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July 20, 2006


B cells play crucial role in HIV infection

HIV infection of T cells requires activation of a molecule on the surface of B cells, a finding that reveals yet another pathway the virus uses in its attack on the immune system, report Graduate School of Public Health (GSPH) and School of Medicine researchers in PLoS Pathogens, a journal published by the Public Library of Science. The findings suggest a need for developing a class of antiviral drugs targeted against this molecule and offer an avenue that may prove critical for the prevention of HIV.

Most efforts to thwart HIV focus on T cells, where the virus replicates and thrives. The new research identifies an important first step in the infection process involving B cells that express a protein called DC-SIGN. The B cells do not become infected, but they play a pivotal role in the virus’s takeover of T cells.

“We have new insight into how the virus does its damage. The pathway is surprisingly simple, yet it has important implications for future studies and drug development efforts that focus on reservoirs of HIV in cells other than T cells,” said Charles R. Rinaldo Jr., professor and chairman of the Department of Infectious Diseases and Microbiology at Pitt’s GSPH and the study’s senior author.

In one set of studies involving cells from healthy subjects, researchers activated DC-SIGN using two molecules that T cells typically engage in their communication with B cells. Once activated, the DC-SIGN B cells were placed in a culture with T cells and a small amount of virus. Within 24 hours, HIV had invaded the T cells while sparing the B cells. When researchers repeated the experiment without B cells, the HIV had little effect on the T cells alone. Pretreating the B cells with a molecule that blocks DC-SIGN activation before culturing them with both T cells and HIV was a deterrent against T cell infection as well, further proof that to invade T cells, HIV requires DC-SIGN expressed on B cells.

DC-SIGN was first identified as a dendritic cell-specific binding site for HIV, but this study shows that B cells expressing DC-SIGN also are used by HIV to facilitate infection of T cells.

“As has been observed in DC-SIGN dendritic cells, we suspect the B cells internalize the virus and that the DC-SIGN serves as sort of a bridge HIV uses to reach the surface of T cells,” said Giovanna Rappocciolo, associate professor of infectious diseases and microbiology at GSPH and the study’s first author.

Other GSPH researchers involved in the study are Paulo Piazza, Craig L. Fuller, Todd A. Reinhart, David T. Rowe, Simon C. Watkins, Mariel Jais and Phalguni Gupta.

The research was supported by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute of the National Institutes of Health.


Bacteriophage study could improve TB treatment

A new five-year, $2.8 million National Institutes of Health grant will fund research into whether a bacteriophage could lead to better treatments for tuberculosis.

Graham Hatfull, Eberly Family Professor of Biotechnology and chair of the Department of Biological Sciences, is collaborating with William Jacobs of the Albert Einstein College of Medicine to study how a bacteriophage isolated from Jacobs’s back yard might prevent tuberculosis from forming its drug-resistant protective coating called a biofilm.

Hatfull and Jacobs already have discovered that when the bacteriophage infects Mycobacterium smegmatis, it disrupts a gene, rendering the germ unable to produce its protective coatings. M. smegmatis is similar to the organism that causes tuberculosis, which has a nearly identical gene.

If it is found that the bacteriophage affects the gene in the tuberculosis-causing germ, it could lead to the development of medications that could make the germ more susceptible to antibiotic treatment.

“We’d like to have an understanding of M. tuberculosis and what happens during an infection that leads to such difficult, prolonged treatment,” said Hatfull, who also co-directs the Pittsburgh Bacteriophage Institute.

“An ideal scenario would be to develop drugs that would allow TB to be treated over a much shorter period of time,” he said. “Shortening the treatment would lead not only to more effective and simple control of the disease, but also would cut down on the development of drug-resistant organisms.”


Chemical engineering research funded

Mohammed Ataai, William Kepler Whiteford Professor of chemical and petroleum engineering, has received $141,000 in funding by the National Energy Technology Laboratory-University Collaboration for his work, “Enzyme-based Capture of Carbon Dioxide.” He will study the use of an immobilized carbonic anhydrase vector for capturing carbon dioxide from combustion flue gases.

A second proposal, in collaboration with Richard Koepsel, a research associate professor of chemical and petroleum engineering at Pitt, and Robert Beitle of the University of Arkansas, has been funded by the National Science Foundation. The work, “Collaborative Research Efficient Bioseparation by Intertwining Strain, Chromatography and Affinity Tail Design,” introduces a concept by which recombinant proteins may be isolated when affinity tail technology is used to dictate purification.


Aneurysm research funded

Anne M. Robertson, associate professor of mechanical engineering, is co-investigator on a program led by researchers at the Mayo Clinic, “Improved Animal Modeling of Saccular Aneurysms.”

The program has received a $2.8 million National Institutes of Health grant to use genomics and proteomics to determine which biological mechanisms are deranged in and around saccular aneurysms to examine the link between aneurysm geometry, hemodynamics and vessel wall dysfunction. The study also will evaluate the success of endovascular therapy.


Acoustic signal processing grant received

Patrick Loughlin, William Kepler Whiteford Professor in electrical and computer engineering, received a four-year, $410,000 grant from the office of Naval Research for his work in underwater acoustic signal processing and classification, particularly in shallow water.


Wastewater as a coolant?

Radisav Vidic, professor of civil and environmental engineering, has been awarded a three-year, $617,000 grant by the U.S. Department of Energy to assess the potential of using secondary treated municipal wastewater, treated coal mine drainage and ash pond effluent as cooling water in coal-fired thermoelectric power generation.

The work, in conjunction with David Dzombak at Carnegie Mellon University, will combine pilot studies, laboratory studies and mathematical modeling.

A second joint project with CMU, “Catalysts for Selective Hydrogen Sulfide Oxidation,” has been awarded a one-year, $197,000 grant.


Greater obesity increases women’s risk of death

A Pitt study published in the Journal of American Medicine finds that extremely obese women have a significantly higher risk of dying than women at normal weight and links the risk of death to specific categories of obesity.

In collaboration with researchers from six other institutions, the Pitt team examined the rates of death and of newly diagnosed coronary heart disease over a seven-year period for 90,185 women in five specific weight categories.

The women, all participants of the Women’s Health Initiative-Observational Study, were categorized based on the body mass index (BMI) weight-to-height ratio as normal, overweight, obesity 1, obesity 2 and extreme obesity.

White women in the obesity 1 category (approximately 60 pounds above a normal weight for a 5-foot, 5-inch tall woman) had a 12 percent higher risk of death over the seven-year follow-up period, but extremely obese women (approximately 110 pounds above a normal weight for a 5-foot, 5-inch tall woman) had an 86 percent higher risk of death than their normal weight counterparts.

Death rates increased substantially with increasing weight categories, ranging from 68.39 deaths per 10,000 person-years in women with normal BMIs to 116.85 deaths per 10,000 person-years in extremely obese women.

The investigators also examined African-American and Caucasian women more closely, finding that both groups experienced increased risks of mortality and new onset of coronary heart disease with each increasing weight category. In addition, the risk for diabetes and hypertension increased as excess weight became more extreme, and even women who were overweight but not obese experienced significant weight-related health consequences.

The prevalence of extremely obese women in the United States differs among racial and ethnic groups, with Asian Americans in this study having the lowest prevalence and African Americans having the highest. The researchers note that they found no difference in the weight-related risk for death from all causes, death due to heart disease, and new onset of heart disease across the diverse racial and ethnic groups, although they point out that the relatively small number of women from certain racial/ethnic groups limited their ability to examine these outcomes within all groups in detail.

The findings, according to lead author Kathleen McTigue, assistant professor of medicine and epidemiology, suggest that degree of obesity has a major impact on health risk. “When a woman and her physician are choosing treatment options for obesity, they should carefully consider the degree of obesity. The degree of obesity will influence how likely it is that her health will be harmed by her current weight. These findings also underscore the importance of learning more about the best treatments for extremely obese women, as well as the need for aggressive diagnosis and treatment of diabetes, high blood pressure and high cholesterol in the obese,” said McTigue.

Other Pitt researchers involved in the study were Alice Valoski and Lewis Kuller of the Graduate School of Public Health.


ICU patient risk factors studied

Sandra Kane-Gill, assistant professor of pharmacy and therapeutics, was awarded $28,279 by the Society of Critical Care Medicine as the 2006 Joseph F. Dasta/Bayer Critical Care Pharmacy Outcomes Research Grant recipient.

Her research project, “An Analysis of Risk Factors for Adverse Drug Events in Critically Ill Patients,” is directed at evaluating several potential risk factors for ICU patients having adverse drug events over a 7.5-year study period.


SIS faculty get wireless, mobile security funding

Prashant Krishnamurthy and Vladimir Zadorozhny of the School of Information Sciences, in conjunction with Vladimir Oleshchuk of Agder University College in Norway, have been awarded a grant from the Research Council of Norway (RCN).

The $24,500 award will be used to extend collaborative research between SIS and Agder on challenges in security and privacy in data management in wireless and mobile network environments. The grant program calls for expertise in the areas of distributed data management, wireless communications, security and privacy.

The work will result in a proposal to the RCN to further this cooperative research.


Social influences affect youth violence

Violence cannot be blamed on individual circumstances alone, but rather on changing societal influences, according to the first study to assess age, era and group effects on youth violence while simultaneously tracking individual risk factors.

The School of Medicine study appears in the July 15 American Journal of Epidemiology, available on line at

The researchers, led by Anthony Fabio, assistant professor of the Center for Injury Research and Control, Division of Neurosurgery at the School of Medicine, used data from a previously conducted local youth study that tracked delinquency and risk factors between two groups of males from 1987 to 2000. This involved interviewing male participants over a 14-year period and obtaining supplemental information from parents and teachers.

The researchers compared differences in self-reported violence between males who entered the study in first grade and those who entered in the seventh grade. Researchers gathered yearly measures of violence by analyzing survey responses to questions regarding violence, which consisted of a positive response to gang fighting, strong-arming, attacking someone with a weapon, an intent to seriously hurt or kill, and rape or forced sex. Other factors taken into account included the participant’s socioeconomic status, whether he was held back in school, drug dealing, heavy drug use and gun use. U.S. Census data for 1990 and 2000 and the Uniform Crime Reports also were included.

While some have posited that risk factors such as drug use and gang membership contribute to violence, there have been conflicting theories as to why violence rates vary over specific time periods.

Some suggest that there is a cohort effect where specific generations have a higher percentage of high-risk children. Others suggest that there is a period effect where circumstances during the period in which a generation grows up increase the risk for that generation. The results of the Pitt study show that while individual factors are important, they do not explain completely the differences in rates of violence between generations. Period effect can account for the remaining difference.

In comparing the groups, researchers noticed that the older group consistently reported more incidents of violence and set out to determine why this difference occurred. “Our data showed that though part of this difference was due to individual factors such as gang participation or drug dealing, the individual factors could not explain the entire difference,” Fabio explained. “However, we found that period effects helped to explain the difference in violence rates between the two groups. We have not yet tested what exactly this period effect or effects might be, but plan to look at various societal processes such as the economy or changes in social norms.”

The study was supported by the U.S. Centers for Disease Control and Prevention, the National Institute of Mental Health and the Office of Juvenile Justice and Delinquency Prevention.

Pitt co-authors are Rolf Loeber of the School of Medicine and the Graduate School of Public Health, and G.K. Balasubramani of GSPH’s Epidemiology Data Center.

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