Cme-ajp-jan-06

ASIP 2012 Journal CME Programs
ASIP Semiannual 2012 AJP CME Program in Pathogenesis
American Society for Investigative Pathology
The American Journal of Pathology
Volume 180, Number 2 (February 2012)
http://www.asip.org/CME/index.cfm
Mark E. Sobel, MD, PhD, Director of Journal CME Programs
CME Questions February # 1-10

1. Modulation of the endocannabinoid system (ECS) has therapeutic potential in a wide range of diseases and
pathologic conditions. Based on the referenced Review, select the ONE statement that is NOT TRUE: [See Am J
Pathol 2012, 180:432-442; DOI: 10.1016/j.ajpath.2011.11.003; the authors of the referenced article did not disclose any
relevant financial relationships.]
a. Endocannabinoids (ECs) are endogenous, bioactive lipid mediators that exert their effects mainly through specific G-protein-coupled receptors: canninoid-1 (CB1) receptor and cannabinoid-2 (CB2) receptor. b. Signaling of CB1 and CB2 receptors always involves inhibition of adenyl cyclase activity and may also involve activation of various mitogen-activated protein kinases (MAPKs), protein kinases A and C, and modulation of various Ca2+ and K+ channels. The two main ECs are anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), which are synthesized “on demand” and are degraded quickly to yield a transient, localized effect. d. The ECs, their specific CB1 and CB2 receptors, and the synthesizing and metabolizing enzymes form the
2. The cannabinoid receptors are, at least in part, responsible for the effects of several natural constituents of
Cannabis sativa. Based on the referenced Review, select the ONE statement that is NOT TRUE: [See Am J Pathol
2012, 180:432-442; DOI: 10.1016/j.ajpath.2011.11.003; the authors of the referenced article did not disclose any relevant
financial relationships.]
a. ∆9-Tetrahydrocannabinol (THC) is the only active ingredient of marijuana and is responsible for its undesirable b. Cannabidol (CBD) is a natural plant-derived constituent with negligible psychotropic effects and is well tolerated without adverse effects when administered in the long term. CBD has been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in Canada, the United Kingdom, and Spain. d. ∆9-Tetrahydrocannabivarin (THCV) behaves like a CB1 receptor antagonist and activates CB2 receptors, thereby decreasing oxidative stress and inflammation.
3. Diabetes mellitus is the seventh leading cause of death in the US. Based on the referenced Review, select the
ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:432-442; DOI: 10.1016/j.ajpath.2011.11.003; the
authors of the referenced article did not disclose any relevant financial relationships.]
a. Diabetes mellitus affects over 8% of the US population.
b. Type I diabetes mellitus (insulin-dependent or juvenile-onset diabetes) commonly has an increased prevalence
of autoantibodies against pancreatic islet cells. Type 2 diabetes (non-insulin-dependent or maturity-onset diabetes) has a prevalence of 0.2% to 0.5% and is more common in women. d. Type 2 diabetes is often characterized by a combination of a progressive insulin secretory defect in pancreatic β cells and resistance to the effects of insulin in peripheral target tissues. The American Society for Investigative Pathology ASIP Semiannual 2012 AJP CME Program in Pathogenesis The American Journal of Pathology, Volume 180, Number 2, February 2012 4. Most diabetic complications are associated with pathologic alterations in the vascular wall. Based on the
referenced Review, select the ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:432-442; DOI:
10.1016/j.ajpath.2011.11.003; the authors of the referenced article did not disclose any relevant financial relationships.]

a. Microvascular complications underlie nephropathy, retinopathy, and peripheral neuropathy.
b. Atherosclerosis is the most common macrovascular complication of diabetes.
c.
Hyperglycemia leads to the accumulation of sorbitol and advanced glycation end products, inhibition of protein kinase C, and activation of the hexosamine pathway. d. The most common upstream event in the pathogenesis of diabetic complications is the formation of reactive oxygen species and reactive nitrogen species.
5. The ECS plays a role in the pathogenesis of diabetes and diabetic complications. Based on the referenced
Review, select the ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:432-442; DOI:
10.1016/j.ajpath.2011.11.003; the authors of the referenced article did not disclose any relevant financial relationships.]
a. Exogenous cannabinoids and ECs increase food intake and promote weight gain by activating CB2 b. Activation of the peripheral ECS in obesity leads to adipogenesis, lipogenesis, hepatic steatosis, and increased insulin resistance, involving both peripheral and central CB1 receptors. Blockade of CB1 receptors with rimonabant (RIO) in clinical trials led to weight loss and improvements in several metabolic risk factors (eg, decreased waist circumference, increased high-density lipoprotein cholesterol levels, and decreased triglyceride levels). d. The CRESCENDO trial was abruptly terminated because of RIO’s neuropsychiatric adverse effects. 6. Successful wound repair relies on a balance of extracellular matrix (ECM) synthesis and resolution, as well as
re-epithelization of damaged epithelial surfaces Based on the referenced article, select the ONE statement that is
NOT TRUE: [See Am J Pathol 2012, 180:484-493; DOI: 10.1016/j.ajpath.2011.10.005; the authors of the referenced
article did not disclose any relevant financial relationships.]
a. Abnormal tissue repair is often associated with excessive ECM production that ultimately leads to fibrosis.
b. ECM-producing lung fibroblasts arise from resident pulmonary fibroblasts, circulating fibrocytes that then
infiltrate into the lung, and alveolar epithelial cells. Epithelial-mesenchymal transition (EMT) allows an epithelial cell to undergo multiple biochemical changes that result in mesenchymal cell features, including enhanced migratory capacity, production of ECM components, and loss of epithelial cell characteristics. d. Transforming growth factor (TGF)-β1 is a central mediator of lung fibrosis by inducing EMT of fibrocytes.

7. Aberrant expression of microRNAs (miRs) is associated with initiation and progression of pathological
processes, but their role in lung fibrosis is not well characterized. Based on the referenced article, select the
ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:484-493; DOI: 10.1016/j.ajpath.2011.10.005; the
authors of the referenced article did not disclose any relevant financial relationships.]
a. In an experimental mouse model of lung fibrosis, three of the miR-200 family members (miR-200a, miR- 200b, and miR-200c) were all down-regulated in the lungs of bleomycin-treated mice. b. miR-200 demonstrated greater expression in AECs than in lung fibroblasts.
c.
Levels of miR-200a, miR-200b, and miR-200c were significantly decreased in the lungs of patients with idiopathic pulmonary fibrosis (IPF) compared with those in the healthy controls. d. MIR200A and MIR200B genes are located in the same genomic locus and controlled by the same promoter.

8. Impaired or immature barrier function plays a key role in the pathogenesis of many intestinal inflammatory
diseases. Based on the referenced article, select the ONE statement that is NOT TRUE: [See Am J Pathol 2012,
180:626-635; DOI: 10.1016/j.ajpath.2011.10.025; the authors of the referenced article did not disclose any relevant
financial relationships.]
a. Tight junctions maintain separation of tissue compartments by sealing the intercellular space while regulating b. During early postnatal maturation, the intestinal barrier tightens and becomes more selectively permeable. c. Dietary and trophic factors (eg, epidermal growth factor) and hormonal factors (eg, endogenous glucocorticoids) are involved in regulating barrier tightening in the immature gut. d. Murine paracellular permeability markedly decreases during postnatal maturation, with the most significant The American Society for Investigative Pathology ASIP Semiannual 2012 AJP CME Program in Pathogenesis The American Journal of Pathology, Volume 180, Number 2, February 2012 9. The immature neonatal intestinal barrier may fail to prevent systemic entry of microbes or microbial products
and other toxins from within the gut lumen, leading to intestinal inflammation and injury. Based on the
referenced article, select the ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:626-635; DOI:
10.1016/j.ajpath.2011.10.025; the authors of the referenced article did not disclose any relevant financial relationships.]
a. Commensal bacteria normally colonize the murine gut during the first several weeks of postnatal life.
b. Neonates with abnormal intestinal microbial composition may be predisposed to idiopathic inflammatory bowel
disease (IBD), infectious enteritis, or necrotizing enterocolitis (NEC). Probiotics composed of commensal bacteria have shown promise in reducing the incidence and severity of IBD, NEC, and infectious diarrhea in infants and children. d. Mature expression of claudin 3 occurs at one week in the postnatal mouse, coincident with maturation in gut
10. Prostate cancer is the most common malignant tumor in men in developed countries. Based on the
referenced article, select the ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:848-861; DOI:
10.1016/j.ajpath.2011.10.021; the authors of the referenced article did not disclose any relevant financial relationships.]
a. Most prostate carcinomas require androgen stimulation to grow.
b. Although most prostate tumors initially respond to androgen ablation therapy, some will become resistant
and progress to castration-resistant prostate cancer (CRPC). Prostate cancer cells with high levels of androgen receptor (AR) expression are particularly sensitive to androgen depletion and do not convert to CRPC. d. CRPC clinically tends to progress more rapidly than earlier disease manifestations.
11. Forkhead transcription factors are structurally characterized by a winged helix three-dimensional structure
similar to that of linker histones, enabling them to open highly compacted chromatin and to facilitate the binding
of other transcription factors. Based on the referenced article, select the ONE statement that is NOT TRUE: [See
Am J Pathol 2012, 180:848-861; DOI: 10.1016/j.ajpath.2011.10.021; the authors of the referenced article did not disclose
any relevant financial relationships.]
a. Forkhead box A1 (FOXA1) gene is up-regulated in prostate cancer tissue. b. Although FOXA1 functionally promotes several steroid hormone receptors, including AR, it does not modulate estrogen receptor (ER) expression. A favorable prognosis in breast cancer is related to high FOXA1 levels. d. FOXA1 has been shown to promote expression of the negative cell cycle regulator p27, as well as expression of the cell cycle promoter cyclin D1.
12. FOXA1 expression in normal prostate and prostate tumors is dependent upon zone of origin. Based on the
referenced article, select the ONE statement that is NOT TRUE: [See Am J Pathol 2012, 180:848-861; DOI:
10.1016/j.ajpath.2011.10.021; the authors of the referenced article did not disclose any relevant financial relationships.]
a. In normal tissues, FOXA1 levels are higher in the transitional zone (TZ) than in the peripheral zone (PZ). b. Benign prostate hyperplasia occurs in the TZ. c. Primary carcinomas arise mostly in the PZ. d. It is important to accurately define the origins of normal tissue for comparative analyses. The American Society for Investigative Pathology ASIP Semiannual 2012 AJP CME Program in Pathogenesis The American Journal of Pathology, Volume 180, Number 2, February 2012

Source: http://www.asip.org/CME/documents/February2012AJPCMEExamFINALFINALFINAL.pdf