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Updated 11:00 AM November 1, 2004




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Research Notes
Scientists identify E. coli genes that cause urinary tract infections

Anyone who thinks scientists lead a glamorous, exciting life should talk to Jennifer Snyder, a graduate student at the University of Maryland's School of Medicine. During July 2003, while all her friends were out enjoying themselves, Snyder spent 10 days trying to get 40 laboratory mice to urinate into little plastic tubes.
The inset panel shows an epithelial cell peeling off from the surface of the bladder during a urinary tract infection. The main panel shows a cell from the bladder wall, which is completely obscured by adhering CFT073 E. coli bacteria. (Photo by Harry Mobley, Medical School)

Snyder's goal was to extract enough genetic material from mouse urine to determine which of the 5,611 genes in a pathogenic strain of E. coli bacteria were turned on, or expressed, in mice with urinary tract infections. The results of her research, conducted in collaboration with scientists from the University of Michigan Medical School and the University of Wisconsin-Madison, are published in the November 2004 issue of Infection and Immunity.

Results from the study could lead to new, more effective treatments of urinary tract infections, which are the cause of an estimated eight million physician visits in the United States each year. Nearly half of all American women have had at least one urinary tract infection, and know all too well how incapacitating and difficult to treat they can be.

"Even though Escherichia coli's genome was sequenced in 2001, we didn't know which genes were active during infection of an animal host or what proteins were present during the infection stage," says Harry L.T. Mobley, a professor and chair of microbiology and immunology. Mobley, now at U-M, directed the study while he was a faculty member at the Maryland.

"Now we can quantify the activity of every gene in a representative strain of uropathogenic E. coli, called CFT073, during infection of the mammalian urinary tract," Mobley says. "Knowing its gene expression profile essentially gives us a snapshot of what's happening inside the urinary tract, from the pathogen's point of view."

The study was funded by the National Institutes of Health.

Pessimistic or optimistic? It may be best to have two different stockbrokers

Brokers who infrequently make recommendations to buy stock tend to give good advice when they do say to buy. But these same investment banks and brokerage firms are not as successful when they advise to hold or sell, says Reuven Lehavy, assistant professor of accounting at the Stephen M. Ross School of Business. Research by Lehavy and colleagues shows that a broker's stock ratings distribution can predict the profitability of its recommendations.

"Pessimistic" brokers—those who issue the smallest percentage of buy recommendations—outperform those brokers who issue the greatest percentage of buy ratings ("optimistic" brokers) by an average of 50 basis points per month. Conversely, downgrades to hold or sell issued by optimistic brokers outperform those of pessimistic brokers by an average of 46 basis points per month.

In their study, Lehavy and colleagues Maureen McNichols of Stanford University and Brad Barber and Brett Trueman of the University of California analyzed 438,000 stock recommendations issued on more than 12,000 firms by 463 investment banks and brokerage firms between January 1996 and June 2003. They examined the distribution of brokers' stock ratings across buys, holds and sells, and determined what effect stricter securities rules—requiring investment banks and brokerage firms to publicly disclose the distribution of their stock ratings—have had on the observed tendency of analysts to issue many more buy than sell recommendations.

The National Association of Securities Dealers (NASD) proposed Rule 2711 in early 2002 as part of an effort to regulate the provision of research on Wall Street. Among other requirements, Rule 2711 requires all analyst-research reports to display the percentage of the issuing brokerage firm's recommendations that are buys, holds and sells.

The researchers' findings "strongly suggest" that the implementation of the rule played an important role in the dramatic decrease of the buy-to-sell ratio, Lehavy says.

Team treats mouth wounds by engineering tissue grafts

U-M researchers are testing a new procedure in which they can take a tiny piece of a person's mouth lining, grow it into a dollar-bill sized piece of tissue and graft that expanded piece into the donor's mouth to heal a wound.

Dr. Stephen Feinberg is leading a team that is working with five patients to treat small mouth wounds with the grafts. The five patients are part of what is called a proof of concept study for the Food and Drug Administration (FDA).

Feinberg, a professor of both dentistry and surgery, is collaborating with Kenji Izumi, a scientist and surgeon who already has seen success with the method in about 80 patients in Japan. Izumi is a visiting assistant research scientist at U-M and a long-time colleague of Feinberg.

Many types of people have trouble with mouth wounds that do not heal well on their own—patients going through cancer chemotherapy, for example, or people with diabetes. Those who have been involved in accidents are candidates as well.

Existing treatments include taking a skin graft from a site such as a leg and stitching it into the mouth. Skin works for covering the wound, but is not as pliable as the mucosal lining of the mouth, and if it is too thick, it might even grow hair inside the mouth. A large skin graft also leaves the patient in pain with lengthy healing time.

Feinberg says tissue engineering has many advantages, including a smaller donor site that heals faster and a graft that is mucosal cells, more like the mouth lining, not skin. After a short healing period, the patient feels mouth lining as it is supposed to feel.

Feinberg and Izumi worked with Cynthia Marcelo, a research professor of surgery with nearly a decade of expertise in cell growth, to use a system she developed that encourages the cells to reproduce more rapidly in a well-defined system acceptable to the FDA. This special environment helps a tiny piece of mucosal mouth lining grow to the size of a quarter within a few weeks, and a dollar bill within about a month. Feinberg and Isumi use the U-M Human Application Lab in University Hospital, an ultra-clean facility that follows the FDA's strict regulations for keeping out potential contaminants.

This research is supported by a $1.25 million grant from the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

Study hones improvements of lung function in premature infants

When babies are born prematurely, their lungs are not able to produce a protein that helps them breathe. Now, with a device already used in the neonatal intensive care unit to monitor lung function in premature infants, U-M Health System (UMHS) researchers have taken a step in helping neonatal specialists administer a replacement substance that helps babies breathe easier.

By comparing two available types of this substance, called surfactant, researchers found one formulation may be more effective in the long run.

"It's more than just comparing Coke and Pepsi. The two different surfactants we looked at seem to have a different course of action," says senior study author Dr. Steven M. Donn, director of neonatal-perinatal medicine at UMHS and professor of pediatrics and communicable diseases at the Medical School.

"Although we didn't see much of a change in lung function immediately after their administration, the Infasurf seemed to have a more lasting effect. Infants didn't show a dramatic effect immediately after receiving it, but they required fewer doses than the babies treated with Survanta. Because these medications are extremely expensive, there's a substantial cost savings when we use less," Donn says.

The study appeared in the October issue of the Journal of Perinatology.

Respiratory distress syndrome is a major complication for babies born prematurely. These infants do not produce enough surfactant, the naturally occurring substance that prevents the collapse of the air sacs within the lungs and enhances the exchange of oxygen and carbon dioxide. Administering animal-derived or synthetic forms of surfactant can help improve lung function, research has shown, and this has increased dramatically the survival of infants born extremely early.

The lead study author was Dr. Mohammad A. Attar, clinical instructor in the Department of Pediatrics and Communicable Diseases at the Medical School. Other authors were Michael Becker and Ronald Dechert from the Department of Critical Care Support Services at UMHS.

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