CS&B - Clinical Correlations (I) Flashcards
1
Q
A deficiency of what enzyme will lead to types A and B Niemann-Pick disease?
A
Acid sphingomyelinase
2
Q
What substance builds up in Niemann-Pick disease types A and B?
This results in what type of cell?
A
Sphingomyelin;
foam cells
3
Q
In what organ systems are foam cells found in cases of Niemann-Pick disease?
A
The spleen, liver, and CNS
4
Q
What disease is characterized by acid sphingomyelinase defects and associated foam cell deposits in the CNS, spleen, and liver?
A
Niemann-Pick disease types A and B
5
Q
Cytokine-related overactivation of what enzyme may contribute to development of multiple sclerosis?
A
Acid sphingomyelinase
6
Q
Defects in acid sphingomyelinase lead to what disease?
Overactivation of acid sphingomyelinase may lead to what disease?
A
Niemann-Pick disease (types A and B);
multiple sclerosis
7
Q
What effect does excess sphingomyelin have on erythrocytes?
This is commonly seen in what disease?
A
Acanthocytosis;
abetalipoproteinemia
8
Q
What is a hematologic result of abetalipoproteinemia?
This is due to an excess of what lipid?
A
Acanthocytosis;
sphingomyelin
9
Q
How does abetalipoproteinemia appear on a peripheral smear?
This is due to a defect involving what substance?
A
Acanthocytosis;
sphingomyelin (on the RBC E-face)
10
Q
Cystic fibrosis involves transport of what ion into the mucus?
A
Chloride
11
Q
What are the three main organs affected by cystic fibrosis?
A
Lungs, pancreas, liver
12
Q
Absence of chloride movement in cystic fibrosis leads to what effect on the mucus?
A
Less H2O movement –> thick, dry mucus
13
Q
Cystic fibrosis results as a genetic mutation in which channel?
The gene for this channel is found on which chromosome?
A
The CFTR
(cystic fibrosis transmembrane regulator);
7
14
Q
A young child presents with progressive muscle weakness and new cardiac arrythmias. You suspect myotonic dystrophy.
What genetic results would confirm your suspicions?
A
CTG repeats
(in the DMPK gene on chromosome 19)
15
Q
A man presents with microcephaly, cognitive deficits, indistinct philtrum, epicanthal folds, a low nasal bridge, and a short nose.
What do you suspect?
What cellular mechanism caused the issue?
A
Fetal alcohol syndrome;
impaired lipid rafts and signaling proteins
16
Q
What effect does phalloidin (found in death cap mushrooms) have on cellular structures?
(What is the primary clinical presentation)
A
Stabilizes F-actin (prevents its degradation)
(acute, extreme hunger due to liver necrosis)
17
Q
Cytochalasins mess with microfilaments and cause what outcome?
A
Apoptosis
18
Q
Hereditary spherocytosis is caused by a deficiency of what protein(s)?
A
Spectrin, ankyrin, or band-3 proteins
19
Q
Primary ciliary dyskinesia (immotile cilia syndrome) is an autosomal recessive disease known by what other name and caused by a defect in the gene coding for what protein?
A
Kartagener’s syndrome;
axonemal dynein
20
Q
How does Kartagener’s syndrome present?
A
Chronic respiratory infections, situs inversus, infertility
21
Q
With what cytoskeletal element does colchicine interact? How?
With what cytoskeletal element do vincristine and vinblastine interact? How?
With what cytoskeletal element does paclitaxel interact? How?
A
Microtubules, inhibits polymerization;
microtubules, inhibits polymerization;
microtubules, inhibits depolymerization
22
Q
What stain would be most useful in diagnosing the most common type of primary brain tumor?
A
GFAP
(astrocytomas)
23
Q
A two-year-old female toddler presents with steady loss of cognitive ability. Her father notes that she seemed cognitively normal and met all her milestones up until she was 18 mo. of age. You notice her near constant hand wringing.
What is the likely diagnosis?
A
Rett syndrome
24
Q
What biochemical defect can lead to Rett’s syndrome?
A
Mutations in MECP2
(this HDAC-recruiting protein -MECP2- is no longer available upon histone methylation);
leading to inappropriate gene expression
(manifesting clinically as cognitive decline and persistent hand wringing)
25
Mutation in the *MECP2* gene has what effect?
What is this condition called?
A lack of MECP2 protein --\> inability to recruit HDAC --\> inability to condense DNA --\> excessive gene expression;
Rett's syndrome
26
How does Rett syndrome typically present in the clinic?
Cognitive decline
(after ~18 mo. of seemingly normal childhood development);
hand wringing
27
An embryo is missing one autosomal chromosome. What will the result be?
This is a lethal mutation
28
An embryo is missing one chromosome and is 45,XO. What will the result be?
Turner's syndrome
29
What are some clinical presentations of Turner's syndrome?
Webbed neck,
widely spaced nipples,
swollen hands and feet,
short stature,
widespread nevi
30
Are individuals with Turner's syndrome female or male?
Female
31
What is the most common human trisomy?
How does it present?
Trisomy 16;
it is lethal
*(fetal death in the first trimester)*
32
What is the most common birth defect?
How does it present?
Trisomy 21;
Down syndrome
33
What is unique about the 21st chromosome?
It is the smallest autosome
34
Do viable (non-lethal) trisomies usually happen in large or small autosomal chromosomes?
Small
35
Patau's syndrome is caused by what defect?
Trisomy 13
36
Edward's syndrome is caused by what defect?
Trisomy 18
37
Trisomy of what chromosome in particular leads to fetal death in the first trimester?
Trisomy 16
38
Trisomy 16 is incompatible with life and results in fetal death at what point?
The first trimester
39
The sphingomyelin affected in abetalipoproteinemia is found in which leaflet of the plasma membrane?
The E-face
40
Defects in occludins may result in severe neurological disorders do to disruption of what structure(s)?
The fetal blood-brain barrier (tight junctions disrupted)
41
Loss of expression of what protein can disrupt the zona adherens and lead to increased malignancy and invasiveness of a developing carcinoma?
E-cadherins
42
Autoimmunity against the protein desmoglein I can lead to skin disorders characterized by reduced intercellular cohesion of what in particular?
This is due to disruption of what epithelial cell junction?
Epidermal cells
Macula adherens (desmosome)
43
Mutations of what protein are related to types of epidermolysis bullosa (blistering skin lesions)?
This is due to disruption of what?
Keratins 5 and 14;
hemidesmosomes
44
Mutations in various connexin genes have been linked to what issues?
This is due to a defect in what type of cell junction?
Peripheral neuropathy and deafness
*(both in very specific situations, not just any PN and deafness);*
gap junctions
45
What pathogens act on proteins of the zona occludens to make cell junctions more permeable?
Cholera toxin;
CMV
46
Cholera toxins and CMV both act on what structure to increase permeability between cells?
The zona occludens
47
What disease is characterized by antibody attacks on proteins of the hemidesmosome?
What disease is characterized by antibody attacks on the desmosome (specifically desmoglein I and III)?
Bullous pemphigoid;
pemphigus vulgaris
48
Antibody attacks on what might cause bullous pemphigoid?
Hemidesmosome proteins
49
Antibody attacks on what might cause pemphigus vulgaris?
Proteins of the desmosome
| (e.g. desmoglein I and III)
50
# Define aneusomy.
What are the three types?
Aberrant number of chromosomes (due to loss or addition);
nullisomy, monosomy, trisomy
51
Define euploidy.
Correct number of chromosome pairs
52
What is the term if an embryo is missing both chromosomes of one chromosomal pair?
What is the term if an embryo is missing one chromosome of a chromosomal pair?
What is the term if an embryo has both chromosomes of one chromosomal pair?
What is the term if an embryo has an extra chromosome in addition to one chromosomal pair?
Nullisomy (-2);
monosomy (-1);
eusomy (-0; just right);
trisomy (+1);
53
What will happen to an embryo with nullisomy of any chromosomal pair?
Embryonic death
54
What will happen to an embryo with monosomy of any autosomal chromosome pair?
Embryonic death
55
What is the only survivable true monosomy?
Turner's syndrome
(any other survivable monosomy is only a partial deletion of a chromosome)
56
What is the term if an embryo has three entire, homologous sets of chromosomes?
What is the term if an embryo has four entire, homologous sets of chromosomes?
Triploidy;
tetraploidy
57
Which usually presents earlier in life, aneuploidy or chromatin remodeling abnormalities?
Aneuploidy
58
What is the typical treatment for Turner's syndrome?
To address what issues?
Hormonal therapy (GH and estrogen);
the slow growth and lack of sexual development
59
**True/false.**
Trisomies of the sex chromosomes (e.g. XXX, XXY, XYY) are all typically associated with only minor problems and a full life span.
True
60
Which type of autosomal trisomy is most likely to result in a viable fetus?
Those of small autosomes (e.g. 13, 18, 21)
61
What is the most common human trisomy?
How does it present?
Chromosome 16;
fetal death in the first trimester
62
Describe the typical clinical presentation of Rett syndrome.
Normal development during first **18 months** of life
Temporary **stagnation**
**Neurodegenerative**
Loss of **communication** skills
Constant **hand-wringing**
Loss of purposeful hand function
63
How does Rett syndrome present in males?
Embryonic death
64
Why is Rett syndrome extremely rare in viable males?
The MECP2 gene is on the X chromosome, so it is normally lethal in males (who only have one X chromosome)
65
The MECP2 gene is found on which chromosome?
The X chromosome
66
A tall patient with tapering fingers presents to the clinic with visual problems related to subluxation of the lens of his right eye. Three days later, he dies of a cardiovascular event.
## Footnote
**What disorder does the patient have, and what causes it?**
**Of what CV event did he likely die?**
Marfan's syndrome, fibrillin-1 defect (a scaffold for tropo-elastin);
aortic dissection
67
A teenager presents to the clinic with hyperextensible joints and skin. You notice in his history that he has been diagnosed with a murmur of one of his heart valves in the past. The patient appears well and normal for age.
## Footnote
**What is a likely diagnosis for this patient?**
**What protein is likely not being produced properly?**
Ehlers-Danlos syndrome;
collagen
68
In what layer of the skin are skin cancers most likely to originate?
The stratum basale of the epidermis
(e.g. basal cell carcinomas and melanomas)
69
A defect in the anchoring fibrils that connect the epidermis to the dermis can result in what condition involving blistering and skin erosion?
Epidermolysis bullosa
70
What are the two primary causes of albinism?
A defect/deficiency in **tyrosinase**;
a decreased **melanin** **production** rate
71
Why is the subcutaneous layer of tissue such a useful location for drug administration?
It is highly vascular
72
What is the term for the layers and sections of fat of the subcutaneous (hypodermic) layer?
What is the layer of striated muscle deep to the subcutaneous tissue?
The panniculus adiposus;
the panniculus carnasus
73
What substance binds keratin together to create the waterproofing of the skin?
Lack of this substance results in what?
Filaggrin;
ichthyosis
74
Filaggrin defect/deficiency leads to what immediate effect in the skin and what compensatory effect?
What is this condition called?
Dehydration/scaly skin, hyperkeratosis;
ichthyosis
75
What blistering condition results from defects in anchoring proteins (e.g. hemidesmosomes)
What blistering condition results as an autoimmune attack on desmosomes (specifically, desmoglein I and III)?
Epidermolysis bullosa;
pemphigus vulgaris
76
What disease is demonstrated here?
How is this disease classified?
Pemphigus vulgaris;
autoimmune (against desmoglein I, III)
77
What disease is demonstrated here?
How is this disease classified?
Epidermolysis bullosa;
genetic (hemidesmosome defect)
78
What disease is demonstrated here?
Psoriasis
79
What type of skin condition results in universally loose fragile skin? Due to a defect in what?
What type of skin condition results in universally impaired elastic recoil? Due to a defect in what?
Ehlers-Danlos, collagen fibers
cutis laxa, elastic fibers
80
Cutis laxa results because of a defect in what protein?
Ehlers-Danlos results because of a defect in what protein?
Elastic fibers;
collagen fibers
81
Cri-du-Chat syndrome is a microdeletion of the short arm of chromosome \_\_.
5
82
A carrier of a Robertsonian translocation has how many chromosomes?
45
83
What is another name for DiGeorge syndrome?
It is due to a deletion of what genetic sequence?
Velocardiofacial syndrome;
22q11
84
What rare type of skin cancer spreads quickly and deeper than BCC, SCC, and melanoma?
Merkel cell carcinomas
85
List the types of skin cancer from most to least common.
Basal cell carc. \> squamous cell carc. \>\> melanoma
\>\>\>\> anything else
86
What is the most common type of cancer worldwide?
Skin cancer
87
Genetic defect of hemidesmosomes causes:
Autoantibodies against hemidesmosomes causes:
Autoantibodies against desmosomes causes:
Epidermolysis bullosa;
bullous pemphigoid;
pemphigus vulgaris
88
Why is acne typically associated with adolescents?
Sebaceous gland activity increases in adolescence
89
Acne is caused by what?
Plugged hair follicles and their associated sebaceous glands
90
What wide-spectrum antibiotic is a bacterial topoisomerase inhibitor?
Ciprofloxacin
91
What is ciprofloxacin?
How does it exert its effect?
A wide-spectrum antibiotic;
inhibiting bacterial topoisomerase
92
What two eukaryotic topoisomerase inhibitors can be used to treat some colon and ovarian cancers?
Which topoisomerase do they inhibit?
Irinotecan and Topotecan;
type I
93
What are Irinotecan and Topotecan?
How do they exert their effect?
Chemotherapeutic agents;
type I topoisomerase inhibition
94
What are Doxorubicin (adriamycin), etoposide, and ellipticine?
How do they exert their effects?
Chemotherapeutic agents;
type II topoisomerase inhibitors
95
What wide-spectrum antibiotic is a bacterial topoisomerase inhibitor?
What are two chemotherapeutic agents that are type I topoisomerase inhibitors?
What are three chemotherapeutic agents that are type II topoisomerase inhibitors?
Ciprofloxacin;
Irinotecan, Topotecan;
Doxorubicin (adriamycin), etoposide, and ellipticine
96
By which types of UV ray are we most at-risk of being harmed?
Which UV ray is blocked by the ozone?
UVA, UVB;
UVC
97
What type of DNA mutation is often caused by UV rays?
Thymidine dimers
98
What is the underlying defect in xeroderma pigmentosum?
What is its inheiritance pattern?
A defect in nucleotide excision repair (to repair thymidine dimers, especially);
autosomal recessive
99
By what age have most individuals with xeroderma pigmentosum developed some sort of skin cancer (often squamous cell carcinoma)?
8
100
**True/False.**
Individuals with xeroderma pigmentosum typically live a normal lifespan.
False.
101
What is the most common cause of death among individuals with xeroderma pigmentosum?
Squamous cell carcinoma
102
In nucleotide excision repair, what enzyme typically removes the damaged section?
An endonuclease
103
In nucleotide excision repair, what enzyme typically refills the removed portion?
DNA polymerase
104
In nucleotide excision repair, what enzyme typically seals up the repaired DNA portion?
DNA ligase
105
Name three enzymes necessary to nucleotide excision repair.
Endonuclease, DNA polymerase, DNA ligase
106
**True/False.**
Squamous cell carcinoma is associated with mutations in the BRAF and RAS genes.
False (SCC is associated with P53 issues);
melanoma is associated with BRAF and RAS
107
Melanoma is associated with mutations in what two genes in particular?
BRAF and RAS
108
What two factors does HPV use to increase growth and potential neoplasia in cells?
What do these factors do?
E6, E7;
block tumor suppressors
109
What is the name for the disease where it appears that the patient's skin is turning into tree bark or elephant skin?
What is the underlying issue?
Epidermodysplasia verruciformis;
excessive, keratinized, HPV wart-like growths
110
How does squamous cell carcinoma usually present?
An **ulcerous, crusty, scaly** lesion on the head, neck, or dorsum of the hand
111
What are some risk factors for squamous cell carcinoma?
Caucasian, immunosuppressed, high sun exposure
112
Squamous cell carcinoma has an association with what infectious agent?
HPV
113
Describe the histology of squamous cell carcinoma.
Neoplastic cells with keratin pearls
114
How does basal cell carcinoma typically present?
Smooth, pink, pearly mass on the head, neck, or dorsum of the hand
(*especially* the nose, upper lip, and cheek)
115
Mutations in what two genes are associated with basal cell carcinomas?
What drug helps block the pathway related to these mutations?
PTCH1, PTCH2;
vismodegib
116
How does basal cell carcinoma present on histology?
Circular blue-purple masses
117
Melanoma is positive for what marker?
S100
118
What type of genetic pathway inhibitor is used in melanoma treatment?
BRAF inhibitors
119
What is a squamous cell carcinoma precursor lesion (not necessary for its development though)?
Actinic keratosis
120
_Cervical epithelial dysplasia_ is to _cervical cancer_
as
_actinic keratosis_ is to \_\_\_\_\_\_\_\_\_\_\_\_\_.
Squamous cell carcinoma
121
**True/False.**
All squamous cell carcinomas develop from actinic keratosis.
False.
122
What is Nikolsky's sign?
What does it indicate?
Epidermal sloughing due to manual stroking;
a very severe blistering disease
123
A patient with severe blisters and associated skin lesions presents to the clinic. You note that the superficial layer of her diseased skin sloughs off when your hand passes gently over it.
What is this sign called and what does it indicate?
Nikolsky's sign;
a severe blistering disease
124
What are the A and B of the ABCDEs of melanoma?
Asymmetry;
border irregularity
125
What are the C and D of the ABCDEs of melanoma?
Color;
diameter
126
What is the E of the ABCDEs of melanoma?
Evolution (change over time)
127
What is the most common type of melanoma?
Is it generally a better or worse prognosis than the others?
Superficial spreading melanoma;
better (relatively treatable)
128
Of the two more common subtypes of melanoma, which is the more aggressive and deadly?
Nodular melanoma
129
What is a slow-growing, in-situ melanoma most often found in the elderly?
Lentigo maligna
130
What very deadly form of melanoma is most often found in patients with darker skin tones?
Acral lentiginous
131
Epidermolysis bullosa simplex is caused by what underlying defect?
How does it typically present?
Defective keratins 5 and 14;
pediatric friction-induced blisters on hands and feet
132
Epidermolysis bullosa simplex affects what cellular junction?
It mostly affects what cell layer?
Hemidesmosomes;
the (epidermal) stratum basale
133
What autoimmune disorder affects hemidesmosomes of the stratum basale?
What congenital disorder affects hemidesmosomes of the stratum basale?
Bullous pemphigoid;
epidermolysis bullosa simplex
134
What autoimmune disorder affects desmosomes of the stratum spinosum?
What congenital disorder affects type VII collagen of the basement membrane?
Pemphigus vulgaris;
dystrophic epidermolysis bullosa
135
A three-year-old girl is brought to the clinic for examination of frequent blisters on her hands and feet.
What is the likely diagnosis and what causes this disorder?
Epidermolysis bullosa simplex;
**congenital** defect in **keratins 5 and 14** (of the hemidesmosomes of the stratum basale)
136
Epidermolysis bullosa simplex affects what layer of the epidermis?
The stratum basale
137
A 55-year-old patient presents with widespread, pruritic ulcers and skin erosions that affect the oral cavity, scalp, chest, and other portions of the body.
Immunofluorescene of a skin biopsy shows a net-like pattern in the stratum spinosum.
What is the diagnosis?
Pemphigus vulgaris
138
Pemphigus vulgaris affects what layer of the epidermis?
The stratum spinosum
139
Which typically presents with blisters, pemphigus vulgaris or bullous pemphigoid?
What antibody type causes both disorders?
Bullous pemphigoid;
IgG
140
Which epidermal layer is typically affected by bullous pemphigoid?
The stratum basale
141
How is pemphigus vulgaris treated?
This is to prevent suppression of autoantibodies against what structure(s)?
Steroids (e.g. prednisone);
desmoglein I and III
142
How does pemphigus vulgaris present on immunofluoresence?
How does bullous pemphigoid present on immunofluoresence?
Net-like pattern in the stratum spinosum;
linear pattern at dermoepidermal junction
143
Bullous pemphigoid is caused by autoantibodies against what two proteins?
This affects what type of cellular junction?
BPAG1, BPAG2;
hemidesmosomes
144
What is a congenital disorder resulting from defects in keratin 5 and 14?
What is an autoimmune disorder resulting from autoantibodies against desmoglein 1 and 3?
What is a congenital disorder resulting from defects in collagen VII?
What is an autoimmune disorder resulting from autoantibodies against BPAG1 and BPAG2?
Epidermolysis bullosa simplex;
pemphigus vulgaris;
dystrophic epidermolysis bullosa;
bullous pemphigoid
145
What is a congenital disorder of the epidermis resulting in hemidesmosomal dysfunction?
What is an autoimmune disorder of the epidermis resulting in desmosomal dysfunction?
What is a congenital disorder of the epidermis of the epidermis resulting in basement membrane dysfunction?
What is an autoimmune disorder of the epidermis resulting in hemidesmosomal dysfunction?
Epidermolysis bullosa simplex;
pemphigus vulgaris;
dystrophic epidermolysis bullosa;
bullous pemphigoid
146
What age range is typically affected by pemphigus vulgaris or bullous pemphigoid?
50s to 60s
147
What protein is affected in dystrophic epidermolysis bullosa?
This leads to what problem?
Collagen VII;
separation of the basal lamina and reticular lamina
148
**True/False.**
Dystrophic epidermolysis bullosa typically results in widespread ulceration, dehydration, infection, and even finger resoprtion. This constellation of issues typically results in early death.
True.
149
Epidermolysis bullosa simplex typically affects what layer of the skin?
Pemphigus vulgaris typically affects what layer of the skin?
Dystrophic epidermolysis bullosa typically affects what layer of the skin?
Bullous pemphigoid typically affects what layer of the skin?
The stratum basale (hemidesmosomes);
the stratum spinosum (desmosomes);
the basement membrane (type VII collagen);
the stratum basale (hemidesmosomes)
150
An 8-year-old girl is brought to see you in the clinic. Her parents show you a small lesion (1 cm diameter) with an ulcerous, scaly center. Upon skin examination, another such lesion is noticed on the back of the hand.
You notice that the patient's face is nearly covered in freckles.
What is the diagnosis of the lesions?
What is the larger diagnosis to be made?
Squamous cell carcinoma;
xeroderma pigmentosum (autosomal recessive)
151
Name the drug that is a thymine analog that blocks reverse transcriptase.
How does it accomplish this?
Zidovudine (AZT);
the 3'-hydroxyl is replaced with a nitrogenous compound
152
Name the drug that is a purine analog that blocks reverse transcriptase.
How does it accomplish this?
2',3'-dideoxyinosine;
the 3’-hydroxyl is replaced with hydrogen groups
153
Zidovudine (AZT) is an analog of what compound?
What enzyme does it block?
What types of disease is it used to treat?
Thymine;
reverse transcriptase;
retroviruses
154
2',3'-dideoxyinosine is an analog of what compound?
What enzyme does it block?
What types of disease is it used to treat?
Purines;
reverse transcriptase;
retroviruses
155
What specific portion of a nucleotide can be modified in order to halt DNA synthesis?
The 3'-hydroxyl
156
What drug is used to treat HSV?
What drug is used to treat CMV?
Acyclovir;
gancyclovir
157
What are acyclovir and gancyclovir?
What are they used to treat, respectively?
Guanosine analogs;
HSV, CMV
158
Will acyclovir and gancyclovir be phosphorylated in all human cells?
Why or why not?
No;
just infected cells (where viral kinase is present)
159
What drug is used to treat HSV?
What forms of HSV?
Acyclovir;
cold sores, varicella zoster, herpes zoster
160
What drug is used to treat CMV retinitis?
Gancyclovir
161
What disease is characterized by a mutation in the *MLH1 or MLH2* genes that begin mismatch excision repair by identifying mispairing?
Hereditary nonpolypoisis colorectal cancer
162
Hereditary nonpolypoisis colorectal cancer is commonly associated with a mutation in one of which two genes?
These genes are related to what normal cellular function?
*MLH1, MLH2;*
mismatch excision repair
163
What type of cancer is commonly linked to a defect in mismatch excision repair?
Hereditary nonpolypoisis colorectal cancer
164
Xeroderma pigmentosum is related to a defect in what normal cellular function?
This normal cellular function is responsible for what process?
Nucleotide excision repair;
fixing thymidine dimers
165
How can one remember that xeroderma pigmentosum is related to defects in nucleotide excision repair?
The proteins are named after xeroderma pigmentosum
(e.g. **XP**-C, **XP**-F, **XP**-G)
166
Besides squamous cell carcinoma and other skin malignancies, what may be some symptoms of xeroderma pigmentosum?
Progressive neurological complications, including loss of sight or hearing.
167
The lifespan of an individual with xeroderma pigmentosum is shortened by how long?
~30 years
168
Besides xeroderma pigmentosum, what is another disease related to defects in nucleotide excision repair?
What are the two main manifestations of this disorder?
Cockayne syndrome;
neurological defects and premature aging
169
Cockayne syndrome is associated with defects in what cellular system?
Cockayne syndrome is associated with mutations of what genes?
Nucleotide excision repair;
*ERCC6; ERCC8*
170
Name the enzyme responsible for each of the following in nucleotide excision repair:
- scanning and recognition of errors -
- helicase activity -
- endonucleases (2) -
XP-C
TFIIH
XP-F, XP-G
171
What form of Cockayne syndrome is associated with a mutation in ERCC8?
What form of Cockayne syndrome is associated with a mutation in ERCC6?
CS **A**
CS **B**
172
What does the WT1 (mutations associated with Wilm's tumor) gene do?
Repress oncogenic function
| (at the proximal promoter)
173
Where on the gene does the WT1 gene repress oncogenic activity?
The proximal promoter
174
Besides phalloidin, what other toxin is found in death cap mushrooms?
How does it exert its toxic effects?
Alpha-amanitin;
prevents RNA polymerase II binding
175
What effect does alpha-amanitin have on normal cellular processes?
How does this manifest?
Blocks RNA polymerase II;
liver damage --\> flu-like symptoms --\> coma --\> death
176
What two toxins do death cap mushrooms contain that stabilize F-actin and block RNA polymerase II, respectively?
Phalloidin;
alpha-amanitin
177
In HIV, viral cyclin T binds host CDK9. What is the effect?
Hyperphosphorylation of RNA polymerase II
178
What effect does HIV have on RNA polymerase II via hyperphosphorylation?
Overactivation
179
Where does the beta-thalassemia mutation occur?
The beta-globulin locus
180
Lupus tends to affect what part of the spliceosome?
This has what immediate effect?
snRNPs;
splicing does not occur, and hnRNA is not turned into mRNA
(hnRNA thus builds up in the nucleus)
181
What is *leukoencephalopathy with CNS hypomyelination and vanishing white matter (VWM)*?
Loss of cerebral white matter / oligodendrocytes following an acute fever
182
What defect causes *leukoencephalopathy with CNS hypomyelination and vanishing white matter (VWM)?*
Why do the neurological symptoms often appear following a fever?
A defect in eukaryotic intiation factor 2 (eIF2);
eIF2 plays a role in responding to cellular stress
(if it is defective, the response is dimished)
183
Besides assisting in formation of the preinitiation complex (PIC) for translation, what else does eukaryotic initiation factor 2 do?
How?
Responds to cellular stress (e.g. heat);
stalls translation during times of heat so that denatured proteins don't build up and accumulate
184
What is a eukaryotic initation factor (eIF) that is involved in translation and also cellular responses to high temperatures?
*(Note: this protein stalls translation during times of high heat in order to prevent accumulation/aggregation of denatured proteins)*
eIF2
185
What is it called when amyloid (not always amyloid though!) protein misfolds and aggregates/accumulates within cells?
What shape are the proteins in when aggregated?
Amyloidosis (not always amyloid!);
beta-sheets
186
Misfolding of what protein is associated with type II diabetes?
What is the effect?
Amylin;
beta-cell apoptosis
187
What is an infectious amyloidosis involving misfolded proteins?
What protein is involved?
Prion disease
PrPc
188
Alzheimer's disease is associated with beta-amyloid plaques that are accumulations of what protein?
Amyloid precursor protein
189
Misfolding of what protein is associated with Huntington's disease?
What are the repeats in the involved gene?
HTT protein;
CAG
190
Misfolding of what protein is associated with Parkinson's disease?
What are the associated aggregates called?
Alpha-synuclein;
Lewy bodies
191
Misfolding of what protein is associated with ALS?
Superoxide dismutase (SOD1)
192
Misfolding of what protein is associated with spinal cerebellar ataxia?
What are the repeats in the involved gene?
Ataxin;
CAG
193
Misfolding of amylin and associated amyloidosis is associated with what disease?
Type II diabetes
194
Misfolding of amyloid precursor protein and associated amyloidosis is associated with what disease?
Alzheimer's disease
195
The PrPc protein and associated amyloidosis is associated with what disease?
Prion diseases (e.g. CJD)
196
Misfolding of the HTT protein and associated amyloidosis is associated with what disease?
Huntington's disease
197
Misfolding of alpha-synuclein and associated amyloidosis is associated with what disease?
Parkinson's disease
| (I think, also Lewy body dementia)
198
Misfolding of the superoxidase dismutase (SOD1) protein and associated amyloidosis is associated with what disease?
Amyotrophic lateral sclerosis
199
Misfolding of ataxin and associated amyloidosis is associated with what disease?
Spinal cerebellar ataxia
200
What effect does phalloidin (found in death cap mushrooms) have on cells?
What effect does alpha-amanitin (found in death cap mushrooms) have on cells?
F-actin stabilization;
RNA polymerase II inhibition
