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October 9, 1997


Scientists discover how genes work together to control neural development

Scientists have discovered how three genes work together to regulate the development of nerve cells — fundamental new knowledge that could boost efforts in other areas, including cancer research.

In the Aug. 8 issue of the journal Cell, two research teams reported that they independently made the same discovery. One team is led by Zhi-Chun Lai, assistant professor of biology, biochemistry and molecular biology at Penn State, and Richard W. Carthew, a Pitt assistant professor of biology. Gerald M. Rubin, of the University of California at Berkeley, leads the other research team.

The research is expected to contribute to understanding of the nervous system and the brain.

Lai and Carthew's team studied fruit-fly eyes to figure out which genes regulate the development of photoreceptor neurons — cells that convert light signals into chemical signals the brain can understand. The team used both genetic studies and cell-culture studies to complement and confirm their findings. "At the very fundamental cellular level, there is no difference between the human cell and the fly cell," Lai said.

External signals tell the developing cells what kind of cell to become by initiating a cascade of internal molecular reactions called "signal-transduction pathway." "Cancer can result if errors occur in the signal-transduction pathway, giving a cell the signal to divide instead of the signal to become a neuron," Carthew explained.

Last year, Lai discovered an important clue about how a component of the signal-transduction pathway — a special kind of cell-growth regulator known as a neural inhibitor — works genetically. He found that proto-eye cells could become neurons only when the gene for making a protein known as Tramtrack was inactivated.

"Tramtrack is a kind of 'gatekeeper' protein that prevents the cell from differentiating into a neuron," Carthew said. "When the cell receives a signal to become a neuron, the signal-transduction pathway is activated, which induces the production of proteins that somehow get rid of Tramtrack." With that discovery pointing the way, Lai, Carthew and their team began a search to discover exactly which proteins destroy Tramtrack.

The researchers narrowed the list to two proteins, Phyllopod and Sina, and demonstrated that they team up to target the Tramtrack protein for destruction. "We are pretty confident that together Phyllopod and Sina bind to the gatekeeper protein, Tramtrack, which is the kiss of death that marks it for destruction by the cell's garbage-disposal enzymes," Carthew said. "Once the gatekeeper Tramtrack protein is removed, the cell is free to become a neuron. Up until a few years ago, everyone thought developing cells always received positive signals, but now evidence is building at a rapid rate that the message often carried by the signal-transduction pathway is 'kill the gatekeeper.'" Lai added, "Many vertebrate proteins, some known to be involved in cancers, carry a structural feature similar to the Tramtrack protein. We are now searching for other biological systems where genes for Tramtrack-like proteins prevent cell development."


Pitt researchers find new way to predict risk of Type 1 diabetes complications

A person's risk of developing life-threatening complications associated with diabetes can be predicted using a measure of how high, and for how long, blood sugar levels have been maintained in an individual with Type 1 diabetes, according to a Pitt study published Sept. 8 in the Archives of Internal Medicine.

The findings indicate that people who maintain low blood sugar levels may delay the onset of complications for more than 40 years, while others with high levels will develop the same complications within 15 years.

"Although this kind of compliance requires vigilant blood sugar monitoring, our results show that individuals can significantly reduce the odds that they will develop disease-related problems, such as blindness, nerve disease or potentially fatal kidney failure," said Trevor Orchard, principal investigator of the study and professor of epidemiology at the Graduate School of Public Health.

Type 1 insulin-dependent diabetes affects more than 500,000 people in the United States. Each year, some 30,000 people develop the disorder, typically before the age of 30. And the disorder's incidence appears to be increasing, particularly among African Americans.


UPMC Health System surgeons to compare coronary surgical techniques

Surgeons at the UPMC Health System have begun a prospective, randomized study comparing traditional coronary artery bypass surgery with a new technique called integrated coronary revascularization (ICR).

ICR is a combination of minimally invasive direct coronary artery bypass followed by conventional angioplasty. In the minimally invasive bypass, surgeons operate on the blocked artery while the heart continues to beat, unlike standard bypass in which the patient is put on the heart-lung bypass machine and the heart is stopped. Surgery is done through a single three-inch incision in the chest, making the stressful procedure of cutting through the breastbone unnecessary.

The study, which will enroll approximately 200 patients, is aimed at determining which procedure is better in managing coronary artery disease.

Marco Zenati, Pitt assistant professor of surgery, director of the Minimally Invasive Cardiac Surgery Program and principal investigator in the study, said, "We have one of the largest experiences with this procedure in the country and since we began minimally invasive heart bypass surgery in June 1995, more than 150 patients have undergone the procedure with very good success. But there has not been a prospective, randomized study to determine which of the procedures works best and which patients may best benefit from each."


Lack of sleep causes differences in thinking patterns, Pitt study shows

"Burning the midnight oil" may do more harm than good. Researchers at Western Psychiatric Institute and Clinic (WPIC) have found that the body's need for sleep, influenced by its circadian rhythms, may slow down thinking processes at night. Also, losing sleep at night can slow down thinking skills the next day, researchers said.

Even when night workers and night drivers are wide awake, they may be thinking more slowly, the WPIC study showed.

The study, published by Timothy Monk, professor of psychiatry, and postdoctoral research fellow Julie Carrier in the academic journal Sleep, suggests that circadian rhythms, the body's internal clock, can affect the speed at which the brain processes information.


Education, exercise, low-fat diet can reduce excessive weight gain in pregnancy

Women who are of normal weight before pregnancy can reduce their chances of gaining too much weight during pregnancy through a program of education, moderate exercise and low-fat eating, say researchers at the Western Psychiatric Institute and Clinic (WPIC).

Pregnancy increases a woman's risk of becoming overweight by 60 percent. Women who gain more than the recommended amount of weight during their pregnancies retain twice as much weight after pregnancy as women who gain within the guidelines.

According to the Institute of Medicine, women of normal weight should gain 25-35 pounds during pregnancy, and overweight women should gain no more than 15-25 pounds. Yet, one-third to one-half of normal-weight women and nearly two-thirds of overweight women gain more than that.

"The strongest predictor of postpartum weight retention is the amount of weight gained during pregnancy," said Betsy A. Polley of WPIC's Behavioral Weight Loss Program.

The WPIC researchers are the first to test whether a program of education, exercise and low-fat eating works to reduce excessive weight gain in healthy pregnant women. According to Polley, many women aren't given guidelines for proper weight gain during their pregnancies.

"In the United States, 35 percent of women are overweight. Since long-term weight loss is difficult to achieve, we need to focus more on ways to prevent obesity," she said.

During the study, a program developed by Polley, psychiatry professor Rena Wing and Cynthia Sims of Magee-Womens Hospital helped two-thirds of normal-weight women stay within Institute of Medicine boundaries. In the group where there was no intervention, 58 percent of the normal-weight women gained too much.

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