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  • Image of the Month—Diagnosis

    Abstract Full Text
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    Arch Surg. 2012; 147(11):1064-1064. doi: 10.1001/archsurg.147.11.1064
  • Test Before You Stop

    Abstract Full Text
    Arch Surg. 2009; 144(8):787-787. doi: 10.1001/archsurg.2009.142
  • Identification of Biomarkers of Adrenocortical Carcinoma Using Genomewide Gene Expression Profiling

    Abstract Full Text
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    Arch Surg. 2008; 143(9):841-846. doi: 10.1001/archsurg.143.9.841
  • JAMA Surgery September 15, 2008

    Figure: Identification of Biomarkers of Adrenocortical Carcinoma Using Genomewide Gene Expression Profiling

    Area under the receiver operating characteristic curve (AUC) when the 5 biomarkers with the highest individual AUC values (IL13RA2, HTR2B, CCNB2, RARRES2, and SLC16A9) were combined (based on 89 samples). The combined use of these biomarkers demonstrated a slight increase in diagnostic accuracy compared with the highest individual marker (IL13RA2: AUC, 0.90), and all 5 genes were more accurate compared with tumor size as a clinical variable for the diagnosis of adrenocortical carcinoma (AUC, 0.79). An AUC of 1 represents the perfect diagnostic biomarker, without any false-negative and false-positive results.
  • Notice of Duplicate Publication: “Pathogenesis of Barrett Esophagus: Deoxycholic Acid Up-Regulates Goblet-Specific Gene MUC2 in Concert With CDX2 in Human Esophageal Cells” (Arch Surg. 2007;142 [6]:540-545)

    Abstract Full Text
    Arch Surg. 2008; 143(8):807-807. doi: 10.1001/archsurg.143.8.807-a
  • JAMA Surgery March 1, 2008

    Figure 1: Use of Gene Expression Profiles in Cells of Peripheral Blood to Identify New Molecular Markers of Acute Pancreatitis

    Scatterplot of the differentially expressed genes in peripheral blood mononuclear cells (PBMCs) isolated from rats with acute pancreatitis compared with those from normal control animals that were not operated on. The axes are arbitrary fold changes. The red points above the line are up-regulated genes, and the blue points below the line are down-regulated genes. Nine hundred forty-seven genes were identified and subjected to further analysis (see Figure 2).
  • JAMA Surgery March 1, 2008

    Figure 2: Use of Gene Expression Profiles in Cells of Peripheral Blood to Identify New Molecular Markers of Acute Pancreatitis

    Venn diagram of differential expression of the 947 genes (identified in Figure 1) in peripheral blood mononuclear cells. Expression was compared between rats who underwent laparotomy and ductal infusion with saline, those undergoing infusion with sodium taurocholate to induce acute pancreatitis, and those with intra-abdominal sepsis induced by cecal ligation and puncture. One hundred forty genes induced specifically during sodium taurocholate acute pancreatitis were identified; the most induced and inhibited are depicted in Table 1 and Table 2, respectively.
  • JAMA Surgery March 1, 2008

    Figure 3: Use of Gene Expression Profiles in Cells of Peripheral Blood to Identify New Molecular Markers of Acute Pancreatitis

    Cluster view of genes differentially expressed in peripheral blood mononuclear cells isolated from rats with acute pancreatitis. A, Genes down-regulated in acute pancreatitis, but up-regulated in abdominal sepsis. B, Genes up-regulated in acute pancreatitis, but down-regulated in abdominal sepsis. The “Normal” column is RNA from saline-infused control animals.
  • Association of Morbid Obesity With FTO and INSIG2 Allelic Variants

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    Arch Surg. 2008; 143(3):235-240. doi: 10.1001/archsurg.2007.77
  • Pathogenesis of Barrett Esophagus: Deoxycholic Acid Up-Regulates Goblet-Specific Gene MUC2 in Concert With CDX2 in Human Esophageal Cells

    Abstract Full Text
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    Arch Surg. 2007; 142(6):540-545. doi: 10.1001/archsurg.142.6.540
  • Genomic Approaches to Surgical Diseases: 21st Annual Samuel Jason Mixter Lecture

    Abstract Full Text
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    Arch Surg. 2006; 141(4):409-413. doi: 10.1001/archsurg.141.4.409
  • JAMA Surgery January 1, 2004

    Figure 1: Estrogen and Androgen Receptors as Comediators of Breast Cancer Cell Proliferation: Providing a New Therapeutic Tool

    Androgen receptor gene expression in cell lines used in this study. Lane 1, 50–base pair (bp) ladder; lanes 2 and 3, positive control complementary DNA (cDNA); lanes 4 and 5, rat 1 cDNA; lanes 6 and 7, T-47D cDNA; lanes 8 and 9: HCC1937 cDNA; lanes 10 and 11, water control (H2O). Total RNA was isolated by phenol-chloroform extraction. Reverse transcriptase polymerase chain reaction amplification of the androgen receptor gene yielded a 137-bp DNA fragment. Amplification of the actin gene served as a positive control. Products were separated by 2% agarose gel electrophoresis and detected by ethidium bromide staining.
  • JAMA Surgery October 1, 2003

    Figure: RNA Silencing in Surgical Disease

    Synthetic "therapeutic" RNA or viral RNA enters a cell. This double-stranded RNA is recognized and processed by the dicer enzyme into small interfering RNAs (siRNAs). The duplex siRNAs are unraveled by the RNA-induced silencing complex (RISC) into single antisense strands. The RISC complex is activated by adenosine triphosphate (ATP), and the antisense RNA strands are amplified by RNA-directed RNA polymerase (RdRP). The short antisense strands then bind and "clog" the target messenger RNA (mRNA), marking this mRNA for degradation by an endonuclease. With this strategy, virtually any human gene (ie, an activated oncogene) or virus (ie, hepatitis or human immunodeficiency virus 1) should by accessible to silencing.
  • Vascular Gene Therapy: A Reality of the 21st Century

    Abstract Full Text
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    Arch Surg. 2002; 137(7):854-861. doi: 10.1001/archsurg.137.7.854
  • JAMA Surgery July 1, 2002

    Figure: Vascular Gene Therapy: A Reality of the 21st Century

    Gene delivery for overexpression of therapeutic proteins vs oligonucleotides to inhibit expression of deleterious host proteins. In gene delivery by a generic vector (A), the vector gets internalized into the cell and releases its nucleic acids (containing transgene). The nucleic acids are translocated into the nucleus, where they may remain distinct or become incorporated into the host DNA. Vector (transgene) messenger RNA (mRNA) is transcribed in the nucleus then translated by ribosomal complexes in the cytoplasm to yield the final transgene protein product. It is the overexpression of this protein that is intended to be of therapeutic value. Antisense oligonucleotides are single-stranded nucleic acids (B); antisense oligonucleotides can prevent protein synthesis at several different levels in the gene expression pathway. They can hybridize to host DNA to form a triple helix or to host mRNA and thus prevent mRNA transcription or splicing and modification, respectively. Additionally, they can prevent mRNA export to the cytoplasm and ribosomal translation into protein. Decoy oligonucleotides are double-stranded nucleic acids (C). These oligonucleotides contain consensus sequences for transcription factor–binding sites. When transfected into cells, transcription factors will bind to these consensus sequences on the decoy oligonucleotides in the cytoplasm and will be prevented from translocating into the nucleus. This will prevent binding to host DNA and activation of host transcription.
  • JAMA Surgery June 1, 2002

    Figure: Genotype-Phenotype Analysis in Multiple Endocrine Neoplasia Type 1

    Schematic representation of the MEN1 gene and localization of germline mutations found in 23 families. Green-labeled mutations correspond to frameshift; red, to nonsense; and purple, to missense mutations; black labels represent deletions. bp indicates base pairs.
  • JAMA Surgery December 1, 2000

    Figure 1: Signaling Mechanisms of Altered Cellular Responses in Trauma, Burn, and Sepsis: Role of Ca 2+

    Diagrammatic sketches showing signaling pathways in skeletal myocyte (A), hepatocyte (B), neutrophil (C), and T lymphocyte (D). Abbreviations, in alphabetical order: AC indicates adenylate cyclase; AGP, α-1 acid glycoprotein; ANG-II, angiotensin II; APP, acute-phase protein; APPg, APP gene; C5a, complement protein 5a; cAMP, cyclic adenosine monophosphate; CER, ceramide; CORT, glucocorticoid; CyclinD, E, C, cell-cycle genes; DAG, diacylglycerol; EPI, epinephrine; ER, endoplasmic reticulum; FBR, fibrinogen; Fyn, an Src protein kinase; Giα, inhibitory G protein α subunit; Gq, G protein implicated in the activation of phospholipase C γ; Gs, G protein that stimulates AC; GCG, glucagon; GLUT4g, GLUT4m, and GLUT4p, glucose transporter gene, messenger RNA, and protein; GM-CSF, granulocyte-macrophage colony stimulating factor; HGB, haptoglobin; IL, interleukin; IL-2R, interleukin 2 receptor; InsP3, inositol trisphosphate; IRS-1, insulin-receptor substrate; Jak, Janus kinases; Lck, an Src protein kinase; Lyn, an Src kinase; MAPK, mitogen activating protein kinase; NEPI, norepinephrine; NFATc, nuclear factor AT cytosolic; NFκβ, nuclear factor kappa B; p47/p67, phosphoproteins responsible for NADPH oxidase activation; PAF, platelet activating factor; PEPCK, phosphoenol pyruvate carboxy kinase; PEPCKg, PEPCK gene; PI-3K, phosphotidylinositol-3-kinase; PKC, protein kinase C; PLC, phospholipase C; PLCβ, phospholipase C β; PLCγ, phospholipase Cγ; PrK, phosphorylase kinase; PTK, protein tyrosine kinase; Rac, phosphoprotein responsible for NADPH oxidase activation; Ras, signaling protein critical in MAPK activation; Raf, signaling protein critical in MAPK activation; ROC, receptor-operated Ca2+ channel; SER, sarcoplasmic endoplasmic reticulum; Shc, adapter signaling protein; STAT 3/5, signal transduction activator protein 3 and 5; TcR, T-cell antigen receptor; TNF-α, tumor necrosis factor α; TST, thiostatin; VOC, voltage-operated Ca2+ channel; VP, vasopressin; and Zap, an Src kinase.
  • JAMA Surgery November 1, 1999

    Figure 1: Functional Genomics: Clinical Effect and the Evolving Role of the Surgeon

    Gene addition seeks to compensate for a defective gene by providing cells with a corrective gene. Most delivery systems introduce corrective genes into the cell's nucleus, where they remain only transiently. Other methods integrate genes into the chromosomes. Integrated genes can be passed on to progeny cells in the course of normal cell division, which may provide long-term therapeutic benefits. Figure 1 is adapted from Kmiec EB. Gene therapy. Am Scientist. 1999;87:240-247. Copyright 1999, Sigma Xi, The Scientific Research Society.
  • JAMA Surgery November 1, 1999

    Figure 2: Functional Genomics: Clinical Effect and the Evolving Role of the Surgeon

    Viruses are used as gene delivery vectors to target the cell's nucleus and potentially provide a corrective gene. Figure 2 is adapted from Kmiec EB. Gene therapy. Am Scientist. 1999;87:240-247. Copyright 1999, Sigma Xi, The Scientific Research Society.
  • Functional Genomics: Clinical Effect and the Evolving Role of the Surgeon

    Abstract Full Text
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    Arch Surg. 1999; 134(11):1209-1215. doi: 10.1001/archsurg.134.11.1209