JCI table of contents

01/21/05

February 1, 2005

Stopping smallpox in its tracks: a new anti-viral approach

Natural or deliberate exposure to smallpox poses a great health threat, especially since routine smallpox vaccinations have been discontinued and no clinically approved treatment currently exists. In the February 1 issue of the Journal of Clinical Investigation, Ellis Reinherz and colleagues from Harvard Medical School propose a new antiviral therapy – a low molecular weight inhibitor of signaling mediated by the smallpox growth factor (SPGF).

SPGF targets the erbB-1 signaling molecule, which normally initiates an intracellular cascade that facilitates viral replication. This study shows that drugs that interfere with erbB-1 signaling inhibit SPGF-induced viral replication and spread. The authors show that treatment with these erbB-1 inhibitors are effective in lowering morbidity and mortality, and boosting T cell immunity, in infected mice.

In an accompanying commentary, Anthony Fauci and Mark Challberg from the National Institutes of Health point out that this approach "may serve to turn the tables on the virus by interfering with the very pathways that are required for viral replication and extrusion."

This study demonstrates, for the first time, that chemical inhibition of host cell signaling pathways exploited by infectious agents represents a new avenue for development of anti-viral therapeutics. These inhibitors, which are already in use in human anti-tumor therapy, may have widespread applications in human viral infections and protection from smallpox. These findings reveal a new approach to the identification and development of antiviral compounds. This is especially critical at a time when the threat of smallpox as a biological weapon is high.

TITLE: Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction

AUTHOR CONTACT:
Ellis L. Reinherz
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Phone: 617-632-3412; Fax: 617-632-3351; E-mail: ellis_reinherz@dfci.harvard.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/379.

ACCOMPANYING COMMENTARY:

TITLE: Host-based antipoxvirus therapeutic strategies: turning the tables

AUTHOR CONTACT:
Anthony S. Fauci
National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA
Phone: 301-496-2263; Fax: 301-496-4409; E-mail: afauci@niaid.nih.gov

This article is available at http://www.jci.org/cgi/content/full/115/2/231.


Single stem cells from bone heal a broken heart

Myocardial infarction results in irreversible damage to the heart that can cause congestive heart failure. The lasting damage results from the limited ability of the myocardium to regenerate and self-repair. Douglas Losordo and colleagues from Tufts University now document the existence of a previously unrecognized subset of human bone marrow–derived stem cells with therapeutic potency for myocardial tissue regeneration following myocardial infarction.

In their study, featured in the February 1 issue of the Journal of Clinical Investigation the authors isolated these human cells at the single cell level and were able to differentiate them into all different cell types. When single human bone marrow–derived stem cells were allowed to divide to form a large population, they were transplanted into a rat model of myocardial infarction. This improved cardiac function because the cells stimulated release of growth factors and anti-apoptotic agents that, in turn, increased the proliferative potential of cardiomyocytes and enhanced survival of host myocardium. This is the first report of endogenous cardiomyogenesis after adult human stem cell transplantation.

Myocardial infarction and heart failure are associated with major morbidity and mortality and there are currently limited therapeutic opportunities for intervention. This study provides the first demonstration of a single, human stem cell population derived from the bone marrow that has the capacity to induce generation of new heart cells and formation of new blood vessels – two key components of successful myocardial repair. The results provide a foundation on which new approaches to repair the damaged heart can be based.

TITLE: A clonally expanded novel population of multipotent stem cells derived from human bone marrow regenerates myocardium after myocardial Infarction

AUTHOR CONTACT:
Douglas W. Losordo
St. Elizabeth's Medical Center, Boston, Massachusetts, USA.
Phone: 617-789-3346; Fax: 617-779-6362; E-mail: Douglas.losordo@tufts.edu

This article is available at http://www.jci.org/cgi/content/full/115/2/326.


IRE1 alpha urges immature B cells to become antibody-secreting plasma cells

B cell development is a two-step process whereby immature B cells develop into plasma cells. New findings in that will appear in the February 1 edition of the Journal of Clinical Investigation from Randal Kaufman and colleagues at the University of Michigan explore the roles of the unfolded protein response (UPR) sensor IRE1 alpha in B cell development (the UPR detects stress in the cell and IRE1 alpha transmits stress signals inside the cell). This new data shows that IRE1 alpha regulates both early and late stages of B cell development. The finding that stress signaling from inside the cell is required for B cell development provides novel insight into the physiological, and not just pathological, roles of the UPR.

An accompanying commentary, Shiv Pillai of Harvard Medical School notes that these findings are quite unexpected and that a role for organelles inside of cells "as a source of signals that drive early events in B cell development is now beginning to emerge."

TITLE: The unfolded protein response sensor IRE1 alpha is required at two distinct steps in B cell lymphogenesis

AUTHOR CONTACT:
Randal J. Kaufman
Howard Hughes Medical Institute, Ann Arbor, Michigan, USA.
Phone: 734-763-9037; Fax: 734-763-9323; E-mail: kaufmanr@umich.edu

This article is available at http://www.jci.org/cgi/content/full/115/2/268.

ACCOMPANYING COMMENTARY:

TITLE: Birth pangs: the stressful origins of lymphocytes

AUTHOR CONTACT:
Shiv Pillai
Harvard University, Boston, Massachusetts, USA.
Phone: 617-726-5619; Fax: 617-724-9648; E-mail: pillai@helix.mgh.harvard.edu

This article is available at http://www.jci.org/cgi/content/full/115/2/224.


Smooth muscle cells ease into new gene profiles after vascular injury

Smooth muscle cells (SMCs) line arteries and aid in normal contraction and vascular function, but change their characteristics and the proteins they express after arterial damage as a result of atherosclerosis, hypertension, and certain cancers. How the cells make these changes is a topic explored in a paper by Gary Owens and colleagues from the University of Virginia that will appear in the February 1 edition of the Journal of Clinical Investigation. The authors provide novel data showing that regions of the SMC genes that control protein expression, called CArG elements, are differentially regulated in response to vascular injury. This regulation ultimately provides the cell with new characteristics.

In an accompanying commentary William J. Mahoney Jr. and Stephen Schwartz point out that this work "may change our focus from vague notions of phenotypic modulation to studying the response by specific genes to specific stimuli."

TITLE: 5'CarG degeneracy in smooth muscle alpha-actin is required for injury-induced gene suppression in vivo

AUTHOR CONTACT:
Gary K. Owens
University of Virginia, Charlottesville, Virginia, USA.
Phone: 434-924-9173; Fax: 434-982-0055; E-mail: gko@virginia.edu

This article is available at http://www.jci.org/cgi/content/full/115/2/418.

ACCOMPANYING COMMENTARY:

TITLE: Defining smooth muscle cells and smooth muscle injury

AUTHOR CONTACT:
Stephen M. Schwartz
University of Washington, Seattle, Washington, USA.
Phone: 206-543-0258; Fax: 206-543-5657; E-mail: steves@u.washington.edu

This article is available at http://www.jci.org/cgi/content/full/115/2/221.


Rab27a helps cells spit out insulin in response to glucose

Patients with type 2 diabetes have impaired insulin secretion in response to glucose. Normally, insulin is stored in vesicles inside pancreatic b cells and upon vesicle transportation to the cell surface and membrane fusion, their insulin content is released. The mechanism used to transport and fuse these vesicles to the b cell membrane is explored in a study by Tetsuro Izumi and colleagues from Gunma University in the February 1 issue of the Journal of Clinical Investigation. The researchers examined pancreatic b cells from mice with a naturally mutated, nonfunctioning form of Rab27a – a protein involved in vesicle trafficking – and showed that mutant cells have a defect in docking of insulin-containing vesicles onto the cell membrane and diminished glucose-stimulated insulin release as a result. The results point to the Rab27a pathway as a new therapeutic target that may be manipulated in order to restore insulin secretion in diabetics.

In an accompanying commentary, Toru Aizawa and Mitsuhisa Komatsu from Shinshu University explain how glucose is metabolized by the b cell and discuss this new found role for Rab27a in facilitating insulin release in response to glucose.

TITLE: Rab27a mediates the tight docking of insulin granules onto the plasma membrane during glucose stimulation

AUTHOR CONTACT:
Tetsuro Izumi
Gunma University, Gunma, Japan.
Phone: 81-27-220-8856; Fax: 81-27-220-8860; E-mail: tizumi@showa.gunma-u.ac.jp

This article is available at http://www.jci.org/cgi/content/full/115/2/388.

ACCOMPANYING COMMENTARY:

TITLE: Rab27a: a new face in b cell metabolism-secretion coupling

AUTHOR CONTACT:
Toru Aizawa
Shinshu University, Matsumoto, Japan.
Phone: 81-263-37-2157; Fax: 81-263-37-2183; E-mail: taizawa@gipac.shinshu-u.ac.jp

This article is available at http://www.jci.org/cgi/content/full/115/2/227.


SOCS2 socks it to growth hormone action

Treatment with growth hormone (GH) is used for a variety of disorders in children and adults. New findings published in the Journal of Clinical Investigation reveal a potential way to augment the anabolic and growth-promoting actions of GH. Christopher Greenhalgh and colleagues from The Walter and Eliza Institute of Medical Research discovered, in a study that will appear in the February 1 edition of the JCI, that a protein called SOCS2 negatively regulates GH action. Targeting SOCS2 may be beneficial for treating growth disorders by increasing the sensitivity of the body to GH.

Derek LeRoith and Peter Nissley, in a related commentary, remark that "the paper sheds light on the role of SOCS2 protein in modulating GH signal transduction" and that understanding the regulation of GH signaling "will be critical in developing treatments for disorders of this system, including acromegaly (a result of excess GH) and growth retardation."

TITLE: SOCS2 negatively regulates growth hormone action in vitro and in vivo

AUTHOR CONTACT:
Christopher J. Greenhalgh
The Walter and Eliza Institute of Medical Research, Victoria, Australia.
Phone: 61-39208-4021; Fax: 61-39208-4100; E-mail: greenhalgh@wehi.edu.au

This article is available at http://www.jci.org/cgi/content/full/115/2/397 .

ACCOMPANYING COMMENTARY:

TITLE: Knock your SOCS off!

AUTHOR CONTACT:
Derek LeRoith
National Institutes of Health, Bethesda, Maryland, USA.
Phone: 301-496-8090; Fax: 301-480-4386; E-mail: derek@helix.nih.gov

This article is available at http://www.jci.org/cgi/content/full/115/2/233.


Insulin-stimulated glucose release is MUN-C business

Impaired glucose transport into muscle and fat is a feature of obesity and diabetes. Insulin stimulates glucose transport by moving the glucose transporter GLUT4 from vesicles inside to the cell to the cell periphery, where GLUT4 is released. The protein Munc18c regulates vesicle trafficking but its role in insulin-induced release of vesicles containing GLUT4 in fat cells has been unclear. This has now been addressed in a study by Yoshikazu Tamori and fellow researchers from Kobe University who, using fat cells lacking Munc18c, found that insulin regulates movement of GLUT4 vesicles towards the cell membrane and fusion with it. Munc18c inhibits fusion of GLUT4 vesicles with the cell membrane without affecting vesicle trafficking to the cell periphery. Regulating Munc18c levels may be useful for increasing glucose transport in type 2 diabetes.

In an accompanying commentary David E. James from the Garvan Institute of Medical Research, Sydney, muses that "an understanding of the molecular determinants of insulin-stimulated glucose transport has been one of the holy grails of hormone action research. A major breakthrough was the discovery that insulin stimulates the [movement of]…GLUT4… to the cell surface. He continues, "elucidating how this process is regulated has remained a challenge." This new study adds to our understand of this process, and as James suggests "one gets the sense that the holy grail of insulin action is within reach."

The study will appear in the February 1 edition of the Journal of Clinical Investigation.

TITLE: Adipocytes from Munc18c-null mice show increased insulin sensitivity in insulin-stimulated GLUT4 externalization

AUTHOR CONTACT:
Yoshikazu Tamori
Kobe University Graduate School of Medicine, Kobe, Japan.
Phone: 81-78-382-5861; Fax: 81-78-382-2080; E-mail: tamori@med.kobe-u.ac.jp

This article is available at http://www.jci.org/cgi/content/full/115/2/291.

ACCOMPANYING COMMENTARY:

TITLE: MUNC-ing around with insulin action

AUTHOR CONTACT:
David E. James
Garvan Institute of Medical Research, Sydney, Australia.
Phone: 61-2-92958100; Fax: 61-2-92958201; E-mail: D.james@garvan.org.au

This article is available at http://www.jci.org/cgi/content/full/115/2/219.


HIV strain properties promote prevalence

A geographical subgroup of HIV, termed clade C, is spreading more rapidly than other clades, invading India, China, and South America. A JCI paper by Monica Sala and colleagues at the Pasteur Institute examines the region of HIV clade C responsible for viral replication, called the promoter, and compares it to those of clades B and E. The viral promoters were known to have different sequences, but the consequences were unknown. Data now show that differences in the clade C promoter triggered massive replication of the virus in cells and during primary infection in monkeys. The preferential replication of clade C in primary infection of monkeys aids our understanding of the spread of human HIV-1 clade C.

The study will appear in the February 1 edition of the Journal of Clinical Investigation.

TITLE: HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo

AUTHOR CONTACT:
Monica Sala
Pasteur Institute, Paris, France.
Phone: 33-140-61-33-09; Fax: 33-145-68-88-74; E-mail: joo@pasteur.fr

This article is available at http://www.jci.org/cgi/content/full/115/2/348.


Molecule predicts colon cancer patient survival

TITLE: Transcriptional activation of integrin b6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma

AUTHOR CONTACT:
Richard C. Bates
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Phone: 617-667-2816; Fax: 617-975-5531; E-mail: rbates@caregroup.harvard.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/339.


Antibody treatment partially reverses nerve damage in Alzheimer disease

TITLE: Anti-Ab antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.

AUTHOR CONTACT:
David M. Holtzman
Department of Neurology, Washington University, St. Louis, Missouri, USA.
Phone: 314-362-9872; Fax: 314-362-2826; E-mail: Holtzman@neuro.wustl.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/428.


T cells target HIV in a relationship on the rebound

TITLE: HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound.

AUTHOR CONTACT:
Rodney E. Phillips
University of Oxford, Oxford, United Kingdom.
Phone: 44-1865-281230; Fax: 44-1865-281890; E-mail: rodney.phillips@ndm.ox.ac.uk

This article is available at http://www.jci.org/content/full/115/2/443.


Erratic lymphatics contribute to asthma

TITLE: Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation.

AUTHOR CONTACT:
Donald M. McDonald
Department of Anatomy, University of California, San Francisco, California, USA.
Phone: 415-476-2118; Fax: 415-476-4845; E-mail: dmcd@itsa.ucsf.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/247.


An IL-6 sense balances pro- and anti-inflammatory effects during asthma

TITLE: The IL-6R a chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo.

AUTHOR CONTACT:
Susetta Finotto
Laboratory of Cellular and Molecular Lung Immunology, University of Mainz, Mainz, Germany.
Phone: 49-06131-3933363; Fax: 49-06131-3933364; E-mail: finotto@mail.uni-mainz.de.

This article is available at http://www.jci.org/cgi/content/full/115/2/313.


With a little help from its friends, RANKL drives bone loss

TITLE: IL-1 mediates TNF-induced osteoclastogenesis.

AUTHOR CONTACT:
Steven L. Teitelbaum
Department of Pathology and Immunology. Washington University School of Medicine, St. Louis, Missouri, USA.
Phone: 314-454-8463; Fax: 314-454-5505; E-mail: teitelbs@wustl.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/282.


Slain brain cells cause mental retardation syndrome

TITLE: The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis.

AUTHOR CONTACT:
David J. Picketts
Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Phone: 613-737-6750; Fax: 613-737-8803; E-mail: dpicketts@ohri.ca.

This article is available at http://www.jci.org/cgi/content/full/115/2/258.


T cell escape from thymic Alcatraz

TITLE: An affinity/avidity model of peripheral T cell regulation.

AUTHOR CONTACT:
Hong Jiang
Department of Medicine, Columbia University, New York, New York, USA.
Phone: 212-305-9988; Fax: 212-305-4943; E-mail: hj4@columbia.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/302.


Researchers identify pathway that jumpstarts the autoimmune response in lupus

TITLE: Human lupus autoantibody–DNA complexes activate DCs through cooperation of CD32 and TLR9.

AUTHOR CONTACT: Andrew D. Luster Massachusetts General Hospital and Harvard University Medical School, Charlestown, Massachusetts USA. Phone: (617) 726-5710; Fax: (617) 726-5651; E-mail: aluster@partners.org.

This article is available at http://www.jci.org/cgi/content/full/115/2/407


Enzyme allows B cells to resist death, leading to leukemia

TITLE: Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis.

AUTHOR CONTACT:
Livio Trentin
Università di Padova, Padova, Italy.
Phone: 011-39-049-821-2298; Fax: 011-39-049-875-4179; E-mail: livio.trentin@unipd.it.

This article is available at http://www.jci.org/cgi/content/full/115/2/369.


Researchers identify the link between heart failure and weight loss

TITLE: Muscle-specific expression of IGF-1 blocks angiotensin II–induced skeletal muscle wasting

AUTHOR CONTACT:
Patrick Delafontaine
Tulane University School of Medicine, New Orleans, Louisiana, USA.
Phone: 504-587-2025; Fax: 504-587-4237; E-mail: pdelafon@tulane.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/451.


To bleed or not to bleed: scientists identify molecules that control the development of blood clots into dangerous thrombi

TITLE: Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy

AUTHOR CONTACT: Anne Angelillo-Scherrer
University of Geneva Medical School, Geneva, Switzerland.
Phone: 41-22-379-55-67; Fax: 41-22-372-92-99; E-mail: Anne.Angelillo@medecine.unige.ch.

This article is available at http://www.jci.org/cgi/content/full/115/2/237.


Live and let die: during bacterial infection Mcl-1 determines life or death of the macrophage

TITLE: Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance

AUTHOR CONTACT:
David H. Dockrell
University of Sheffield, Sheffield, United Kingdom.
Phone: 44-114-2724072; Fax: 44-114-2713892; E-mail: d.h.dockrell@sheffield.ac.uk.

This article is available at http://www.jci.org/cgi/content/full/115/2/359.


Blocking the allergic response in the eye

TITLE: Macrophage inflammatory protein-1a as a costimulatory signal for mast cell–mediated immediate hypersensitivity reactions

AUTHOR CONTACT: Santa Jeremy Ono
University College London, London, United Kingdom.
Phone: 44-0207-608-4069; Fax: 44-0207-608-4044; E-mail: santa.ono@ucl.ac.uk.

This article is available at http://www.jci.org/cgi/content/full/115/2/434.


The type of immune response mounted following exposure to a foreign antigen is site-specific

TITLE: MyD88-dependent induction of allergic Th2 responses to intranasal antigen.

AUTHOR CONTACT:
Damani A. Piggott
Yale University School of Medicine, New Haven, Connecticut, USA.
Phone: 203-785-5391; Fax: 203-737-1765; E-mail: piggotda@biomed.med.yale.edu.

This article is available at http://www.jci.org/cgi/content/full/115/2/459.


A wee role for Tamm-Horsfall glycoprotein in protecting against urinary tract infection

TITLE: Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4–dependent mechanism.

AUTHOR CONTACT:
Gerhard J. Zlabinger
Institute of Immunology, Medical University Vienna, Vienna, Austria.
Phone: 431-4277-64971; Fax: 431-4277-64972; E-mail: Gerhard.Zlabinger@meduniwien.ac.at.

This article is available at http://www.jci.org/cgi/content/full/115/2/468.


Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
    Published on PsychCentral.com. All rights reserved.

 

 

Don't be too timid and squeamish about your actions. All life is an experiment. The more experiments you make the better.
-- Ralph Waldo Emerson
 
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