General pathology 2008-2009 Compiled by Bhupinder Bawa Q1.

Which of the following can be used as a marker to identify neural stem cells? A. B. C. D. E. Glial fibrillary acidic protein Neuron specific enolase Stem cell factor Nestin None

Q2. Which of the following are permanent cells that have lost their ability to proliferate? 1. Hepatocytes 2. Neurons 3. Fibroblasts 4. Cardiac myocytes 5. Urinary bladder transitional epithelium A. B. C. D. E. Q3. A. B. C. D. E. 1 1,2 2,4 1,4,5 2,3,4 Which of the following best describes Asymmetric replication? Cells replicate throughout life Cells replicate only after injury prolonged self-renewal capacity in every cell division each cell retains its pluripotential properties One cell retains its self renewing capacity and the other becomes differentiated

Q4. Which of the following embryonic stem cell proteins is named after the Celtic land of the Ever-young? A. B. C. D. E. Wnt-β-catenin Neverland Myogenin Nanog Elysia

Q5.Which of the following locations has not been shown to harbor tissue stem cells? A. B. C. D. E. Olfactory bulb and dentate gyrus in rodent brains Isthmus of stomach glands The base of hair follicles Limbus of the cornea Canals of Hering

General pathology 2008-2009 Compiled by Bhupinder Bawa Q6. Bone marrow stromal cells do not generate A. B. C. D. E. Myocytes Adipocytes Osteoblasts Chondrocytes Endothelial cell precursors

Q7. The correct order of replication in a quiescent cell after injury is 1. 2. 3. 4. 5. A. B. C. D. E. G0 G1 G2 S M 1,2,3,4,5 1,2,4,3,5 1,2,5,3,4 1,3,4,2,5 1,3,5,2,4

Q8. Non-dividing (permanent) tissues contain cells that are in which stage of the cell cycle? A. B. C. D. E. G0 G1 G2 S None of the above

Q9. Non-dividing parenchymal cells of liver, kidney, and pancreas are considered to be in which stage of the cell cycle? A. B. C. D. E. G0 G1 G2 S None of the above

Q10. Tissue stem cell niches include all of the following except… A. Bone marrow B. Limbus of cornea C. Base of colonic crypts D. Bulge area of hair follicle E. Isthmus of stomach glands

General pathology 2008-2009 Compiled by Bhupinder Bawa Q11. A. B. C. D. E. Pluripotent bone marrow stromal cells can differentiate into all except… Myoblasts Osteoblasts Adipocytes Chondroblasts Progranulocytes

Q12. Which of the vascular endothelial growth factor (VEGF) is not required for vasculogenesis or angiogenesis? A. B. C. D. E. VEGF-A VEGF-B VEGF-C VEGF-D VEGF-E

Q13. Which of the following statements regarding TGF-β is false? A. B. C. D. E. It is a pleiotropic agent. It is a potent fibrogenic agent. It is a strong anti-inflammatory agent. It stimulates the proliferation of fibroblasts and smooth cells. It is a growth stimulator for most epithelial cell types and for leukocytes.

Q14. Following ligand binding to a tyrosine kinase receptor, which of the following proteins is responsible for cycling RAS between its active and nonactive form? A. B. C. D. E. SOS RAF FOS GAP GRB2

Q15. Which of the following are sources of PDGF? 1. 2. 3. 4. 5. Platelets Keratinocytes Macrophages Endothelial cells Smooth muscle cells A. 1,2,3,4,5 B. 1,3,4,5 C. 1,3,4

General pathology 2008-2009 Compiled by Bhupinder Bawa D. 3,4,5 E. 4,5 Q16. Members of the FGF family of growth factors can cause which of the following? 1. 2. 3. 4. 5. A. B. C. D. E. angiogenesis hematopoiesis lung maturation skeletal muscle development macrophage and endothelial cell migration 1,2,3,4,5 1,3,4,5 1,3,5 2,4,5 3,4,5

Q17. Effects of TGF-β include all of the following except? A. B. C. D. E. Growth inhibitor of most epithelial cells Increased expression of INK4.ARF Stimulates proliferation of fibroblasts Growth inhibitor of leukocytes Pro inflammatory effects

Q18. Receptors with intrinsic tyrosine kinase activity activate which of the following downstream pathways? 1. IP3 pathway 2. cAMP pathway 3. PI3 kinase pathway 4. MAP-kinase pathway 5. JAK/STAT pathway A. B. C. D. E. 1,2,3,4,5 1,3,4 2,3,4 3,4,5 3,4

Q19. Which of the following cell membrane receptors use PLC-γ to activate downstream effects? A. G-protein coupled receptors B. Receptors with tyrosine kinase activity C. Receptors without tyrosine kinase activity D. A & B E. All of the above

General pathology 2008-2009 Compiled by Bhupinder Bawa Q20. Activation of which of the following receptors can cause the release of calcium from endoplasmic reticulum through the IP3 pathway? A. B. C. D. E. Receptors without tyrosine kinase activity Receptors with tyrosine kinase activity G-protein coupled receptors Steroid hormone receptors B&C

Q21. Which of the following is not considered to be a ‘quiescent’ tissue? A. B. C. D. E. Liver Pancreas Fibroblasts Resting lymphocytes Transitional epithelium

Q22. Which of the following is not a recognized niche for stem cells? A. B. C. D. E. Canals of Hering Hair follicle bulge Limbus of the eye Crypt cells of the colon High endothelial venules in the spleen

Q23. Which of the following tissues is not of mesoderm origin? A. B. C. D. E. Myocytes Adipocytes Osteoblasts Red blood cells Oligodendrocytes

Q24. Ligands for receptors with intrinsic tyrosine kinase activity include... 1. Insulin 2. Histamine 3. Growth Hormone 4. Epidermal Growth Factor 5. Platelet Derived Growth Factor A. B. C. D. E. 1,3,4 1,4,5 2,3,4 2,4,5 3,4,5

General pathology 2008-2009 Compiled by Bhupinder Bawa Q25. Cells become irreversibly committed to DNA replication after passing which restriction point(s) in the cell cycle? A. B. C. D. E. G0-G1 G1-S S-G2 G2-M both b and d

Q26. The cAMP second messenger pathway results from signaling from which receptor family? A. B. C. D. E. Steroid hormone receptors 7-transmembrane G-protein-couples receptors Receptors with intrinsic tyrosine-kinase activity Receptors lacking intrinsic tyrosine-kinase activity that recruit kinase None of the above

Q27. The most abundant glycoprotein in the basement membrane is? A. B. C. D. E. Integrin Cadherin Laminin Collage type IV Collagen type II

Q28 All of the following are examples of fibrillar collagen except? A. B. C. D. E. Type I Type II Type III Type IV Type V

Q29. Priming of hepatocytes to enter cell cycle is mediated by? A. B. C. D. E. TNF IL-6 HGF A and B All of the above

Q30. Which of the following cytokines are involved in the G0/G1 transition? 1. IL-1 2. IL-6

General pathology 2008-2009 Compiled by Bhupinder Bawa 3. TNF 4. TGF-β 5. TGF-α A. B. C. D. E. 1,2,3 1,3 2,3 2,4,5 3,5

Q31. Fibrillar collagens include which of the following? 1. I 2. II 3. III 4. IV 5. V A. B. C. D. E. 1,2,3,4,5 1,2,3,4 1,2,3,5 2,3,4,5 2,3,5

Q32. Hydroxylation of proline and lysine during collagen production occurs in which of the following locations? A. B. C. D. E. Endoplasmic reticulum Extracellular space Cytoplasm Golgi all of the above

Q33. . Which of the following statements FALSE regarding cross linking of collagen fibrils? A. B. C. D. E. results from oxidation of lysine and hydroxylysine residues mediated by the enzyme lysyl oxidase Stabilizes the molecule occurs outside the cell requires vitamin C

Q34. Which of the following signaling pathways can induce inhibition of cell proliferation? A. MAP kinase

General pathology 2008-2009 Compiled by Bhupinder Bawa B. C. D. E. JAK/STAT WNT PKC PI-3

Q35. The extracellular matrix serves which of the following functions? A. B. C. D. E. Enables cell to cell interactions Provides a reservoir for growth factors Provides a substratum for cells to adhere to Sequesters water to provide turgor to soft tissues All of the above

Q36. Basement membranes are composed of all the following except? A. B. C. D. E. Laminin Fibronectin Proteoglycan Heparan sulfate Type IV collagen

Q37. Which of the following enzymes is responsible for collagen cross-linking? A. B. C. D. E. Lysyl oxidase Collagen oxidase Collagen synthetase Proline hydroxylase Hydrogen peroxidase

Q38. Type 1 collagen is found in 1. 2. 3. 4. 5. A. B. C. D. E. Skin Bone Tendon Cartilage Vitreous 1 1,2 1,2,3 1,2,3,4 1,2,3,4,5

Q39. The necessary cofactor for MMP is A. Zinc

General pathology 2008-2009 Compiled by Bhupinder Bawa B. C. D. E. Calcium Magnesium Phosphorus MMP binding factor

Q40. The following factors cause quiescent cells to go from G0 to G1? 1. 2. 3. 4. 5. A. B. C. D. E. TNF IL-6 HGF TGF α TGF β 1 1,2 2,4 2,5 2,4,5

Q41. Which of the following is not part of the ECM? A. Elastin B. Integrin C. Collagen D. Proteoglycans E. Hylaronic acid   Q42. Which of the following is incorrect regarding liver regeneration? A. The cytokines TNF and IL-6 are implicated in G0/G1 transition B. Restoration of liver mass is achieved without regrowth of resected lobes C. The growth factors HGF and TGF-α are involved in cell-cycle progression after cells reach G1 D. Intrahepatic stem cells play an important role in the compensatory growth that occurs following partial hepatectomy E. Hepatocyte regeneration is mostly dependent on paracrine effects of growth factors and cytokines produced by hepatic nonparenchymal cells Q43. Basement membranes are composed of primarily which type of collagen? A. B. C. D. E. Type I Type II Type III Type IV Type V

General pathology 2008-2009 Compiled by Bhupinder Bawa Q44. Regarding cell adhesion molecules, which statement is false? A. B. C. D. Cadherins play a role in cell to cell contact inhibition Cadherins are involved with calcium dependent heterotypic cell interactions Integrins bind to both matrix proteins as well as adhesion proteins of other cells There is functional overlap and interaction between integrin and growth factor receptors E. Cadherins and integrins link the cell surface with the cytoskeleton through the binding to actin and intermediate filaments Q45. MMP includes all of the following except? A. B. C. D. E. Serine proteases Collagenases Stromelysins Gelatinases A and B

Q46. Stabilization of newly formed blood vessels is mediated by all of the following except? A. B. C. D. E. Angiopoietins 1 Angiopoietins 2 PDGF FGF-2 TGF-β

Q47. The proliferation phase of wound healing is characterized by the following events? 1. 2. 3. 4. 5. A. B. C. D. E. 1,2,3 2,3,4 3,4,5 2,3,4,5 1,2,3,4 Q48. The most common inducer of angiogenesis A. Wound healing B. Inflammation C. Hypoxia vasoconstriction Angiogenesis Epithelization Fibroplasia Contracture

General pathology 2008-2009 Compiled by Bhupinder Bawa D. A & C E. All Q49. The most important growth factor in adults undergoing physiological angiogenesis A. B. C. D. E. FGF-2 VEGF PDGF TGF-B GM-CSF

Q50. The growth factor involved in the recruitment of smooth muscle cells during angiogenesis that help in stabilization of the newly formed blood vessels A. B. C. D. E. FGF-2 VEGF PDGF TGF-B GM-CSF

Q51. The functions of VEGF include all except A. B. C. D. E. Angiogenesis Increase vascular permeability Stimulate endothelial cell migration Stimulate endothelial cell proliferation Regulates the production of ECM proteins

Q52. Which of the following plays an important role during tissue remodeling? A. B. C. D. E. MMP GCSF VEGF A&B All

Q53. During the process of tissue remodeling the continuous degradation of ECM is inhibited by A. B. C. D. E. MMP TIMPs TGF-B A&B B&C

General pathology 2008-2009 Compiled by Bhupinder Bawa Q54. The obvious gross morphological feature that differentiates healing by second intension from first intension is A. B. C. D. E. Scab Inflammation Wound contraction A&B B&C

Q55. Which of the following is not a function of VEGF? A. B. C. D. E. Promotes angiogenesis Stimulates vasoconstriction Increases vascular permeability Stimulates endothelial cell migration Stimulates endothelial cell proliferation

Q56. Which of the following is not a function of TGF-β? A. B. C. D. E. Chemotactic for monocytes Inhibits endothelial proliferation Promotes increased synthesis of collagen Promotes fibroblast migration and proliferation Inhibits degradation of ECM by metalloproteinases

Q57. Which of the following statements about MMPs is incorrect? A. B. C. D. E. Q58. A. B. C. D. E. Inhibited by TGF- β Stimulated by PDGF, EGF, and Il-1 and TNF Plasmin cleaves procollagenases to collagenases Steroids accelerate the degradative action of MMPs Inhibited by tissue-inhibitors of metalloproteinase (TIMPs) Which of the following is false regarding VEGF? Increases vascular permeability Important for stabilization of newly formed capillaries Binding to VEGFR-2 in endothelial cells triggers angiogenesis It is the most important growth factor in adult tissues undergoing angiogenesis Promotes angiogenesis involving both endothelial cell precursors and pre-existing capillaries

Q59. Matrix metalloproteinases are inhibited by… 1. EGF 2. IL-1 3. TGF-β

General pathology 2008-2009 Compiled by Bhupinder Bawa 4. 5. A. B. C. D. E. PDGF Steroids 1,3 3,5 4,5 1,2,4 1,2,5

Q60. The feature that most clearly differentiates primary from secondary wound healing is… A. B. C. D. E. Wound contraction Formation of a scar Formation of a fibrin clot Formation of granulation tissue Presence of an inflammatory reaction

Q61. Expression of genes responsible for wound repair is regulated to a large degree by tissue levels of... A. Glucose B. Oxygen C. Cytokines D. Carbon dioxide E. Serum proteins Q62. The scirrhous reaction involves which phase of the healing process? A. Hemostasis B. Acute inflammation C. Proliferation (granulation) D. Remodeling (maturation, contraction) E. Both b and c Q63. Healing by fibrous placement occurs by (Robbins 107) 1. 2. 3. 4. Contraction Angiogenesis Tissue remodeling Synthesis of ECM proteins 5. Inflammation and removal of damaged tissue A. B. C. D. E. 2,5,4,3,1 5,2,4,3,1 5,2,3,4,1 5,4,2,3,1 5,4,3,2,1

General pathology 2008-2009 Compiled by Bhupinder Bawa Q64. VEGF is not induced by A. B. C. D. E. TGF-α TGF-β FGF-2 PDGF HREs

Q65. PDGF does not affect A. Collagen synthesis B. Fibroblast migration C. Collagenase secretion D. Fibroblast proliferation E. Initiation of Angiogenesis Q66. Endothelial cell proliferation is not induced by A. B. C. D. E. EGF FGF VEGF Ephrins Angiogenins

General pathology 2008-2009 Compiled by Bhupinder Bawa

Q1. D; (Robbins pp 94) Q2. C; (Robbins pp90) Q3. E. (p91 Robbins) Q4. D (p91 Robbins). Named after Tir na n’Og. Wnt-β-catenin has also been implicated in maintaining pluripotency Q5. C (p 93-94 Robbins) The bulge area contains the tissue stem cells and is located between the bulb and the shaft. The canals of Hering hold Oval cells which can differentiate into bile epithelium of hepatocytes. The canals themselves connect bile canaliculi to bile ducts. Q6. A (Robbins 93) (they generate myoblasts, not myocytes) Q7. B (Robbins 90) Q8. E (Robbins p.91) Non-dividing (permanent) tissues contain cells that have left the cell cycle and cannot divide. Q9. A. (Robbins p. 90) Quiescent (stable) tissues contain cells considered to be in G0 stage but can be stimulated to enter G1 Q10. A (Robbins p.93) Stem cells located outside of the bone marrow are generally referred to as tissue stem cells. Another tissue niche is the liver stem cells (oval cells) in the canals of Hering Q11. E (Robbins p.94) The pluripotent hematopoietic stem cells (HSCs) generate all of the blood cells Q12. B; (Robbins pp 96) VEGF-B binds to VEGFR1 and their role is not well understood; VEGF (also referred to as VEGF A) interacts with VEGF R2 and play a role in vasculogenesis and agniogenesis; VEGF R3 interacts with VEGF C and VEGF D and play a role in lymphangiogenesis; Thee is no VEGF E Q13. E (Robbins pp 96-97); it is an inhibitor for most epithelial cells and leukocytes Q14. D (Robbins pg. 99), Fig. 3-10

General pathology 2008-2009 Compiled by Bhupinder Bawa Q15. A (p95 Table 3-1 Robbins) Q16. A (p96 Robbins) Q17. E (p 97 Robbins) TGF-β has strong anti-inflammatory effects. Q18. B (p98 Figure 3-9 Robbins) The cAMP path is activated by g-protein coupled receptors. Receptors without tyrosine kinase activity activate the JAK/STAT pathway. Q19. D (p 98 figure 3-9 Robbins. Q20. E (p 98-99 Robbins) Q21. E (Robbins p. 90) transitional epithelium is a continuously dividing tissue Q22. E (Robbins p. 93) Q23. E (Robbins P. 94) oligodendrocytes are of ectodermal origin Q24. B (Robbins p.98)Ligands for receptors with intrinsic tyrosine kinase activity include most growth factors such as (EGF, TGF-α, HGF, PDGF, VEGF, FGF, c-KIT ligand, and insulin Ligands for receptors lacking intrinsic tyrosine kinase activity that recruit kinases include many cytokines (interleukins), interferons, erythropoietin, granulocyte colony-stimulating factor, growth hormone, and prolactin Ligands for 7-transmembrane G-protein-coupled receptors include vasopressin, serotonin, histamine, epinephrine and norepinephrine, calcitonin, glucagon, PTH, corticotropin, rhodopsin, and many pharmacologic drugs Q25. B (Robbins p.100)Progression through the cell cycle, and particularly the G1/S transition, is tightly regulated by proteins called cyclins and associated enzymes called cyclin-dependent kinases (CDK’s) Q26. B (Robbins p.100) Q27. C; (Robbins pp 105) Q28. D; (Robbins pp 104) Type IV is non fibrillar collagen Q29. D; (Robbins pp 102) Priming is mediated by TNF and IL-6 and after priming HGF and TGF-α mediate proliferation of hepatocytes Q30. C p102 Robbins. TGFα along with HGF are involved in cell cycle progression after the cells reach G1. TNF gives a priming effect that allows full mitogenic effect of HGF and TGF-α. TGF-β is a growth inhibitor along with activinss. Q31. C (p104 Robbins) Type IV is non-fibrillar (forms sheets) and is the main component of basement membranes along with laminins. Q32. A (p105 Robbins). Hydroxylation of proline and lysine, and glycosylation of lysine occurs after translation in the ER, helix formation occurs in the golgi (procollagen), and pro-collagen is cleaved by proteases in the extracellular space. Q33. E (p104-105 Robbins) Vitamin C is required for Hydroxylation of procollagen (activation of prolyl and lysyl hydroxylases). Copper is a cofactor in lysyl oxidase. Q34. C (p105 Robbins). Β- catenin links cadherins with α- catenin which connects to actin. This also can account for inhibition of cell proliferation. Free β catenin, acting independently of cadherins can regulate nuclear transcription factors and inhibit cell proliferation by the Wnt signaling pathway. Q35. E (Robbins p. 103) Q36. B (Robbins p. 103) Q37. A (Robbins p. 104) Q38. C, (PBVD 180) Q39. A, (PBVD 181)

General pathology 2008-2009 Compiled by Bhupinder Bawa Q40. B (Robbins p. 102) (HGF and TGFα cause cell cycle progression) Q41. B (Robbins p. 103) (Integrins are cell surface receptors for ECM proteins) Q42. D (Robbins p. 101-103) Intrahepatic stem cells do not play a role in the compensatory growth that occurs after partial hepatectomy, and there is no evidence for hepatocyte generation from the bone marrow. It is hepatocytes that replicate. Q43. D (Robbins p. 104) Q44. B (Robbins p. 104-105) Cadherins are generally involved in calcium-dependent homotypic interactions. Homotypic interactions involve same cell types, heterotypic interactions involve different cell types Q45. A; (Robbins pp 111) Q46. D; (Robbins pp 104) FGF-2 mediates proliferation, differentiation and migration endothelium Q47. B; (PBVD 175) Vasoconstriction takes place in early inflammation phase and contracture takes place in late remodeling phase. Q48. C Q49. B Q50. C Q51. E (ECM proteins regulate VEGF) Q52. A Q53. E Q54. C Q55. B (Robbins pp 109) Q56. B (Robbins pp 110) Q57. D (Robbins pp 110) steroids inhibit production of procollagenases Q58. B (Robbins p. 109) Stabilization requires recruitment of pericytes and smooth muscle cells and the deposition of ECM proteins. Angiopoietins 1 and 2, PDGF, and TGF-β participate in the stabilization process Q59. B (Robbins p. 110) The others stimulate MMPs Q60. A (Robbins p. 113) Q61. B (PBVD p.178) - With hypoxia HIF activates transcription of genes of the hypoxia response elements (HRE) Q62. D (PBVD p.185) Q63. B (Robbins pp 107) Q64. C (Robbins pp 109) (FGF-2 acts similarly to VEGF) Q65. E (Robbins pp 111) Q66. A (PBVD 186) (EGF causes endothelial migration)

PBVD Chapter 3 Acute Inflammation BGC

General pathology 2008-2009 Compiled by Bhupinder Bawa 1. Morphologic characteristics of Bovine Leukocyte Adhesion deficiency include: 1. oral ulcers 2. Intestinal mucosal ulcers 3. thickened intestinal serosa 4. Lack of neutrophils in spleen 5. Lack of leukocytes in peyers patches A. 1,2,3,4,5 B. 1,3,4 C. 1,2,3 D. 2,3 E. 4,5 Answer: C p115 2. Use of a leukocyte migration inhibitors as a therapeutic strategy for Mannheimia pneumonia makes sense because… A. Alveolar migration of leukocytes via selectin is inhibited B. Bronchiolar migration of leukocytes via Beta-2 integrins is inhibited C. such a strategy would prevent excessive leukocyte infiltration into the lung D. All of the above E. None of the above Answer: D p116 3. Which of the following statements is true regarding basophils and mast cells? 1. Fibroblasts and endothelial cells produce a glycoprotein that induces CD34+ cells to mature. 2. Basophils and mast cells are derived form different stem cell lines 3. They arise from a common CD34+ progenitor in bone marrow 4. Basophils later differentiate into tissue mast cells 5. Differentiation is dependent on stem cell factor A. 1,3,5 B. 1,3,4 C. 2,3,4 D. 3,4,5 E. 4,5 Answer: A p117 4. Mast cell degranulation releases which of the following substances in rodents? A. TNF-alpha B. Proteases C. Serotonin D. tryptase

General pathology 2008-2009 Compiled by Bhupinder Bawa E. All of the above Answer: E p118 5. Basophils have what effect in the allergic response? A. Basophils switch B lymphocytes to produce IgE B. Basophils produce IgE that mediate allergies C. They can cause mast cells to degranulate D. All of the above E. None of the above Answer: A p118 6. Which of the following substances can prevent apoptosis of tissue neutrophils? 1. GM-CSF 2. G-CSF 3. TNF 4. IL-8 5. IL-3 A. 1,2 B. 1,2,5 C. 1,3,4 D. 3,4,5 E. 4,5 Answer: A p118 7. Phagocytosis by Neutrophils occurs by which of the following means? 1. Opsonization by binding of Fc portions of Ig to Fc receptors 2. Opsonization by the binding of C3b to Mac-1 3. Phagocytosis can occur without opsonization 4. Opsonizationn by C3a and C5a 5. Opsonization by C5b A. 1,2,3,4,5 B. 1,2,3 C. 1,3,4 D. 2,3,4 E. 2,3 5 Answer: B p119 8. Heterophil is the neutrophil equivalent in which of the following species: A. Birds

General pathology 2008-2009 Compiled by Bhupinder Bawa B. Rabbits C. Guinea Pigs D. All of the above E. None of the above Answer: D p120 9. CHemotactic factors for eosinophils include all of the following except: A. IL-8 B. IL-5 C. C5a D. CCL-11 E. Histamine Answer: A. p120-121

10. Which of the following cells are the primary source of Histamine and serotonin? A.Lymphocytes B. Macrophages C. Neutrophils D. Basophils E. Mast cells Answer: E p122 11. Which of the following cells are the primary source of Bradykini? 1. Vascular endothelial cells 2. Macrophages 3. Lymphocytes 4. Neutrophils 5. Platelets A. 1,2,3,4,5 B. 1,2,3,4 C. 1,,3,5 D. 2,3,4 E. 3,4,5 Answer B: p122- Note Robbins states Bradykinin is produced in the liver as HMWK and activated by kallikrein to form Bradykinin. PBVD states that Bradykinin is produced by b vascular endothelium and leukocytes. 12. Substance P is released by which of the following cells?

General pathology 2008-2009 Compiled by Bhupinder Bawa 1. Basophils 2. Mast cells 3. endothelium 4. Macrophages 5. C-reactive nerve fibers A. 1,2,3 B, 1,2,4 C. 1,2,5 D. 2,4, E. 2,4,5 Answer: C: p122 13. Which of the following are effects of Histamine? 1. Increased vascular permeability via H2 receptors 2. Vasodilation via H1 and H2 receptors 3. Neural and vagal reflexes 4. bronchial constriction 5. release of PGF2alpha A. 1,2,3,4,5 B. 1,2,3,4 C. 1,2,4,5 D. 2.3.4 E. 2.3.4.5 Answer: E p122 14. Release of histamine from mast cells results from which of the following? 1. IgE 2. C3a 3. C5b 4. Substance P 5. ATP A. 1,2,3,4,5 B. 1,2,4,5 C. 1,2,3 D. 2,3,4,5 E. 3,4,5 Answer: B p123. C5a not C5b releases histamine. Alsp heat and cold, and other products from leukocytes, endothelial cellc, and platelets

General pathology 2008-2009 Compiled by Bhupinder Bawa 15. Serotonin is released from plateelts by which of the following? 1. Platelet aggregation on collogen 2. Thrombin 3. C5a,c3a 4. ADP 5. PAF A. 1,2,3,4,5 B. 1,2,4,5 C. 1,2,3,4 D. 2,3,4,5 E. 2,4,5 Answer: C p123 Histamine is released from platelets by the same stimuli 16. What is the function of the serpin family of serum proteases? A. To block the proteolytic activity of complement and coagulation systems B. To regulate the activity of the complement system C. They break down FDP’s after clot removal D. To breaksown Angiotensin II E. None of the above Answer: A p123. The serpin family includes serum alpha2-macroglobulin (C1-INH), alpha 1-antichymotrypsin, alpha 1- antitrypsin, and antithrombin III 17. Which of the following are effects of Substance P? 1. Vasoconstriction 2. Vasodilation 3. increased vascular permeability 4. Leukocyte activation and chemotaxis 5. Activation and degranulation of Mast cells and basophils A. 1,2,3,4,5 B. 1,3,4,5 C. 2,3,4,5 D. 2,3,4 E. 2,3,5 Answer: A. p124 Substance P binds to NK-1R on Mast cells, endotheliual cells, and macrophages. The release of Substance P from nerver fibers can also be induced by Capsaicinoids. 18. Which of the following substances can activate complement proteins?

General pathology 2008-2009 Compiled by Bhupinder Bawa 1. Venoms 2. Exotoxins 3. Endotoxin 4. Immunoglobulins 5. Complex polysaccharides A. 1,2,3,4,5 B. 1,2,3,4 C. 1,3,4,5 D. 3,4,5 E. 3,4 Answer : C p124. 19. Which of the following is not a function of C5a? A. Opsonization B. Histamine release C. Leukocyte chemoattractant D. Induction of endothelial adhesion molecule E. None of the above Answer: A p124 20. Which of the following can not activate the Alternative pathway of complement activation? A. Microbial surface polysaccharides B. Coagulation cascade C. Kinin system D. Plasmin E. none of the above Answer: E p124-126 C3 can be cleaved by kallikrein, plasmin, activated HF (XIIa) as well as microbial polysaccharides and LPS. 21. The delayed anti-inflammatory effect of corticosteroids is due to the production of which of the following? A. Lipocortin B. enterocoxib C..Phospholipase A2 D. None of the above E. Prostaglandin cyclase

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: A p128 Corticosteroids signsl the cell to synthesize the polypeptide Lipocortin (Lipomodulin) which acts to inhibit PLA2 22. The major effects of Leukotrienes include which of the following? 1. Increased vascular permeability 2. Chemotaxis for leyukocytes 3. Plateelt activation 4. Vasoconstriction 5. Vasodilation A. 1,2,3,4,5 B. 1,2,4,5 C. 1,3,5 D. 2,3,5 E. 3,4 Answer: B p128 23. Cell mediated immune responses involve which of the following? 1. IFN-gamma 2. TH-1 cells

General pathology 2008-2009 Compiled by Bhupinder Bawa 3. IL-12 4. IL-10 5. IL-3 A. 1,2,3 B. 1,3,5 C. 2,3,4 D. 3,4 E. 1,4,5 Answer: A p130 24. Which of the following statements are true of NK cells?

General pathology 2008-2009 Compiled by Bhupinder Bawa 1. IL-21 appears to regulate differentiation and apoptotic cell death induced by NK cells 2. NK cells secrete granules containing cytotoxic molecules 3. NK cells are stimulated by IL-4 and IL-12 4. NK cells do not express CD3 5. NK cells release IFN-gamma A. 1,2,3,4,5 B. 1,2,4,5 C. 2,3,4,5 D. 2,3,4 E. 3,4,5 Answer: A. p130-131

Robbins Chapter 3 BGC 1. Which of the following are NOT examples of labile tissues? A. fibroblasts B. Oral mucosa C. Uterus epithelium D. Urinary tract epithelium E. Lining of all excretory ducts and glands Answer: A. p90 2. Which of the following words best describes the following statement: In every cell division, one of the cells retains its self-renewing capacity while the other enters a differentiation pathway. A. Checkpoint growth B. Regressive replication C. Asymmetric replication D. Non-differentiation pathway E. None of the above Answer: C p91 3. Which of the following is not true regarding EGF receptors? A. EGFR is a family of tyrosine kinase receptors B. One EGFR is expressed in breast cancer C. EGFR responds to EGF and TNF-α

General pathology 2008-2009 Compiled by Bhupinder Bawa D. The main EGFR is ERB B1 E. None of the above Answer: E. p96 ERB B2 (Also HER-2/Neu) is expressed in breast cancer cells and may be a therapeutic target. EGF is found in saliva, urine, and sweat and causes mitogenesis of epithelial cells, hepatocytes and fibroblasts. It is produced by keratinocytes, macrophages and others. 4. Which of the following is not a source of HGF? A. Endothelium B. Hepatocytes C. Fibroblasts D. Platelets E. Serum Answer: B HGF is produced by liver non-parenchymal cells and has mitogenic effects on hepatocytes, biliary epithelium, lung epithelium, mammary epithelium, and skin 5. Which of the following is not a function of FGF? A. Angiogenesis B. Wound repair C. Development D. Hematopoiesis E. Synthesis of MMP’s Answer: E p96-97 PDGF stimulates production of MMP’s. FGF is chemotactic for fibroblasts,mitogenic for fibroblasts and keratinocytes, stimulates keratinocyte migration, andgiogenesis and fam wound contraction and matrix deposition. 6. Please choose the correct sequence from beginning to end that describes TGF-β activated DNA transcription. 1. TGF-β cleavage 2. binding to type II receptor 3. Forms heterodimer with Smad 4 4. Phosphorylation of Smad 2 and 3 5. Forms a complex with type I receptor 6. enters nucleus and associates with DNA binding proteins A. 1,2,3,4,5,6 B. 1,2,4,3,5,6 C. 1,2,5,4,3,6 D. 5,2,4,3,1,6 E. 1,5,2,4,2,6

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: C p96 7. Examples of autocrine regulated processes include: 1. Some tumors 2. Epithelial growth 3. Liver regeneration 4. Enterocyte proliferation 5. proliferation of antigen stimulated lymphocytes A. 1,2 B. 1,2,3 C. 1,3,5 D. 2,3 E. 3,5 Answer: C p97 8. Intrinsic tyrosine kinase receptor signaling can involve which of the following downstream effector molecules? 1. PLC 2. GRB2 3. RAS/GDP 4. PI3 kinase 5. MAP-kinase A. 1,2,3,4,5 B. 1,3,4,5 C. 2,3 D. 2,5 E. 3,4,5 Answer: A 9. Which of the following are cell cycle inhibitors? A. c-MYC B. c-JUN C. AP-1 D. p53 E. None of the above Answer: D p100

General pathology 2008-2009 Compiled by Bhupinder Bawa 10. The retinoblastoma susceptibility protein forms a tight complex with what transcription factor and thereby halting the cell cycle? A. p53 B. E2F C. NFκB D. Transcription activating factor-1 E. None of the above Answer: B p100- RB/E2F copmplex needs to be phosphorylated to free up E2F for driving the cell cycle/. 11. In hepatic compensatory growth which two gene products dimerize to form AP-1 transcription factor? A. c-FOS and c-JUN B. c-JUN and c-MYC C. c-FOS and c-MYC D. NFKb and STAT-3 E. None of the above Answer: A. p102 c-FOS and c-JUN dimerize to form c-MYC (AP-1) which encodes for transcription factor that activates many genes and other transcription factors- (NFκB, STAT-3, and C/EBP) 12. After a partial hepatectomy which cytokines induce hepatocytes to go from the quiescent G0 to G1 stage of the cell cycle? A. TNF, IL-6 B. HGF, TGF-β C. TGF-α, Activin D. Norepinephrine, Insulin E. None of the above Answer: A. p 102 TNF and IL-6 and others activate the quiescent hepatocyte. HGF and TGF-a induce proliferation with NE and Insulin, growth hormone, and thyroid hormone. After proliferation Growth inhibitors like TGF-β, activin, and increase in cell cyle inhibitors and decrease in GF and Metabolic demands slow down and halt proliferation 13. True or False- Stem cells participate in hepatic regeneration after a partial hepatectomy? Answer- False p 102 14. Cross linking of collagen fibers is caused by which of the following enzymes?

General pathology 2008-2009 Compiled by Bhupinder Bawa A. Lysyl oxidase B. Lysyl synthetase C. Collagen hydroxylase D. Hysroxylysyl oxidase E. None of the above Answer: A, p104- Lysyl oxidase oxidizes lysyl and hydroxylysyl residues forming crosslinks between adjacent chains 15. Examples of CAM’s include which of the following? 1. Immunoglobulins 2. MHC proteins 3. cadherins 4. integrins 5. selectins A. 1,2,3,4 B. 1,3,4,5 C. 1,3,4 D. 2,3,4 E. 2,3,4,5 Answer : B p104 16. Which of the following statements in NOT true of fibronectin ? A. fibronectin binds to integrins B. Two forms exist, tissue and plasma fibronectin C. Fibronectin binds to collagen, fibrin, proteoglycans D. Tissue fibronectin binds to fibrin at wound healing sites E. none of the above Answer: D- Plasma fibronectin bind to fibrin, tissue fibronectin forms fibrillar aggregates at wound healing sites. 17. Which of the following statements about Laminin are NOT true? (choose one) A. Laminin has binding domains for both ECM and cell-surface receptors. B. Tightly bound networks are formed by Laminin and Type V collagen C. Laminin can mediate the attachment of cells to Connective tissue D. Laminin is the most abundant glycoprotein in the BM E. None of the above Answer: B p 105 Laminin binds tightly to Type IV collagen (in the BM)

General pathology 2008-2009 Compiled by Bhupinder Bawa 18. Which of the following statements about cadherins is not true? A. cadherins form desmosomes and zonula adherens B. cadherins link to the cytoskeleton through catenins C. cadherins participate in interaction between cells of the same type D. Cadherin interactions connect the plasma membranes of adjacent cells E. None fo the above Answer: E p 105 cell-cell interaction mediated by cadherins play a major role in contact inhibition 19. Angiogenesis or neovascularization in adults can occur by which of the following mechanisms? 1. Mobilization of endothelial precursor cells from the bone marrow 2. Establishment of a primitive vascular network by angioblasts 3. From pre-existing vessels such as capillaries 4. Neoangiogenesis 5. Vasculogenesis A. 1,2,3,5 B. 1,3 C. 2,3,5 D. 2.5 E. 3 Answer: B. p107 20. The hemangioblast is a common precursor to all of the following cells EXCEPT? A. Hemopoietic stem cells B. Smooth muscle cells C. Satellite cells D. Angioblasts E. Pericytes Answer: C p 108 Smooth muscle cells of the vascular wall are called periendothelial cells 21. Endothelial precursor cells express Which of the following? 1. Vascular endothelial cadherin 2. Tie2 receptor 3. E-Selectin 4. ICAM-1 5. PECAM

General pathology 2008-2009 Compiled by Bhupinder Bawa A. 1,2,3,4,5 B. 1,2,3,4 C. 1,2,3 D. 1,2 E. 1 Answer: C p 108 22. all of the following are inducing agents of VEGF EXCEPT? A. PDGF B. FGF-2 C. TGF-α D. TGF-β E. Hypoxia Answer: B p109 23. All of the following participate in “Stabilization” of new capillaries EXCEPT? A. angioproteins 1 and 2 B. TGF-α C. TGF-β D PDGF E. Tie2 Answer: C p109. Ang1 interacts with tie 2 receptor on endotheluial cells to recruit periendothelial cells. PDGF participates in the recruitment of smooth muscle cells. TGFβ stabilizes new vessels by inducing ECM protein production 24. Which of the following cytokines causes fibriblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM by metalloproteinases, as well as chemotactic for monocytes. A. TGF-β B. TNF-β C. PDGF D. IL-1 E. EGF Answer: A p110 25. MMP production is induced by which of the following? 1. Steroids

General pathology 2008-2009 Compiled by Bhupinder Bawa 2. PDGF 3. TNF 4. EGF 5. IL-1 A. 1,2,3,4,5 B. 2,3,4,5 C. 3,4,5 D. 4,5 E. 5 Answer: B p110 (Figure 3-19) Robbins Ch 3 Q. All of the followings are correct, EXCEPT a. b. c. d. e. (A. Skin is a continuously dividing tissue Liver is a quiescent tissue Smooth muscle is a quiescent tissue Skeletal muscle is a quiescent tissue Cardiac muscle is a nondividing tissue d. ref. Page 90-91)

Q. All of the followings are correct, EXCEPT a. b. c. d. e. (A. PPARγ leads stem cells to fat cells CBFA1 leads stem cells to osteoblasts TGF-β leads stem cells to chondroblasts Myo D and myogenin lead stem cells to myotube VEGF and FGF2 lead stem cells to endothelial cells c. ref. Page 94 fig 3-6)

Q. All of the followings are correct, EXCEPT a. b. c. d. e. TGF-β is a pleiotropic factor BMPs is a member of TGF-β family TGF-β is a growth inhibitor for leukocytes TGF-β binds to its receptors with tyrosine kinase activity Smads are cytoplasmic transcription factors phosphorylized by TGF-β

General pathology 2008-2009 Compiled by Bhupinder Bawa (A. d ref Page 96)

Q. All of the followings are correct, EXCEPT a. b. c. d. e. A. Type I collagen is the main collagen component of the bone Type I collagen is the main collagen component of the fibrous cartilage Type I collagen is the main collagen component of the articular cartilage Type III collagen is a fibrillar collagen Type IV is the main collagen component of the basement membrane c ref. page 104, Table 3-2

Q. All of the followings are correct, EXCEPT a. b. c. d. e. A. One third of collagen fibrils are made up of proline Vitamin C is essential for a posttranslational modification of collagen Proteoglycan is composed of a core protein with glycosaminoglycans Leukocytes bind to hyaluronate through CD44 Integrin is involved in mechanotransduction signaling pathways a ref. page 104

Q. Select one of the most appropriate orders of wound repair by healing. 1. 2. 3. 4. 5. Infiltration of inflammatory cells Parenchymal cell proliferation Synthesis of ECM Tissue remodeling Angiogenesis a. b. c. d. e. A. 1-2-3-4-5 1-2-3-5-4 1-2-5-3-4 1-3-2-5-4 1-3-2-4-5 c. ref. Page 107

Q. Which of the followings is the correct combination regarding the newly formed vessel stabilization.

General pathology 2008-2009 Compiled by Bhupinder Bawa a. Angiopoietin 1, PDGF, TGF-β – recruitment of pericytes b. Angiopoietin 1, PDGF, TGF-β – deposition of ECM c. Angiopoietin 1, TGF-β – recruitment of pericytes, PDGF – recruitment of smooth muscle cells d. Angiopoietin 1, TGF-β – deposition of ECM, PDGF – recruitment of smooth muscle cells e. Angiopoietin 1 – recruitment of pericytes, PDGF – recruitment of smooth muscle cells, TGF-β – deposition of ECM A. e ref. 109

Which of the following is not fibrogenic? A) B) C) D) E) Interferon alpha Tumor necrosis factor Fibroblast growth factor Insulin-like growth factor – 1 Transforming growth factor beta Page #’s: 95-96, 71

Answer: A Which of the following are cytokine receptors? A) B) C) D) E)

MAP-kinase receptors Epinephrine receptors Receptors with intrinsic kinase activity Receptors without intrinsic kinase activity Seven transmembrane G-protein-coupled receptors Page #: 98-99

Answer: D

Hematopoeitic stem cells can generate the following cells, except: A) Neurons B) Hepatocytes C) Chondrocytes D) Red blood cells E) Epithelial cells of lung Answer: C pages 92, 94

General pathology 2008-2009 Compiled by Bhupinder Bawa Which part of the cell cycle is considered the DNA synthesis phase: A) G2 B) G1 C) G0 D) S phase E) M phase Answer: D page 90

The following are true regarding the various isoforms of VEGF except: A) Has a role in angiogenesis B) Has a role in vasculogeneis C) Has a role in lymhangiogenesis D) Utilizes 3 tyrosine kinase receptors E) Released VEGF associates with heparin sulfate in ECM Answer: E , page 96

The following are true regarding FGF except: A) Induces blood vessel formation B) Has strong anti-inflammatory effect C) Role in skeletal muscle development D) Participates in fibroblast migration in damaged tissues E) Involved with differentiation of specific lineages of blood cells Answer: B , pages 96-97

The following substances bind to cell surface receptors except: A) IL-2 B) TGF-α C) Histamine D) Steroid hormones E) Epidermal Growth Factor (EGF) Answer: D pages 98-100

The following are true regarding cell adhesion proteins except: A) Cadherin is involved in forming zonula adherens

General pathology 2008-2009 Compiled by Bhupinder Bawa B) Cadherins generally participate in heterotypic interactions C) Many integrins bind to RGD sequences in the fibronectin molecule D) Focal adhesion complexes are formed with ligand binding to integrins E) Linkage of cadherins with cytoskeleton occurs through α and β catenins Answer: B , pages 55, 104,105

The following are true regarding angiogenesis except: A) Ang2/Tie 2 interactions stabilize new vessels B) B) Tissue hypoxia stimulates VEGR expression C) C) Ang1/Tie2 interactions recruit periendothelial cells D) D) Angiogenesis occurs from EPCs or capillary sprouting E) VEGFR-2 is the most important receptor in angiogenesis Answer: A pages 108-109 The growth factor PDGF induces all of the following except? a) b) c) d) e) Collagen synthesis Fibroblast proliferation and migration Angiogenesis Monocyte chemotaxis Collagen secretion

A:

C

Page 111 Table 3-4

The following are true regarding TGF-β except: A) Potent fibrogenic agent B) Chemotactic to leukocytes C) Induces TGF-β production D) Binds to seven transmembrane G-protein coupled receptors E) Increases expression of cell cycle inhibitors (Cip/Kip and INK4/ARF families) Answer: D pages 95,96

The receptors without intrinsic tyrosine kinase activity predominately use which pathway to activate gene transcription on the nucleus: A) PI3 kinase B) IP3 pathway C) PLCγ pathway D) cAMP pathway E) JAK/STAT pathway

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: E page 99

Centrosome duplication occurs during which phase of the cell cycle: A) S phase B) M phase C) G0 phase D) G1 phase E) G2 phase Answer: D page 90

The cell-cycle check points are between the following cell cycle phases: 1) G1/ S phase 2) G2 / M phase 3) S phase/ G2 4) G1/ G2 5) G0 / G1 A) 1,2 B) 1,3 C) 2,3 D) 3,4 E) 4,5 Answer: A page 90

Pluripotent stem cells will differentiate into fat cells due to stimulation by the following factor: A) VEGF B) FGF2 C) Sox9 D) CBFA1 E) PPARγ Answer: E page 94

November 1, 2005 Robbins Chap 3. page 101-106 Kei K. Which of the following gene is over-expressed first in liver regeneration?

General pathology 2008-2009 Compiled by Bhupinder Bawa a. b. c. d. e. p53 c-fos Bcl-X mdm2 Cyclins ref. page 101, fig 3-11)

(Answer

Which of the following is the main collagen of basement membrane? a. b. c. d. e. Collagen type I Collagen type II Collagen type III Collagen type IV Collagen type V ref. page 103)

(Answer

Vitamin C is required for which of the following process of procollagen? a. b. c. d. e. Phosphorylation Hydroxylation Methylation Acetylation Prenylation ref. page 104)

(Answer

Which of the following adhesion protein is particularly important in mechanotransduction (signal transduction by mechanical forces)? a. b. c. d. e. Immunoglobulin family CAMs (cell adhesion molecules) Cadherins Selectins Integrins Tenacins

(Answer ref. page 105) Which one of the following growth factors does not bind to a receptor with intrinsic tyrosine kinase activity? (p. 98) A) EGF B) FGF C) PDGF D) TGF-β E) VEGF

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: D (serine/threonine kinase activity) The most important receptor involved in vasculogenesis and angiogenesis A) VEGRR-1 B) VEGFR-2 C) VEGFR-3 D) A and B E) All 1) B; Page 96; VEGF binds to VEGFR-2; VEGFR-1 binds to VEGF-B and its role is not completely understood; VEGFR-3 binds with VEGF-C and VEGF-D and are critical for lymphangiogenesis.

TGF-β has inhibitory effect on growth of the following cell types 1) Leukocytes 2) Fibroblasts 3) Epithelial cells 4) Smooth muscle cells A) 1, 2, 3, 4 B) 1, 3, 4 C) 1, 3 D) 2 E) 3 C; Page 96-97; it stimulates proliferation of fibroblasts and smooth muscle cells.
Which of the following statements are false concerning vascular endothelial growth factor (VEGF)? a. Produced by mesenchymal cells b. Increases vascular permeability c. Mitogenic for endothelial cells d. Platelets are a source e. Promotes angiogenesis in tumors D pgs 95-96 Receptors without intrinsic tyrosine kinase activity activate which important pathway? f. Jak/STAT pathway g. PI3 kinase pathway h. MAP-kinase pathway

General pathology 2008-2009 Compiled by Bhupinder Bawa
i. j. IP3 pathway All of the above

A, fig 3-9, pg 98 Which of the molecules are ligands for receptors lacking intrinsic kinase activity? k. IL-2 l. Prolactin m. Erythropoietin n. Interferons o. Growth hormone a. a, d b. a, d, e c. a, c, d, e d. a, b, c, d, e e. d only D, all are ligands pg 99 TNF is not secreted by which cell type? p. Macrophage q. B lymphocytes r. T lymphocytes s. Mast cells t. All of the above secrete TNF B, table 3-1 pg 95

1) G0/G1 transition of hepatocytes during regeneration is mediated by which of the following? p102 1) HGF 2) Il-6 3) TGF-β 4) TNF 5) TGF-α A) 1, 5 B) 1, 2 C) 1, 3 D) 2, 4 E) 2, 5 Answer: D 2) After reaching G1, progression of the hepatocyte cell cycle is dependent on which of the following? p102

General pathology 2008-2009 Compiled by Bhupinder Bawa 1) HGF 2) Il-6 3) TGF-β 4) TNF 5) TGF-α A) 1, 2 B) 1, 5 C) 1, 2, 4 D) 1, 3, 5 E) 2, 4 Answer: B 3) Basement membranes predominantly consist of? p103 1) Laminin 2) Proteoglycan 3) Type I collagen 4) Type II collagen 5) Type IV collagen A) 1, 4 B) 1, 2, 4 C) 1, 2, 5 D) 2, 3 E) 5 Answer: C 4) “Contact inhibition” of epithelial cells in cell cultures is likely regulated by which of the following? p105 A) Cadherins B) Integrins C) Selectins D) Immunoglobulin family CAMs Answer: A The following is NOT true regarding liver regeneration after partial hepatectomy A) Endpoint of regeneration is restitution of functional mass B) Intrahepatic stem cells or bone marrow stem cells are not involved

General pathology 2008-2009 Compiled by Bhupinder Bawa C) Restoration of liver mass is achieved with regrowth of resected lobes D) Hepatocyte replication is followed by replication of nonparenchymal cells E) Growth factor responses are increased by priming of hepatocytes by cytokines C; Page 101; restoration is by enlargement of the remaining lobes The following genes are expressed during G0/G1 transition 1) c-FOS 2) c-JUN 3) c-MYC 4) NF-κB 5) Bcl-X A) 1, 2, 3, 4, 5 B) 1, 2, 3, 4 C) 1, 2, 3 D) 1, 2 E) 1 B; page 102; this is referred to as immediate early gene response; some other early genes include STAT-3 and C/EBP Vitamin C is involved in A) Preprocollagen formation B) Procollagen helix formation C) Lysine glycosylation of procollagen chain D) Cleavage of polypetides from procollagen E) Lysyl/hydroxylysyl oxidation leading to cross-linking of collagen molecules B; page 104 and figure 3-15; procollagen helix is formed from preprocollagen after hydroxylation of proline and lysine residues followed by glycosylation of lysine on procollagen chain. Vit C is a co-factor for prolyl and lysyl hydroxylase involved in hydroxylation of proline and lysine. Therefore, vitamin C deficiency results in abnormal procollagen helix formation Bovine Marfan syndrome is a result of inherited defect in A) Elastin B) Fibrillin C) Collagen D) Procollagen E) Collagen secretion

General pathology 2008-2009 Compiled by Bhupinder Bawa B; page 104 1) Which of the following statements is incorrect: PBVD pp178-179

A) Prolyl hydroxylase hydroxylates HIF-α B) Hydroxylated HIF-α is degraded by the ubiquitin pathway C) Reduced hydroxylated HIF-α concentrations occur in hypoxic tissues D) Hydroxylated HIF-α aggregates with HIF-β and induces transcription of HRE’s. Answer: C 2) Matrix metalloproteinase secretion is induced by: Robbins p111 1) PDGF 2) EGF 3) Il-1 4) TNF 5) TGF-β A) 1, 2 B) 1, 2, 3 C) 1, 2, 3, 4 D) 1, 2, 3, 4, 5 E) 1, 3, 4, 5 Answer: C Stabilization of newly formed vessels requires which of the following growth factors? (p. 109) 1) TGF-α 2) TGF-β 3) PDGF 4) FGF-2 5) VEGF A) B) C) D) E) 1, 2 1, 3 2, 3 3, 4 4, 5

Answer: C All of the following growth factors are involved in promoting collagenase secretion necessary for wound healing except: (p. 111)

General pathology 2008-2009 Compiled by Bhupinder Bawa A) B) C) D) E) FGF TNF EGF PDGF TGF-β

Answer: E (TGF-β inhibits collagenase secretion) 1) During angiogenesis the following factors play a role in stabilization of blood vessels except, A) Angiopoietin-1 B) Angiopoietin-2 C) PDGF D) VEGF E) TGF-β D; page 109; VEGF is required for proliferation and motility of endothelial cells. FGF-2 is also involved in endothelial proliferation, differentiation and migration; Angiopoietin-1 is involved in periendothelial cell recruitment; Angiopoietin-2: see next question; PDGFassociated with smooth muscle proliferation; TGF-β- enhances ECM production. 2) The Tie-2 receptor on endothelial cells interacts with the following molecule to result in periendothelial cell recruitment A) Angiopoietin-1 B) Angiopoietin-2 C) PDGF D) VEGF E) TGF-β A; page 109; interaction of Tie-2 with angiopoietin-2 either makes endothelial cells more responsive to growth factors such as VEGF or more responsive to inhibitors of angiogenesis, in the absence of VEGF 3) This is NOT a function of VEGF A) Promotes angiogenesis B) Increases vascular permeability C) Stimulates endothelial cell migration D) Stimulates endothelial cell proliferation E) Up-regulates endothelial expression of plasminogen E; Page 109; Table 3.3; Up-regulates endothelial expression of plasminogen activator, plasminogen activator inhibitor-1, tissue factor, and interstitial collagenase

General pathology 2008-2009 Compiled by Bhupinder Bawa 4) The following stimulates matrix metalloproteinase synthesis except, A) IL-1 B) TNF C) EGF D) PDGF E) TGF-β E; page 110, figure 3-19; steroids also inhibit the synthesis; phagocytosis and physical stress also stimulate synthesis. 5) The activity/expression of the following molecules is enhanced during wound healing 1) HIF-α 2) EGR-1 3) Prolyl hydroxylase 4) Hypoxia responsive elements A) 1, 2, 3, 4 B) 1, 2, 3 C) 1, 2, 4 D) 3, 4 E) 4 C; PBVD 178-179 and figure 4-21; prolyl hydroxylase activity is enhanced in normal tissues with enough oxygen- this enzyme prevents binding of HIF-α with P300BP- this results in degradation of HIF by ubiquitin pathway; In hypoxia this process do not occur and HIF-α binds with HIF-β which results in transcription of hypoxia responsive elements (HRE) which include genes for glycolytic enzymes, grwoth factors and iron binding proteins; EGR-1 (early growth response gene-1) activity increases in hypoxia results in expression of genes for glycolysis (glucose transporters; hexokinase 1 and 2; Lactate dehydrogenase; phosphofruktokinase), endothelial and fibroblast proliferation (VEGF and TGF-β) and iron sequestration (ceruloplasmin, trasferrin receptor) 6) The following molecule is NOT involved in vascular remodeling A) FGF B) Tie-2 C) EphB4 D) EphrinB2 E) Angiopoietin 2

General pathology 2008-2009 Compiled by Bhupinder Bawa A; PBVD page 187; Tie 2 is a receptor for Angiopoietin; EphB4 is a receptor for EphrinB2; all these and TGF-β are involved in remodeling; FGF is involved in proliferation, differentiation and maturation 7) The following are anti-angiogenic molecules 1) Thrombospondin 2) Angiostatin 3) Endostatin 4) IP-10 5) PF4 A) 1, 2, 3, 4, 5 B) 1, 2, 3, 4 C) 1, 2, 3 D) 2, 3 E) 4, 5 A; PBVD 187; IP10 and PF4 are chemokines lacking ELR motif and are antiangiogenic along with others in the above list. 8) The following transcription factors are involved in epithelial cell differentiation, except A) GATA-6 B) HFH-4 C) HNF-β D) TTF-1 E) NFκB E; PBVD 189 figure 4-33; TTF-thyroid transcription factor; HNF- hepatocytes nuclear factor; HFH- hepatocytes factor homolog; NfκB inhibits these factors Q1. Which of the following is NOT TRUE about hypoxia inducing factor -α ? (PVBD pp 178-179) A. Hydroxylation by prolyl hydroxylase deactivates HIF-α B. Activated HIF-α is degraded by ubiquitin pathway. C. Nonhydroxylated HIF-α binds to HIF-β to induce transcription of HRE D. HRE includes genes for glycolyic enzymes, growth factors and iron binding proteins. E. Hypoxic condition reduces prolyl hydroxylase activity and reduced hydroxylation of HIF-α . Answer B

General pathology 2008-2009 Compiled by Bhupinder Bawa

Q2. All of the following can most likely inhibit ECM degradation by MMPs except? (PBVD pp 179-181) A. TGF-β B. TIMP C. Steroids D. PAI E. Zinc F. Answer E. Zn is a Co-factor necessary for MMP activation Q3. Which of the following is NOT an angiogenesis inhibitor? (PBVD pp 187) A. CXCL10 (IP-10) B. Endostatin C. Thrombospondin D. CXCL9 (MIG) E. Angiopoietin 1 Answer E. CXC lacking the ELR motif, platelet factor 4, interferon -inducible protein 10, and monokine
induced by –interferon

Q. MMP-3 deficiency can cause which of the following wound defect? (Robbins pp 115) A. Wound dehiscence B. Wound ulceration C. Contracture D. Proud flesh E. Keloid F. Answer C. Deficiency of MMP-3 leads to reduced proteolysis of actin containing fibroblasts leading to excessive contraction of wound.

Q. Which of the following is TRUE about liver regeneration after partial hepatectomy ? (Robbins pp 101-102) 1. 2. 3. 4. 5. Regeneration of liver involves replication of stem cells. Regrowth of resected lobes in rat can take place as early as 10 days. The priming of hepatocytes is mediated by HGF and TGF-α . There is increased expression of proto-oncogenes like c-myc, c-fos, and c-jun. The hepatocyte replication is followed by replication of non-parenchymal cells

General pathology 2008-2009 Compiled by Bhupinder Bawa A. B. C. D. E. 1,2,3 3,4,5 1,2,3,4,5 4,5 2,4,5 Answer D Q. Osteogenic imperfecta is a genetic disorder of what type of collagen? (Robbins pp 104) A. B. C. D. E. I II III IV V

Answer A Which of the following is not a nitch for tissue stem cells? A. B. C. D. E. Disse’s space Corneal limubs Crypts of the colon Isthmus of stomach glands Dentate gyrus of hippocampus A ref. page 93 fig 3-5)

(Answer

Parenchymal cells of the liver are typically in which phase of the cell cycle? A. B. C. D. E. S M G0 G1 G2 pg 90-91

Answer: C

Which of the following is NOT a ligand for receptors with intrinsic tyrosine kinase activity? A. EGF

General pathology 2008-2009 Compiled by Bhupinder Bawa B. C. D. E. IFN-γ PDGF Insulin c-KIT ligand B ref. page 98, fig 3-9)

(Answer

1. Which of the vascular endothelial growth factor (VEGF) is not required for vasculogenesis or angiogenesis? (p 96) A. VEGF-A B. VEGF-B C. VEGF-C D. VEGF-D E. VEGF-E Answer: B 2. Which of the following statements regarding TGF-β is false? (pp 96-97) A. B. C. D. E. Answer: E 3. Which of the following receptors transmit extracellular signals to nucleus using Janus kinase (JK) proteins? (pp 98-100) A. B. C. D. E. Answer: D Following ligand binding to a tyrosine kinase receptor, which of the following proteins is responsible for cycling RAS between its active and nonactive form? F. G. H. I. J. SOS RAF FOS GAP GRB2 Steroid hormone receptors Receptors with intrinsic tyrosine kinase activity Receptors with extrinsic tyrosine kinase activity Receptors without intrinsic tyrosine kinase activity Seven transmembrane G-protein-coupled receptors It is a pleiotropic agent. It is a potent fibrogenic agent. It is a strong anti-inflammatory agent. It stimulates the proliferation of fibroblasts and smooth cells. It is a growth stimulator for most epithelial cell types and for leukocytes.

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: D pg. 99, Fig. 3-10

Which pathway is responsible for calcium release from the endoplasmic reticulum? A. B. C. D. E. IP3 pathway cAMP pathway PI3 kinase pathway JAK/STAT pathway MAP-kinase pathway pg 98, Fig. 3-9

Answer: A FOS functions as which of the following? A. B. C. D. E. RAS activator bridging protein apoptosis inhibitor transcription factor growth factor receptor

Answer: D

pg 99

Which of the following collagen is not a fibrillar collagen? A. B. C. D. E. Type I Type II Type III Type IV Type V D ref. page 104)

(Answer

Which of the following adhesive proteins inhibits angiogenesis? (p 105) 1. 2. 3. 4. 5. Thrombospondin Osteonectin Osteopontin Cadherin Selectin A. B. C. D. E. 1, 2 1, 2, 3 2, 3, 4 3, 4 4, 5

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: A Which of the following markers is a surface marker expressed by leukocytes and binds hyaluronic acid (HA)? (p 106) A. B. C. D. E. CD1 CD14 CD44 CD45 CD62

Answer: C Which of the following is false concerning cadherins? A. B. C. D. E. desmosomes are found in muscle cells they calcium dependent adherence proteins altered expression of β-catenins is linked to neoplasia development linkage to the cytoskeleton is completed by β-catenin linking to actin zonula adherens are spotlike junctions near the apical surface of epithelial cells pg 105

Answer: D

All of the following are active during the G0-G1 transition during liver regeneration except: A) c-FOS B) c-JUN C) c-MYC D) STAT-3 E) Cyclin D-CDK4 Answer: E pages 101-102

Which of the following cytokines are important in the G0-G1 transition (priming) in hepatocyte regeneration: 1) TNF 2) IL-6 3) HGF 4) TGF-α 5) TGF-β A) 1,2

General pathology 2008-2009 Compiled by Bhupinder Bawa B) 2,3 C) 2,4 D) 3,4 E) 4,5 Answer: A page 102

Which of the following steps in collagen synthesis requires vitamin C? A) Synthesis of procollagen B) Cross-linking of collagen C) Procollagen secretion from cell D) Alignment of 3 procollagen chains E) Transcription from collagen genes to form preprocollagen Answer: B page 104

If lack L-gulonolactone oxidase the can’t convert L-gulonolactone to L-ascorbic acid Which of the following receptor expressed by endothelial cells bind fibrin and fibronectin for formation of newly formed blood vessels? A. Tie2 B. EphB4 C. VEGFR-1 D. VEGFR-2 E. a5β3 integrin (Answer E. page109. Pathologic basis of vet diz page 188, fig 4-32. EphB4: receptor for Ephrin B2, mediate vascular remodeling) Which of the following growth factors is the most important growth factor in adult tissues undergoing angiogenesis? A. B. C. D. E. EGF FGF VEGF PDGF TGF-β pg 109

Answer: C

Which of the following components of wound healing may be triggered by TGF-β? 1. collagen synthesis

General pathology 2008-2009 Compiled by Bhupinder Bawa 2. 3. 4. 5. A. B. C. D. E. fibroblast migration collagenase secretion fibroblast proliferation monocytes chemotaxis 1,2,3 1,2,5 2,3,4 2,3,5 3,4,5 pg 111, Table 3-4

Answer: B

Which of the following components is the most important growth factor involved in the inflammatory fibrosis? (p 110) A. B. C. D. E. Answer: D PDGF is involved in all of the following steps in wound healing EXCEPT: (p 111) A. B. C. D. E. Angiogenesis Collagen synthesis Fibroblast migration Monocytes chemotaxis Fibroblast proliferation FGF IL-1 PDGF TGF-β TNF-α

Answer: A Which of the following components inhibits the secretion of metalloproteinase? (p111) F. G. H. I. J. Answer: D Robbins Chap. 3 p. 95-101 FGF IL-1 PDGF TGF-β TNF-α

General pathology 2008-2009 Compiled by Bhupinder Bawa Which one of the following growth factors is produced by platelets and macrophages? (p. 95) A) tumor necrosis factor B) insulin-like growth factor-1 C) transforming growth factor α D) transforming growth factor β E) vascular endothelial growth factor Answer: D Which one of the following intracellular signal transduction pathways is activated by binding of ligands to receptors without tyrosine kinase activity? (p. 98) A) IP3 pathway B) cAMP pathway C) PI3 kinase pathway D) JAK/STAT pathway E) MAP-kinase pathway Answer: D Robbins Chap. 3 p. 101-106 Which type of collagen is found in basement membranes? (p. 104) A) Type II B) Type IV C) Type V D) Type VII E) Type IX Answer: B (Type II and Type IX are found in cartilage; Type V in soft tissues and blood vessels; Type VII in anchoring fibrils at dermal-epidermal junctions) Robbins Chap. 3 p. 107-116 Stabilization of newly formed vessels requires which of the following growth factors? (p. 109) 6) TGF-α 7) TGF-β 8) PDGF 9) FGF-2 10) VEGF F) G) H) I) J) 1, 2 1, 3 2, 3 3, 4 4, 5

General pathology 2008-2009 Compiled by Bhupinder Bawa Answer: C All of the following growth factors are involved in promoting collagenase secretion necessary for wound healing except: (p. 111) F) FGF G) TNF H) EGF I) PDGF J) TGF-β Answer: E (TGF-β inhibits collagenase secretion) All of the following induce the secretion of MMPs (Matrix metalloproteinase) except: 1) FGF 2) PDGF 3) TGF-β 4) Steroids 5) IL-l and TNF A) 1,2 B) 1,3 C) 2,3 D) 3,4 E) 3,5 Answer: D Page 109

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