USMLE USMLE-STEP-1 Online Practice Questions and Exam Preparation

USMLE USMLE-STEP-1 Online Questions & Answers

• Question 361:

  The term "genomic imprinting" refers to the phenomenon of gene expression dependence on the mode of inheritence. A typical example of this phenomenon is the control of the expression of the growth factor IGF- II. Genomic imprinting, termed "epigenesis," is defined by which of the following?

  A. Gene expression results from regulated levels of DNA methylation.
  B. Gene expression that is restricted to a specific cell lineage.
  C. Gene regulation is exerted by sex-type specifc factors.
  D. Genotype differences are not reflected by phenotype differences.
  E. Phenotype differences are independent of genotype variation.
  E. Phenotype differences are independent of genotype variation.

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  Explanation

  Section: Biochemistry Epigenesis refers to the phenomenon where phenotypic differences are present in the same species, but this difference is not due to differences in the genotype of the organism. None of the other examples (choices AD) define epigenesis.

• Question 362:

  Obesity, genetic profile, and aging all contribute to the development of Type II diabetes. Of the following, which is the most important additive factor for these three conditions in the development of Type II diabetes?

  A. elevated hepatic ketogenesis
  B. elevated pancreatic glucagon secretion
  C. impaired renal clearance of glucose
  D. increased adipose tissue activity leading to hyperlipidemia
  E. muscle resistance to insulin
  E. muscle resistance to insulin

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  Explanation

  Section: Biochemistry The influence of obesity, genetic profile, and age on overall metabolism is most significant at the level of skeletal muscle sensitivity to the actions of insulin (below figure). Due to the overall mass of skeletal muscle in the body, the uptake of glucose by this tissue, and consequently its role in blood glucose homeostasis, is a significant factor in insulin responses. Progressive loss of skeletal muscle sensitivity to insulin leads to increased rates of visceral cell lipolysis and pancreatic beta-cell compensation.

  Eventually, the pancreas can no longer continue compensating for impaired insulin responses and pancreatic beta-cell decompensation occurs, further exacerbating the problem. The disrupted insulin response leads to increased hepatic gluconeogenesis, which further increases circulating glucose levels. The overall outcome of these reposnses is development of progressisely worsening Type II diabetes. Whereas, each of the other options (choices AD) will ensue due to impaired insulin responses in skeletal muscle, none is significant in the development of diabetes.

• Question 363:

  The ventricular action potential labeled N in below figure represents a normal ventricular action potential. Which of the other action potentials (labeled AE) would be most characteristic of the ventricular cell after administration of a drug that partially blocks slow calcium channels?

  

  A. A
  B. B
  C. C
  D. D
  E. E
  D. D

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  Explanation

  Section: Physiology The slow calcium channels function in the ventricular myocardial cell to allow the influx of calcium into the cell, which has the dual role of triggering the calcium-mediated contractile mechanism and maintaining the depolarized state after the voltage-gated sodium channels close, soon after the rapid upstroke. Hence, blocking these channels will shorten the plateau phase of the action potential as seen in choice D, while also decreasing the contractile force of the heart. In choice A action potential duration is also shortened, but in a manner that would reflect blockade of the rapid voltagegated sodium channels, not the slow calcium channels. Choice B represents no change in the action potential. Choice C would occur if the drug prolonged the open state of the slow calcium channels. The hyperpolarization of choice E is more likely the result of increased potassium channel currents.

• Question 364:

  Regulation of cholesterol, fatty acid, phospholipid, and triglyceride synthesis is controlled in part by the level of sterols. These sterol-regulated biosynthesis pathways involve a unique family of transcription factors that are best described by which of the following?

  A. Binding of sterols to these factors induces a conformational change preventing interaction with RNA polymerase.
  B. They are membrane-bound proteins and only released on activation of a sterolregulated protease.
  C. They contain zinc fingers that bind sterols leading to their activation.
  D. They require interaction with sterols, much like steroid hormone receptors, prior to binding to DNA.
  E. On sterol binding, these factors are recognized by the proteosome and thus targeted for degradation.
  B. They are membrane-bound proteins and only released on activation of a sterolregulated protease.

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  Explanation

  Section: Biochemistry The continual alteration of the intracellular sterol content occurs through the regulation of key sterol synthetic enzymes, as well as by altering the levels of cell-surface LDL receptors. As cells need more sterol they will induce their synthesis and uptake, conversely when the need declines synthesis and uptake are decreased. Regulation of these events is brought about primarily by sterol-regulated transcription of key rate-limiting enzymes and by the regulated degradation of HMGR. Activation of transcriptional control occurs through the regulated cleavage of the membrane- bound transcription factor SREBP (there are three SREBPs). Sterol control of transcription affects more than 30 genes involved in the biosynthesis of cholesterol, triacylglycerols, phospholipids, and fatty acids. Transcriptional control requires the presence of an octamer sequence in the gene termed the sterol regulatory element, SRE-1. It has been shown that SREBP is the transcription factor that binds to SRE- 1 elements. All three SREBPs are proteolytically regulated by sterols. Full-length SREBPs have several domains and are embedded in the membrane of the ER. The N-terminal domain contains a transcription factor motif of the basic helix-loop-helix (bHLH) type that is exposed to the cytoplasmic side of the ER (see below figure). When sterols are scarce, cleavage of the full-length SREBP takes place with the result being that the N-terminal bHLH motif is released into the cytosol. The bHLH domain then migrates to the nucleus to direct transcription. Conversely, when sterols are abundant, cleavage of SREBP is inhibited. To control the level of SREBP-mediated transcription, the soluble bHLH domain is itself subject to rapid proteolysis. The cleavage of SREBP is carried out by two distinct enzymes, one of which is regulated by sterols. The regulated cleavage occurs in the lumenal loop between the two transmembrane domains. This cleavage is catalyzed by site-1 protease, S1P. High sterol content blocks the activity of S1P. The second cleavage, catalyzed by site-2 protease, S2P, occurs in the first transmembrane span, leading to release of active SREBP. In order for S2P to act on SREBP, site-1 must already have been cleaved. Additional studies on sterol-regulated gene expression demonstrated that cleavage of SREBP by S1P is controlled by the level and action of an additional protein termed, SREBP leavage-activating protein, SCAP.

  

  SCAP is a large protein also found in the ER membrane and contains at least eight transmembrane spans. The C-terminal portion, which extends into the cytosol, has been shown to interact with the C- terminal domain of SREBP. This C-terminal region of SCAP contains four motifs called WD40 repeats. The WD40 repeats are required for interaction of SCAP with SREBP. The function of SCAP is to positively stimulate S1P-mediated cleavage of SREBP. The function of sterols is to inhibit this positive action of SCAP. The activity of SCAP involves movement from the ER to the Golgi and back. Because the C-terminus of SCAP interacts with SREBP, movement of SCAP takes SREBP along for the ride. When sterols are low, SCAP and SREBP move to the Golgi. This transit is required for SREBP cleavage as S1P is Golgi-localized. When sterols are high, movement of SCAP is halted. Thus, the overall effect of sterols is to regulate the ability of SCAP to present SREBP to S1P. None of the other choices (A, CE) represent the mechanisms of sterol-mediated regulation of gene expression.

• Question 365:

  The tetracycline antimicrobials are effective specifically in prokaryotes due to which of the following activities?

  A. They are transported into prokaryotes but not into eukaryotes.
  B. They bind to prokaryotic and not eukaryotic DNA-directed RNA polymerase.
  C. They bind to prokaryotic but not eukaryotic membranes.
  D. They bind to prokaryotic but not eukaryotic aminoacyl-tRNAs.
  E. They inhibit prokaryotic protein synthesis initiation, which specifically requires formylmethionyl tRNA.
  A. They are transported into prokaryotes but not into eukaryotes.

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  Explanation

  Section: Microbiology/Immunology The specificity of the tetracycline antibiotics is attributable to an energy-dependent transport system present in prokaryotes, but not in eukaryotic cells. This transport system results in accumulation of the drug inside the bacterial cell, where it binds to the ribosome and interferes with binding of aminoacyl tRNA to the acceptor site. Tetracyclines bind to the bacterial ribosome, but not to DNA-directed RNA polymerase, or prokaryotic membranes (choices B and C). Tetracyclines do not inhibit initiation of protein synthesis, which specifically requires formylmethionyl tRNA (choice E). Both prokaryotic and eukaryotic cells bind tetracyclines. However, the prokaryotic cells have much more effective tetracycline transport systems than eukaryotic cells. Thus, prokaryotic cells accumulate higher intracellular concentrations of tetracyclines than eukaryotic cells, which induce a significant inhibition of protein synthesis only in prokaryote cells (choice D).

• Question 366:

  The graph in below figure shows the pressurevolume curve of the left ventricle of this patient (shaded area). The pressurevolume curve of a normal subject is shown for comparison (broken lines). Compared to normal, which term best describes this patient's heart?

  

  A. decreased afterload
  B. decreased preload
  C. decreased stroke volume
  D. increased force of contraction
  E. increased preload
  D. increased force of contraction

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  Explanation

  Section: Physiology Note that the end-diastolic volume of this patient is the same as that of a normal subject. Because the patient's stroke volume is larger than that of a normal subject, the force of contraction must also be larger. This could be due to increased sympathetic tone or to the fact that the patient took inotropic medications. The volume remaining after the ventricular contraction is correspondingly smaller compared to normal. Preload (choices B and E) equals end-diastolic volume and is the same in the patient and normal subjects. Afterload (choice A) is equal to arterial pressure. Both afterload and stroke volume (choice C) are larger in this patient compared to normal.

• Question 367:

  A 54-year-old construction worker collapses at his work site and is brought to the emergencyroom in a comatose state. His skin is dry and hot and his rectal temperature is 105<pdf2txt-u>癋</pdf2txt-u>. Which of the following is the most likely diagnosis?

  A. heat cramps
  B. heat exhaustion
  C. heat stroke
  D. malignant hyperthermia
  E. pyrexia
  C. heat stroke

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  Explanation

  Section: Pathology and Path physiology Heat stroke is a life-threatening condition resulting from a failure of heat regulation. It is marked by high body core temperature and the failure of sweating. Heat cramps (choice A) are the result of the loss of fluid and electrolytes through sweating. Painful cramping of muscles can occur, but core temperature remains normal. Heat exhaustion (choice B) results from excessive sweating and failure to replace the lost fluid. This results in hypovolemia, venous pooling, and reduced cardiac output. The skin is wet and the temperature is usually normal. Heat exhaustion is not life threatening, and there is usually spontaneous recovery when the person is moved to a cool place. Malignant hyperthermia (choice D) is an inherited condition in which there is an increased temperature when the person is exposed to certain anesthetics. It has no relationship to environmental temperature. Pyrexia (choice E) is fever and is usually defined as a cytokine-mediated increase in body temperature as part of a response to disease.

  This results in the hypothalamus having a higher "set point" for the body's temperature.

• Question 368:

  A 52-year-old male patient with a history of alcoholism is brought to the emergency room because of a sudden onset of right upper quadrant pain, nausea, blood in the vomitus, and fever. Ultrasound diagnosis reveals a portal vein obstruction caused by liver cirrhosis and accompanied by esophageal varices. Proper portal circulation must be reestablished to alleviate the esophargeal varices, and the attending surgeon decides on an end-to-side portocaval shunt. Which of the following describes the chosen procedure?

  A. anastomosis by communication between the portal vein and the inferior vena cava
  B. anastomosis by prosthetic vascular graft between the inferior vena cava and the superior mesenteric vein
  C. anastomosis by suturing the inferior end of the portal vein to the inferior vena cava
  D. anastomosis of the splenic vein to the left renal vein
  E. placement of an expandable stent between a hepatic vein and the portal vein
  C. anastomosis by suturing the inferior end of the portal vein to the inferior vena cava

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  Explanation

  Section: Anatomy Suturing the inferior end of the portal vein to the inferior vena cava is termed end-to-side portocaval shunt, whereas establishing a communication between the portal vein and the inferior vena cava (choice A) is a side-to-side portocaval shunt. Placing a prosthetic vascular graft between the inferior vena cava and the superior mesenteric vein (choice B) is termed a mesocaval shunt. Anastomosis of the splenic vein to the left renal vein (choice D) is a splenorenal or Warren shunt. Placement of an expandable stent between the hepatic vein and portal vein (choice E) is called a transjugular intrahepatic portosystemic shunt or TIPS.

• Question 369:

  Which of the following beta-lactam drugs has good activity against beta-lactamase-producing organisms and penetrates readily into cerebrospinal fluid?

  A. amoxicillin
  B. cefazolin
  C. clavulanic acid
  D. imipenem
  E. ticarcillin
  D. imipenem

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  Explanation

  Section: Pharmacology Imipenem is the only drug listed that is effective against many beta-lactamase-producing organisms and penetrate the bloodbrain barrier. Clavulanic acid C. is an inhibitor of beta lactamase and is used with an antibiotic but is not an antibiotic itself. None of the other drugs (choices A, B, D, and E) readily penetrate in the cerebrospinal fluid.

• Question 370:

  Zolpidem is a newer sedative-hypnotic drug approved for use as a sleeping pill. Which of the following statements describes the major difference between zolpidem and older hypnotics such as barbiturates and benzodiazepines?

  A. associated with thrombocytopenia
  B. does not act on chloride channels in the CNS
  C. has significant anticonvulsant activity
  D. much longer duration of action
  E. reduced addiction liability
  E. reduced addiction liability

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  Explanation

  Section: Pharmacology Zolpidem has greatly reduced addiction liability compared to barbiturates and benzodiazepines even though it does act on chloride channels (choice B). Zolpidem does not have major anticonvulsant actions (choice C), a longer duration of action (choice D), or thrombocytopenic toxicity (choice A).