MRCP 1 Onexamination Basic Sciences 2014

1. You are investigating the properties of a novel oral TNF-alpha antagonist in late stage clinical trials.

Which of the following would be an expected property of this agent?

(Please select 1 option)

Decreased endothelial reactivity

Decreased HDL cholesterol

Decreased insulin sensitivity

Decreased protein catabolism CORRECT
Increased acute phase protein production

Increased levels of TNF-alpha are known to result in protein catabolism, weight loss and muscle weakness, all
features of disseminated carcinoma where TNF-alpha is elevated. As such an antagonist of TNF-alpha would
be expected to result in decreased protein catabolism.

Chronic inflammatory disorders including those associated with elevated tumour necrosis factor (TNF) are
noted to be associated with increased arteriolar stiffness and decreased endothelial reactivity.

TNF-alpha elevation is also known to be associated with increased insulin resistance and associated lipid
abnormalities such as decreased high-density lipoprotein (HDL) cholesterol.

Increased acute phase protein production is a feature of chronic inflammation, as such a TNF-alpha antagonist
is recognised to reduce this.
2. In one gene mapping technique, denatured deoxyribonucleic acid (DNA) from metaphase chromosomes is
hybridised with a radioactively labelled probe. This DNA is then exposed to film to reveal the approximate
chromosomal location of the DNA in the probe.

Which technique does this best describe?

(Please select 1 option)

Fluorescence in situ hybridisation (FISH)
In situ hybridisation CORRECT
Single strand conformation polymorphism (SSCP) analysis

Southern blotting

Somatic cell hybridisation

The technique described is 'in situ hybridisation'. It uses a labelled complementary DNA or RNA probe to
localise a specific sequence within a tissue. Firstly, the tissues are treated to fix the target, then the probe is
added. This then hybridises to the target, following which excess probe is washed away. In the classical form,
the probe is labelled with radio-labelled bases, which can then be identified using plain film. FISH is a form of

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in situ hybridisation in which the probe is labelled with fluorescent bases, which can then be visualised under a
fluorescent microscope.

Southern blotting is a laboratory procedure in which DNA fragments that have been electrophoresed through a
gel are transferred to a solid membrane, such as nitrocellulose. The DNA can then be hybridised with a
labelled probe and exposed to x ray film.

Somatic cell hybridisation is a physical gene mapping technique in which somatic cells from two different
species are fused and allowed to undergo cell division. Chromosomes from one species are selectively lost,
resulting in clones with only one or a few chromosomes from one of the species.

SSCP is a technique for detecting variation in DNA sequence by running single-stranded DNA fragments
through a non-denaturing gel. Fragments with differing secondary structure (conformation) caused by
sequence variation will migrate at different rates.
3. Suppose you are attempting to find a disease-causing gene, and you have identified a number of families
in which the disease is transmitted.

If you have no knowledge of the gene product and no reasonable candidate locus, which of the following
would be the first technique you would be most likely to use?

(Please select 1 option)

Southern blotting

Somatic cell hybridisation

Fluorescence in situ hybridisation (FISH)

Linkage analysis CORRECT

Single strand conformation polymorphism (SSCP) analysis

Linkage analysis is correct. This is used to determine the rough location of the gene responsible for disease,
relative to another DNA sequence which has its position already known (a 'genetic marker'). Disease genes are
mapped by measuring recombination against a panel of different markers. This can identify the region of the
genome in which the disease gene lies, then allowing more detailed investigation of this region.

Southern blotting is a laboratory procedure in which DNA fragments that have been electrophoresed through a
gel are transferred to a solid membrane such as nitrocellulose. The DNA can then be hybridised with a labelled
probe and exposed to x ray film.

Somatic cell hybridisation is a physical gene-mapping technique in which somatic cells from two different
species are fused and allowed to undergo cell division. Chromosomes from one species are selectively lost
resulting in clones with only one or a few chromosomes from one of the species.

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MRCP 1 Onexamination Basic Sciences 2014

FISH is a molecular cytogenetic technique in which labelled probes are hybridised with chromosomes and then
visualised under a fluorescence microscope.

SSCP is a technique for detecting variation in DNA sequence by running single-stranded DNA fragments
through a non-denaturing gel. Fragments with differing secondary structure (conformation) caused by
sequence variation will migrate at different rates.
4. Which of the following genetic mutations is responsible for Marfan syndrome?

(Please select 1 option)

Collagen

Elastin

Fibrillin CORRECT
Mircrofilament

Microtubule

Marfan syndrome occurs due to a mutation in the fibrillin gene.

Most patients, who are prone to develop an aortic aneurysm as a component of Marfan syndrome, can be
identified by detection of mutations in the fibrillin-1 gene.

Patients with the rarer form of Marfan syndrome, which is characterised by contracturalarachnodactyly instead
of loose joints, can usually be identified by detection of a mutation in the fibrillin-2 gene that is similar in
structure to the gene for fibrillin-1.

Preliminary data suggest that patients with mutations in the fibrillin-2 gene are not prone to develop
aneurysms.
5. Which of the following does N-acetylcysteine replenish?

(Please select 1 option)

Cystathionine

Cytochrome P450

Glucuronyltransferase
Glutathione CORRECT
Sulfatase

Acetylcysteine, the N-acetyl derivative of the naturally occurring amino acid l-cysteine, is a mucolytic agent
and sulfhydryl donor acting as an antidote for paracetamoloverdosage.
6. A 24-year-old man presents with proteinuria, haematuria and sensorineural deafness.

Which of the following protein structures is likely to be abnormal?

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MRCP 1 Onexamination Basic Sciences 2014

(Please select 1 option)

Fibrillin

Laminin

Type 1 collagen

Type 3 collagen

Type 4 collagen CORRECT

The diagnosis is Alport's syndrome, which is a disorder of type 4 collagen assembly and is inherited as an X
linked disorder in 85% of cases.

Fibrillin gene abnormalities are associated with Marfan's syndrome.

Type 1 collagen disorders are associated with osteogenesisimperfecta; it is the main type of collagen in tendon
and bone.

Type 3 collagen is the main component of reticular fibres.

7. A patient is found to have an acquired syndrome associated with defective breakdown and disposal of
intracellular fatty acids.

Which intracellular organelle is concerned with the breakdown of fatty acids?

(Please select 1 option)

Golgi appartus

Lysosomes

Mitochondria

Peroxisomes CORRECT
Smooth endoplasmic reticulum

Mitochondria are concerned with aerobic cell respiration and Golgi bodies are likely to be responsible for
transporting products synthesised in the smooth endoplasmic reticulum.

Smooth endoplasmic reticulum is a site of lipid synthesis within the cell.

Lysosomes (lysis- breakage, soma- body) contain digestive enzymes which break down expendable cell
organelles, engulfed viruses and other intracellular detritus.

Peroxisomes are responsible for the metabolism of fatty acids within cells.
8. A patient is diagnosed with an abnormality of oligopeptide disposal.

Which intracellular organelle is associated with the catabolism of oligopeptides?

(Please select 1 option)

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Golgi apparatus
Lysosomes CORRECT
Peroxisomes

Ribosomes

Smooth endoplasmic reticulum

Lysosomes (lysis- breakage, soma- body), carry hydrolases that degrade

Nucleotides
Proteins
Lipids
Phospholipids.

They also remove carbohydrate, sulfate, or phosphate groups from molecules.

Ribosomes are intimately associated with the rough endoplasmic reticulum and are responsible for protein
translation.

Peroxisomes are responsible for the metabolism of fatty acids within cells.

The Golgi apparatus is part of the cellular endomembrane system, which packages proteins inside the cell prior
to secretion.
9. In which part of the body is conjugated bilirubin metabolised to urobilinogen?

(Please select 1 option)

Common bile duct

Hepatic sinusoids
Large intestine CORRECT
Small intestine

Splenic macrophages

Unconjugated bilirubin is conjugated to glucuronic acid in the hepatocyte.

Conjugated bilirubin passes into the enterohepatic circulation and the bilirubin which evades this system is
metabolised by bacteria, primarily in the large intestine, to urobilinogen, then stercobilinogen and eventually
oxidised to stercobilin.

Stercobilin gives faeces its brown colour.

10. Which of the following arteries are branches of the axillary artery?

(Please select 1 option)

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MRCP 1 Onexamination Basic Sciences 2014

Inferior ulnar collateral artery

Internal thoracic artery

Profundabrachii artery
Subscapular artery CORRECT
Superior ulnar collateral artery

The internal thoracic artery arises from the subclavian artery.

The inferior and superior ulnar collateral arteries and the profundabrachii are branches of the brachial artery.

The subscapular artery arises from the axillary and is its largest branch, eventually anastomosing with the
lateral thoracic and intercostal arteries.
11. You are investigating the properties of a novel oral TNF-alpha antagonist in late stage clinical trials.

Which of the following would be an expected property of this agent?

(Please select 1 option)

Decreased endothelial reactivity

Decreased HDL cholesterol

Decreased insulin sensitivity

Decreased protein catabolism CORRECT
Increased acute phase protein production

Increased levels of TNF-alpha are known to result in protein catabolism, weight loss and muscle weakness, all
features of disseminated carcinoma where TNF-alpha is elevated. As such an antagonist of TNF-alpha would
be expected to result in decreased protein catabolism.

Chronic inflammatory disorders including those associated with elevated tumour necrosis factor (TNF) are
noted to be associated with increased arteriolar stiffness and decreased endothelial reactivity.

TNF-alpha elevation is also known to be associated with increased insulin resistance and associated lipid
abnormalities such as decreased high-density lipoprotein (HDL) cholesterol.

Increased acute phase protein production is a feature of chronic inflammation, as such a TNF-alpha antagonist
is recognised to reduce this.

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