ScienceCache

Vol. 195
Feb. 18, 2005

GENE THERAPY CONVERTS DEAD BONE GRAFT TO NEW, LIVING TISSUE
Researchers have created a way to transform the dead bone of a transplanted skeletal graft into living tissue in an experiment involving mice. The advance, which uses gene therapy to stimulate the body into treating the foreign splint as living bone, is intended to eventually aid people with various cancers or injuries whose treatment involves the replacement of large sections of bone. To make the transplanted bone more robust, a team led by Edward M. Schwarz, associate professor of orthopedics and of microbiology and immunology, looked into the activity of the genes and proteins that govern its health. His team replaced sections of bones in dozens of mice, using both healthy and dead segments, then scanned the surrounding inflammatory tissue for differences in the levels of the active genes. He discovered that the genes that create two key proteins in living bone, called RANKL and VEGF, were barely expressed around the dead bone. He then modified a harmless virus to carry these genes, devised a method of freeze-drying a paste containing the virus so it could be easily handled, and painted it directly onto a bone graft during surgery. Numerous tests in mice confirmed that the virus permeated the inflammatory tissue around the dead bone and turned on the genes. The findings were posted online this week and will appear in the March 1 issue of Nature Medicine.
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PCBS, FUNGICIDE OPEN BRAIN CELLS TO PARKINSON'S ASSAULT
Scientists investigating the link between PCBs, pesticides and Parkinson's disease have demonstrated new and intricate reactions that occur in certain brain cells, making them more vulnerable to injury after exposures. In two papers published in the journal Neurotoxicology, the group describes how polychlorinated biphenyls (PCBs) disrupt dopamine neurons, which are the cells that degenerate during the course of Parkinson's disease. Researchers also show that low levels of maneb, a fungicide commonly used in farming, can injure the antioxidant system in those same types of cells. Environmental contaminants might make dopamine cells more vulnerable to damage from normal aging, infection, or subsequent exposure to pollutants, researchers say. “If we can identify the mechanisms by which PCBs or pesticides perturb dopamine neuron function, it may lead to the development of therapies that can prevent, slow or stop the progression of Parkinson's," says Lisa Opanashuk, assistant professor of environmental medicine, who led the work. Her studies focus on oxidative stress and antioxidant responses to PCBs in dopamine neurons. She showed that just as in exposure to PCBs, cells treated with low levels of maneb also undergo changes that disturb the balance in the antioxidant defense system.
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RESEARCHERS EYE LINK BETWEEN CHEMOTHERAPY AND SLEEP PATTERNS
Fatigue is a common complaint from people undergoing chemotherapy treatment for cancer. And it couldn’t come at a worse time – because that’s when they need the most energy to endure the emotional and physical challenges of beating the disease. Oncologists encourage patients to get more sleep at night and take naps during the day. But many people are still exhausted, which has cancer and sleep researchers wondering if chemotherapy drugs alter sleep rhythms. “The fatigue persists long after their treatment for many people, no matter how much they sleep,” says Michael Perlis, associate professor of psychiatry and director of the URMC Sleep Research Laboratory. “This suggests to us that factors beyond the disease, or the side effects of treatment, may mediate the chronic fatigue that occurs with breast cancer. Part of the goal of this study is to identify these factors and determine what treatments might best bring relief.” A research team from the sleep lab and the James P. Wilmot Cancer Center suspects the difficulties may lie in the quality, not quantity, of sleep that patients get. They’ve secured a $729,000 grant from the American Cancer Society to study patients with lymphomas or breast or colon cancers. “If the chemotherapy prevents people with cancer from reaching the most restful, healing phase of sleep, it’s not a surprise that they are fatigued and exhausted,” says Joseph Roscoe, research assistant professor of radiation oncology and the principal investigator of the study.
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Exploring the nuances of the brain keeps Charles Duffy busy

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