CELL BIOLOGY: BOARDS AND BEYOND Flashcards
(296 cards)
1
Q
What are telomeres?
A
Telomeres are nucleotide sequences located at the ends of chromosomes that protect them from deterioration or fusion with neighboring chromosomes.
2
Q
What is the role of telomerase in cellular division?
A
Telomerase prevents the loss of telomeres, thus preventing the shortening of chromosomes with each cycle of DNA replication. It is especially important for rapidly dividing cells.
3
Q
Why is telomerase particularly important for rapidly dividing cells?
A
Rapidly dividing cells are at risk of losing telomeres during cellular division, which can lead to chromosome shortening and potential genomic instability. Telomerase helps maintain telomere length in these cells.
4
Q
How do cardiac myocytes relate to telomerase activity?
A
Cardiac myocytes are permanent cells that do not undergo cell division; therefore, they would not be affected by medications that inhibit telomerase.
5
Q
What is polymyositis?
A
Polymyositis is an autoimmune inflammatory muscle disorder characterized by proximal muscle weakness, often affecting women aged 40 to 50 years
6
Q
What are classic presenting symptoms of polymyositis?
A
Classic symptoms include proximal muscle weakness, difficulty climbing stairs, getting up from a chair, and carrying groceries.
7
Q
What lab finding is commonly associated with polymyositis?
A
Serum creatinine kinase levels are increased due to muscle inflammation.
8
Q
What is the most common antibody seen in polymyositis?
A
The most common antibody is anti-Jo1, which is directed against histidyl-tRNA synthetase.
9
Q
What is the function of histidyl-tRNA synthetase?
A
Histidyl-tRNA synthetase catalyzes the transfer of histidine amino acids to the 3’ end of tRNA molecules during the process of tRNA charging.
10
Q
What is diphtheria and what organism causes it?
A
Diphtheria is an infectious disease caused by the gram-positive bacillus Corynebacterium diphtheriae.
11
Q
What are the common clinical features of diphtheria?
A
Clinical features include sore throat, malaise, low-grade fever, and cervical lymphadenopathy.
12
Q
What classic examination finding is associated with diphtheria?
A
Examination of the pharynx typically shows a gray-white membrane composed of fibrin, inflammatory cells, bacteria, and necrotic debris.
13
Q
Why is diphtheria rarely seen outside the developing world?
A
Diphtheria is rarely seen outside the developing world due to widespread vaccination against it.
14
Q
What is the mechanism of action of diphtheria toxin?
A
Diphtheria toxin inactivates elongation factor 2 in human cells, which inhibits protein synthesis and leads to cell death.
15
Q
What role do elongation factors play in protein synthesis?
A
Elongation factors facilitate the elongation phase of translation at ribosomes, allowing peptides to grow in length once translation has been initiated.
16
Q
What aspects of protein synthesis are not directly affected by diphtheria toxin?
A
Charging of tRNA, initiation and termination of translation, and post-translational modification are not directly affected by diphtheria toxin.
17
Q
What is the primary effect of diphtheria toxin on protein synthesis?
A
Diphtheria toxin primarily inhibits the activity of elongation factor 2, which arrests protein synthesis and leads to cell death.
18
Q
What processes are involved in cellular protein synthesis?
A
Cellular protein synthesis involves:
- Charging of tRNA
- Initiation of translation
- Elongation of the polypeptide chain
- Termination of translation
- Post-translational modification
19
Q
What is the most common cause of dilated cardiomyopathy?
A
Coronary artery disease, also known as ischemic cardiomyopathy.
20
Q
Why is a coronary angiogram performed in patients with new-onset dilated cardiomyopathy?
A
A coronary angiogram is commonly performed to assess for ischemic causes of cardiomyopathy. A normal angiogram indicates a non-ischemic cause.
21
Q
What is one of the non-ischemic causes of dilated cardiomyopathy associated with mitochondrial DNA?
A
A small number of cases of non-ischemic dilated cardiomyopathy are caused by mutations in mitochondrial DNA that code for tRNA molecules.
22
Q
What is the significance of mutations in tRNA molecules related to dilated cardiomyopathy?
A
Mutations that alter the aminoacyl acceptor stem at the 3’ end of tRNA molecules can negatively affect protein synthesis, as this is where amino acids bind to tRNA.
23
Q
How do modifications to tRNA affect protein synthesis?
A
Any negative modification to tRNA, including at the acceptor stem, decreases protein synthesis because tRNA is responsible for transporting amino acids to growing protein chains.
24
Q
What does “terminally differentiated” mean in the context of cardiac myocytes?
A
“Terminally differentiated” means that cardiac myocytes do not divide and cannot regenerate after cell death, such as in a myocardial infarction.
25
How do cardiac myocytes respond to stressors like hypertension?
Cardiac myocytes develop hypertrophy (increase in cell size) but do not undergo hyperplasia (increase in cell number) when exposed to stressors like hypertension.
26
How do mutations in mitochondrial DNA affect oxidative phosphorylation?
Mutations in mitochondrial DNA decrease, rather than increase, the process of oxidative phosphorylation.
27
Would a change in cellular tRNA affect mitochondrial function?
No, a change in cellular tRNA would not affect the mitochondria directly, as tRNA operates in the cytoplasm for protein synthesis.
28
What is the function of aminoacyl-tRNA synthetases?
Aminoacyl-tRNA synthetases are enzymes that attach the appropriate amino acids to the 3’ end of tRNA molecules as part of protein translation.
29
How many different aminoacyl-tRNA synthetases are there in the human body?
There are 20 different aminoacyl-tRNA synthetases in the human body, one for each amino acid of the genetic code.
30
What additional function do aminoacyl-tRNA synthetases perform besides attaching amino acids to tRNA?
Aminoacyl-tRNA synthetases perform hydrolytic editing, which involves scrutinizing amino acid attachments to ensure the correct amino acid is present on the tRNA.
31
What does it mean if a tRNA molecule has an incorrect amino acid attached?
This condition, known as a "mischarged" tRNA, indicates an error in the function of aminoacyl-tRNA synthetase.
32
What are the three stages of protein translation?
The three stages of protein translation are initiation, elongation, and termination.
33
What role does peptidyl transferase play in protein synthesis?
Peptidyl transferase, which is part of the ribosome, catalyzes the transfer of amino acids bound to tRNA to the growing peptide chain.
34
What would be the consequence of a failure in the peptidyl transferase enzyme?
Failure of peptidyl transferase would result in a failure of protein synthesis but would not cause mischarging of tRNA molecules.
35
What is the role of RNA polymerase III in protein synthesis?
RNA polymerase III synthesizes tRNA molecules.
36
What does it indicate if there is an abnormal tRNA molecule despite a normal genetic code?
An abnormal tRNA molecule despite a normal genetic code indicates an error in tRNA synthesis by RNA polymerase III.
37
What happens when there are functional errors in aminoacyl-tRNA synthetases?
Functional errors in aminoacyl-tRNA synthetases lead to mischarged tRNA molecules, where the attached amino acid does not match the genetic code of the tRNA anticodon.
37
What is the function of aminoacyl-tRNA synthetases?
Aminoacyl-tRNA synthetases are enzymes that attach the appropriate amino acids to the 3’ end of tRNA molecules during protein translation.
38
What process does mRNA undergo before it exits the nucleus?
mRNA undergoes splicing, which removes introns from the transcript.
39
What are the signals that identify introns during splicing?
Introns are identified by a GU at the 5’ end and an AG at the 3’ end.
40
What happens to the mRNA sequence after splicing?
After splicing, the mRNA sequence will be similar to the original DNA sequence, with the bases between GU and AG (the introns) removed.
41
What is the significance of splicing in eukaryotic gene expression?
Splicing is crucial for producing a mature mRNA transcript that can be translated into a functional protein, allowing for proper gene expression.
42
What are the presenting symptoms of acute liver injury in this case?
The woman presents with jaundice, altered mental status, and marked elevations in serum aminotransferases.
43
What is the significance of marked elevations in aminotransferases (>1000)?
Marked elevations in aminotransferases indicate acute liver injury and have a limited differential diagnosis, including acute viral hepatitis, acute alcoholic hepatitis, acetaminophen toxicity, shock liver, and toxin exposure
44
What mushroom is associated with severe liver toxicity?
The death cap mushroom (Amanita phalloides) is associated with severe liver toxicity.
45
What toxin does the death cap mushroom produce, and what is its effect?
The death cap mushroom produces alpha amanitin, which inhibits RNA polymerase II in liver cells, preventing hepatocytes from synthesizing mRNA from DNA.
46
What are potential complications of Amanita phalloides poisoning?
Complications can include life-threatening hepatic failure, hypoglycemia, coagulopathy (evidenced by increased INR), and multi-organ failure.
47
What does an increased INR indicate in the context of liver injury?
An increased INR indicates coagulopathy, which can result from liver dysfunction due to acute liver injury.
48
What are the key symptoms of pulmonary tuberculosis (TB) in this patient?
The patient presents with night sweats, weight loss, hemoptysis, and the presence of acid-fast organisms in his sputum.
49
What is the standard treatment regimen for tuberculosis?
The standard treatment regimen for TB includes a combination of rifampin, isoniazid, pyrazinamide, and ethambutol.
50
What unique side effect is associated with rifampin?
Rifampin is known for causing orange-red discoloration of tears, saliva, urine, and feces due to its metabolites.
51
Is the orange-red discoloration caused by rifampin harmful?
No, the orange-red discoloration is a benign change that patients often notice and report to healthcare providers.
52
What is the mechanism of action of rifampin?
Rifampin works by inhibiting bacterial RNA polymerase, which is essential for RNA synthesis in bacteria.
53
What is the mechanism of action of beta-lactam antibiotics?
Beta-lactam antibiotics prevent cross-linking of peptidoglycan in bacterial cell walls.
54
What is the mechanism of action of macrolide antibiotics?
Macrolide antibiotics inhibit bacterial protein synthesis by preventing ribosome translocation.
55
Inhibits the synthesis of mycolic acids, a key component of mycobacterial cell walls.
Isoniazid
56
What is a key characteristic that distinguishes enhancer DNA regions from promoters?
Enhancers bind transcription factors and increase gene transcription, while promoters are located directly upstream of a gene.
57
Where can enhancers be located in relation to the gene they regulate?
Enhancers can be found many nucleotides up or downstream of the gene they act upon due to DNA coiling.
58
What role do enhancers play in gene transcription?
Enhancers increase gene transcription by binding transcription factors.
59
hat do both enhancers and promoters have in common regarding transcription factors?
Both enhancers and promoters bind to transcription factors.
60
Where are promoters typically located in relation to the gene they regulate?
Promoters are found upstream of the gene they act upon.
61
Can enhancers be located only upstream of the gene they regulate?
No, enhancers can be found both upstream and downstream of the gene they act upon.
62
What is the TATA box?
The TATA box, with the sequence TATAAA, is a classic promoter region.
63
What identifies RNA fragments as mRNA?
The presence of a 5’ 7-methylguanosine cap identifies RNA fragments as mRNA.
64
What are the types of mRNA found in the nucleus?
Multiple types of mRNA found in the nucleus include pre-mRNA (which contains introns) and mature mRNA.
65
What types of RNA are closely associated with ribosomes during translation?
Messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA) are all found associated with ribosomes during translation.
66
Where is messenger RNA moved to in the cytoplasm?
Messenger RNA is moved to processing bodies in the cytoplasm.
67
What other types of RNA can be found in processing bodies besides mRNA?
micro RNA (miRNA).
68
What are introns, and where are they found?
Introns are nucleotide sequences that are removed by RNA splicing and are found within mRNA and also tRNA.
69
What are the key findings consistent with aplastic anemia in this boy?
The boy has anemia, thrombocytopenia, and neutropenia.
70
What physical features suggest a diagnosis of Fanconi anemia?
Short stature and abnormal thumbs suggest a diagnosis of Fanconi anemia.
71
What causes Fanconi anemia?
mutations in DNA repair genes.
72
What is the major role of Fanconi anemia genes?
The major role of Fanconi anemia genes is to repair DNA interstrand crosslinks.
73
How are DNA interstrand crosslinks typically repaired in normal cells?
In normal cells, lesions are removed by enzymes that create a double-strand DNA break at the site of the crosslink, and then the break is repaired.
74
What happens to children with Fanconi anemia regarding DNA repair?
Children with Fanconi anemia have impaired repair of DNA interstrand crosslinks, leading to accumulation of crosslinks and failure of double-strand repair mechanisms.
75
What is the mechanism by which pyrimidine dimers are removed from DNA?
Through nucleotide excision repair.
76
What condition is caused by defects in nucleotide excision repair?
Xeroderma pigmentosa
77
What is the function of mismatch repair during DNA synthesis?
Mismatch repair resolves incorrectly paired bases or nucleotides during DNA synthesis.
78
What can failure of mismatch repair lead to?
Failure of mismatch repair can lead to microsatellite instability and Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
79
Is a substance used widely as a solvent for industrial manufacturing processes (e.g., rubber manufacturing). Exposure can lead to aplastic anemia. This child has poor growth and abnormal thumbs, suggesting a genetic cause rather than an environmental cause of his condition.
Benzene
80
What does a variable number of repeating DNA segments among cells indicate in this man with colon cancer?
This is termed microsatellite instability, which is due to a failure in DNA mismatch repair.
81
When does DNA mismatch repair occur in the cell cycle?
DNA mismatch repair takes place during the S/G2 phase of the cell cycle when DNA replication is occurring.
82
What are the two mechanisms that repair DNA double-strand breaks?
DNA double-strand breaks are repaired by homologous recombination and non-homologous end joining.
83
What conditions may result from the failure of DNA double-strand break repair mechanisms?
Failure of these mechanisms may lead to Fanconi anemia or ataxia telangiectasia.
84
What are the typical clinical features of ataxia telangiectasia (AT)?
Being confined to a wheelchair, recurrent upper respiratory infections, and telangiectasias on the skin.
85
What genetic mutation causes ataxia telangiectasia?
Mutation in the ATM gene.
86
How does the mutation in the ATM gene affect DNA repair?
The mutation prevents the repair of double-stranded DNA breaks through non-homologous end joining.
87
What is the consequence of the DNA repair defect in children with ataxia telangiectasia?
Affected children are at increased risk for DNA damage from ionizing radiation, which can lead to cancer.
88
What is the cause of sensitivity to UV radiation in xeroderma pigmentosum?
Sensitivity to UV radiation in xeroderma pigmentosum is due to defective nucleotide excision repair.
89
When do affected children typically start showing sensitivity to sunlight in xeroderma pigmentosum?
Affected children are sensitive to sunlight starting in infancy and typically have numerous freckles on their skin.
90
What type of radiation are patients with ataxia telangiectasia sensitive to?
Ionizing radiation, not UV radiation.
91
What defines ionizing radiation?
Ionizing radiation is radiation with enough energy to knock electrons from molecules, causing ionization. UV radiation is non-ionizing and comes largely from the sun, while ionizing radiation has enough energy to cause ionization.
92
What initiates the base excision repair process?
Base excision repair begins when DNA glycosylase removes damaged nitrogenous bases, leaving a “baseless” nucleotide.
93
What is the role of AP endonuclease in base excision repair?
AP endonuclease breaks the bond at the 5’ end of the baseless nucleotide.
94
What does AP lyase do during base excision repair?
AP lyase breaks the bond at the 3’ end of the baseless nucleotide, removing the entire damaged nucleotide.
95
Which enzymes fill in the gap after a damaged nucleotide is removed in base excision repair?
DNA polymerase and ligase fill in the gap.
96
What does the presence of a bond remaining at the 3’ end of a baseless nucleotide indicate?
It indicates a lack of AP lyase function, whose normal role is to break the 3’ bond.
97
This child with extreme sun sensitivity, freckles, and dry skin has xeroderma pigmentosum, a disease caused by defective nucleotide excision repair. This repair mechanism is responsible for
Removing pyrimidine dimers caused by UV light exposure.
98
What is a silent mutation?
Is a nucleotide change that does not alter the final protein product of a gene.
99
Why do point mutations that occur in the third position of a codon often result in silent mutations?
Point mutations at position 3 of a codon are often silent because codons that differ at this position can generate the same amino acid, as described by the "Wobble" hypothesis.
100
Point mutations involving a start codon are
Never silent
101
UAA
A stop codon
102
In the context of Duchenne muscular dystrophy (DMD), how can a parent carry a germline mutation yet test negative using standard techniques?
The parent will test negative for the mutation because standard techniques often sample DNA from somatic cells (like the oral mucosa), where the mutation is not present.
103
What are two genetic disorders associated with germline mutations?
Osteogenesis imperfecta (OI) and Duchenne muscular dystrophy (DMD)
104
How can a child inherit a genetic disorder from parents who do not show the disease gene?
A child can inherit the disorder due to a new (sporadic, spontaneous, or de novo) mutation, which may not be present in the parents’ somatic cells.
105
When is a germline mutation revealed in families where the parents do not initially test positive?
The germline mutation is revealed when additional children are born with the same mutation, indicating it originated from one of the parents.
105
What is a nonsense mutation?
A nonsense mutation is a DNA point mutation that results in an early stop codon, leading to a shortened amino acid sequence.
106
What are the three RNA stop codons?
UAG
UGA
UAA
107
What are the corresponding coding strand DNA sequences for the RNA stop codons?
The corresponding coding strand DNA sequences are:
UAG → TAG
UGA → TGA
UAA → TAA
108
What must a point mutation result in to cause a nonsense mutation?
A point mutation must result in one of the stop codon sequences (TAG, TGA, or TAA) to cause a nonsense mutation.
109
What are common symptoms of sickle cell anemia?
Common symptoms include hemolytic anemia, dyspnea, and recurrent pain crises that may resolve with fluid and blood transfusions.
110
What genetic mutation causes sickle cell anemia?
Sickle cell anemia is caused by a missense mutation in the beta globin gene.
111
What is a missense mutation?
A missense mutation is a genetic alteration that substitutes one amino acid for another in a protein.
112
What amino acid substitution occurs in sickle cell anemia?
In sickle cell anemia, valine is substituted for glutamate in the beta chains of hemoglobin.
113
What effect does the sickle cell mutation have on hemoglobin?
The mutation causes hemoglobin to denature and precipitate in the deoxygenated state, leading to the sickling of red blood cells.
114
What are the consequences of sickled red blood cells in the body?
Sickled red blood cells can damage cell membranes, leading to hemolytic anemia, tissue ischemia, and pain due to blockage in small caliber vessels.
115
Are caused by insertions or deletions of nucleotides in multiples not divisible by three. Because of the genetic code which places amino acids based on three-nucleotide DNA sequences, a frameshift mutation “shifts the reading frame”, resulting in completely different protein products of translation.
Frameshift mutations
116
What genetic mutation causes cystic fibrosis (CF)?
Cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7.
117
What is a common initial presentation of cystic fibrosis in infants?
A common initial presentation of cystic fibrosis is meconium ileus, where the first stool is thick and sticky, leading to bowel obstruction.
118
What clinical features are associated with meconium ileus?
Clinical features include abdominal distension, bilious vomiting, and dilated loops of bowel with air-fluid levels on X-ray.
119
What is the primary diagnostic technique for cystic fibrosis?
Sweat chloride testing is the primary diagnostic technique for cystic fibrosis.
120
What is the most common mutation associated with cystic fibrosis?
The most common mutation is the deletion of three DNA nucleotides in the CFTR gene, known as the “delta F508 mutation.”
121
What is the result of the delta F508 mutation?
The delta F508 mutation results in the loss of a phenylalanine in the protein product, leading to improperly folded chloride channel proteins.
122
Why does the delta F508 mutation not cause a frameshift?
The deletion is a multiple of three nucleotides, which means it does not disrupt the reading frame of the gene, resulting in a non-frameshift mutation.
123
What effect does a single nucleotide insertion in a gene have on protein coding?
A single nucleotide insertion leads to a frameshift mutation, altering the reading frame of the gene.
124
Why is a single nucleotide insertion considered a frameshift mutation?
It is considered a frameshift mutation because the insertion is a number not divisible by three, disrupting the codon alignment.
125
What is the likely consequence of a frameshift mutation in a large gene?
A frameshift mutation in a large gene commonly leads to the formation of an early stop codon, resulting in premature termination of translation.
126
What are the stop codons that may be affected by a frameshift mutation?
The stop codons include TAA, TAG, and TGA.
127
How does a frameshift mutation impact the overall protein product?
The frameshift mutation may lead to a truncated protein product, often losing functional domains and potentially resulting in loss of function.
128
What is the primary purpose of polymerase chain reaction (PCR) in molecular biology?
PCR is used to amplify small amounts of DNA into larger quantities for analysis.
129
How does PCR benefit the detection of infectious diseases?
PCR allows for the detection of bacterial DNA at very early stages of infection, often before sufficient amounts of proteins or antigens are present.
130
What bacterium is associated with antibiotic-associated diarrhea and is diagnosed using PCR?
Clostridioides (formerly Clostridium) difficile.
131
What are the two methods for diagnosing C. difficile infections?
Laboratory testing for C. difficile toxin and testing for C. difficile toxin genes.
132
What does NAAT stand for, and what does it involve?
NAAT stands for nucleic acid amplification testing, which involves PCR and the detection of DNA in stool samples.
133
What is the primary use of flow cytometry in cell analysis?
Flow cytometry is used to detect and analyze surface markers on cells.
134
What does the presence of CD3 on a lymphocyte indicate?
The expression of CD3 indicates that the lymphocyte is a T cell.
135
What type of cells can be analyzed using flow cytometry?
Flow cytometry can analyze various types of cells, including lymphocytes, and detect specific surface markers.
136
What is the southwestern blot technique used for?
It is used for the detection of DNA binding proteins.
137
What techniques does southwestern blotting combine?
It combines southern and western blotting techniques.
138
What do southwestern blots use to detect proteins?
They use DNA probes, which are traditionally used in southern blotting.
139
What antibodies can be detected in Lyme disease using enzyme-linked immunosorbent assay (ELISA)?
IgM antibodies.
140
What is the primary use of ELISA?
To detect antibodies and antigens, depending on the type of ELISA test performed.
141
What is the role of ferritin in the body?
Ferritin is an intracellular protein that stores iron.
142
What laboratory technique is used to detect proteins like ferritin?
Western blot.
143
How does the Western blot technique work?
It separates proteins by size, and a labeled antibody is used to detect and quantify the target protein.
144
What does the Northern blot technique detect?
It detects gene expression by quantifying the amount of cellular messenger RNA (mRNA).
145
How does the Northern blot technique work?
It separates RNA molecules by size, and a labeled nucleic acid probe is used to detect and quantify the target mRNA.
146
What happens to ferritin content in hepatocytes cultured in high iron media?
There is increased ferritin content.
147
Is there a change in ferritin messenger RNA (mRNA) in hepatocytes under high iron conditions?
No, there is no change in ferritin mRNA.
148
What could lead to increased protein content in cells?
Increased gene expression (transcription) or increased translation of mRNA.
149
The stable amount of mRNA indicates
No change in DNA transcription.
150
What does restriction fragment length polymorphism (RFLP) do?
RFLP breaks DNA at specific base sequences, creating fragments of varying lengths unique to particular genes.
151
In the context of Duchenne muscular dystrophy (DMD), what is the inheritance pattern of this X-linked disorder?
Males cannot be carriers; the disease gene can only be inherited from the mother.
152
What does it mean if the proband has RFLP fragments of a single length?
It indicates that the proband has inherited the same allele from the mother.
153
If the mother has a fragment of similar length to the proband, what does this imply?
It implies that she is the source of the disease gene.
154
What does it indicate if Sister B has a fragment of the same length as the proband?
It indicates that Sister B is a carrier of the disease gene on one of her two X chromosomes.
155
What do CD4+ and CD8+ T-cells represent in immunological studies?
CD4+ T-cells are helper T-cells, while CD8+ T-cells are cytotoxic T-cells.
156
In the context of the study, what does a higher number of CD4+ T-cells among patients with pouchitis indicate?
It indicates an increased ratio of CD4
lymphocytes in samples from patients with pouchitis.
157
What is the significance of analyzing the population of T-cells in patients with and without pouchitis?
It helps to understand the immune response and potential inflammatory changes associated with pouchitis.
158
Where are CD4+ and CD8+ T-cells located in the flow cytometry analysis image?
CD4+ T-cells are indicated in the top left quadrant, and CD8+ T-cells are in the bottom right quadrant.
159
How is the HIV p24 antigen detected using ELISA?
In ELISA, antibodies specific to the HIV p24 antigen are coated along the base of a well. If p24 antigens are present in a serum sample, they will bind to the antibodies. A detecting antibody is then added, which binds only if p24 antigens are present. A color change indicates the presence of the p24 antigen.
160
What is the process of a sandwich enzyme-linked immunosorbent assay (ELISA)
In a sandwich ELISA, the patient's serum is added to a well-coated plate with capture antibodies that bind the antigen (if present) in the serum. A second antibody, also binding the antigen, is added, creating a "sandwich" of the antigen between two antibodies. The second antibody is enzyme-linked, generating a color change if the antigen is present.
161
What distinguishes a sandwich ELISA from direct and indirect ELISA tests?
In a sandwich ELISA, the patient's serum is added to a well containing capture antibodies that bind the antigen to the surface. This is different from direct and indirect ELISA tests, which typically do not use capture antibodies.
162
How does a competitive ELISA work?
In a competitive ELISA, a primary antibody to the antigen of interest is incubated with the serum sample before applying it to an antigen-coated plate. This mixture prevents the antigen from binding to the plate, allowing for quantification based on the amount of unbound primary antibody.
163
In a reverse ELISA
A polystyrene rod is inserted into the serum sample instead of applying the serum to a well. This allows for the binding of antibodies from the serum to the rod for subsequent analysis.
164
What does the term “in situ” mean in the context of fluorescence in situ hybridization (FISH)?
The term “in situ” means “in its original place.”
165
What is the main purpose of fluorescence in situ hybridization (FISH)?
FISH is used to detect genes in their original location on a chromosome using fluorescent probes.
166
How does FISH work to identify the presence of a specific gene?
FISH involves separating chromosomes in metaphase and adding a fluorescent DNA probe for a gene of interest. If the gene is present, a portion of the chromosome will light up; if absent, no fluorescence will be seen.
167
What is the significance of the BCR-ABL fusion gene?
The BCR-ABL fusion gene occurs in chronic myelogenous leukemia, indicating the presence of a fusion gene formed from the BCR and ABL genes that are normally found on separate chromosomes.
168
In the FISH technique for detecting the BCR-ABL fusion gene, what colors are used for the probes?
A green fluorescent probe is used for the BCR gene, and a red probe is used for the ABL gene.
169
What is osteogenesis imperfecta (OI) commonly known as?
Osteogenesis imperfecta is commonly known as "brittle bone disease."
170
What is the primary genetic defect in osteogenesis imperfecta?
Osteogenesis imperfecta is caused by abnormal type I collagen production.
171
What are the classic clinical presentations of a child with osteogenesis imperfecta?
Affected children typically present with fractures, often after minor trauma, and may also exhibit blue sclerae.
172
Why do children with osteogenesis imperfecta often have blue sclerae?
Blue sclerae occur due to thinning of the sclera from abnormal connective tissue, allowing choroidal veins to show through.
173
What type of hearing issues may occur in children with osteogenesis imperfecta?
Hearing loss can occur due to diminished type I collagen content in middle ear structures, including the ossicles (malleus, incus, and stapes).
174
What would X-ray imaging typically show in a child with osteogenesis imperfecta?
X-ray imaging would show multiple fractures in various states of healing.
175
What is Alport syndrome?
A disorder characterized by abnormal type IV collagen.
176
What are the classic symptoms of Alport syndrome?
Children with Alport syndrome may develop renal failure, hearing loss, and vision problems.
177
How does Alport syndrome affect different organs?
Diminished type IV collagen affects basement membranes in the kidney (leading to renal failure), cochlea (causing hearing loss), and eye (resulting in vision problems).
178
What condition is caused by vitamin C deficiency?
Scurvy
179
Why is vitamin C important for the body?
Vitamin C is required for the synthesis of collagen
180
What are some clinical manifestations of scurvy?
Impaired wound healing and bleeding gums.
181
What leads to the symptoms seen in scurvy?
Lack of normal collagen production due to vitamin C deficiency.
182
What genetic condition is characterized by a deficiency in the connective tissue glycoprotein, fibrillin?
Marfan syndrome.
183
What are two major cardiovascular complications associated with Marfan syndrome?
Aortic dissection and mitral valve prolapse.
184
What is the primary defect in Marfan syndrome?
Deficient production of fibrillin.
185
What is the genetic disorder characterized by abnormalities in collagen synthesis and includes hypermobility of joints and abnormal skin?
Ehlers-Danlos syndrome (EDS)
186
Which gene is commonly mutated in the vascular subtype of Ehlers-Danlos syndrome?
COL3A1
187
What are some key physical features of the vascular subtype of EDS?
Thin, translucent skin; short stature; large eyes; thin nose; lobeless ears
188
What is a significant risk associated with vascular Ehlers-Danlos syndrome?
Risk of internal organ rupture, including rupture of the colon and uterus.
189
What clinical presentation might indicate spontaneous colon rupture in a patient with vascular EDS?
Acute abdominal pain with guarding and rebound tenderness.
190
What serious complication should be considered in young patients with ischemic stroke who may have vascular EDS?
Intracranial aneurysms.
191
What are classic skin manifestations of scurvy?
“Perifollicular hyperkeratotic papules” (red-blue spots surrounding hairs, often in the shins) and easy bruising.
192
What oral symptoms are commonly associated with scurvy?
Swelling, redness, and bleeding of the gums.
193
In which population is scurvy most commonly found in the United States?
Malnourished patients with no access to fruits or vegetables.
194
Why is vitamin C important for collagen synthesis?
Vitamin C is necessary for the hydroxylation of proline to form hydroxyproline in collagen.
195
What other important roles does vitamin C play in the body?
Absorption of iron and dopamine synthesis.
196
What is the role of vitamin K in the body?
Vitamin K is required for the gamma carboxylation of glutamate residues on clotting factors.
197
Is required for keratinization of skin.
Vitamin A
198
What is dehydrogenation in biochemical processes?
Is the removal of hydrogen from a substrate, often involving the conversion of a substrate to a higher oxidation state.
199
Which enzymes are responsible for dehydrogenation in metabolic pathways?
Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and alpha-ketoacid dehydrogenase.
200
What vitamin is essential for the function of dehydrogenase enzymes?
Vitamin B1 (thiamine).
201
What are the consequences of thiamine deficiency?
Thiamine deficiency can lead to conditions such as Wernicke-Korsakoff syndrome and beriberi, affecting energy metabolism and nerve function.
202
What is Alport syndrome?
Alport syndrome is an inherited form of glomerular disease characterized by hematuria, hearing loss, and visual problems due to defective production of type IV collagen.
Common features include recurrent episodes of hematuria with red blood cell casts, hearing loss, and visual problems.
203
What are the two layers of basement membranes?
The two layers are the basal lamina and the reticular layer (reticular lamina).
204
What is contained within the basal lamina?
The basal lamina contains type IV collagen and is located directly beneath epithelial cells.
205
What is found in the reticular layer of the basement membrane?
The reticular layer contains reticular fibers, which are a form of connective tissue made of type III collagen.
206
Deficiency of factor VIII is the cause of ?. This presents in childhood, usually with recurrent joint bleeding.
Hemophilia A
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Von Willebrand factor (VWF) is a glycoprotein that circulates bound to
Factor VIII.
208
Patients with Von Willebrand disease have deficient levels of ? which leads to bleeding such as nosebleeds or menorrhagia (heavy menstrual periods).
VWF
209
What are the cardiovascular complications associated with Marfan syndrome?
Marfan syndrome can lead to progressive dilation of the thoracic aorta, resulting in aortic aneurysm and an increased risk of aortic dissection, which is the most common cause of death in affected individuals.
210
What physical characteristics are commonly observed in individuals with Marfan syndrome?
Patients are typically tall with a long wingspan. They may also exhibit a decreased upper segment to lower segment ratio and an increased arm span to height ratio.
211
What ocular feature is associated with Marfan syndrome?
Ectopia lentis, which is the displacement of the lens, is a common ocular feature.
212
What cardiac condition is often seen in patients with Marfan syndrome?
Mitral valve prolapse
213
What is the classic histologic description of squamous cell carcinoma (SCC)?
SCC is characterized by sheets of polygonal cells with "crisp" eosinophilic cytoplasm and intercellular bridges (desmosomes).
214
What is a notable feature of the nuclei in squamous cell carcinoma cells?
The nuclei in SCC cells are often pleomorphic, meaning they vary in size and shape.
215
Which immunohistochemical marker is commonly positive in squamous cell carcinoma?
SCC will stain positive for antibodies to high-molecular-weight cytokeratin.
216
What types of cells are typically found in melanoma?
Melanomas contain both epithelioid and spindle cells.
217
What is the classic immunohistochemistry antibody staining marker for melanoma?
S100
218
Rhabdomyosarcoma is a malignant muscle tumor. The classic antibodies for these tumors are
Vimentin and desmin.
219
What is the mechanism of action of vincristine?
Vincristine binds beta tubulin and inhibits the polymerization of tubulin monomers into microtubule polymers, preventing rapidly-dividing cancer cells from completing metaphase during cellular division.
220
What is the major, dose-limiting toxicity of vincristine?
The major, dose-limiting toxicity of vincristine is neuropathy.
221
What causes the neuropathy associated with vincristine?
The neuropathy results from the disruption of microtubules in neurons and interference with axonal transport.
222
When does vincristine-related neuropathy typically begin and what are its initial symptoms?
Neuropathy usually begins after several weeks of therapy with paresthesias in the fingertips and feet.
223
What are the potential progression symptoms of vincristine-induced neuropathy?
The neuropathy can progress to pain and weakness.
224
What role do microtubules play in mitosis?
Microtubules form the mitotic spindle, which separates chromosomes during mitosis. Microtubules consist of polymers made from tubulin monomers.
225
What is the mechanism of action of colchicine?
Colchicine inhibits microtubule formation by binding to tubulin monomers.
226
How is colchicine used in research studies?
Colchicine and its derivatives are used to arrest cells during mitosis in research studies.
227
Is used in the treatment of gout, pericarditis, and Familial Mediterranean fever.
Colchicine
228
What is believed to be the mechanism behind colchicine's anti-inflammatory effects?
Colchicine's anti-inflammatory effect is believed to derive from tubulin inhibition, which inhibits the immune response through several mechanisms.
229
What is primary ciliary dyskinesia (PCD)?
PCD is a congenital disorder characterized by ciliary motility impairment, resulting in immotile cilia.
230
What are the main respiratory symptoms associated with PCD?
Recurrent respiratory infections due to impaired ciliary clearance, leading to conditions like bronchitis and bronchiectasis.
231
How does ciliary dysfunction affect the nasal passages and Eustachian tubes in PCD patients?
Ciliary dysfunction leads to a constantly runny nose and recurrent otitis media due to impaired mucus clearance.
232
What is bronchiectasis, and how is it related to PCD?
Bronchiectasis is the dilation of large airways due to mucus accumulation, which facilitates bacterial growth and causes recurrent pulmonary infections in PCD patients.
233
At what age do most patients with PCD typically present?
Most patients with PCD present in childhood, around age 5.
234
What is situs inversus, and how is it associated with PCD?
Situs inversus is a congenital anomaly where visceral organs are positioned on the opposite side of the body. About 50% of patients with PCD have this condition due to impaired ciliary function during development.
235
What is Kartagener’s syndrome?
Kartagener’s syndrome is characterized by the combination of situs inversus, chronic sinusitis, and bronchiectasis, often seen in patients with PCD.
236
What genetic mutations are commonly associated with PCD?
More than 30 gene mutations have been described in PCD, with the majority involving genes for dynein, a microtubule motor protein.
237
What is the role of dynein in ciliary motility?
Dynein is essential for normal ciliary motility; its dysfunction leads to the immotility of cilia seen in PCD.
238
Is caused by defects in the Bruton tyrosine kinase gene. Children with this condition have deficient antibody production by B-cells. This leads to recurrent respiratory bacterial infections and gastrointestinal infections.
X-linked agammaglobulinemia (also called Bruton’s agammaglobulinemia)
239
Is caused by mutations in the lysosomal trafficking regulator gene. This leads to microtubular dysfunction and abnormal intracellular trafficking of lysosomes. Affected children develop albinism from abnormal melanocytes, and recurrent infections due to neutrophil abnormalities.
Chediak-Higashi syndrome
240
Abnormalities of the adenosine deaminase gene cause ?. In this disorder, T-cells and B-cells are absent or greatly diminished. This leads to an absence of adaptive immunity. Infants with SCID have recurrent infections, chronic diarrhea, and poor growth.
Severe Combined Immunodeficiency (SCID)
241
What is rhabdomyosarcoma?
Rhabdomyosarcoma is a rare malignancy derived from immature cells that normally form striated muscle. The majority of new cases are diagnosed in children less than six years of age, although rare cases can occur in adults. The most common site is the head and neck, including the orbit, ear, nose, sinuses, and other locations. Diagnosis is made through tissue biopsy.
242
What is the most common subtype of rhabdomyosarcoma?
The most common subtype is the embryonal subtype, composed of malignant cells that are round and eosinophilic with skeletal muscle differentiation.
243
Which stains are positive in rhabdomyosarcoma?
Staining for desmin, vimentin, and myoglobin will be positive.
244
What is desmin, and where is it found?
Desmin is a muscle filament found in striated muscle cells.
245
What is vimentin, and in which cells is it typically found?
Vimentin is a protein found in cells of mesenchymal origin, including striated muscle myocytes.
246
What is retinoblastoma?
Retinoblastoma is an inherited form of childhood cancer that affects the retina, accounting for 13% of tumors in children under 1 year of age.
247
What is the classic presentation of retinoblastoma?
The classic presentation is leukocoria (loss of the red reflex) in a child less than 3 years of age.
248
What does leukocoria indicate?
Leukocoria indicates an abnormal white reflection when light is shone into the back of the eye, which can be seen in retinoblastoma, cataracts, and vitreous hemorrhage.
249
What gene is mutated in retinoblastoma?
Retinoblastoma is caused by mutations in the retinoblastoma (Rb) gene, which encodes a tumor-suppressor protein.
250
What is the function of the retinoblastoma protein?
The retinoblastoma protein normally limits cell growth, and decreased synthesis or function leads to uncontrolled cell growth and malignancy.
251
What genetic state do retinal cells have in a child with inherited retinoblastoma?
At birth, retinal cells are heterozygous for the Rb gene, with one mutated and one normal copy.
252
What happens if a cell loses the normal copy of the Rb gene?
If a cell loses the normal copy, it becomes homozygous for the Rb gene mutation, leading to cancer development.
253
What is loss of heterozygosity?
Loss of heterozygosity is a process where a heterozygous cell loses its normal copy of a tumor-suppressor gene, resulting in uncontrolled cell growth due to absence of tumor-suppressor activity.
254
What is Knudson's two-hit hypothesis?
Knudson's two-hit hypothesis posits that cancer arises from tumor-suppressor gene inactivation through the acquisition of a "second hit," often involving loss of heterozygosity.
255
What does "non-mutational event" mean in the context of loss of heterozygosity?
Loss of heterozygosity is considered a non-mutational event because it leads to cancer through loss of genetic material rather than through a mutation.
256
What is anaplastic thyroid carcinoma?
Anaplastic thyroid carcinoma is a highly malignant form of thyroid cancer. The mean age of diagnosis is 65 years.
257
What is the common presentation of anaplastic thyroid carcinoma?
The typical presentation is an enlarging thyroid mass, occurring in 85% of cases.
258
What symptoms may accompany anaplastic thyroid carcinoma?
Symptoms may include neck pain, dysphagia, dyspnea, hoarseness, or cough.
259
Is anaplastic thyroid carcinoma often metastatic at diagnosis?
Yes, it is often metastatic at the time of diagnosis, with 90% of cases involving the lungs
260
How does anaplastic thyroid carcinoma differ from most other thyroid cancers in presentation?
Most thyroid cancers present as painless nodules, while anaplastic thyroid carcinoma is often symptomatic.
261
What genetic mutation is commonly associated with anaplastic thyroid carcinoma?
Mutations of the p53 tumor-suppressor gene are well-documented in anaplastic thyroid carcinoma
262
What is cervical dysplasia?
Cervical dysplasia is an abnormal growth of cervical epithelial cells that may lead to cervical cancer. Infection with human papilloma virus (HPV) is necessary for the development of cervical dysplasia. HPV subtypes 16 and 18 cause approximately 70% of cervical cancers, while subtypes 31, 33, 45, 52, and 58 account for an additional 20%.
263
What is the function of the HPV oncogene E6?
The HPV oncogene E6 leads to the synthesis of the E6 protein, which binds to the p53 protein, leading to its degradation.
264
How does the degradation of p53 occur?
Degradation of p53 occurs via ubiquitination, where p53 is bound to the protein ubiquitin, targeting it for degradation in proteasomes
265
What is Li-Fraumeni syndrome?
Li-Fraumeni syndrome is an inherited, autosomal dominant disorder characterized by multiple malignancies. It is sometimes called the Sarcoma, Breast, Leukemia, and Adrenal gland (SBLA) cancer syndrome. Is caused by a mutation in the p53 tumor-suppressor gene. The ultimate result is a failure of apoptosis, allowing malignant cells to divide indefinitely.
266
What is benign prostatic hyperplasia (BPH)?
BPH is a common condition among men over age 50 characterized by the hyperplasia (increased number) of glandular prostate cells, leading to prostate enlargement.Symptoms include urinary frequency, nocturia (waking to urinate), hesitancy (difficulty initiating urination), and slow urinary flow due to incomplete bladder emptying. The symptoms result from the enlarged prostate impeding the passage of urine.There is an increase in the frequency of cell division, leading to cell growth that exceeds the rate of cell loss.There is an increase in the frequency of cell division, leading to cell growth that exceeds the rate of cell loss.
267
What is I-cell disease?
I-cell disease is a rare lysosomal storage disorder caused by a deficiency of the enzyme UDP-N-acetylglucosamine-1-phosphotransferase in the Golgi apparatus.
268
What is the function of UDP-N-acetylglucosamine-1-phosphotransferase?
This enzyme adds mannose-6-phosphate (M6P) to lysosomal enzymes, which is crucial for their proper intracellular trafficking to lysosomes.
269
What happens to lysosomal enzymes in the absence of M6P in I-cell disease?
Without M6P, enzymes are secreted into the extracellular space rather than being directed to lysosomes.
270
What hallmark finding can be detected in the plasma of children with I-cell disease?
Elevated levels of lysosomal enzymes can be detected in the plasma.
271
What accumulates within cells in I-cell disease, and how does this manifest microscopically?
Complex molecules that are normally degraded in lysosomes accumulate within cells, appearing as cellular "inclusions" under the microscope.
272
How does I-cell disease differ from other lysosomal storage diseases?
Most lysosomal storage diseases involve deficient activity of a lysosomal enzyme, whereas I-cell disease involves a deficiency in an enzyme in the Golgi apparatus, leading to secondary deficiencies in multiple lysosomal enzymes.
273
What are some clinical features of I-cell disease that develop over the first year of life?
Coarse facial features, enlarged skull, wide nasal bridge, flattened midface, developmental delay, recurrent sinus and respiratory infections, corneal clouding, and hepatosplenomegaly.
274
What skeletal abnormality pattern can be identified on X-ray in I-cell disease?
A pattern of skeletal abnormalities known as dystosis multiplex.
275
What role does clathrin play in cells?
Clathrin is a protein that plays a significant role in receptor-mediated endocytosis, allowing cells to absorb extracellular elements through inward budding of the plasma membrane.
276
What is another name for clathrin-mediated endocytosis?
It is sometimes referred to as clathrin-mediated endocytosis due to the significant role clathrin plays in the process.
277
What is ubiquitin?
Ubiquitin is a small protein found in human cells that plays a key role in protein degradation.
277
What happens during clathrin-mediated endocytosis?
Clathrin coats membranes that are endocytosed from the plasma membrane, leading to the creation of clathrin-coated vesicles.
277
What types of proteins does clathrin interact with during endocytosis?
Clathrin interacts with many accessory proteins and other cellular adaptors that facilitate membrane trafficking within cells.
277
What are two classic examples of clathrin-mediated endocytosis?
The recycling of iron-bound transferrin and the uptake of low-density lipoproteins (LDL).
278
What is the process of adding ubiquitin to a protein called?
Ubiquitination.
279
What happens to proteins that are tagged with ubiquitin?
Proteins attached to ubiquitin are tagged for degradation and are trafficked to proteasomes, where they are broken down into amino acids.
280
What is the role of the E6 protein in HPV-infected cells?
The E6 protein interacts with the p53 protein, leading to its rapid ubiquitination and subsequent degradation in proteasomes.
281
What is Gaucher’s disease?
Gaucher’s disease is a lysosomal storage disease caused by the absence of the enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside.
282
What is a characteristic cell type found in Gaucher’s disease?
Gaucher cells are macrophages that have accumulated excessive glucocerebroside within lysosomes, appearing as "crumpled tissue paper" on histological examination.
Clinical features include splenomegaly, bone marrow suppression (leading to anemia, thrombocytopenia, or leukopenia), bone pain, and fractures.Most cases are diagnosed before age 20, although presentation can occur at any age.
283
How is Gaucher’s disease diagnosed?
Diagnosis is made by demonstrating reduced glucocerebrosidase activity in leukocytes.
284
What is the prognosis for patients with Gaucher’s disease?
Prognosis is variable, but many patients live into their 60s or 70s. Treatment is available with recombinant glucocerebrosidase enzyme replacement therapy.
285
What is a peroxisomal disorder?
A peroxisomal disorder is a rare inborn error of metabolism caused by insufficient function of peroxisomes, which are cellular organelles involved in various metabolic processes. Peroxisomes perform the metabolism of very-long-chain fatty acids, detoxify hydrogen peroxide, and carry out other metabolic functions.
286
What are common clinical features of peroxisomal disorders?
Common features include hypotonia, hepatomegaly, and facial abnormalities.
287
What laboratory findings suggest a diagnosis of a peroxisomal disorder?
Elevated levels of very-long-chain fatty acids, phytanic acid, and pristanic acid in the plasma suggest a peroxisomal disorder.
288
What is the metabolic pathway involving phytanic acid and pristanic acid in peroxisomes?
Phytanic acid is metabolized in peroxisomes into pristanic acid, which is further converted into medium-chain fatty acids.
289
How are medium-chain fatty acids processed in the body?
Medium-chain fatty acids are metabolized by mitochondria through beta-oxidation.
290
What is a key diagnostic clue for recognizing peroxisomal disorders?
The finding of elevated very-long-chain fatty acids is the most important clue for diagnosis.
291
