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As world health workers watch for a re-emergence of SARS, Columbia Genome Center researchers are busy preparing a biochip that could help diagnose the disease.

The new chip takes advantage of a recent development by Dr. Denong Wang, research scientist in the Genome Center, that facilitates the attachment of proteins, glycoproteins, and carbohydrates to the chips.

Last year, Dr. Wang produced the world's first carbohydrate microarray, a chip capable of binding and targeting thousands of different sugars, which could eventually help clinicians diagnose many common infectious diseases from a few microliters of blood. There are now four different sugar chips, but Dr. Wang's chip is also inexpensive and simple to produce. His chips use commercially available glass slides coated with nitrocellulose and can bind thousands of different sugar types, each displayed as separate spots no larger than the tip of a pin.

Chips that bind proteins while maintaining their functional properties are more difficult to construct because immobilizing a protein on the chip surface can alter the protein's structure. Because a protein's function depends on its shape, retaining the shape of a protein on a chip is a major challenge for proteomics researchers.

Dr. Wang recently found that the same surface he used to make carbohydrate chips can also accommodate proteins without compromising their antigenic reactivities.

With the help of collaborators at Peking Union Medical College and support from the Northeast Biodefense Center, Dr. Wang's group constructed a SARS chip by dotting the surface of each of his chips with proteins from the SARS virus along with proteins and sugars from other infectious agents. The chip may be able to detect who is infected and ill with the virus when a sample of blood is passed over the chip. If the virus is causing the person's illness, antibodies in his or her blood will bind to the SARS proteins on the chip surface. Because proteins and sugars from several other pathogens can be placed on the chip, doctors may be able to use the chip to predict or diagnose other disease-causing agents, if not the SARS virus.

Dr. Wang has tested the chip with blood from SARS-CoV-vaccinated monkeys and is planning a trip to China to test the chip with stored blood from people who were ill from the virus.

—Susan Conova

Lead is probably most dangerous to children, as it can disrupt normal body and brain development. But lead exposure may cause problems for adults, too. According to new research by Columbia and Mount Sinai School of Medicine researchers, lead is associated with a common type of tremor many people develop in middle and older age.

Dr. Elan D. Louis, associate professor of neurology at P&S and first author of the study, decided to investigate the link between lead and essential tremor because few researchers have studied the connection, even though other environmental toxins are thought to play a role in causing essential tremor. Lead is known to cause brain damage, specifically in the cerebellum, the part of the brain that helps direct coordinated muscle movements. The risk of exposure to lead has dropped since lead was largely removed from paint and gasoline in the 1970s and 1980s. But people still come in contact with lead contained in paint in older buildings as well as through industrial and organic exposures, such as from eating seafood contaminated by offshore waste sites that contain lead.

Essential tremor, which affects as many as one in five people who are over age 65, is a progressive, disabling and incurable disease that also results from damage to the cerebellum and its connections in the brain. Essential tremor usually causes the hands to shake, but it may also affect the head, neck, voice and trunk.

The study compared the levels of lead in the blood of 100 essential tremor patients and 143 people without the disorder. Blood lead concentrations were higher in essential tremor patients even after adjusting for age, sex, smoking, diet and occupational history. "Determining whether this association is due to increased exposure to lead or a difference in how essential tremor patients' bodies metabolize lead requires further investigation," Dr. Louis says. The paper was published in the November issue of Environmental Health Perspectives.

Next, Dr. Louis wants to look more closely at lead in people's bones. Lead in bone is a more accurate way to measure chronic lead levels because lead stays in bone longer than it does in blood. Since essential tremor is a chronic disease, this information will be important. In collaboration with Dr. Andrew Todd, associate professor of community medicine at Mount Sinai, Dr. Louis will perform noninvasive scans of the knee to measure bone lead levels.

The research was supported by grants from the National Institutes of Health.

—Matthew Dougherty

The terrorist attacks of Sept. 11, 2001, and the anthrax attacks that followed prompted the government to pump more funds into public health. The funds are sorely needed because the public health workforce-to-population ratio may have declined by as much as 10 percent in the past 20 years, according to a study by Columbia School of Nursing researchers.

The ratio of public health workers to population was an estimated 220 per 100,000 in 1980, but that number fell to 158 per 100,000 in 2000. Perhaps the more significant problem than shrinking numbers of workers is the difficulty of collecting data, because no standard information system exists, says Jacqueline Merrill, a doctoral student in nursing and public health informatics at the School of Nursing and first author of the study published in the November-December issue of the Journal of Public Health Management and Practice.

"Public health workforce development initiatives have assumed greater urgency and broadened scope due to the substantial federal funding after the events of 2001," Ms. Merrill says. "In the absence of a system to reliably collect workforce data, the information we do have is difficult to interpret or use for planning education, recruitment, and retention."

It hasn't always been this way. Policy-makers in the first half of the past century were very interested in knowing the makeup of the public health workforce and conducted direct surveys of health departments, says Dr. Kristine Gebbie, Elizabeth Standish Gill Associate Professor of Nursing, director of the Center for Health Policy, and senior author of the paper.

"We were surprised by how much was known, especially just before and after the Great Depression. That is in stark contrast to the situation today," Dr. Gebbie says. The last direct federal survey took place in 1964. Since then, workforce size has been estimated, as funds to gather the data were cut.

But the federal government is starting to realize that the situation must change. Workforce composition monitoring is part of a Department of Health and Human Services disease prevention program, Healthy People 2010, and a Centers for Disease Control and Prevention strategic plan for workforce development. More recently the Health Resources and Services Administration sponsored a white paper outlining a strategy for a system to count the total number of public health workers.

"We need such a measurement system to help us chart and evaluate public health agency performance and program outcomes and sustain a well-planned public health infrastructure into the future," Dr. Gebbie says.

The research was supported by a cooperative agreement from the Health Resources and Services Administration and the Association of Teachers of Preventive Medicine.

—Matthew Dougherty


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