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July 26, 2012

Research Notes

No more yearly flu shots?

A vaccine strategy that protects against all strains of seasonal influenza and avoids the need for annual vaccination is the goal of a collaboration between Pitt researchers and vaccine-maker Sanofi Pasteur.

Ted M. Ross and his team at Pitt’s Center for Vaccine Research (CVR) are exploring new vaccine technologies intended to protect against all strains of seasonal influenza and to be made in less than half the time of the traditional vaccine. The new vaccine could potentially cover influenza strains circulating over multiple seasons, eliminating the need for a seasonal flu shot.

The U.S. Centers for Disease Control and Prevention (CDC) estimates that annual flu-associated deaths in the United States range from 3,000 to 49,000.

While the traditional flu vaccine uses a mix of inactivated viruses, the experimental shot would be a synthetic vaccine created from the genetic sequence of flu viruses. Termed “computationally optimized broadly reactive antigen” or COBRA, the method would produce protection against all strains of seasonal influenza, including those not yet in existence. So, the synthetic flu shot may be effective far longer than the traditional flu vaccine.

Ross, a faculty member in microbiology and molecular genetics, School of Medicine, previously used the COBRA method to produce a vaccine against bird flu, H5N1. This vaccine protects against all known strains of bird flu and has been well-tolerated in pre-clinical trials.

The new vaccine potentially could replace the seasonal flu vaccine in about a decade.


Scans reflect brain anatomy

High definition fiber tracking, or HDFT, provides colorful, detailed images of the brain’s fiber network that accurately reflect brain anatomy observed in surgical and laboratory studies, according to a School of Medicine report in the August issue of Neurosurgery. The findings support the notion that HDFT scans can provide valuable insight into patient symptoms and the prospect for recovery from brain injuries, and can help surgeons plan their approaches to remove tumors and abnormal blood vessels in the brain.

In deep brain surgery, the neurosurgeon may need to cut or move brain fiber tracts, meaning the neuronal cables connecting the critical brain areas, in order to get to a mass, said Juan Fernandez-Miranda, a faculty member in the Department of Neurological Surgery. Depending on the location of the tumor and the surgical path the surgeon takes to get to it, fiber tracts that control abilities such as language, memory and motor function could be damaged.

“HDFT is an imaging tool that can show us these fiber tracts so that we can make informed choices when we plan surgery,” Fernandez-Miranda said.

Co-author Walter Schneider, a faculty member at the Learning and Research Development Center (LRDC) and in the Department of Psychology, Dietrich School of Arts and Sciences,  led the team that developed HDFT.

Fernandez-Miranda and his colleagues obtained HDFT scans of 36 patients with brain lesions, including cancers, and six neurologically healthy individuals. They found that HDFT correctly replicated important anatomical features, including the peaks and valleys of brain tissue; a region called the centrum semiovale where multiple fiber tracts cross; the sharp curvature of the optic radiations that carry information to the visual cortex, and the endpoints on the brain’s surface of the branches of the arcuate fasciculus, which is involved in language processing.

For the second part of the study, the team conducted HDFT scans in 36 patients prior to surgery, along with the imaging studies typically done as part of the pre-operative process. They compared fiber involvement predicted by HDFT with what they found during surgery.

“The scans accurately distinguished between displacement and destruction of fibers by the mass,” said study co-author Robert Friedlander, UPMC chair in the Department of Neurological Surgery.

Co-authors included Sudhir Pathak, Kevin Jarbo and Timothy Verstynen of LRDC; Jonathan Engh and Arlan Mintz of the Department of Neurological Surgery; Fernando Boada of the Magnetic Resonance Research Center, Department of Radiology, and Frank Yeh, Carnegie Mellon University.

The project was funded by The Copeland Fund of The Pittsburgh Foundation and the Defense Advanced Research Projects Agency.


Old method, faster devices?

With the advent of semiconductor transistors — invented in 1947 as a replacement for bulky and inefficient vacuum tubes — has come the demand for faster, more energy-efficient technologies. To fill this need, Pitt researchers have proposed a new spin on an old method: a switch from the use of silicon electronics back to vacuums as a medium for electron transport. Their findings were published online in Nature Nanotechnology.

For the past 40 years, the number of transistors placed on integrated circuit boards in devices like computers and smart phones has doubled every two years, producing faster and more efficient machines. This doubling effect, commonly known as “Moore’s Law,” occurred because of scientists’ ability to shrink the transistor size continually, thus producing computer chips with all-around better performance.

However, as transistor sizes have approached lower nanometer scales, it’s become increasingly difficult and expensive to extend Moore’s Law further. “Physical barriers are blocking scientists from achieving more efficient electronics,” said Hong Koo Kim, principal investigator on the project and Bell of Pennsylvania/Bell Atlantic Professor in the Swanson School of Engineering.

The ultimate limit of transistor speed, Kim said, is determined by the electron transit time, or the time it takes an electron to travel from one device to the other. Electrons traveling inside a semiconductor device frequently experience collisions or scattering in the solid-state medium. Kim likens this to driving a vehicle on a bumpy road: Cars cannot speed up very much. Likewise, the electron energy needed to produce faster electronics is hindered.

“The best way to avoid this scattering — or traffic jam — would be to use no medium at all, like vacuum or the air in a nanometer scale space,” said Kim.

However, Kim said, conventional vacuum electronic devices require high voltage, and they aren’t compatible with many applications. Therefore, his team decided to redesign the structure of the vacuum electronic device. With the assistance of Siwapon Srisonphan, a Pitt PhD candidate, and Yun Suk Jung, a Pitt postdoctoral fellow in electrical and computer engineering, Kim and his team discovered that electrons trapped inside a semiconductor at the interface with an oxide or metal layer can be extracted easily into the air. The electrons harbored at the interface form a sheet of charges, called two-dimensional electron gas.

Kim found that the interaction between electrically charged particles in the electron layer enables the easy emission of electrons from silicon. The team extracted electrons from the silicon structure efficiently by applying a negligible amount of voltage and then placed them in the air, allowing them to travel ballistically in a nanometer-scale channel without any collisions or scattering.

“The emission of this electron system into vacuum channels could enable a new class of low-power, high-speed transistors, and it’s also compatible with current silicon electronics, complementing those electronics by adding new functions that are faster and more energy efficient,” said Kim.

Funding was provided by the National Science Foundation.


Tracking the history of drought

Through an exploration of tree rings and oxygen isotopes, Pitt researchers now are able to pinpoint better the history of droughts in the arid and semiarid areas of the American West.

A paper published in the online Proceedings of the National Academy of Sciences explores the medieval climate anomaly, a particularly warm period occurring in the northern hemisphere of the American West around 950-1250 C.E. While this time period is known as a “dry period,” the researchers have discovered an unexpected complexity to the patterns of drought.

“East of the Cascade Mountains, the Pacific Northwest is now dry and hot in the summer and wet in the winter,” said Byron A. Steinman, principal investigator on the project who earned his PhD in geology from Pitt last year and now is a postdoctoral researcher at Penn State. “We’ve found that it may not have been dry in the winter in the Pacific Northwest during the medieval climate anomaly.”

Steinman, who worked with Pitt professor of geology and planetary science Mark B. Abbott, began by studying tree rings, which can record precipitation and temperatures. However, tree rings are more accurate at recording this information during the spring and summer months, when the tree is growing.

To determine the validity of the tree-ring data, the researchers studied oxygen isotopes for comparison. They explored isotopes found in nearly 1,500 years of bottom-of-lake sediments from Castor Lake and Lime Lake in Washington state. The isotopic composition of these sediments, said Steinman, can reflect the amount of water entering a lake.

The researchers paid particular attention to the calcium carbonate in the water (shown in the form of calcite), as the oxygen in this mineral relates directly to the isotope ratio of lake water.

Castor Lake is on a plateau, and the water inflow comes only from precipitation and groundwater. Therefore, no water is lost through evaporation. However, Lime Lake loses the majority of its water through a permanent outflow stream. By comparing the two lakes, researchers could determine the water balance between evaporation and precipitation.

To pinpoint the time of the drought, the researchers looked at two stable isotopes of oxygen — oxygen 16 and oxygen 18 — in the sediments. Oxygen 16 is lighter than oxygen 18, and so during evaporation more of it is released; the calcite in the sediments contains more of the oxygen 18. If the lakes are full of water, however, there will be more oxygen 16 in the calcite. The layers of sediments that are laid down each year can be dated either using carbon 14 dating of organic material or by locating layers of tephra (volcanic ash).

In the end, however, what they found was a mismatch of data.

“The tree ring and isotope data matched up on a short-term, decadal scale,” said Steinman. “However, on a longer-term, century scale, the records diverged. The tree-ring data suggests dry conditions during the medieval climate anomaly summers while the isotope data suggest wetter-than-expected winters.”

In the paper, the researchers suggest a strong centennial relationship over the past 1,500 years between winter precipitation and the climate variability patterns that shift about every 20-30 years in the Pacific (known as Pacific decadal oscillation or PDO). PDO is linked to the El Niño Southern oscillation, a tropical phenomenon that influences global weather patterns.

“Before and during the medieval climate anomaly, the North Pacific Ocean was warmer, and Washington had a greater precipitation than during the Little Ice Age, which occurred from 1450 to about 1850 C.E., when there was less precipitation,” said Steinman.

Nathan D. Stansell, who earned his PhD at Pitt and now is a research fellow at Ohio State University, was among the project’s researchers.

The project was funded by the National Science Foundation.


Alcohol increases social bonding in groups

A Pitt study shows that moderate amounts of alcohol consumed in a social setting can enhance positive emotions and social bonding and relieve negative emotions among those drinking.

While it is usually taken for granted that people drink to reduce stress and enhance positive feelings, many studies have shown that alcohol consumption has the opposite effect. According to the researchers in a study published online in Psychological Science, previous alcohol studies testing the impact of alcohol on emotions involved social drinkers consuming alcohol in isolation.

Michael A. Sayette, lead author and faculty member in psychology in the Dietrich School of Arts and Sciences, said: “We felt that many of the most significant effects of alcohol would more likely be revealed in an experiment using a social setting.”

Sayette and his colleagues assembled small groups using 720 male and female participants. Researchers assessed individual and group interactions using the Facial Action Coding System (FACS) and the Grouptalk model for speech behavior.

They concluded that alcohol stimulates social bonding, increases the amount of time people spend talking to one another and reduces displays of negative emotions.

The Pitt researchers took care in the methods they employed to form the groups. Each participant was randomly assigned to a group of three unacquainted “strangers.” Each group was instructed to drink an alcoholic beverage, a placebo or a nonalcoholic control beverage. Twenty groups representing each gender composition (three males; one female and two males; two males and one female, and three females) were assigned to the three different beverage scenarios.

Group members sat around a circular table and consumed three drinks over a 36-minute time span. Each session was video recorded, and the duration and sequence of the participants’ facial and speech behaviors were systematically coded frame by frame.

Results showed that alcohol not only increased the frequency of “true” smiles, but also enhanced the coordination of these smiles. In other words, alcohol enhanced the likelihood of “golden moments,” with groups provided alcohol being more likely than those offered nonalcoholic beverages to have all three group members smile simultaneously. Participants in alcohol-drinking groups also reported greater social bonding than did the nonalcohol-drinking groups and were more likely to have all three members stay involved in the discussion.

Other Pitt researchers on the project were psychology faculty members Jeffrey Cohn, John Levine and Richard Moreland and graduate psychology students Kasey Creswell, John Dimoff and Catharine Fairbairn.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.


Pitt to lead lung disease study

Pitt researchers will lead a national effort to learn more about the causes and progression of two potentially deadly yet under-studied lung diseases, alpha-1 antitrypsin (A1AT) deficiency and sarcoidosis, and possibly to identify new treatments for them.

The team will explore the relationships among bacteria that live in the lungs, gene activation patterns and disease progression.

The three-year, $8.3 million grant comes from the National Heart, Lung and Blood Institute.

The Genomic Research in A1AT and Sarcoidosis study (GRADS) Genomics and Informatics Center will obtain patient samples from seven clinical centers across the nation.

Lead principal investigator is Naftali Kaminski, a faculty member in the School of Medicine’s Division of Pulmonary, Allergy and Critical Care Medicine and director of the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease.

Co-principal investigators are Michael Becich, chair of the medical school’s Department of Biomedical Informatics, and Stephen R. Wisniewski, a faculty member in the Department of Epidemiology and associate dean for research in the Graduate School of Public Health.

Kevin Gibson, a faculty member in the Division of Pulmonary, Allergy and Critical Care Medicine and clinical director of the Simmons Center, is the principal investigator of the local GRADS clinical center.

Other collaborating and clinical GRADS centers are at Vanderbilt University, the University of South Carolina, the University of California-San Francisco, the University of Illinois-Chicago, Yale, the J. Craig Venter Institute, the University of Pennsylvania, National Jewish Health and Johns Hopkins University.


Why consumers choose sharing services

Businesses that want to successfully market commercial sharing programs like Zipcar should focus on cost effectiveness and product availability rather than popularity or environmental benefits, according to recently published Pitt research.

The study — by Cait Poynor Lamberton, Fryrear Faculty Fellow and faculty member in the Katz Graduate School of Business and College of Business Administration, with Randall L. Rose of the University of South Carolina — examined the likelihood of consumers using companies that shared cars, cell phone minutes and bicycles. The researchers found that consumers focus on the cost of the service and the resources available.

The research was published in the July issue of the Journal of Marketing.

Lamberton said while companies are anxious to encourage consumers by marketing the popularity of sharing systems, that tactic may not garner the participation desired.

“Consumers know if companies are advertising that everyone is using their services, there may not be a product available for them when they want to use it,” she said. “If the pool is too crowded, there may not be any room for me.”

In the study, a fictional car-sharing service was presented to an online panel of more than 300 licensed drivers. Borrowing product information from a popular car-sharing company, including usage rates, users were asked whether they would sign up for the car-share program, how likely they would be to use the car and whether they were concerned the car would be available when they needed it.

They also answered questions about the social acceptance and environmental benefits of sharing, and whether they had any antipathy toward the industry in question.

Lamberton said the study found consumers who would save money were more likely to choose the car-sharing service, especially since it provided access to a car in most major cities throughout the country. The likely availability of cars was a greater contributor to sharing likelihood than almost any other factor, researchers found.

In two other studies — one involving a cell phone program that would allow users to share minutes and the other concerning a bicycle-share program — researchers found consumers were less likely to want to share with other consumers who were like themselves.

“Consumers realized if they shared with people who were similar to themselves, they would have the same needs at the same time and the product might be unavailable,” Lamberton said.

“Marketers like to play on cohesion and popularity of a product, but in this case that may not be the best angle,” she said. “Social factors like the environmental benefits of using shared programs don’t seem to be primary drivers for consumer use, at least at the point of decision. At that point, in addition to cost savings, marketers need to emphasize that the resources will be available when consumers want them.”


Amniotic fluid may help some preemies

Lack of exposure to amniotic fluid could be the reason that preterm infants are more susceptible to the gastrointestinal inflammatory disease necrotizing enterocolitis (NEC), according to researchers at the School of Medicine and Children’s Hospital.

In an online report in the Proceedings of the National Academy of Sciences, they show that feeding amniotic fluid to young mice reduced the risk of NEC in an experimental model, suggesting new therapeutic avenues for warding off the deadly condition.

Senior author David Hackam, Watson Family Professor of Surgery in the Department of Surgery and co-director of Children’s Fetal Diagnosis and Treatment Center, said NEC is the leading cause of death from gastrointestinal disease in babies, and most commonly affects those who are born six-eight weeks early. Twelve-15 percent of all premature babies develop NEC.

The causes of NEC are not well understood. In previous research, Hackam’s team determined that a molecular switch called Toll-like receptor 4 (TLR4) was turned on in intestinal tissue affected by NEC. Healthy infants born at term have relatively low levels of TLR4 in the gut. The protein is important in fending off infection because it is involved in the recognition of bacteria, leading the researchers to posit that unlike in healthy newborns, something goes wrong with the TLR4 response when preemies get colonized with normal gut flora.

“One big difference between a 34-week-old baby developing in its mother’s uterus and one in the neonatal intensive care unit is that the first one is floating in and swallowing amniotic fluid,” Hackam said. “Early delivery means that exposure to the fluid is gone, so we speculated that components of the fluid could help prevent NEC by keeping TLR4 in check.”

The researchers showed that injecting small amounts of amniotic fluid into the intestine of premature mice, or feeding the fluid to them, stopped NEC from developing. That’s because the fluid is rich in epidermal growth factor (EGF), a wound healing protein; when the researchers removed it from the fluid or blocked or removed the EGF receptor on intestinal cells, amniotic fluid no longer had a protective effect.

“It appears that EGF in amniotic fluid is able to shut off TLR4 activity and prevent NEC,” Hackam said. “Perhaps if we one day banked amniotic fluid after premature delivery, we could give it to newborns at risk for the problem. We also could identify a drug that inhibits TLR4 activity to try to save these babies.”

The research team included Feras Alkhudari, Misty Good, Sapana Shah and Dennis Slagle of pediatrics; Amin Afrazi, Maria F. Branca, George K. Gittes, Zachary Grant, Charlotte E. Egan, Hongpeng Jia, Joyce Lin, Congrong Ma, Matthew D. Neal, Jose Paredes, Thomas Prindle, Richard H. Siggers, Chhinder P. Sodhi and Ibrahim Yazji of surgery, and John Ozolek of pathology.

The study was funded by National Institutes of Health, the Children’s Hospital of Pittsburgh Foundation and the Hartwell Foundation.


Pharmacy faculty get research funds

Pamela Smithburger, a faculty member in pharmacy and therapeutics, has received a $19,924 grant from the American Society of Health-System Pharmacists to pursue her research entitled “A Multicenter Evaluation of Off-Label Medication Use and Adverse Drug Event in Adult Intensive Care Unit Patients.”

Smithburger plans to evaluate off-label use of medications in the ICU and apply what is found by creating a pharmacist-led, active-medication monitoring system utilized to reduce injury.

Yong Tae Kwon, a faculty member in pharmaceutical sciences, has received a four-year, $1.4 million grant from the National Institutes of Health to pursue studies on “The Role of Ubiquitin in the Cardiovascular System.”

Janice Pringle, a faculty member in pharmacy and therapeutics, has received a $902,357 grant from Merck Sharp & Dohme for a “Prospective Study to Assess the Effect of Adherence Interventions on Reducing Patients’ Non-Persistence to Chronic Medications.”


Approach hikes clinical trial enrollment

Adolescents and young adults who have cancer were more likely to enroll in clinical trials with the establishment of a unified program of both pediatric and adult cancer specialists, according to a Children’s Hospital and University of Pittsburgh Cancer Institute (UPCI) study.

Results of the study, led by Peter Shaw, faculty member in the School of Medicine’s pediatrics department and director of the adolescent and young adult (AYA) oncology program at Children’s Hospital, were published in the July 15 issue of Cancer.

“Since 1975, there have been dramatic increases in the survival rates of pediatric and older cancer patients, but we haven’t seen similar improvements in adolescent and young adult patients ages 15-40,” said Shaw.

Shaw and colleagues previously published research indicating lower clinical trial enrollment when adolescent and young adult patients were treated at an adult oncology center instead of at a pediatric oncology center.

Pediatric oncologists at Children’s Hospital and medical oncologists at UPCI established a joint AYA oncology program with the primary objective of improving outcomes by increasing clinical trial enrollment in this population.

Fifty-seven patients, ages 15-22, were referred to the AYA program.

Eight patients were referred for consultation only and were not treated at UPCI or Children’s Hospital.

Nine of 27 patients (33 percent) who received treatment at the adult cancer center were enrolled in a clinical trial. In the three years before the start of the AYA program, only 4 percent of patients in this age range who received treatment at UPCI were enrolled in clinical trials.

“Our research demonstrates that establishing a unified AYA oncology program can lead to increased clinical trial enrollment for patients who are treated at medical oncology centers,” said Shaw.


How good is “good” cholesterol?

Pitt research suggests that doubts raised about the protective effects of high density lipoprotein (HDL), or “good,” cholesterol by a genetic study and several recent clinical trials of HDL-raising drugs could be put to rest by using a better indicator of HDL status.

A national team of researchers led by Pitt’s Graduate School of Public Health (GSPH) analyzed blood samples of 5,598 healthy men and women and found that when assessing coronary heart disease risk, it appears more beneficial to measure — and make treatment decisions based on — HDL particles, not HDL cholesterol. The results will be published in the Aug. 7 Journal of the American College of Cardiology.

Rachel Mackey, faculty member in epidemiology and lead author, said: “We found that higher levels of HDL cholesterol and HDL particles were both associated with less carotid atherosclerosis and fewer heart attacks and other cardiovascular events. However, the risk associated with lower HDL cholesterol levels could be explained by other risk factors, such as higher levels of triglycerides. In contrast, after accounting for these other risk factors, higher levels of HDL particles remained strongly associated with lower coronary heart disease risk.”

HDL particles carry HDL cholesterol, along with proteins and fats, to the liver where the cholesterol is removed from the body. Low-density lipoprotein (LDL) particles carry cholesterol to the arterial wall, causing atherosclerosis. When doctors measure cholesterol and report HDL and LDL levels, they are referring to HDL and LDL cholesterol, not to the particles that carry this cholesterol.

Samia Mora, of the Brigham and Women’s Hospital and senior author of the paper, said: “We found that the number of HDL particles had stronger cardio-protection than HDL cholesterol.”

Mackey noted: “HDL particles are known to have a variety of functions, including anti-oxidant, anti-inflammatory and anti-thrombotic properties, in addition to reverse cholesterol transport. Measuring the concentration of HDL particles, rather than their cholesterol content, may better reflect HDL functionality.”

The study used a commercially available NMR spectroscopy technique to measure lipoprotein particle concentrations in blood samples provided by study participants who were followed for an average of six years as part of the Multi-Ethnic Study of Atherosclerosis (MESA).

Efforts are underway to further evaluate HDL functionality and to determine which aspects of it are related causally to heart disease and could be modified through lifestyle or therapeutic interventions.

The research was supported by the National Heart, Lung and Blood Institute and LipoScience.


Program extended at PSC

The National Resource for Biomedical Supercomputing (NRBSC) at the Pittsburgh Supercomputing Center (PSC) recently completed soliciting proposals for another round of research with Anton, a special-purpose supercomputer that has enabled researchers to achieve exceptional results in the simulation of biomolecules.

Anton allows researchers to execute ultra-fast “molecular dynamics” (MD) simulations of proteins and nucleic acids, such as DNA and RNA, over much longer time periods than have previously been accessible to computational study. Insights into biomolecular structure and function facilitated by the use of Anton could potentially lead to the development of new and better therapeutic drugs and other improvements in disease treatment.

The NRBSC program marked the first time Anton has been available to the general biomedical community.

Initial funding to cover operational costs came from a $2.7 million grant from the National Institute of General Medical Sciences. Third-round allocations will be awarded in late 2012.


Smart materials get SMARTSer

Few synthetic materials have been able to mimic the human body’s ability to regulate itself — until now. In the July 12 issue of Nature, engineers from Pitt and Harvard presented a strategy for building self-regulating microscopic materials, ultimately paving the way toward so-called smart buildings with more energy-saving features and smarter biomedical engineering applications.

Anna Balazs, co-investigator and Distinguished Professor of Chemical and Petroleum Engineering in the Swanson School of Engineering, said: “Consider what happens when a typical hair dryer becomes too hot: The device just shuts off. The hair dryer does not, however, turn itself back on when the system has cooled down. Hence, this is a very passive way of regulating temperature. Our design is a much more active way of continuously sensing and regulating the temperature.”

The Pitt team, which included Olga Kuksenok, also a faculty member in the Swanson school, crafted a multi-scale model for the novel material, created by embedding “posts,” or tiny hairs, into a hydrogel.

“This model captured salient features of our experimental work, including the presence of two fluids lying above the embedded posts and the posts’ tips (decorated with catalysts), which interact with chemical reagents in the upper fluid and thereby produce heat,” said Kuksenok. “Thus, the scale model captured the components and range of complex phenomena occurring within our experimental system.”

This model helped the Harvard team optimize the behavior of the system that the Pitt team created, which they called SMARTS — a Self-regulated Mechano-chemical Adaptively Reconfigurable Tunable System. SMARTS offers a customizable way to trigger chemical reactions on cue and reproduce the type of stable feedback loops found in biological systems. The Harvard team was able to integrate the desired features into the material itself. Whether it is a pH level, temperature or pressure, SMARTS can interact directly with the desired stimulus, presenting a platform that is customizable, reversible and efficient. The researchers anticipate that this technique could be integrated into handheld portable diagnostics, which are playing a growing role in bringing medicine to developing or rural areas.

The U.S. Department of Energy and the National Science Foundation provided support.


Peds cancer researcher gets Hyundai award

J. Anthony Graves, a faculty member in pediatrics and director of research education and development in the Division of Pediatric Hematology/Oncology at Children’s Hospital, has been awarded a $75,000 Hyundai scholar grant. His research involves tumor cells with c-Myc elevation, and has an end goal of developing novel cancer therapies for children with cancer.

The grant is part of Hyundai Hope on Wheels, a program of Hyundai Motor America and its more than 800 U.S. dealers to raise awareness about childhood cancer.

In addition, the program awarded Children’s $10,000 for the purchase of personal technology and electronics as part of the Hyundai Hot Spot Award, which is designed to fill the void of in-care activities available to teen patients.


New help for some severe asthma cases

Pitt researchers have identified a subset of severe asthma that improves with drug regimens that suppress the immune system. In the American Journal of Respiratory and Critical Care Medicine, they dubbed the condition “asthmatic granulomatosis” after the characteristic small areas of focal inflammation that can be found in the lungs of those who have it.

Five-10 percent of patients with asthma have disease that can be classified as severe, meaning it is difficult to treat and often causes life-threatening breathing problems, said lead author Sally E. Wenzel, faculty member in the medical school’s Division of Pulmonary, Allergy and Critical Care Medicine and director of the Pitt/UPMC Asthma Institute.

The team examined a group of patients with severe asthma. Nineteen patients underwent biopsies of their lung tissue. Ten of them not only had airway changes typical of asthma, but also lesions called granulomas, which are nodules of inflammation sometimes seen with certain infections or with autoimmune diseases.

However, 70 percent of the patients had a personal or family history of autoimmune-like disease such as lupus and rheumatoid arthritis. Because granulomas can be produced by an over-active immune system, the team treated the 10 cases with drugs that suppress it, including azathioprine, mycophenolic acid, methotrexate or infliximab. Nine of them reduced their steroid doses and had improvements in standard lung-function tests while one had difficulty tolerating the powerful immune-suppressants.

Of the other nine patients who had biopsies, six had tissue changes that reflected asthma, but no granulomas, and three had other issues. “The unexpected finding of granulomas in a subset of patients with severe asthma warrants approaching it as a newly described disease, which we’ve named asthmatic granulomatosis,” Wenzel said.

Asthma specialists should consider getting tissue biopsies in atypical severe asthmatics, the researchers said.

Co-authors included Catherine Vitari, medicine; Manisha Shende, surgery; Diane C. Strollo, radiology; Allyson Larkin, pediatrics, and Samuel A. Yousem, pathology.

The project was funded by the Dellenback Research Fund.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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