Brian's Cards

Front 1

screening tests for cystic fibrosis

Back 1

1. IRT
2. DNA analysis
3. Sweat Test (>60)

Front 2

Pathophysiology of Cystic Fibrosis

Back 2

1. Increased mucous viscosity w/ obstruction of lungs, GI tract, Liver, gall bladder, reproductive tract.
2. Respiratory tract colonization/ infection with unique organism
3. increased sodium chloride in serous secretions

Front 3

Common Treatmnet of Cystic Fibrosis

Back 3

1. pulmozyme (DNAse)
2. Tobramycin (TOBI)
3. Azithromycin
4. Inhaled hypertonic saline
5. Inhaled Aztreonam (Caystor)
[airway clearance]
[diet/ high protein]
[pancreatic enzyme supplements]

Front 4

Primary Cause of Down's Syndrome

Back 4

Non-disjunction in Meiosis I in the maternal line resulting in three copies of chromosome 21. [95% of cases]

Front 5

Diagnosis of Down's Syndrome

Back 5

Karyotyping; FISH may be used to get a quick preliminary diagnosis, but it should always be followed by a karyotype to verify.

Front 6

Prenatal Screening for Down's Syndrome

Back 6

Serum Measurements [indicative, but not diagnostic]
amniocentesis for karyotyping

Front 7

Pathology of Down's Syndrome

Back 7

1. Growth delay
2. Cardiac
a. atrioventricular septal defects[AVSD]
b. ventricular septal defect [vsd]
c. atrial septal defect [asd]
3. gastrointestinal: duodenal atresia or stenosis, imperforate anus
4. myopia and cataracts; protruding tongue; hearing loss
[leukemia 400X more likely]

Front 8

Most Common Mode of Lysosomal Storage Disease

Back 8

AR: inability to break down glycoproteins

Front 9

Biochemical Abnormalities Leading to Lysosomal Storage Disease

Back 9

1. enzyme deficiency
2. inability to activate lysosomal enzymes
3. abnormality of lysosomal membrane proteins
4. inability to transport enzymes to lysosomes
5. abnormal lysosome structure

Front 10

Clinical Features of Lysososomal Storage Disease

Back 10

Abnormal facial features, thickened oral and airway tissues, skeletal abnormalities, enlarged organs, CNS [neurodegeneration, cerebral atrophy, leukodystrophy, mental retardation, seizures]

Front 11

Therapy of Lysosomal Storage Disease

Back 11

substrate reduction and enzyme replacement therapy [sometimes chaperone therapy, bone marrow transplantation, liver transplantation, gene therapy]

Front 12

Treatments for Sickle Cell

Back 12

1. penecillin until the age of 5
2. hydroxyurea- stimulates the synthesis of HgF to replace HgB
[for crises: heat and hydration NSAID and Narcotic]

Front 13

Osteogenesis Imperfecta

Back 13

"Brittle Bone Disease"
impairs triple helix formation of collagen
especially bad if point mutation occurs near the C-terminus

Front 14

What is necessary to form crosslinks between tropocollagens?

Back 14

Lysyl oxidase and copper

Front 15

What is needed to hydroxylate the proline in collagen formation?

Back 15

prolyl hydroxylase, iron, and vitamin C [ascorbate]

Front 16

Ehlers-Danlos Syndrome

Back 16

characterized by stretchy skin; loose joints; poor wound healing; failure of vessel/ organ structure
no cross-linking or no removal of the n-peptide end of tropocollagen [not converted to insoluble form]

Front 17

Elastin

Back 17

rubber protein [3d network of crosslinks
made of small nonpolar AA; abundant in proline and lysine
2 chains with 4 crosslinks formed by lysyl oxidase and copper

Front 18

Elastase

Back 18

1. degrades elastin for remdeling
2. inhibited by alpha-antitrypsin

Front 19

Emphysema

Back 19

mutation in alpha- antitrypsin; elastase degrades elastin in the lungs at too rapid a rate

Front 20

Keratin

Back 20

1. repeats of 7 AA
2. has polar and non-polar surfaces
micro to macroscale; alpha helix-protofibril-microfibril-macrofibril of har
3. cystine cross links; insoluble and not stretchy

Front 21

What happens if trypsin is activated prematurely?

Back 21

Accute pancreatitis; early activation [cleaving of zymogen in the pancreas, rather than in the intestines] will lead to digestion, by trypsin, of the pancreas

Front 22

Types of Post-translational Modification

Back 22

1. folding [aided by chaperones]
2. proteolytic cleavage [cleavage into segments or removal of ends]
3. chemical modification [phosphorylatio, glycosylation, ubiquitination]

Front 23

Phosphorylation Is very common on which Amino Acid?

Back 23

Serine; Threonine; Tyrosine

Front 24

Glycoprotein

Back 24

n-linked are constructed and then added in the RER
o-linked are built directly on in the Golgi Apparatus

Front 25

How does the cell recognize which glycoproteins are destined for the lysosome?

Back 25

the protein is labeled with the mannose-6-phosphate sugar

Front 26

Proteosomes degrade what?

Back 26

ubiquitinated intracellular proteins

Front 27

Types of Enzymes?

Back 27

1. oxidoreductases
2. transferases
3. hydrolases
4. lyases
5. isomerases
6. ligases

Front 28

Enzymes may use which cofactors?

Back 28

1. Metal ions [2/3 of enzymes need metal]
2. coenzyme
3. prosthetic group

Front 29

Diagnostic lab test for pancreatitis?

Back 29

blood work to look for elevated levels of pancreatic lipase and anylase

Front 30

Types of Inhibitors

Back 30

1. Irreversible; covalent; inactivates the enzyme [ie. Aspirin on cyclooxygenases]
2. reversible
a. competitive; higher Km
b. noncompetiteve; lower Vmax.

Front 31

Control of Enzyme Activity [FAST]

Back 31

[S] or allosteric controls

Front 32

Control of Enzyme activity [ intermediate]

Back 32

1. covalent modification
2. modular proteins
3. zymogen activation

Front 33

Control of Enzyme Activity [SLOW]

Back 33

transcription or translation

Front 34

tPA

Back 34

activates plasmin to cut fibrin
removes the clot
given medicinally to limit the size of an infarction

Front 35

Aspirin

Back 35

irreversible inhibitor of cyclooxygenases; inhibits clotting [ regenerated by healthy endothelial cells, not platelets]

Front 36

EACA

Back 36

E-aminocaproic acid; competetive plasmin inhibitor
slows clot removal [often used in surgery, but keep heparin rady]

Front 37

What is special about Selenocyseine

Back 37

a special tRNA for 'stop' codon

Front 38

Basic Structure of the Nuclear Hormon Receptors

Back 38

a DNA binding domain [DBD] and a ligand binding domain {LDB}
DNA binding proteins[ zinc fingers]
conformational change upon ligand binding.

Front 39

Types of dimerization

Back 39

homo dimerization [same type of protein]
heterodimerization [different type of protein]

Front 40

G-Protein Coupled Receptors [GPCR]

Back 40

seven transmembrane domain receptors;
largest family of cell surface receptors;
30% of drugs target GPCR;

Front 41

cAMP

Back 41

cyclic AMP;
created by adenyl cyclase;
activates PKA, CREB, BCL-2;
deactivated by phospodiesterase

Front 42

PIP2

Back 42

activated by GPCR;
activates IP3 Ca channel;
activates protein kinase C which binds to DAG

Front 43

Calmodulin

Back 43

helps Ca do its job

Front 44

RTK activation

Back 44

receptor tyrosine Kinase; dimerized and phosphorylated

Front 45

RTK activates which important protein?

Back 45

RAS

Front 46

PTEN

Back 46

tumor suppressor on the PIP2 pathway

Front 47

Howis PIP3 made and what does it do?

Back 47

PIP2 is converted by p85, p110, and PI3K which activates PTEN

Front 48

JAK/STAT

Back 48

Jaks activate stats which dimerize and transcribe

Front 49

Functions of TGF-B

Back 49

1. inhibit epithelial growth
2. inhibit immune functions
3. promotion of connective tissue growth

Front 50

TGF-B pathway

Back 50

activates SMAD2; which binds to SMAD 4; leads to transcription

Front 51

What will a mutation in the TGF-B receptor lead to?

Back 51

colon and gastic cancer

Front 52

What will mutations in the SMAD4 protein lead to?

Back 52

pancreatic and colorectal tumors

Front 53

What will mutations in the SMAD2 protein lead to?

Back 53

colon cancer

Front 54

Why is TGF-B bad?

Back 54

can exacerbate tumor growth by suppression of immune surveilance and by fostering tuor invasion and metastisis

Front 55

WNT pathway

Back 55

ligand binds to frizzeled and WNT; bind to axin; allowing B catenin to transcribe

Front 56

Functions of WNT

Back 56

cell fate; remodeling, polarity and morphology, adhesion, growth;
especially important in embryogenesis

Front 57

carcinogenesis

Back 57

the process by which cells acquire attributes that confer a malignant phenotype

Front 58

What does telomerase do in respect to cancer?

Back 58

helps the cell to avoid senescence or natural cell aging; leading to avoidance of apoptosis

Front 59

The loss of cadherins is a major factor in what hallmark of cancer?

Back 59

metastasis; cells are no longer bound together and may move freely

Front 60

What do cancer cells do to harness more energy?

Back 60

Aerobic glycolysis;
inefficient, but may get energy slightly faster

Front 61

How do cancer cells escape immunodetection?

Back 61

turnoff antigen expression; secrete antiproliferative factors;
TGF-B

Front 62

Microsatellite instability reflects?

Back 62

decreased DNA repair; NER

Front 63

miRNA

Back 63

microRNA
noncoding; downregulate gene expression in development and oncogenesis

Front 64

Hematoma

Back 64

coagulated blood tissue

Front 65

choristoma

Back 65

ectopic or heterotopic normal tissues [normal in an abnormal location]

Front 66

granuloma

Back 66

chronic inflammation

Front 67

H & E staining

Back 67

hematoxylin + basophilic; RNA, DNA, cartilage
Eosin - acidophilic; proteins

Front 68

hamartoma

Back 68

overgrowth

Front 69

neoplasms

Back 69

1. benign tumors
2. malignancies; metastisize
3. hamartomas

Front 70

Carcinoma

Back 70

cancer of the epithelium; non-glandular

Front 71

adenocarcinoma

Back 71

cancer of the wpithelium; glandular

Front 72

sarcoma

Back 72

cancer of connective tissue

Front 73

leukemia

Back 73

cancer blood

Front 74

lymphona

Back 74

cancer of lymph tissue

Front 75

high-grade cancer

Back 75

does not look like tissue of origin [anaplatic]

Front 76

oncogene

Back 76

KRAS, HER2
normal gene that, when mutated to active form, contributes toward the neoplastic phenotype

Front 77

tumor suppressor gene

Back 77

pRB, TP53
when tumor suppressor gene is absent, cellular events that either express the malignant phenotype proceed at a higher rate

Front 78

Hallmarks of Cancer

Back 78

1. resist cell death [apoptosis]
2. sustain proliferatice signaling
3. evade growth suppressors
4. induce angiogenesis
5. enable replicative immortality
6. activate invasion and metastisis

Front 79

function of BCL-2

Back 79

limits the signal for apoptosis

Front 80

HER2

Back 80

RTK; if mutated, patient may be responsive to herceptin [trastuzumab]

Front 81

Function of RB

Back 81

inhibit the growth signal;
antigrowth signal>cell surface receptor>cyclin D> RB> E2F
Master brake for the G1/S phase checkpoint

Front 82

Prostate Cancer preferentially metastisizes where?

Back 82

bone marrow>liver>lungs>brain

Front 83

Pancreatic cancer preferentially metastisizes where?

Back 83

Liver> lungs

Front 84

Breast Cancer preferentially metastisizes where?

Back 84

bone marrow>lungs>liver>brain

Front 85

Colon Cancer preferentially metastisizes where>

Back 85

liver> lungs> bone marrow

Front 86

Key Guardian of the genome?

Back 86

p53 a tumor suppressor

Front 87

Chronis Myelogenous Leukemia is characterized by?

Back 87

anemia and fatigue
philadelphia chromosome
BCR-ABL

Front 88

What tumor suppressor works on early adenomas?

Back 88

APC

Front 89

What tumor suppressor works on intermediate adenomas?

Back 89

KRAS

Front 90

What tumor suppressor works on late adenomas?

Back 90

DCC

Front 91

What tumor suppressor works on carcinomas?

Back 91

p53

Front 92

Familial Adenomatous Polyposis

Back 92

Carpeting of Polyps in the colon [AD]
usually caused by a loss of APC, a tumor suppressor

Front 93

Genes expressed from the inactive X chromosome

Back 93

XIST specifically[ 16 total form the pseudoautosomal region]

Front 94

3 major types of fibrous proteins

Back 94

1. collagen
2. elastin
3. keratin

Front 95

what is the most abundant protein?

Back 95

collagen

Front 96

Structure of collagen?

Back 96

GPx; glycine every 3 AA
triple helix; proline is posttranslationaly modified to hydroxyproline
induces mor H-bonding between fibers in the helix

Front 97

What is hydroxylated in collagen synthesis?

Back 97

proline and lysine

Front 98

What is glycosylated in collagen synthesis?

Back 98

hydroxylysine

Front 99

Which way does the triple helix structure of collagen zip up?

Back 99

c to n-terminus

Front 100

What happens after the procollagen is secreted from the cell?

Back 100

1. n and C ends are cleaved
2. tropocollagens stagger [1/4] together
3. cross-linking of lysines by lysyl oxidase

Front 101

Scurvy

Back 101

skin lesions; poor wound healing; fragile bones; and bloody gums after brushing
caused by a vitamin C deficiency; lysyl oxidase does not work

Front 102

Kinases

Back 102

phosphorylate proteins

Front 103

phosphatases

Back 103

enzymes that remove phosphates

Front 104

What proteins usually undergoes glycosylation?

Back 104

on extracellular and embrane bound proteins

Front 105

How does the cell know where the protein go?

Back 105

the proteins contain a sorting signal recognized by the destination site; the nucleus uses importin alpha and beta

Front 106

erythrocyte

Back 106

RBC [red blood cell] contains hemoglobin

Front 107

Location of Myoglobin

Back 107

Muscle

Front 108

Locaton of Hemoglobin

Back 108

blood

Front 109

heme

Back 109

complex of iron and porphyrin
[sheilded from water by Hb and Mb- If water does get in <MHb> methemoglobin]

Front 110

Hb basic structure

Back 110

2 alpha and 2 beta subunits each holding a hem in place with his

Front 111

Does Mb or Hb have a higher affinity for O2

Back 111

Mb

Front 112

how can you tell, graphically, what has a higher affinity?

Back 112

lower Km

Front 113

Forms of Hb? [allosterism]

Back 113

raelaxed and taut

Front 114

What is the effect of lower pH on Hb?

Back 114

decrease of affinity for O2

Front 115

What effect does CO2 have on hemoglobin?

Back 115

decreases its affinity for O2

Front 116

What does BPG do to Hb?

Back 116

tightens the bonding; decreases the affinity for O2
necessary to get mor O2 to the body in high altitudes

Front 117

Does HgF interact with BPG?

Back 117

very little

Front 118

Why does fetal hemoglobin take O2 from the maternal blood?

Back 118

The HgF does not bind well with bpg, increasing its relative affinity for O2 compared to the maternal blood. So as the O2 is released from the maternal blood, the fetal blood will act like myoglobin and pick it up.

Front 119

Effect of CO on Hb?

Back 119

binds 200X more tightly than O2, severely decreased affinity for O2;
treat with excess O2

Front 120

Effect of CN on Hb?

Back 120

nothing; Bad for mitochondria

Front 121

how do you treat CN in body?

Back 121

amyl nitrate

Front 122

What does amyl nitrate do in blood?

Back 122

converts Hb to methemoglobin which bind to CN; done to save the mitochondria. Should be careful in dosing, only give enough o convert some of the hemoglobin. Too much would be fatal.

Front 123

Hb Kansas

Back 123

ultrarelaxed hemoglobin form: cells will compensate for decreased O2 affinity by cramming 20% more Hb into the RBC

Front 124

Hb S, Hb D, Hb E, Hb C

Back 124

forms of sickle cell: decreased solubility and sickling occurs when the cell reaches the deoxy or tight form.

Front 125

Thalassemias

Back 125

truncation of Hb polypeptide; may have limited function
can sometimes activate HbF to compensate

Front 126

How do you turn on HbF?

Back 126

hydroxyurea

Front 127

What does cyanate do in respect to Sickle Cell?

Back 127

increases O2 affinity; no deoxy form

Front 128

Methods of Enzyme Catalysis

Back 128

concentrating, orienting, straining, dividing

Front 129

How do enzymes catalyze

Back 129

decreasing the activation energy by stabilizing the transitional state

Front 130

Enzyme RXN pathway

Back 130

E + S= ES= E+P

Front 131

Assumption of Michaelis-Menten Model of Enzyme Catalysis:

Back 131

[S] or allosteric controls

Front 132

Why is an allosteric enzymes plot sigmoidal?

Back 132

it controls itself based on the [s] and[p]

Front 133

von Willebrand factor

Back 133

1. exposed in the collagen of subendothelial cells
2. binds to receptors on platelets
3. aids in the formation of soft blug

Front 134

Charge of activated platelets?

Back 134

negative: PS flips to create the - charge on the surface

Front 135

Which pathway do hemopheliacs use for the coagulation cascade?

Back 135

extrinsic; they are usually fine except in muscles and joints where tissue factor is not present.

Front 136

Coumarin

Back 136

a competitive inhibitor for gamma-carboxyglutaminase/ vitaminK

Front 137

Heparin

Back 137

widely used anti coagulant helpd thrombin and antithrombin III get together

Front 138

Removal or change of single amino acids can do what in proteins?

Back 138

1. perturb the structure and conformation
2. remove a critical residue
3. alter the interaction of one protein with another
4. destabilize a protein resulting in a shorter biological half-life

Front 139

Basic structure of an amino acid

Back 139

alpha carbon flanked by an amino group and a carboxyl group; with an R constituent

Front 140

What is special about glycine?

Back 140

has an H side chain; small and packs tightly

Front 141

What is special about cysteines?

Back 141

can form a disulfide crosslink

Front 142

What is special about proline?

Back 142

has a cyclic side chain that is incompatible with the alpha helix that creates a kink or quick turn

Front 143

Levels of Protein Structure

Back 143

1. primary; peptide
2. secondary; alpha helix, beta sheets
3. tertiary; 3d structure of a single protein
4. Quarternary; multiple protein structure

Front 144

Types of post-translational modifications

Back 144

1. disulfide crosslinking
2. phosphorylation
3. glycosylation
4. proteolytic processing
5. accessory /co-factor

Front 145

Prion

Back 145

diseased protein that has undergone a conformation change; when a prion comes in contact with a non-diseased protein it will induce the same conformational change in the protein.

Front 146

What is a peptide bond?

Back 146

the bond between amino acids in a polypeptide chain; water is given off

Front 147

Intracrine Signaling

Back 147

signal is produced within a cell and targets cell

Front 148

Autocrine signaling

Back 148

signal is excreted and targets the same cell

Front 149

Juxtacrine signaling

Back 149

signal is sent via direct connection to target cell

Front 150

Paracrine signaling

Back 150

signal over a short distance

Front 151

Endocrine signaling

Back 151

signal over a long distance (estradiol)

Front 152

What kind of ligand can enter the cell?

Back 152

hydrophobic

Front 153

Types of nuclear hormone receptors

Back 153

HSP; heat shock protein
constitutively nuclear

Front 154

Agonist

Back 154

bind and activate

Front 155

Antagonist

Back 155

bind and repress

Front 156

Effect of Cholera Toxin on cAMP

Back 156

prolonged elevation

Front 157

Effect of Pertussis Toxin on cAMP

Back 157

increased cAMP levels

Front 158

Notch Pathway

Back 158

disposable; only one signal can be used

Front 159

NF-kB Pathway

Back 159

activates IkB kinase; usually involved in inflammatory or autoimmune response

Front 160

HNPCC

Back 160

Lynch Syndrome; hereditary non-polyposis colon cancer

Front 161

What mutation predicts decreased responsiveness to monclonal Ab (herceptin) therapy agains EGFR?

Back 161

KRAS mutations

Front 162

BRAF

Back 162

associated with melanomas mutations in the RAS pathway; may respond to BRAF kinase inhibitor

Front 163

Which neoplasms are always malignant

Back 163

melanoma, lymphoma, glioma, teratoma

Front 164

fibro-

Back 164

connective tissue

Front 165

leiomyo-

Back 165

smooth muscle

Front 166

rhabdomyo

Back 166

striated or skeletal muscle

Front 167

lipo-

Back 167

fat

Front 168

chondro-

Back 168

cartilage

Front 169

osteo-

Back 169

bone

Front 170

lymphangio-

Back 170

lymph fluid

Front 171

hemangio-

Back 171

blood

Front 172

scirrhous

Back 172

hard

Front 173

zonula adherens

Back 173

cadherin adhesion belt at apical end

Front 174

zonula occludens

Back 174

tight junctions at apical end

Front 175

Desmosome

Back 175

junction in cells anchored with keratin; cadherin in between cells

Front 176

gap junction

Back 176

pores made of connexons; known as connexins; allow rapid flow of small particles between adjacent cells

Front 177

relative sizes of microfilaments

Back 177

actin< keratin< microtubules

Front 178

Cilia

Back 178

doublets of micrtubules at the plasma membrane that aid in movement

Front 179

centriole

Back 179

starting point of microtubules; aid in cell division

Front 180

microvilli

Back 180

have an actin skeleton about 1/10 the size of cilia

Front 181

gated transport

Back 181

used by the nucleus

Front 182

peroxisome

Back 182

carries out oxidation reactions

Front 183

Lysosomes

Back 183

pH of 5 break down waste

Front 184

mannose-6-phosphate

Back 184

ligand for lysosomal pathway

Front 185

1st cellular pathway

Back 185

at the end of G1, starts the synthesis of DNA, asks if the environment is favorable?

Front 186

G2/M checkpoint

Back 186

Is all Dna replicated? Is environment favorable?

Front 187

Metaphase to Anaphase Checkpoint

Back 187

Are all chromosomes attached to the spindle?

Front 188

Cyclin dependent Kinase

Back 188

inhibited by p21 , moves cell through checkpoints

Front 189

Do cancer cells have cilia?

Back 189

No

Front 190

Mitogen

Back 190

Cell growth ligand

Front 191

p53

Back 191

will transcribe a protein that inhibits cdk; which inhibits mitosis and cell division

Front 192

medullary

Back 192

soft

Front 193

colloid

Back 193

muconous or secreting mucous

Front 194

cystic

Back 194

having a void space lined with epithelial cells

Front 195

papillary

Back 195

nipple-like projection

Front 196

villous

Back 196

having a frond-like pattern

Front 197

cribriform

Back 197

inside a duct/ having a cookie cutter appearance

Front 198

hemidesmosomes

Back 198

on the basal surface incvolve integrins

Front 199

mRNA has distinctive features

Back 199

1. 5' cap
2. polyA tail
3. Uracil instead of T

Front 200

Central Dogma of Genetics

Back 200

Trascription>Translation>Modification

Front 201

Stop Codons

Back 201

1. UAG
2. UGA
3. UAA

Front 202

Start Codon

Back 202

AUG

Front 203

Alternate Splicing

Back 203

The splicing of different exons in a gene to code for different proteins

Front 204

What does imprinted mean?

Back 204

inactivated or silenced

Front 205

Mitochondria code for how many peptides and where are they utilized?

Back 205

13 peptides used exclusively in the mitochondria

Front 206

Do mitochondria have introns in their DNA?

Back 206

no

Front 207

What are analogues of purine/pyramidines currenlty being used for?

Back 207

cancer treatments or antiretroviral; they are introduced into DNA and replace normal nucleotides; this causes a degredation of the DNA

Front 208

DNA Cloning?

Back 208

used for copying a small fragment of DNA; used to create DNA libraries.

Front 209

PCR

Back 209

Polymerase Chain Reaction; a fst, cheap, easy method to amplify DNA of interest using TAQ; completely in vitro

Front 210

RT-PCR

Back 210

reverse-transcriptase PCR; can compare with normal PCR to detect splice site mutations

Front 211

Southern Blot

Back 211

DNA gel electrophoresis

Front 212

Northern Blot

Back 212

RNA gel electrophoresis

Front 213

Western Blot

Back 213

Protein Gel electrophoresis

Front 214

SNP

Back 214

single nucleotide polymorphism

Front 215

Sanger's sequencing

Back 215

substitution of dideoxysugar base with a standard nucleoside; severs chain at that point; measure and sequence[ run 4 times for each type of nucleotide]

Front 216

Missense

Back 216

SNP leading to a different amino acid

Front 217

Nonsense

Back 217

SNP leading to a premature stop codon

Front 218

splice site mutation

Back 218

SNP leading to the addition or removal of a splice site

Front 219

Types of long mutation

Back 219

1. deletion
2. duplication
3. insertion
4. expansion

Front 220

Frameshift Mutation

Back 220

a mutation causing a change in the 'reading' frame

Front 221

Anticipation

Back 221

growth of a mutation [in expansion related mutation] through geneology

Front 222

What test is good for large changes in DNA?

Back 222

Southern Blot; also PCR

Front 223

Hot' spots for Mutations on DNA

Back 223

CpG islands; usually by spontaneus deamination of a methylated cytosine

Front 224

NER

Back 224

nucleotide excision repair; removes thymine dimers

Front 225

What causes xeroderma pigmentosum?

Back 225

lack of NER; only treatment is to avoid UV light

Front 226

BER

Back 226

base excision repair; mutations associated with colorectal polyposis

Front 227

How is a mitochondrial disorder passed on?

Back 227

by the mother to all of her progeny. Variable expression due to heteroplasmy.

Front 228

AD

Back 228

Autosomal Dominant; 50 % chance of passing it on for each child of an affected parent; variable expression due to non-penetrance, and imprinting

Front 229

AR

Back 229

Autosomal Recessive; 25% chance for each child and 50 % chance of being a carrier; cariable expression due to consanguinity, population genetics

Front 230

XLR

Back 230

X linked recessive; 50 % chance for sons of female carriers; variable expression due to x inactivation

Front 231

Multifactorial Disease

Back 231

Mendelian genetics vs. environmental factors

Front 232

Hardy-weinberg equation

Back 232

p^2+2pq+q^2=1; q= homozygous recessive

Front 233

RFLP

Back 233

restriction fragment length polymorphism; DNA is cut and run to determine lengths and approximate sequence using specific cutting tools

Front 234

Linkage

Back 234

mapping of crossing-over events of chromosomes in the tetrad formation; can use markers to determine how frequently thay are recombinant; if they are infrequently seperated, they are said to be linked

Front 235

1 cM

Back 235

1 centiMorgan; the genetic distance between two loci where there is only 1% chance of seperation by recombination; approximately 1 Mb

Front 236

LOD score

Back 236

Odds of Linkage; >3 evidence of linkage, <-2 evidence against linkage

Front 237

homozygosity mapping

Back 237

only useful in AR; determining location by geneology and mapping

Front 238

Exome sequencing

Back 238

the use of SNPs to attempt to find missense/ nonsense mutations in distinctive cases

Front 239

Locus heterogeneity

Back 239

mutations on different genes causing the same disease

Front 240

Allelic heterogeneity

Back 240

mutations on the same chromosome causing the different diseases

Front 241

G-Banding

Back 241

Giemse Stain; the standard for staining chromosomes during metaphase or prometaphase in order to identify them.

Front 242

euploidy

Back 242

chromosomes are a multiple of 23

Front 243

aneuploidy

Back 243

chromosomes are not a multiple of 23

Front 244

A chromosomal microdeletion is best diagnosed by?

Back 244

Fish Analysis; flourescent in situ hybridization

Front 245

Prader Willi Syndrome needs which working copy?

Back 245

Paternal UBE3A

Front 246

Angelman Syndrome needs which working copy?

Back 246

Maternal UBE3A

Front 247

What are the possible uses of FISH?

Back 247

1. diagnose chromosomal microdeletion
2. diagnose aneuploidies
3. indentify chromosome translocations [robertsonian also]

Front 248

CBAVD

Back 248

congenital bilateral absence of Vas Deferens

Front 249

deltaF508

Back 249

most common mutation in cystic fibrosis

Front 250

Sweat test for Cystic Fibrosis

Back 250

>60 mmol/L sweat Cl- in two occurrences; used to diagnose 90% of CF

Front 251

Cystic Fibrosis

Back 251

1. AR
2. chronic respiratory tract infection
3. pancreatic insufficenccy
4. elevated sweat electrolytes
5. CBAVD- most males infertile
[prevalent in caucasians of european descent]

Front 252

Huntington's Disease

Back 252

1. AD
2. chorea movements
3. progressive dementia
4. CAG triplet expansion[34-120 repeats] leading to a gain of function
5. anticipation present
[prevalent in europeans and esp. venezualans.

Front 253

How does Huntington's disease expand?

Back 253

through the paternal line

Front 254

What is ptosis?

Back 254

Bedroom eyes; can be associated with Oculopharyngeal Muscular Dystrophy

Front 255

Duchenne's Muscular Dystrophy

Back 255

1. XLR
2. hypotonia
3. progressive muscle weakness and wasting
4. gower's maneuver
5. mostly affects males
6. out-of-frame mutation

Front 256

How do you test for Duchenne's MD?

Back 256

1. PCR
2. Gower's maneuver
3. southern blot
4. northern blot
5. serum creatine kinase [ elevated 50-100 fold]
6. last resort- muscle biopsy

Front 257

Cause of DMD?

Back 257

Large deletion on the dystrophin gene causing a frameshift nonsense mutation

Front 258

What is Becker's Muscular Dystrophy?

Back 258

similar to Duchenne's, although the deletion resulted in an infram shift. Some dystrophin is still produced. Symptoms are milder

Front 259

Exon 'hot' spots for mutations on the Dystrophin Gene

Back 259

1-20 and 45-53

Front 260

What is the ratio for DMD de novo cases?

Back 260

0.33333333333333

Front 261

How do you confirm the clinical diagnosis of DMD?

Back 261

1. uimmunohistochemical staining
2. western blot
3. PCR/ southern blot

Front 262

What is Gonadal Mosaicism?

Back 262

Mutation in the germline cells; mother can have this mutation and not be a 'carrier' for the mutation.

Front 263

Gentamicin may be used for what?

Back 263

treatment of Duchenne's MD; forces a read-through of the nonsense mutation;
possibly restore reading frame and decrease severity of symptoms

Front 264

Fragile X Syndrome

Back 264

1. XLD
2. CGG expansion through maternal line [>230 repeats][hypermethylated]
3. FMR1 gene
4. prepubertal males; language delays; hyperactivity

Front 265

FXTAS

Back 265

prefragile X syndrome; expanded maternally

Front 266

Sensitivity

Back 266

frequency of + test when the disease is present

Front 267

specificity

Back 267

frequency of - test when the disease is absent

Front 268

Prenatal Screening Programs

Back 268

1. maternal serum alpha fetoprotein [MSAFP][identify fetus w/open neural tube defect
2. triple test [identify fetus with down's]

Front 269

Types of prenatal screens [procedure]

Back 269

1. amniocentesis [detects neural tube defects][ late in pregnancy]
2. chorion villus sampling [early in pregnancy]

Front 270

Antisense oligonucleotides

Back 270

are being used to induce exon skipping to restore open reading frame.

Front 271

Number of genes in the human genome

Back 271

approx. 25000

Front 272

number of genes in mitochondrial DNA

Back 272

37

Front 273

Percentage of the human genome actually coding for proteins

Back 273

1-2%

Front 274

Pyramidines

Back 274

CUT

Front 275

Purines

Back 275

AG

Front 276

Acrocentric

Back 276

centromere is located grossly to one side of the chromosomes [13,14,15,21,22]

Front 277

Metacentric

Back 277

centromere is located in the middle of the chormosome

Front 278

submetacentric

Back 278

centromere is located away from the middle and the ends of the chromosomes

Front 279

Reciprocal translocation

Back 279

parts of chromosomes are 'swapped' equally

Front 280

robertsonian translocation

Back 280

part of one chromosome is moved ot another

Front 281

telomere

Back 281

The end of the chromosomes; seems to protect the functional portion of DNA; preserved by telomerase

Front 282

Tandem Repeats

Back 282

short repeats of codonc or nucleotides used in paternity testing;

Front 283

euchromatin

Back 283

active

Front 284

heterochromatin

Back 284

inactive
1. always off-constitutive
2. facultative- switched on/off

Front 285

methylation

Back 285

process to deactivate segments of DNA; occurs at CpG islands

Front 286

What is needed to synthesize DNA?

Back 286

1. primers
2. DNA template
3. DNA polymerase
4. dNTPs
5.Mg+

Front 287

Charge and handedness of DNA molecule

Back 287

[-] charge and right-handed in beta-form

Front 288

Types of DNA transfer

Back 288

1. transformation
2. conjungation
3. transduction

Front 289

What is a zygote?

Back 289

fertilized egg

Front 290

Ribosome

Back 290

responsible for mRNA translation for production of amino acids

Front 291

Okizaki Fragments

Back 291

additions by short fragments of DNA to the 5' end of the lagging strand during semi0-conservative replication

Front 292

Where does replication begin?

Back 292

in an A-T rich region followed by Dna A boxes

Front 293

Centromere

Back 293

compacted 'middle' of the chromosome

Front 294

nucleolus

Back 294

where ribosomal subunits are assembled

Front 295

chromatin

Back 295

relaxed and jumbled chromosomes

Front 296

what is a chiasma?

Back 296

a tetrad formation of chromosomes in meiosis

Front 297

Steps to mitosis?

Back 297

1. Prophase
2. Metaphase
3. Anaphase
4. telophase
5. interphase

Front 298

Steps to Meiosis?

Back 298

1. Prophase I
2. Metaphase I
3. anaphase I
4. telophase I
5. Prophase II
6. Metaphase II
7. Anaphase II
8. Telophase II

Front 299

What is the gestational age based on?

Back 299

age based upon the time from the last normal menstrual period
normal parturition=40 wks

Front 300

What is fertilization age based on?

Back 300

age based on the actual time of fertilization
normal parturition is 38 weeks

Front 301

What weeks in early human development are considered to be the embryonic stage?

Back 301

weeks 1-8
characterized by the organogenic period
also the time most susceptible to teratogens

Front 302

What are the characteristics of the Fetal period in early human development?

Back 302

weeks 9-38
further development of organs and systems
extensive growth

Front 303

At which point in development does it become possible to survive premature birth and why?

Back 303

at 24 weeks, the lungs have developed sufficiently; however extensive care will be necessary

Front 304

What happens to the lungs after birth?

Back 304

Because only 10-15% of alveoli necessary for survival are present at birth, further development and growth will continue after birth.

Front 305

What happens in the cardiovascular system after birth?

Back 305

the closure of fetal chunts and vessels

Front 306

What happens to the nervous system postnatally?

Back 306

continued neuronal development

Front 307

What are the five key processes that must occur for the development of a zygote into a neonate?

Back 307

1. proliferation
2. growth
3. differentiation
4. pattern formation
5. morphogensis

Front 308

How is differentiation defined?

Back 308

the process by which cells or tissues become different from one another.
Also, the progressive acquisition of structural and biochemical specializations leading to unique or highly developed cellular functions

Front 309

Define totipotent.

Back 309

able to differentiate into all cell types

Front 310

Define Pluripotent.

Back 310

able to differentiate into many cell types

Front 311

Define Multipotent.

Back 311

able to differentiate into a restricted group of cells.

Front 312

Define Unipotent.

Back 312

determined as to differentiated cell form

Front 313

Does differential gene activity lead to irreversible turning off of genes?

Back 313

No

Front 314

What is the SHH factor important for?

Back 314

sonic hedgehog
inducing positional growth formations

Front 315

What is syndactyly?

Back 315

a malformation due to altered morphogenesis in which two fingers are fused together due to the lack of apoptosis in the cells between the fingers in development

Front 316

Briefly describe what happens during the first week of development.

Back 316

1. oocyte released and fertilized
2. rampant cleavage; development of morula
3. compaction and fusion of outer blastomeres; formation of blastocyst
4. hatching of blastocyst from the zona pellucida
5. implantation with syncytiotrophoblasts leading the invasion

Front 317

In the blastocyst, what is the differentiation potential of the innercell mass?

Back 317

pluripotential

Front 318

What are the syncytriotrophoblasts known to secrete?

Back 318

Human chorionic gonadotropin
metalloproteinases to enviade

Front 319

What is the most imvsive type of carcinoma?

Back 319

choriocarcinoma

Front 320

What does hCG do?

Back 320

stops the menstrual cycle

Front 321

What is the percentage of spontaneus abortions?

Back 321

thought to be at least 60%

Front 322

What is an ectopic pregnancy?

Back 322

pregnancy in which the implantation of the blastocyst has occurred in the fillopian tube, not the uterine body

Front 323

What is meant by placental previa pregnancy?

Back 323

the blastocyst implanted in the lower part of the uterine body, possibly on the cervix; leading to the placenta being below the fetus during development and possibly birth

Front 324

What is the differentiatio potential of blastomeres?

Back 324

totipotential

Front 325

What are 6 possible indications for the use of IVF?

Back 325

In Vitro Fertilization
1. blocked fallopian tubes or pelvic adhesions
2. male factor infertility
3. failed 2-4 cycles of ovarian stimulation with intrauterine insemination
4. unexplained infertility
5. vasectomy or tubal ligation
6. preimplantation genetic diagnosis

Front 326

What occurs during the second week of development?

Back 326

1. implantation is completed; lies totally within the endometrium
2. formation of primitive uteroplacental circulation
3. formation of bilaminar emryo
4. formation of extraembryonic membranes and cavitied

Front 327

How does the conceptus hide form the maternal immune system?

Back 327

1. reduces the expression of major histocompatibility complex (MHC) class I antigen
2. produces locally immunosuppressor molecules

Front 328

What is the lacunar network?

Back 328

network of syncytiotrophoblasts that allow maternal blood to leave the maternal vascular system and enter the embryonic system.

Front 329

What is the bilaminar disk?

Back 329

one layer of epiblasts on top of one layer of hypoblasts; above is amniotic cavity, below is blastocyst cavity

Front 330

How is the primary yolk sac formed?

Back 330

migration/ expansion of hypoblasts around the blastocyst cavity

Front 331

After the thickening of the conceptus wall, what proliferates around the edges?

Back 331

extraembryonic mesoderm; which will form the somatic extraembryonic mesoderm, splanchnic extraembryonic mesoderm and the extraembryonic coelom

Front 332

How is the secondary yolk sac formed?

Back 332

the splanchnic extraembryonic mesoderm 'pinches' inward. Excess is degraded and absorbed

Front 333

What is the Chorion comprised of form out to in?

Back 333

lacunar network [syncytiotrophoblasts and maternal vascular system], cytotrophoblasts, somatic extraembryonic mesoderm

Front 334

what is the allantois, when is it formed, where is ite?

Back 334

part of the secondary yolk sac formed caudaly of the caudal end of the bilaminar disk.

Front 335

What is a hydatidiform Molar Pregnancy?

Back 335

over development of extraembryonic structures; paternal only genome

Front 336

what drives trophoblast development?

Back 336

paternal genome

Front 337

What drives innercell mass development?

Back 337

maternal genome

Front 338

3 characcteristics of an epithelial cell?

Back 338

1. polarized
2. apical and basal surface
3. sit on top of the extracellular matrix (ECM)

Front 339

3 characteristics of mesenchymal cells

Back 339

1. not polarize din ECM
2. surrounded by ECM
3. migrate through the ECM

Front 340

What layer of the bilaminar disk are all three germ layers formed from?

Back 340

The epiblast.

Front 341

What is gastrulation?

Back 341

the process by which the epiblast differentiates into the ectoderm, mesoderm, and endoderm

Front 342

What does the ectoderm form?

Back 342

outler layer, skin, nervous system

Front 343

What does the mesoderm form?

Back 343

middle layer, muuscle, heart, skeleton

Front 344

What does the endoderm form?

Back 344

inner layer, lining of GI tract

Front 345

Describe gastrulation.

Back 345

1. occurs through the primitive streak
2. primitive streak is formed by the thickening of the epiblast.
3. ingression of epiblast through primitive groove forms the mesoderm
4. epiblast that ingresses throught the primitive groove replaces hypoblast to form endoderm
5. begins early in the 3rd week of development as is completed by the end of the 4th week.

Front 346

Describe neuralation.

Back 346

1. process by which the neural tube is formed [brain and spinal cord]
2. neural tube formed and closed by the end of the 4th week of development
3. neural crest cells form as neural tube closes
4. neural crest cell form peripharal ganglia and scwann cells of the nervous system.

Front 347

Another name for neural crest cells.

Back 347

ectomesenchyme

Front 348

Neural tube defects are detected how?

Back 348

ultrasound or measuring alpha-fetoprotein (AFP) in amniotic fluid

Front 349

Why is folic acid important?

Back 349

reduces the occurrence of neural tube defect.

Front 350

Describe meningocele

Back 350

effect caused by too late degradation of primitive groove; characterized by the meninges protruding into the spine.

Front 351

What is meninges?

Back 351

membrane that protects the nervous system.

Front 352

Describe meningomyelocele?

Back 352

primitive streak degraded prematurely; causes expose spinal cord out of the spine, but not to the surface; often leads to paralysis beyond that point.

Front 353

Describe myelochisis.

Back 353

the premature degradation of the primitive streak resulting in exposure of the spinal cord to the external environment. Often not compatible with life due to infections.

Front 354

What is hisrchsprung's disease?

Back 354

aganglionic megacolon; malformation of neural crest cells migration

Front 355

What does BMP-4 do?

Back 355

promotes formation of ventral structures

Front 356

What does hensen's node do?

Back 356

secretes factors that block BMP-4 [chordin, noggin]

Front 357

How does the embryo differentiate between left and right formations?

Back 357

beating of cilia, to the left from the henson node

Front 358

Describe what happens during the fourth week of development.

Back 358

1. organization of mesoderm into groups of tissue [notochord, paraxial mesoderm, intermediate mesoderm, lateral plate mesoderm]

2. segmentation of paraxial mesoderm into somites
3. body folding

Front 359

What will the cephalic somitomeres go on to form?

Back 359

the skull

Front 360

What will the occipital somites go on to form?

Back 360

skeleton and muscles

Front 361

How many cephalic somitomers are there?

Back 361

7

Front 362

How many somite [occipital + trunk] are there?

Back 362

42-44

Front 363

In sclerotome formation [axial skeleton] what do SHH and PAX1 do?

Back 363

induce formation of sclerotome and cartilage and bone formation respectively

Front 364

In dermamyotome formation, what do WNT, MYF5, BMP4 nad MYOD do?

Back 364

1. induce dermamytome formation
2. epaxial musculature
3. hypaxial musculature

Front 365

What does Hox do?

Back 365

determines the spatial structure pattern [legs where legs are supposed to go]

Front 366

What causes holoprosencephaly?

Back 366

defect in SHH gene possibly from alcohol consumption

Front 367

What is produced when a stem cell divides?

Back 367

a stem cell and a cell that must differentiate

Front 368

What is transdifferentiation?

Back 368

the conversion of one cell type directly to another

Front 369

4 types of stem cell research.

Back 369

1. nuclear transfer
2. iPS cells
3. lineage swithc
4. direct conversion

Front 370

What doe s the triple screen test for

Back 370

msAFP, betahCG, uE3

Front 371

What does the quad screen test

Back 371

all of the triple test, and dimeric inhibin A

Front 372

What is pleiotropy?

Back 372

a birth defect demonstrates pleiotropy when a single underlying causative agent results in abnormalities of more than one organ system in different parts of the embryo or in multiple structures that arise at different times during intrauterine life.

Front 373

Define syndrome.

Back 373

a syndrome is generally recognized and defined as a well-characterized constellation of major and minor anomalies that occur together in a predictable fashion presumably due to a single underlying etiology which may be monogenic, chromosomal, mitochondrial, or teratogenic in origin.

Front 374

What is an association?

Back 374

an association is a group of anomalies that occur more frequently togetherr than would be expected by chance alone, but that do not have a predictable pattern of recognition and or a suspected unified underlying etiology.

Front 375

VACTERL

Back 375

an associatio disorder [anal atresia, cardiac anomalies, other]

Front 376

Sequence

Back 376

a sequence is a group of related anomalies that generally stem froma single initial major anomaly that alters the development of other surrounding or related tissues or structures

Front 377

Field defect

Back 377

the term field defect is often used to describe raltted malformations in a particular region

Front 378

Malformation

Back 378

a malformation signifies that fetal growth and development did not procedd normally due ot underlying genetic, epigenetic, or environmentla factors that altered the development of a particular structure

Front 379

deformation

Back 379

a deformation is caused by an abnormal external force on the fetus during in utero development that results in abnormal growth or formation of the fetal structure

Front 380

Dysplasia

Back 380

dysplasia occurs where the intrinsic cellular architecture of a tissue is not normally maintained thoughout growth and development.

Front 381

BMSC

Back 381

bone marrow stem cell

Front 382

non seeded technique in bladder

Back 382

creating a biodegradeable scaffolding for the natural cells to use

Front 383

Seeding

Back 383

use of stem cells to regenerate

Front 384

What is used in recent technology to dice up DNA?

Back 384

miRNA

Front 385

What are the number one and number two leading causes of death in the US?

Back 385

1. heart disease
2. cancer

Front 386

what are the top three most prevalent types of cancer for men?

Back 386

1. prostate cancer
2. lung
3. colon

Front 387

what are the top most prevalent types of cancer in women?

Back 387

1. breast
2. lung
3. colon

Front 388

What is the deadliest type of cancer?

Back 388

apparently lung, also the most preventable

Front 389

Stages of cancer

Back 389

stage 1: small, localized, generally resectable
stage 2: larger, less resectable, still fairly localized
stage 3: lymph node involvement, large, diffuse
stage 4: metastasis to one or mor distal sites

Front 390

At what level does the staging analysis occur?

Back 390

the whole organ level.

Front 391

How many grades of cancer are there?

Back 391

4

Front 392

What is the first line in cancer therapy?

Back 392

surgery or radiotherapy

Front 393

What is the first line in cancer therapy, if surgery and radiotherapy are not safe or effective?

Back 393

chemotherapy

Front 394

TPMT

Back 394

thiopurine methyl transferase
metabolizes thiopurine drugs

Front 395

When giving thiopurine drugs, what is it important to test for?

Back 395

for functioning TPMT

Front 396

What are the criteria for combination chemotherapy?

Back 396

1. single therapy alone is effective (for a time)
2. should act by different mechanisms of action
3. should have different mechanisms of resistance

Front 397

Are chemotherapy drugs given simultaneously in combination therapy?

Back 397

no, the drugs are given individually, but alternating about every 4 weeks

Front 398

When is cancer considered cured?

Back 398

when it has been in remission for 10 years

Front 399

Toxicities associated with chemotherapy.

Back 399

bone marrow, GI mucosa, oral mucusa, skin [light sensitivity], hair follicle [alopecia], gonads.

Front 400

Define Amelioration.

Back 400

to make better

Front 401

how to ameliorate myelosuppression in chemotherapy

Back 401

1. Erythrpoietin [EPO][epoetin][epogen]
2. granulocyte colony-stimulating factor [G-CSF][Filgrastim]
3. Granulocyte-macrophage colony-stimulating factor [GM-CSF][Sargramostim/Leukine]

Front 402

EPO

Back 402

erythropoeitin [epoeitin][epogen]
fx: stimulates production of erythrocytes
admin: SC or IV
t.5:4-13 h
sfx: hypertension, sweating, thrombosis, myocardial infarction, iron deficiency
TX:do not use in erythroid based cancer

Front 403

G-CSF

Back 403

[granulocyte colony-stimulating factor][Filgrastim]
fx: stimulates the production of neutrophiles
t.5: ~3 h, but with PEGylation 15-18 h
sfx: fever, bone pain
TX: do not use in leukemias

Front 404

GM-CSF

Back 404

[granulocyte-macrophage colony stimulating factor][Sargramostim/Leukine]
fx: stimulates the production of monocytes and granulocytes]
t.5: ~3h
sfx: fever, rash, bone pain, muscle pain

Front 405

S-phase specific chemotherapy drugs:

Back 405

antimetabolites

Front 406

M-phase specific chemotherapy drug:

Back 406

Taxanes, Vinca alkaloids

Front 407

G1-S phase specific chemotherapy:

Back 407

Topoisomerase II inhibitors

Front 408

Is it easier to kill dividing cells?

Back 408

yes

Front 409

What are cell-cycle nonspecific drugs?

Back 409

1. alkylating agent
2. platinum analogs
3. anthracycline
4. antitumor antibiotics
5. topoisomerase I inhibitors

Front 410

What do alkylating agents do?

Back 410

[cyclophosphamide][nitrogen mustard]
fx: irreversible changes in DNA[cross-linking og guanines]
sfx: mutagenic, teratogenic, carcinogenic
USED: lymphoma, leukemia, prostate, lung, breast and ovarian cancer

Front 411

What do antimetabolites do?

Back 411

[s-phase][methotrexate][folic acid analog]
fx:inhibits dihydrofolate reductase, retards DNA/RNA synthesis also inhibits protein synthesis
USED: head, neck, breast and lung carcinoma, sarcoma, testicular and bladder tumors

Front 412

Mercaptopurine (6-MP)

Back 412

[thiopurine][antimetabolite][s-phase]
acute leukemia, chronic myelogenous leukemia
Test for mutations of TPMT!

Front 413

Azothiopurine

Back 413

[thiopurine][antimetabolite][s-phase]
Test for Mutations of TPMT!

Front 414

6-Thioguanine (6-TG)

Back 414

[thiopurine][antimetabolite][s-phase]
Test for Mutations of TPMT!

Front 415

Thiopurines:

Back 415

1. prodrugs requiring activation through the purine salvage pathway
2. act by inducing mutations and by inhibition of de novo purine synthesis
3. toxicity is delayed, since passage through S phase is required
4. also effective as anti-inflammatory and immunosuppressive drugs.

Front 416

5-FU

Back 416

[antimetabolite][Fluorouracil]
FX: blocks thymidylate synthase
converted to FdUMP, FdUTP, FUTP
USED: lung, breast, overy, prostate, cervix, bladder, head and neck carcinoma, GI adenocarcinoma

Front 417

FdUMP

Back 417

1. inhibits thymidylate synthase by blocking access of dUMP
2. causes dNTP imbalance and increased dUTP levels, which lead to DNA damage

Front 418

FdUTP

Back 418

1. incorporated into DNA
2. induces NER, which is futile in the presence of high FdUTP/dTTP levels, this leads eventually to DNA strand breaks and death

Front 419

FUTP

Back 419

1. incorporated into RNA
2. inhibits many processes, including processing of pre-mRNA into mature RNA and modification of tRNA
3. profound effects on cell metabolism and viability

Front 420

Vinka Alkaloids

Back 420

[M-phase][Vinblastine]
1. isolated from vinca rosea
FX: bind tubulin and prevent mitotic spindle formation
USED: hodgkin's disease, lymphoma, leukemia, kaposi's sarcoma, breast cancer, cervix, lung, ovary, bladder, and testis

Front 421

Taxoids

Back 421

[M-phase][Paclitaxel/Taxol]
isolated from yew tree bark
FX: induce polymerization and stabilization of microtubules
USED: metastatic cancer of breast and ovary

Front 422

Actinomycin D

Back 422

[antibiotic]
FX: intercalates in DNA and inhibits transcription and DNA synthesis
USED: Wilm's tumor, ewing tumors, osteosarcoma. Neuroblastoma

Front 423

Doxorubicin

Back 423

[Adriamycin][anitbiotic]
FX: intercalates in DNA
USED: acute leukemia, sarcoma, hodgkin's disease, neuroblastoma, carcinoma of lung, GI tract, endometrium, ovary,thyroid and breast, wilm's tumor, multiple myeloma

Front 424

Mitomycin

Back 424

[antibiotic]
FX: after intracellular activation, reacts with DNA and inhibits its synthesis
USED: carcinoma of head, neck, lung, GI tract, breast, cervix and bladder

Front 425

Bleomycin

Back 425

[anitbiotic]
FX: chelates metal ions>produces superoxide and hydroxide free radicals>Dna cleavage, lipid peroxidation

Front 426

Topotecan

Back 426

[isolated from happy tree][nonspecific cell cycle][captothecin]
FX: inhibits topoisomerase I, which leads to single-strand breaks in DNA; inhibits replication and transcription
USED: metastatic carcinoma of ovary

Front 427

Irinotecan

Back 427

[isolated from happy tree][nonspecific cell cycle][captothecin]
FX: inhibits topoisomerase I, which leads to single-strand breaks in DNA; inhibits replication and transcription
USED: metastatic cancer of colon and rectum

Front 428

Etoposide

Back 428

[Epipodophyllotoxins][S-phase]
[isolated from Mayapple plant]
FX: inhibit topoisomerase II, which leads to double strand breaks in DNA; causes errors during DNA replication and eventually apoptosis

Front 429

Teniposide

Back 429

[Epipodophyllotoxins][S-phase]
[isolated from Mayapple plant]
FX: inhibit topoisomerase II, which leads to double strand breaks in DNA; causes errors during DNA replication and eventually apoptosis

Front 430

Cisplatin

Back 430

FX: intra-interstrand crosslinks in DNA
USED: carcinoma of testes, ovary, head, neck, cervix, endometrium, sarcoma, neuroblastoma

Front 431

As2O3

Back 431

USED: acute promyelocytic leukemia

Front 432

Asparaginase

Back 432

FX: depletes Asn levels
USED: acute lymphocytic leukemia

Front 433

Androgens

Back 433

USED: metastatic breast cancer [may be bad]

Front 434

Anti-androgens

Back 434

USED:prostate carcinoma
[Flutamide]

Front 435

Estrogens

Back 435

USED: high dose used in postmenopausal breast cancer ; prostate cancer [may be bad]

Front 436

Anti-Estrogens

Back 436

[Tamoxifen]
USED: postmenopausal breast cancer, metastatic melanoma [maybe]

Front 437

Letrozole

Back 437

[aromatase inhibitor][estrogen pathway]
FX: prevents the conversion of testosterone to estradiol
USED: advanced breast cancer; used in tamoxifen resistance

Front 438

Fulvestrant

Back 438

[Estrogen pathway downregulator]
FX: leads to the destruction of estrogen receptor
USED: given to tamoxifen-resistant patients; generally used after letrozole, though some recommend skipping letrozole.

Front 439

Tretinoin

Back 439

[retanoic acid receptor][acid form of vit A]
FX: induce the differentiation of undifferentiated cancer cells, targets RAR
USED: acute promyelocytic leukemia [APL]
Q15d, Q3m
SFX:teratogenicity
OTHER: acne vulgaris, keratosis pilaris, cosmetics
OSFX: sensitivity to sunlight, skin irritation

Front 440

Alitretinoin

Back 440

[ret acid rec]
FX:target RAR and RXR to induce differentiation of undifferentiated cancer cells
USED: treatment of AIDS-related Kaposi's sarcoma
Other: severe chronic hand eczema

Front 441

Bexarotene

Back 441

[retinoic acid receptor]
FX:targets RXR to induce differentiation of undifferentiated cancer cells
USED: treatment of cutaneous T cell lymphoma
Other: lung cancer, breast cancer, kaposi's sarcoma

Front 442

What type of treatment is used to stop cancer cells from evading growth suppressors?

Back 442

cyclin-dependent kinase inhibitors

Front 443

What typ of treatment is used to stop cancer cells from avoiding immune detection?

Back 443

immune activating anti-CTLA4 mAb

Front 444

What type of treatment is used to stop cancer cells from enabling replicative immortality?

Back 444

telomerase inhibitors

Front 445

What type of treatment is used to stop cancer cells from having tumor promoting inflammation?

Back 445

selective anti-inflammatory drugs

Front 446

What type of treatment is used to stop cancer cells from activating invasion and metastisis?

Back 446

inhibitors of HGF/c Met

Front 447

What type of treatment is used to stop cancer cells from inducing angiogenesis?

Back 447

inhibitors of VEGF signaling

Front 448

What type of treatment is used to stop cancer cells from creating genome instability and mutation?

Back 448

PARP inhibitors

Front 449

What type of treatment is used to stop cancer cells from resisting apoptosis?

Back 449

Proapoptotic BH3 mimetics

Front 450

What type of treatment is used to stop cancer cells from deregulating cellular energetics?

Back 450

aerobic glycolysis inhibitors

Front 451

What type of treatment is used to stop cancer cells from sustaining proliferative signaling?

Back 451

EGFR inhibitors

Front 452

Imatinib

Back 452

[Gleevec]
FX:tyrosine kinase inhibitor [Abl, cKit, PDGFR]
USED: chronic myeloid leukemia, acute lymphocytic leukemia, gastrointestinal stromal tumors

Front 453

Trastuzumab

Back 453

[herceptin][stop proliferative signaling]
FX: humanized monoclonal anti-HER2 antibody used in mutated HER2 patients
T.5: 6 d
Q7d IV with chemotherapy
Q21d IV after surgery/ chemotherapy
SFX: cardiac dysfunction

Front 454

Lapatinib

Back 454

[kinase inhibitor]
FX: HER2 mutation
t.5: 24h
q1d
sfx: nausea, vomiting, heartburn, fatigue

Front 455

Erlotinib

Back 455

[Tarceva][stop proliferative signaling]
FX:EGFR inhibitor
USED: advanced NSCLC; 3 month life extension
SFX: rash, diarrhea, fatigue

Front 456

Gefitinib

Back 456

[Iressa][stop proliferative signaling]
FX: EGFR inhibitor
USED: advanced NSCLC
SFX: acne, diarrhea, nausea, vomiting

Front 457

Cetuximab

Back 457

[Erbitux][stop proliferative signaling]
FX: prevents EGF binding
USED: squamous cell carcinoma and colon cancer
TEST: check for mutation on KRAS

Front 458

Bevacizumab

Back 458

[Avastin][angiogenesis inhibitor]
FX: prevents VEGF from binding to its receptor
USED: metastatic breast cancer
OTHER: age-related macular degeneration
SFX: risk of bleeding, bowel proliferation

Front 459

Sunitinib

Back 459

[Sutent][angiogenesis inhibitor]
FX: inhibitor of VEGFRs, PDGFRs, and cKit
USED: RCC and imatinib-resistant GIST

Front 460

Sorafenib

Back 460

[Nexavar][angiogenesis inhibitor]
FX: inhibitor of VEGFR2-3, PDGFR, cKit, Raf-1, B-Raf
USED: advanced renal cell carcinoma and unresectable hepatocellular carcinoma

Front 461

Vemurafenib/zelboraf

Back 461

[Zelboraf][kinase inhibitor]
FX:inhibits V600E B-Raf, not wild type
USED: late stage melanoma; 6 months life ext.; regression for 2-18 m

Front 462

Bortezomib/velcade

Back 462

[Velcade][proteasome inhibitor]
FX: inhibits active site of 26 S proteasome
USED: multiple myeloma

Front 463

What preserves methylation?

Back 463

DNMT1

Front 464

What may be unique about a cancer epigenome?

Back 464

1. genome-wide hypomethylation
2. site-specific CpG island promoter hypermethylation

Front 465

What is one possible bad reason for hypermethylation?

Back 465

the silencing of tumor suppressors

Front 466

Azacytidine

Back 466

[Vidaza][DNA demethylating Agent]
FX: inhibits DNA methyltransferase after incorporation into DNA; reactivation of tumor suppressor genes
USED: myelodysplastic syndrome

Front 467

5-Aza-2'-deoxyxytidine

Back 467

[decitabine][DNA demethylating agent]
FX: similar to azacytidine
USED: myelodysplastic syndrome

Front 468

What is HDAC?

Back 468

histone deacetylases

Front 469

Vorinostat/ SAHA

Back 469

[Zolinza][HDAC]
FX: reactivates tumor suppressor
USED: cutaneous T-cell lymphoma

Front 470

Romidepsin

Back 470

[Istodax][HDAC]
FX: reactivates tumor suppressor
USED: cutaneous t-Cell lymphoma

Front 471

To improve results when treating epigenetically, what would you use synergistically?

Back 471

1. HDAC
2. demethylating agents

Front 472

Define immunotherapy.

Back 472

treatment of disease by inducing, enhancing or suppressing an immune response.

Front 473

What are the three reasons to use immunotherapy in cancer treatment?

Back 473

1. immune cells kill tumor cells
2. immune cells affect cancer growth and metastisis
3. adjunct treatment to ameliorate SFX of chemotherapy

Front 474

IL-2

Back 474

[immunotherapy]
FX:antigen binding to T cell receptor leads to secretion of IL-2
T.5:30-90 min
Admin: IV
USED: metastatic renal carcinoma and malignant melanoma
SFX: especially capillary leak [due to activated T cells damaging the endothelium]

Front 475

IFN-alpha2a

Back 475

[immunotherapy]
FX: induced by viral infection and produced by leukocytes
t.5: 2.5 h
Admin: SC or IM
USED: renal cell carcinoma
SFX: myelosuppression and flulike symptoms

Front 476

IFN-gamma

Back 476

[immunotherapy]
FX: induced by viral infections and produced by T-lymphocytes and NK cells
Admin: SC and IV
T.5: 30 min
USED: renal cell carcinoma
SFX: flulike symptoms, GI upset

Front 477

Levamisole

Back 477

[immunotherapy]
FX: non-specific immunostimulatory properties
USED: colon cancer, melanoma, head and neck cancer
SFX: suppress the production of leukocytes, inflammatory destruction of blood vessels
WITHDRAWN FROM US; common in COCAINE

Front 478

Briefly describe adoptive immunotherapy for cancer.

Back 478

Take out T cells, select and stimulate IFN-gamma producers, suppress immune system, put selected T cells back

Front 479

CAR

Back 479

chimeric antigen receptor [artificial T cell receptor]

Front 480

Provenge

Back 480

[sipuleucel-T]
FX: autologous cellular immunotherapy 'cancer vaccine'
3 courses Q 14d ($90000)
USED: metastatic, castration-resistant prostate cancer
SFX: fever, fatigue, chills, nausea, joint and headache

Front 481

Ipilimumab

Back 481

[immunotherapy]
FX: blocks CTLA-4
USED: late stage melanoma; possible proatate and lung cancer
SFX: potentially fatal immunological adverse effects, GI, Fever

Front 482

Denileukin Diftitox

Back 482

[Ontak][immunotoxin]
FX:IL-2 conjugated to diptheria toxin
USED: cutaneous T cell Lymphoma

Front 483

Adcetris

Back 483

[immunotoxin]
FX: antibody conjugated to poison
USED: refractory Hodgkin's lymphoma and systemis anaplastic large cell lymphoma

Front 484

On what mutation was the first succesful gene therapy done on?

Back 484

X-linked IL2RG mutation

Front 485

ONYX-015

Back 485

oncolytic virus involving p53

Front 486

Measles

Back 486

leads to spontaneous regression of leukemias and lymphomas

Front 487

What are the common pleiotropic manifestations of neurofibromatosis 1?

Back 487

1. 6 café-au-lait spots over 15mm
2. 1 plexiform neurofibroma or 2 other neurofibromas
3. axillary or inguinal freckling
4. distinstinctive osseous lesion
5. optic glioma
6. 2 lisch nodules
7. affect 1st degree relative
8. mutation in NF1

Front 488

How many pleiotropic manifestations are required before you can clinically diagnose neurofibromatosis 1?

Back 488

2

Front 489

Genetics of neurofibromatosis

Back 489

Autosomal Dominant; 50 % os cases de novo

Front 490

Diagnosis of Neurofibromatosis 2

Back 490

1. bilateral vestibular schwannomas, or
2. a first degree relative with NF2, plus either
a. unilateral vestibular schwannoma under age 30y
b. Two of the following: neurofibroma, meningioma, gliomma, schwannoma, juvenile posterior subscapsular lenticular opacity 'cataract'
3. unilateral vestibular schwannoma and any two: neurofibroma, meingioma, glioma, schwannoma, cataract
4. multiple meningiomas and
a. inilateral vestibular schwannoma
b. any two of: neurofibroma, glioma, schwannoma, cataract

Front 491

Legius Syndrome

Back 491

SPRED1
café au lait spots
axillary freckling
nodules are lipomas, not neurofibromas
mild disorder

Front 492

What did Osler believe?

Back 492

The body is a machine and there is one root cause proximate; look for similarity between cases

Front 493

What did Garrod believe?

Back 493

Disease is caused by incongruence between the body and environment, disease can come from many causes, near or far, and every case is different.