
April 2003 From Journal of Clinical Investigation JCI Table of Contents, April 15, 2003 ONLINE FIRST ARTICLE
Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors CONTACT: Gabriele Bergers UCSF San Francisco Dep. of Neurosurgery Preuss Laboratory HSE722 513 Parnassus Ave San Francisco, CA 94143-0520 USA Phone 1: 415-476-6786 Fax 1: 415-476-0388 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17929.pdf TABLE OF CONTENTS
The risks and benefits of accelerating suicide. Failure to undergo activation-induced cell death is a major cause of autoimmune diseases, suggesting that enhancing a T cell's sensitivity to apoptosis might have therapeutic potential for the treatment of autoimmunity. Based on the fact that the PKC inhibitor Bis VIII can sensitize CD4+ T cells for death receptor�induced apoptosis, Thomas Brunner and colleagues analyzed the ability of Bis VIII to sensitize CD8+ T cells for accelerated suicide and the consequences of a CD8+ T cell�mediated response. Their findings (pages 1191�1199) � that Bis VIII is able to sensitize CD8+ cells but decreases the normal protective immune response � suggest that resistance to death receptor�mediated apoptosis is necessary for mounting an efficient immune response against life-threatening infections. Bis VIII�based therapies for autoimmune diseases, therefore, must be applied under well-controlled conditions to avoid immune deficiency against opportunistic viral or bacterial infections. CONTACT: Thomas Brunner University of Bern, Institute of Pathology Division of Immunopathology PO Box 62 Murtenstrasse 31 Bern, NULL 3010 SWEDEN Phone 1: 41-31-632-4971 Fax 1: 41-31-381-8764 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16344.pdf
Alterations in PDX1 levels affect islet survival. PDX1 belongs to a family of homeobox genes that regulate initial pancreatic development and the lifelong maintenance of insulin-producing b cells. Human heterozygote carriers develop MODY4, a form of maturity-onset diabetes of the young, a monogenic form of type 2 diabetes characterized by early disease onset, autosomal-dominant inheritance, and defective insulin secretion. In studying Pdx1+/� mice, Kenneth Polonsky and colleagues found that Pdx1+/� islets and b cells were more susceptible to apoptosis at basal glucose concentrations when compared to controls (pages 1147�1160). They also observed early abnormalities in islet architecture in the Pdx1+/� mutants. The data suggest that increased apoptosis and abnormal regulation of islet number and b cell mass are key mechanisms by which partial PDX1 deficiency leads to defective insulin secretion and diabetes. CONTACT: Kenneth S. Polonsky Department of Medicine, Washington University School of Medicine, Box 8066, St. Louis, Missouri 63110 USA. Phone: 314-362-8061 Fax: 314-362-8015 E-mail: [email protected]. View the PDF of this article at: https://www.the-jci.org/press/16537.pdf
Modeling uveitis. Intraocular inflammatory disease, or uveitis, appears to be due in large part to noninfectious, cell-mediated mechanisms. Experimental autoimmune uveitis (EAU) in animals has been a valuable tool for better understanding underlying mechanisms of this disorder and also has provided the possibility of evaluating new approaches to therapy. Both human uveitis and EAU are genetically controlled. Human autoimmune uveitis, in which patients exhibit immunological responses to retinal antigens, has been associated with HLA genes. As they report (pages 1171�1180), Rachel Caspi and colleagues have now succeeded in generating a "humanized" transgenic mouse model of EAU in which disease-relevant epitopes appear to be largely restricted by the human class II molecules. These mice offer a more relevant approximation of human uveitis and should facilitate the characterization of uveitogenic epitopes presented by different HLA class II types. CONTACT: Rachel Caspi National Institute of Health Laboratory of Immunology, NEI 10 Center Drive, 10/10N222 Bethesda, Maryland 20892-1857 USA Phone 1: 301-435-4555 Fax 1: 301-480-6668 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/15155.pdf
Factor H: protector of tissue integrity. Factor H is a potent suppressor of the alternative complement pathway. As a complement regulator, Factor H maintains tissue integrity and possesses anti-inflammatory properties. Mutations in the gene encoding factor H have been found in individuals with hemolytic uremic syndrome. These patients have widespread microthrombi and reactive endothelial proliferation. As a consequence, they suffer from hemolytic anemia, thrombocytopenia, and acute renal failure. On pages 1181�1190, Peter Zipfel and colleagues describe the functional consequences of three-point mutations in the factor H gene associated with hemolytic uremic syndrome. The features of the defective protein help to explain progression of vascular damage in patients and underline a role for factor H in tissue integrity during thrombus formation. CONTACT: Peter Zipfel Hans Knoell Institute for Natural Products Research Department of Infection Biology Beutenbergstrasse 11a D-07745 Jena, GERMANY Phone 1: 49-3641-656900 Fax 1: 49-3641-656902 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16651.pdf
Cannabinoids and multiple sclerosis. Previous in vitro studies have demonstrated the immunomodulatory effects of cannabinoids; however, little is known about their immunosuppressive properties in autoimmune diseases such as multiple sclerosis (MS). Using a mouse model of virus-induced chronic�progressive MS, Stephen Miller and J. Ludovic Croxford investigated the immunosuppressive potential of the cannabinoid receptor agonist R(+)WIN55,212 (pages 1231�1240). The authors demonstrated that R(+)WIN55,212, when given at the time of initial infection, can suppress the development of MS-like disease. When administered at the onset of symptoms or during established disease, R(+)WIN55,212 significantly inhibited levels of IL-1b, IL-6, TNF-a, and IFN-g, important inflammatory mediators in the induction and progression of autoimmune disease in a number of MS-like mouse models of disease and presumably in MS. The data suggest that the potent immunosuppressive properties of R(+)WIN55,212 or other cannabinoids may have therapeutic potential in halting disease progression in individuals with MS in addition to providing symptomatic relief of limb spasticity, tremor, and pain. CONTACT: Stephen D. Miller Northwestern University Medical School Department of Microbiology-Immunology 303 E. Chicago Ave. Chicago, IL 60611 USA Phone 1: 312-503-7674 Fax 1: 312-503-1154 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17652.pdf
CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes CONTACT: Markus F. Neurath University of Mainz Laboratory of Immunology I. Medical Clinic Langenbeckstrasse 1 55101 Mainz, GERMANY Phone 1: 49-613-117-2489 Fax 1: 49-613-117-5508 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16432.pdf ACCOMPANYING COMMENTARY: Azathioprine:Old drug, new actions CONTACT: Gary A. Koretzky Abramson Family Cancer Research Institute University of Pennsylvania School of Medicine, 415 BRB II/III 421 Curie Boulevard Philadelphia, Pennsylvania 19104 USA. Phone: 215-746-5522 Fax: 215-746-5525 Email: [email protected]. View the PDF of this commentary at: https://www.the-jci.org/press/18384.pdf
Genetic Disruption of gamma-Melanocyte Stimulating Hormone Signaling Leads to Salt-Sensitive Hypertension in the Mouse CONTACT: Michael H. Humphreys University of California, San Francisco Box 1341 San Francisco, CA 94143 USA Phone 1: 415-476-4104 Phone 2: 415-476-4638 Fax 1: 415-282-8182 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16993.pdf ACCOMPANYING COMMENTARY: Salt-sensitive hypertension: If only it were as simple as rocket science CONTACT: Timothy L. Reudelhuber Clinical Research Institute 110 Pine Avenue West Montreal, Quebec H2W 1R7, CANADA Phone 1: 514-987-5716 Fax 1: 514-987-5717 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18397.pdf
Nonreduntant roles of antibody, cytokines and perforin for the immune eradication of established Her-2/neu carcinomas CONTACT: G. Forni University of Turin Dip. Sci. Clin. Biologiche Ospedale San Luigi Gonzaga Orbassano, 10043 ITALY Phone 1: 39-011-670-8119 Fax 1: 39-011-903-8639 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17426.pdf ACCOMPANYING COMMENTARY: Coordinated tumor immunity CONTACT: Glenn Dranoff Dana Farber Cancer Institute 44 Binney St. Dana 510E Division of Hematologic Malignancies Boston, MA 02115 USA Phone 1: 617-632-5051 Fax 1: 617-632-5167 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18359.pdf
Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in man CONTACT: Philip M. Murphy NIH/NIAID Laboratory of Host Defenses Bldg. 10, Room 11N113 Bethesda, MD 20892 USA Phone 1: 301-496-8616 Fax 1: 301-402-4369 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/16790.pdf ACCOMPANYING COMMENTARY: The fractalkine receptor CX3CR1 is a key mediator of atherogenesis CONTACT: Myron I. Cybulsky Toronto General Research Institute 200 Elizabeth St., CCRW 1-855 Toronto, ON M5G 2C4 CANADA Phone 1: 416-340-3578 Fax 1: 416-340-3578 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18237.pdf
Role of RANK Ligand in Mediating the Increased Bone Resorption in Early Postmenopausal Women CONTACT: Lawrence B. Riggs Mayo Clinic Osteoporosis Research 200 1st St. SW North 6 Plummer Rochester, MN 55905 USA Phone 1: 507-284-3961 Phone 2: 507-284-2511 Fax 1: 507-284-8271 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17215.pdf ACCOMPANYING COMMENTARY: RANKL and the regulation of skeletal modeling CONTACT: Norman H. Bell Bone & Mineral Metabolism Medical University of South Carolina 114 Doughty Street, PO Box 250775 Charleston, SC 29425 USA Phone 1: 843-876-5162 Fax 1: 843-876-5163 E-mail: [email protected] View the PDF of this commentary at: https://www.the-jci.org/press/18358.pdf
Epidermal growth factor amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia CONTACT: Michael Moskowitz Dept. Neurology Mass. General Hospital 149 13th Street, Rm 6403 Charlestown, MA 02129 USA Phone 1: 617-726-8440 Fax 1: 617-726-2547 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17170.pdf
Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension: Role of the NADPH-oxidase CONTACT: David G. Harrison Emory University School Of Medicine Division of Cardiology 1639 Pierce Drive 319 WMB Atlanta, GA 30322 USA Phone 1: 404-727-8147 Fax 1: 404-727-3585 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/14172.pdf
A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of fgf with its receptor CONTACT: David Naor The Lautenberg Center for General and Tumor Immunology The Hebrew University-Hadassah Medical School Jerusalem 91120 ISRAEL Phone: 972-2-675-8722 Fax: 972-2-642-4653 E-mail: [email protected] View the PDF of this article at: https://www.the-jci.org/press/17100.pdf |