August 2007 | VOL. 6, NO. 8 | www.McGowan.pitt.edu

The McGowan Institute was honored by the Ladies Hospital Aid Society (LHAS) when the Institute was selected as the principal beneficiary of the LHAS 2007 annual black-tie gala. This year's gala, "Music, Magic and Moonlight," took place on Saturday, August, 25, 2007 at the Omni William Penn Hotel. Known throughout the area as one of the premier social events of the year, the gala was also a fundraiser on behalf of McGowan Institute. Dr. Alan Russell was presented with a check from the LHAS in the amount of $100,000 to further the programs of the Institute.

The LHAS is well-known for their altruistic efforts to support and perpetuate vital healthcare and healthcare research. The LHAS began in 1898 when 17 women banded together to establish a much needed hospital. Through those early volunteer efforts, $25,000 was raised, and Montefiore Hospital was founded.

The McGowan Institute is grateful to today's counterparts of those original members for their efforts to promote and support the field of regenerative medicine. Thank you LHAS for your vision, dedication, generosity and leadership. The scientists, engineers, and clinicians thank you for joining the McGowan team that offers the promise of a radically different paradigm to treat a growing list of injuries and diseases. The patients that regenerative medicine therapies assist--and will assist in the future--also thank you.

The McGowan Institute welcomes Prashant Kumta, PhD, as the new Edward R. Weidlein Chair in the University of Pittsburgh's School of Engineering. Dr. Kumta, a current McGowan faculty member, is making the transition from Carnegie Mellon University to Pitt and will have appointments in mechanical engineering and materials science, bioengineering, and chemical and petroleum engineering.

Dr. Kumta obtained his Bachelor of Technology in Metallurgical Engineering from the Indian Institute of Technology in Bombay, India. He earned his M.S. and Ph.D. from the Department of Materials Science and Engineering at the University of Arizona. Dr. Kumta is the author and co-author of more than 125 refereed publications and has given more than 160 conference presentations. He was also the recipient of the Research Initiation Award from the National Science Foundation in 1993 and has been continuously listed in Who's Who in Science and Engineering, Who's Who in America, Who's Who in the World and Who's Who in American Education since 1999. He was a founding organizer of the Annual Meeting of the American Ceramics Society and remains actively involved. Dr. Kumta holds six patents, and is the current U.S. Editor-in-Chief of Materials Science and Engineering, B, Solid-State Materials for Advanced Technology, an International Journal by Elsevier Publications.

Dr. Kumta's research interests are in ceramics as applied to biomaterials and energy storage. The main focus of research in both these areas is to develop novel low temperature approaches and study the relationships of the process parameters, the ensuing microstructure and crystallographic structure, to the electrochemical activity in the former and biological response in the latter. Another important aspect of the biomaterials research program is to study the role of bio-ceramics and genetically engineered proteins for engineering and design of new biomaterial interfaces and morphologies used to investigate stem cell plasticity.

The National Multiple Sclerosis Society recognizes, on an annual basis, the outstanding design innovations of individuals and organizations aimed at helping the disabled overcome barriers and further empower all people. Rory Cooper, PhD, director of the University of Pittsburgh Human Engineering Research Laboratories and professor at the School of Health and Rehabilitation Sciences, has been selected to receive the 2007 da Vinci Lifetime Achievement Award from the National Multiple Sclerosis Society Michigan Chapter. This prestigious honor recognizes a lifetime of significant contributions to advancing accessibility. Dr. Cooper will be honored Friday, September 28, 2007, at the da Vinci Awards black-tie gala at the Ritz Carlton in Dearborn, Michigan.

The da Vinci Awards honor outstanding engineering achievements relative to design that exceed the legally mandated requirements, such as those contained in the Americans with Disabilities Act. This recognition drives the marketplace to stimulate development of further creative advances, eventually enabling everyone to participate and contribute to make a better society.

In the late 1970s, Dr. Cooper qualified to represent the U.S. Army during the Olympic trials. His dream was tragically cut short when he was involved in a serious bicycle accident that left him paralyzed. After his spinal cord injury, Dr. Cooper went on to earn an undergraduate, masters, and ultimately a doctoral degree in engineering. His interest and devotion to the field of rehabilitation engineering and assistive technology is renowned.

Dr. Cooper also recently served as emcee of the Pennsylvania Disabled Veterans Rehabilitation Vocational Retraining Project: Community Response Symposium II, in Johnstown, PA, which took place in July. Dr. Cooper wanted to be involved in this project because of the need for local involvement to ensure that returning veterans have the support and resources needed to return to full participation in their communities.

Congratulations, Dr. Cooper! Read More

The results of a study published by John A. Kellum, MD, Michael P. Pinsky, MD, Russell L. Delude, PhD, Derek C. Angus, MD, MPH, and others from the University of Pittsburgh School of Medicine in the August 13/27 issue of the Archives of Internal Medicine indicates that past interpretations of how the immune system responds to infection – interpretations on which many experimental treatments were based – were incorrect.

Sepsis is the 10th leading cause of death in the United States. While incidence rates of sepsis have been steadily increasing over the years, little is known about the condition. Past investigational treatments have been based on data from small studies, and most of these therapies have failed.

This first large-scale natural history study of sepsis found that not all patients with sepsis mount the same immune response, even when they look the same clinically. The study tracked 1886 patients with community-acquired pneumonia presenting at 28 US hospital emergency departments. The pneumonia led to severe sepsis in 583 patients; 149 of these patients died.

The researchers believe that these treatments failed, at least in part, because of insufficient data to fully understand the complexity and variability of the inflammatory response to sepsis. To gain a better understanding into the mechanisms behind the condition, the researchers conducted the Genetic and Inflammatory Markers of Sepsis study (GenIMS), which collected extensive clinical and laboratory data geared to help analyze the risks of a person developing sepsis and dying.

"With sepsis, we're dealing with one of the deadliest diseases, yet we know so little about the condition. The situation is similar to what this country experienced over 50 years ago with heart disease and stroke – we knew that too many people were dying of cardiovascular disease, but we didn't know enough about the disease to effectively treat and prevent it," said Dr. Angus, professor and vice chair of research, department of critical care medicine, University of Pittsburgh School of Medicine. "In response, the National Institutes of Health embarked on the Framingham Heart Study, the results of which have influenced everything we know about the prevention and treatment of cardiovascular disease. With our study, we're hoping to do the same for sepsis, providing a greater understanding of the disease on which future treatment and prevention strategies can be based." Read More

Dennis McNamara, MD, professor of medicine and director of Heart Failure Transplantation at the University of Pittsburgh Medical Center, is a member of a research team recently funded by the National Institutes of Mental Health to develop a novel intervention strategy for simultaneously treating congestive heart failure and major depression. The NIMH awarded $500,000 for the 3-year study to Dr. McNamara and his team to obtain the necessary feasibility and clinical data required to plan a large-scale trial.

Depression is present in approximately 20 to 50% of heart failure patients and is linked strongly to increased morbidity and mortality and reduced quality of life. However, although UPMC and several other integrated health care delivery systems in the US have implemented outpatient care programs for heart failure, none routinely screen for and treat depression.

The study of the connections between mental health and cardiovascular disease have been previously studied by McNamara's co-investigators, Bruce L. Rollman, MD, MPH and Charles F. Reynolds III, MD, in an NIH-funded clinical trial entitled Bypassing the Blues. The aim of Bypassing the Blues was to examine the impact of treating depressive symptoms following coronary artery bypass graft (CABG) surgery.

The research team will modify the Bypassing the Blues strategy for treating post-coronary artery bypass graft surgery depression. They will employ the UPMC outpatient guidelines for treating heart failure and then pilot their "blended" treatment strategy for treating depressed heart failure patients. They will recruit approximately 500 patients admitted for an acute episode of heart failure from several UPMC hospitals, and then conduct follow-up telephone assessments at 1, 3, and 6 months to estimate suitably sensitive and specific cut-off scores for treating depression by gender and severity of heart failure.

"Cardiologists can help their patients if they are provided with the knowledge of depression's devastating effects on heart disease. Early studies have demonstrated that if patients are treated for depression after heart surgery or any invasive heart procedure, they are more likely to stick to their scheduled treatments and have a better, more positive outlook toward recovery," says Dr. McNamara. Read More

"Door-to-balloon" time is a phrase commonly used in hospitals to describe the amount of time it takes doctors to perform a procedure called angioplasty on emergency room patients. The ER goal is within 90 minutes of arrival—a time that cuts the risk of dying by about 40%. It's also a quality-ranking factor for hospitals nationwide.

"We took a look at ourselves and said this is really taking too long," said Dr. Joon Sup Lee, clinical director of the Cardiovascular Institute at the University of Pittsburgh Medical Center and McGowan faculty member. "We found that unacceptable.";

In the past year, UPMC Presbyterian has cut its door-to-balloon time from 110 minutes to 73 minutes. Among other things, the Oakland hospital has achieved this by evaluating all potential victims of a heart attack within 5 minutes of their arrival and by allowing ER doctors to make key decisions instead of consulting with cardiologists.

A study published in the November issue of the New England Journal of Medicine explained that angioplasties can be done quickly if several guidelines are followed, including having paramedics perform an electrocardiogram en route to the hospital.

Already several emergency medical service organizations have the EKG machines in their vehicles, and that has greatly contributed to decreasing the door-to-balloon time, Lee said.

"Ideally, if you get an EKG before the patient comes in, you've already pre-identified that patient as someone that needs rapid transit through the system," he said. Read More

Johnathan and Ali are recovering and doing well today following their late June liver transplants—Children's Hospital of Pittsburgh's first-ever domino liver transplant involving a pediatric recipient. The transplants were led by surgeon George V. Mazariegos, MD, director of Pediatric Transplantation at Children's Hillman Center for Pediatric Transplantation as well as a McGowan faculty member.

Domino transplants are so named for the sequential nature of the transplants—an organ from a deceased donor is transplanted into the first recipient. The first recipient's organ is then transplanted into a second recipient. Last year, Children's surgeons were involved in a domino transplant involving two adult recipients.

Johnathan Devantier, 9, of St. Louis, MO, was diagnosed as a newborn with maple syrup urine disease (MSUD), in which the body is unable to process certain amino acids. He received a donor liver, and his former liver was transplanted into Ali Al-Garni, 24, of Saudi Arabia, who suffers from a genetic disease that can cause liver failure.

Devantier's MSUD was not passed to Al-Garni in the surgery, said Dr. Mazariegos. The disease does not originate in the liver, but instead is caused by a lack of enzymes in the body, making a domino transplant possible, he said.

"Domino transplants are rare because there are very few conditions for which you can cure one patient with a transplant and then transplant his or her organ into someone else without passing on the disease. MSUD is one such disease," Mazariegos said. "Children's Hospital is uniquely poised to begin offering domino transplants as an option to more and more families."

And this option—to take and give as well—is something that one mother is very grateful for.

"As a mother, that is the best option possible," Dana Devantier, Johnathan's mom, told the Pittsburgh Tribune-Review. "Not only did someone else's gift save Johnathan, but he was able to save another person." Read More

The colorful pigment found in raspberries, strawberries, grapes, and cherries may offer significant protection against cancer in general and may also aid in treating tumors. According to research published in the Journal of Biological Chemistry, the pigmentation chemical that makes grapes and wines red has been found to kill human leukemia and lymphoma cells cultured in a lab. These results must be confirmed in further animal and human studies.

Xiao-Ming Yin, MD, PhD, of McGowan Institute, who is also an associate professor in the University of Pittsburgh's department of pathology, a member of the Comprehensive Cancer Center and a member of the Biomedical Graduate Program reported that black raspberry extract killed leukemia cells in cultures while sparing healthy cells. Dr. Yin is also the associate director, division of molecular diagnostics in the department of pathology at Presbyterian-Shadyside Hospital.

"Current treatments for leukemia, such as chemotherapy and radiation, often damage healthy cells and tissues and can produce unwanted side effects for many years afterward," said study coauthor Dr. Yin. "So, there is an intensive search for more targeted therapies for leukemia worldwide."

Yin's team found that C-3-R (cyanidin-3-rutinoside (C-3-R)—a water-soluble flavonoid that provides color to flowers, leaves, fruits, and vegetables) caused the cells to produce peroxides, a type of free radical that, in turn, activated a pathway within the cancer cells that caused them to die. In contrast, when the researchers treated normal human blood cells with C-3-R, they did not find any increased accumulation of free radicals and there were no apparent toxic effects on these cells. Read More

The McGowan high school intern programs concluded in August with two significant presentation events. Kim Autore, the Wiegand intern at McGowan Institute, gave a PowerPoint presentation at a luncheon on August 2, 2007. Special guests were Barbara Wiegand, the sponsor of the program, and past Wiegand interns Dave Willis, currently employed at PPG, and Rachael Werner, an undergraduate at Washington and Jefferson. In her presentation, Autore outlined the highlights of what she learned at the various labs she came in contact with during the summer. Autore will be a freshman at Pitt this fall.

The PTEI interns, Usman Chatta, Nisha Maharaja, and Marvin Porter took part in the PTEI Undergraduate Scientific Poster Session held at the Sheraton Station Square on August 8, 2007. They each wrote abstracts that summarized their 4 week experience as well as designed posters for display. The PTEI Poster Session featured approximately 120 presenters and guests including special guest speakers Priya Ramaswami, a doctoral candidate from McGowan, Thomas Walters, PhD from the U.S. Army Institute of Surgical Research, and Steve Abramowitch, PhD. from the University of Pittsburgh's Musculoskeletal Research Center.

On June 25, 2007, Dr. Brack Hattler dipped the rear wheel of his bike into Puget Sound in Seattle, WA, and began a 3,300-mile trek across America to raise funds and awareness for the American Lung Association’s critical research, education, and advocacy programs. The final destination was the nation’s capital in Washington, D.C. Dr. Hattler traveled with a group of cyclists composed of almost 40 riders between the ages of 18-70.

During his journey, he wrote a blog which was shared on the McGowan website. If you haven’t been keeping up with the blog, you still have time to read what was so eloquently communicated by Dr. Hattler, his wife, and his son (for part of the ride), as they made their way across the country. Even when his ride ended unexpectedly due to an accident, other riders carried on his presence—several of his cycling colleagues wore Dr. Hattler’s McGowan Institute bicycle shirts for the rest of the journey.

The 2007 Big Ride Across America is a fund raising event. Supporters whose pledges benefited the vital programs and research of the American Lung Association sponsored each rider. The total money raised through pledges to all participants was $354,458.12. And, Dr. Hattler was this year’s #1 fundraiser with pledges in the amount of $28,750!!!

In a reflective manner, Dr. Hattler ended his experience and conversation with readers so very meaningfully:

Some final thoughts about the ride now that I have had some time to recover and reflect: I am convinced more than ever that to see the greatness of this country one must travel at slow motion. To understand its form one must view it from horizon to horizon. To experience its mood one must see it in all its manifestations, from sunrise to sunset, in strong winds and gentle rain, in storm and in soothing breezes, a grandeur that is as varied as the people who inhabit it. The ride, even shortened as it was, was well worth taking.

Thank you, Dr. Hattler! Read More

The Regenerative Medicine Podcasts continue to gain loyal listeners. There have been over 25,000 downloads to date. The most recent podcasts are:

#37 – George Christ, PhD - Wake Forest Institute for Regenerative Medicine
Dr. Christ’s research interests are in the area of functional genomics, that is, establishing a verifiable link between changes in gene expression and alterations in cell/organ/tissue function and dysfunction.  This information is then used to improve the understanding, diagnosis and treatment of smooth muscle diseases and disorders.  To hear more, please visit: http://www.regenerativemedicinetoday.com/cblog/index.php

Other recent podcasts: #36-Milica Radisic, PhD, University of Toronto and #35-Alejandro Nieponice, PhD, McGowan Institute and Austral University Hospital in Buenos Aires, Argentina.

Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.

Authors:	Kim GG, Donnenberg VS, Donnenberg AD, Gooding W, Whiteside TL
Title:	A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: Comparisons to a 4 h (51)Cr-release assay.
Summary:	Natural killer (NK) cell-or T cell-mediated cytotoxicity traditionally is measured in 4-16 h (51)Cr-release assays (CRA). A new four-color flow cytometry-based cytotoxicity assay (FCC) was developed to simultaneously measure NK cell cytotoxicity and NK cell phenotype (CD3(-)CD16(+)CD56(+)). Target cells, K562 or Daudi, were labeled with Cell Tracker Orange (CTO) prior to the addition of effector cells. Following co-incubation, 7 amino-actinomycin D (7-AAD) was added to measure death of target cells. The phenotype of effectors, viability of targets, the formation of tumor-effector cell conjugates and absolute numbers of all cells were measured based on light scatter (FSC/SSC), double discrimination of the fluorescence peak integral and height, and fluorescence intensity. Kinetic studies (0.5 and 1 to 4 h) at different effector to target (E:T) cell ratios (50, 25, 12, and 6) confirmed that the 3 h incubation was optimal. The FCC assay is more sensitive than the CRA, has a coefficient of variation (CV) 8-13% and reliably measures NK cell-or lymphokine-activated killer (LAK) cell-mediated killing of target cells in normal controls and subjects with cancer. The FCC assay can be used to study a range of phenotypic attributes, in addition to lytic activity of various subsets of effector cells, without radioactive tracers and thus, it is relatively inexpensive. The FCC assay has a potential for providing information about molecular interactions underlying target cell lysis and thus becoming a major tool for studies of disease pathogenesis as well as development of novel immune therapies.
Source:	J Immunol Methods. 2007 Aug 31;325(1-2):51-66

 

PIs:	Kacey G. Marra, PhD
Co-PIs:	Douglas Weber, PhD
Title:	Surface Modified Polymer Conduits for Peripheral Nerve Repair
Description:	The project seeks to increase the understanding of the effects of biomaterial surface properties on nerve regeneration, and also to enhance the integrated research and education activities of graduate, undergraduate and pre-college students.  The plan includes outreach programs and innovative research in the exciting areas of biomaterials and tissue engineering.  Specifically, the research plan is focused on developing biodegradable conduits with modified inner luminal surfaces that enhance peripheral nerve repair over long gaps, and the educational plan is focused on enhancing and maintaining the involvement of women and underrepresented minorities in engineering.
Source:	NSF-Biomaterials Program-Division of Materials Research
Term:	3 years
Amount:	$300,000

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