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RESEARCH BRIEFSA Glass of Their OwnThe expression "heart of glass," popularized by the classic song of the same name by Blondie, may be more than just a metaphor. The cells that make up the heart, lungs, and many other organs in the body display glasslike properties, according to a report in the October Physical Review Letters. Looking at living cells as glass objects can explain their remarkable mechanical resilience, says Jeffrey Fredberg, HSPH professor of bioengineering and physiology and senior author on the study.
The plasticity of cells, such as the rat fibroblast above, may be due to their glasslike properties. Courtesy of BioMedical Image Laboratory, Harvard School of Public Health Intrigued by the plasticity of the smooth muscle cells that surround the lung's airways and that are impaired in asthma, Fredberg's main research interest, he and his colleagues began to probe the mechanical properties of the cells. Using a method they invented in 1992, in which magnetized beads stretch and pull at cultured cells, the researchers came up with a series of surprising measurements. "They did not fit any preconceived notions about how muscle cells should behave--or how any cells should behave," Fredberg said. Perplexed, research associate and lead author Ben Fabry showed the data to a colleague, who handed him a paper on soft glasses, which include substances such as foam, slurries, and colloidal suspensions. Though different in many respects, these substances all share several features. They all contain discrete units--the bubbles in foam, the particles in slurries. They all have weak attractive interactions that are unpredictable and disordered. Conceptually, the theory appeared to fit their observations of living cells. But the real surprise came when they crunched the numbers into the mathematical formulas. "Lo and behold, the theory fit our data perfectly," said Fredberg. In addition to smooth muscle cells, the researchers have tested macrophages, neutrophils, and fibroblasts, and their behavior fits too. "We wondered if this is the grand unifying theory of cell mechanics," he said. Fredberg and his colleagues believe that just as heat can turn an apparently solid champagne glass into liquid, cells are made more fluid--and therefore able to contract, crawl, and divide--by internal jostlings within the cell, what is called noise temperature. "Maybe all these functions are controlled by cells changing their internal noise temperature," he said. "We say that cells are hot to trot. When they're hot, they move. When they've cooled down, they stay put." --Misia Landau
No Patient Surge After Gatekeeping RemovedThe practice of gatekeeping, which was intended to discourage patients from making too many visits to specialists, may not be influencing patient behavior as expected. HMS researchers report in the Nov. 1 New England Journal of Medicine that patients were no more likely to see specialists when relieved of the requirement of having their HMO approve specialist referrals. On April 1, 1998, Harvard Vanguard Medical Associates did away with a 25-year-old gatekeeping system. Timothy Ferris, HMS clinical instructor in medicine at Massachusetts General Hospital; Steven Pearson, HMS assistant professor of ambulatory care and prevention at Harvard Pilgrim Health Care; and their colleagues compared adult patient visits to specialists in the three years before gatekeeping was eliminated and for a year and a half afterwards. The average number of visits made by a patient to a specialist over a six-month period was 0.78 both before and after gatekeeping elimination. Visits to orthopedists and physical or occupational therapists did increase slightly, however, most for lower back pain. "Given the extent to which people in the United States seek alternative care for back pain, it is not surprising that we found an increase in the percentage of visits to specialists for this condition after gatekeeping has been eliminated," write the authors. --Misia Landau
Fine Particulates Guilty in Personal Exposure StudiesMake no mistake: when it comes to public health, gaseous air pollutants such as ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide all may be potential troublemakers. But health effects attributed to the ambient gases may actually be caused by exposure to particulate matter of 2.5 microns or less (PM2.5), according to a study in the October Environmental Health Perspectives. Often spewed together from tailpipes and smokestacks, gaseous pollutants tend to hang in the air with fine particulates. When pollution levels and emergency room visits for asthma attacks both go up in urban areas, epidemiologists often have trouble pinpointing the culpable air pollutant. Currently, statistical models handle commingled pollutants as statistical confounders, amounting to seemingly meaningless results such as the reported link between respiratory hospital visits and ambient levels of carbon monoxide, which is not a respiratory irritant. In a study that may clarify these findings, doctoral student Jeremy Sarnat and his colleagues at HSPH have fingered PM2.5 as the only pollutant with a strong correlation between what is measured outdoors and what people actually breathe. Measurements of personal exposure to ambient gases were much lower than ambient measurements of these gases and seemingly unrelated to them. For purposes of statistical modeling, this means that rather than being statistical confounders, both ambient PM2.5 concentrations and ambient gaseous concentrations are surrogates only for personal PM2.5 exposures. "I don't know if anyone is breathing easier," said Sarnat, "but it does provide a little more evidence that PM2.5-associated health effects that have been observed in many, many studies are attributable, in fact, to exposure to fine particles and not due to a spurious statistical artifact or some other form of bias." For their study, the researchers outfitted 56 people in Baltimore with new personal environmental monitors, developed in the HSPH lab of Petros Koutrakis, who leads the research group. Each subject wore a monitor for eight to 12 consecutive days in the summer and then again in winter. The investigators sampled and evaluated data from three vulnerable groups with a range of activity patterns and lifestyles: senior citizens, schoolchildren, and people suffering from chronic obstructive disease.
Evidence Seen for Organized Olfactory Wiring in BrainThe brain takes only a split second to perceive and respond to a smell, whether it be the aroma of roasting turkey or the sour odor of leftovers gone bad. But it has taken a long time for researchers to meticulously trace sensory information from the nose to the brain, which ultimately perceives thousands of different odors. Now, researchers have shown how information from nasal odor receptors is organized in the brain's olfactory cortex. The olfactory cortex has a sensory map that is virtually identical in different individuals, report Howard Hughes investigator Linda Buck, an HMS professor of neurobiology; postdoctoral fellow Zhihua Zou; and their colleagues in the Nov. 8 Nature. The nose has about 1,000 different types of odor receptor. In the study, information from each of two types of receptor reached distinct clusters of neurons in all five olfactory cortical regions except for the amygdala. The patterns were consistent among 10 knock-in mice for each of the two individual receptors studied. "This was in the mouse, but humans use the same strategies to detect and discriminate odors," Buck said. "The invariant arrangement may explain in part why people have similar sensations of particular odor chemicals. Most people agree that skunks do not smell good, but roses do." Finding odor patterns in the brain may be enough of a surprise for some people, but the results also suggest a reorganization and possible integration of information from different odor receptors for further distribution to higher processing levels, where they may trigger different odor perceptions as well as instinctive and emotional responses. And inputs from the same receptors may be processed at the same time by functionally distinct areas of the olfactory cortex before the information is forwarded in the brain. "We still don't know exactly how different chemical structures are ultimately translated into perceived odors," Buck said, "but we do know now that sensory information undergoes a dramatic transformation in the olfactory cortex, and that there is a highly organized pattern of sensory inputs--order that some people thought did not exist." --Carol Cruzan Morton |
