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: ejsmart@uky.edu
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: jeff.balser@vanderbilt.edu
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: icharo@gladstone.ucsf.edu
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: diamond@aecom.yu.edu
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: khavari@cmgm.stanford.edu
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 Lévesque 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: linda_bendall@wmi.usyd.edu.au
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 Fernández-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 Fernández-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: checa229@yahoo.com
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: arhoffman@stanford.edu
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: aschecht@helix.nih.gov
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: kingsb@wfu.edu
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: rossetti@aecom.yu.edu
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: ghotamis@hsph.harvard.edu
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: wmckenna@sghms.ac.uk
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: kchien@ucsd.edu
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: rbergman@usc.edu
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**
Journal
Journal of Clinical Investigation