March 2003

From Journal of Clinical Investigation

JCI Table of Contents, March 14, 2003

Journal of Clinical Investigation is the source of these articles

ONLINE FIRST ARTICLES

WNK kinases regulate thiazide-sensitive Na-Cl cotransport

CONTACT:
David H. Ellison
Oregon Health Sciences University
Nephrology/Suite 262
3314 SW US Veterans Hospital Rd
Portland, OR 97201
USA
Phone 1-503-494-8490
Fax 1-503-494-5330
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/17443.pdf

Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation

CONTACT:
J. Julio Perez Fontan
Washington University School of Medicine
St. Louis Children's Hospital
Department of Pediatrics
One Children's Place
St. Louis, MO 63110
USA
Phone 1-314-454-2527
Fax 1-314 361 0733
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/17458.pdf

TABLE OF CONTENTS

Immune suppression by measles virus

Measles virus infection is often associated with a generalized state of immunosuppression that facilitates health- and life-threatening secondary infections. To understand the mechanisms of immunosuppression, Michael Oldstone and colleagues studied mice that were genetically engineered to be susceptible to measles virus infection. These mice were infected with measles virus five days before challenge with Listeria monocytogenes and compared with age-matched naive and L. monocytogenes�infected mice that did not receive measles virus. The results (pages 805�810) demonstrated that concurrent measles virus infection suppresses innate as well as adaptive immune responses, which prevents effective clearance of the bacterial infection. Future studies are needed to determine how the virus exerts its effects, and it is hoped that these will aid in the development of improved treatment strategies.

CONTACT:
Michael B.A. Oldstone
Dept. Of Neuropharmacology
The Scripps Research Inst.
10550 N. Torrey Pines Road (IMM-6)
La Jolla, CA 92037
USA
Phone 1-858-784-8798
Fax 1-858-784-9981
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/13603.pdf

Proinsulin, diabetes, and the NOD mouse

Accumulating evidence supports a role for proinsulin as a key autoantigen in type I diabetes. In contrast to humans, who have one proinsulin gene, mice express two proinsulin isoforms, which are encoded by different genes. To study the role of proinsulin 2, the predominant isoform in the thymus, Christian Boitard and colleagues have introduced a null mutation for the gene into mice of the NOD genetic background, which spontaneously develop diabetes at a high frequency. As they report (pages 851�857), the absence of proinsulin 2 in these animals was associated with accelerated insulitis and diabetes, increased capacity to transfer diabetes, and elevated levels of anti-insulin autoantibodies. These results demonstrate the importance of proinsulin as an autoantigen in the NOD mouse and suggest that future studies in this system could shed light on the pathogenic or regulatory role of insulin-directed autoimmunity.

CONTACT:
Christian Boitard
Contact: Boitard, Christian
INSERM U561
Hopital St. Vincent de Paul
82 Bd Denfert Rochereau
75014 Paris,
FRANCE
Phone 1-331-4048-8249
Fax 1-331-4048-8352
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/16584.pdf

Cathepsin S promotes atherosclerosis

Remodeling of the ECM contributes to atherosclerosis at multiple stages, and several lines of evidence have implicated the elastolytic cathepsins S (Cat S) and K. Seeking direct evidence for a role of Cat S, Guo-Ping Shi and colleagues crossed mice lacking Cat S with atherosclerosis-prone LDL receptor�deficient mice. They found (pages 897�906) that the double mutants -- when fed a high-cholesterol diet -- had an attenuated response: atherosclerosis was reduced by more than 50% after 12 weeks on an atherogenic diet, and by 30% after 26 weeks. While this study does not reveal the mechanism by which Cat S contributes to atherogenesis, it does suggest several possible modes of action and underscores the possibility that Cat S may serve as a therapeutic target in arterial diseases.

CONTACT:
Guo-Ping Shi
University of California, San Francisco
Surge 203, Box 0911
90 Medical Center Way
San Francisco, CA 94143
USA
Phone 1-415-514-1208
Fax 1-415-476-9749
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/14915.pdf

Stem cells mobilized by crisis

Sickle cell disease affects 150 million people worldwide. The only curative therapy is hematopoietic stem cell transplantation. Because of the limited number of matched donors and the toxicity associated with allogeneic transplants, various gene therapy approaches in autologous stem cells are under development. Encouraged by the observation that sickle cell patients have increased numbers of cells expressing stem cell markers in the peripheral blood, Catherine Verfaillie and colleagues tested peripheral blood from patients during acute crisis and chronic stages of disease for the presence of primitive hematopoietic progenitors (pages 811�819). They found that during acute crisis, patients spontaneously mobilize significant numbers of progenitors with multiple-lineage and repopulation potential into the peripheral blood, suggesting that collection of these progenitors could yield a source of autologous cells suitable for genetic manipulation and subsequent transplantation.

CONTACT:
Catherine M. Verfaillie
University of Minnesota
MMC 716
420 Delaware Street SE
Minneapolis, MN 55455
USA
Phone 1-612-624-3921
Fax 1: 612-624-2436
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/15956.pdf

Mismatch repair awry in lung cancer

Mutations in DNA mismatch repair genes cause inherited colon cancer syndromes, and somatic mutations and promoter methylation of these genes have been found in a variety of human cancers characterized by microsatellite instability (MSI). Having previously shown that MSI and loss of hMLH1 protein expression is common in lung cancer patients from Taiwan, Yi-Ching Wang and colleagues now report (pages 887�895) results from a comprehensive genetic and epigenetic analysis of 77 resected primary non-small cell lung tumors. Of these tumors, 70% had lost expression of either hMLH1 or hMSH2, and promoter methylation seemed to be the predominant cause. Moreover, promoter methylation of hMLH1 (whose expression is lost in over 50% of the samples) appears to be an early event in tumorigenesis and can be detected in sputum samples. Thus it might serve as a potential diagnostic marker.

CONTACT:
Yi-Ching Wang
National Taiwan Normal University
Department of Biology
No. 88, Sec. 4
Tingchou Road
Taipei 116,
TAIWAN
Phone 1-8862-2933-6876
Fax 1-8862-293-12904
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/15475.pdf

Immunization with Neuronal Nicotinic Acetylcholine Receptor Induces Neurological Autoimmune Disease

CONTACT:
Vanda A. Lennon
Neuroimmunology Lab., 828 Guggenheim
Mayo Medical School
200 First Street S.W.
Rochester, MN 55905
USA
Phone 1-507-284-8727
Fax 1-507-284-1814
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/17429.pdf

ACCOMPANYING COMMENTARY:
Autonomic "Myasthenia": The case for an autoimmune pathogenesis

CONTACT:
Daniel B. Drachman
Neurology/Neuromuscular Unit
Johns Hopkins School Of Medicine
600 N. Wolfe St., 5-119 Meyer Bldg.
Baltimore, MD 21205
USA
Phone 1-410-955-5406
Fax 1: 410-955-1961
E-mail: [email protected]

View the PDF of this commentary at: https://www.the-jci.org/press/18180.pdf

Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation

CONTACT:
Ian P. Wicks
The Walter & Eliza Hall Institute of Medical Res.
Reid Rheumatology Laboratory
Division of Autoimmunity & Transplantation
Post Office, The Royal Melbourne Hospital
Victoria 3050,
AUSTRALIA
Phone 1-61-3-9345-2466
Fax 1-61-3-9347-0852
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/16156.pdf

ACCOMPANYING COMMENTARY:
Can SOCS make arthritis better?

CONTACT:
Lionel B. Ivashkiv
Hospital for Special Surgery
Department of Medicine
535 East 70th Street
New York, NY 10021
USA
Phone 1-212-606-1653
Fax 1-212-774-2337
E-mail: [email protected]

View the PDF of this commentary at: https://www.the-jci.org/press/18113.pdf

Mechanisms of TNF-alpha and RANKL mediated osteoclastogenesis and bone resorption in psoriatic arthritis

CONTACT:
Christopher Ritchlin
University of Rochester
601 Elmwood Ave
Box 695
Rochester, NY 14642
USA
Phone 1-585-273-2125
Fax 1-585-506-1979
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/16069.pdf

The Role of the Grb2-p38 MAPK Signaling Pathway in Cardiac Hypertrophy and Fibrosis

CONTACT:
Anthony J. Muslin
Washington University School of Medicine
Departments of Medicine, Cell Biology, & Physiol
Center for Cardiovascular Res. Campus Box 8086
660 S. Euclid Ave
St. Louis, MO 63110
USA
Phone 1-314-747-3525
Fax 1-314-362-0186
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/16290.pdf

DNA damage is a novel response to sublytic complement C5b-9�induced injury in podocytes

CONTACT:
Stuart J. Shankland
University of Washington Medical Center
Division of Nephrology
Box 356521
1959 NE Pacific Avenue, BB1269
Seattle, WA 98195-6521
USA
Phone 1-206-543-3792
Fax 1-206-685-8661
E-mail: [email protected]

View the PDF of this article at: https://www.the-jci.org/press/15645.pdf



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