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May 1, 2008

RESEARCH NOTES

Bird flu report touts vaccines

A team of researchers reports that widespread vaccination likely will be a key public health strategy for controlling an H5N1 bird flu pandemic.

In a report in The Lancet, the scientists note that any vaccine must be broadly protective and rapidly reproducible to be effective.

“If H5N1 influenza viruses acquire the capacity for effective human-to-human transmission while retaining their characteristically high pathogenicity, the ensuing pandemic would be devastating,” Andrea Gambotto, assistant professor of surgery at the School of Medicine, and his colleagues stated. “Therapeutic approaches for control of the disease can be restricted, leaving widespread vaccination as the probable cornerstone of public-health measures for pandemic control. Continued research into influenza pathogenesis and development of broadly protective vaccines that can be rapidly produced is needed in anticipation of an H5N1 influenza virus pandemic.”

The authors note also that diagnosis of the disease may be difficult because the virus is time-consuming to isolate and requires high-level biocontainment laboratory facilities.

The preferred method for rapid diagnosis is reverse transcriptase-polymerase chain reaction (RT-PCR) assays, several of which have been developed by the U.S. Centers for Disease Control and Prevention and approved by the U.S. Food and Drug Administration for diagnostic use in human beings, Gambotto and his colleagues noted.

In addition, the authors highlight their concerns over genetic variants of the H5N1 virus, which they say provide constant challenges to the reliability of RT-PCR assay design. Because of these challenges, genetic sequence information of the most recent human and bird H5N1 isolates are essential.

“Improving accessibility of databases within the World Health Organization’s influenza networks that are restricted, and in which such information is mostly stored, would help with and improve the establishment and maintenance of reliable diagnostics in many laboratories in countries affected by H5N1 influenza virus,” the authors wrote.

The authors also considered problems associated with inadequate drug concentrations and resistance and examined the pros and cons of a number of the vaccines for H5N1 that have been tested in clinical trials so far.

Among other authors of the report is Simon M. Barratt-Boyes of the Graduate School of Public Health.

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Surroundings affect early visual development

A team of researchers that included Pitt-Bradford biology professor David Merwine in collaboration with researchers at the University of Southern California (USC) has found that a lack of visual contrast during early development alters the development of cells in the retina and may affect normal visual processing. Merwine joined the UPB faculty this year from the Department of Biomedical Engineering at USC.

Their paper, “Developmental Regulation of the Morphology of Mouse Retinal Horizontal Cells by Visual Experience,” is published in the European Journal of Neuroscience.

The researchers reared mice in different environments — some in the dark, some in abnormally high-contrast checkerboard-patterned environments and others in no-contrast gray surroundings.

The retinas of control animals and those raised in dark and high-contrast environments developed normally, but those raised in no-contrast gray environments did not. Their cells developed in a way that mimicked the processes found in retinitis pigmentosa.

In the 1970s, Merwine said, “Researchers discovered that brain development depends on experience, but we only recently learned that the same is true of the eye.”

Their findings may be relevant for young people who have cloudy vision due, for example, to cataracts. The researchers note that the absence of contrast due to blurred vision could cause detrimental developmental alterations and said that early intervention could be critical for normal retinal and visual development.

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UPCI receives GIST grants

For the third year in a row, University of Pittsburgh Cancer Institute researchers have received funding from the GIST Cancer Institute — a patient-driven organization that funds research on gastrointestinal stromal tumors (GISTs), which are particularly difficult to treat over time.

The $135,000 award supports the research of Anette Duensing, a research assistant professor of pathology in the School of Medicine. Duensing said the GIST research in her laboratory aims to better understand the biology of GIST responses to the drug Gleevec, as well as the mechanisms underlying drug resistance to aid in development of more effective treatment options for GIST patients.

“A large number of patients with GIST develop resistance to Gleevec about two or three years after being treated successfully,” said Duensing. “The goal of our research is to avoid and overcome resistance to Gleevec and to help patients achieve long-term remission.”

This year’s award represents a significant increase from years past. In 2006 Duensing received $5,000; last year she received $26,000.

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International forces provide best protection for refugees

Refugees and those in camps for internally displaced persons (IDPs) would be best served if protected by armed international peacekeepers rather than government forces, suggests a new report from Pitt’s Ford Institute for Human Security.

Researchers found that government forces are attacked most often despite their size, and in some cases commit crimes against the camp populations they are charged with protecting. They also found that having a symbolic protective force does not ensure a camp’s protection. Instead, the size of a protection force and its composition, mandate and war-fighting capability are crucial in their ability to protect camps.

The study, led by professor of international affairs and Ford Institute director Simon Reich, aims to understand factors that determine the security of populations in IDP and refugee camps.

Ford Institute researchers determined that the abduction of children from these camps could help explain the variations in the rates of child soldiers in African conflicts. The study examined what makes IDP or refugee camps safe or unsafe for the communities they serve and what the international community can do to make camps safer from external attack.

The researchers found a general correlation between camp population size and the overall number of attacks, noting that large camps with little protection are prone to attack and that proximity to roadways often is significant — allowing attackers easy access and easy escape.

They also found that protection of IDP and refugee camps is especially crucial throughout the early stages of conflicts and that policymakers also need to address the protection of water supplies used by camp residents.

Reich will present recommendations based on the study to the United Nations Office of Children and Armed Conflict today, May 1, in New York City.

The full report is online at www.fordinstitute.pitt.edu.

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Metal-like conductivity seen in fullerenes

Pitt researchers have discovered that some carbon-based hollow-shell molecules can conduct electricity as well as metal, a property that could be useful in the development of nano-scale electronic devices.

The findings, which appear in the April 18 edition of Science, offer a new strategy for designing smaller, cheaper and faster electronic technologies using organic conductors.

The research was performed by Pitt post-doctoral associates Min Feng and Jin Zhao.

The Pitt team found that the hollow carbon molecules known as fullerenes can hold and transfer an electrical charge much like the most highly conductive atoms, explained project head Hrvoje Petek, professor of physics and chemistry and co-director of Pitt’s Petersen Institute for NanoScience and Engineering.

When an electron was introduced into a fullerene molecule, the shape of the electron distribution mimicked that of a hydrogen atom or an atom from the alkali metal group, which includes lithium, sodium and potassium. Moreover, when two fullerenes were placed next to each other on a copper surface, they showed the electron distribution of their chemical bond and appeared as a hydrogen molecule. The assembly exhibited metal-like conductivity when the team extended it to a wire one molecule wide.

“Our work provides a new perspective on what determines the electronic properties of materials,” Petek said. “The realization that hollow molecules can have metal-like conductivity opens the way to develop novel materials with electronic and chemical properties that can be tailored by shape and size.”

Although the team worked with fullerenes, the results apply to all hollow molecules, Petek added, including carbon nanotubes — rolled, one-atom-thick sheets of graphite 100,000 times smaller than a human hair.

Organic conductors typically have been found not to conduct electrical current very well, Petek said.

The Pitt team’s discovery could enable scientists to overcome that problem, he noted. “Metal-like behavior in a molecular material — as we have found — is highly surprising and desirable in the emerging field of molecular electronics,” he said.

“Our work is a unique example of how nanoscale materials can be used as atom-sized building blocks for molecular materials that could replace silicon and copper in electronic devices, luminescent displays, photovoltaic cells and other technologies.”

The paper is available online at www.sciencemag.org.

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Pitt opens lab at Navy SEAL base

A new human performance research laboratory designed by sports medicine researchers at Pitt and UPMC has opened at the U.S. Naval Amphibious Base Little Creek in Norfolk, Va.

At the lab, researchers will study injuries and training techniques of Navy SEALs, aiming to reduce preventable musculoskeletal injuries; maximize the effects of training to reduce fatigue and optimize performance; prolong the operational life, and enhance quality of life after service.

With a $2.1 million U.S. Department of Defense grant, awarded to the Pitt research team, the 2,200-square-foot laboratory employs state-of-the-art biomechanical and physiological instrumentation and techniques currently used for elite athletes. The lab is modeled after Pitt’s Neuromuscular Research Laboratory (NRL) at the UPMC Center for Sports Medicine.

A similar research laboratory at Fort Campbell, Ky., is operated by Pitt’s Department of Sports Medicine and Nutrition faculty and supported by a $2.75 million U.S. Department of Defense grant to study the Army’s 101st Airborne Division.

“The operator himself is the most important weapons system of naval special warfare,” said Captain Chaz Heron, commander of Naval Special Warfare Group TWO. “We are always seeking ways to improve our operators’ success on the battlefield. The last thing I want as a leader is for my men to be engaged in a fair fight. I want every advantage possible to give my operators a better chance for success on the battlefield. We’re optimistic the research and practical applications from our Human Performance Research Laboratory will achieve just that, while improving the quality of life for our SEALs after their service.”

Physical training and conditioning are the greatest cumulative source of acute and chronic injuries in this group, according to Pitt’s Scott Lephart, the grant’s principal investigator and director of the new lab.

Lephart is a professor in the Department of Sports Medicine and Nutrition in the School of Health and Rehabilitation Sciences (SHRS) and in the Department of Orthopaedic Surgery at Pitt’s School of Medicine. He is the founding director of Pitt’s NRL.

“As with an elite athletic team, musculoskeletal injuries significantly limit the war-fighting capability and readiness of the naval special warfare combatant force. Optimal physical training and conditioning are the cornerstones of the maintenance of the weapons platform of the Navy SEAL operator,” Lephart said.

The lab is staffed by exercise physiologist Greg Hovey and certified athletic trainer Anthony Zimmer, both of SHRS’s Department of Sports Medicine and Nutrition.

Lephart’s co-principal investigators are professors John Abt and Timothy Sell of the Department of Sports Medicine and Nutrition.

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Grant aims to develop regenerative solutions for injured soldiers

Pitt’s McGowan Institute for Regenerative Medicine is among the leaders of a national $85 million program to use the science of regenerative medicine to develop new treatments for wounded soldiers.

The project will be dedicated to repairing battlefield injuries through the use of regenerative medicine — science that takes advantage of the body’s natural healing powers to restore or replace damaged tissue and organs. The program also will benefit the civilian population with burns or severe trauma due to illness or injury.

A new federally funded institution — the Armed Forces Institute of Regenerative Medicine (AFIRM) — will be made up of the U.S. Army Institute of Surgical Research and consortia involving one team led by McGowan and the Wake Forest Institute for Regenerative Medicine and another led by Rutgers University and the Cleveland Clinic. Each group was awarded $42.5 million.

Twenty-nine McGowan research teams will be joined by 16 at Wake Forest and 33 more research teams at 15 other institutions and companies focusing on regenerative medicine including the Allegheny Singer Research Institute, Carnegie Mellon University and the Pittsburgh Tissue Engineering Initiative. Several treatments now are being evaluated in patients and more than 50 technologies from these researchers already have had an impact on treatments for illness and injury.

AFIRM will be co-directed by McGowan director Alan J. Russell and Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine.

The McGowan team has committed to develop clinical therapies over the next five years that will focus on burn repair; wound healing without scarring; craniofacial reconstruction; limb reconstruction, regeneration or transplantation, and compartment syndrome, a condition related to inflammation after surgery or injury that can lead to increased pressure, impaired blood flow, nerve damage and muscle death. AFIRM will have multiple research teams working in each area.

“Our goal is to use our position as the international leader in developing restorative therapies for battlefield trauma to improve the outcomes for our wounded,” said Russell, who is founding president of the Tissue Engineering and Regenerative Medicine International Society. “Our ability to provide these treatments is in part due to our team’s long experience in this field and our broad pipeline of technologies.”

Researchers associated with McGowan have launched more than 10 clinical trials (three with the Army) using tissue-engineered products that have been implanted in more than 1 million patients.

Government sponsors of AFIRM are the U.S. Army Medical Research and Materiel Command, the Office of Naval Research, the U.S. Air Force and the National Institutes of Health.

In addition to the announced government funding, the universities and their partners will provide more than $180 million from academic institutions, industry and state and federal agencies for the projects — for a total of more than $250 million available for soldier regeneration research.

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The University Times Research Notes column aims to inform readers about funding awarded to Pitt researchers and to report briefly on findings arising from University research. We welcome submissions from all areas of the University, not only health sciences areas.

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