
January 2003 From Journal of Clinical Investigation JCI table of contents, January 15 2003 Find below two the full Table of Contents for the issue.ONLINE FIRST ARTICLES HIV Protease Inhibitors Promote Atherosclerotic Lesion Formation Independent of Dyslipidemia by Increasing CD36-Dependent Cholesteryl Ester Accumulation in Macrophages CONTACT: Eric Smart University of Kentucky Department of Physiology 423 Sanders-Brown 800 South Limestone Lexington, KY 40536 USA Phone 1: 859-323-6412 Fax 1: 859-323-1070 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16261.pdf A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation in a patient with cardiac conduction disease CONTACT: Jeffrey Balser Vanderbilt University 560 Preston Research Building 2220 Pierce Avenue Nashville, TN 37232-6602 USA Phone 1: 615-936-0277 Fax 1: 615-936-2980 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16879.pdf Decreased atherosclerosis in CX3CR1�/� mice reveals a role for fractalkine in atherogenesis CONTACT: Israel Charo Gladstone Institutes of Cardiovascular Disease P.O. Box 419100 San Francisco, CA 94141-9100 USA Phone 1: (415) 826-7500 Fax 1: 415-285-5632 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15555.pdf TABLE OF CONTENTS Prolactin modulates the naive B cell repertoire In addition to playing a critical role in lactation, prolactin is thought to affect cells of the immune system and augment autoimmunity. Both B and T cells express prolactin receptors, and the hormone has been shown to influence T cell development and proliferation. Focusing on the effects of prolactin on B cells, Betty Diamond and colleagues found (see pages 275-283) that a two-fold increase in prolactin can break tolerance to certain self-antigens and induce lupus-like disease in a transgenic mouse model. Increased prolactin levels affected B cell development and maturation, and promoted the survival of high-affinity autoreactive B cells that would normally undergo deletion. While these alterations were consistently observed in one genetic background, they were not seen in a second mouse strain, suggesting that susceptibility to hormone-mediated autoantibody development is genetically determined. CONTACT: Betty Diamond Albert Einstein College of Medicine Department of Microbiology & Immunology and Dept. of Medicine 1300 Morris Park Avenue Room 405, Forchheimer Building Bronx, NY 10461 USA Phone 1: 718/430-4081 Phone 2: 718/430-2811 ext. 4081 Fax 1: 718-430-8711 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16530.pdf Direct Injection of Genetically Engineered Fibroblasts Corrects Epidermolysis Bullosa Skin Dystrophic epidermolysis bullosa refers to a family of severe skin disorders caused by mutations in the type VII collagen gene (COL7A1). Patients lack anchoring fibrils that ensure adhesion of the epidermis to the dermis and develop subepidermal blisters in response to minor mechanical stress. The current lack of treatment is an impetus to develop gene therapy strategies that will restore anchoring fibrils. Paul Khavari and colleagues have focused on fibroblasts, cells that are easy to isolate from patients, manipulate ex vivo, and readminister. As they now report (pages 251-255), intradermal injection of fibroblasts engineered to overexpress COL7A1 into patient skin transplanted onto a mouse was able to restore anchoring fibrils and prevent blistering. CONTACT: Paul A. Khavari Stanford University School of Medicine Dept. of Dermatology P204, MSLS Bldg. Stanford, CA 94305 USA Phone 1: 650-725-5266 Fax 1: 650-723-8762 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17193.pdf Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by G-CSF or cyclophosphamide Hematopoietic progenitor cells, which have the ability to reconstitute the blood and immune systems, reside primarily in the bone marrow. However, they can be mobilized into the circulation by cytokines, and peripheral blood-derived progenitor cells are used for the majority of hematopoietic rescue transplants. Studying the mechanism of progenitor cell mobilization, Jean-Pierre L�vesque and colleagues have examined the role of the chemokine CXCL12 and its receptor CXCR4, both of which are essential for homing and retention of progenitors in the bone marrow. They found (pages 187-196) that mobilization in mice coincides with lower levels of CXCL12 in the marrow on one hand, and cleavage of CXCR4 on the surface of progenitor cells, which renders them unresponsive to CXCL12, on the other. This suggests that inactivation of the CXCR4/CXCL12 pathway by neutrophil-derived proteases might play a critical role in allowing the egress of progenitor cells into the circulation. CONTACT: Linda Bendall Westmead Millennium Institute Westmead Institute for Cancer Research Darcy Rd Westmead, NSW 2145 AUSTRALIA Phone 1: 61-2-98459069 Fax 1: 61-2-98459102 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15994.pdf Defective tumor necrosis factor-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice TNF-alpha induces apoptosis in many different cell types. In some of them, including liver cells, mitochondria play a crucial role in the apoptotic pathway. Ceramide, synthesized in response to TNF-alpha by two sphingomyelinases, neutral SMase and acidic SMase (ASMase), is a pro-apoptotic signaling intermediate. Having found that ASMase-deficient mice are protected from TNF-alpha�mediated hepatocellular apoptosis (pages 197-208), Jose Fern�ndez-Checa and colleagues went on to demonstrate that in response to TNF-alpha (and promoted by ASMase), not ceramide, but glycosphingolipids, including GD3, are targeted to the mitochondria. They conclude that mitochondrial targeting of glycosphingolipids is likely to be the key event that sets off the apoptotic cascade. CONTACT: Jose Fern�ndez-Checa Hospital Clinic i Provincial Instituto Investigaciones Biomdicas IDIBAPS Consejo Superior Investigaciones Cientificas Villarroel, 170 08036-Barcelona, SPAIN Phone 1: +34 93 227 5709 Fax 1: +34 93 451 5272 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16010.pdf A methylated oligonucleotide inhibits IGF2 expression and enhances survival in a model of hepatocellular carcinoma IGF2, which encodes a mitogenic peptide, is overexpressed in a variety of tumors, including hepatocellular carcinoma, and thought to stimulate tumor growth in an autocrine fashion. Having previously shown that inhibition of DNA methylation increases IGF2 transcription from one of its promoters, Andrew Hoffman and colleagues sought to methylate this specific promoter region in the hope of decreasing IGF2 levels and ultimately inhibiting tumor growth. As they report (pages 265-273), treatment with a methylated oligonucleotide that is complementary to the human IGF2 P4 promoter induced de novo methylation in the P4 region. Moreover, IV injection of the oligo prolonged survival of mice implanted with human hepatocarcinoma cells. Future experiments will determine whether such oligos can be used more generally to manipulate mammalian gene expression and whether they have therapeutic potential in liver cancer. CONTACT: Andrew Hoffman VA Palo Alto Health Care System Building 101 Suite B2-125 3801 Miranda Ave. Palo Alto, CA 94304 USA Phone 1: 650-493 5000 63930 Fax 1: 650 856 8024 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15109.pdf Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase CONTACT: Alan N. Schechter Chief, Lab. Chem. Biol. NIDDK, NIH Bldg. 10, Rm. 9N307 9000 Rockville Pike Bethesda, MD 20892 USA Phone 1: 301-496-5408 Fax 1: 301-402-1213 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16672.pdf ACCOMPANYING COMMENTARY: A role for nitric oxide in hydroxyurea-mediated fetal hemoglobin induction CONTACT: Bruce King Wake Forest University Chemistry Department Winston-Salem, NC 27109 USA Phone 1: (336) 758-5774 Fax: (336) 758-4656 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/17597.pdf Adipose-derived resistin and gut-derived RELMbeta selectively impair insulin action on glucose production CONTACT: Luciano Rossetti Albert Einstein College Of Medicine Department of Pharmacology and Diabetes Research and Training Center 1300 Morris Park Ave. Bronx, NY 10461 Phone 1: 718/430-4118 Phone 2: 718-430-4215 Fax 1: 718-430-8557 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16521.pdf ACCOMPANYING COMMENTARY: The irresistible biology of resistin
CONTACT: Gokhan Hotamisligil Harvard School Of Public Health 665 Huntington Ave. Boston, MA 02115 USA Phone 1: 617/432-1950 Fax 1: 617-432-1941 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/17605.pdf Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac Troponin I mutations CONTACT: William J. McKenna St. George's Hospital, Medical School Department of Cardiological Sciences Cranmer Terrace Tooting London, SW17 0RE GREAT BRITAIN Phone 1: 4420-8725-5911 Fax 1: 4420-8682-0944 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16336.pdf ACCOMPANYING COMMENTARY: Genotype, phenotype: upstairs downstairs in the family of cardiomyopathies CONTACT: Kenneth R. Chien University of California, San Diego UCSD Institute of Molecular Medicine 9500 Gilman Drive 0613-C La Jolla, CA 92093 USA Phone 1: 858-534-6835 Fax 1: 858-534-8081 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/17612.pdf Burst-like control of lipolysis by the sympathetic nervous system in vivo CONTACT: Richard N. Bergman University of Southern California School of Medicine Department of Physiology & Biophysics 1333 San Pablo Street, MMR 626 Los Angeles, CA 90033 USA Phone 1: 323-442-1920 Fax 1: 323-442-1918 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/14466.pdf **Please mention the Journal of Clinical Investigation as the source of these articles** |