NBME CBSE (usmle step 1)MEDICAL - 190 Questions and
Answers Already Graded A+ Premium Exam Tested And
Verified
Subject Area NBME CBSE (USMLE Step 1) Medical
Description This comprehensive examination assesses foundational knowledge in basic
medical sciences, including anatomy, physiology, biochemistry, pathology,
pharmacology, microbiology, immunology, and behavioral sciences. It is designed
to evaluate the ability to integrate and apply concepts to clinical scenarios,
reflecting the rigor of USMLE Step 1.
Expected Grade A+
Total Questions 190
Duration 3 hours
Learning Outcomes 1. Apply principles of molecular and cellular biology to disease mechanisms.
2. Interpret physiological and pathological data to diagnose conditions.
3. Analyze pharmacological interventions and their mechanisms of action.
4. Integrate knowledge of microbiology and immunology in infectious disease
management.
5. Utilize biostatistics and epidemiology to evaluate medical literature.
Accreditation This examination aligns with the standards of the National Board of Medical
Examiners (NBME) and is designed to meet the rigorous expectations of top-tier
US medical schools.
Page 1
,1. A 35-year-old individual presents with episodic hypertension, palpitations,
and severe headaches. Laboratory studies show elevated plasma
metanephrines. Imaging reveals a 3 cm adrenal mass. Which of the following
enzymatic defects is most likely associated with the pathogenesis of this tumor?
Answer: Succinate dehydrogenase deficiency
Pheochromocytomas are often associated with mutations in succinate
dehydrogenase (SDH) subunits, leading to pseudohypoxia and tumorigenesis.
Tyrosine hydroxylase is rate-limiting for catecholamine synthesis but not a
common defect. PNMT converts norepinephrine to epinephrine; deficiency would
shift catecholamine profile but is not causative. MAO-A deficiency affects
catecholamine metabolism but is not linked to tumor formation.
2. A researcher is studying a signaling pathway where a ligand binds to a
receptor tyrosine kinase, leading to activation of Ras and subsequent MAP
kinase cascade. Which of the following mutations would most likely result in
constitutive activation of this pathway independent of ligand binding?
Answer: Loss-of-function mutation in the GTPase-activating protein (GAP)
for Ras
GAPs accelerate GTP hydrolysis by Ras, inactivating it. Loss-of-function of GAP
leads to persistent Ras-GTP, constitutive signaling. Receptor phosphatase
mutations would reduce dephosphorylation but not directly activate Ras. Grb2
SH2 domain loss impairs signaling. MEK mutation preventing phosphorylation
would decrease signaling.
3. A study investigates the effect of a new drug on cardiac contractility. In
isolated cardiomyocytes, the drug increases the amplitude of calcium transients
without affecting L-type calcium channel current. Which of the following is the
most likely mechanism of action?
Answer: Inhibition of phospholamban
Phospholamban inhibits SERCA; its inhibition increases SR calcium uptake,
augmenting calcium stores and subsequent release, increasing transient
amplitude without affecting L-type current. Ryanodine receptor activation would
increase release but also deplete stores. NCX inhibition could increase cytosolic
calcium but not specifically transients. SERCA activation also increases stores,
but phospholamban inhibition is a more direct regulator.
Page 2
,4. A 45-year-old individual with a history of recurrent sinopulmonary
infections and autoimmune hemolytic anemia is found to have a serum protein
electrophoresis showing hypogammaglobulinemia. Flow cytometry of
peripheral blood shows decreased CD19+ B cells and absence of class-switched
memory B cells. Which of the following defects is most likely?
Answer: CD40 ligand deficiency
CD40 ligand deficiency (X-linked hyper-IgM syndrome) impairs germinal center
formation, leading to lack of class-switched memory B cells,
hypogammaglobulinemia, and recurrent infections with autoimmune
phenomena. ICOS deficiency causes common variable immunodeficiency with
defective germinal centers but class switching may be partially preserved. BTK
deficiency (XLA) has absent B cells. AID deficiency prevents class switching but
B cell numbers are normal.
5. A 30-year-old individual presents with fatigue, arthralgias, and a malar
rash. Laboratory findings include positive antinuclear antibody (ANA),
anti-double-stranded DNA antibodies, and low complement levels. Renal
biopsy shows diffuse proliferative glomerulonephritis with subendothelial
deposits. Which of the following immunologic mechanisms is most directly
responsible for the renal injury?
Answer: Type III hypersensitivity
SLE with diffuse proliferative glomerulonephritis is a classic immune
complex-mediated disease (Type III hypersensitivity). Subendothelial deposits
represent immune complexes that activate complement and recruit inflammatory
cells. Type I involves IgE/mast cells. Type II involves antibodies against cell
surface antigens. Type IV is T-cell mediated.
Page 3
, 6. A 60-year-old individual with chronic obstructive pulmonary disease
(COPD) is prescribed a new bronchodilator. The drug is a muscarinic receptor
antagonist. Which of the following receptor subtypes does this drug most likely
target to achieve bronchodilation?
Answer: M3
M3 receptors are located on airway smooth muscle and mediate
bronchoconstriction. Antagonism of M3 leads to bronchodilation. M1 receptors
are on parasympathetic ganglia; M2 are presynaptic autoreceptors that inhibit
acetylcholine release; M4 is less relevant in airways. Thus, M3 is the primary
target.
7. A researcher is studying a bacterium that produces a toxin that cleaves a
host protein essential for neurotransmitter release. The toxin acts as a
zinc-dependent metalloprotease. Which of the following toxins is most
consistent with this description?
Answer: Botulinum toxin
Botulinum toxin is a zinc metalloprotease that cleaves SNARE proteins,
preventing acetylcholine release at neuromuscular junctions. Tetanus toxin also
cleaves SNARE proteins but acts on inhibitory interneurons. Cholera toxin is an
ADP-ribosyltransferase. Diphtheria toxin inhibits protein synthesis via
ADP-ribosylation of elongation factor 2.
8. A clinical trial compares two treatments for hypertension. The mean
reduction in systolic blood pressure is 12 mmHg for drug A and 8 mmHg for
drug B. The p-value for the difference is 0.04. Which of the following is the
most appropriate interpretation?
Answer: The probability of observing a difference of 4 mmHg or more if no
true difference exists is 4%
The p-value is the probability of obtaining the observed results (or more extreme)
under the null hypothesis of no difference. Option B correctly defines this. Option
A misinterprets p-value as probability of null being true. Option C is a relative
effect not directly derived. Option D is false because p<0.05 indicates the CI
excludes zero.
Page 4
Answers Already Graded A+ Premium Exam Tested And
Verified
Subject Area NBME CBSE (USMLE Step 1) Medical
Description This comprehensive examination assesses foundational knowledge in basic
medical sciences, including anatomy, physiology, biochemistry, pathology,
pharmacology, microbiology, immunology, and behavioral sciences. It is designed
to evaluate the ability to integrate and apply concepts to clinical scenarios,
reflecting the rigor of USMLE Step 1.
Expected Grade A+
Total Questions 190
Duration 3 hours
Learning Outcomes 1. Apply principles of molecular and cellular biology to disease mechanisms.
2. Interpret physiological and pathological data to diagnose conditions.
3. Analyze pharmacological interventions and their mechanisms of action.
4. Integrate knowledge of microbiology and immunology in infectious disease
management.
5. Utilize biostatistics and epidemiology to evaluate medical literature.
Accreditation This examination aligns with the standards of the National Board of Medical
Examiners (NBME) and is designed to meet the rigorous expectations of top-tier
US medical schools.
Page 1
,1. A 35-year-old individual presents with episodic hypertension, palpitations,
and severe headaches. Laboratory studies show elevated plasma
metanephrines. Imaging reveals a 3 cm adrenal mass. Which of the following
enzymatic defects is most likely associated with the pathogenesis of this tumor?
Answer: Succinate dehydrogenase deficiency
Pheochromocytomas are often associated with mutations in succinate
dehydrogenase (SDH) subunits, leading to pseudohypoxia and tumorigenesis.
Tyrosine hydroxylase is rate-limiting for catecholamine synthesis but not a
common defect. PNMT converts norepinephrine to epinephrine; deficiency would
shift catecholamine profile but is not causative. MAO-A deficiency affects
catecholamine metabolism but is not linked to tumor formation.
2. A researcher is studying a signaling pathway where a ligand binds to a
receptor tyrosine kinase, leading to activation of Ras and subsequent MAP
kinase cascade. Which of the following mutations would most likely result in
constitutive activation of this pathway independent of ligand binding?
Answer: Loss-of-function mutation in the GTPase-activating protein (GAP)
for Ras
GAPs accelerate GTP hydrolysis by Ras, inactivating it. Loss-of-function of GAP
leads to persistent Ras-GTP, constitutive signaling. Receptor phosphatase
mutations would reduce dephosphorylation but not directly activate Ras. Grb2
SH2 domain loss impairs signaling. MEK mutation preventing phosphorylation
would decrease signaling.
3. A study investigates the effect of a new drug on cardiac contractility. In
isolated cardiomyocytes, the drug increases the amplitude of calcium transients
without affecting L-type calcium channel current. Which of the following is the
most likely mechanism of action?
Answer: Inhibition of phospholamban
Phospholamban inhibits SERCA; its inhibition increases SR calcium uptake,
augmenting calcium stores and subsequent release, increasing transient
amplitude without affecting L-type current. Ryanodine receptor activation would
increase release but also deplete stores. NCX inhibition could increase cytosolic
calcium but not specifically transients. SERCA activation also increases stores,
but phospholamban inhibition is a more direct regulator.
Page 2
,4. A 45-year-old individual with a history of recurrent sinopulmonary
infections and autoimmune hemolytic anemia is found to have a serum protein
electrophoresis showing hypogammaglobulinemia. Flow cytometry of
peripheral blood shows decreased CD19+ B cells and absence of class-switched
memory B cells. Which of the following defects is most likely?
Answer: CD40 ligand deficiency
CD40 ligand deficiency (X-linked hyper-IgM syndrome) impairs germinal center
formation, leading to lack of class-switched memory B cells,
hypogammaglobulinemia, and recurrent infections with autoimmune
phenomena. ICOS deficiency causes common variable immunodeficiency with
defective germinal centers but class switching may be partially preserved. BTK
deficiency (XLA) has absent B cells. AID deficiency prevents class switching but
B cell numbers are normal.
5. A 30-year-old individual presents with fatigue, arthralgias, and a malar
rash. Laboratory findings include positive antinuclear antibody (ANA),
anti-double-stranded DNA antibodies, and low complement levels. Renal
biopsy shows diffuse proliferative glomerulonephritis with subendothelial
deposits. Which of the following immunologic mechanisms is most directly
responsible for the renal injury?
Answer: Type III hypersensitivity
SLE with diffuse proliferative glomerulonephritis is a classic immune
complex-mediated disease (Type III hypersensitivity). Subendothelial deposits
represent immune complexes that activate complement and recruit inflammatory
cells. Type I involves IgE/mast cells. Type II involves antibodies against cell
surface antigens. Type IV is T-cell mediated.
Page 3
, 6. A 60-year-old individual with chronic obstructive pulmonary disease
(COPD) is prescribed a new bronchodilator. The drug is a muscarinic receptor
antagonist. Which of the following receptor subtypes does this drug most likely
target to achieve bronchodilation?
Answer: M3
M3 receptors are located on airway smooth muscle and mediate
bronchoconstriction. Antagonism of M3 leads to bronchodilation. M1 receptors
are on parasympathetic ganglia; M2 are presynaptic autoreceptors that inhibit
acetylcholine release; M4 is less relevant in airways. Thus, M3 is the primary
target.
7. A researcher is studying a bacterium that produces a toxin that cleaves a
host protein essential for neurotransmitter release. The toxin acts as a
zinc-dependent metalloprotease. Which of the following toxins is most
consistent with this description?
Answer: Botulinum toxin
Botulinum toxin is a zinc metalloprotease that cleaves SNARE proteins,
preventing acetylcholine release at neuromuscular junctions. Tetanus toxin also
cleaves SNARE proteins but acts on inhibitory interneurons. Cholera toxin is an
ADP-ribosyltransferase. Diphtheria toxin inhibits protein synthesis via
ADP-ribosylation of elongation factor 2.
8. A clinical trial compares two treatments for hypertension. The mean
reduction in systolic blood pressure is 12 mmHg for drug A and 8 mmHg for
drug B. The p-value for the difference is 0.04. Which of the following is the
most appropriate interpretation?
Answer: The probability of observing a difference of 4 mmHg or more if no
true difference exists is 4%
The p-value is the probability of obtaining the observed results (or more extreme)
under the null hypothesis of no difference. Option B correctly defines this. Option
A misinterprets p-value as probability of null being true. Option C is a relative
effect not directly derived. Option D is false because p<0.05 indicates the CI
excludes zero.
Page 4
