Biochemistry

First Aid Express 2015 workbook: BIOCHEMISTRY page 1

Copyright © 2015 by MedIQ Learning, LLC All rights reserved v1.0

Biochemistry

Using this table as a guide, read the Facts in First Aid for the USMLE Step 1 2015, watch the corresponding First Aid Express 2014 videos, and then answer the workbook questions.

Facts in First Aid for the USMLE Step 1 2015

Corresponding First Aid Express 2015 videos

Workbook questions

62.1–71.3 Molecular (4 videos) 1–23

72.1–77.3 Cellular (3 videos) 24–44

77.4–79.4 Laboratory Techniques (2 videos) 45–51

80.1–88.1 Genetics (5 videos) 52–71

88.2–95.1 Nutrition (2 videos) 72–73

95.2–115.3 Metabolism (13 videos) 74–91

How to Use the Workbook with the Videos

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It was generated on 2015-08-12T14:06:10-04:00

page 2 First Aid Express 2015 workbook: BIOCHEMISTRY


MOLECULAR

1. Which histone is not part of the nucleosome core? (p. 62) ________________________________

2. What is DNA called when it is condensed and transcriptionally inactive? (p. 62) _______________

3. What is the name for transcriptionally active DNA? (p. 62)_________________________________

4. What effect does greater G-C content have on the melting temperature of DNA? (p. 63) ______________________________________________________________________________

5. Which enzyme is inhibited by hydroxyurea? (p. 63) _____________________________________

6. 5-Fluorouracil inhibits _______________, whereas both methotrexate and trimethoprim inhibit _______________. (p. 63)

7. A 12-year-old boy with moderate intellectual disability visits his physician because of painful swollen joints. During the examination, the boy makes several uncontrolled spastic muscle movements. His medical history includes muscular hypotonia diagnosed when he was 5 months old. When he was 3 years old he was referred to a pediatric dentist for severe repetitive biting of his lip and tongue. What is the most likely diagnosis? (p. 64) _____________________________

______________________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

8. What enzyme “proofreads” DNA synthesis with its exonuclease activity in prokaryotic DNA replica-tion? In which direction can it remove nucleotides? (p. 65) ________________________________

9. What enzyme degrades the RNA primer and replaces it with DNA during prokaryotic DNA replication? (p. 65) _______________________________________________________________

10. Which category of drugs inhibits DNA gyrase? (p. 65) ____________________________________

11. Silent mutations often result from changes in which position of a codon? (p. 66) _______________

12. What kind of mutation denotes a DNA change that results in the misreading of all nucleotides downstream from it? (p. 66) ________________________________________________________

13. What specific DNA repair mechanism is defective in xeroderma pigmentosum? (p. 67) _________

______________________________________________________________________________

14. In single-stranded DNA repair, how are nucleotide-excision and base-excision repair different? (p. 67) ___________________________________________________________________________

15. Hereditary nonpolyposis colorectal cancer results from the loss of which DNA repair mechanism? (p. 67) _________________________________________________________________________

Questions





16. What commonly results from a mutation within a promoter? (p. 68) _________________________

17. What type of RNA is the largest? The smallest? The most numerous? (p. 68) ________________

______________________________________________________________________________

18. What poisonous protein that inhibits RNA polymerase II is found in death cap mushrooms? (p. 68) ______________________________________________________________________________

19. In eukaryotes, what enzyme makes mRNA? (p. 68) _____________________________________

20. In eukaryotes, what enzyme makes tRNA? (p. 68) ______________________________________

21. Patients with which disease make antibodies to spliceosomal small nuclear ribonucleoproteins? (p. 69)_________________________________________________________________________

22. β-Thalassemia can be caused by a mutation causing splicing defects in a process that combines different exons within a single gene. What mechanism allows the same gene to encode for various different proteins? (p. 69) __________________________________________________________

23. Explain the three steps of the elongation phase of protein synthesis. (p. 71) __________________

______________________________________________________________________________

______________________________________________________________________________

CELLULAR

24. Fill in the boxes on the following diagram, noting the phases of the mitotic cell cycle. (p. 72)

25. Which transition in the cell cycle is prevented by Rb and p53 tumor suppressors? (p. 72) _______

______________________________________________________________________________





26. Match the cell type with its description. (p. 72)

_____ A. Cells remain in G0 and regenerate from stem cells 1. Labile cells _____ B. Enter G1 from G0 when stimulated 2. Permanent cells _____ C. Never go to G0 and divide rapidly with a short G1 3. Stable (quiescent) cells

27. Name two cells that are rich in rough endoplasmic reticulum. (p. 72) ________________________

28. Name two cells that are rich in smooth endoplasmic reticulum. (p. 72) _______________________

29. A child presents with coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. What is the most likely diagnosis? (p. 73) _______________

30. Which molecular motor protein is used for anterograde transport along microtubules? (p. 74) _____

______________________________________________________________________________

31. Which antifungal agent targets microtubules? (p. 74) ____________________________________

32. Which antihelminthic drugs target microtubules? (p. 74) __________________________________

33. A 22-year-old woman presents with a history of recurrent pneumonia. X-ray of the chest shows dextrocardia. What is the most likely diagnosis? (p. 74) __________________________________

34. Cilia, flagella, mitotic spindles, neurons, and centrioles are composed of which cytoskeletal element? (p. 74) _________________________________________________________________

35. Vimentin, desmin, cytokeratin, glial fibrillary acid proteins, and neurofilaments are examples of which type of cytoskeletal element? (p. 74) ____________________________________________

36. What effect does digoxin’s inhibition of Na+-K

+ ATPase have on cardiac contractility? (p. 75) _____

______________________________________________________________________________

37. What type of collagen is found in each structure? (p. 75)

_____ A. Basement membrane or basal lamina 1. Type I collagen _____ B. Bone, skin, tendon, dentin, fascia, cornea, 2. Type II collagen late wound repair 3. Type III collagen _____ C. Cartilage, vitreous body, nucleus pulposus 4. Type IV collagen _____ D. Skin, blood vessels, uterus, fetal tissue, granulation tissue

38. British sailors in the 17th century were often unable to hydroxylate proline and lysine residues for collagen synthesis. What disease did they have, and why did the treatment work? (p. 76) ______________________________________________________________________________

39. What disease leads to an inability to form procollagen from pro α chains? (p. 76) _____________

______________________________________________________________________________

40. A baby is born with multiple fractures and hearing loss. What finding would most likely be seen during the ophthalmologic examination? (p. 76) ________________________________________

41. A patient presents with hyperextensible skin, easy bruising, and hypermobile joints. What is the most likely diagnosis? (p. 77) _______________________________________________________





42. Which enzyme involved in collagen synthesis will have decreased activity in a patient who has a mutation that impairs copper absorption and transport? (p. 77) _____________________________

43. Marfan syndrome is caused by a defect in what protein? (p. 77) ____________________________

44. Which lung disorder can result from excess elastase activity? (p. 77) ________________________

LABORATORY TECHNIQUES

45. Why can’t human DNA polymerase be used for PCR? (p. 77) _____________________________

______________________________________________________________________________

______________________________________________________________________________

46. Which would travel farther on an agarose gel, a fragment of 10 kD or of 100 kD, and why? (p. 77)

______________________________________________________________________________

47. Describe each of the following blot techniques: Southern, Northern, and Western. (p. 78)

Southern blot: __________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

Northern blot: __________________________________________________________________

______________________________________________________________________________

______________________________________________________________________________

Western blot: __________________________________________________________________

______________________________________________________________________________

48. Which assay can measure the expression level of many genes simultaneously? (p. 78) _________

_______________________________________________________________________________

49. What is the advantage of a Western blot over an ELISA? (p. 78) ___________________________

_______________________________________________________________________________

50. What is the advantage of fluorescence in situ hybridization over karyotyping? (p. 79) __________

______________________________________________________________________________

51. What is the most direct lab technique for detecting autosomal trisomies? (p. 79) ______________

______________________________________________________________________________





GENETICS

52. Explain loss of heterozygosity. (p. 80) ________________________________________________

______________________________________________________________________________

53. A genetic disease that shows _______________________________ may have mutations at one of several different loci that produce the same phenotype. (p. 80)

54. In terms of p and q, what is the heterozygote prevalence in a population that is in Hardy-Weinberg

equilibrium? (p. 81) _______________________________________________________________

55. How is Prader-Willi syndrome inherited? What are the symptoms? (p. 81) ____________________

______________________________________________________________________________

56. How is Angelman syndrome inherited? What are the symptoms? (p. 81) ____________________

______________________________________________________________________________

57. Which mode of inheritance is represented by each of the following pedigrees? (p. 82)

_____ A. _____ B. _____ C.

_____ D. _____ E.

1. Autosomal dominant 2. Autosomal recessive 3. Mitochondrial inheritance 4. X-linked dominant 5. X-linked recessive

58. What percentage of sons of a carrier mother is expected to inherit an X-linked recessive disease? (p. 82) _________________________________________________________________________

59. True or False: A mother with an X-linked dominant disease may pass the disease to her sons but not to her daughters. (p. 82) ________________________________________________________

60. Adult polycystic kidney disease is inherited in an autosomal- _______________ (dominant/ recessive) pattern, whereas infantile polycystic kidney disease is associated with an autosomal-_______________ (dominant/recessive) pattern. (p. 83)





61. A patient has multiple telangiectasias and skin discolorations, and notes recurrent epistaxis. What vascular pathology would you expect to find? (p. 83) ____________________________________

______________________________________________________________________________

62. What is an effective “cure” for hereditary spherocytosis? (p. 83) ___________________________

63. A tall man comes to the emergency room with the combination of a dissecting ascending aorta and acute mitral valve prolapsed. What disorder best explains these findings? (p. 83) _____________

______________________________________________________________________________

64. You notice café-au-lait spots and cutaneous neurofibromas all over a patient’s skin. On which chromosome is the gene that causes this disorder? (p. 83) _______________________________

65. Cystic fibrosis results from a defect in which gene? Which chromosome? Which ion channel? (p. 84) _________________________________________________________________________

66. Which drug can be used to loosen mucus plugs in patients with cystic fibrosis? (p. 84) __________

67. A patient with cystic fibrosis has an increased risk a deficiency of which vitamins? (p. 84) ______________________________________________________________________________

68. A 4-year-old boy needs to use his upper extremities to push against his legs in order to stand up. What maneuver is he using? (p. 85) _________________________________________________

69. A male patient has a long face, a large jaw, large ears, autism, and macroorchidism. What is the most likely diagnosis? (p. 85) _______________________________________________________

70. Before his anticipated death, a 42-year-old man had received many years of treatment for depression, severe cognitive decline, and involuntary writhing movements. His father had similar symptoms shortly before his death. What is the cause of this patient’s most likely disease? (pp. 85, 459) __________________________________________________________________________

______________________________________________________________________________

71. A newborn is diagnosed with Down syndrome. She is vomiting bilious material. What is the most likely cause? (p. 86) ______________________________________________________________





NUTRITION

72. Match each set of symptoms/conditions with the vitamin that is deficient. (pp. 89-94)

_____ A. Bruising, anemia, swollen gums, and poor wound healing 1. Biotin _____ B. Cheilosis and corneal vascularization 2. Folic acid _____ C. Convulsions, hyperirritability, peripheral neuropathy, 3. Vitamin A and sideroblastic anemia 4. Vitamin B1 _____ D. Dermatitis, enteritis, and alopecia 5. Vitamin B2 _____ E. Dermatitis, enteritis, alopecia, and adrenal insufficiency 6. Vitamin B3 _____ F. Diarrhea, dermatitis, and dementia 7. Vitamin B5 _____ G. Hemolytic anemia, muscle weakness, and neuropathy 8. Vitamin B6 _____ H. Hemorrhagic disease of the newborn 9. Vitamin B12 _____ I. Hypocalcemic tetany 10. Vitamin C _____ J. Macrocytic, megaloblastic anemia with no 11. Vitamin D neurologic problems 12. Vitamin E _____ K. Macrocytic, megaloblastic anemia, subacute combined 13. Vitamin K degeneration, paresthesia, and optic neuropathy _____ L. Night blindness _____ M. Wernicke-Korsakoff syndrome

73. Which vitamin or mineral is a cofactor for many transcription factors, and has dysgeusia as a symptom of its deficiency? (p. 94) ___________________________________________________

METABOLISM

74. Match each of the following processes with its rate-determining enzyme. (p. 96)

_____ A. Cholesterol synthesis 1. Acetyl-CoA carboxylase _____ B. De novo purine synthesis 2. Carbamoyl phosphate synthetase I _____ C. De novo pyrimidine synthesis 3. Carbamoyl phosphate synthetase II _____ D. Fatty acid oxidation 4. Carnitine acyltransferase I _____ E. Fatty acid synthesis 5. Fructose-1,6-bisphosphatase _____ F. Glycogenesis 6. Glucose-6-phosphate dehydrogenase _____ G. Glycolysis 7. Glutamine-PRPP amidotransferase _____ H. Gluconeogenesis 8. Glycogen phosphorylase _____ I. Glycogenolysis 9. Glycogen synthase _____ J. HMP shunt 10. HMG-CoA reductase _____ K. Ketogenesis 11. HMG-CoA synthase _____ L. TCA cycle 12. Isocitrate dehydrogenase _____ M. Urea cycle 13. Phosphofructokinase-1





75. In the following diagram, fill in the rectangles with the intermediates and products. Which steps of glycolysis are reversible? (Add one- or two- sided arrows to the squares.) (p. 97)

Glucose

Fructose-6-P

Glyceraldehyde-3-P

3-phosphoglycerate

2-phosphoglycerate

Pyruvate

PDH

Fumarate

Succinate

Isocitrate

Citrate





76. How many ATP molecules can be created by the aerobic and anaerobic metabolism of glucose? (p. 98) ________________________________________________________________________

______________________________________________________________________________

77. The α-ketoglutarate dehydrogenase complex and the pyruvate dehydrogenase complex require the same five cofactors; what are these cofactors? (pp. 99-100) _______________________________

_______________________________________________________________________________

78. List the four irreversible enzymes in gluconeogenesis. (p. 101) _____________________________

_______________________________________________________________________________

79. What are Heinz bodies? What are bite cells? (pp. 102, 388-389) ___________________________

______________________________________________________________________________

______________________________________________________________________________

80. Fill in the boxes on the image below, noting the substrates of the urea cycle. (p. 105)

81. A child has megaloblastic anemia not responsive to vitamin B12 or folate administration. She is small for her age. Serum studies show increased orotic acid and hyperammonemia. What is the most likely diagnosis? (p. 106) __________________________________________________





82. Fill in the boxes in the following chart, noting the enzymes that catalyze each step of catecholamine synthesis. (p. 107)

83. A 16-year-old boy presents for a routine visit. Physical examination shows symptoms consistent with Fabry disease. What is the inheritance pattern of this disease? (p. 111) _________________

______________________________________________________________________________





84. Using the list in the box, name the deficient enzyme and accumulated substrate(s) for each lysosomal storage disease listed in the chart below. (p. 111)

Disease Deficient Enzyme Accumulated Substrate

Fabry disease

Gaucher disease

Hunter syndrome

Hurler syndrome

Krabbe disease

Metachromatic leukodystrophy

Niemann-Pick disease

Tay-Sachs disease

85. Most mucopolysaccharidoses are inherited in a(n) _______________-_______________ pattern; the exception is _______________. (p. 111)

86. Most sphingolipidoses are inherited in a(n) _______________-_______________ pattern; the exception is _______________. (p. 111)

• α-galactosidase A

• Hexosaminidase A

• Sphingomyelinase

• α-L-iduronidase

• GM2 ganglioside

• β-glucocerebrosiderase

• Cerebroside sulfate

• Galactocerebrosidase

• Galactocerebroside

• Sphingomyelin

• Arylsulfatase A

• Glucocerebroside

• Ceramide trihexoside

• Heparan sulfate / dermatan sulfate

• Iduronate sulfatase

(Some answers may be used more than once)





87. Which cell-type(s) cannot use ketones as an energy source? Why? (p. 113) __________________

_______________________________________________________________________________ 88. What is the target enzyme of the drug lovastatin? (p. 114) ________________________________ 89. Which apolipoprotein binds to the LDL receptor? On which lipoproteins is it found? (p. 115) _____

______________________________________________________________________________

90. Match the lipoprotein with its function. (p. 115)

_____ A. Delivers dietary TGs to peripheral tissues 1. Chylomicron _____ B. Delivers hepatic cholesterol to peripheral tissues 2. HDL _____ C. Delivers hepatic TGs to peripheral tissues 3. IDL _____ D. Delivers TGs and cholesterol to liver 4. LDL _____ E. Mediates cholesterol transport from periphery to liver 5. VLDL 91. In which organ(s) is HDL produced? (p. 115) __________________________________________





MOLECULAR

1. H1.

2. Heterochromatin.

3. Euchromatin. (It is less condensed and accessible to transcription factors.)

4. Increased melting temperature.

5. Ribonucleotide reductase.

6. Thymidylate synthase; dihydrofolate reductase. 7.This child has Lesch-Nyhan syndrome, which is characterized by intellectual disability, self-mutilation, aggression, hyperuricemia, gout, and choreoathetosis. It is caused by the absence of HGPRT, which leads to a defective purine salvage pathway.

8. DNA polymerase III has 3' to 5' exonuclease activity for proofreading.

9. DNA polymerase I.

10. Fluoroquinolones. (They impair bacterial DNA synthesis.)

11. The third position (due to tRNA wobble).

12. Frameshift.

13. Nucleotide excision repair.

14. During nucleotide repair, the entire nucleotide structure is removed and replaced. During base excision repair, the base is clipped off of the sugar and repaired without the entire backbone of the DNA being taken apart.

15. The mismatch repair system.

16. A significant decrease in gene transcription.

17. mRNA is the largest type, tRNA is the smallest, and rRNA is the most numerous type of RNA.

18. α-Amanitin. (When consumed, it causes liver failure.)

19. RNA polymerase II.

20. RNA polymerase III.

21. Lupus.

22. Alternative splicing. (In this case, the alternative splicing yields a pathologic protein.)

Answers





23. (1) Aminoacyl-tRNA binds to the A site. (2) Peptidyltransferase adds a peptide to the amino acid chain at site A. (3) The ribosome advances three nucleotides in the 3′ direction, thereby moving the peptidyl tRNA to the P site.

CELLULAR

24.

25. Transition from G1 to S phase. (Defective cells are not allowed to undergo DNA synthesis.)

26. A-2, B-3, C-1.

27. Goblet cells (secrete mucus) and plasma cells (secrete antibodies).

28. Liver hepatocytes and steroid-hormone–producing cells of the adrenal cortex.

29. I-cell disease.

30. Kinesin.

31. Griseofulvin.

32. Mebendazole..

33. Kartagener syndrome.

34. Microtubules.





35. Intermediate filaments.

36. It increases cardiac contractility by increasing intracellular calcium concentration.

37. A-4, B-1, C-2, D-3.

38. Scurvy; the limes supplied the sailors with the vitamin C they needed during their long voyage (and earned them the nickname "limeys").

39. Osteogenesis imperfecta.

40. Blue sclerae.

41. Ehlers-Danlos syndrome.

42. Lysyl oxidase.

43. Fibrillin.

44. Emphysema. (α1-Antitrypsin inhibits elastase, which degrades elastin; therefore, lack of α1-antitrypsin can lead to loss of elastin in the lungs, thereby resulting in emphysema.)

LABORATORY TECHNIQUES

45. The DNA polymerase in PCR needs to be stable at high temperatures, since you need to repeatedly melt the DNA into a single-stranded form. Therefore, the heat-stable polymerase from the thermophilic bacteria Thermos aquaticus (Taq polymerase) is used.

46. A fragment of 10 kD; smaller molecules travel farther since they are less hindered by the gel.

47. Southern: DNA is run on an electrophoresis gel and transferred to a filter; the DNA on the filter is denatured and exposed to a labeled DNA probe; the double-stranded DNA is visualized when the filter is exposed to film.

Northern: RNA is run on an electrophoresis gel and transferred to a filter; the RNA on the filter is exposed to a labeled DNA probe; the hybrid DNA-RNA molecule is visualized when the filter is exposed to film.

Western: Sample protein is separated via gel electrophoresis and transferred to a filter; labeled antibody is used to bind and detect the protein of interest.

48. Microarrays.

49. A Western blot has greater specificity than an ELISA because it also detects the size of the target being identified.

50. FISH allows for identification of anomalies at the molecular level, including deletions that are too small to see on a karyotype.

51. Karyotyping.





GENETICS

52. When a tumor suppressor gene has only one functional allele due to an inherited mutation or deletion of the other, and then a cell loses the remaining allele as well. Consequently, having no functional alleles permits a neoplastic transformation.

53. Locus heterogeneity.

54. 2pq.

55. Prader-Willi syndrome is inherited via deactivation of the paternal copies of genes on chromosome 15 or can occur via uniparental disomy. Symptoms include mental retardation, hyperphagia, obesity, hypogonadism, and hypotonia.

56. Angelman syndrome is inherited via deactivation of the maternal copies of genes on chromosome 15 or can occur via uniparental disomy. Symptoms include mental retardation, seizures, ataxia, and inappropriate laughter.

57. A-5, B-1, C-2, D-3, E-4.

58. 50%.

59. False. (Her sons and daughters may be affected.)

60. Dominant; recessive.

61. Arteriovenous malformations. (This constellation of symptoms is typical of hereditary hemorrhagic telangiectasia.)

62. Refractory hereditary spherocytosis can be cured by splenectomy.

63. Marfan syndrome. (It is associated with cystic medial necrosis of the aorta [which may lead to a dissection] as well as a floppy mitral valve prone to prolapse.)

64. Chromosome 17.

65. CF is due to a defect in the CFTR gene on chromosome 7 that affects the chloride channel.

66. N-acetylcysteine.

67. Vitamins A, D, E, and K (all of which are fat soluble).

68. Gowers maneuver. (This action is necessary due to weakness of the proximal muscles.)

69. Fragile X syndrome. (Remember: Fragile X = eXtra large testes, jaw, and ears.)

70. The patient has classic symptoms of Huntington disease, which is caused by an expansion of CAG trinucleotide repeats on chromosome 4.

71. Duodenal atresia.





NUTRITION

72. A-10, B-5, C-8, D-1, E-7, F-6, G-12, H-13, I-11, J-2, K-9, L-3, M-4.

73. Zinc.

METABOLISM

74. A-10, B-7, C-3, D-4, E-1, F-9, G-13, H-5, I-8, J-6, K-11, L-12, M-2.

75.

Glucose

Fructose-6-P

Fructose-1,6-BP

Glyceraldehyde-3-P

1,3-BPG

3-phosphoglycerate

2-phosphoglycerate

Pyruvate

PDH

PEP

Acetyl-CoA

Glucose-6-P

Oxaloacetate

Malate

Fumarate

Succinate Succinyl-CoA

Isocitrate

Citrate

α-ketoglutarate





76. Aerobic glucose metabolism produces 32 ATP molecules per molecule of glucose in heart and liver and 30 in muscle. Anaerobic glucose metabolism products only 2 net ATP molecules per molecule of glucose.

77. Vitamins B1, B2, B3, and B5, and lipoic acid.

78. Pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase.

79. Heinz bodies are clumps of denatured hemoglobin precipitates that stick to an RBC’s membrane. When the RBC passes through the spleen, macrophages remove the Heinz bodies, which make the cell look as if a bite were taken out of it.

80.

81. Ornithine transcarbamylase deficiency. (Orotic aciduria does not have hyperammonemia.)





82.

83. X-linked recessive.

84.

Disease Deficient Enzyme Accumulated Substance(s)

Fabry disease α-galactosidase A Ceramide trihexoside

Gaucher disease β-glucocerebrosiderase Glucocereboside

Hunter syndrome Iduronate sulfatase Heparan sulfate, dermatan sulfate

Hurler syndrome α-L-iduronidase Heparan sulfate, dermatan sulfate

Krabbe disease Galactocerebrosidase Galactocerebroside

Metachromatic leukodystrophy

Arylsulfatase A Cerebroside sulfate

Niemann-Pick disease Sphingomyelinase Sphingomyelin

Tay-Sachs disease Hexosaminidase A GM2 ganglioside





85. Autosomal-recessive; Hunter disease.

86. Autosomal-recessive; Fabry disease.

87. Erythrocytes, because they have no mitochondria.

88. HMG-CoA reductase. 89. B-100; VLDL, IDL, LDL. 90. A-1, B-4, C-5, D-3, E-2. 91. Liver and intestine.



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