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January 22, 1998


University gets $4.3 million for arthritis center

The National Institutes of Health (NIH) has awarded Pitt $4.3 million to establish a Multipurpose Arthritis and Musculoskeletal Diseases Center. The center, one of 14 NIH-designated ones in the country, will enhance, encourage and expand ongoing interdisciplinary programs for arthritis and musculoskeletal disease research within the University.

The center includes 47 investigators from 13 Pitt departments. Its director is Timothy M. Wright, associate professor of medicine and of molecular genetics and biochemistry, and chief of the division of rheumatology and clinical immunology.

Center projects underway include:

* A study to determine what contributes to bone loss in older men. In the United States, nearly one-third of all hip fractures occur in men. Spine fractures are nearly as common in men as in women.

* A study to learn why women with systemic lupus erythematosus suffer acute flare-ups of the disease during certain times of their menstrual cycles.

* A study in which muscle cells are being used to transfer therapeutic genes into joints. The goal is to provide a permanent source of medication inside an arthritic joint to alleviate its destruction and inflammation.

* A study to learn how gene expansion causes muscular dystrophy. Duchenne muscular dystrophy, the most common muscle-wasting disease, is caused when one section of a normal gene is produced over and over. The resulting expanded gene leads to disease.

Pitt created an arthritis center six years ago. New basic and clinical research programs are being developed and a network of arthritis care — the UPMC Arthritis Network — has been established in parallel with the expanded research. The network includes 22 rheumatologists at 11 practice sites in southwestern Pennsylvania and West Virginia.


Prof awarded NSF grant

The National Science Foundation program in tectonics and crustal structure has awarded a two-year, $78,373 grant to William Harbert, a Pitt associate professor of geophysics and an adjunct faculty member in the Center for Russian and East European Studies.

The grant will fund a new, cooperative program of paleomagnetic, geochemical and geochronological sampling and analysis of selected terranes of the Kamchatka Peninsula in northeastern Russia. Harbert will collaborate with professors from the University of South Florida and the University of Alaska.


Researchers use 'fish' and 'sky' to study chromosomes

Using state-of-the-art technologies, scientists at Pitt's Department of Human Genetics are lighting up human chromosomes in a colorful display to easily locate errors that give rise to disease.

Each person has 23 pairs of chromosomes, large coils of genetic material. Pitt researchers are probing human chromosomes with fluorescence in situe hybridization (FISH) and spectral karyotyping (SKY). These technologies reveal the tapestry of genes that instruct the body to develop and function properly and to yield information that could help biomedical researchers develop sensitive tests to detect disease and possibly aid in choosing the best treatments for specific disorders.

"Already, these technologies are allowing us to detect chromosomal alterations in otherwise normal looking cells lining the mouths of patients with oral cancer. These alterations identify cells that may grow into new cancers," said Susanne Gollin, associate professor of human genetics and director of Pitt's Cytogenetics Laboratory.

"Using such information, we may be able to screen individuals at risk for oral cancer, as well as develop and apply much better prevention and treatment strategies." Pitt's cytogenetics capabilities are unique in the region. Aside from detecting the most subtle chromosomal flaws underlying disease, FISH and SKY can be used to learn whether a chromosome has received a new gene delivered as part of a gene therapy; to track the integration of foreign, disease-causing viruses into chromosomes; and to assess how anti-cancer drugs alter chromosomes before they kill tumor cells.


Physicians can detect lung cancer earlier with new tool

Physicians at the University of Pittsburgh Cancer Institute (UPCI) can detect lung cancer earlier and may increase patient survival with a new diagnostic tool. The new LIFE (Lung Imaging Fluorescence Endoscopy)-Lung system uses a fluorescence imaging system and a helium cadmium-laser to help identify pre-cancerous tissue.

"In a recent, multi-center clinical trial in the United States and Canada, the use of LIFE-Lung bronchoscopy nearly tripled detection rates of pre-malignant lesions and microinvasive cancers over conventional bronchoscopy detection," said Tracey Lee Weigel, assistant professor of surgery and director of the LIFE-Lung Bronchoscopy Program. "With the development of non-invasive curative therapies such as photodynamic therapy, detection of early microinvasive lesions could finally decrease mortality attributable to lung cancer." People most likely to benefit from bronchoscopic screening with LIFE-Lung include those at high risk for developing lung cancer, those with known or previously removed lung cancer, those with head and neck primary tumors, those with symptoms such as persistent coughing, and those with positive screening cytologies and negative standard routine bronchoscopic exams.

In related research, Jill Siegfried, director for basic research at UPCI's Lung Cancer Center and associate professor of pharmacology, will study biological changes in pre-cancerous tissue specimens taken with LIFE-Lung. Her team will characterize markers physicians can use to identify early lung cancer.

Lung cancer will cause an estimated 160,000 U.S. deaths this year, accounting for 29 percent of all cancer deaths, and some 190,000 new cases will be diagnosed, according to the American Cancer Society. Currently, the five-year survival rate for patients diagnosed with lung cancer is only 14 percent due to its advanced stage at diagnosis.

LIFE-Lung is used following standard bronchoscopy, an endoscopic examination of the major airways of the lungs using a hollow tube with a fluoroptic white light and lens attached. The LIFE-Lung uses a helium-cadmium laser to deliver a blue light source that stimulates auto-fluorescence of the bronchial mucosa, using the principal that healthy tissue fluoresces differently than cancerous tissue. The system detects and enhances these differences which are displayed on a color monitor. Normal tissue appears green and suspicious tissue appears reddish brown.

The LIFE-Lung is manufactured by Xillix Technologies Corp. of Richmond, B.C., Canada.


Researchers construct novel delivery system for gene therapy of liver disorders

Like a car that transports its passengers, layers of lipids form a protective barrier for their passenger DNA molecules, safely whisking them past DNA-degrading enzymes and quickly delivering them to their destinations, or target cells.

A Pitt research team has constructed the first prototype of this "car," a delivery mechanism for genes called a reconstituted chylomicron remnant (RCR) that has resulted in the extended production of therapeutic proteins in an animal model, according to a report published in the Dec. 23 Proceedings of the National Academy of Sciences.

"We have developed the first non-viral vector that resembles a naturally occurring lipoprotein," said Leaf Huang, professor of pharmacology. Typically, lipoproteins pick up fat and take it to the liver where it is released and processed.

"In our studies, we placed genes into the RCR structures instead of fat and found that these genes were released into liver cells and their blueprints were used to build new proteins," he said.


Research may free juvenile diabetics from daily insulin injections

Juvenile diabetes patients may one day be freed from the rigors of daily insulin injections, thanks to a Pitt research project recently funded by the Pittsburgh Foundation.

The three-year, $150,000 grant will fund research seeking to develop molecularly thin barriers to protect transplanted pancreatic islet cells from immune rejection. The resulting islet transplantation may ultimately provide a therapy for juvenile diabetes.

The research team is headed by William R. Wagner, of bioengineering, chemical engineering, and surgery, with co-investigators Alan Russell and Eric Beckman of chemical engineering, and Harsha Rao of the medical school.


Pitt receives $1.7 million grant for training in MD genetics

An anonymous donor has granted $1.7 million to the University of Pittsburgh Duchenne Muscular Dystrophy Research Center.

"We are extremely grateful for this generous gift and will use the money to establish an intensive international post-doctoral training program in genetic research and therapy for Duchenne Muscular Dystrophy," said center director Eric Hoffman. "By inspiring young scientists to embark on scientific and clinical studies for DMD, we hope to develop a talented, innovative and enthusiastic team to work toward better treatments for this disorder." Hoffman, a Pitt associate professor in the departments of molecular genetics and biochemistry, human genetics, pediatrics and neurology, identified dystrophin, the protein defect responsible for DMD. He also was part of the original research team that discovered the genetic flaw underlying DMD.

Duchenne Muscular Dystrophy is one of the most common and most devastating inherited diseases. Caused by a defect in a gene responsible for maintaining the structure of muscles, it leads to progressive weakening of the muscles in young boys, leaving them confined to a wheelchair. Often, boys afflicted with DMD die before the age of 20.


Bigger liver transplant programs have better survival rates, analysis shows

An analysis of survival rates at U.S. liver transplant centers identifies 11 centers of excellence (including the UPMC Health System) and confirms previous studies that show survival rates are significantly better at centers that do a large volume of liver transplants.

But because of growth in the transplant industry, with more centers doing small numbers of transplants, patients must become more educated to assure they choose a high quality centers, says a policy research consultant for UPMC Health System, which has argued for more government oversight of the transplant system.

CONSAD Research Corp. used data from a federal government report that provides patient and graft survival rates at the 103 U.S. liver transplant centers in operation between Jan. 1, 1988 and April 30, 1994. (There are now 122 such centers.) The report was published in December by the Department of Health and Human Services for its contractor, the United Network for Organ Sharing (UNOS), which operates the national system.

Liver transplant programs were evaluated in relation to their risk-adjusted expected survival rates. UNOS found that 24 percent of the programs fell below their expected marks and 11 percent surpassed them. The rest were judged to be performing at their expected levels.

"Our analysis shows very convincingly that there is a strong relationship between a center's success rate and the volume of transplants it annually performs," said Fred Reuter, CONSAD vice president. "UNOS conducted a similar study in 1994 after its release of center-specific survival rates and reached the same conclusion then. The centers that do better tend to be ones that do many transplants. The centers that do worse tend to be low-volume centers." UPMC Health System performed 360 liver transplants annually during the years evaluated, the highest volume of any such program.


Pitt center wins sports medicine award

A team of researchers at Pitt's Musculoskeletal Research Center has received the 1997 O'Donoghue Sports Injury Research Award from the American Orthopaedic Society for Sports Medicine.

The award recognized a project, "Growth Factors Can Improve MCL Healing in Vivo," by center researchers Kevin Hildebrand, Savio Woo and several other authors. The work demonstrated that the presence of growth factors at the site of a complete MCL tear can reduce the size of the scar tissue mass and improve the histological and biomechanical quality of the healing tissue.

The O'Donoghue Award is the highest and most prestigious award given by the society. The award carries with it a $2,500 honorarium, an award certificate, the opportunity to present the paper at the annual meeting of the American Orthopaedic Society for Sports Medicine, and publication of the manuscript in The American Journal of Sports Medicine.


Many local children still not protected by seatbelts, survey finds

Even though seatbelt usage has been proven to save lives, 37 percent of local children are still not buckled up, according to a survey conducted by the UPMC Health System's Center for Injury Research Control and the Allegheny County Police.

The survey looked at seatbelt and child restraint usage and motor vehicle seating positions of children 12 years of age and younger. During the first two weeks of December, 405 vehicles were observed at random locations throughout Allegheny County, including elementary schools and shopping malls.

A total of 521 children were observed. Of those who were not in a car seat, there were 209 boys and 212 girls; 43 percent of the boys and 32 percent of the girls were not belted in, for an overall non-usage rate of 37 percent. Of the 405 vehicles, 50 percent had children sitting in the front seat even though there was room in the back.

The National Highway Transportation Safety Administration has found that over the last decade, seatbelt usage has prevented an estimated 55,000 deaths and 1.3 million injuries, and has saved $105 billion.

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