Medicine and Health Sciences Commons^™

Increased Susceptibility To Metabolic Syndrome In Adult Offspring Of Angiotensin Type 1 Receptor Autoantibody-Positive Rats., Suli Zhang, Xi Zhang, Lihong Yang, Zi Yan, Li Yan, Jue Tian, Xiaoyu Li, Li Song, Li Wang, Xiaoli Yang, Ronghua Zheng, Wayne Bond Lau, Xinliang Ma, Huirong Liu

Department of Emergency Medicine Faculty Papers

Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free …

Decorin Antagonizes The Angiogenic Network: Concurrent Inhibition Of Met, Hypoxia Inducible Factor 1Α, Vascular Endothelial Growth Factor A, And Induction Of Thrombospondin-1 And Timp3, Thomas Neill, Hannah Painter, Simone Buraschi, Rick T. Owens, Michael P. Lisanti, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a small leucine-rich proteoglycan, inhibits tumor growth by antagonizing multiple receptor tyrosine kinases including EGFR and Met. Here, we investigated decorin during normoxic angiogenic signaling. An angiogenic PCR array revealed a profound decorin-evoked transcriptional inhibition of pro-angiogenic genes, such as HIF1A. Decorin evoked a reduction of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor A (VEGFA) in MDA-231 breast carcinoma cells expressing constitutively-active HIF-1α. Suppression of Met with decorin or siRNA evoked a similar reduction of VEGFA by attenuating downstream β-catenin signaling. These data establish a noncanonical role for β-catenin in regulating VEGFA expression. We found that exogenous …

Graft Versus Host Disease Of The Brain Following Allogeneic Stem Cell Transplant For Myelodysplastic Syndrome, Janet Yoo, Lindsay Simon, Zi-Xuan Wang, Phd, Lawrence C. Kenyon

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality following bone marrow transplantation (BMT). GVHD occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. GVHD, which can present either acutely or chronically, typically involves the skin, gastrointestinal tract, and liver. In contrast, GVHD involving other organs such as the heart and kidney is highly uncommon and involvement of the central nervous system has only very rarely been described in the literature. We report an unusual case …

Blood-Brain Barrier Abnormalities Caused By Hiv-1 Gp120: Mechanistic And Therapeutic Implications., Jean-Pierre Louboutin, David S Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs). These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and …

A Novel Survival-Based Tissue Microarray Of Pancreatic Cancer Validates Muc1 And Mesothelin As Biomarkers., Jordan M Winter, Laura H Tang, David S Klimstra, Murray F Brennan, Jonathan R Brody, Flavio G Rocha, Xiaoyu Jia, Li-Xuan Qin, Michael I D'Angelica, Ronald P Dematteo, Yuman Fong, William R Jarnagin, Eileen M O'Reilly, Peter J Allen

Department of Surgery Faculty Papers

BACKGROUND: One-fifth of patients with seemingly 'curable' pancreatic ductal adenocarcinoma (PDA) experience an early recurrence and death, receiving no definable benefit from a major operation. Some patients with advanced stage tumors are deemed 'unresectable' by conventional staging criteria (e.g. liver metastasis), yet progress slowly. Effective biomarkers that stratify PDA based on biologic behavior are needed. To help researchers sort through the maze of biomarker data, a compendium of ∼2500 published candidate biomarkers in PDA was compiled (PLoS Med, 2009. 6(4) p. e1000046).

METHODS AND FINDINGS: Building on this compendium, we constructed a survival tissue microarray (termed s-TMA) comprised of short-term …