WILKES-BARRE – The Commonwealth Medical College will hold a local open house for prospective students on Monday, as the nation’s newest medical school gears up for the 2010-11 academic year.
Debra Stalk, director of admissions, said 2,734 applications had been received as of this week, more than twice the number that applied for the inaugural class that began its studies in September.
The application deadline is Dec. 15 and Stalk expects about another 1,000 applicants. Last year, 1,291 applications were received and the school accepted 60 students into its doctor of medicine program. It will accept the same number this time.
The school has changed its one-year Master’s of Biomedical Sciences requirements and expanded the class. The 13 students accepted for the 2009-10 academic year were required to pursue a career in medicine for acceptance. That could have been in dentistry, nursing, pharmacy or another medical field. This year, 30 to 40 students will be accepted, but they’ll have to be working toward becoming physicians.
The open house will take place from 4 to 7 p.m. on Monday at the Best Western Genetti Hotel, 77 East Market Street. It is open to prospective students, parents of prospective students and community members interested in learning more about the new school and its mission. Reservations are not required.
Clinical faculty and representatives of the school’s admissions, financial aid and student affairs offices will be on hand to discuss the programs and eligibility and admission requirements.
In addition to grades and MCAT score, a student’s geography will play a role in acceptance.
The school set a goal of 70 percent of its student body coming from Pennsylvania and a share of them from Northeast and Central Pennsylvania. Scranton-based TCMC has satellite campuses in Wilkes-Barre and Williamsport,
Stalk said about one-fifth of applicants for the second class are from Pennsylvania. In the inaugural class, 70 percent of the students were from Pennsylvania with 18 hailing from the region between Williamsport and the Poconos.
Dr. Robert D’Alessandri, the school’s dean and president, said students from all 50 states have applied for admission and now that the school is established, its name is being circulated at undergraduate schools across the country.
“Things have gone so well, it’s a little scary,” D’Alessandri said.
He pinned the low number of applicants last year on the fact half the application period occurred before the school received its national accreditation and because it wasn’t a known entity.
“We were a new school. People didn’t know about us,” D’Alessandri said. The number of applicants this year proves that’s changed.”
Source
Monday, December 28, 2009
Tuesday, December 15, 2009
Med school making dreams real
WILKES-BARRE – As a married mother of seven, Diana Freyberger had very few options if she wanted to attend medical school. The nurse at Berwick Hospital has wanted to be a doctor for 20 years, but home and work duties, coupled with no medical college within driving distance, made that option hard.
But with this year’s opening of The Commonwealth Medical College, with its main campus in Scranton and satellite branches in Williamsport and Wilkes-Barre, the Nescopeck woman’s longtime dream has become more realistic.
“I’m really happy they’re within driving distance,” said Freyberger, 47.
She was one of a handful of perspective students stopping by the Grand Ballroom at the Best Western Genetti Hotel & Conference Center on Monday for an open house and information session for the new college.
College officials, including those specializing in admissions, were on hand to answer questions, offer advice and provide materials about the school.
Though fewer than 10 people showed up during the three-hour session, those who did said it was worth their while and they hope to be students as early as 2011. The deadline for the fall 2010 academic year is Dec. 15 and the college has already received more than 2,700 applications to fill 60 spots. Last year, 1,291 applications were received.
Dr. Robert D’Alessandri, the school’s dean and president, said students from all 50 states have applied for admission, and now that the school is established, its name is being circulated at undergraduate schools across the country.
Amy Blackwell, 37, of Kingston, said the 2011 incoming class is her goal, and with the coursework she still needs to complete to get her master’s degree at Saint Joseph College in West Hartford, Conn., plus having to take the MCAT exams, that’s feasible.
The Wyoming Valley West High School and King’s College graduate said that when she first heard a medical school was proposed for Northeastern Pennsylvania “I thought, ‘Oh my God, I hope this happens.’ ” She said she’s been keeping an eye on the school’s progression from concept to reality and she believes it will keep a lot of local students in the region instead of heading to medical school hours or time zones away.
Freyberger said she appreciates that the medical school realizes there are a lot of non-traditional students in the region looking for a place close to home where they can further their education.
She said the Penn State College of Medicine in Hershey was the closest option for her, but the commute was too much and she is unable to move. The proximity of The Commonwealth Medical College spurred her to inquire about the program. She also knows admission will be very competitive and there are no guarantees she will be accepted.
Source
But with this year’s opening of The Commonwealth Medical College, with its main campus in Scranton and satellite branches in Williamsport and Wilkes-Barre, the Nescopeck woman’s longtime dream has become more realistic.
“I’m really happy they’re within driving distance,” said Freyberger, 47.
She was one of a handful of perspective students stopping by the Grand Ballroom at the Best Western Genetti Hotel & Conference Center on Monday for an open house and information session for the new college.
College officials, including those specializing in admissions, were on hand to answer questions, offer advice and provide materials about the school.
Though fewer than 10 people showed up during the three-hour session, those who did said it was worth their while and they hope to be students as early as 2011. The deadline for the fall 2010 academic year is Dec. 15 and the college has already received more than 2,700 applications to fill 60 spots. Last year, 1,291 applications were received.
Dr. Robert D’Alessandri, the school’s dean and president, said students from all 50 states have applied for admission, and now that the school is established, its name is being circulated at undergraduate schools across the country.
Amy Blackwell, 37, of Kingston, said the 2011 incoming class is her goal, and with the coursework she still needs to complete to get her master’s degree at Saint Joseph College in West Hartford, Conn., plus having to take the MCAT exams, that’s feasible.
The Wyoming Valley West High School and King’s College graduate said that when she first heard a medical school was proposed for Northeastern Pennsylvania “I thought, ‘Oh my God, I hope this happens.’ ” She said she’s been keeping an eye on the school’s progression from concept to reality and she believes it will keep a lot of local students in the region instead of heading to medical school hours or time zones away.
Freyberger said she appreciates that the medical school realizes there are a lot of non-traditional students in the region looking for a place close to home where they can further their education.
She said the Penn State College of Medicine in Hershey was the closest option for her, but the commute was too much and she is unable to move. The proximity of The Commonwealth Medical College spurred her to inquire about the program. She also knows admission will be very competitive and there are no guarantees she will be accepted.
Source
Monday, October 12, 2009
Penn study: EHR's can be used to test efficacy of treatments
PHILADELPHIA, PA -- For years controversy has surrounded whether electronic medical records (EMR) would lead to increased patient safety, cut medical errors, and reduce healthcare costs. Now, researchers at the University of Pennsylvania School of Medicine have discovered a way to get another bonus from the implementation of electronic medical records: testing the efficacy of treatments for disease.
In the first study of its kind, Richard Tannen, M.D., Professor of Medicine at the University of Pennsylvania School of Medicine, led a team of researchers to find out if patient data, as captured by EMR databases, could be used to obtain vital information as effectively as randomized clinical trials, when evaluating drug therapies. The study appeared online last week in the British Medical Journal.
"Our findings show that if you do studies using EMR databases and you conduct analyses using new biostatistical methods we developed, we get results that are valid," Tannen says. "That's the real message of our paper -- this can work."
In January 2009, President Barack Obama unveiled plans to implement electronic medical records nationwide within five years, arguing that such a plan was crucial in the fight against rising health care costs. Of the nearly $900 billion in Obama's planned stimulus package currently before the United States Senate, $20 billion is proposed for electronic health records.
Tannen says he and his group recognized that the large EMR databases containing compiled medical information could potentially give researchers the ability to study groups reflective of the total population, not just those who participate in clinical trials, and circumvent studies too costly or unethical for clinical trials. However, such databases contain observational information, which critics argue do not offer the same level of control as randomized trials.
"Our study cautiously, yet strongly, suggests that enormous amounts of information within electronic medical records can be used to expand evidence of how we should or shouldn't manage healthcare,"
Source
In the first study of its kind, Richard Tannen, M.D., Professor of Medicine at the University of Pennsylvania School of Medicine, led a team of researchers to find out if patient data, as captured by EMR databases, could be used to obtain vital information as effectively as randomized clinical trials, when evaluating drug therapies. The study appeared online last week in the British Medical Journal.
"Our findings show that if you do studies using EMR databases and you conduct analyses using new biostatistical methods we developed, we get results that are valid," Tannen says. "That's the real message of our paper -- this can work."
In January 2009, President Barack Obama unveiled plans to implement electronic medical records nationwide within five years, arguing that such a plan was crucial in the fight against rising health care costs. Of the nearly $900 billion in Obama's planned stimulus package currently before the United States Senate, $20 billion is proposed for electronic health records.
Tannen says he and his group recognized that the large EMR databases containing compiled medical information could potentially give researchers the ability to study groups reflective of the total population, not just those who participate in clinical trials, and circumvent studies too costly or unethical for clinical trials. However, such databases contain observational information, which critics argue do not offer the same level of control as randomized trials.
"Our study cautiously, yet strongly, suggests that enormous amounts of information within electronic medical records can be used to expand evidence of how we should or shouldn't manage healthcare,"
Source
Monday, September 28, 2009
Best medical schools in the nation
The best medical schools for research are dominated by private and pricey institutions. The top four, in descending order are Harvard, Johns Hopkins, University of Pennsylvania, and Washington University in St. Louis. The fifth place, however, goes to a public institution in California, according to US News and World Report.
The University of California – San Francisco, School of Medicine (5th) is the top rated California program from research and primary care. The UCSF Medical Center also has been named one of the top 10 hospitals in the country, and it is also the best hospital in the Bay Area.
Stanford School of Medicine (6th) aims to identify candidates who are committed to serving the needs of all members of society and whose accomplishments reveal originality and a capacity for independent, critical thinking. Our students are best characterized by a strong desire to develop into exceptional clinicians and innovators in the biomedical sciences and public health.
The David Geffen School of Medicine at UCLA (tied 11) has more than 2,000 full-time faculty members, almost 1,300 residents, more than 750 medical students and almost 400 Ph.D. candidates. The medical school is also ranked ninth in the country in research funding from the National Institutes of Health and third in the United States in research dollars from all sources.
UCSD’s School of Medicine (tied15) and its Division of Medical Education help aspiring and current physicians in their quest for life long learning. Its aim is to train physicians to give state of the art, scientifically astute, and compassionate care to patients. The 120 members of the Division work with the faculty of the School of Medicine to encourage intelligent and humanistic individuals to pursue medicine as a career and to, in practice, fulfill their potential to develop, deliver, and assess the curricular materials needed for them to learn the science of medicine as well as the art.
Source
The University of California – San Francisco, School of Medicine (5th) is the top rated California program from research and primary care. The UCSF Medical Center also has been named one of the top 10 hospitals in the country, and it is also the best hospital in the Bay Area.
Stanford School of Medicine (6th) aims to identify candidates who are committed to serving the needs of all members of society and whose accomplishments reveal originality and a capacity for independent, critical thinking. Our students are best characterized by a strong desire to develop into exceptional clinicians and innovators in the biomedical sciences and public health.
The David Geffen School of Medicine at UCLA (tied 11) has more than 2,000 full-time faculty members, almost 1,300 residents, more than 750 medical students and almost 400 Ph.D. candidates. The medical school is also ranked ninth in the country in research funding from the National Institutes of Health and third in the United States in research dollars from all sources.
UCSD’s School of Medicine (tied15) and its Division of Medical Education help aspiring and current physicians in their quest for life long learning. Its aim is to train physicians to give state of the art, scientifically astute, and compassionate care to patients. The 120 members of the Division work with the faculty of the School of Medicine to encourage intelligent and humanistic individuals to pursue medicine as a career and to, in practice, fulfill their potential to develop, deliver, and assess the curricular materials needed for them to learn the science of medicine as well as the art.
Source
Monday, September 14, 2009
Docs speak out on health care reform
The health care system in the United States is broken. That much was in agreement among those who spoke at a health care reform meeting hosted by state Rep. Josh Shapiro, D-153, Monday at Holy Redeemer Hospital.
“Clearly we’ve got to address access,” Holy Redeemer Health System President and CEO Mike Laign said. “Everyone should have access” to some measure of health care “so they are not living in fear.”
About 50 physicians, hospital administrators and other health care providers attended the forum aimed at soliciting input for a plan to meet President Obama’s goal of universal access to health care in the country. Shapiro was named last week as one of 32 state legislators nationwide to serve on the White House Team of State Legislators for Health Reform.
The team has been tasked with “helping the president shape the health care debate,” and subsequently to “cheerlead” for passage of a plan, Shapiro told the attendees, adding, “We are in the shaping phase.”
Access and cost are the two main factors, he said, with issues in Pennsylvania, such as not having enough primary care physicians and ob/gyns to treat people, shared by many states. Congressional committees are in the process of drafting legislation and “ideally a package will be ready to vote on in September or October,” Shapiro said.
“The current path — the status quo — in unsustainable,” he said. “The time is right; I need your help.”
Defensive medicine in the form of unnecessary tests, the high cost of medical school, the inflated cost of medical supplies and pharmaceuticals, patient expectations and philosophical issues regarding end of life care were among topics addressed by about 20 who offered comments at the meeting. Many also cautioned about rushing to formulate a plan.
The government “should be taking the time to do it right,” said Dick Jones, CEO of Abington Memorial Hospital.
Hospitals are working to reduce infection rates, unnecessary tests and hospital stays, but “something has to be done about tort reform,” Jones said. “We’re playing our part, but we can’t be totally nailed to the wall on cost,” he added, noting most hospitals make no margin on Medicare.
According to a report released in June by the Pennsylvania Health Care Cost Containment Council, hospitals’ operating margins dropped from 4.82 percent to 3.98 percent in fiscal year 2007-08, and almost a third of 169 that reported data had negative total margins.
Health care reform “is complicated” and “payment is not just the [only] issue,” said Dr. Arnie Cohen, chairman of obstetrics and gynecology at Einstein Hospital.
Patient expectations need to be changed, physicians need to be in charge of treatment and “tort reform belies everything we do in medicine,” Cohen said. “Everything we do every day is based on protecting ourselves.”
“Malpractice reform must be a key element of any reform. We need to resolve conflicts in a different fashion,” Montgomery County Medical Society President Mark Lopatin agreed.
“Patient expectation is huge … that to me is the core of the problem,” he said. Access is not impacted just by a lack of insurance, “there are backups due to unnecessary tests.” Defensive medicine costs about $100 billion a year, he said.
More than 80 percent of health care costs occur in the first and last years of people’s lives, said a doctor who identified himself as a nephrologoist who works at seven hospitals. There is a need to determine how to address “extra care for those who have no chance of survival.”
Source
“Clearly we’ve got to address access,” Holy Redeemer Health System President and CEO Mike Laign said. “Everyone should have access” to some measure of health care “so they are not living in fear.”
About 50 physicians, hospital administrators and other health care providers attended the forum aimed at soliciting input for a plan to meet President Obama’s goal of universal access to health care in the country. Shapiro was named last week as one of 32 state legislators nationwide to serve on the White House Team of State Legislators for Health Reform.
The team has been tasked with “helping the president shape the health care debate,” and subsequently to “cheerlead” for passage of a plan, Shapiro told the attendees, adding, “We are in the shaping phase.”
Access and cost are the two main factors, he said, with issues in Pennsylvania, such as not having enough primary care physicians and ob/gyns to treat people, shared by many states. Congressional committees are in the process of drafting legislation and “ideally a package will be ready to vote on in September or October,” Shapiro said.
“The current path — the status quo — in unsustainable,” he said. “The time is right; I need your help.”
Defensive medicine in the form of unnecessary tests, the high cost of medical school, the inflated cost of medical supplies and pharmaceuticals, patient expectations and philosophical issues regarding end of life care were among topics addressed by about 20 who offered comments at the meeting. Many also cautioned about rushing to formulate a plan.
The government “should be taking the time to do it right,” said Dick Jones, CEO of Abington Memorial Hospital.
Hospitals are working to reduce infection rates, unnecessary tests and hospital stays, but “something has to be done about tort reform,” Jones said. “We’re playing our part, but we can’t be totally nailed to the wall on cost,” he added, noting most hospitals make no margin on Medicare.
According to a report released in June by the Pennsylvania Health Care Cost Containment Council, hospitals’ operating margins dropped from 4.82 percent to 3.98 percent in fiscal year 2007-08, and almost a third of 169 that reported data had negative total margins.
Health care reform “is complicated” and “payment is not just the [only] issue,” said Dr. Arnie Cohen, chairman of obstetrics and gynecology at Einstein Hospital.
Patient expectations need to be changed, physicians need to be in charge of treatment and “tort reform belies everything we do in medicine,” Cohen said. “Everything we do every day is based on protecting ourselves.”
“Malpractice reform must be a key element of any reform. We need to resolve conflicts in a different fashion,” Montgomery County Medical Society President Mark Lopatin agreed.
“Patient expectation is huge … that to me is the core of the problem,” he said. Access is not impacted just by a lack of insurance, “there are backups due to unnecessary tests.” Defensive medicine costs about $100 billion a year, he said.
More than 80 percent of health care costs occur in the first and last years of people’s lives, said a doctor who identified himself as a nephrologoist who works at seven hospitals. There is a need to determine how to address “extra care for those who have no chance of survival.”
Source
Tuesday, September 1, 2009
Remarks of President Barack Obama – As Prepared for Delivery
It’s great to be here in Annandale, and I’m looking forward to answering questions from the folks here with us today as well as the Americans who’ve submitted questions online.
Discuss
COMMENTS (3)
But before I begin, I just want to say a few words about where we are as a nation and where we need to go.
We are living through extraordinary times. This generation of Americans – our generation – has been called to confront challenges of a magnitude unmatched in recent history – challenges that few generations of Americans have ever been asked to confront. In addition to the immediate threats we face – two wars and a deep recession – our economy has also been weakened by the failure to solve problems that have plagued us for decades: the crushing cost of health care, the state of our schools, and our dependence on foreign oil.
Now, I know there are some who say that in tackling all these problems, my administration is taking on too much at once – that we’re moving too fast, too soon.
Well I say that America has waited long enough. It’s not too soon to fix our schools when we’re already behind other nations in graduation rates and achievement. It’s not too soon to wean ourselves off dirty sources of energy when we’ve been talking about our oil dependence since Richard Nixon was president. It’s not too soon to reform our health care system when we’ve been talking about fixing it since Teddy Roosevelt was president.
We are at a defining moment for this nation. If we act now, we can rebuild an economy that is strong, and competitive, and prosperous once more. We can lead this century as we lead the last. But if we don’t act – if we let this moment pass – we could see this economy sputter along for years, if not decades. We could see our children inherit a world that is poorer and more dangerous than the one we found. I know that people say the cost of fixing our problems is great, but I can assure you – we have reached a point where the cost of doing nothing is far greater.
Source
Discuss
COMMENTS (3)
But before I begin, I just want to say a few words about where we are as a nation and where we need to go.
We are living through extraordinary times. This generation of Americans – our generation – has been called to confront challenges of a magnitude unmatched in recent history – challenges that few generations of Americans have ever been asked to confront. In addition to the immediate threats we face – two wars and a deep recession – our economy has also been weakened by the failure to solve problems that have plagued us for decades: the crushing cost of health care, the state of our schools, and our dependence on foreign oil.
Now, I know there are some who say that in tackling all these problems, my administration is taking on too much at once – that we’re moving too fast, too soon.
Well I say that America has waited long enough. It’s not too soon to fix our schools when we’re already behind other nations in graduation rates and achievement. It’s not too soon to wean ourselves off dirty sources of energy when we’ve been talking about our oil dependence since Richard Nixon was president. It’s not too soon to reform our health care system when we’ve been talking about fixing it since Teddy Roosevelt was president.
We are at a defining moment for this nation. If we act now, we can rebuild an economy that is strong, and competitive, and prosperous once more. We can lead this century as we lead the last. But if we don’t act – if we let this moment pass – we could see this economy sputter along for years, if not decades. We could see our children inherit a world that is poorer and more dangerous than the one we found. I know that people say the cost of fixing our problems is great, but I can assure you – we have reached a point where the cost of doing nothing is far greater.
Source
Thursday, August 20, 2009
Metro crash victims 'inseparable' since high school prom
David and Ann Wherley were high school sweethearts who were king and queen of their high school prom in York, Pennsylvania. They were preparing to celebrate their 40th wedding anniversary next month, but their lives were tragically cut short last week in the Metro train crash in Washington.
Retired Maj. Gen. David Wherley Jr. and his wife, Ann, were killed in last week's Metro crash.
1 of 3more photos »
A former commanding general of the District of Columbia National Guard, David Wherley was also the military man who, on September 11, 2001, deployed planes over Washington to protect the White House and take out any aircraft that threatened the Capitol.
"They said, 'Challenge them, try to turn them away; if they don't turn away, use whatever force is necessary to keep them from hitting buildings downtown,' " Wherley told the Washington Post in 2002.
Wherley, a 40-year military veteran, served as the commanding general of the D.C. Guard from 2003 to 2008.
"I am personally grieved by this unbelievable tragedy. David and Ann were two of the best people you could ever want to know. This community will grieve, as will many throughout the country who knew and loved them both," said Maj. Gen. Errol R. Schwartz, who succeeded Wherley when he retired.
The two were among the nine killed June 22 when two trains crashed on the Red Line of Washington's Metro commuter rail. It was the deadliest train crash in the history of the Washington Metropolitan Area Transit Authority.
The Wherleys, both 62, were interred during a ceremony at Arlington National Cemetery on Tuesday.
At one point, fighter jets flew over the cemetery in missing man formation, followed by a traditional three-shot volley, a bugler playing taps and the folding of the American flag, as is tradition, 12 times.
The Wherleys' grown children were presented a flag, as was an elderly couple sitting with them. About 200 people attended the service, including Army Secretary Peter Geren.
Source
Retired Maj. Gen. David Wherley Jr. and his wife, Ann, were killed in last week's Metro crash.
1 of 3more photos »
A former commanding general of the District of Columbia National Guard, David Wherley was also the military man who, on September 11, 2001, deployed planes over Washington to protect the White House and take out any aircraft that threatened the Capitol.
"They said, 'Challenge them, try to turn them away; if they don't turn away, use whatever force is necessary to keep them from hitting buildings downtown,' " Wherley told the Washington Post in 2002.
Wherley, a 40-year military veteran, served as the commanding general of the D.C. Guard from 2003 to 2008.
"I am personally grieved by this unbelievable tragedy. David and Ann were two of the best people you could ever want to know. This community will grieve, as will many throughout the country who knew and loved them both," said Maj. Gen. Errol R. Schwartz, who succeeded Wherley when he retired.
The two were among the nine killed June 22 when two trains crashed on the Red Line of Washington's Metro commuter rail. It was the deadliest train crash in the history of the Washington Metropolitan Area Transit Authority.
The Wherleys, both 62, were interred during a ceremony at Arlington National Cemetery on Tuesday.
At one point, fighter jets flew over the cemetery in missing man formation, followed by a traditional three-shot volley, a bugler playing taps and the folding of the American flag, as is tradition, 12 times.
The Wherleys' grown children were presented a flag, as was an elderly couple sitting with them. About 200 people attended the service, including Army Secretary Peter Geren.
Source
Monday, July 20, 2009
Protein Structures from the Human Immune System’s Oldest Branch Shed Light on a Range of Diseases
PHILADELPHIA – How molecules of the oldest branch of the human immune system have interconnected has remained a mystery. Now, two new structures, both involving a central component of an enzyme important to the complement system of the immune response, reveal how this system fights invading microbes while avoiding problems of the body attacking itself.
The structures may pave the way to more efficient therapeutics for such complement-mediated diseases as age-related macular degeneration, rheumatoid arthritis, or systemic lupus erythematosus, as well as give insight into the pathogenesis of other immune and inflammatory diseases.
The complement system, an evolutionarily old arm of the immune system, comprises a network of proteins that “complement” the work of antibodies in destroying foreign invaders. They serve as a rapid defense mechanism in most species, from primitive sponges to humans. When complement proteins are triggered into action by a microbe, the proteins ultimately form a complex enzyme called C3 convertase, initiating a cascade of immune and inflammatory reactions. In order to avoid self-attack, regulatory proteins such as factor H bind with C3b, a central component of C3, to help the immune system recognize the body’s own tissue and keep complement in check.
Researchers at the University of Pennsylvania School of Medicine, in collaboration with colleagues at Utrecht University in the Netherlands, have determined the structure of C3 convertase and of the C3b fragment in complex with factor H. The work appears this month in two companion papers in Nature Immunology.
“Research on the complement system has waited more than 30 years for these structures," says senior author John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine at Penn.
In the case of the C3 convertase structure, the researchers were able to make crystals by stabilizing the convertase complex with an inhibitor from the Staphylococcus aureus bacteria, called SCIN. SCIN freezes C3 convertase in an inactive state, preventing complement proteins from working further, and in turn, protecting the bacteria from attacking immune cells.
As a central component of C3 convertase, C3b forms an enzyme complex that cleaves its parent molecule C3, which leads to the generation and deposition of more C3b on the bacterial surface. The structure of C3 convertase provides important details about the molecular mechanisms behind these activation and amplification processes. When SCIN is bound to C3 convertase, the enzyme can no longer generate C3b and amplify the complement response, which likely renders the immune system less effective against staphylococcal infections.
“We plan to look for potential drugs that mimic the interaction of SCIN and C3 convertase and inhibit complement without triggering an adverse immune response,” says Lambris. The crystals were therefore examined for critical interaction points between the SCIN inhibitor and C3 convertase.
The second study, describing the structure formed between C3b and factor H, a key regulator of the complement system, is important because of its suspected involvement in a number of immune-related diseases. “It was a surprise to see that the factor H fragment is spread across the entire C3b complex,” notes Lambris.
Factor H binding inhibits C3 convertase activity and prevents the complement response from attacking the host's own cells. “This gives us a structural model for designing new therapies for several immune-mediated diseases,” said Lambris.
Mutations in factor H are associated with age-related macular degeneration, the major cause of blindness in elderly people in the U.S; atypical hemolytic uremic syndrome, a rare but severe kidney disease that causes acute renal failure and high blood pressure; and membranoproliferative glomerulonephritis type II, another rare, progressive renal disorder also known as dense deposit disease.
“We observed that mutations in factor H could weaken its binding activity to C3b, and thus may lead to a loss of regulatory activity in the disease states,” explains Lambris. Correlating disease-related mutations with functional consequences is likely to give insight into the pathogenesis of these and other diseases with immune or inflammatory components.
Current work is focused on designing drugs to counter the effect of SCIN or use it as a template for complement system-targeting therapeutics that target complement-mediated diseases: understanding the implications of the various factor H mutations on diseases, and developing an updated and more dynamic model of complement regulation.
Co-authors in these studies, in addition to Lambris, were Daniel Ricklin, You-Qiang Wu, and Apostolia Tzekou from Penn, who prepared proteins and performed biophysical and biochemical characterization of the complexes, and Piet Gros, Jos van Strijp, Jin Wu, Suzan Rooijakkers, Maartje Ruyken, Robert van Domselaar, Karel Planken, and Bert Janssen from Utrecht who prepared additional proteins, formed the structural crystals, and analyzed the effect of SCIN.
Source
The structures may pave the way to more efficient therapeutics for such complement-mediated diseases as age-related macular degeneration, rheumatoid arthritis, or systemic lupus erythematosus, as well as give insight into the pathogenesis of other immune and inflammatory diseases.
The complement system, an evolutionarily old arm of the immune system, comprises a network of proteins that “complement” the work of antibodies in destroying foreign invaders. They serve as a rapid defense mechanism in most species, from primitive sponges to humans. When complement proteins are triggered into action by a microbe, the proteins ultimately form a complex enzyme called C3 convertase, initiating a cascade of immune and inflammatory reactions. In order to avoid self-attack, regulatory proteins such as factor H bind with C3b, a central component of C3, to help the immune system recognize the body’s own tissue and keep complement in check.
Researchers at the University of Pennsylvania School of Medicine, in collaboration with colleagues at Utrecht University in the Netherlands, have determined the structure of C3 convertase and of the C3b fragment in complex with factor H. The work appears this month in two companion papers in Nature Immunology.
“Research on the complement system has waited more than 30 years for these structures," says senior author John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine at Penn.
In the case of the C3 convertase structure, the researchers were able to make crystals by stabilizing the convertase complex with an inhibitor from the Staphylococcus aureus bacteria, called SCIN. SCIN freezes C3 convertase in an inactive state, preventing complement proteins from working further, and in turn, protecting the bacteria from attacking immune cells.
As a central component of C3 convertase, C3b forms an enzyme complex that cleaves its parent molecule C3, which leads to the generation and deposition of more C3b on the bacterial surface. The structure of C3 convertase provides important details about the molecular mechanisms behind these activation and amplification processes. When SCIN is bound to C3 convertase, the enzyme can no longer generate C3b and amplify the complement response, which likely renders the immune system less effective against staphylococcal infections.
“We plan to look for potential drugs that mimic the interaction of SCIN and C3 convertase and inhibit complement without triggering an adverse immune response,” says Lambris. The crystals were therefore examined for critical interaction points between the SCIN inhibitor and C3 convertase.
The second study, describing the structure formed between C3b and factor H, a key regulator of the complement system, is important because of its suspected involvement in a number of immune-related diseases. “It was a surprise to see that the factor H fragment is spread across the entire C3b complex,” notes Lambris.
Factor H binding inhibits C3 convertase activity and prevents the complement response from attacking the host's own cells. “This gives us a structural model for designing new therapies for several immune-mediated diseases,” said Lambris.
Mutations in factor H are associated with age-related macular degeneration, the major cause of blindness in elderly people in the U.S; atypical hemolytic uremic syndrome, a rare but severe kidney disease that causes acute renal failure and high blood pressure; and membranoproliferative glomerulonephritis type II, another rare, progressive renal disorder also known as dense deposit disease.
“We observed that mutations in factor H could weaken its binding activity to C3b, and thus may lead to a loss of regulatory activity in the disease states,” explains Lambris. Correlating disease-related mutations with functional consequences is likely to give insight into the pathogenesis of these and other diseases with immune or inflammatory components.
Current work is focused on designing drugs to counter the effect of SCIN or use it as a template for complement system-targeting therapeutics that target complement-mediated diseases: understanding the implications of the various factor H mutations on diseases, and developing an updated and more dynamic model of complement regulation.
Co-authors in these studies, in addition to Lambris, were Daniel Ricklin, You-Qiang Wu, and Apostolia Tzekou from Penn, who prepared proteins and performed biophysical and biochemical characterization of the complexes, and Piet Gros, Jos van Strijp, Jin Wu, Suzan Rooijakkers, Maartje Ruyken, Robert van Domselaar, Karel Planken, and Bert Janssen from Utrecht who prepared additional proteins, formed the structural crystals, and analyzed the effect of SCIN.
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Monday, July 6, 2009
Appetite-Stimulating Hormone is First Potential Medical Treatment for Frailty in Older Women
PHILADELPHIA – Older women suffering from clinical frailty stand to benefit from the first potential medical treatment for the condition, according to a study presented last week by Penn Medicine researchers at ENDO, The Endocrine Society’s 91st Annual Meeting. Ghrelin, a hormone that stimulates appetite, was administered to older women diagnosed with frailty, a common geriatric syndrome characterized by unintentional weight loss, weakness, exhaustion and low levels of anabolic hormones which increases risk of falls, hospitalizations, disability, and death. Those who received ghrelin infusions consumed 51 percent more calories than the placebo group, with an increase in carbohydrate and protein intake, not fat. Their growth hormone levels were also higher throughout the ghrelin infusion.
“As Americans are increasingly living into their 80s and 90s, we need to identify ways to prevent or treat common geriatric conditions, such as unexplained weight loss and frailty, which have serious health consequences,” said senior author Anne Cappola, MD, ScM, Assistant Professor of Medicine in Endocrinology, Diabetes, and Metabolism at the University of Pennsylvania School of Medicine. “We’re gaining a better understanding of the hormonal changes that occur as we get older and, with treatments like ghrelin, we can start intervening to prevent some of the common health problems that keep elderly people from living their most productive lives.”
In the pilot study, funded by the National Institutes of Health and Penn’s Institute on Aging, five frail women and five healthy women, all over the age of seventy, were randomized to receive an infusion of the hormone ghrelin or placebo. After a ghrelin transfusion, frail women in the study had a stronger, healthy appetite and increased anabolic hormone activity. The only side effect reported during the treatment was a transient sense of warmth that occurred in four women who received the ghrelin transfusion.
Now that safety and initial efficacy has been proven in this pilot study, larger follow-up studies will look at the potential therapeutic role of ghrelin or ghrelin mimetic agents in the frail population. At this time, these agents are only available for research use and are not yet commercially available.
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“As Americans are increasingly living into their 80s and 90s, we need to identify ways to prevent or treat common geriatric conditions, such as unexplained weight loss and frailty, which have serious health consequences,” said senior author Anne Cappola, MD, ScM, Assistant Professor of Medicine in Endocrinology, Diabetes, and Metabolism at the University of Pennsylvania School of Medicine. “We’re gaining a better understanding of the hormonal changes that occur as we get older and, with treatments like ghrelin, we can start intervening to prevent some of the common health problems that keep elderly people from living their most productive lives.”
In the pilot study, funded by the National Institutes of Health and Penn’s Institute on Aging, five frail women and five healthy women, all over the age of seventy, were randomized to receive an infusion of the hormone ghrelin or placebo. After a ghrelin transfusion, frail women in the study had a stronger, healthy appetite and increased anabolic hormone activity. The only side effect reported during the treatment was a transient sense of warmth that occurred in four women who received the ghrelin transfusion.
Now that safety and initial efficacy has been proven in this pilot study, larger follow-up studies will look at the potential therapeutic role of ghrelin or ghrelin mimetic agents in the frail population. At this time, these agents are only available for research use and are not yet commercially available.
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