the right species can be teratogenic

Question 587

What are Wilson’s principles of teratology?

Answer 587

4 basic manifestations of abnormal development= loss, malformations, growth retardation, and functional deficits; susceptibility dependent on genotype, nature of damage depends on timing and exposure, rate and severity are dose dependent, syndrome of outcomes is specific to insult, plausible biological explanation for the mechanism of action of the teratogen

Question 588

How important is paternal exposure?

Answer 588

not well studied but little evidence it causes birth defects

Question 589

What are some examples of teratogens and matching outcomes that have a genetic component causing increased susceptibility?

Answer 589

Alcohol-FAS, Smoking-Oral clefts, Retinoic Acid-Embryopathy

Question 590

What is the outcome to teratogenic exposure at each point in gestation? 0-15 days, 15-60 days, 60-80 days, 2nd and 3rd trimester?

Answer 590

0-15: miscarriage, fetal death; 15-60: fetal death, major malformations, growth retardation and impaired IQ; 60-80: fetal death, vascular disruption by hypoxia, hemorrhage, and tissue loss; 2nd and 3rd Tri: stillbirth, growth retardation, impaired IQ

Question 591

What are some results of exposure to alcohol during pregnancy and breastfeeding?

Answer 591

loss, FAS: growth retardation, CNS dysfunction (retardation or hyperactivity), characteristic facial features (microcephaly, flat maxillary area, flat philtrum, thin upper lip), malformations, breastfeeding mom BAL= concentration in milk, >1 a day=drowsiness and delays

Question 592

When is a higher dose of folic acid recommended?

Answer 592

on anticonvulsant, diabetes, inflammatory bowel disease, have had previous child with spina bifida, CL/CP or a heart defect

Question 593

What are the effects of chemotherapeutic agents during pregnancy? When and what dose is appropriate if any?

Answer 593

high dose: malformations 1st tri, IUGR, Pancytopenia, CNS damage, cardiomyopathy, pregnancy loss or prematurity, low dose for autoimmune disorders after 7 weeks significantly lower risk

Question 594

What effects does Accutane have in pregnancy? What is being done?

Answer 594

2x risk miscarriage, 25% chance of major birth defect, possible long term effects on development; iPledge program

Question 595

What is the recommendation on vaccinatons during pregnancy?

Answer 595

caution with live organism (Varicella or MMR during breastfeeding and pregnancy), attenuated usually ok, some even encouraged, Influenza shot not mist, Tdap (20 wks)- pass immunity to baby who will not be able to receive immunization; no evidence any leads to autism

Question 596

What is the purpose and key characteristics of innate immunity?

Answer 596

first line, slow growth of infectious agents until adaptive immunity kicks in, a means of directing adaptive immunity via inflammatory response, activation of dendritic cells, production of cytokines that specialize response, fast, non-specific, and no memory

Question 597

What are the different components of innate immunity?

Answer 597

mechanical barrier (skin, mucous membranes, and normal flora), humoral component (lysozymes, interferons and complements) and cellular components (macrophages, neutrophils, monocytes and nature killer cells)

Question 598

What are the types of phagocytic pattern recognition receptors and what do they bind?

Answer 598

mannose and glucan receptors= bacterial carbs on cell surface, scavenger receptor= negatively charged ligands like on gram + bacteria, CD14= lipopolysaccharide (gram -)

Question 599

What are the different phagocytic opsonin receptors and what do they bind? what does it do?

Answer 599

Fc= bacteria with IgG antibody on surface have Fc region exposed;
complement= C3b(part of complement);
enhances phagocytosis

Question 600

What is the function of toll like receptors?

Answer 600

class of 10 different receptors, recognize distinct set of molecular patterns characteristic of pathogenic microbs, ligation of TLR activates transcription factor NFkB and induction of proinflammatory cytokines and chemokines, some on cell membrane (extracellular infection)and some on nuclear envelope facing in (intracellular infection)

Question 601

How does the complement system work?

Answer 601

20 diff serum proteins, several are proteases that become activated by presence of pathogen, opsonize pathogen for engulfment by phagocytes, chemoattractants to recruit phagocytes, kill bacteria by creating pores in bacterial membrane

Question 602

Which cells are phagocytes in innate response?

Answer 602

macrophage and neutrophil

Question 603

What mechanisms are used to destroy cell in phagocyte? Where are they found? Enzymes?

Answer 603

Primary grannules: NADPH oxidase=toxic oxygen products, inducible nitric oxide synthase: toxic nitrogen products, and Myeloperoxidase: acidification; Secondary grannules: antimicrobial peptides, lysozymes, and defensin (increase permeability of bacterial membrane), lysosomes= digestive enzymes

Question 604

How do natural killer cells work?

Answer 604

recognize transformed cells (infected) by low MHC1 expression, activity of NK has activating and inhibiting receptors, MHC1 binds inhibitory receptor and blocks activation, when activated relase cytotoxic grannules containing granzymes and perforin, perforin creates pore in membrane and granzymes initiate apoptosis

Question 605

What causes the inflammatory response?

Answer 605

invasion of WBC, swelling= increase vascular permeability and migration of leukocytes, redness= increased blood volume, heat increased blood volume and endogenous pyrogens

Question 606

What is the function of the inflammatory response?

Answer 606

local inflammation restricts damage to site of infection, microbes activate macrophages and dendritic cells via PR receptors, activated macrophages produce proinflammatory cytokines and chemokines, dendritic cells migrate to lymph nodes and initiate adaptive immune response

Question 607

What are the two components of acquired immunity?

Answer 607

antibody mediated humoral immunity and T cell medicated immunity

Question 608

What are the components and types of T cell receptors? Where are they found? What are they found in complex with?

Answer 608

2 polypeptide chains: alpha and beta or gamma sigma, 95% peripheral t cells are alpha beta and gamma sigma are abundant in epithelial and mucosal surfaces, CD3 complex (sigma, gamma, epsilon and s chain both together contain ITAM (immunoreceptor tyrosine activation motif)

Question 609

What is MHC? characteristics?

Answer 609

major histocompatibility complex, aka HLA, cell surface molecule responsible for antigen presentation and lymphocyte recognition, polygenic and polymorphic (diff genes and varieties), major reason for transplant rejection, are promiscuous and bind many peptides but not all (diff set for diff peptides)

Question 610

Characteristics of MHC 1 class?

Answer 610

alpha chain big and has 3 domains, beta chain small, expressed on most cell types, presents to CD8+ cytotoxic T cells, peptides presented are sampling of intracellular environment

Question 611

Characteristics of MHC 2 class?

Answer 611

alpha and beta equal, only on antigen presenting cells mostly dendritic but also B cells and macrophages, presents to CD4+ T helper cells, peptides presented are sampling of extracellular environment

Question 612

What is antigen processing? What are the two pathways? cells and receptors involved?

Answer 612

metabolic process of degrading proteins into peptides 8-10 AA that are capable of binding MHC and being presented; exogenous=MHC II and CD4+, endogenous=MHCI and CD8+

Question 613

What is the general pathway of T cell delopment?

Answer 613

progenitor T cells-> CD4-CD8 Double negative (1,2,3,4)-> Cd4+CD8+ double positive thymocytes–> Cd4+ or CD8+ single positive cells–> exit thymus

Question 614

How does positive selection work?

Answer 614

DP T cells which recognize self-MHC receive a survival signal from specialized APCs in thymus and are positively selected, occurs in cortex, if fail they are eliminated via apoptosis

Question 615

What is negative selection?

Answer 615

T cells which demonstrate too high an affinity for self MHC molecules are deleted in medulla, ensures self tolerance

Question 616

What are the three signals naïve T cells need to become fully activated?

Answer 616

1) antigen specific signal from specific peptide:MHC complex with T receptor 2) co-stimulatory signals derived by B7 and CD28 3) signal directing T cell differentiation into different subsets of effector CD4+ T helper cells

Question 617

What are the 4 accessory signaling molecules in T cell activation and their function?

Answer 617

CD4 and CD8 stabilize TCR and MHC interaction/ signal transduction; CD28 a homodimer on T cells function to interact with B7 on APC; and B7 expressed on APC and function to interact with CD28

Question 618

What does activation of TCR do?

Answer 618

triggers signal cascade leading to induction of IL-2 which is critical for T cell proliferation and differentiation

Question 619

What are the subsets of cells that CD4+ differentiates into after signal 3? function of each?

Answer 619

Th1= secrete IFNgamma and activate macrophage, antibody class switch; Th2 secrete IL4 and IL5, activate B cells and antibody response; Th17= secrete IL17 and trigger inflammation; T regulatory cells= secrete TGF-beta and IL10 and inhibit dendritic and T cell activation (important for immune tolerance maintanence

Question 620

CD8+ T cells are not fully active upon leaving thymus, what must they do to differentiate?

Answer 620

binds to APC and receives signal to proliferate and differentiate and are now active to kill virus infected cells

Question 621

How do CD8+ active cells (CTL) kill cells (induce apoptosis)?

Answer 621

contain perforin and granzymes- perforin makes hole in membrane and granzymes enter to initiate caspase cascade and activate nucleases

Question 622

What are the 5 different heavy chain constant regions or classes of antigens?

Answer 622

A (alpha), D (delta), E (epsilon), G (gamma), M (mu)

Question 623

What are the two different areas of antibodies and their function?

Answer 623

Fab- antigen binding has a variable end to allow binding of different antigens to bind; Fc- effector function- IgE binds mast cells and basophils, IgG crosses placenta, IgA is in mucosal immunity

Question 624

What are the roles antibodies play in humoral immunity?

Answer 624

B-cell activation by antigen and T cell results in antibody secretion by plasma cells-> neutralization (prevent bacterial adherence), opsonization (promotes phagocytosis), complement activation (activates complement which enhances opsonization and lyses some bacteria

Question 625

describe the changes in antibody formation occurring in the developing B cell.

Answer 625

pro B- heavy chain rearrangement, pre-B light chain rearrangement, immature B stage formation of b cell receptor (BCR) on cell surface IgM and induction of central tolerance to get rid of autoreactive B cells, mature B cells express both IgM and IgD on cell surface

Question 626

What are the steps to B cell activation?

Answer 626

antigen cross linking IgM activates tyrosine kinase (Blk, Fyn, or Lyn) which phosphorylates B cell receptor cytoplasmic domains, Syk tyrosine kinase binds to phosphorylated Igbeta and becomes activated and phosphorylates CD19, BLNK, phospholipase C, GEFs and Tec kinase, PLC cleaves PIP2 to yield DAG and IP3, Dag and Ca2+ activate PKC which activates transcription factor NFkB, small G proteins activate MAPK which induces and activates Fos a component of AP1 transcription factor, IP3 increases intracellular Ca2+ activating phosphatase calcineurin which activates transcription factor NFAT; NFAT, NFkB and AP-1 act to induce specific gene transcription->prolif and diff.

Question 627

What occurs in a germinal center? What is needed to form one?

Answer 627

intense B cell proliferation, differentiation, somatic hypermutation (point mutations induced in V region genes for higher affinity to antibody), class switching (allows antibody with single antigenic specificity to associate w/ variety of C region chains and have different effector functions), plasma cell generation (antibody producing) and memory B cell generation; requires helper T cells (B and T cells recognize same antigen)

Question 628

What class of antibody is involved in primary and secondary immune response?

Answer 628

primary= IgM, secondary=IgG

Question 629

What is clonal selection?

Answer 629

each lymphocyte has a single type of receptor w/ unique specificity, interaction with foreign molecule and receptor with high affinity= activation, differentiated effector cells from activated lymphocyte have identical specificity to parent, lymphocytes with receptors for self molecules are deleted early and are absent from mature lymphocytes; theory behind adaptive immunity

Question 630

What are the 4 types of medical genetics? define each

Answer 630

biochemical- metabolic disorders including enzymes and protein; clinical cytogentics- aberrations in chromosome number and structure =microscopic; molecular- mutations in single genes or group of genes, expression and function; and clinical genetics- clinical care including diagnosis counseling and management

Question 631

What is dysmorphology?

Answer 631

study of abnormal form= abnormal morphogenesis, physical development, congenital anomalies

Question 632

What is epigenetics and what are some change?

Answer 632

study of heritable changes in gene expression that occur without change in DNA sequence; chromatin folding, packaging of DNA, histone modification, DNA methylation, imprinting

Question 633

What can DNA methylation effect?

Answer 633

imprinting, x chromosome inactivation, transcriptional silencing, protecting genome from transposition, tissue specific gene expression

Question 634

What is IUGR, causes, and what impact can it have?

Answer 634

Intrauterine Growth Retardation; smoking, placental insufficiency, alcohol, maternal nutrition, and stress; increase type 2 diabetes, obesity, CAD, and hypertension susceptibility

Question 635

Reasons for pediatric genetic consultation

Answer 635

1 or more major organ malformation, abnormal growth, Mental retardation or delay, Blind/Deaf, presence or suspected genetic disorder/ chromosomal abnormality, abnormal newborn screening, family hx

Question 636

Reasons for prenatal or preconception genetic consultation

Answer 636

mom >35, abnormal screens, personal or fam hx, known or suspected teratogen, 2+ losses, consanguous mating, ethnic predisposition, maternal medical condition effecting fetal growth

Question 637

Reasons for adult or adolescent genetic consultation.

Answer 637

MR, personal or family hx, blind/deaf, development of degenerative disease, risk assessment for pregnancy, hereditary cancer hx

Question 638

What are all the etiologies for abnormal development?

Answer 638

chromosomal, single gene- autosomal dominant or recessive or x linked, multifactorial, or environmental

Question 639

If onset is prenatal and it is a single anomaly, what is are potential classifications for the anomaly?

Answer 639

malformation, deformation or disruption

Question 640

If onset is prenatal and multiple anomalies, what is are potential classifications for the anomaly? etiologies?

Answer 640

syndrome, sequence, or association; chromosomal, single gene, multifactorial, teratogenic or unknown

Question 641

If onset of abnormality is postanatal what are the etiologies?

Answer 641

genetic, environmental or unknown

Question 642

What is a malformation? Examples.

Answer 642

abnormal formation of tissue, genetically coded to happen; dysmorphic features, congenital heart malformations

Question 643

What is a deformation? Examples. Causes?

Answer 643

unusual forces on normal tissue; cranial molding, mandibular asymmetry, external ear, tibial torsion, club foot, crowded toes, facial nerve palsy or erb’s palsy; large or multiple fetuses, oligohydraminos, small uterine or mom, fibroids

Question 644

What is a disruption? Examples

Answer 644

breakdown of normal tissues; vascular disruption or ischemia, gastroschesis, early amniotic bands or rupture missing limbs or digits, facial clefts

Question 645

What is a syndrome? examples.

Answer 645

primary developmental anomaly of two or more systems due to common etiology; Noonan syndrome or DiGeorge syndrome

Question 646

what is association? examples.

Answer 646

non-random recurring pattern of malformations with no defined etiology; VACTERL: Vertebral, Anal atresia, Cardiac, TracheoEsophageal fistula, Renal malformations, and Limb anomalies

Question 647

What is a sequence? examples.

Answer 647

pattern of malformations due to a cascading effect from a single minor alteration early in morphogenesis; Peirre Robin sequence because small chin can be part of other syndromes, Potter sequence: low fluid inutero, deformation from constraint, abdominal wall cant close

Question 648

What is functional genomics?

Answer 648

study of functional elements of an organisms genome

Question 649

what is transcriptomics?

Answer 649

study of all of the expressed RNA elements of genome

Question 650

what is Proteomics?

Answer 650

study of structure and function of proteins expressed in a cell, tissue, organism

Question 651

what was important in 1990 in genetics?

Answer 651

1st bacterial whole genome sequenced and identified BRCA1

Question 652

what was important in 2005 in genetics?

Answer 652

Phase 1 HapMap, chmp and Dog, 1st GWAS published

Question 653

what was important in 2008 in genetics?

Answer 653

Genetic information Nondiscrimination Act passed

Question 654

what was important in 2013 in genetics?

Answer 654

exome sequencing available and obtainable for patients with rare disease

Question 655

What is gene localization? Advantages?

Answer 655

finding chromosomal region that contains the gene; establish that a trait is genetic, genetic heterogeneity (diff genes and same presentation of disease) genetic counseling and presymptomatic diagnosis, 1st step in ID

Question 656

What is gene identification? Advantages?

Answer 656

finding the gene and determining its sequence; precise diagnosis and counseling, understand pathogenesis, discovery of related genes, treatment

Question 657

what is RFLP?

Answer 657

restriction fragment length polymorphism, variation in sequence which affects presence or absence of a restriction site

Question 658

What is VNTR?

Answer 658

variable number of tandem repeats; variation in number of repeated bases btwn restriction sites

Question 659

What is STRP?

Answer 659

short tandem repeat polymorphisms; Di, tri and tetranucletide repeats

Question 660

What is SNP?

Answer 660

single nucleotide repeat polymorphism, microarray, sequencing

Question 661

What is a LOD score?

Answer 661

ratio of probability that two genes are linked to probability they are not linked expressed as a log, score of 3+ means linked

Question 662

What is recombination frequency?

Answer 662

symbol theta, if 0 genes are highly linked if 0.5 genes are independently assorted, between 0 and 0.5 there is linkage

Question 663

What is a CNV?

Answer 663

copy number variant, microarray or comparative genomic hybridization (deletion or duplication), important if gene is dose sensitive, expose variation on other allele if deletion or disruptive duplication

Question 664

What is NGS?

Answer 664

next generation sequencing, high throughput sequencing technology, allows sequence thousands or millions of short sequences simultaneously in single run, correspond to many genes, increase in genetic info, decrease in cost and time, reversible terminator based method with fluorescence

Question 665

What is Sjorgen-Larrson Syndrome?

Answer 665

autosomal recessive, ichthyosis, mental retardation, spastic diplegia or tetraplegia, deficient fatty aldehyde dehydrogenase

Question 666

What is sialidoses type II?

Answer 666

neurominadase deficiency; developmental delay with neurodegenerative course, bone abnormalities, hepatomegaly, macular cherry red spots, myoclonic seizures, coarse facial features, abnormal glycopeptide,

Question 667

What is gaucher disease?

Answer 667

defect in glucocerebrosidase enzyme so build up of glucosylceramide which can’t be broken down, all have hepatosplenomegaly, bone marrow depression and pulmonary infiltration; Type 1: non-neuronopathic effects kids and adults, Type 2: acute neuronopathic effects infants and is fatal, Type 3: sub acute neuronopathic effects children and is fatal

Question 668

How is enzyme replacement feasible in lysosomal storage diseases? Which ones use it?

Answer 668

during normal function the enzyme is secreted from the cell and reabsorbed via endocytosis; gaucher, hurler, hunter, Pompe, and Fabry; not effective on neuropathic forms as it cant cross blood brain barrier

Question 669

What is Acute intermittent Porphyria?

Answer 669

autosomal dominant, most carriers have no symptoms, increased ALA and PBG precursors to heme no feedback inhibition and no heme either, onset after puberty, acute attacks precipitated by drugs, diet, or stress, abdominal pain, nausea, vomiting, neuropathy, psychiatric disturbances, and tachycardia, treat with heme

Question 670

What is peroxisome biogenesis disorders?

Answer 670

defective peroxisome assembly, symtpoms appear at birth or early infancy; hypotonia, seizures, psychomotor retardation, liver disease, dysmorphic facial features , ex. PTS1 receptor problem, not recognized by docking protein, deficiency in numerous enzymes carried by PTS1

Question 671

What is nephropathic cystinosis?

Answer 671

genetic defect in lysosomal membrane protein necessary for efflux of cysteine out of lysosome, intralysosomal cysteine storage in tissues results in renal damage, hypothyroidism, photophobia, bony abnormalities, (hexagonal crytals taking up whole lyososome), cysteamine therapy- binds cysteines and utilize lysine transporter out

Question 672

What methods are used to process newborn screens?

Answer 672

enzyme assays, immunoassays, electrophoresis, tandem mass spectroscopy

Question 673

What is PKU?

Answer 673

phenylketonuria, cant break phenylalanine down; mental retardation, microcephaly, fair complexion and hair, seizure disorder in 15%, hypomyelination, tooth enamel hypoplasia, in brain Phl competitively inhibits Try and Trp which are needed for dopamine and serotonin, few false positives on newborn screen, therapy diet, increase in outcome for earlier detection

Question 674

What is galactosemia?

Answer 674

decresed activity of transferase, cant transport galactose into cell; vomiting, diarrhea, hepatomegaly, liver dysfunction, cataracts, ovarian failure susceptibility to gram negative sepsis, lactose restriction; therapy can reverse liver and renal, cataracts disappear, but ovarian cant be reversed (prenatal damage)

Question 675

What is biotinidase deficiency cause?

Answer 675

failure to thrive, alopecia, scaling dermatitis, vomiting, metabolic acidosis, seizures, hypotonia, ataxia, MR, hearing loss

Question 676

What are mitochondrial fatty acid oxidation disorders?

Answer 676

13 known, different enzymes involved, most asymptomatic initially, episodic metabolic decompensation- fasting hypoglycemia, metabolic acidosis, muscle weakness, cardiomyopathy, rhabdomyolysis, neurological sequel or death

Question 677

What is medium-chain acyl-CoA dehydrogenase deficiency?

Answer 677

most common FAO defect, variable onset with episodic symptoms, accumulation of fatty acid oxidation metabolites, acidosis, liver dysfunction, therapy is preventative only, strict avoidance of fasting

Question 678

What is HELLP syndrome of pregnancy?

Answer 678

hemolysis, elevated liver enzymes and low platelets, associated with mothers carrying fetus with fatty acid oxidation defect, accumulation of baby’s substrates goes into mom’s circulation, acute fatty liver of preganacy, pre-eclampsia

Question 679

What is Homocystinuria?

Answer 679

mental retardation, dislocated optic lenses, thromboembolic events, thinning and lengthening of long bones, cystathionine deficiency; 50$ respond to high dose of enzyme cofactor, or can use betaine to turn homocysteine to methionine

Question 680

What is the purpose of dendritic receptor binding and costimulation of T cell by dendritic cells?

Answer 680

proliferation and differentiation of T cell to acquire effector function