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The Yale Alumni Magazine is owned and operated by Yale Alumni Publications, Inc., a nonprofit corporation independent of Yale University. The content of the magazine and its website is the responsibility of the editors and does not necessarily reflect the views of Yale or its officers. |
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One of the most common ailments among American adults has been fingered as a possible precursor to one of the deadliest. Obstructive sleep apnea, in which blockage of the upper respiratory airway triggers short arousals from slumber as the body struggles to breathe, has been found to double and even triple the risk of stroke, says Klar Yaggi of the Yale Center for Sleep Medicine. The results of Yaggi’s study appeared in the November 10 issue of the New England Journal of Medicine. Clinicians and researchers have noted an unusually high prevalence of obstructive sleep apnea in stroke survivors, but it has not been clear whether this was simply a consequence of the stroke. To find out, Yaggi and his colleagues tracked the health outcomes of two groups of patients at the Center for Sleep Medicine. Some patients suffered from obstructive sleep apnea but had never suffered stroke; others had come to the center for different reasons. After adjusting for conditions such as obesity and hypertension, the researchers found that sleep apnea was a significant risk factor in its own right. Overall, it produced a twofold increase in risk of stroke—or death by any cause. Those who suffered an extreme level of apnea faced a threefold increase. “This is a remarkably high risk of stroke,” says Virend Somers, a professor of medicine and consultant in cardiovascular disease at the Mayo Clinic, who praised the study for its thoroughness. “And a lot of these people were actually being treated. So maybe the risk if we didn’t treat them is even higher.” Obstructive sleep apnea is most common in men, particularly those with excess weight in the gut and neck area. As the upper airway loses muscle tone during sleep, it closes off partially or entirely, forcing patients to wake up for one or two seconds to get air down to their lungs. Most sufferers remain unaware of their affliction, which makes for a pernicious nocturnal cycle of near-suffocation. “Over and over throughout the night there is a lack of oxygenated blood going to tissues in the body, and then a reperfusion of oxygen,” says Yaggi. “We know that this stress can cause inflammation of the blood vessels within the body and lead to narrowing of the blood vessels. And the awakening part—those transient arousals with a surge of adrenaline—is associated with a significant surge in blood pressure.” These repeated jumps in blood pressure also bode ill for cardiovascular health. Fortunately, there are effective treatments for obstructive sleep apnea, among them losing weight, avoiding alcohol, and various kinds of surgery to remove excess nose and throat tissue. In many cases, doctors prescribe a continuous positive airway pressure (CPAP) device to keep the throat open. In a study that also appeared in the November 10 NEJM, a group of Canadian researchers showed a relationship between central sleep apnea, a condition in which the brain doesn’t send the proper signals to the muscles that control breathing, and chronic heart failure. (While CPAP did not reduce the number of deaths among those patients, it increased quality of life—something treatment can often do for sufferers and those who try to sleep beside them.) Considering that stroke is the second-leading cause of death worldwide and the leading cause of long-term disability, Yaggi hopes his study will change the status quo in sleep apnea awareness: only about half of sufferers get diagnosed or seek treatment. “About four to five percent of the adult population has obstructive sleep apnea,” he observes. “To put that in context, that’s more than asthma and diabetes in the adult population.” And as the trend toward obesity in Western countries continues to rise, the picture is expected to get worse.
Crystals in Real Time A team of materials scientists at Yale has moved a step closer to their equivalent of the Holy Grail: the ability to predict and control the structure of a substance as it forms and to determine in advance how its structure will relate to its properties. In the September issue of Applied Physics Letters, Ainissa Ramirez, assistant professor of engineering, and her colleagues describe their investigations of the formation of nickel-titanium crystals—in which, for the first time, they were able to verify predictions made by theoretical models. The Ramirez team created thin films of the alloy and then placed the samples in a specially designed heat chamber of a transmission electron microscope. “The material is amorphous when it’s deposited,” says Ramirez. “Like a bunch of kindergartners, there’s no order to its structure at all.” But when the alloy is heated, nickel-titanium molecules rearrange themselves into the orderly structure called a crystal. “We monitor the process every two seconds at a host of different temperatures and count the rate of crystal assembly and the rate at which the crystals grow,” says Ramirez. These rates matched the theory very closely. The result has enabled Ramirez to create what she calls a “microstructural map—you tell me the temperature you want to use, and I can tell you the microstructure of the material.” In the future, she hopes this map will be beneficial to engineers who are attempting to use nickel-titanium alloys in various kinds of micromachines. The material is currently used in biomedical stents, dental braces, and thermostat shut-off switches.
The Reading Gene If you’re having trouble reading this, you might have a particular variant of the gene DCDC2. Jeffrey R. Gruen, a molecular geneticist at the School of Medicine, and his colleagues have identified a gene believed to be involved in dyslexia. The discovery offers a genetic marker that could help diagnose the disability much sooner than is now possible. “Good intervention is available, but it works best when it’s implemented early—before reading problems start, before self-esteem suffers,” says Gruen. Three lines of evidence led Gruen and his team to this piece of DNA (whose discovery was announced in the November 22 issue of Proceedings of the National Academy of Sciences). First, the researchers found that out of 536 people, most of those with dyslexia shared versions of this gene. Many of them were missing exactly the same part of DCDC2: a regulatory region that tells the gene where and when to make its particular protein. Second, the parts of the brain in which DCDC2 usually makes protein also happen to be the reading centers of the brain. The gene is most active in the temporal cortex, prefrontal gyrus, and posterior cingulate gyrus. Imaging studies from the Yale Center for the Study of Learning and Attention show that activation patterns of these reading centers differ in dyslexics compared with fluent readers. Finally, to find out if DCDC2 really matters, the researchers suppressed the expression of the gene in the developing brains of rats. Normally, what are called progenitor cells in the lining of a rat embryo’s ventricles give rise to immature neurons that then migrate outwards to populate all layers of the brain’s cortex. But in the absence of DCDC2, the orderly migration is not completed. “These cells are arrested about halfway in an intermediate layer of the cortex,” says Gruen. “Our data suggest that DCDC2 is involved in the normal course of neuronal development in the brain.” The Gruen team’s discovery marks the third gene that is thought to play a role in dyslexia. The first was announced two years ago by a team of researchers from the University of Helsinki; the second was proposed earlier this year by scientists from Oxford. Since “there is overwhelming evidence that dyslexia is a genetically complex condition,” wrote the Finnish scientists who found the first candidate gene, all the genes found to date could be involved. Up to 17 percent of all United States schoolchildren have dyslexia. It certainly doesn’t prevent success; Whoopi Goldberg, Erin Brockovich, and Charles Schwab have reading disabilities. But identifying the genes associated with it could make many children’s lives better sooner. “They’re intelligent and talented, but they learn to read differently from fluent readers and we have to accommodate that,” says Gruen. |
Growth Strategy Space scientists have long suspected that when galaxies grow, they behave like aggressive corporations: mergers and acquisitions are the norm. In the December issue of Astrophysical Journal, Pieter van Dokkum, assistant professor of astronomy, presented hard evidence. Van Dokkum studied 126 relatively nearby massive galaxies that had been photographed during deep-sky surveys. The images show galaxies in various stages of coming together; more than half of those van Dokkum examined showed signs of having grown this way. He says: “It’s a never-ending story of things colliding—small things colliding to make big things, big things colliding to make bigger things.” |
Noted Older Americans may be faring better than has been assumed. According to Thomas M. Gill, an associate professor of medicine, the rate of chronic disability among people 70 and older has been overestimated by about 40 percent. In the December 12 Archives of Internal Medicine, Gill and his colleagues estimate that, as of 1999, the proper number was about 5 million, not 7 million, as had been generally assumed by policy makers. Minority participation in health research studies is small relative to the number of whites, but the reason, says Cary Gross, an associate professor of internal medicine, is not necessarily a lack of willingness to join, as is generally believed. Rather, say Gross and his colleagues in the December 6 issue of PLoS Medicine, the well-known gap can be attributed to a frequent failure to ask minorities to participate as research subjects. Using yeast cells as a proxy, Michael Snyder, the Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology, and his colleagues have created the first comprehensive map of the protein and enzyme signaling network that controls some basic cellular processes of higher organisms—including growth, cell division, and cell differentiation. Snyder’s team presented its findings about the interaction between proteins and master regulatory molecules called protein kinases in the December 1 issue of Nature. Protein kinases are important targets of anti-cancer drugs. Among patients with cancer, the prevalence of major mental illness is similar to that found in the general population. But in the December 15 issue of Cancer, Nina S. Kadan-Lottick, an associate research scientist at the School of Medicine, and her colleagues report that fewer than half the patients with advanced cancer they studied took advantage of psychiatric services. Caucasians were more likely to seek mental health help than non-whites, Dr. Kadan-Lottick reports. Meditation has been found to aid the treatment of high blood pressure and other ailments. In the November NeuroReport Jeremy Gray, assistant professor of psychology, and his colleagues report that the practice can also increase the thickness of brain regions important for sensory, cognitive, and emotional processing. The researchers used magnetic resonance imaging to document the increase in 20 people who practiced Buddhist “insight” meditation 40 minutes per day. They also found that meditation may slow age-related thinning of the frontal cortex. |
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