- Press Release Distribution

JCI table of contents: Jan. 25, 2011

( EDITOR'S PICK: Possible new approach to treating a life-threatening blood disorder

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease of the blood system. The condition is caused by the presence of ultralarge multimers of the protein von Willebrand factor, which promote the formation of blood clots (thrombi) in small blood vessels throughout the body. Current treatments are protracted and associated with complications. However, a team of researchers, led by José López, at the Puget Sound Blood Center, Seattle, has generated data in mice that suggest that the drug N-acetylcysteine (NAC), which is FDA approved as a treatment for chronic obstructive lung disease and as an antidote for toxicity due to acetaminophen (paracetamol), might provide a rapid and effective treatment for patients with TTP through its ability to decrease the size of von Willebrand factor multimers.

In an accompanying commentary, Michael Berndt and Robert Andrews, concur with the conclusions of López and colleagues, although they caution that there are a number of caveats to the view that NAC could be used to treat patents with TTP.

TITLE: N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice

José A. López
Puget Sound Blood Center, Seattle, Washington, USA.
Phone: 206.398.5930; Fax: 206.587.6056; E-mail:

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TITLE: Thrombotic thrombocytopenic purpura: reducing the risk?

Michael C. Berndt
Dublin City University, and Royal College of Surgeons in Ireland, Dublin, Ireland.
Phone: 353.1.7007658; Fax: 353.1.7006558; E-mail:

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ONCOLOGY: Not such a good anticancer approach: inhibiting the protein Notch1

Excessive signaling through the protein Notch1 has been linked to several types of cancer. Inhibiting the Notch1 signaling cascade is therefore being considered as an anti-cancer therapy. Previous preclinical studies have indicated that short-term blockade of Notch1 signaling has minimal side effects. However, Raphael Kopan and colleagues, at Washington University, St. Louis, have now determined in mice that loss of the Notch1 gene, in a context that mimics chronic Notch1 inhibition, leads to blood vessel tumors in the liver and decreased survival. These data raise concerns regarding the safety of chronic use of drugs targeting Notch1, leading the authors and, in an accompany commentary, Sandra Ryeom, at the University of Pennsylvania School of Medicine, Philadelphia, to suggest that the development of Notch1 therapies should be reevaluated.

TITLE: Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice

Raphael Kopan
Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
Phone: 314.747.5520; Fax: 314.747.5503; E-mail:

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TITLE: The cautionary tale of side effects of chronic Notch1 inhibition

Sandra W. Ryeom
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Phone: 215.573.5857; Fax: 215.573.2014; E-mail:

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CARDIOLOGY: Developmental misstep results in extremely fast heartbeat

Wolff-Parkinson-White syndrome is characterized by periods of an extremely fast heartbeat. These occur because of the presence of additional electrical pathways in the heart that cause the bottom chambers of the heart (the ventricles) to contract prematurely. The developmental reasons for premature ventricular contraction (also known as ventricular preexcitation) are not well understood. However, two independent research groups have now identified in mice a new mechanism by which additional electrical pathways in the heart can form, resulting in ventricular preexcitation. Specifically, the data from both groups — one led by Jonathan Epstein, at the University of Pennsylvania, Philadelphia; and the other by Vincent Christoffels, at the Academic Medical Center, The Netherlands — indicate that additional electrical pathways in the heart form as a result of inappropriate development of a structure in the embryonic heart known as the AV canal.

In an accompanying commentary, Hiroshi Akazawa and Issei Komuro, at the Osaka University Graduate School of Medicine, Japan, discuss the importance of these two papers for understanding the mechanisms of physiologic and pathologic heart development.

TITLE: Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways

Jonathan A. Epstein
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Phone: 215.898.8731; Fax: 215.573.2094; E-mail:

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TITLE: Defective Tbx2-dependent patterning of the atrioventricular canal myocardium causes accessory pathway formation in mice

Vincent M. Christoffels
Academic Medical Center, Amsterdam, The Netherlands.
Phone: 0031.20.566.7821; Fax: 31.20.697.6177; E-mail:

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TITLE: Navigational error in the heart leads to premature ventricular excitation

Issei Komuro
Osaka University Graduate School of Medicine, Osaka, Japan.
Phone: 81.6.6879.3631; Fax: 81.6.6879.3639; E-mail:

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IMMUNOLOGY: To modify or not to modify proteins with inflammatory function

A team of researchers, led by Martin Bergo, at the University of Gothenburg, Sweden, has generated in mice surprising data with clinical implications that call into question current dogma that modification of proteins known as Rho proteins by the fat molecule geranylgeranyl are critical to the function of inflammatory cells.

Geranylgeranyl modification of Rho proteins by geranylgeranyltransferase type I (GGTase-I) is considered essential for their function and that of inflammatory cells. Bergo and colleagues therefore hypothesized that mice lacking GGTase-I in immune cells known as macrophages would be protected from inflammatory disease. However, these mice were found to develop severe joint inflammation resembling erosive rheumatoid arthritis. Importantly, the disease was initiated by the GGTase-I–deficient macrophages, which hypersecreted inflammatory molecules known as cytokines. As the authors note and Mark Philips, at New York University, New York points out, in an accompanying commentary, these data have important implications for drug development, where GGTase-I inhibitors have been proposed as a strategy to treat inflammatory disorders and are under development as anticancer drugs.

TITLE: Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice

Martin O. Bergo
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Phone: 46.31.342.78.58; Fax:; E-mail:

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TITLE: The perplexing case of the geranylgeranyl transferase–deficient mouse

Mark R. Philips
New York University Cancer Institute, New York, New York, USA.
Phone: 212.263.7404; Fax: 212.263.9210; E-mail:

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IMMUNOLOGY: More regulators of Th17 immune cell generation

A subset of immune cells known as Th17 cells have an important role in clearing certain bacterial and fungal infections. However, they are also thought to sometimes attack other cells and tissues of the body, causing autoimmune diseases such as multiple sclerosis. Understanding the regulatory pathways underlying the generation of these cells is therefore of immense clinical interest. In this context, a team of researchers, led by Ying Qin Zang, at the Chinese Academy of Sciences, Shanghai, has now determined that the protein LXR negatively regulates the generation of both mouse and human Th17 cells. Importantly, LXR activation in mice ameliorated disease in a model of multiple sclerosis, whereas LXR deficiency exacerbated disease. Further analysis defined the signaling pathway underlying LXR-mediated regulation of Th17 cell generation. Thus, as highlighted by Liang Zhou and colleagues, at Northwestern University, Chicago, in an accompanying commentary, these data have important implications for those seeking to develop treatments for Th17 cell–mediated autoimmune diseases.

TITLE: Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation

Ying Qin Zang
Institute for Nutritional Sciences, Chinese Academy of Sciences, Shanghai, China.
Phone: 86.21.54920913; Fax: 86.21.54920913; E-mail:

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TITLE: Nuclear receptors take center stage in Th17 cell–mediated autoimmunity

Liang Zhou
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Phone: 312.503.3182; Fax: 312.503.8240; E-mail:

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ONCOLOGY: Stromal instigation promotes tumor growth

Critical to the growth and progression of a tumor is the aberrant fibrous tissue, which is known as the tumor stroma, that surrounds the cancer cells. More complete understanding of how the tumor stroma forms might provide new targets for anticancer therapeutics. In this context, a team of researchers, led by Sandra McAllister, at Harvard Medical School, Boston, has now identified in mice a mechanism by which certain types of tumor at one site can stimulate the growth of indolent tumors at distant sites, providing potential new therapeutic targets.

Preclinical data have indicated that certain tumors, which have been termed instigators, stimulate cells in the bone marrow to enter the circulation and subsequently promote the growth of otherwise indolent cancer cells (responders) at distant sites. In this study, McAllister and colleagues have characterized the bone marrow cells involved in this process and found that they secrete the protein granulin, which promotes the formation of a tumor stroma around the responding cancer cells. The clinical relevance of these data are highlighted by the observation that high levels of granulin expression in human breast cancer correlated with an aggressive form of breast cancer and reduced patient survival. The authors therefore suggest that granulin and the cells that produce it might provide new targets for anticancer therapeutics, a point with which Andrew Bateman, at McGill University, Montreal, concurs in an accompanying commentary.

TITLE: Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice

Sandra S. McAllister
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Phone: 617.355.9059; Fax: 617.355.9093; E-mail:

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TITLE: Growing a tumor stroma: a role for granulin and the bone marrow

Andrew Bateman
Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Phone: 514.934.1934; Fax: 514.843.2819; E-mail:

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After stroke, admission to designated stroke center hospitals associated with reduced risk of death

Patients who had an ischemic stroke and were admitted to hospitals designated as primary stroke centers had a modestly lower risk of death at 30 days, compared to patients who were admitted to non-designated hospitals, according to a study in the January 26 issue of JAMA. Stroke is the leading cause of serious long-term disability and the third leading cause of death in the United States. Responding to the need for improvements in acute stroke care, the Brain Attack Coalition (BAC) published recommendations for the establishment of primary stroke centers in 2000, and ...

Occurrence of stroke after coronary artery bypass graft surgery appears to be decreasing

An analysis of data on more than 45,000 patients who underwent coronary artery bypass graft (CABG) surgery at an academic medical center over the past 30 years finds that the occurrence of stroke after CABG has declined, despite an increase in risk profiles of patients, according to a study in the January 26 issue of JAMA. Stroke is a devastating and potentially preventable complication of CABG surgery. Because it increasingly is being reserved for elderly patients with extensive coronary disease and co-existing conditions, prevalence of stroke after CABG is likely to ...

Cholera vaccination beneficial, post-outbreak

Cholera vaccination beneficial, post-outbreak Researchers newly report evidence that vaccination against cholera can be beneficial even after an outbreak has begun. Rita Reyburn, Dr. Lorenz von Seidlein, Dr. John Clemens and colleagues at the International Vaccine Institute (IVI) in Seoul, Korea analyze the impact that vaccination could have had on recent outbreaks around the globe in "The case for reactive mass oral cholera vaccinations", and Drs. Dang Duc Anh and Anna Lena Lopez and colleagues at IVI and in Vietnam report on the impact of such "reactive" use of vaccine ...

Study: Get thee to a stroke center

Hospitals with designated stroke centers are associated with up to 20 percent higher survival rate for patients with ischemic stroke and significantly greater use of acute stroke therapy. That is the conclusion of a study appearing today in the Journal of the American Medical Association which compares treatment and outcomes in stroke care between hospitals in New York State. "The basic premise of stroke centers and stroke care – that coordinated care delivered around a specific disease can likely improve outcomes – is widely accepted," said University of Rochester ...

Report examines life expectancy in US and other high-income nations

Over the last 25 years, life expectancy in the U.S. has been rising at a slower rate than in many other high-income countries, such as Japan and Australia, despite our spending more on health care than any other nation. EXPLAINING DIVERGENT LEVELS OF LONGEVITY IN HIGH-INCOME COUNTRIES, a new report from the National Research Council, identifies factors that contribute to the U.S. shortfall in life expectancy. ###Reporters who wish to obtain copies should contact the Office of News and Public Information at 202-334-2138 or e-mail Advance copies will be available ...

Protection of pregnant women against malaria still inadequate

A study published today in The Lancet Infectious Diseases finds that methods to protect pregnant women from malaria are still underutilised in sub-Saharan Africa (SSA). A review of national control strategies by a team of international researchers, led by the Malaria in Pregnancy Consortium and funded by the Consortium and the Wellcome Trust, has concluded that despite major efforts, coverage is still inadequate in many areas and needs to be scaled up. Malaria infection in pregnancy can lead to devastating consequences for both mother and child. The World Health Organization's ...

Fluorescent color of coral larvae predicts whether they'll settle or swim

Fluorescent color of coral larvae predicts whether theyll settle or swim
AUSTIN, Texas—Young staghorn coral that fluoresce redder are less likely to settle and develop into coral polyps than their greener peers, University of Texas at Austin biologists have discovered. The finding may help scientists monitor how corals adapt to global warming because the less likely coral larvae are to settle, the more likely they will disperse from their reef of origin. "By simply looking at the color of a larval population, we may soon be able to say which larvae are going to be long-range dispersers and which will be short-range dispersers," says Mikhail ...

Star performer in basic biology labs diagnosed with first virus

A workhorse of modern biology is sick, and scientists couldn't be happier. Researchers at Washington University School of Medicine in St. Louis, the Jacques Monod Institute in France and Cambridge University have found that the nematode C. elegans, a millimeter-long worm used extensively for decades to study many aspects of biology, can be targeted by naturally occurring viral infections. The discovery means C. elegans is likely to help scientists study the way viruses and their hosts interact. The findings will be published next week in the online, open access journal ...

Shining new light on air pollutants using entangled porous frameworks

Kyoto, Japan -- Certain types of pollution monitoring may soon become considerably easier. A group of researchers centered at Kyoto University has shown in a recent Nature Communications paper that a newly-formulated entangled framework of porous crystals (porous coordination polymers, or PCPs) can not only capture a variety of common air pollutants, but that the mixtures then glow in specific, easily-detected colors. Lead author for the paper was Dr. Yohei Takashima. Until now, chemical sensors have generally needed to be custom-designed to recognize specific compounds, ...

Heart-targeting Listeria increase cardiac disease risk

Heart-targeting Listeria increase cardiac disease risk
Certain strains of the food pathogen Listeria are uniquely adapted to infect heart tissues and may put people at a higher risk from serious cardiac disease, according to a new study published in the Journal of Medical Microbiology. Developing new diagnostic tests to identify these potentially fatal strains could protect those most at risk, such as those with heart valve replacements. Researchers from the University of Illinois, Chicago have shown that a sub-population of the bacterium Listeria monocytogenes display an enhanced ability to infect cardiac tissue. They found ...


Human activity: A double-edged sword in the face of drought

Portfolio performance in financial management: apraize, analyze, act.

Landmark Nature Medicine study reports promising new treatment reduces suffering in Sanfilippo syndrome

Membrane protein analogues could accelerate drug discovery

Berkeley Lab researchers advance AI-driven plant root analysis

Cleveland Clinic study shows weight loss surgery cuts risk of heart complications and death in patients with obstructive sleep apnea and obesity

SQUID pries open AI black box

Resiliency shaped by activity in the gut microbiome and brain

Inspired by nature: synthetic nightshade molecule effective against leukemia cells

Promise green hydrogen may not always be fulfilled

Unifying behavioral analysis through animal foundation models

Up to 30 percent more time: Climate change makes it harder for women to collect water

Heart failure in space: scientists calculate potential health threats facing future space tourists in microgravity

Experts offer guidance on talking with children about racism at pediatrician's office

Drugs for HIV and AIDS trialed as brain tumor treatment for first time

Breakthrough in nanoscale force measurement opens doors to unprecedented biological insights

Scientists discover new behavior of membranes that could lead to unprecedented separations

When inflicting pain on others pays off T

The Lancet: Managing gestational diabetes much earlier in pregnancy can prevent complications and improve long-term health outcomes, experts say

New study finds dinosaur fossils did not inspire the mythological griffin

NASA astronaut Woody Hoburg to deliver keynote address at ISSRDC focused on developing a space workforce

Study: Fatigue-management training improved sleep, safety, well-being for Seattle police

Guiding humanity beyond the moon: OHIO’s Nate Szewczyk and students coauthor papers published in “Nature” journals that revolutionize human space biology

Grant supports research to identify barriers to health care for Black women

Scientists at uOttawa develop innovative method to validate quantum photonics circuits performance

New report on community-centered approach to providing vaccine education and resources to persons experiencing homelessness during COVID-19

Government updates race and ethnicity data collection standards: implications and insights

Dr. Vivek S. Kavadi named CEO of the American Society for Radiation Oncology (ASTRO)

Dietary sucrose determines activity of lithium on gene expression and lifespan in drosophila melanogaster

Assessment of CEA, CA-125, and CA19-9 as adjuncts in non-small cell lung cancer management

[] JCI table of contents: Jan. 25, 2011