Neurology:
Alzheimer's Plaques Reversed in Mice by Blocking Cholesterol Pathway
Metabolism:
Cellular Stress Appears to Link Obesity, Diabetes
Structural Biology:
Interdisciplinary Team Yields High-res Clathrin Model
Pathology:
Blood Flow Mechanics Affect Genetics in Vascular Cells
School History:
Book and Forum Recognize Achievement of African Americans at HMS
Medical Education:
Education Reform Aims for Longitudinal Clinical Experience
Muscle Loss Pathways Proliferate
Fine-particle Pollution Linked to Blood Pressure Boost
Human Cell Therapy Center Created at CBR Institute
Lieberman to Head Faculty Affairs
Five Faculty Members Become AAAS Fellows
Ground Broken for New Fenway Housing
Grant Funds HSPH Initiative for Preparedness Against Terrorism
Long-term Care: Averting a National Crisis
Muscle Loss Pathways Proliferate
Extensive loss of muscle is a common complication of cancer, AIDS, diabetes, kidney disease, and just plain aging. In work that could eventually lead to therapies for this debilitating and sometimes life-threatening pathology, Steven Shoelson and his colleagues at Joslin Diabetes Center have fingered the inflammatory transcription factor NF-kappa B as a major culprit in muscle destruction.When the researchers engineered mice with NF-kappa B activated in muscle, the animals developed small muscle fibers that shrank with age. Muscle loss was reversed by blocking NF-kappa B either by boosting its physiological inhibitor or by treating the mice with a pharmacological inhibitor, salicylate. Mice with inhibited NF-kappa B resisted muscle shrinkage after nerve damage and showed decreased muscle wasting and prolonged survival in a cancer model.
| "We've had some hints from in vitro studies that NF-kappa B might be important for muscle wasting, but our mouse studies show its importance in living animals." |
Decreased muscle size results from increased protein breakdown, and the researchers showed that NF-kappa B boosted the expression of MuRF-1, an enzyme that steers proteins toward proteasomal degradation. Regulation of MuRF-1 by NF-kappa B echoes the discovery earlier this year by other Harvard researchers of a parallel muscle degradation pathway involving a MuRF-1 relative, atrogin, and FOXO transcription factors (see Research Briefs, Focus, April 30, 2004).
While the relative contribution of the two pathways in different diseases remains to be worked out, cancer is a natural focus for further work on NF-kappa B. The cytokine tumor necrosis factor (TNF), a potential participant in the muscle wasting seen in cancer, is an activator of NF-kappa B. Shoelson intends to initiate a clinical trial to look directly at NF-kappa B activity in the muscle of cancer patients and to test salicylate or similar compounds for a muscle-sparing effect.
--Pat McCaffrey
Fine-particle Pollution Linked to Blood Pressure Boost
The fine particulate pollution that spews from vehicles and power plants may put some people with cardiovascular disease at higher risk of recurring problems by elevating their blood pressure during exercise, researchers from HSPH and Brigham and Women's Hospital report in the Oct. 12 Circulation.Fine particulates are a category of pollutant measuring 2.5 micrometers or smaller--so tiny that it would take several thousand of them to cover the period at the end of this sentence. Small enough to lodge deep in the lung, fine particulates have been linked to asthma, bronchitis, acute and chronic respiratory symptoms, and premature deaths. They also make up much of the haze that obscures the horizon in many areas.
In a project led by Diane Gold, HMS associate professor of medicine at BWH, researchers found higher pollution levels associated with elevated resting blood pressure in repeated measures of 62 people in a cardiac rehabilitation program at BWH. Some people, those with resting heart rates of 70 beats per minute or higher, also showed higher blood pressure during exercise after two days of high pollution.
The findings may partially explain the biologic mechanism underlying the association of pollution with increased risk of acute cardiac events in people with cardiac disease, said first author Antonella Zanobetti, a research associate in the HSPH Exposure Epidemiology and Risk Program. After a heart attack, controlling blood pressure can reduce the risk for subsequent disease and premature death. The researchers speculate that increased blood pressure could reflect a rise in systemic inflammation and endothelial dysfunction.
--Carol Cruzan Morton