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November 7, 2002


Follow-up shows no significant increase in cancer deaths among Three Mile Island residents

In a 20-year follow-up study of mortality data on residents living within a five-mile radius of Three Mile Island (TMI), researchers at Pitt’s Graduate School of Public Health (GSPH) found no significant increase overall in deaths from cancer.

The findings were published Nov. 1 on the web site of Environmental Health Perspectives, a journal of the National Institutes of Health’s National Institute of Environmental Health Sciences. The paper will appear in the journal’s March 2003 issue.

“This survey of data, which covers the normal latency period for most cancers, confirms our earlier analysis that radioactivity released during the nuclear accident at TMI does not appear to have caused an overall increase in cancer deaths among residents of that area over the follow-up period, l979 to l998,” said Evelyn Talbott, professor of epidemiology at GSPH and principal investigator on the study. Talbott’s previous study, published in the June 2000 issue of Environmental Health Perspectives, analyzed 13 years of mortality data.

The TMI incident occurred at a nuclear power plant near Harrisburg on March 29, 1979, when a reactor leaked small amounts of radioactive gases. Scientists have calculated that the average person present in the area during the 10 days following the incident was exposed to considerably less radiation than the annual dose an individual receives from the everyday environment in the United States. However, little is known about the long-term health effects of low-level radiation.

The new Pitt study examined causes of death that included heart disease and malignancies as well as specific cancers known to be sensitive to radioactivity: bronchus, trachea and lung; breast (women only); lymphatic and hematopoietic tissue (blood-forming organs), excluding chronic lymphocytic leukemia and Hodgkin’s disease; and the central nervous system. Thyroid cancer was considered, but only one death was reported during the study period.

Researchers used information collected by the Pennsylvania Department of Health from 32,135 TMI residents within two months of the accident. Information included education level, occupation, smoking status, residential history, medical history, previous radiation exposure and daily travel into and out of the area during the 10 days following the accident. This exposure data was combined with mortality data from the Pennsylvania Department of Health.

The ratio of the number of observed deaths in the TMI “exposed” population was compared with the expected number of deaths in the general population. The overall number of cancer deaths among men and women in the TMI population was not significantly different from the general population, but there was a slight increase in the number of deaths from lymphatic and hematopoietic cancers in women in the TMI population.

Comparisons of mortality risks also were performed to assess the impact of the radiation related exposures on the cancer rates in the cohort. After adjusting for background radiation, educational level and smoking, no significant differences were noted. There was, however, a slight increase in the risk of lymphatic and hematopoietic cancers among males, which may be related to radiation exposure from the accident, according to Talbott. There also was an increased risk of mortality from lymphatic and hematopoietic cancers in women, related to everyday background radiation exposure.

“While these findings overall convey good news for TMI residents, the slight increased risk of death from lymphatic and hematopoietic cancers may warrant further investigation,” Talbott said.

The research was supported by the Three Mile Island Public Health Fund.


Professor receives NSF grant to study wide area applications

Vladimir Zadorozhny, an assistant professor in the Department of Information Science and Telecommunications in Pitt’s School of Information Sciences, has received a three-year, $450,000 grant from the National Science Foundation (NSF) to study ways of improving the performance of networks known as wide area applications (WAAs).

The study, titled “ITR Digital Resource Profiling for Wide Area Applications,” is a collaborative research project that also includes investigators from the University of Maryland at College Park and Technicon University in Haifa, Israel. The Corporation for National Research Initiatives (CNRI) will be the commercial partner in the study.

WAAs can be defined loosely as large computer networks that connect users, allowing, for instance, a researcher in the U.S. to access a database in Australia that contains massive amounts of information about the stars.

NSF initiated the Information Technology Research (ITR) program in 2000. In the first year, the program focused on fundamental research and education in information technology (IT). In the second year, the program was expanded to include an additional focus on research and education activities that applied IT to science and engineering challenges. The program now includes a component to enable research and education in multidisciplinary areas such as bioinformatics.

Today, the performance of WAAs may be unpredictable due to the variability of access to data and the ability to deliver it. Zadorozhny and his colleagues will study the changing behavior of digital resources over time and across different applications accessed through a dynamic wide area network such as the Internet. They intend to develop resource profiles that can be used to customize service and information delivery to clients. The goals are to establish a consistent framework for this process, called profiling, and to determine the extent to which profiling can be used to improve accessibility to resources. The results of the research will considerably improve performance of WAAs by speeding delivery of resources and optimizing the consumption of bandwidth resources.

Both undergraduate and graduate students will participate in the research, and a course familiarizing students with this next generation aspect of the Internet will be developed and will include an internship program with CNRI.


Researchers target genetic, environmental threats to maternal, fetal health

The Pittsburgh Development Center of the Magee-Womens Research Institute — and four other Oakland-based health care and academic institutions — will share a $5.9 million grant from the National Institutes of Health’s Office of Research on Women’s Health to study genetic and environmental causes of adverse pregnancy outcomes over five years.

Researchers from the Pittsburgh Development Center, Pitt, Children’s Hospital and Carnegie Mellon University will be partners in the project as an NIH-designated Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women’s Health. The Pittsburgh-based team will be one of 11 designated by the NIH in the U.S., and the only one in Pennsylvania.

Leading the effort will be principal investigator Gerald Schatten, director of the Pittsburgh Development Center, and Sarah Berga, a professor in the medical school’s departments of obstetrics, gynecology and reproductive sciences and psychiatry.

“We all know that genetic inheritance plays a vital role in overall health,” said Schatten, who also is vice chair for research development and professor of obstetrics, gynecology, reproductive sciences, cell biology and physiology at Pitt. “But prenatal environmental exposures also help to trace a lifelong health history.”

The Pittsburgh team will conduct clinical and pre-clinical studies that focus on the genetic components of recurrent miscarriage, normal and abnormal pregnancy and the maternal and fetal consequences of tobacco smoke exposure. Research protocols will use non-invasive diagnostic imaging scans including magnetic resonance imaging, positron emission tomography and computed tomography. Through use of unique genetic markers and imaging, researchers should be able to track development at the cellular level, mapping the effects of genetic variants that jeopardize healthy fetal growth and pregnancy.

“This is tremendously exciting for us,” said Berga, who also is director of the Division of Reproductive endocrinology and Infertility at Magee-Womens Hospital. “Data that we gather may one day answer questions about major women’s health problems regarding the dynamic interplay among fetal and maternal genetics and the costs of our earliest environmental exposures.”

The NIH’s SCOR grants are given in partnership with the Office of Research on Women’s Health to foster interdisciplinary and collaborative research on issues affecting women’s health. The aim is to improve the health of women through biomedical and behavioral research.


Pitt center wins grant for tendinitis study

James H-C. Wang, a researcher at Pitt’s Musculoskeletal Research Center (MSRC) and an assistant professor in the departments of orthopaedics, bioengineering, and mechanical engineering, was recently awarded a $1 million grant by the National Institutes of Health (NIH) for a multidisciplinary study of mechanisms of tendinitis.

With the receipt of this grant, total NIH grant funding received by the MSRC exceeds $11 million.

Repetitive motion disorders such as tendinitis affect millions of people in workplaces in the United States. Despite the increasing prevalence of repetitive motion disorders and the fact that they have become a costly public health problem, there are important gaps in knowledge about pathophysiological mechanisms for these disorders.

The objective of this project is to elucidate the pathophysiological mechanisms for tendinitis using a novel in vitro model and an animal model.

The co-investigator for the tendinitis study is David Stone, an assistant professor in the orthopaedic surgery department and team physician for Pitt’s athletics department.

Consultants include Sudha Agarwal, Christopher Niyibizi, Mohamed Virji, Savio L-Y. Woo and Tong Wu, all faculty members at Pitt and UPMC.


Study shows cumulative effects of multiple concussions in high school athletes

A high school athlete with a history of three or more concussions who sustains a new concussion may be up to nine times more likely to experience common symptoms compared to high school athletes with no history of concussion, according to a Pitt study published in the November issue of the journal Neurosurgery.

“The study is the first to actually demonstrate what have been the commonly assumed cumulative effects of multiple concussions in high school athletes,” said lead author Michael W. “Micky” Collins, a neuropsychologist and assistant director of the Center for Sports Medicine’s concussion program. “The study indicates for the first time in the high school athlete population that prior concussions may indeed lower the threshold for subsequent concussion injury and increase symptom severity in even seemingly mild subsequent concussions,” he said.

“Our findings are significant because high school athletes in contact sports are at high risk for repeated concussions, yet it is a population that has been understudied regarding concussion management,” Collins said. “Quite often the athlete’s concussion history has weighed heavily in the return-to-play decision process, although this has been based on little scientific data. Our findings highlight the need for more long-term outcome studies in this population.”

Concussion symptoms are not always reported by the athlete and the effects are difficult to measure objectively. Thus, the determination of when it is safe to return an athlete to play is not always straightforward, according to Collins. Research has shown that allowing enough time for the brain to heal and recover before return-to-play is crucial in preventing more severe damage from possible further brain trauma during contact play. Generally, he said, most athletes who sustain an initial concussion can recover completely as long as they are not returned to contact sports too soon.

More than 10 percent of high school athletes participating in contact sports in the United States sustain a concussion each season, according to previous studies. A concussion can occur when the brain is violently rocked back and forth inside the skull due to a blow to the head or upper body. A concussion is a trauma-induced alteration of mental status that may or may not result in loss of consciousness. Other symptoms may include disorientation, confusion, dizziness, amnesia and uncoordinated hand-eye movements.

Collins’s team investigated 88 high school athletes who sustained concussions during the 2000-2001 school year and were evaluated as patients of the University of Pittsburgh Center for Sports Medicine’s concussion program. Sixty athletes with no prior concussion history were compared to 28 athletes with a history of three or more concussions. The two groups were compared in terms of on-the-field presentation of four concussion severity markers following an in-study concussion. The symptom markers measured involved loss of consciousness, anterograde amnesia (loss of memory of events after injury), retrograde amnesia (loss of memory of events before injury) and confusion.

Compared to the group with no concussion history, the group of athletes with three or more concussions were nine times more likely to experience three out of the four on-the-field severity markers — loss of consciousness, anterograde amnesia and confusion. 

The group with a history of three or more concussions were more than six times more likely to experience loss of consciousness, nearly four times more likely to have anterograde amnesia, and four times more likely to be confused.

Athletes in the study were from high schools in Pennsylvania, Michigan, Illinois, Oregon and Maine. Among the group with no prior concussion history, 92 percent were males; the average age was 15.8 years. Seventy-eight percent were football players, 8 percent were soccer players, and 5 percent were basketball players. A very small percentage of the group participated in baseball, ice hockey, lacrosse, cheerleading and wrestling, collectively.

Among the group with concussion history, 82 percent were males; the average age was 16.1 years. Fifty-four percent played football, 18 percent played soccer, and a very small percentage of the group played basketball, ice hockey, lacrosse, wrestling and volleyball.

Other study authors are: Mark R. Lovell, director of the University of Pittsburgh Center for Sports Medicine’s concussion program; Joseph Maroon and Melvin Field, both of the medical school’s neurological surgery department, and researchers from the University of British Columbia and Emerson Hospital, Concord, Mass.


Gene linked to depressive disorders in women

Researchers from the University of Pittsburgh Medical Center have made significant progress in identifying the first susceptibility gene for clinical depression, the second leading cause of disability worldwide, possibly providing an important step toward changing the way doctors diagnose and treat major depression that affects nearly 10 percent of the population.

Research results, which were accepted for rapid publication and published Oct. 31 in the American Journal of Medical Genetics, show significant evidence for linkage of unipolar mood disorders to a specific region of chromosome 2q33-35 in women.

The findings suggest that a gene in this region contributes to the vulnerability of women in families afflicted with recurrent, early onset major depressive disorder (RE-MDD), to developing mood disorders of varying severity. Men with the same genetic background did not have any more chance of developing mood disorders than normal.

“We have narrowed our search for a susceptibility locus for clinical depression to a small region of chromosome 2 that constitutes only 0.01 percent of the human genome,” said lead author George S. Zubenko, professor of psychiatry at Pitt’s School of Medicine and adjunct professor of biological sciences at Carnegie Mellon University. “These results confirm our earlier findings this year that the susceptibility gene in this region selectively affects the vulnerability of women, but not men, to developing severe depression.”

According to Zubenko, women are twice as likely to develop depression as men, and this study provides evidence that genetic differences may account for some of that disparity. The narrow region of chromosome 2 highlighted by the researchers contains only about eight genes, including a gene called CREB1, which is an excellent candidate for a susceptibility gene for mood disorders. The CREB1 gene encodes a regulatory protein (CREB) that orchestrates the expression of large numbers of other genes that play important roles in the brain.

Alterations in CREB1 expression have been reported in the brains of patients who died with major depression, those of animal models of major depression and related disorders and in the brains of animals treated with antidepressant drugs. CREB also has been implicated in neuronal plasticity, cognition and long-term memory, abnormalities of which commonly occur in patients with major depression, may predispose patients to the onset or recurrence of major depression, and may be related to the eventual development of irreversible dementias like Alzheimer’s disease in some patients. Interactions of CREB with estrogen receptors might explain how inherited variants of CREB1 could affect the susceptibility of major depression only in women.

This is the second study this year by Zubenko and his Pittsburgh team providing evidence that vulnerability to depression is influenced by gender. Research published in March 2002 revealed surprising information that RE-MDD is caused by different genes in men and women, and in fact suggested sex-specificity of genetic susceptibility was commonplace. In that study, the researchers revealed that of 19 chromosomal regions associated with the development of RE-MDD, 16 were associated with the disorder in either men or in women — but not both.

“Studies such as this one are providing us with a better understanding of the biology of complicated disorders such as major depression, which is unlikely to represent a single disease with a unitary cause,” Zubenko said. “Instead, clinical depression is probably more like anemia. Both of these disorders are defined by a collection of clinical features that result from different causes in different people. Treatment or prevention efforts are usually most successful when they are aimed at the specific causes of a disorder.”

Further progress in diagnosis and treatment of clinical depression that result from these findings likely will proceed along several avenues, according to Zubenko.

“The identification and characterization of susceptibility genes and their products will provide new opportunities for drug development and disease prevention, and new information about the biology of mood and its regulation,” he said. Zubenko explained that these developments are time and resource intensive, and that it would be unlikely that the results of this avenue of research would affect clinical care in less than a decade. However, other applications may have important implications in the nearer future.

“Genotyping markers in chromosomal regions that harbor susceptibility genes may provide more immediate advances in the treatment of major depression. For example, individuals with particular genetic markers in these regions may respond better to particular current treatments than others. This strategy may enable clinicians to use genetic markers to better match individual patients to treatments to which they will optimally respond, while minimizing side effects,” Zubenko said. “In current practice, the choice of a particular antidepressant for a patient is largely a hit or miss proposition that often leads to multiple medication trials before the depression remits. Side effects can be debilitating.”


Immunology faculty get grants

The National Institutes of Health have issued a new grant to Russell Salter, associate professor of immunology. The title is “Ig-Reactive T Cells in Rheumatoid Arthritis.” Total funding for this project amounts to $149,500.

Karen Norris, associate professor of immunology, recently received a $50,000 supplement to her grant entitled “Pneumocystis Carinii Pneumonia Model in Rhesus Macaques.” The AIDS-related administrative supplement brings the three-year award to total funding of $488,172.

Olivera Finn, professor and chair of immunology, received a National Cancer Institute grant in July for “T Cell Immunity to Epithelial Tumor Mucins.” The projected five-year total for this award is $1,471,495.

Finn also was awarded a projected total of $862,279 for a new five-year project on the continuation of the program project grant “Vaccine Development for Oral Carcinoma.” The principal investigator of this program project is Theresa Whiteside, a professor of pathology and immunology.

Finn’s Department of Defense training grant received an additional $6,480 to help cover the expenses of sending four trainees to the Era of Hope 2002 meeting in Orlando. The total for this training award is $788,615.

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