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B1 > Week 3 > Flashcards

Week 3 Flashcards

1
Q

In autosomal dominant disorders, for related, unaffected individuals (no info on parents available), you cannot determine genotype without test
TRUE OR FALSE

A

True

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2
Q

In autosomal dominant disorders, for unrelated individuals (married in), you cannot assume that they are homozygous normal
TRUE OR FALSE

A

FALSE - you can UNLESS dz frequency is over 1/20

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3
Q

In FH, what is the chance that individuals are non-penetrant heterozygotes?

A

1/500

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4
Q

In autosomal dominant disorders, you can assume that affected individuals are heterozygotes unless what? (2)

A
  • both parents affected

- dz frequency >1/20

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5
Q

In autosomal dominant disorders, disease frequency is equal to?

A

2q (heterozygote frequency)

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6
Q

In autosomal recessive disorders, disease frequency is equal to?

A

q^2

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7
Q

In autosomal recessive disorders, carrier frequency is equal to?

A

2q

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8
Q

In an autosomal recessive disorder, if there are NO affected individuals in a sibship and you know that at least ONE of parents is a carrier, what is the probability that an UNAFFECTED child is a carrier?

A

1/2

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9
Q

In an autosomal recessive disorder, if there ARE affected individuals in a sibship OR you know that BOTH of the parents are carriers, the probability that an UNAFFECTED child is a carrier is?

A

2/3

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10
Q

In an autosomal recessive disorder, if one parent is homozygous affected and you do not know the carrier status of the UNAFFECTED, UNRELATED spouse, probability of an AFFECTED child is

A

1/2X the carrier frequency (= q)

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11
Q

When should you recommend carrier testing to an unaffected, unrelated spouse?

A

When other parent is homozygous affected or if they are a known carrier

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12
Q

In autosomal recessive disorders, affected individuals are often compound heterozygotes unless what?

A

There is cosanguinity

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13
Q

What protein is affected in cystic fibrosis?

A

cystic fibrosis transmembrane regulator (chloride channel in lungs and pancreas)

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14
Q

OCA1 is caused by what defect in the phenylalanine metabolism pathway?

A

Dopamine –> Melanin (catalyzed by tyrosinase)

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15
Q

How common is OCA1?

A

1/40K are affected, 1/100 are carrier

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16
Q

How does calcium get into the cell to raise cytosolic levels in

  • nerve cell
  • regular cell
  • cardiac muscle cell
A

1) signal depolarizes PM –> ca++ channels open
2) signal activates receptor –> PLCB stimulated via Gq protein –> Ip3 produced –> Ca++ released from ER
3) Signal depolarizes cell and voltage gated channels open

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17
Q

Describe how foot odor is detected (6 steps)

A

1) Odorant binds to GPCR on olf neurons
2) Activates Golf protein (GDP–>GTP)
3) Alpha subunit activates adenylyl cyclase
4) cAMP produced
5) cAMP opens Na+ channels
6) Na+ influx into cell

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18
Q

Describe how the eye works in response to light

A

Rhodopsin is activated which activates Gt which increases PDE which decreases cGMP. Na+ channels close so cell is repolarized.

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19
Q

Describe how the eye works in response to dark

A

Rhodopsin is inactivated which inactivates Gt which decreases PDE which increases cGMP - Na++ channels open so the cell is depolarized

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20
Q

In GPCR densitization, activated GPCR sitmulates Grk to phosphorylate GPCR on multiple sites. This ATP-driven reaction allows what to bind and densitize the GPCR?

A

ARRESTIN! :D

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21
Q

What are the five classes of NZ linked receptors

A

1) receptor tyrosine kinase (RTKs)
2) RTK assoc receptors
3) receptor like protein tyrosie phosphatases
4) receptor/guanylylcyclase
5) receptor ser/threonine kinases

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22
Q

Epidermal growth factor, insulin, nerve growth factor, platelet derived growth factor, MCSF, fibroblast growth factors, ephrins, and vascular endothelial growth factors all act via ___________________

A

receptor tyrosine kinases

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23
Q

How do ligands induce dimerization? (3 ways)

A

1) ligand is a dimer with each subunit containing one receptor binding domain
2) monomeric signaling protein forms multimers by binding to heparin sulfate proteoglycans to crosslink its receptor
3) in contact dependent signaling, clusters formed in PM of signaling cell and then crosslink the receptors on target cell

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24
Q

Dimerization and autophosphorylation of receptor tyrosine kinases has what two effects?

A

1) phosphorylation @ some tyrosines promotes complete activation of kinase domains
2) phosphorylation @ tyrosines in other parts of receptor generates dockig sites for intracellular proteins –> form complexes that broadcast signals

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25
Q

PI3-kinase makes ______________ in the plasma membrane which are required for several signaling pathways

A

PIP2 and PIP3

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26
Q

______ inactivates Ras pathways while ______ activates Ras pathways

A

GAP, GEF

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27
Q

PLC-y produces _______ and _______

A

DAG, IP3

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28
Q

Describe a generic Ras-MAPK pathway

A

4) Activated Ras recruits MAPKKK (raf) to PM and activates it*
5) Ras recruits MAPKK (mek) to PM and activates it*
6) Ras activates MAPK (erk) *
7) Erk phosphorylates proteins, protein kinases, transcription regulators etc to cause changes in cell behavior*

  • ATP catalyzed
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29
Q

What is the major function of PI3 kinase?

A

Stimulate cell growth

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30
Q

Generation of PIP2 and PIP3 by PI3 kinase generates docking sites for signaling proteins that have ___________________

A

PH domains

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31
Q

Describe PI3 kinase signaling pathway that leads to B cell activation

A

B cell receptor binds to PI3 kinase which produces PIP3. BTK binds to PIP3 via PH domain. PLC-y is activated and produces IP3 and DAG. Calcium is released from the ER –> activation of downstream pathways lead to clonal expansion then activation, translation, and regulated exocytosis of Igs

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32
Q

Describe X-linked agammaglobinemia

  • mutation
  • manifestations
  • treatment
A
  • caused by mutation in gene that codes for BTK, most common is mutation in PH domain that prevents BTK from binding to PIP3
  • very low serum Ig levels, lack of plasma cells in secondary lymphoid organs
  • tx: ABX and passive IgG therapy
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33
Q

PI3 kinase promotes cell survival via phosphorylation and activation of Akt protein which inactivates ______ so that it cannot bind to and inhibit the ______________. This leads to promotion of cell survival

A

Bad, apoptosis inhibitory proteins

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34
Q

Akt protein is phosphorylated and activated by ______ and ________

A

PDK1 and mTOR

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35
Q

Which of these is not a cytokine

a) interferon
b) interleukin
c) tumor necrosis factor
d) all of above are cytokines

A

d

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36
Q

The SRC family belongs to non-receptor ___________

A

tyrosine kinases

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37
Q

JAKs cross phosphorylate each other on tyrosines once their associated receptors bind to a cytokine, then _______ dock on receptors and are phosphorylated by the JAKS as well

A

STATs

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38
Q

Once STATs are phosphorylated, they dissociate from receptor and dimerize via _____ domain which allowed the to translocate to nucleus and activate gene transcription

A

SH2

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39
Q

In rheumatoid arthritis, pathological lesions driven by TNF-alpha induced production of inflammatory mediators that is mediated by transcription factor ________________

A

NF-kappa-B

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40
Q

in the NF-kappa-B pathway, binding of TNF-alpha causes rearrangement and activation of a protein kinase that phosphorylates and activates ____ which then phosphorylates ____ into two serines. This marks protein for ubiquitylation and degradation in proteasomes. _____ is released and translocated into nucleus where it stimulates transcription.

A

IKK, IKB, NFKB

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41
Q

______ is major co-inflammatory cytokine that activates NF-KB pathway

A

TNF-alpha

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42
Q

Crohn’s disease is initiated by an inappropriate innate and acquired immune response to normal enteric flora, which is primarily driven by ________ and macrophage dependent chronic activation.

A

TNF-alpha

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43
Q

Infliximab blocks action of _____ by binding to it and preventing it from signaling to its receptors on cell surfaces, and has been approved to treat autoimmune diseases

A

TNF-alpha

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44
Q

Group each category below by type of receptor

a) cAMP, cGMP, DAG, IP3, Ca++
b) Ras activation, MAPK pathway
c) Src, Tyr phosphorylation, PI phosphorylation, JAK stats, NF-kappa-B

A

a) GPCRs
b) RTKs
c) NZ linked receptors

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45
Q

By end of embryonic period (weeks 3-8), _____________ system is fully functional and developed

A

cardiovascular

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46
Q

Define safety pharmacology

A

relatively new discipline that focuses on mechanism of action of unwanted actions and drugs

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47
Q

Ibuprofen is a ____________ name whereas Advil or Motrin would be a ________________

A

generic name, trade name

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48
Q

The _________ name of a drug is listed in one of the following publications: 1) US Pharmacopoiea, National Formulary, US Adopted Names

A

official

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49
Q

In 1937, sulfaniimade liquid form was released and led to deaths because solvent was never tested. This prompted passing of Food Drug and Cosmetic act in 1938. What were 3 actions of this act?

A
  • enforced labeling and safety of drugs
  • assigned enforcement to FDA
  • required NDA (new drug application)
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50
Q

In 1960s, thalidomide caused severe birth defects in newborns. The Harris-Refauver Amendment was passed in 1962 and enforced what (3)

A
  • proof of efficacy
  • required investigational new drug application prior to clinical testing
  • clinical trials are done AFTER animal testing, full consent required, full details of investigations
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51
Q

What were the lessons learned from recent TGN1412 disaster that results in all human participants suffering a cytokine storm?

A
  • During first human trial, do not give all patients drug simultaneously
  • Incorporate NOEL (no observed effect level) with MABEL (minimum anticipated bio effect level) to decide dose
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52
Q

After lab and animal testing, the drug sponsor submits what application to FDA to begin phase I of human trials?

A

Investigational New Drug

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53
Q

Describe amount of volunteers and purpose of each phase
Phase I
Phase II
Phase III

A

Phase I - 20-100 volunteers, looks at safety and dosage
Phase II - 100-500 volunteers, efficacy and side effects
Phase III - 1-5K volunteers, long term use study

54
Q

After phase III is successful, sponsor submits what application to FDA for formal approval and license?

A

New Drug Application

55
Q

Describe purpose of Phase IIIb and IV

A

follow-up testing
IIIb - additional safety data
IV - expansion of testing to broader popn

56
Q

Sensitivity

A

True Positive / Total Number with Disease

57
Q

Specificity

A

True Negative / Total Number Unaffected

58
Q

PPV

A

True Positive / Total Positive Results

59
Q

NPV

A

True Negative / Total Negative Results

60
Q

_____ of patients leave office not knowing what MD said

A

50%

61
Q

What are the three elements of functional analysis?

A

Antecedents (Triggers), Behaviors, Consequences (Pay Offs)

62
Q

Classical conditioning involves learning by cues and behaviors are malleable : True or False

A

False, behaviors are not malleable

63
Q

What percentage of birth defects are of unknown cause?

A

43%

64
Q

True/False - During first two weeks of organogenesis (up to embryonic disc) the fetus is susceptible to teratogenesis

A

FALSE - teratogen shock will result in death

65
Q

Maternal serum screening can be used to indicate ALL BUT which of the following

a) open NTD
b) abdominal wall defects
c) translocations
d) trisomy 18 or 21
e) aneuploidy

A

translocations

66
Q 
Common malformations due to teratogens -
up to 16 weeks =
4-6 weeks =
4-9 weeks =
7-9 weeks =
A

16: NTDs and mental retardation
4-6: cleft lip
4-9: low set/malformed ears and deafness
7-9: cleft palate

67
Q

Thalomide was prescribed to pregnant women for nausea and caused __________ derived from the latin word for “seal”

A

phocomelia

68
Q

Any binge drinking or 2-3OZ per day would cause what signs in a fetus?

A

Pre and post natal growth deficiency, mental retardation

69
Q

EtOH is toxic to _________ cells and _________ (organelle)

A

immature neural cells and mitochondria

70
Q

What are the signs of fetal alcohol syndrome?

A

skin folds at corner of eye, low nasal bridge, short nose, indistinct philtrum, small head, small eye opening, small midface, thin upper lip

71
Q

How does nicotine affect fetal growth?

A

Vasoconstrictor –> constriction of uterine blood vessels –> compromises blood flow, nutrient exchange, O2

72
Q

What chemical causes smoking-related toxicity?

A

Cadmium - causes placental necrosis and adhesion to cell wall

73
Q

Describe the features of phenytoin caused congenital malformations

A

IUGR (intrauterine growth restriction), microcephaly, mental retardation, distal phalange hypoplasia, specific facial features

74
Q

Retinoic acid, which is used to treat nodular acne and promyelotic anemia, causes impact in 2nd to 5th week. What are associated features?

A

Craniofacial dysmorphism, cleft palate, thymic aplasia, NTDs

75
Q

Warfarin-X or Coumadin embryopathy is thought to be caused by ___________. What are the features?

A

Vitamin K deficiency, inhibits enzymes involved in bone formation –> facial dysmorphism, cardiac defects, epiphyseal dysplasia, skeletal deformities, growth retardation

76
Q

ACE inhibitors affect 50% of pregnancies. What are features?

A

IUGR, renal dysplasia (enlargement), pulmonary hypoplasia (incomplete development), patent ductus arteriosis, incomplete ossification of skull

77
Q

What are effects of ionizing radiation?

A

Microcephaly, mental retardation and skeletal malformation

78
Q

What infections are assoc with congenital malformations? (7)

A

Toxoplasmoses, Rubella, CMV, HIV/Herpes, Varicella, Treponema

79
Q

Embryonic mesoderm differentiates into what two tissues?

A

Neuroectoderm - CNS and PNS

Epidermal

80
Q

Describe the fates of somitomeres in head and in body

A

a) somitomeres in head (1-7) –> neuromeres

b) somitomeres in body –> sclerotome and dermatomyotome

81
Q

What does the sclerotome form?

A

Vertebrae, ribs, some base of skull

82
Q

Intermediate mesoderm leads to

A

Ducts of urogenital tract (also connective tissue, smooth muscle in most organs)

83
Q

Lateral plate mesoderm differentiates into what two types?

A

Somatic - connective tissue and smooth muscle of trunk and extremity
Sphlancnic - connective tissue of all endothermal lined organs and all tissues of CV system

84
Q

What occurs in lateral folding?

A

Endoderm becomes folded into long narrow tube in middle with mesoderm separating two layers and ectoderm and amniotic cavity completely encircling embryo

85
Q

Endoderm forms epithelial lining of ________ and lines pharyngeal buds, lung buds, liver, pancreas and gallbladder bluds

A

GI tract

86
Q

During neurulation, _____ is blocked allowed induction of neural plate by notochord and prechordal plate

A

BMP4

87
Q

Describe derivatives of neural crest cells

A

connective tissue and bones of face and skull, cranial nerve ganglia, thyroid gland, odontoblasts, derms in face and neck, conotruncal septum of heart, brain cells

88
Q

Somites develop occipital to caudal and can be used to approximate age of embryo. At day 20, you have _____ somites and by day 30 you have ____ with a rate of increase of roughly ___ per day

A

1-4, 34-35, 3

89
Q

What does the myotome consist of ?

A

Skeletal muscles of body and limbs

90
Q

S1-S5 innervates?

A

butt, back of legs, genitals

91
Q

L1-L5 innervates?

A

pelvic region and anterior legs

92
Q

What drives cephalocaudal folding?

A

Rapid head and tail growth cause embryo to curl towards ventral surface

93
Q

Lateral folding initiates to connect ___ and ______ then ventral abdominal wall closes and gut is suspended from dorsal abdominal wall

A

gut and yolk sac

94
Q

What are the distinct phases of the embryonic period?

A

growth (cell division), morphogenesis (forming shapes), differentiation

95
Q

What is the first major organ system to be fully developed and function prenatally?

A

CV system

96
Q

In animal cells, dephosphorylation is carried out by 4 groups of ______________

A

ser/thr phosphatases

97
Q

cAMP is synthesized by _________ and hydrolyzed by _________ to 5’ amp

A

adenlylyl cyclase, phosphodiesterase

98
Q

Cholera toxin binds to alpha subunit of Gs and causes disease how?

A

locks Gs so cannot hydrolyze GTP
cAMP keeps being produced
Large efflux of Cl- and H2O into gut –> severe diarrhea

99
Q

Acetylcholine activates Gi protein and causes decrease in heart rate and force of contraction how?

A

Alpha subunit inhibits adenlyl cyclase

By subunit binds to K+ channels and opens them which makes it harder to depolarize cells

100
Q

Pertussis toxin binds to Gi protein and causes disease how?

A

Gi remains locked, cannot inhibit AC
cAMP keeps getting produced
Increase in insulin and other systemic effects

101
Q

Vasopressin-mediated glycogen breakdown, Ach-mediated amylase secretion and muscle contraction, and Thrombin-mediated blood platelet aggregation all act via cell responses in which GPCR’s activate ________

A

PLC-beta - stimulated via Gq

102
Q

PLC-beta produces what two second messengers?

A

IP3 - stimulates release of Ca++ from ER

DAG - remains in PM, activates PKC

103
Q

Which of the following is NOT a function of cAMP?

a) involved in vision
b) gene transcription
c) activates PKA
d) hormone-induced cell responses
e) involve din olfactory

A

a) that is cGMP

104
Q

According to the Haldane principle, in a population with a stable disease frequency, rate of spontaneous new mutation is equal to ______________

A

loss of alleles (1/3 in DMD)

105
Q

Hemophilia is caused by defects in clotting factors. A and B are characterized by?

A

A - factor 8

B - factor 9

106
Q

What causes G6PD deficiency?

A

Decreased protein stability, RBCs lack nucleus and ribosomes and cannot produce G6PD once formed, body compensates but when under stress cannot produce enough RBCs

107
Q

DMD is caused by defects in gene that codes for what protein?

A

dystrophin

108
Q

Male pattern baldness can be caused by mutations on what two chromosomes?

A

X - linked recessive

Chrom 20 - auto dom

109
Q

What is lyonization

A

One X chromosome in each somatic cell in females is inactivated randomly (1/2 cells express from dad X and 1/2 from mom X)

110
Q

How is X chromosome inactivated?

A

DNA methylation –> Xist RNA –> DNA condensation into Barr body

111
Q

Inactivation occurs early in development and is fixed so that all daughter cells will be inactivated which results in _____________

A

mosaicism

112
Q

What are the two types of NON-random X-cell inactivation (results in NO mocaism)

A

1) structural abnormality in one X so that one is inactivated
2) balanced translocation between one X chromosome and an autosome, normal X is inactivated

113
Q

What is potentiation? (pharm)

A

Creation of toxic effect of one drug due to presence of another

114
Q

Loss of receptor function leads to ______ desensitization while decrease in receptor number leads to ______ and more _______ desensitization

A

RAPID, SLOW, LONG TERM

115
Q

Non-deleterious effects are called _____ while deleterious effects are called _____

A

side effects, toxic

116
Q

Types of drugs that operate via receptors (4)

A
  • ion channels
  • GPCRs
  • growth factor (hormone/peptide receptors)
  • steroid hormones
117
Q

More spare receptors leads to INCREASE in ED50 . True or false

A

False, leads to decrease, increase in efficacy

118
Q

Describe convergent signaling by andrenergic and cholingeric receptors in cardiac tissue

A
  • Andrenergic –> stimulate production of cAMP via Gs

- Cholinergic –> decrease in cAMP via Gi

119
Q

Describe action of competitive antagonist

A

binds to same binding site as agonist reversibly, does not affect efficacy but reduces potency (curve shifts to right and ED50 increases)

120
Q

Describe action of non-competitive antagonist

A

binds covalently to same site as agonist or a site distinct from agonist. Decreases efficacy (shifts curve to right and down)

121
Q

Define reverse agonist

A

Binds to same receptor as an agonist but induces a pharmacological response that is OPPOSITE

122
Q

Quantal Dose Responses are all or known and include what three factors?

A 
ED50 = median effective dose
LD50 = median lethal dose
TD50 = median toxic dose
123
Q

What is the therapeutic index in humans?

A

TD50/ED50

124
Q

Therapeutic window is generally the ratio between?

A

Minimum effective concentrations and minimum toxic concentration

125
Q

If a drug is equieffective what does this mean?

A

reaches same max

126
Q

Define PIC/NIC

A

Positive/Negative, Immediate/Future, Certain/Uncertain

127
Q

________ describes the removal of a negative outcome by certain behavior which reinforces that behavior

A

negative reinforcement

128
Q

_____ describes the removal of a desired behavior or stimulus after undesired behavior which decreases the undesired behavioral

A

negative punishent

129
Q

What are the stages of change?

A

Precontemplation, contemplation, preparation, action, maintenance

130
Q

DIfference between lapse and relapse?

A

lapse - minor setback (expected)

relapse - complete reversion to previous pattern or behavior

131
Q

Describe activation of Ras

A

1) Grb adaptor protein recognizes phosphorylated tyrosine on activated receptor via an SH2 domain
2) Sos (Ras-GEF) stimulates inactive Ras to replace GDP with GTP
3) Ras activated

B1 (18 decks)

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