CIS plus other small details Flashcards
1
Q
What is Acute Chest Syndrome Indicated By?
What Symptoms?
A
New pulmonary infiltrate on Chest X ray
-Fever, Chest Pain, Hypoxemia, Wheezing, Cough, Respiratory Distresss
2
Q
What is Acute Chest Syndrome?
A
Infection( w/ new infiltrates in the lungs on the CXR)
- Mycoplasma
- Streptococcus Pneumioniae
Infection due to Thrombosis
embolic phenomena due to fat embolism 20 bone marrow infarction
second most common cause of hospitalization in KIDS
3
Q
Splenic Sequestration Crisis?
A
- vaso-occulsion in the spleen secondary to sickle cells
- splenic pooling of Red cells (marked fall in hemoglobin)
- elevated reticulocyte count
- rapidly enlarging spleen
- Hypovolemic shock
4
Q
Autosplenectomy makes children susceptible to which encapsulated organism?
A
- streptococcus pneumoniae
- Neesieria meningitdis
- Klebsiella pnemondia
- Influenzae
- Salmonella typhi
- Cryptococcus neoformans
- pseudomonas aerugionosa
5
Q
Name the beta globin AA substitution and chromosome involved in sickle cell disease?
A
Glu–> Val
Point, missense mutation
Chromosome 11
6
Q
Which AA residues on Histone protein tails are the targets of PTMs?
Phosphorylation is the exception?
A
Lysine and Arginine
Serine and threonine
7
Q
Nucleosome?
Protein + DNA = ?
A
8 histone proteins (octamer)
Chromatin
8
Q
CGH array
A
comparative genome hybridization
copy # varation
compare to “normal” reference
9
Q
Histone Deacetylation
A
Represses gene expression
-compact and repressed (beads tight on string)
10
Q
Histone Acetylation
A
Open and transcriptionally active (beads are wound loosely on strings cause Acetylgroups unwind em)
11
Q
DNA methylation on which nucleotides?
what effect does it have and what areas are targeted?
can it be passed on to daughter cells?
A
Cytosine and Adenine
Represses Gene (silencing) transcription when it is at promoter region (CpG islands)
Yes, ex) gene imprinting and epigentics
12
Q
Topoisomerase inhibitor names?
what effects as anti cancer agents?
A
Irinotencan (Type 1 topo)
Etoposide & anthrocyclines (type 2 topo)
block the cell cycle, generate single and double stranded breaks, harm the integrity of the genome which leads to apoptosis and cancer cell death.
13
Q
Ionizing radiation (uranium) can cause
A
- strand breaks
- DNA-protein cross-links (e.g., thymine-tyrosine cross-link).
14
Q
Non-ionizing radiation (UV) causes
A
pyrimidine cyclobutane dimers (corrected by photolyase)
15
Q
what is depurination?
WHat is deanimation?
A
base is broken from the sugar phosphate
where C is changed to U. A to HypoX. G to X
16
Q
Methylation gone wrong? What enzyme must fix (inefficient)
A
- Deamination of methyl-C produces T which is now mismatched with G
- glycolsyalse
17
Q
Cross linking agents (DNA damge)
A
Nitrogen mustard, cisplatin, mitomycin C,
Carmustine
18
Q
alkylating agents
A
Dimethyl sulfate (DMS) and MMS
19
Q
Intercalating agents
A
Thalidomide
20
Q
BRCA2/breast cancer
DNA repair pathway?
A
Repaired by homologous recombination
21
Q
Xeroderma Pigmentosum
DNA repair pathway?
A
- skin cancer, UV sensitivity
- Mismatch repair
22
Q
Cockayne Syndrome
DNA repair pathway?
A
Transcription coupled repair( normally RNA poly stalls ast lesions and directs repair machinery there)
disease: RNA poly is permenantly stalled at sites of damage
23
Q
MSH2, MSH6, HNPCC
DNA repair pathway?
A
Mistmatch repair
-colon cancer
24
Q
HDAC keeps genes repressed
what are some ant cancer drugs that affect this?
A
Valproic acid, varinostat
25
Inhibitors of HAT are showing promise in treatment of several diseases? why
HATS activate Genes so the mechanism is probably to inhbit thtis and to keep the genes repressed?
26
What is the one thing Staudinger kept saying about PTMS (phosphorylation, acetylation. ubiquination, SUMOylation, methylation?
All PTMS talk to each other and work together
they do not work in a vaccum(alone)
27
How are Antibiotics generally used?
They target prokaryotic translational machinery
28
Streptomycin
binds to small 30s to disrupt INITITATION
29
Tetracycline
binds to small 30s subunit to disrupt ELONGATION
30
Clindamycin and Erythromycin(pertussis reatment)
bind to the large 50s subunit to, bloacking translocation of the ribosome
31
Chloramphenicol
inhibits peptidyl transferase(ELONGATION), prok and mitochondria
32
Cycloheximide
inhibits peptidyl transferase in eukaryotes
33
Ricin and Shiga toxin
binds to 60S subunit blocking entry of aminoacyl-tRNA to ribosomal complex.
34
Diphtheria toxin
inactivates EF2-GTP and inhibits elongation.
35
Puromycin
ELongation inhibitor in both euk and prok
premature chain relase
36
Cytoplasmic Pathway
What is needed to go to each of these destinations?
Cytosol(no sequence)
mitochondria(N-terminal hydrophobic alpha-helix)(TIM AND TOM)
Nucleus( nuclear localization signals: 4 continuous basic AA residues (arg and lys) (Nuclear Pore)
peroxisome(SKL sequence)
-translation on free ribosome in cytosol
37
Secretory Pathway
whats needed in first 20 AA to go to this pathway?
what is needed to go to each of these destinations?
- ER targeting sequence to go this pathway((1-2 basic positively charged near N-terminal; Hydrophobic (10-15 AA near C terminus)
Plasma membrane(Stop Transfer Sequence)
excretion from cell (Tryptophan rich domain)
,
ER( ER retention signal--> KDEL)
lysosome(Mannose 6P)
Translation paused on free ribosomes and Signal recognition particle brings ribosome-mrna-peptide complex to ER
38
I-Cell disease
Lyosomal proteins do not make it lysosome because mannose 6p target sequence is defective
- high plasma levels of lysosome enzymes
- failure to thrive
39
Acetylation attaches to what group? and what residue is affected?
NH3 (amine) and Lysine
Acetyl coA is donor
40
Glycosylation attaches what group? and what residue is affected
happens in ER lumen
-OH(hydroxyl) or N
Ser or Threonine groups
N or O glyc link
41
Phosporylation attaches what group? and what residue is affected
Ser or Thr or Tyrosine kinase
| -OH
42
Collagen needs what to be fully functional? and what Vitamin helps with that?
Vitamin C scurvy
lysyl hydroxylase
43
Alzheimer’s disease (β-amyloid): amyloid β
Alzheimer’s disease (β-amyloid): Misfolding/aggregation of Aβ forms plaques in extracellular brain.
Hyperphosphorylation of Tau causes neurofibrillary tangles intracellularly. Can have familial or sporadic forms
44
Parkinson’s disease (α-synuclein (AS)):
Aggregation of AS proteins deposit as Lewy bodies in dopaminergic neurons in substantia nigra. This causes a reduced availability to dopamine. Both familial and sporadic forms.
45
Huntington’s disease (poly-glutamine(CAG) repeat diseases):
Mutation in Huntingtin gene results in expansion of CAG triplet repeats → Polyglutamine repeats in abnormal HTT protein. Selective death of cells in basal ganglia cause the symptoms.
46
Creutzfeldt-Jakob/Kuru/Mad Cow disease (prion proteins):
Misfolded prion proteins. Transmissible (can convert normal proteins to misfolded form), thus belongs to TSE family of diseases
spongy brain.
47
• Summarize the different types of signaling
o Endocrine: Hormone signaling through the blood. Example is epinephrine
o Paracrine: signal diffuses to a neighboring target cell of a different cell type. E.g. testosterone.
o Autocrine: Secrete a signaling molecule which signals themselves. E.g. interleukin-1
o Juxtacrine: Signaling molecule binds to itself, which then bind to a receptor on a target cell. E.g. heparin
48
• Summarize the types of signaling molecules and their receptors
o Lipophilic: Can pass through the plasma membrane. Once bound to intracellular receptors, they act as transcription factors.
---- Hydrophilic: Cannot penetrate the plasma membrane. They have to interact with cell surface receptors ex( GPCR, RTK)
49
What are the viral, his risk strains of HPV?
16 and 18
50
HPV protein E6 inhibits which protein in cell cycle?
p53, E6 has a super high affinity for p53
- p53 pauses cell cycle, so without it == bad
51
HPV protein E7 inhibits which protein in cell cycle?
Rb, E7 has a super high affinity for Rb
Rb, sequesters E2F, which helps stop cell cycle. With Rb gone, E2F constantly expressed
52
Southern Blot is?
North Blot is?
Western Blot is?
DNA-DNA
DNA-RNA
Protein or antibody measurmenet
53
PCR advantages
Disadvantages?
Adv:-very small amount of DNA template needed, 10^9 fold amplification from trade
Disadv: Need to know the sequence of the flanking DNA for primer design, error prone, amplification of contaminating DNA
54
qPCR or real time pcr
This is used to quantify copy number of a specific gene in two or more samples in real time. This technique also uses a probe which fluoresces only in the presence of a PCR product. This is used to detect levels of an infectious agent, or determine levels of gene expression.
cell cycle number n
X^N power
55
Norman Human Insulin has Proline at what position, terminus and which chain?
Has Lysine at what?
Lispros reversal of these AA positions resulted in what?
Insulin Aspart had the same results as Lispros, but what was change about the original sequence?
28, C Terminus, B chain
29, C terminus, B chain
Insulin that was faster absorbed
Proline at 28 taken out and aspartic acid put in
56
ELISA looking for what?
Indirect Elisa measures what? what is method?ex?
Sandwhich measures what? what is method? ex?
levels of specific antigen or antibody
IE: target is to measure amount of ANTIBODY. Antigen first, antibody of interest, then antibody w/ enzyme attached
ex) diagnosing HIV,
SE: goal is to measure amount of ANTIGEN. Antibody first, then antigen of interest, then antibody w enzyme attached(sandwhich)
ex) Myocardioal Infarction(troponin levels)
ex) pregnancy test
57
Western Blotting
detect levels of a target PROTEIN(ex) HIV antigen)
```
SDS page(e field and size)
same mechanism as Indirect Elisa
```
Protein(antigen) first, then primary antibody then secondary with enzyme tag
if patient no HIV infection then nothing on the western blot(using your blood check if antibody there)
ex) confirmation of HIV
58
Rifampicin is a inhibitor of what?
inhibitor of mRNA synthesis (transcription)
59
Robertsonian Translocation
Can lead to what?
Long arms of two acrocentric(very short arm on oneside) chromosomes combined and short arms lost.
can lead to a heritable type of down syndrome
60
Labile cells
Stable cells
Permanent cells
never enter G0 and are constantly dividing to replace cell populations that are continuously lost
those that retain the ability to exit G0 and enter G1 when stimulated by growth factors
Permanent cells stuck in G0
61
Chronic Myelogenous Leukemia
Translocation of chromosome 9 and 22 (genes BCR and ABL together now)
Philadelphia chromosome(BCR-ABL)
Reciprocal translocation
62
Turner Syndrome
```
45XO
short
female
infertile, low hairline,
normal intellgience
```
63
Klinefelter syndrome
47XXY
- male
- varying degrees of cognitive problems
- small testes
- tall
- infertile,
- can have even more than just two X chromosomes
64
Trisonomy 21 Downs sydnrome
- occur via nondisJ or robersonian transloc t(14,21)
- most common because most stable to survive
- increased risk with maternal age
65
Genomic Imprinting
is essentially Gene silencing
- through methylation of 5' region of gene
- chromatin condensation
- epigenetic imprints remain at life times
- in germ cells, epigenetics arereset at each generation during meiosis
66
How many genes are paternally imprinted?
Maternally?
30 genes paternally imprinted( silenced), maternally expressed
70 Genes maternally imprinted(silenced), paternally expressed
67
Prader Wili Syndrome Deletion in what chromosome # and in what chromosome maternal or Paternal?
chromosome 15
Paternal chromosome deletion
-short, hypotomia, obese,
68
Angelman Syndrome
chromosome 15
maternal deletion
Severe intellectual disability
69
True or False: Individuals with distinct genotypes can have single phenotype
True
70
Pleiotropy
individuals with the same genotype can have multiple phenotypes
-environment effects
71
X linked recessive disease
Duchene
72
X linked dominant disease
Hypopospatemia
73
Autosomal dom disease
Polydactyl
74
autosomal recessive disease
albinism
75
Penetrance
% the gene manifests itself if you have it
ex) retinoblastoma
76
Locus Heterogeneity
SIngle disorder, trait, cause dby mutations in genes at different chromosomal loci
77
Hrady-weinberg
Not easy to find genotype (not like co dominance)
- making algorithm based on if we we only know the amount of alleles in the population
assume random mating
78
Mitochondrial (mtDNA)
- circular
- dsDNA
- transcription indep of nucleus
- no introns
- INHERITED Exclusively through MATERNAL line
- only daughters pass on to all kids
79
Multifactorial inheritance
- environment factors cause variation
- combined effects of multiple genes are (POLGYGENIC)
- follow bell shape curve
80
Multifactorial inheritance: liability distribution
Need to pass a threshold of liability to be considered expressing the disease
- below threshold normal, above effected Ex(3/5 genes defected you are effected but 2/5 not)
- threshold higher in female, but can be passed on easier to male kids too
81
G1 Phase what is needed?
lot of growth and protein production
82
Where are the checkpoints in Cell cycle?
Restriction point?
G1, G2, Metaphase
R point is before G1 check point
83
What is the restricting factor in G1 restriction point?
Growth factors are limited(2 hours before S phase)
-after pass R point its GF independent
84
G1 check point checks for?
DNA damage around same time as R point. Must fix errors
85
G2 check point checks for?
Verifying complete genomic duplication, and no errors
86
Metaphase check point?
Ensure chromosome attached to mitotic spindle
87
Myc (from the MAPK, pathway) is a transcription factor that does what?
- Increases levels of CDK
- CDK (w cyclin(partially active) and 1 phosphate group (fully active) phoshphorylates Rb
- inactivates it and it releases E2F
88
What does Rb do?
what does E2F do?
How is G1 check point bypassed?
-sequesters E2F(in active form)
- E2F is transcription factor that drives cell from G1 to S b
- it does this by increasing the gene for making G1 cyclins(Cyclin E) and S phase cyclin (Cyclin A)
- both stimulate CDK even more making Rb even more hyperphosphorylated and inactive. This drives Cell into S phase where Cyclin A is used
89
Cyclin Dependent Kinase(CDK)
How is CDK partially and full active?
- are inactive without cyclin
- Cyclin-CDK complex drives phosphoration of specific substrates
- Cyclin-CDK comples only partially active
-to be fully active needs CDK-activating Kinase( CAK) to phosphorylate the T loop(cave site)
(opening up active site fully)
90
Inhibitors of CDK? How they work?
P27(CKI protein)--> inactivates Cyclin-CDK-P complex by binding to it. making a p27-cyclin-CDK-P complex
P27 in G1 to S transition
Wee1 Kinase--> phosphorylates the roof site of Cyclin-CDK complex (2 phosphates)
91
Cyclin D what phase and point?
Resctrition point
G1
CDK 4 and 6
92
Cyclin E what phase and point?
Cyclin A?
B?
G1/S
G1 checkpoint
S phase and Mitosis
Mitosis
93
Anaphase promoting complex( APC/C) or cyclosome
how does it work?
- Ubiquitin Ligase Family member
- APC/C activated by binding to CDC20(activating subunit)
- active form poly-ubiquinates its substrate (S and M cyclin complexes)
- cyclins degraded by proteasome
- absence of Cyclins inactivates CDKs
- Repression of Cell cycle
94
What keeps p53 inactive/degraded?
MDM2!! an E3 ubiquitin ligase that always tags it for proteasome degradation in inactive/quiescent cells
-
95
p53(guardian of genome) is a transcription factor, how is it activated what does it do?
- activated by DNA damage(PK) (not broken down)
- p53 is stabilized/activated by phosphorylation
- activation of P53 leads to increase in transcription p21(CKI) and causes cell cycle arrest
96
p21
is a CKI that binds to cyclin-CDK2 complexes causing them to be inactive
- this means no phosphorylation of Rb
- which means Rb is active and sequesters E2F and pauses cell cycle
97
Caspases
- -inactive precursor (zymogen)
- need proteolytic cleavage
- when cleaved form heterodimer
98
Initiator Caspases?
| Executioner Caspase?
Caspase 8 and 9 are initiators of the caspase
cascade
- Caspase 3 is executioner (destroys target-- this is apoptosis)
99
BCL-2 are anti or pro apoptotic?
BCL2 family are anti-apoptotic
100
Intrinsic Apoptosis
what protein is mainly involved?
what is released that activates the rest of the cascade?
- DNA damage stimuli
- inactive BAX proteins in mitochondrial membrane aggregate in response to signal
- Cytochrome C
101
Cytochrome C release from mitochondria activates what protein?
what is formed? and what does this product activate?
APAF1 combined with cytochrome C and makes an Apoptosome( many ATP used)
Apoptosome cleaves procaspase 9 which becomes caspase 9
102
Caspase 8 from which pathway?
Caspase 9 from which pathway?
at what point do they become one pathway? whats the final step that's in common?
8--> extrinsic
9--> intrinsic
both of them cleave procaspases 3, 6, 7
to become caspase 3 which is an executioner that executes apoptosis
103
Gain of function mutation?
what are some proto oncogenes?
- point mutation, deletion, gene amplication, or translocation
- increased expression of protein products
- expression of altered protein (oncoprotein) that does not respond to normal signals
- GFs and TFs and there receptors
- signal transducers
104
HER2 receptor(RTK) could become and oncogene from two different ways what are they?
- Simple Gene amplification
| - Point mutation from valine to Glutamine
105
HER2 point mutation what is changed? and what is the new name of this oncogene?
Valine to Gln
- NEU
its always active cause always dimerized even without ligand
106
Tumor Supressor Genes
- Repress cell cycle Progression
- promote apoptosis
- couple DNA damge to cell cycle
- DNA repair proteins (BRCA)
ex) P53, Rb
107
Loss of function in tumor repressor genes
- have to lose both copies
108
Hall marks of Cell cancer
1. self sufficiency in growth
2. Evading growth repressors
3. activating invasion and metastasis
4. enabiling replicative immortality
5. Inducible angiogenesis
6. Resisting Cell death
1. deregulating cellur energetics
2. avoding immune desctruction
3. tumor-promoting inflammation
4. Genome instability/mutation
109
Herceptin is an anti cancer inhibitor of what?
what type of cancer
HER 2 and its oncogene counter part NEU
Breast cancer
110
Gleevec anticancer agent that inhibits?
treatment in what?
BCR-ABL fusion protein
treatment in
Chronic myelogenous leukemia
111
viral oncogenesis
Viral genome injects its DNA into a healthy cell and the viral DNA is taken up near a proto-oncogene. The virus then hijacks the cell and transcribes the viral genome. Since there is little error correcting in transcription, the proto-oncogene mutates into an oncogene.
112
alkylating agents
block dna rep
113
cytoxic agents
intercalate to inhibit DNA synth
114
Antimetabolites
inhibit enzymes of DNA synth
115
Albumin does what
Source of major colloid osmotic pressure ( on vessel walls)
| -carrier proteins
116
Hereditary spherocytosis
Ad mutation
- affects ankyrin complex (band 3 and 4.2)
- leads to detachment of membrane and peel off
- makes spherical RBCs
117
Hereditary elliptocytosis
AD mutation
- Spectrin-spectrin bonds and band 4.1
- membrane fails to rebound and progressively elongates
- ellpitcal RBC
118
Neutrophils
- multilobed
- acute inflammation and tissue injury
- secrete enzymes
- Puss?
- bind to foreign bacteria
119
Eosnophils
- bi lobed
- pink
- histaminASE (NOT ACTUAL HISTAMINE THATS BASOPHIL)
- remove antigen-antibody complex
- attack PARASITES
120
Basophil
- very visible granules hard to see nucleus
- Purple
- anaphalaxis
- realse HISTAMINE
- vasoactivators??
121
Lymphocytes
- Big nucleus covering all of cell
- These are the main functional cells of the immune system
- not terminally differentiate(will make T and B lymphocytes)
122
Monocytes
- heart, kidney shape nucleus
- small granules
- phagocytic system
- macrophages of connective tissue,
- can leave blood supply
123
o T cells
differentiate in the thymus; long life span and are involved in cell-mediated immunity.
124
o B cells
Form and differentiate in the bone marrow; transform into plasma cells → secrete Antibodies
125
o Diapedesis
when neutrophils leave the circulation and migrate to their site of action in tissues. This is controlled by cell adhesion molecules that interact with ligands on endothelial cells. They can be further directed to injury site via chemotaxis.
126
Thrombocytes(platelets)
Thrombocytosis
- hemostasis- control of bleeding
- Platelets release serotonin which is a potent vasoconstrictor causing smooth muscle contraction in order to reduce blood flow at injury site
- they release ADP and thromboxane A2 which increase aggregation of platelets to form the primary hemostatic plug
-These platelets provide a surface for conversion of soluble fibrinogen → fibrin, causing fibrin to form a mesh over the initial plug entrapping platelets. This is causing the formation of the secondary hemostatic plug.
127
Nuclear Lamina made from?
Intermediate filaments
128
Progeria disease
- messed up nuclear lamina
129
Taxol
- binds at stabilizes Microtubules
- prevents depolymerization
- beneficial in cancer to stop mitosis
130
Colcine,colcemid
Vinblastine, vincristine
binds the tubulin DIMERS and prevents there poly
131
Actin Filaments (F- actin aka filamentous actin)
- made up of G-actin monomer(twisted together)
| - all cell types, unstable , essential for movment
132
Phalloidin (toxic mushrrom)
Binds and stabilizes actin FILAMENTS( F-actin) not monomors
-prevent depolymerization
133
Cytochalasin
Latrunculin
C: caps filament plus ends(no depoly)
L: binds actin monomers preventing poly
134
Collagen is the main structural protein in?
- extra cellular matrix and ECM/connective tissue
135
Collage formation?
- heterotrimer
- triple helix formation is done in the ER lumen by hydroxylation and glycosylation
- comes out to ECM via vesicle as ProCollagen
- it is then cleaved and self assembly into fibrils and then fibers
136
Scurvy
what enzyme?
what vitamin?
- Strength of Collagen is lost
- Prolyl Hydroxylase cofactor is Ascorbate( Vit C)
- wounds reopen, loss of teeth, pale skin
137
Anchoring Junction
Junctions from cell-cell, cell-BM, or cell-ECM. Important to recognize that it is interacting with cytoskeletal filaments.
138
Occluding Junction
Help maintain cell polarity and prevent movement from things between cells or out of cells.
139
Channel forming Junction
Allows for the movement of cellular components between cells.
140
Signal relaying junction
Example is a neuronal junction.
141
Cadherins
Ca2+ dep
- important in junction formation b/n cells
- Homophilic interaction
- interacts with cytoskeleton (actin)
142
E cadherin stands for?
N Cadherin stands for?
classical or atypical?
Epithelial cadherin
Neural Cadherin
Classical (type 1)
143
VE cadherin stands for?
LI cadherin
classical or atypical?
Vascular-ENDOthelial
Liver- Intestine
atypical
144
EMT in transitional bladder cancer? what results in increase metatstic potential?
E-cadherin way down
| N cadherine way up
145
Ig super family
- immune cell interaction
- hetero or homophilic
- involved in recognition, binding or adhesion
- calcium dep
146
Selectins
- calc dep
- binds to EC carbohydrates
- important role in host defense mechanism
- increased during inflammatory response
- WBC markers are ligands for selectin
- Low-affinity of selectins for leukocyte allow "ROLLING" slowing down of leuk cyte
147
Integrin
- couple EC to cytoskeleton
- can activate signaling pathways
- cell cell interactions via B2 FAMILY!!! integrins on leukocytes allow for adhesion and diapedesis
- higher affinity for ligands then selectin causes WBC to STOP!
148
Stem cell basic characteristics
not terminally differentiated, can divide without limit (due to telomerase), undergo slow division.
149
Cord blood is what type of potency?
multipotent
Hemopoietic
stem cells
150
Founder stem cells
cells capable of clonally dividing and giving rise to a large number of cells. Each tissue is given a fixed number of founder cell populations. They are programmed to have a fixed number of divisions. These cells define the size of large final structures.
151
Transit amplifying cell
These are not stem cells. These cells divide frequently, and transit from a cell with stem cell characteristics to a differentiated cell. These leave the basal layer and incorporate into the layers above. They are finite (programmed to only have a limited number of divisions). These cells are committed.
152
o Multipotent
o Pluripotent:
o Totipotent
: ability to give rise to different cell types of a given lineage (e.g. adult stem cells).
Ability to give rise to all cells of an embryo and subsequently, adult tissues (e.g. embryonic stem cells).
: Ability to give rise to all cells of an organism, including embryonic and extraembryonic tissues (e.g. a zygote is totipotent).
153
Pluripotent cell TFs
GFs
Induced pluripotent stem cells(iPS)
-Nanog, Oct4, Sox2, FoxD3
-Cripto, GDF3
could be a common molecular blue print of gene expression in pluripotent cells
If you could get these Tfs to be active in humans adult stem cells
you can exhibit ES cell like properties (pluripotency)
--VERY HIGH POTENTIAL FOR terAtoMA
154
Adult stem cells
- respond to growth and repair
- found in tissues
- strictly imposed molecular restraint on genes
155
Mesenchymal stem cells : found in ? and form what?
Bone marrow
connective tissues,
156
Somatic cell nuclear transfer
- somatic cell fusion with egg cell(must remove egg cell nucleus first)
- extract inner cell mass of blastocyte
and culture pluripotent cell
- very unethical(clones)
- DOLLY THE LAMB
- very inefficient( need 100s of oocytes)
- less teratoma potential
157
Erythropoeisis stages?
Hemocytoblast--> proerythroblast--> early erythroblast--> late erythrblast-->Normoblast--> reticulocyte--> RBC
158
All chains of hemoglobin derived from what two chromosomes?
16 and 11
159
Hydroxyurea
used to induce HbF, in hobes to cure sickle cell disease.Since HbF uses gamma chain instead of Beta chain (beta is the problem)
-toxic
160
HbF doesn't bind well to 2.3BPG therefore
has highher affinity for oxygen
161
Normal body iron?
Heriditary Hemochromatosis?
3-5g
15g
162
Hepcidin activation
Transferrin receptor releases Hfe when Transferin comes in/
- Hfe goes to TfR2 where it is internalized and stimulates Hepcidin production
163
What does Hepcidin do?
-it binds ferroporin and causes internalization of it.
ferro porin then destroyed by proteolysis
LOWERS iron absorption when [Iron} is HIGH
164
Folic Acid is absorbed in what part of intestine?
How much folic acid does liver store? and how long last?
Jejunum
5-10 mg, 3-6 months
165
Once folic acid absorbed by intestine it is reduced to its methyl THF form(primary form circulating in blood). why is this a problem and what u need to fix?
Cant convert toanything else
Folate trap
Need b12 cobalamin
166
B12 absorption
- dietary b12 binds to R binder (stomach)
- Intrinsic factor made by parietal cells
- proteases(pancreas) degrade R-binder
- Intrinsic factor binds to Cobalamin in duodenum and carries it to the ileum where the receptors bring it into the blood(receptor mediated endocytosis of IF-cobalamin)
167
Cobalamin travels through blood as what form
Transcobolamin
168
Pernicious Anemia
-megaloblastic macrocytic anemia from lack of intrinsic factor (needed for absoroption)
169
What is to find out the cause of B12 deficiency?
Schilling Test part one:
if labeled cobalamin not present in urine than (pernicious anemia) gotta do part two
Should see cobalamin in urine regularlry
170
Schilling Test part 2
(
again need oral dose of labeled B12 this time add Intrinsic factor
- if radioactive b12 present in urine then lack of intrinsic factor is reason for pernicious anemia
171
Biosynthesis of Heme in?
liver and erythroid cells
172
Heme Degradation
Retiuculo endothelial
173
Porphyria cutanea Tarda (PCT)
- uroPorhyrinogen decarboxylase
both hepatic and erythropoietic
174
Acute intermittent Poryphyria
PBG deaminase
hepatic
-4 rings put togehter
175
Congenital Erythropoetic poryhyria
Uropporghyingen 3 cosynthase
build up of uropor 1
- red teeth, red urine, skin photosensitivity
176
Variegate poryhria
Celebrity
King George 3
uro p 9 oxidade
