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July 22, 2004

Research Notes

Immunologist gets 3 grants

“The Department of Immunology’s Dr. Binfeng Lu has received funding for his projects from no fewer than three sponsors.

The National Institutes of Health has granted $143,695 in funding for two years, via the Division of Rheumatology’s Rheumatic Diseases Core Center grant for his project entitled “Molecular Mechanisms of Anti-Proliferation and Apoptosis by Members of the Gadd45 Family in T Cells.”

The National Multiple Slerosis Society is providing a total of $427,647 for three years, for his project entitled “Immune Regulation by Gadd45b and Gadd45g.” Llastly, the Cancer Research Institute is granting a four-year award in the amount of $200,000 for his project entitled “Immune Regulation by Genes of the Gadd45 Family.”

Group B strep vaccine tested

A vaccine for Group B strep infection is being investigated in a clinical study now enrolling at the Magee-Womens Hospital of the University of Pittsburgh Medical Center. The leading cause of life-threatening infection in newborns, Group B streptococcus (GBS) bacteria naturally lives in the reproductive and intestinal tracts, and often comes and goes in healthy women without causing illness. Although it can cause serious illness in adults such as blood infection and pneumonia, it is especially dangerous to babies.

Called the Streptococcal Prevention in Non-pregnant Women (SPIN) Study, the trial is testing whether a single inoculation with an investigational GBS type III vaccine can stop GBS type III bacteria from invading the reproductive tract. Newborns typically become infected with GBS while traversing the birth canal during labor.

“Since some 70 percent of women are colonized with GBS over a year’s time, infection risk can be substantial,” said Sharon Hillier, Ph.D., professor of obstetrics, gynecology and reproductive sciences and of molecular genetics and biochemistry at the University of Pittsburgh School of Medicine. “The GBS type III vaccine we are testing is active against one of the most common types of GBS that is known to cause disease in newborns.”

In 1996, the Centers for Disease Control and Prevention recommended a screening test for GBS during pregnancy for all women between the 35th and 37th week of gestation. Before such screening became routine, one or two babies out of 1,000 were affected by neonatal sepsis, a severe infection caused by GBS, said Dr. Hillier. Since 1996, that number has been reduced at Magee to 0.2 per 1,000 births.

“This is one of the greatest public health victories in the past 10 years,” added Dr. Hillier, who also is director of the Center of Excellence in Women’s Health at the Magee-Womens Hospital of the University of Pittsburgh Medical Center and a senior investigator at the Magee-Womens Research Institute. “But 25 percent of laboring women still get antibiotics during delivery because of a positive GBS test. Having a vaccine that may prevent women from carrying the organism in the reproductive tract would be a valuable additional strategy.”

For the SPIN study, investigators are seeking women between the ages of 18 and 30 who are not pregnant and who have been sexually active in the four months previous to enrollment. Those who participate in the study also should expect to live in the Pittsburgh region for at least 18 months after enrollment to facilitate 11 follow-up visits.

Research participants will be tested for GBS. If the screening is negative and other study criteria are met, women will be randomized to receive either a single injection of investigational vaccine or a tetanus shot. Investigational vaccines similar to that being used in the SPIN study have been tested in more than 400 women. These vaccines are not made with live bacteria and do not cause illness.

For more information about GBS, visit

For more information on the SPIN study or to enroll, call the infectious disease research office at Magee at 412-641-4242.

The study is being funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Airbags minus seatbelts causes more spinal injuries

Drivers and front-seat passengers who have airbags but do not use seatbelts are much more likely to sustain a spinal injury in frontal crashes than drivers and front-seat passengers with airbags who do use seatbelts, according to a study by the University of Pittsburgh School of Medicine’s department of orthopaedic surgery, division of spinal surgery.

“If you do not wear a seatbelt, the airbag can be a weapon, a source of injury. If you do wear a seatbelt, the airbag most likely will be helpful,” said study co-author William F. Donaldson III, M.D. “By not buckling your seatbelt, you increase the likelihood of a spinal fracture and spinal cord injury when your airbag deploys in a frontal collision.” Dr. Donaldson is an associate professor of orthopaedic surgery and neurological surgery and chief of the division of spinal surgery in the University of Pittsburgh School of Medicine’s department of orthopaedic surgery.

The research team studied the outcomes of 86,000 patients who were drivers or passengers in frontal collisions occurring in Pennsylvania between 1990 and 2002, according to data from the Pennsylvania Trauma Systems Foundation.

Drivers who had airbagss but were not wearing seatbelts were 1.7 times more likely to sustain a cervical spine fracture and 2.4 times more likely to have a spinal cord injury than those drivers who used airbags and seatbelts. Front-seat passengers had even more significant results: The passengers with airbags alone and no seatbelt restraint were 6.7 times more likely to sustain a fracture with spinal cord injury than those passengers who were protected with an airbag and seatbelt.

“What prompted us to do the study was the number of injuries we were seeing in the UPMC orthopaedic spine clinic that we attributed to potentially out-of-position and unrestrained victims of motor vehicle crashes in which airbag deployment may have caused spinal injury,” said Dr. Donaldson. “This concerns us because 25 percent of Pennsylvania drivers still do not wear seatbelts regularly.”

Although airbags are credited with saving thousands of lives and preventing thousands of serious injuries each year, the safety of airbags revolves around proper use, according to Dr. Donaldson. “Hundreds of cases of serious injury and deaths have occurred when car occupants were unrestrained and in an unplanned position or were too close to the airbag when it deployed during a crash,” he said. The airbag deploys at about 140 to 220 miles per hour and rapidly deflates.

“It is critical to understand that if you are in the front of a car with an airbag, you need to be wearing your seatbelt and you need to maintain 10 inches between the airbag and your sternum,” Dr. Donaldson stressed. Although children were not included in the study, Dr. Donaldson emphasized with particular concern that children under 12 should never sit in the front seat.

Of the 86,000 patients studied, 12,678 had spinal injuries. Of those, 5,506 had cervical spine injuries, 203 were using both airbags and seatbelts, 187 used the airbag only, 1,658 used a seatbelt only and 3,458 were unprotected. The drivers who were unbelted with no airbag were 1.3 times more likely to have a cervical spine fracture and 1.8 times more likely to sustain a cervical spine fracture with a spinal cord injury than those drivers who were protected by both an airbag and seatbelt. As for the passengers who were unbelted with no airbag, they were 7.9 times more likely to have a fracture with spinal cord injury compared to those passengers with airbags and seatbelts.

“Fortunately, new airbag technology that will improve various aspects of the effectiveness and safety of the airbags is on the horizon, but even new technological advances cannot replace common sense – a person needs to buckle their seatbelt,” said Dr. Donaldson.

Dr. Donaldson was invited to present the study at the annual meeting of the International Society for the Study of the Lumbar Spine in Porto, Portugal in June 2004. The study also was named best clinical paper at the Cervical Spine Research Society’s annual meeting in December 2003. Molly Vogt, Ph.D., and Steve Hanks, M.D., were co-authors of the study.

Associate Professor Receives $260,000 NSF Grant

Ian Nettleship, associate professor in the Department of Materials Science and Engineering and member of the McGowan Institute of Regenerative Medicine, has been awarded a $260,000 grant by the National Science Foundation to produce unique, highly oriented porous ceramics aimed at tissue engineering applications including bioreactors and scaffolds as well as environmental applications such as filters and catalyst carriers.

The principles used in the directional solidification of eutectic metal alloys are being used to control the solidification of ice through aqueous sols containing ceramic nanoparticles. The pore structure is then achieved by freeze drying and sintering the structure.

Visit Nettleship’s Web site:

Research could help predict prostate cancer risk, progress

According to a study published in the July 15 issue of the Journal of Clinical Oncology, genes expressed in benign tissue adjacent to prostate cancer tissue are much more similar to those expressed in prostate cancer tissue than previously thought. This finding, the first of its kind, may help predict populations both at risk for prostate cancer and for disease progression based on gene expression patterns, say researchers at the University of Pittsburgh.

“It is not clear what molecular events are responsible for the progression of prostate cancer to a lethal form of the disease,” said Jian-Hua Luo, M.D., Ph.D., senior author of the study and assistant professor, department of pathology, University of Pittsburgh School of Medicine. “But by exploring the biology of prostate cancer through the identification of genes and patterns of gene expression, we can more precisely understand what genetic changes cause the disease to progress and develop therapeutic targets to prevent its progression at an earlier stage.”

In the study, Dr. Luo, also director of the gene array laboratory at the University of Pittsburgh, and colleagues used high throughput quantitative analysis to genetically profile prostate cancer tissue and noncancerous prostate tissue samples. They analyzed 152 human tissue samples including 66 samples of prostate cancer tissue, 60 samples of benign prostate tissue adjacent to the tumor, 23 samples of donor prostate tissue free of genitourinary disease and three prostate cancer cell lines. Through the analysis, the researchers identified a set of 671 genes whose expression levels were significantly altered in prostate cancer tissue compared to disease-free tissue and found that patterns of gene expression in benign adjacent prostate tissue were much more similar to prostate cancer tissue than to disease-free tissue.

According to Dr. Luo, the gene expression patterns of benign adjacent tissue were significantly overlapped with those of prostate cancer and distinctly different than the disease-free tissue. Furthermore, the adjacent tissue was so genetically altered that it resembled a cancer field effect, undergoing genetic changes similar to prostate cancer, even though it was morphologically benign tissue.

“It appears that genetic alterations in the prostate occur in parts of the gland that otherwise look benign,” said Joel Nelson, M.D., professor and chairman, department of urology, University of Pittsburgh and co-author of the study. “We have long suspected a so-called field change in the prostate gland containing cancer, meaning some alteration has occurred throughout the prostate tissue. This study lends support for such a hypothesis.”

The researchers also created a gene model using GeneSpringTM software to predict the aggressiveness of the disease and found that the expression profile model was more than 80 percent accurate in predicting the aggressiveness of the disease.

“Since only a fraction of prostate cancers are metastatic, identifying variables that predict the behavior of a prostate cancer tumor based on gene expression patterns should prove important in clinical management of the disease,” said Dr. Luo. “The results of this study are a first step in that direction.”

Prostate cancer is second only to skin cancer as the most commonly diagnosed malignancy in American men. One man in six will be diagnosed with the disease during his lifetime and approximately 30,000 men die from prostate cancer annually.

The study was supported in part by two grants from the National Cancer Institute. Co-authors include Douglas Landsittel, Ph.D., with the biostatistics center, University of Pittsburgh Cancer Institute and department of biostatistics, University of Pittsburgh; Dr. Joel Nelson; and Yan Ping Yu, M.D., Ling Jing, M.D., Ph.D., Baoguo Ren, M.D., Lijun Liu, M.D., Courtney McDonald, B.S., Ryan Thomas, B.S., Rajiv Dhir, M.D., Sydney Finkelstein, M.D., George Michalopoulos, M.D., Ph.D., and Michael Becich, M.D., Ph.D., with the department of pathology, University of Pittsburgh School of Medicine.

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