SCIENCE TIP SHEET May 1999
Contacts:
Karen Young Kreeger
[email protected] or
Franklin Hoke
(215) 662-2560
Philadelphia, Pa. -- Below are three story ideas based on ongoing research at
the University of Pennsylvania Medical Center.
Structure of HDL Cholesterol Determined: Using novel methods for performing infrared spectroscopy recently developed in his laboratory, assistant professor of pharmacology Paul H. Axelsen, MD, and his colleagues have resolved a contentious scientific debate over the structure of high-density lipoproteins, or HDL particles, the so-called "good" cholesterol. The team's findings are reported in the May 21 issue of the Journal of Biological Chemistry. HDL is thought to be responsible for ferrying cholesterol from various body tissues to the liver for reprocessing or elimination. In this way, HDL particles are thought to play a crucial role in reducing the risk of atherosclerotic cardiovascular disease. Prior to this study, many scientists thought HDL particles consisted of two-layered disks of fatty molecules, or lipids, surrounded by a "picket fence" of proteins at the disk's edge. A smaller number of investigators also believed that the lipid molecules comprised a two-layered disk, but that the proteins surrounding the disk were wrapped around the disk's perimeter in a "belt" formation. Existing tools for determining molecular structure were technically limited, leaving advocates for the competing models of HDL's structure at odds and without means to resolve the controversy. The best known tool for determining molecular structure, X-ray crystallography, could not be employed because no one knows how to form HDL particles into the requisite crystals. NMR and older forms of infrared spectroscopy both require samples to be dried at one point in their preparation. However, lipoprotein structures are disrupted in the drying process, because they are held together by their mutual repulsion from water, a phenomenon known as the hydrophobic effect. The novel infrared spectroscopy methodology developed by Axelsen and his coworkers enabled them to study HDL particles in water and in their native state. Their results verify the lipid bilayer structure in the particles, presumed in both the "picket fence" and "belt" models, and point unambiguously to the belt model for the orientation of the surrounding proteins. "These findings turn our understanding of HDL structure, not on its head but on its side," Axelsen says. "It's now clear that the proteins in HDL are rotated 90 degrees from what had been the prevailing view."
Cellular Implants Explored for Brain Trauma: For the last decade, the lab of Tracey McIntosh, PhD, director of Penn's Head Injury Center and professor of neurosurgery, bioengineering, and pharmacology, has been investigating neural implants to one day correct brain injuries, which affect nearly two million people every year. For the most part, neuronal transplantation has concentrated on stroke, neurodegenerative disorders, and spinal-cord injuries. Last year, hNT cells -immortalized human nerve cells developed at Penn ten years ago - were successfully transplanted into a stroke patient in Pittsburgh. Recent articles in the Journal of Neurosurgery and Journal of Neurotrauma describe ongoing studies in which Penn researchers are studying how implanted hNT cells might improve brain function in an injured rat. "We found that cells implanted directly adjacent to the injured site 24 hours after the initial trauma survive, appear healthy, and integrate into the host tissue," says Ramesh Raghupathi, PhD, assistant professor of neurosurgery and coauthor on both studies. In one study, 83 percent of the rats had healthy grafts two weeks after the injury. In the second study, 92 percent had healthy grafts at four weeks. Both studies also showed that there was not an enhanced response to the hNT cells by the rat immune system. Both studies, however, did not show an improvement in cognitive skills as measured by a water maze test or in tests of motor function. In hopes of improving rats' performance on these trials, the group's next steps will be to carry out parallel studies with stem cells, inject hNT cells into more than one spot around an injury, and infuse growth factors along with the transplanted cells.
Cardiovascular Phenomenon Explained After 150 Years: When blood vessels are healthy they act like smart pipes: Flow increases, they dilate; if flow decreases, they constrict. This is the body's way of ensuring that the correct amount of oxygen is delivered to the surrounding tissues. "When a heart patient has a narrowed artery, however, the flow patterns are more complex as blood squeezes through the narrowing," says Scott Diamond, PhD, a bioengineer with Penn's Institute of Medicine and Engineering. In 1842, physicians at a Parisian hospital observed that when they put a band around a blood vessel to mimic a constricted area, the vessel unexpectedly hyperdilated downstream of the narrowing. The fluid mechanics and vessel response to narrowing are complicated and have been studied for years, with no plausible explanation, until now. Using a rabbit model, Diamond and colleagues studied the role of nitric oxide -- a powerful chemical messenger that causes vessels to dilate during exercise -- as a mediator of the anomalous dilation. "While a narrowed vessel prevents adequate blood flow, perhaps the high-speed jet of blood that does squeeze through the narrowing could expose the vessel to high blood flow," explains Diamond. The artificial constriction observed 150 years ago tricks the vessel into experiencing a high flow, so it keeps on dilating. But the process spirals out of control since the blood flow velocities never reset as they do in a normal vessel. "Sure enough, if we blocked nitric oxide we were able to block the downstream hyperdilation," notes Diamond. The solving of this 150-year-old problem in cardiovascular medicine has important clinical implications for children with abnormal narrowing of the aorta. Also, the vessel ballooning is sometimes a precursor of aneurysms, so this knowledge may provide insight into the onset of harmful bulges in blood vessel walls. These findings were published in the March issue of Circulation.
The University of Pennsylvania Medical Center's sponsored research and training ranks second in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation -- $201 million in federal fiscal year 1998. In addition, the institution continued to maintain the largest absolute growth in funding for research and training among all 125 medical schools in the country since 1991. News releases from the University of Pennsylvania Medical Center are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to the medical center's home page (http://www.med.upenn.edu) and to the electronic news service Newswise (http://www.newswise.com).
###
RSS