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Question 1
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A 56-year-old woman comes to the clinic with a breast lump that she has noticed for a few weeks. She is worried because her family has a history of breast cancer. She undergoes an urgent referral for further evaluation. A biopsy of the lump is performed to check for chromosomal abnormalities, specifically extra copies of the HER2 gene.
Which method is best suited for detecting these abnormalities?Your Answer: Fluorescence in situ hybridisation
Explanation:Eastern blotting is a technique that can be used to study post-translational modifications of proteins, including the addition of lipids and phosphates. It is a valuable tool for investigating protein function and regulation.
Overview of Molecular Biology Techniques
Molecular biology techniques are essential tools used in the study of biological molecules such as DNA, RNA, and proteins. These techniques are used to detect and analyze these molecules in various biological samples. The most commonly used techniques include Southern blotting, Northern blotting, Western blotting, and enzyme-linked immunosorbent assay (ELISA).
Southern blotting is a technique used to detect DNA, while Northern blotting is used to detect RNA. Western blotting, on the other hand, is used to detect proteins. This technique involves the use of gel electrophoresis to separate native proteins based on their 3-D structure. It is commonly used in the confirmatory HIV test.
ELISA is a biochemical assay used to detect antigens and antibodies. This technique involves attaching a colour-changing enzyme to the antibody or antigen being detected. If the antigen or antibody is present in the sample, the sample changes colour, indicating a positive result. ELISA is commonly used in the initial HIV test.
In summary, molecular biology techniques are essential tools used in the study of biological molecules. These techniques include Southern blotting, Northern blotting, Western blotting, and ELISA. Each technique is used to detect specific molecules in biological samples and is commonly used in various diagnostic tests.
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This question is part of the following fields:
- General Principles
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Question 2
Incorrect
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A 28-year-old surgical trainee (ST) is conducting a research study in orthopedics to investigate the effectiveness of a new pain relief medication compared to a placebo. The ST wants to ensure that the study has enough power to detect a significant difference between the two groups if one truly exists.
What is the statistical parameter that the ST is attempting to optimize in the design of the study?Your Answer: P value
Correct Answer: Power
Explanation:Significance tests are used to determine the likelihood of a null hypothesis being true. The null hypothesis states that two treatments are equally effective, while the alternative hypothesis suggests that there is a difference between the two treatments. The p value is the probability of obtaining a result by chance that is at least as extreme as the observed result, assuming the null hypothesis is true. Two types of errors can occur during significance testing: type I, where the null hypothesis is rejected when it is true, and type II, where the null hypothesis is accepted when it is false. The power of a study is the probability of correctly rejecting the null hypothesis when it is false, and it can be increased by increasing the sample size.
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This question is part of the following fields:
- General Principles
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Question 3
Incorrect
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A 45-year-old woman presents with chest wall cellulitis after a mastectomy. Upon examination, her skin appears significantly red. Among the following acute inflammatory mediators, which one is unlikely to cause vasodilation?
Your Answer: Complement component C5a
Correct Answer: Serotonin
Explanation:Erythema is a common characteristic of acute inflammation, which is caused by various potent mediators that promote vascular dilatation. These mediators include histamine, prostaglandins, nitric oxide, platelet activating factor, complement C5a (and C3a), and lysosomal compounds. Although serotonin is also associated with acute inflammation, it acts as a vasoconstrictor. However, the effects of serotonin depend on the condition of the vessels in the tissues. When tissues and vessels are healthy, they respond to a serotonin infusion with vasodilation, resulting in flushing (as seen in carcinoid syndrome). Conversely, when released from damaged platelets, serotonin worsens cardiac ischemia in myocardial infarcts.
Acute inflammation is a response to cell injury in vascularized tissue. It is triggered by chemical factors produced in response to a stimulus, such as fibrin, antibodies, bradykinin, and the complement system. The goal of acute inflammation is to neutralize the offending agent and initiate the repair process. The main characteristics of inflammation are fluid exudation, exudation of plasma proteins, and migration of white blood cells.
The vascular changes that occur during acute inflammation include transient vasoconstriction, vasodilation, increased permeability of vessels, RBC concentration, and neutrophil margination. These changes are followed by leukocyte extravasation, margination, rolling, and adhesion of neutrophils, transmigration across the endothelium, and migration towards chemotactic stimulus.
Leukocyte activation is induced by microbes, products of necrotic cells, antigen-antibody complexes, production of prostaglandins, degranulation and secretion of lysosomal enzymes, cytokine secretion, and modulation of leukocyte adhesion molecules. This leads to phagocytosis and termination of the acute inflammatory response.
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This question is part of the following fields:
- General Principles
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Question 4
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A pharmaceutical company is conducting tests on a new insulin formulation. As part of their analysis, they have verified that tyrosine kinase receptors are activated by insulin. What is the impact of these receptors on the target molecules?
Your Answer: Target molecule phosphorylation
Explanation:Activation of tyrosine kinase receptors leads to the phosphorylation of target molecules, which can result in various effects such as cell growth and differentiation. Insulin is an example of a drug that acts through tyrosine kinase receptors. It is important to note that target molecule oxidation, lysis, and reduction are not processes typically associated with tyrosine kinase receptor activation.
Pharmacodynamics refers to the effects of drugs on the body, as opposed to pharmacokinetics which is concerned with how the body processes drugs. Drugs typically interact with a target, which can be a protein located either inside or outside of cells. There are four main types of cellular targets: ion channels, G-protein coupled receptors, tyrosine kinase receptors, and nuclear receptors. The type of target determines the mechanism of action of the drug. For example, drugs that work on ion channels cause the channel to open or close, while drugs that activate tyrosine kinase receptors lead to cell growth and differentiation.
It is also important to consider whether a drug has a positive or negative impact on the receptor. Agonists activate the receptor, while antagonists block the receptor preventing activation. Antagonists can be competitive or non-competitive, depending on whether they bind at the same site as the agonist or at a different site. The binding affinity of a drug refers to how readily it binds to a specific receptor, while efficacy measures how well an agonist produces a response once it has bound to the receptor. Potency is related to the concentration at which a drug is effective, while the therapeutic index is the ratio of the dose of a drug resulting in an undesired effect compared to that at which it produces the desired effect.
The relationship between the dose of a drug and the response it produces is rarely linear. Many drugs saturate the available receptors, meaning that further increased doses will not cause any more response. Some drugs do not have a significant impact below a certain dose and are considered sub-therapeutic. Dose-response graphs can be used to illustrate the relationship between dose and response, allowing for easy comparison of different drugs. However, it is important to remember that dose-response varies between individuals.
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This question is part of the following fields:
- General Principles
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Question 5
Incorrect
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A 4-week-old infant born in the UK presents to the emergency department with a non-blanching rash that is rapidly progressing. The baby is irritable and has a fever. The initial diagnosis is meningitis, and further investigations are pending. What is the probable causative agent?
Your Answer: Neisseria meningitidis
Correct Answer: Group B streptococci
Explanation:Lyme disease is caused by Borrelia burgdorferi.
Meningitis is a serious medical condition that can be caused by various types of bacteria. The causes of meningitis differ depending on the age of the patient and their immune system. In neonates (0-3 months), the most common cause of meningitis is Group B Streptococcus, followed by E. coli and Listeria monocytogenes. In children aged 3 months to 6 years, Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae are the most common causes. For individuals aged 6 to 60 years, Neisseria meningitidis and Streptococcus pneumoniae are the primary causes. In those over 60 years old, Streptococcus pneumoniae, Neisseria meningitidis, and Listeria monocytogenes are the most common causes. For immunosuppressed individuals, Listeria monocytogenes is the primary cause of meningitis.
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This question is part of the following fields:
- General Principles
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Question 6
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A three-year-old boy is presented to the pediatrician by his father due to repeated episodes of otitis media. The pediatrician has attempted delayed antibiotic treatments in the past, but they have not been effective. As the child has a penicillin allergy, the pediatrician follows hospital protocol and prescribes a course of macrolide antibiotic, clarithromycin.
What is the mode of action of the prescribed antibiotic?Your Answer: Inhibit protein synthesis by binding to a ribosomal subunit and blocking translocation
Explanation:Macrolides prevent protein synthesis by binding to the 50S ribosomal subunit and blocking translocation through their interaction with 23S rRNA. This is the correct mechanism of action.
Folate antagonists (such as trimethoprim) inhibit cell division by antagonizing vitamin B9, making this answer incorrect.
Tetracyclines (such as doxycycline) inhibit bacterial growth by binding to bacterial ribosomes, making this answer incorrect.
Nitroimidazoles (such as metronidazole) disrupt microbial DNA in anaerobic bacteria and protozoa, inhibiting nucleic acid synthesis, making this answer incorrect.
Macrolides are a class of antibiotics that include erythromycin, clarithromycin, and azithromycin. They work by blocking translocation during bacterial protein synthesis, ultimately inhibiting bacterial growth. While they are generally considered bacteriostatic, their effectiveness can vary depending on the dose and type of organism being treated. Resistance to macrolides can occur through post-transcriptional methylation of the 23S bacterial ribosomal RNA.
However, macrolides can also have adverse effects. They may cause prolongation of the QT interval and gastrointestinal side-effects, such as nausea. Cholestatic jaundice is a potential risk, but using erythromycin stearate may reduce this risk. Additionally, macrolides are known to inhibit the cytochrome P450 isoenzyme CYP3A4, which metabolizes statins. Therefore, it is important to stop taking statins while on a course of macrolides to avoid the risk of myopathy and rhabdomyolysis. Azithromycin is also associated with hearing loss and tinnitus.
Overall, while macrolides can be effective antibiotics, they do come with potential risks and side-effects. It is important to weigh the benefits and risks before starting a course of treatment with these antibiotics.
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This question is part of the following fields:
- General Principles
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Question 7
Incorrect
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Mrs Green is admitted via the emergency department and found to have a large liver abscess. She undergoes CT guided aspiration and the fluid is sent off for analysis. Initial microscopy demonstrates a large population of neutrophils.
Which of the following cytokines is likely to have been responsible for this cell infiltration?Your Answer: Interleukin-10
Correct Answer: Interleukin-8
Explanation:Interleukins (IL) are cytokines that have various important roles in the immune system. One such IL is IL-8, which is produced by macrophages and is responsible for the chemotaxis of neutrophils. This is crucial in the acute inflammatory response, as neutrophils are recruited to areas of inflammation.
Another important IL is IL-2, which is produced by T helper 1 cells and stimulates the growth and development of various immune cells, including T cells, B cells, and natural killer cells. This makes it essential for fighting infections.
IL-4, produced by T helper 2 cells, activates B cells and can also induce the differentiation of CD4+ T cells into T helper 2 cells. It plays a crucial role in dealing with infections.
IL-5, also produced by T helper 2 cells, primarily stimulates the production of eosinophils.
Finally, IL-10 is produced by both macrophages and T helper 2 cells. It is an anti-inflammatory cytokine that inhibits cytokine production from T helper 1 cells.
Overview of Cytokines and Their Functions
Cytokines are signaling molecules that play a crucial role in the immune system. Interleukins are a type of cytokine that are produced by various immune cells and have specific functions. IL-1, produced by macrophages, induces acute inflammation and fever. IL-2, produced by Th1 cells, stimulates the growth and differentiation of T cell responses. IL-3, produced by activated T helper cells, stimulates the differentiation and proliferation of myeloid progenitor cells. IL-4, produced by Th2 cells, stimulates the proliferation and differentiation of B cells. IL-5, also produced by Th2 cells, stimulates the production of eosinophils. IL-6, produced by macrophages and Th2 cells, stimulates the differentiation of B cells and induces fever. IL-8, produced by macrophages, promotes neutrophil chemotaxis. IL-10, produced by Th2 cells, inhibits Th1 cytokine production and is known as an anti-inflammatory cytokine. IL-12, produced by dendritic cells, macrophages, and B cells, activates NK cells and stimulates the differentiation of naive T cells into Th1 cells.
In addition to interleukins, there are other cytokines with specific functions. Tumor necrosis factor-alpha, produced by macrophages, induces fever and promotes neutrophil chemotaxis. Interferon-gamma, produced by Th1 cells, activates macrophages. Understanding the functions of cytokines is important in developing treatments for various immune-related diseases.
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This question is part of the following fields:
- General Principles
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Question 8
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A 25-year-old female presents to her GP with concerns about her acne. Despite trying topical benzoyl peroxide and isotretinoin, she has not seen any improvement. The GP decides to prescribe a prolonged course of doxycycline. What is a potential side effect of this medication?
Your Answer: Photosensitivity
Explanation:Photosensitivity can be caused by tetracyclines, including doxycycline. Co-amoxiclav and flucloxacillin can lead to cholestatic jaundice, while aminoglycosides like gentamicin can cause ototoxicity. Vancomycin is associated with ‘red man syndrome’ and both aminoglycosides and glycopeptides (such as vancomycin) can be nephrotoxic.
Understanding Tetracyclines: Antibiotics Used in Clinical Practice
Tetracyclines are a group of antibiotics that are commonly used in clinical practice. They work by inhibiting protein synthesis, specifically by binding to the 30S subunit and blocking the binding of aminoacyl-tRNA. However, bacteria can develop resistance to tetracyclines through increased efflux by plasmid-encoded transport pumps or ribosomal protection.
Tetracyclines are used to treat a variety of conditions such as acne vulgaris, Lyme disease, Chlamydia, and Mycoplasma pneumoniae. However, they should not be given to children under 12 years of age or to pregnant or breastfeeding women due to the risk of discolouration of the infant’s teeth.
While tetracyclines are generally well-tolerated, they can cause adverse effects such as photosensitivity, angioedema, and black hairy tongue. It is important to be aware of these potential side effects and to use tetracyclines only as prescribed by a healthcare professional.
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This question is part of the following fields:
- General Principles
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Question 9
Incorrect
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As a junior doctor on the infectious diseases ward, you come across a 42-year-old man who has been experiencing shortness of breath, haemoptysis, weight loss, and cough for the past two months. He has lost 5kg in weight and has recently returned from India where he worked for 18 months. Blood tests show no abnormalities, but a chest x-ray reveals left upper zone consolidation surrounding a round, mass lesion. Further evaluation through high-resolution CT (HRCT) of the chest shows left upper lobe consolidation surrounding a 1.7cm, smooth rimmed lesion with a degree of calcification, with no evidence of cavitation or other acute lung pathology. The diagnosis is primary tuberculosis with evidence of tuberculoma formation. Which cytokine is integral to the development of this man's CT findings?
Your Answer: Tumour necrosis factor alpha
Correct Answer: Interferon-gamma
Explanation:Interferon-gamma is primarily produced by natural killer cells and T helper cells, and plays a key role in macrophage activation, leading to the formation of granulomas. It is also important in preventing tuberculosis by inhibiting intracellular phagolysosomal maturation, allowing for the destruction of infected cells. Interferon-alpha, produced by leukocytes and dendritic cells, has strong antiviral action and activates natural killer cells to form an antiviral and anti-tumor response. Interferon-beta, produced primarily by fibroblasts, also has strong antiviral action and is important in the formation of antiviral and anti-tumor responses. Interleukin-12 is important in tuberculosis infection by activating T helper cell differentiation and natural killer cell activation, and aiding in interferon-gamma release for further macrophage activation, but it does not lead to granuloma formation.
Understanding Interferons
Interferons are a type of cytokine that the body produces in response to viral infections and neoplasia. They are categorized based on the type of receptor they bind to and their cellular origin. IFN-alpha and IFN-beta bind to type 1 receptors, while IFN-gamma binds only to type 2 receptors.
IFN-alpha is produced by leucocytes and has antiviral properties. It is commonly used to treat hepatitis B and C, Kaposi’s sarcoma, metastatic renal cell cancer, and hairy cell leukemia. However, it can cause flu-like symptoms and depression as side effects.
IFN-beta is produced by fibroblasts and also has antiviral properties. It is particularly useful in reducing the frequency of exacerbations in patients with relapsing-remitting multiple sclerosis.
IFN-gamma is mainly produced by natural killer cells and T helper cells. It has weaker antiviral properties but plays a significant role in immunomodulation, particularly in macrophage activation. It may be beneficial in treating chronic granulomatous disease and osteopetrosis.
Understanding the different types of interferons and their functions can help in the development of targeted treatments for various diseases.
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This question is part of the following fields:
- General Principles
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Question 10
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A 23-year-old woman with known allergies presents to the emergency department with difficulty breathing after eating at a restaurant.
Upon arrival, she exhibits an audible wheeze, swelling of her lips and tongue, and a widespread urticarial rash. Intramuscular adrenaline is promptly administered, resulting in rapid improvement of her condition.
After being observed for a period of time, she is discharged with two auto-injectors containing the same medication for future use and a plan for outpatient follow-up at an allergy clinic.
What is the receptor targeted by this medication?Your Answer: G protein-coupled
Explanation:Adrenaline exerts its effects through G protein-coupled receptors, which are transmembrane proteins that activate intracellular signaling pathways. This mechanism is responsible for the vasoconstriction induced by adrenaline, which is used to counteract the vasodilation and increased vascular permeability seen in anaphylaxis. However, adrenaline does not act on guanylate cyclase receptors, ligand-gated ion channel receptors, or serine/threonine kinase receptors, which are other types of transmembrane proteins that respond to different chemical messengers.
Membrane receptors are proteins located on the surface of cells that receive signals from outside the cell and transmit them inside. There are four main types of membrane receptors: ligand-gated ion channel receptors, tyrosine kinase receptors, guanylate cyclase receptors, and G protein-coupled receptors. Ligand-gated ion channel receptors mediate fast responses and include nicotinic acetylcholine, GABA-A & GABA-C, and glutamate receptors. Tyrosine kinase receptors include receptor tyrosine kinase such as insulin, insulin-like growth factor (IGF), and epidermal growth factor (EGF), and non-receptor tyrosine kinase such as PIGG(L)ET, which stands for Prolactin, Immunomodulators (cytokines IL-2, Il-6, IFN), GH, G-CSF, Erythropoietin, and Thrombopoietin.
Guanylate cyclase receptors contain intrinsic enzyme activity and include atrial natriuretic factor and brain natriuretic peptide. G protein-coupled receptors generally mediate slow transmission and affect metabolic processes. They are activated by a wide variety of extracellular signals such as peptide hormones, biogenic amines (e.g. adrenaline), lipophilic hormones, and light. These receptors have 7-helix membrane-spanning domains and consist of 3 main subunits: alpha, beta, and gamma. The alpha subunit is linked to GDP. Ligand binding causes conformational changes to the receptor, GDP is phosphorylated to GTP, and the alpha subunit is activated. G proteins are named according to the alpha subunit (Gs, Gi, Gq).
The mechanism of G protein-coupled receptors varies depending on the type of G protein involved. Gs stimulates adenylate cyclase, which increases cAMP and activates protein kinase A. Gi inhibits adenylate cyclase, which decreases cAMP and inhibits protein kinase A. Gq activates phospholipase C, which splits PIP2 to IP3 and DAG and activates protein kinase C. Examples of G protein-coupled receptors include beta-1 receptors (epinephrine, norepinephrine, dobutamine), beta-2 receptors (epinephrine, salbuterol), H2 receptors (histamine), D1 receptors (dopamine), V2 receptors (vas
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