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September 25, 2008


Cells found that impact steroid resistant asthma

Researchers at Children’s Hospital have identified cells that may play a key role in some forms of steroid-resistant asthma.

The identification of a lineage of cells known as T Helper Type 17 (Th17) may help scientists in the development of new treatments that lead to better control of asthma, according to the study’s senior author, Jay K. Kolls, the Niels K. Jerne Professor of Pediatrics and Immunology at the School of Medicine and chief of the Division of Pediatric Pulmonary Medicine, Allergy and Immunology at Children’s Hospital.

Of the more than 22 million Americans who have asthma, as many as half of them have asthma that can be resistant to the steroids that are intended to reduce lung inflammation during an asthma attack, Kolls said.

“Asthma is a challenging condition to treat. For many patients, if they take preventive medications regularly, the condition can be controlled and they can lead relatively normal lives,” Kolls said.“Inhaled steroids are an important treatment for patients to prevent asthma attacks. Unfortunately, some patients have attacks despite the use of inhaled steroids, meaning they don’t respond to steroids or they need such high doses that side effects are experienced.”

In a study published in the September issue of the Journal of Immunology, Kolls and colleagues found that Th17 cells mediated steroid-resistant airway inflammation and hyper-responsiveness in animal models of asthma. Th17 cells are part of the immune system and are found where the body comes in contact with the external environment, such as the lungs and the lining of the gastrointestinal tract.

“Identifying Th17 cells as a potential mechanism by which steroid-resistant asthma occurs gives us a potential new target for the development of drugs that focus on these cells and lead to better overall control of asthma,” said Kolls.


Resveratrol fights radiation damage

Resveratrol, the natural antioxidant commonly found in red wine and many plants, may offer protection against radiation exposure, according to a study by School of Medicine researchers. When altered with acetyl, resveratrol administered before radiation exposure proved to protect cells from radiation in mouse models. The results of the research were presented recently at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

The study, led by Joel Greenberger, chair of radiation oncology, was overseen by Pitt’s Center for Medical Countermeasures Against Radiation. The center is dedicated to identifying and developing small molecule radiation protectors and mitigators that easily can be accessed and administered in the event of a large-scale radiological or nuclear emergency.

“Currently there are no drugs on the market that protect against or counteract radiation exposure. Our goal is to develop treatments for the general population that are effective and non-toxic,” Greenberger said. “New, small molecules with radioprotective capacity will be required for treatment in case of radiation spills or even as countermeasures against radiological terrorism,” said Greenberger. “Small molecules which can be easily stored, transported and administered are optimal for this, and so far acetylated resveratrol fits these requirements well.”

Greenberger and his team are conducting further studies to determine whether acetylated resveratrol eventually can be translated into clinical use as a radioprotective agent. 

The study was funded by a $10 million grant from the National Institute of Allergy and Infectious Diseases.


Medicare HMO rules may deter study subjects

Newly diagnosed cancer patients who are enrolled in Medicare’s Health Maintenance Organization (HMO) plans may be unlikely to participate in clinical trials because of prohibitive costs, according to a study by the University of Pittsburgh Cancer Institute (UPCI). Under these HMO plans that cover people age 65 and older, patients must pay both a deductible and 20 percent of the treatment cost.

The study results were announced during the American Society for Therapeutic Radiology and Oncology’s 50th annual meeting.

According to Chyongchiou Lin, lead author of the study and associate professor of health economics in UPCI’s Department of Radiation Oncology, two-thirds of cancer patients are age 65 or older, with 60 percent of new cancers and 70 percent of cancer-related deaths occurring in this age group. At the same time, less than one-third of clinical trial enrollees fall into this age group, and patients often cite cost and insurance coverage as barriers to their participation. Because the Medicare HMO payment policy requires significant personal expense, Lin and her team believe the disparity in clinical trials representation and the payment policy are likely to be related.

“Clinical trials are the cornerstone in finding better, more effective cancer treatments,” said Lin. “The National Cancer Institute has made clinical trial participation a national priority, yet current Medicare reimbursement policies present a participation barrier for a large number of patients, cutting them off from cutting-edge treatments. The current policy should be re-examined to be consistent with NCI initiatives.”

The study shows the overall proportion of newly diagnosed cancer patients who had consultations and were insured by Medicare HMOs increased from 21 percent in 2003 to 27 percent in 2007 in five hospitals participating in the UPMC McKeesport radiation oncology community outreach program. The research team in one of the participating hospitals found in 2007 that patients eligible for innovative clinical trials often opted out of enrolling in a Medicare-qualifying clinical trial due to the financial burden of participating.


Genetic link to organ rejection found

Researchers at Children’s Hospital have identified a genetic mutation that enables them to predict which transplant recipients may experience organ rejection. Results of the study were published in the September issue of Gastroenterology.

The team led by Rakesh Sindhi, director of Pediatric Transplant Research in the Hillman Center for Pediatric Transplantation, studied DNA samples from 80 children who received liver transplants and their parents to find the genetic variation associated with rejection.

“By establishing a genomic fingerprint for rejection and applying personalized anti-rejection strategies before the transplant even occurs, we are hopeful we can reduce rejection rates and drug-induced side effects for children with liver transplants from 50 percent to 20 percent or less,” Sindhi said.

Daniel E. Weeks of the Department of Human Genetics collaborated on the project.


Genetics behind cleft palate risk reported

Researchers from the School of Dental Medicine have identified a series of genetic mutations that appear to be linked to significant risk for cleft palate and other dental abnormalities.

As reported in the September issue of Genetics in Medicine, Alexandre Vieira and colleagues collected and evaluated genetic material from the saliva and blood of more than 500 individuals in family groups with two or more siblings affected with cleft lip or palate, and an additional 100 people from unrelated families whose samples were used for general-population comparison data.

The researchers analyzed 1,489 variations in DNA sequences, known as single-nucleotide polymorphisms, in 150 genes.

“We found a group of more than a dozen gene mutations that appear to be significantly associated with cleft lip and palate, as well as other dental abnormalities,” said Vieira, assistant professor in the Department of Oral Biology and pediatric dental specialist. “Here we report, for the first time, an extensive candidate gene analysis for cleft susceptibility, a crucial step that may allow for better estimates of recurrence risk in individual families.”

Cleft lip and palate is a common birth defect, on average affecting about one in 700 live births worldwide.

“The hope is to be able to narrow down the genes that cause clefts and to screen for that risk — and, eventually, to possibly lead to gene therapy targets, although that may not happen in my lifetime,” Vieira said.

Other study authors include Mary L. Marazita and Toby G. McHenry of the Department of Oral Biology.


Pneumonia causes in Parkinson’s patients studied

Impaired coordination between breathing and swallowing may be the underlying cause of aspiration pneumonia in patients with Parkinson’s disease, report School of Medicine researchers in a recent issue of the journal Dysphagia.

At least half of all Parkinson’s patients report having difficulty swallowing, and a higher percentage show swallowing abnormalities on X-ray tests. Aspiration pneumonia, a leading cause of death for individuals with Parkinson’s, often develops as a complication of mealtime swallowing problems that lead to the inhalation of food and drink. 

While the underlying cause of swallowing problems in Parkinson’s has not been well understood, prior research has found that healthy adults swallow most often during exhalation and that exhalation regularly follows the swallow, even when a swallow occurs during inhalation. The study looked at 25 Parkinson’s patients and a control group of healthy adults as they ate to determine where swallowing took place in the respiratory cycle.

Researchers found the Parkinson’s patients inhale during and after swallowing significantly more often than the healthy adults and swallowed at low lung volumes more often than the healthy adults.

Lead investigator Roxann Diez Gross, assistant professor in the Department of Otolaryngology, said, “Most Parkinson’s patients don’t know they have swallowing problems — even though aspiration pneumonia often is a severe complication of the disease — and Parkinson’s drugs most often do not improve these patients’ swallowing function. Now that we know the respiratory system may play an important role in swallowing problems in patients with Parkinson’s disease, we can develop therapies to help these patients re-coordinate breathing and swallowing patterns to improve swallowing function and possibly avoid aspiration pneumonia.”

Gross, who also is a speech language pathologist and director of UPMC’s Swallowing Disorders Center, has begun to incorporate this and other research into therapies for the center’s Parkinson’s patients.

Additional authors included Sheryl B. Ross, Department of Otolaryngology; Charles W. Atwood Jr., Department of Pulmonary, Allergy and Critical Care Medicine and VA Pittsburgh Healthcare System, and Kimberly A. Eichhorn and Patrick J. Doyle of the VA Pittsburgh Healthcare System.


Hyundai gives $50K for cancer research

Children’s Hospital has received $50,000 to support the research of pediatric oncologist J. Anthony Graves, who has been named a Hyundai scholar.

Launched in 2007 by Hyundai Motor America and its dealers, the Hyundai Scholars Pediatric Cancer Fellowship program aims to raise more than $10 million for pediatric cancer research over five years.


Sexual lyrics analyzed

More than one-third of popular music contains sexual references, with most of those representing degrading sexual portrayals, according to a School of Medicine study in the September/October issue of Public Health Reports.

The study analyzed 279 of the Billboard charts’ most popular songs of 2005. Of those, 103 contained references to sexual activity, and 67 of those references were classified as degrading.

Furthermore, songs with degrading sexual portrayals were more likely to reference substance use, violence and weapons.

“Studies have suggested that exposure to degrading sexual references in music is linked to risky sexual behaviors among young people,” said Brian Primack, assistant professor of medicine and pediatrics and lead author of the study. “Knowing this, we thought it especially important to ascertain how many of these references are contained in today’s popular music.”

For this study, degrading sexual lyrics were defined as those where sexual value was placed solely on physical characteristics and where one person, usually male, was portrayed as having an insatiable sexual appetite while the partner was objectified.

Researchers found that sexual references differed significantly by musical genre. Songs with degrading references were most commonly found in the rap genre with 64 percent of all noted degrading references and in rhythm & blues/hip-hop with 22 percent.

Non-degrading sexual lyrics were most often found in the country genre, with 45 percent of all such references, and in rhythm & blues/hip hop with 28 percent.

“Adolescents listen to an average of two to four hours of music each day,” said Primack. “While we can’t expect to change the music industry, understanding what young people are exposed to can help parents know what’s out there. It also can assist educators in developing media literacy programs to teach kids how to interpret the messages they hear in popular music.”

Pitt co-authors of the study were Melanie Gold of pediatrics and Eleanor Schwarz of medicine and obstetrics, gynecology and reproductive medicine.


$1.5M given for heart tissue research

Bradley Keller and William Wagner, researchers at the McGowan Institute for Regenerative Medicine, have received a National Institutes of Health grant of more than

$1.5 million for research on the regulation of embryonic heart muscle cells using an engineered early embryonic cardiac tissue (EEECT) they developed.

Keller, professor of pediatrics and a graduate faculty member in cell biology and molecular physiology, and Wagner, deputy director at the McGowan Institute and a professor of surgery, bioengineering and chemical engineering, will study the proliferation and differentiation of the tissue to generate tissues with optimal properties for cardiac repair.

Preliminary data show that EEECT can be implanted to help repair damaged adult heart tissue.


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