WHAT:

Hundreds of University of Chicago Medicine staff, faculty members, students, their family and friends will mobilize across Chicago’s South Side to tackle a host of community projects as part of the 10th annual Day of Service and Reflection (DOSAR). From cleaning and painting community spaces to weeding gardens and stocking food pantry shelves, volunteers will take on tasks large and small at more than 20 sites in the 10 neighborhoods that the medical campus serves. DOSAR has a decade-long legacy of fostering community engagement by bringing together resources to meet the needs of South Side neighborhoods.

WHEN:

8 a.m. to 2 p.m. Saturday, May 12, 2012

WHO:

More than 300 volunteers, including 12 from the United Way of Metropolitan Chicago, are expected to participate in DOSAR. Organizers say DOSAR, the brainchild of First Lady Michelle Obama when she was an executive at the medical center, is one of the campus’ most anticipated annual events. The event attracts increasing number of participants each year, growing from 35 volunteers a decade ago to more than 200 last year.

“The University of Chicago Medicine’s Day of Service and Reflection is a critical event that will make a positive impact in our South Side community,” said Wendy DuBoe, chief executive officer at United Way of Metropolitan Chicago. “United Way is proud to leverage our network of volunteers to participate in this day of service.”

WHY:

Many nonprofit community service providers are facing greater economic challenges than ever before. The need for community cooperation is critical in meeting their missions. The University of Chicago Medicine has a longstanding tradition of community service. DOSAR is a part of the University of Chicago Medicine’s Urban Health Initiative, created to bring together medical and community partners to improve health and access to quality care for the South Side of Chicago.

WHERE:

Projects will take place at the following locations:

Brickyard Garden, 6121 S. Woodlawn Ave.
Community Garden, 65th Street and Woodlawn Ave.
All Faith Pavilion Nursing, 3500 S. Giles Ave.
Angelic Organics Learning Center, 6400 S. Kimbark Ave.
Eden Place Nature Center, 4417 S. Stewart Ave.
Gary Comer Youth Center, 7200 S. Ingleside Ave.
Henry’s Sober Living, 6634 S. Drexel Ave.
Park Shore East Elderly, 6250 S Harper Ave.
Prosperity House, 6620 South Evans Ave.
The Renaissance Collaborative, 3757 S. Wabash Ave.
Till Learning Garden, 6612 S. Champlain Ave.
Ronald McDonald House, 5444 S. Drexel Ave.
Rainbow Beach, E. 75th Street at Lake Michigan
Canaryville Little League, 455 W. 45th Place
Casa Kirk Apartments, 3248 East 92nd St.
Claretian Associates, 9108 S. Brandon Ave.
It Takes a Village Shelter, 544 W. 123rd St.
Namaste Charter School, 3737 S. Paulina St.
Vital Bridges Food Pantry, 151 West 75th St.

For more news from the University of Chicago Medicine, follow us on Twitter at @UChicagoMed, or visit our Facebook page at facebook.com/UChicagoMed, our research blog at sciencelife.uchospitals.edu, or our newsroom at uchospitals.edu/news.

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May 15, 2012

A novel mechanism for anxiety behaviors, including a previously unrecognized inhibitory brain signal, may inspire new strategies for treating psychiatric disorders, University of Chicago researchers report.

By testing the controversial role of a gene called Glo1 in anxiety, scientists uncovered a new inhibitory factor in the brain: the metabolic by-product methylglyoxal. The system offers a tantalizing new target for drugs designed to treat conditions such as anxiety disorder, epilepsy, and sleep disorders.

The study, published in the Journal of Clinical Investigation, found that animals with multiple copies of the Glo1 gene were more likely to exhibit anxiety-like behavior in laboratory tests. Further experiments showed that Glo1 increased anxiety-like behavior by lowering levels of methylglyoxal (MG). Conversely, inhibiting Glo1 or raising MG levels reduced anxiety behaviors.

“Animals transgenic for Glo1 had different levels of anxiety-like behavior, and more copies made them more anxious,” said Abraham Palmer, PhD, assistant professor of human genetics at the University of Chicago Medicine and senior author of the study. “We showed that Glo1 was causally related to anxiety-like behavior, rather than merely correlated.”

In 2005, a comparison of different mouse strains found a link between anxiety-like behaviors and Glo1, the gene encoding the metabolic enzyme glyoxylase 1. However, subsequent studies questioned the link, and the lack of an obvious connection between glyoxylase 1 and brain function or behavior made some scientists skeptical.

“When people discover a gene, they’re always most comfortable when they discover something they already knew,” Palmer said. “The alarming thing here was there was a discovery of something that nobody knew, and therefore it seemed less likely to actually be correct.”

A 2009 study from Palmer’s laboratory suggested that differences in Glo1 expression between mouse strains were due to copy number variants, where the segment of the genome containing the gene is repeated multiple times. To test this hypothesis, lead author Margaret Distler inserted two, eight or ten copies of the Glo1 gene into mouse lines. She then ran experiments such as the open field test, in which researchers measure how much time a mouse spends in the center of an arena versus along the walls, to detect changes in anxiety behavior.

The results confirmed a causative role for Glo1 copy number variants, as mice with more copies of the Glo1 gene exhibited higher anxiety-like behavior in their experiments.

“It’s the first study to show that it’s the copy number variant that has the potential to change Glo1 expression and behavior,” said Distler, an MD/PhD student in the Pritzker School of Medicine’s Medical Scientist Training Program. “Our study was a physiological representation of what it means to increase Glo1 expression for anxiety.”

The researchers then set about answering the mystery of how Glo1 expression influences anxiety-like behaviors. The primary function of glyoxylase 1 is to metabolize and lower cellular levels of methylglyoxal, a waste product of glycolysis. Distler produced the opposite effect by injecting MG to artificially increase its levels in the brain, finding that raising MG levels quickly reduced anxiety symptoms in mice.

“Methylglyoxal changed behavior within 10 minutes of administration, which means it’s a rapid onset. It’s not changing gene expression, and it’s not having long-term downstream effects,” Distler said. “That was our first breakthrough.”

The short time course suggested that MG might have a direct effect on neuronal activity. MG also demonstrated sedative effects at high doses, a hallmark of drugs that activate inhibitory GABA receptors on neurons. In collaboration with Leigh Plant, now at Brandeis University, the researchers demonstrated that MG activated GABA-A receptors on neurons, a previously unknown inhibitory mechanism.

“It’s a completely different system that is tying neuronal inhibitory tone into metabolic activity,” Palmer said. “That’s potentially really exciting in terms of re-evaluating what we thought we knew about inhibitory tone in the CNS. It turns out now that methylglyoxal, which has been around ever since glycolysis evolved, was also acting at these receptors, and nobody knew that.”

Conventionally, anxiety has been treated with drugs that activate the GABA-A receptor, such as benzodiazepines and barbiturates, which are prone to abuse and dangerous side effects. The researchers theorized that targeting the Glo1/MG interaction could provide a more selective strategy for reducing anxiety symptoms by subtly influencing inhibitory tone.

“The GABA-A receptor agents already out there have a lot of side effects, such as sedation and hypothermia, as well as a high abuse liability,” Distler said. “It’s possible that taking a Glo1 inhibitor will increase only MG levels to a certain maximum. You could have the potential for more specificity, given that you’re activating a system that’s already in place, not just dumping methylglyoxal or some other GABA-A receptor agent throughout the brain.”

Preliminary experiments with a small molecule inhibitor of Glo1 supported the theory. Injections of the inhibitor, developed by John Termini at the Beckman Research Institute of the City of Hope, reduced anxiety-like symptoms in mice.

“It’s a different way of hitting these GABA-A receptors,” Palmer said. “We have yet to determine if that’s a better way of doing it, but it’s certainly different, and it gives us a unique angle of attack on this system and potential advantages that we have yet to evaluate.”

Such a drug may also be useful in treating epilepsy and sleep disorders, where GABA-A drugs have shown success. While the therapeutic potential of manipulating this system is yet to be determined, the research clears the fog around the role of Glo1 in anxiety by adding behavioral and cellular evidence.

“What’s neat is that we started with exploratory, open-ended genetic studies in mice, and we’ve now gotten into some fundamental new physiology that nobody had appreciated or put together before,” Palmer said. “Now we’re starting to reap some of the fruit from those types of genetic studies to enrich our understanding of more classical aspects of biology.”

The paper, “Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal,” will be published online May 15 by the Journal of Clinical Investigation. In addition to Distler, Palmer, Plant and Termini, authors on the paper include Greta Sokoloff, Andrew Hawk, Ivy Aneas, Stephen Meredith and Marcelo Nobrega of the University of Chicago, and Gerald Wuenschell of the Beckman Research Institute of the City of Hope.

The research was funded by grants from the National Institute of Mental Health, the National Institute on Drug Abuse, National Institute of General Medical Sciences and the University of Chicago Diabetes Research and Training Center.

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May 15, 2012

University of Chicago Medical Center President Sharon O’Keefe, a nationally recognized authority on hospital operations, health care quality and patient satisfaction, and the mother of a child with epilepsy, has been named to the board of Citizens United for Research in Epilepsy (CURE).

CURE was founded by parents of children with epilepsy who joined forces to spearhead the search for a cure by raising funds for research and increasing awareness of the disorder. The nonprofit organization has worked to establish epilepsy as a disease that merits crucial federal research funding. Since its inception in 1998, CURE has raised more than $18 million. CURE funds seed grants to explore new areas and collect the data necessary to apply for further funding from the National Institutes of Health (NIH). To date, CURE has supported 126 cutting-edge projects across the globe.

“Sharon O’Keefe has the professional skills, profound energy and personal commitment to bring a wealth of resources to our organization,” said Susan Axelrod, chair and founding member of CURE and a past member of the NIH’s National Advisory Neurological Disorders and Stroke Council. “She is a recognized leader in the hospital industry and works closely with the University of Chicago Medicine’s nationally recognized programs in pediatric and adult epilepsy.”

In people with epilepsy, the brain produces sudden bursts of electrical energy that can produce seizures that interfere with consciousness, movements or sensations. An estimated 2.2 million Americans have epilepsy, with approximately 150,000 new cases diagnosed in the United States each year, according to a recent report from the National Academy of Science’s Institute of Medicine. That equals nearly 500 new cases every day. Approximately one in 26 people will develop epilepsy at some point in their lives, according to the report. The onset of epilepsy is highest in children and older adults.

“I have seen how epilepsy can disrupt the life and plans of patients and their families. Our daughter, now 17, was diagnosed at the age of 5,” O’Keefe said. “I also have seen remarkable progress toward understanding this disease through innovative research. I am honored to have been selected to serve on the CURE board and look forward to this new role in helping speed up the pace of progress in understanding, treating and, we hope, curing this disorder.”

A Chicago native, O’Keefe, 60, began her health care career as a nurse at Loyola University Medical Center, then moved into hospital administration, first at Johns Hopkins Hospital in Baltimore, then at Montefiore Medical Center in the Bronx in New York. From 1987 to 1989, she served as senior manager for health care at the accounting firm Ernst & Whinney (now Ernst & Young), where she developed a consulting practice focused on organizational design, operations improvement and large-scale change management.

She returned to hospital administration in 1989 and spent 10 years as senior vice president for operations at the University of Maryland Medical System in Baltimore, where she focused on clinical program development and customer satisfaction. Her efforts helped the medical system become the first health care organization to receive the U.S. Senate Productivity Award in 1997.

In 1999 she moved to Boston’s Beth Israel Deaconess Medical Center, a teaching affiliate of Harvard Medical School. As executive vice president and chief operating officer, O’Keefe developed and implemented a financial recovery plan for the recently merged but financially challenged hospitals. In 2002, she became chief operating officer at Barnes-Jewish Hospital, consistently ranked as one of the top 10 hospitals in the United States. In April 2009, she became president of Loyola University Medical Center in Maywood, Ill., where she served until her appointment at the University of Chicago Medicine in February 2011.

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May 21, 2012

Patients who watch an online instructional video are more likely to keep their appointments and arrive prepared for a scheduled colonoscopy than those who do not, according to a study by gastroenterologists at the University of Chicago Medicine.

The study, presented at the 2012 annual Digestive Diseases Week meeting in San Diego, CA, found that among patients age 50 to 65 — the primary target for colon cancer screening — those who watched the video were 40 percent less likely to cancel an appointment. That suggests many more cancers could be prevented or detected and treated early if more thorough instruction were given.

“Although early detection of colon cancer can save lives, only about half of those who could benefit take advantage of this screening test,” said Archita P. Desai, MD, fellow in the section of gastroenterology at the University of Chicago Medicine. “Use of this video-preparation approach could increase the number of people who complete the process. Thanks to such screening, the death rate from colorectal cancer has been dropping for more than 20 years, but there is still plenty of room for improvement.”

Colorectal cancer is the second leading cause of cancer-related deaths in the United States, responsible for nearly 50,000 deaths a year. The American Cancer Society recommends that men and women should have a colonoscopy every 10 years, beginning at age 50. When colon cancer is caught early, 90 percent of patients remain alive five years later, but when the cancer has already spread, five-year survival falls to 12 percent.

In the United States, only 53 percent of those older than 50 follow the recommendations for colorectal cancer screening. Far more people than that schedule a colonoscopy, but surveys show only 23 percent to 58 percent of patients who schedule a colonoscopy keep those appointments. This wastes resources, increases costs and extends the waiting time for those seeking an appointment.

The 30-minute web-based interactive program (watch a four-minute segment) produced by Chicago-based Emmi Solutions, walks the viewer though the entire process. It explains how colonoscopy is performed, why preparation is necessary, and how to weigh the risks and benefits. Viewers can pause the video, ask questions or review the information to make sure they understand it. Doctors can enable the viewer to type a question to them or their staff. The questions that patients ask can alert the doctor to address remaining concerns.

In this study, the researchers compared all 1,740 patients referred by their primary care physicians for a colonoscopy at the University of Chicago Medicine in the six months from Dec. 1, 2009, to June 1, 2010 — before the colonoscopy video was available — to all 1,415 patients referred Dec. 1, 2010, to June 1, 2011, half of whom were told to watch the video. More than three out of four patients with access to the video watched it all the way through.

The researchers looked for “preventable cancellations,” patients who did not complete the test because they skipped the appointment, arrived unprepared, failed to follow instructions about taking or discontinuing certain medications, or faced transportation issues.

The preventable cancellation rate for those who watched the video was significantly lower, falling from 11 percent for patients screened before the video was available to 8 percent for those who had access to the video. The biggest improvement was seen among those age 50 to 65, in which the no-show rate fell from 12 percent for those without access down to 7 percent for those who watched.

“This appears to be an effective and inexpensive way to improve compliance,” Desai said. “Our next steps will be to track the outcomes of patients who did not watch the video after being assigned to do so as this group has the highest cancellation and poor-preparation rates. It will be important to identify how to successfully screen this group of patients.”

The study (DDW abstract number Sa1127) was presented at Digestive Disease Week (DDW) 2012 in San Diego, CA. Additional authors include Mark Mulert, Lisa Vinci, and Leslie W. Yang of the University of Chicago Medicine.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 19 – 22, 2012, at the San Diego Convention Center. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

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May 22, 2012

When Lou Byrd opened Lou’s Barber Shop in Chicago’s South Shore neighborhood in 1966, he was the first black business owner on the block.

“It was just me and five raggedy chairs,” he said. “But I had guts, know-how and prayer. It wasn’t much, but mama always said, ‘You can change things.’”

It seems she was right. Over his more than 40 years serving this community, Byrd’s business has thrived while the one constant, he says, has been change.

“I’ve seen people come and go,” Byrd said. “I’ve evolved with every new hair trend. I survived the last big recession, now I’m toughing it through this one. The South Side is a good place to be, but you’ve got to pay attention to the people.”

Those words couldn’t ring more true for organizers of a new photo project under way at the University of Chicago Medicine. Byrd is among the first South Siders to be photographed as part of a large-scale undertaking aimed at capturing people, places and scenes that uniquely represent the South Side of Chicago. The goal of the project, known as the South Side Photo Show, is to showcase the South Side that is rarely seen in the pages of a newspaper and to give a visual tribute to the neighborhoods that the hospital serves as it unveils its New Hospital Pavilion in January.

“I’ve been very pleased with many of the images we’ve collected so far,” said Cheryl Reed, director of strategic communications for the medical center, who is leading the project with social media specialist Matthew Wood. “We’re going beyond what people think they know about the South Side. We’re capturing a moment in life, including little oddities and surprises — stories that have potential to make a real connection with people.”

Photographers assigned to the project haven’t had to look far for inspiration. From Sunday church services and activities in parks, to birthday parties, iconic businesses, nighttime hangouts, schools and more, impromptu snapshots are archiving a slice of life for people who call the South Side home.

Organizers are now calling for members of the community to submit their own photos and ideas. If a submitted photo is selected for the show, the photographer will receive a cash stipend.

“Community engagement is what will truly make this project special,” Reed said. “We can’t capture the South Side from one lens. Everyone sees the community differently. We want people to tell us about the things, places and events they truly care about.”

The final collection, which will feature up to 60 images, will be displayed during several events leading up to the New Hospital Pavilion opening. There are plans for the photos to be shared more broadly via a traveling exhibit across the city. Ultimately, the vision may even include a coffee table-style photo book.

“The New Hospital Pavilion will be an incredible gift to this community,” Reed said. “The University of Chicago Medicine has always been a very proud member of the community and its strongest supporter. We’re thrilled to have found a meaningful way to celebrate who we are and the people we serve.”

While there have been many photo projects featuring Chicago, none has focused on life south of Roosevelt Road. Perceptions shaped by media reports often leave the area’s vibrant landscape, diversity and abundance of activities unnoted.

Byrd said he’s glad he was asked to take part in the show, and hopes people will take the hospital up on its offer to get involved.

“It’s a nice picture,” he said, “and I felt proud placing it among all the other pieces of history on these walls. I look forward to seeing the exhibit.”

Submit your photos

The University of Chicago Medicine welcomes contributions from the community for consideration in the South Side Photo Show. Email your photo submission and a few lines of caption information to Southsidephoto@uchospitals.edu. For more information, call 773-795-7652.

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May 22, 2012

For decades, scientists believed that a spine with multiple segments was an exclusive feature of land-dwelling animals. But the discovery of the same anatomical feature in a 345-million-year-old eel suggests that this complex anatomy arose separately from — and perhaps before — the first species to walk on land.

Tarrasius problematicus was an eel-like fish that lived in shallow bodies of water in what is now Scotland, in the Carboniferous period between 359 million and 318 million years ago. Like many fish, Tarrasius was thought to have a vertebral column divided simply into body and tail segments. But in a new description of Tarrasius published in Proceedings of the Royal Society B, Lauren Sallan describes a five-segment column much more similar to the spinal anatomy of land-dwelling animals called tetrapods, including humans.

The surprising find argues against a common assumption paleontologists use to determine from fossils whether an ancient species lived on land or in water.

“It’s the last trait to fall,” said Sallan, a graduate student in the Program in Integrative Biology at the University of Chicago Biological Sciences. “First, limbs were thought to show that a species was on land and walking, and now the vertebral morphology doesn’t mean that they’re on land either. So a lot of the things we associate with tetrapods actually arose first in fishes, and this is another example of that.”

Tetrapods, which include the first species to walk on land as well as all modern mammals, reptiles, birds and humans, possess vertebrae organized into five distinct segments. From head to tail, the spinal vertebrae can be categorized into cervical, thoracic, lumbar, sacral and caudal sections, each with its own characteristic anatomy.

By contrast, fish vertebrae are typically categorized anatomically into two segments: caudal and pre-caudal. But the spinal column of Tarrasius shows a complexity more like that seen in tetrapods, with five segments separated by abrupt transitions.

“The morphology is just completely different in each series of vertebrae,” Sallan said. “Like a tetrapod, you can tell which segment you’re looking at from the basic morphology.”

When Sallan began her research on Tarrasius, she wasn’t looking for an unusual spine, but rather how the species fit evolutionarily among other early ray-finned fishes. While examining undescribed fossils at the National Museums Scotland in Edinburgh, Sallan found some unexpected features. Instead of the flexible notochord characteristic of most ancient fish species, Tarrasius possessed heavy vertebral bones organized into five anatomically distinct sections.

Armed with this new anatomical information, Sallan re-examined many other fossils of the species and detected evidence for spinal complexity that researchers previously had missed.

“This was in a different museum from where most of the specimens are, and previous workers had just been looking at the same fossils over and over,” Sallan said. “It’s basically an issue of finding what you expect to be there instead of what’s actually there.”

The appearance of tetrapod-like spinal organization in a ray-finned fish shatters the presumed relationship between complex vertebral anatomy and both walking and terrestriality. The eel-like Tarrasius possessed no hind fins and a long dorsal fin, indicating it used its surprisingly intricate spinal column for swimming, not walking. And while Tarrasius lived several million years after the first tetrapods with hands and feet, the discovery of these spinal features in a fish species confirms that this anatomy can evolve separate from the evolution of walking behavior.

“You can’t use this trait to say that something was definitely on land or to identify a tetrapod, which is the way it is used in the field now,” Sallan said.

Instead, the commonalities suggest that similar environments or other selective pressures may produce convergent evolution of this complex spinal organization. It also questions whether tetrapod-like expression of a family of factors responsible for body patterning — the Hox genes — is ancestral for both vertebrates and fishes, or truly essential for the development of these spinal segments. Since most knowledge about the relationship between Hox genes and body pattern development is based on genetic studies of modern tetrapods, the new finding emphasizes the need for more testing in fish species.

“Part of the problem is that the Hox expression data is available only for a few model organisms,” Sallan said. “What’s really needed is some expression data from other ray-finned fishes and tetrapods, things that are not mouse and chick and zebrafish. We need to try to get the full diversity of Hox expression.”

It’s also unclear how Tarrasius used its unexpectedly intricate spinal column in its daily life. Sallan speculates that the bony vertebrae may have been useful in propelling the fish’s body during fast swimming, similar to the stiff vertebrae of modern marlins.

“I think it must help with stiffening the body, because the tail is so flexible,” Sallan said. “If you look at the general shape, it’s more like a tadpole or an early tetrapod, so it might just function to hold the body steady because the tail is flapping.”

The paper, “Tetrapod-like axial regionalization in an early ray-finned fish,” will be published May 23 by Proceedings of the Royal Society B. Sallan is the sole author on the article. Funding for the research was provided by the National Science Foundation, the Palaeontological Association, the Paleontological Society, the American Society of Icthyologists and Herpetologists, and the Evolving Earth Foundation.

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May 23, 2012

Donations from Jim and Karen Frank and others will endow the Janet Davison Rowley, MD, Professorship in Cancer Research at the University of Chicago Medicine. This new named professorship will honor one of the University’s most distinguished scientists and alumni, Janet D. Rowley, MD’48, the Blum-Riese Distinguished Service Professor of Medicine, Molecular Genetics and Cell Biology, and Human Genetics.

Rowley, 87, a pioneer in understanding the connections between genetics and cancer, remains an active member of the faculty. She rides her bicycle to work every day.

In the early 1970s, Rowley made the first of a series of fundamental discoveries demonstrating that specific chromosomal changes caused certain types of leukemia. She then struggled for years to convince fellow researchers that cancer was essentially a genetic disease.

Her discoveries eventually gained acceptance. They brought her widespread recognition, including the Lasker Award, the National Medal of Science and the Presidential Medal of Freedom. In the last six months, she received the Ernest Beutler Prize and the Japan Prize for Healthcare and Medical Technology.

“Dr. Rowley, a graduate of the University’s Laboratory Schools, the College and the Medical School, has long been a shining example of the power of a University of Chicago education,” said medical center trustee Jim Frank, of Winnetka. “She is also a model of what that kind of training, combined with enormous talent and dedication, can do. Karen and I are proud to help celebrate her accomplishments and support the outstanding researchers who will be honored to hold this endowed chair.”

“All of us in the Cancer Center are excited to see Janet’s remarkable career recognized in this enduring way,” said colleague Michelle Le Beau, PhD, director of the University of Chicago Medicine Comprehensive Cancer Center, who trained under Rowley. “She has received just about every imaginable honor. Now someone with extraordinary promise will benefit from this support, from the history of Janet’s discoveries and the immediate recognition that comes with selection as the Rowley Professor.”

Rowley was born Apr. 5, 1925, in New York City. At age 15, she won a scholarship to enroll in the University of Chicago’s Hutchins College, which combined the last two years of high school with the first two years of college. “The U of C,” Rowley later recalled, “taught me to stick to my convictions — if I really thought that I was correct — even when others disagree.”

She completed a bachelor of philosophy degree in 1944 and graduated from medical school in 1948. The next day, she married fellow medical student Donald Rowley, MD, now a professor emeritus of pathology at the University. She spent the next 20 years raising their four boys while working three days a week at various sites, including a Chicago clinic for children with Down syndrome, a genetic condition caused by an extra chromosome.

Her interest in chromosomes and cancer gained focus in 1962, after a year at Oxford University, where she learned newly developed techniques of chromosome analysis. Back in Chicago, Leon Jacobson, MD, a colleague and mentor, suggested she apply those techniques to the study of chromosomes from patients with leukemia.

She made her first big discovery in 1972. Rowley found that the chromosomes of a patient with acute myeloid leukemia (AML) appeared to have made a trade: part of chromosome 21 had broken off and moved to chromosome 8, and part of 8 had moved to chromosome 21 — an exchange now known as a “translocation.” When she looked at more patients with this same kind of leukemia, she saw the same process.

She later found that patients with a different disease, chronic myelogenous leukemia (CML), had a different translocation. One end of chromosome 22 was exchanged for a piece of chromosome 9. Because of this transfer, important genes that regulated cell growth and division were no longer located in their normal position. The result was the uncontrolled cell growth of cancer.

The two consistent translocations — one in AML and one in CML — argued that such translocations were tied to specific types of leukemia. In 1977, Rowley and colleagues identified a third example, the 15;17 translocation that causes acute promyelocytic leukemia, a rare disease but one where every patient had the same genetic flaw. “That made me a believer,” she would later recall. “That was the frosting on the cake.”

Understanding the 9;22 translocation eventually led to the development of the drug imatinib (Gleevec), one of the most successful targeted cancer therapies to date. Gleevec blocks an abnormal growth-regulating protein produced by the 9;22 translocation.

Picking up on her lead that specific translocations defined specific forms of cancer, scientists around the world joined the search for chromosomes that either exchanged genetic material or lost it altogether. Others used the translocations as road maps to find specific genes disrupted by chromosome damage, thus opening up the current era of cancer genetics.

“Establishing the Rowley Professorship is one more way to celebrate Janet’s remarkable series of discoveries, a process that is still under way,” said Kenneth Polonsky, MD, Dean of the Biological Sciences Division and the Pritzker School of Medicine at the University of Chicago. “Any future professor to hold this chair will find that the honor comes with high expectations.”

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May 8, 2012

The U.S. Department of Health and Human Services has awarded $5.9 million to a University of Chicago Medicine-led program to set up a real-time automated system that will link a patient with up-to-date information about community-based services and resources.

CommunityRx, a system to be managed by the University of Chicago Medicine’s Urban Health Initiative, was among the 26 programs selected nationwide — and the only one in Illinois — to receive part of the $122.6 million in federal Health Care Innovation awards, made possible by the Affordable Care Act. The 26 projects were selected for their innovative solutions to efficiently deliver high quality medical care and enhance the health care workforce. The preliminary awardees announced today expect to reduce health spending by $254 million over the next three years.

The CommunityRx program is expected to serve approximately 200,000 beneficiaries of the South Side, many of whom are covered by Medicare, Medicaid or the Illinois Comprehensive Health Insurance Plan.

The Urban Health Initiative, in partnership with Chicago Health Information Technology Regional Extension Center (CHITREC) and the Alliance of Chicago Community Health Services, will develop the CommunityRx system, a continuously updated electronic database of community health resources that will be linked to the electronic health records of local safety net providers. In real time, the system will process patient data and print out a “Health.eRx” for the patient, including referrals to community resources relevant to the patient’s condition and health status.

“Our innovation helps people stay healthy and manage disease by connecting them to businesses and support organizations in their community,” says Stacy Tessler Lindau, MD, associate professor of obstetrics and gynecology at the University of Chicago Medicine and lead researcher for this project. “The outcome will be better and more efficient health care delivery and stronger, more vital communities. That’s ultimately the way we’ll cut cost from the system. I see this investment as a validation of the innovative, community-engaged approach that the University of Chicago Medicine and its South Side partners, including our youth, are taking to transform urban health.”

Aggregated data on patient diagnoses and referrals will be used to generate reports for community-based service providers to use to inform programming. The CommunityRx builds on infrastructure supported by funding from the National Institute on Aging. Anticipated outcomes include better population health, better use of appropriate services, increased compliance with care, and fewer avoidable visits to the emergency room with estimated savings of approximately $6.4 million.

“We can’t wait to support innovative projects that will save money and make our health care system stronger,” Health and Human Services Secretary Kathleen Sebelius said in a statement today announcing the winners. “It’s yet another way we are supporting local communities now in their efforts to provide better care and lower cost.”

The 26 new projects include collaborations of leading hospitals, doctors, nurses, pharmacists, technology innovators, community-based organizations, and patients’ advocacy groups, among others, located in urban and rural areas that will begin work this year to address health care issues in local communities. This initiative allows applicants to come up with their best ideas to test how we can quickly and efficiently improve the quality and affordability of health care.

The awardees were also chosen for their focus on creating a well-trained health care workforce that is equipped to meet the need for new jobs in the 21st century health system. The Bureau of Labor Statistics projects the health care and social assistance sector will gain the most jobs between now and 2020.

The CommunityRx system will train and create new jobs for an estimated 90 individuals from this high-poverty, diverse community. This includes high school youth who will to collect data on community health resources as part of the Urban Health Initiative’s MAPSCorps program. It will also include the creation of a new type of health worker, Community Health Information Experts (CHIEfs), who will assist patients in using the Health.eRx and engage community-based service providers in meaningful use of the CommunityRx reports.

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April 24, 2012

New research confirms that the controversial decision by Warren Buffet — the 81-year-old CEO of Berkshire Hathaway — to undergo a blood test screening for prostate cancer despite his age is hardly unusual. Despite recommendations in 2008 from the United States Preventive Services Task Force against testing for prostate cancer in men aged 75 years or older, almost half of men in that age group continue to get screening tests.

In 2005, before the recommendations were released, 43 percent of men age 75 and above elected to take the prostate-specific antigen (PSA) test. In August 2008, the Task Force stated it “recommends against the service,” arguing “there is moderate or high certainty the service has no net benefit or that the harms outweigh the benefits.”

Survey results from 2010, however, published in the April 25, 2012, issue of JAMA, found that two years after the Task Force’s recommendations were announced, the screening rate for that group of men had gone up slightly, to 43.9 percent. This is higher than the rates for men in their 40s (12.5 percent) or 50s (33.2 percent), who are more likely to benefit from early diagnosis and treatment. Only men aged 60 to 74 were more likely to get the screening test (51.2 percent).

“PSA screening for more than 40 percent of men 75 or older is inappropriate,” said study author Scott Eggener, MD, assistant professor of surgery at the University of Chicago Medicine. “Selective screening is reasonable to consider for the healthiest men over age 75, but for the large majority of men in this age group, early detection can lead to treatment of a disease that will probably never cause a problem. A substantial proportion of men over 75 with an elevated PSA will die from something else before a prostate cancer interferes with the quality or duration of their life.”

“Our data are likely an underestimate,” the authors note. They worked with information from the 2005 and 2010 Cancer Control Supplements, part of the annual National Health Interview Survey (NHIS), which gathers information through in-person interviews and is a representative sample of the US population. “Self-reported screening rates in the NHIS,” they note, “are predominantly lower compared with medical record extraction.”

The revised draft recommendations presented in October 2011 by the USPSTF are even more critical of PSA screening than the 2008 version, suggesting there was not enough evidence that PSA screening improves health outcomes to routinely recommend the test for men at any age. “Prostate-specific antigen–based screening results in small or no reduction in prostate cancer–specific mortality,” the Task Force concludes. It is associated with “harms related to subsequent evaluation and treatments, some of which may be unnecessary.” These draft recommendations are not finalized yet but are expected to be forthcoming soon.

Clinical practice patterns following the 2011 USPSTF recommendations “should be monitored,” the study authors conclude. Even if PSA screening is discouraged in the final USPSTF recommendation, “I’m not anticipating a massive change in utilization,” Eggener said, based on a general tendency for individuals and physicians to support cancer screening, evidence that fewer men are dying of prostate cancer since the introduction of PSA, subsequent confusion about the recommendation among the general public, and ongoing concern about the disease.

The study was funded by the US Department of Defense and the University of Chicago Medicine. Additional authors include Sandip Prasad, Michael Drazer, and Dezheng Huo of the University of Chicago and Jim Hu, now at the University of California, Los Angeles.

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May 4, 2012

An over-the-counter natural remedy derived from honeybee hives arrests the growth of prostate cancer cells and tumors in mice, according to a new paper from researchers at the University of Chicago Medicine.

Caffeic acid phenethyl ester, or CAPE, is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives. Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells.

In a paper published in Cancer Prevention Research, researchers combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells’ system for detecting sources of nutrition.

“If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace,” said Richard B. Jones, PhD, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study. “So it doesn’t kill the cancer, but it basically will indefinitely stop prostate cancer proliferation.”

Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims. While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds.

“It’s only recently that people have examined the mechanism by which some of these herbal remedies work,” Jones said. “Our knowledge about what these things are actually doing is a bit of a disconnected hodge-podge of tests and labs and conditions. In the end, you’re left with a broad, disconnected story about what exactly these things are doing and whether or not they would be useful for treating disease.”

To study the purported anti-cancer properties of CAPE, first author Chih-Pin Chuu (now at the National Health Research Institutes in Taiwan) tested the compound on a series of cancer cell lines. Even at the low concentrations expected after oral administration, CAPE successfully slowed the proliferation of cultured cells isolated from human prostate tumors.

CAPE was also effective at slowing the growth of human prostate tumors grafted into mice. Six weeks of treatment with the compound decreased tumor volume growth rate by half, but when CAPE treatment was stopped, tumor growth resumed its prior rate. The results suggested that CAPE stopped cell division rather than killing cancerous cells.

To determine the cellular changes that mediated this effect, the researchers then used an innovative proteomics technique invented by Jones and colleagues called the “micro-western array.” Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples.

Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth — experiments that would have been prohibitively expensive without the new technique.

“What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that’s never been possible before,” Jones said. “It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies.”

The micro-western array results allowed researchers to quickly build a new model of CAPE’s cellular effects, significantly expanding on previous work that studied the compound’s mechanisms. Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.

“It appears that CAPE basically stops the ability of prostate cancer cells to sense that there’s nutrition available,” Jones said. “They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition.”

The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.

“A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy,” Jones said. “Now we’ll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds.”

The paper, “Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signaling networks,” will be published online May 4 by Cancer Prevention Research. In addition to Chuu and Jones, authors include Mark F. Ciaccio, John M. Kokontis, Ronald J. Hause, Jr., Richard A. Hiipakka and Shutsung Liao of the University of Chicago; and Hui-Ping Lin of the National Health Research Institutes in Taiwan.

Research was supported by grants from the Cancer Research Foundation, American Cancer Society, National Institutes of Health, U.S. Department of Health, and National Science Council.

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April 18, 2012

A large-scale study of medical claims data shows that introducing sophisticated biologic therapies early in the course of treatment for Crohn’s disease improves response to medication and reduces the need for surgery.

There is no known cure for Crohn’s disease, and traditional treatment is focused on a “step-up” strategy of managing inflammatory symptoms, starting with simpler and less costly oral medications such as aminosalicylates (5-ASAs) and corticosteroids, and escalating through a series of steps to more expensive biological therapies that target specific proteins in the immune system’s inflammatory response.

David Rubin, MD, associate professor of medicine and co-director of the University of Chicago Medicine’s Inflammatory Bowel Disease Center, studied a newer “top-down” strategy that reverses this order of treatment. He found that patients treated with biologic therapies earlier were significantly less likely to need steroids, lose response to their biologic therapy, and require surgery related to their Crohn’s disease. “We’re essentially reversing the management strategy in Crohn’s disease,” Rubin said.

He emphasized that the medications often used first for patients with Crohn’s are also the least effective and carry risks for side effects. “We’ve long discussed and debated that 5-ASAs don’t work in the majority of Crohn’s patients, and certainly don’t change any outcomes,” he said. “Steroids are ineffective long-term and are also dangerous because they have significant side effects such as infections.”

Crohn’s is a disorder in which the body’s immune system appears to have lost the ability to regulate itself and becomes overactive, causing progressive damage to the bowel structure and function. Patients often need bowel surgery to repair this damage. Researchers have made great progress finding genetic and environmental contributors to Crohn’s disease, but the actual cause is unknown.

Rubin said that physicians have questioned the effectiveness of the step-up strategy because patients experience little relief while being treated with medications before they receive the biological therapies. During that time, they suffer from active disease, have low rates of remission and often appear to lose response to the biological therapies.

In recent years a treatment strategy that starts with the targeted biologic therapy as a first option has been explored in controlled clinical trials. The encouraging results suggested that such an approach results in higher remission rates. However, it was not clear whether this top-down approach would translate to the general population of patients with Crohn’s disease, or whether such an approach would maintain the response to biologic therapy and decrease the need for surgery.

The Food and Drug Administration approved the first targeted biologic therapy for Crohn’s disease in 1998 and the second two in 2007 and 2008. Rubin said physicians are hesitant to prescribe them earlier because they are expensive, must be administered through injections instead of pills and are typically saved until last. “Patients and doctors are nervous about immune suppressive therapies. The perception in the current treatment algorithm is that the therapies saved for last must also be the most dangerous,” he said. “But that’s the wrong thinking, and by delaying their prescription it may be a self-fulfilling prophecy because by then patients have suffered more damage to their bowels and are less likely to respond favorably.”

In the study, published in the journal Inflammatory Bowel Diseases, Rubin and his colleagues analyzed health insurance claims from a database that includes records from more than 94 commercial health plans throughout the United States. Patients eligible for the study had to be enrolled in the same health plan continuously for at least six months before the first claim related to Crohn’s and stay enrolled for at least 12 months after the first claim for anti-TNF treatments.

Rubin then separated these patients into three groups: those who followed the traditional step-up therapy starting with 5-ASAs or corticosteroids before anti-TNF treatment, those who had immunosuppressive therapy (but not 5-ASAs) before anti-TNF treatment, and those who started anti-TNF treatment within 30 days of their first prescription for Crohn’s disease.

In general, the group that started anti-TNF treatment early had significantly lower rates of continuous steroid use to treat flare-ups than the other groups, lower rates of escalation of dosage for their medications and needed fewer surgeries related to Crohn’s disease. “This is the first time we did a large assessment of the top-down, early-TNF strategy using claims databases,” Rubin said. “It gave us lots of detail and lots of information, much larger than with a controlled trial. We could look at hundreds of thousands of patients in order to get a big picture of how effective these approaches are in treating Crohn’s. It’s also the first time we were able to examine surgical outcomes associated with this strategy.”

“Having a new class of therapies and having a culture change in GI takes a lot of discussions,” he said. “This paper contributes to the discussion about how important this kind of treatment is because it changes the outcomes for people suffering from Crohn’s disease.”

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April 13, 2012

An unusual clinical trial based at the University of Chicago Medicine is seeking to determine whether a drug approved for patients with advanced prostate cancer might be safer and just as effective if taken at a much lower dose with food instead of at the full dose on an empty stomach.

The results of the trial could affect future dosage recommendations, potentially saving patients who take the drug thousands of dollars a month.

Abiraterone acetate (trade named Zytiga) has a greater positive food effect–an increase in the mount absorbed when taken with food–than any other marketed drug that is labeled to be taken on an empty stomach. Five times as much of the drug is taken up with a low-fat meal as on an empty stomach, and up to 10 times as much with a high-fat meal. Yet patients are told not to eat for two hours before and for one hour after taking their pills. As a result, taking Zytiga as directed means the amount of the drug absorbed by the body to fight cancer is decreased by 80 to 90 percent.

“This clinical trial is designed to assess the risks and benefits of taking this effective but costly drug with food,” said Russell Szmulewitz, MD, assistant professor of medicine at the University of Chicago Medicine and director of the study. “Taking one pill with a meal, rather than four pills on a empty stomach, is much more convenient for patients, so it may improve compliance. It would also reduce the cost.”

The savings to patients and their insurance companies from taking lower doses of the drug would be significant. The drug costs $5,000 a month. “By taking one-fourth of the dose with a low-fat breakfast,” Szmulewitz said, “patients may be able to get the full medical benefit and save about $3,750 per month.”

The convenience would appeal to patients. Many dislike having to fast for hours before and after taking their medication, which can upset an empty stomach. Since patients with advanced prostate cancer tend to be older, most take multiple medications for additional health issues, fitting each medication into a complicated daily routine. Many patients who take Zytiga wake up during the night, for example, to take the medicine, then go back to sleep, allowing them to eat soon after they wake up.

The results of the trial could affect future dosage recommendations, potentially saving patients who take the drug thousands of dollars a month.

Abiraterone acetate was approved in 2011 for the treatment of metastatic prostate cancer that did not respond to standard chemotherapy. An estimated 30,000 men in the United States will die of advanced castration-resistant prostate cancer this year; the majority could benefit from this drug, which works by blocking production of male hormones anywhere within the body. Spending for the brand Zytiga is predicted to exceed $1 billion a year in the United States by 2015.

Although a large clinical trial showed that Zytiga reduced pain and extended the life of patients with advanced prostate cancer by nearly four months, the London-based National Institute for Health and Clinical Excellence, which counsels the British National Health System, advised it not to cover the drug because of the expense.

There is also an overdose risk if a patient takes the standard 1,000 mg after fasting, then gets hungry and eats a meal. Taking the full dose with food could boost blood levels of Zytiga up to 10 times the intended dose.

In this clinical trial, one-half of the study participants will take the standard 1,000 mg dose of Zytiga–four pills each morning while fasting. The other half will take one 250 mg pill each morning with a low-fat breakfast. All trial participants also will take prednisone, a steroid that helps prevent common side effects of Zytiga such as high blood pressure, low potassium levels and fluid accumulation.

The researchers hope to enroll about 30 people in the trial at the University of Chicago Medicine and an additional 40 patients at a network of trial sites. The study is funded by the University of Chicago Medicine and not by the maker of Zytiga, Johnson & Johnson. The drug must be purchased by patients who enroll in the trial, ideally with the assistance of health insurance.

Patients who are already taking Zytiga for prostate cancer should not “conduct such experiments on their own,” cautions co-investigator Mark Ratain, MD, the Leon O. Jacobson professor of medicine and director of the Center for Personalized Therapeutics at the University of Chicago Medicine. The drug has not been carefully studied when taken with food. Careful monitoring of drug levels in the blood and its ability to stop or slow the growth of the cancer are central to the study.

“We do not yet know how well the drug will be absorbed or how it will impact the patient and his disease when delivered in this way,” Ratain said. “We know only what happens when it is taken on an empty stomach. In that setting, most of it gets flushed away at considerable expense.”

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The American Society of Hypertension (ASH), the largest organization of hypertension researchers and health care providers in the United States, has designated the University of Chicago Medicine as a Comprehensive Hypertension Center, the first in the Chicago area. This designation is the highest level of formal recognition by ASH for academic medical centers that demonstrate expertise in treating patients with complex hypertension and its co-morbidities.

The University of Chicago Medicine Hypertension Center is directed by George Bakris, MD, a designated hypertension specialist and professor of medicine. “The Comprehensive Hypertension Center designation is a feather in the cap for the University of Chicago Medicine,” said Bakris, who is also the president of the board of directors for ASH. “It distinguishes the University as a center of excellence for hypertensive diseases, because no one else in the city has it.”

ASH created the Designated Hypertension Center program to recognize medical centers and large practices that treat complex hypertension cases and support or participate in advanced research. A comprehensive hypertension center must devote more than 50 percent of its practice to patients with hypertension and related disorders, employ staff certified in advanced blood pressure monitoring techniques including patient self-monitoring and 24-hour ambulatory blood pressure monitoring devices, conduct cardiovascular risk assessments and participate in investigator-initiated research or multicenter trials and studies. In addition, the center must be located in an academic medical center or large multispecialty clinic, have the capability to perform extensive multispecialty examination and treatment, conduct basic and applied research, provide hypertension specialist training and publish scholarly articles on hypertension and related disorders.

The University of Chicago Medicine Hypertension Center offers individualized care through inpatient and outpatient consultation to patients who have hypertension in addition to other complex health conditions, including early kidney disease, diabetes, high risk for heart attack or stroke, and previous occurrence of heart attack or stroke.

The center is also a national leader in hypertension research. Bakris is the national co-principal investigator of the Simplicity HTN-3 trial on refractory hypertension, and principal investigator of the AMETHYST trial dealing with potassium management in people with kidney disease and hypertension. The center provides patients with leading-edge treatment techniques, including quantitative echocardiography, exercise testing, measurement of arterial compliance, ankle-brachial index testing and cardioid Doppler measurements. “Basically, it’s one-stop shopping for hypertension,” Bakris said.

In addition to Bakris, the hypertension center is staffed by Matthew Sorrentino, MD, professor of medicine and designated hypertension specialist, a dedicated hypertension fellow and nursing and research staff. The University is also recruiting an additional designated hypertension specialist. Fellows from the cardiology and endocrinology programs rotate through the hypertension center along with internal medicine trainees.

ASH was founded in 1985 in order to provide a forum for the exchange of information among basic scientists, clinical investigators and others involved in the study or management of high blood pressure. Its specific focus is to translate current research findings on hypertension into effective treatment strategies, in order to better address the needs of hypertensive patients.

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The ranking of a monkey within her social environment and the stress accompanying that status dramatically alters the expression of nearly 1,000 genes, a new scientific study reports. The research is the first to demonstrate a link between social status and genetic regulation in primates on a genome-wide scale, revealing a strong, plastic link between social environment and biology.

In a comparison of high-ranking rhesus macaque females with their low-ranking companions, researchers discovered significant differences in the expression of genes involved in the immune response and other functions. When a female’s rank improved, her gene expression also changed within a few weeks, suggesting that social forces can rapidly influence genetic regulation.

“We were able to use gene expression to classify individuals based on their rank,” said Yoav Gilad, PhD, associate professor of human genetics at the University of Chicago Biological Sciences and senior author of the study in PNAS. “Demonstrating these very plastic and temporal changes was novel and quite interesting.”

The research, led by University of Chicago postdoctoral researcher Jenny Tung, was conducted with rhesus macaques housed in groups of five at the Yerkes National Primate Research Center in Atlanta. As in the wild, each group self-organizes into a dominance hierarchy, defined by which individual yields first during competition over food, water and grooming partners. In captivity, dominance is determined by the order of introduction into the group, giving researchers an opportunity to study how changes in rank lead to biological effect.

“In the wild, females would not ordinarily leave the social group they were born into,” said Tung, PhD, now an assistant professor of evolutionary anthropology at Duke University. “They inherit their social rank from their mothers. But in this unnatural situation, order of introduction determines rank — the newcomer is generally lower status.”

Previous research on rhesus macaques discovered that social rank influenced components of the stress response, brain, and immune system. With gene chip technology for measuring the expression of over 6,000 different genes, Tung, Gilad and colleagues at Yerkes, Emory University, and Johns Hopkins looked for the first time in primates at the effects of social rank on genetic function.

Comparing 49 different female monkeys of different rank revealed significant changes in the expression of 987 genes, including 112 genes associated with immune system function. The result fits with data in monkeys where low rank and chronic stress lead to compromised immune function, and, more loosely, with human studies linking low socioeconomic status and high social stress to elevated disease risk.

The overall genetic “signature” of expression changes was robust enough that researchers could predict an individual monkey’s social rank with high accuracy from their gene expression profile alone. That predictive power also enabled an unanticipated second test of whether gene expression would reflect unplanned changes in dominance rank.

“It was a fortunate event in the experiment,” Gilad said. “When a couple of animals were removed from cages for various reasons and new ones were introduced to the groups, it turned out to improve the rank of a few monkeys. We could take advantage of this switch and see if our classifier still works.”

By analyzing blood samples from these monkeys before and after their move, the researchers were able to use gene expression signatures to correctly predict the change in rank for six of seven monkeys. The result demonstrates that socially-induced gene expression changes are not stable, but can change rapidly in response to changes in social environment.

“There’s a spooky side to this kind of research, in that an individual’s social rank is partially determining health status,” Tung said. “But there’s also a hopeful side. For the seven females that changed ranks, their gene status changed with them. They’re not stuck in place, and I think that says something more broadly about the capacity for change.”

The researchers also investigated the mechanisms by which social status could influence gene expression. Dominance rank affected signaling of the glucocorticoid “stress hormone” system and the cell composition of blood samples, both of which contributed to changes in gene expression.

Experiments also demonstrated for the first time that social rank influenced the DNA methylation status of many genes, an epigenetic mechanism of transiently turning genes on and off. Genes that changed expression with rank status were more likely to be methylated than unaffected genes, suggesting that this mechanism also plays a role in the social influence on genetic regulation.

“That’s a novel mechanism that people haven’t considered in primates,” Gilad said. “I know that some have been resistant to the possibility of methylation changes on this timescale, but this is a demonstration that this mechanism also matters.”

The authors caution that the experiments used monkeys in captivity, and stressed that the relationship between stress and gene regulation in the wild might not look the same. The influence of social factors on human genetics also remains to be tested, and measuring status while controlling for confounding factors in people would be a difficult endeavor, Gilad said. But if social stress does in fact influence human health, the current research provides some optimism.

“An encouraging message to humans is the fact that the effects are plastic, reversible and change on a really large scale when rank changes,” Gilad said. “Whatever it is that causes stress through social environment, you might be able to fix.”

The study, “Social environment is associated with gene regulatory variation in the rhesus macaque immune system,” will be published online in PNAS Early Edition the week of April 9th, 2012. In addition to Tung and Gilad, authors include Luis Barreiro and Kateyln Michelini of the University of Chicago Biological Sciences, Zachary Johnson, Vasiliki Michopoulos, Donna Toufexis and Mark Wilson of Yerkes National Primate Research Center, and Kasper Hansen of Johns Hopkins School of Medicine. Funding for the research was provided by the National Institutes of Health.

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April 4, 2012

Low doses of a commonly used atypical antipsychotic drug improved survival in a mouse model of anorexia nervosa, University of Chicago researchers report this month. The result offers promise for a common and occasionally fatal eating disorder that currently lacks approved drugs for treatment.

Mice treated with small doses of the drug olanzapine were more likely to maintain their weight when given an exercise wheel and restricted food access, conditions that produce activity-based anorexia (ABA) in animals. The antidepressant fluoxetine, commonly prescribed off-label for anorexic patients, did not improve survival in the experiment.

“We found over and over again that olanzapine was effective in harsher conditions, less harsh conditions, adolescents, adults — it consistently worked,” said the paper’s first author Stephanie Klenotich, graduate student in the Committee on Neurobiology at the University of Chicago Biological Sciences.

The study, published in Neuropsychopharmacology, was the product of a rare collaboration between laboratory scientists and clinicians seeking new treatment options for anorexia nervosa. As many as one percent of American women will suffer from anorexia nervosa during their lifetime, but only one-third of those people will receive treatment.

Patients with anorexia are often prescribed off-label use of drugs designed for other psychiatric conditions, but few studies have tested the drugs’ effectiveness in animal models.

“Anorexia nervosa is the most deadly psychiatric disorder, and yet no approved pharmacological treatments exist,” said Stephanie Dulawa, PhD, assistant professor of Psychiatry & Behavioral Neuroscience at the University of Chicago Medicine and senior author of the study. “One wonders why there isn’t more basic science work being done to better understand the mechanisms and to identify novel pharmacological treatments.”

One challenge is finding a medication that patients with anorexia nervosa will agree to take regularly, said co-author Daniel Le Grange, PhD, professor of Psychiatry & Behavioral Neuroscience and director of the Eating Disorders Clinic at the University of Chicago Medicine. Drugs that directly cause weight gain or carry strong sedative side effects are often rejected by patients.

“Patients are almost uniformly very skeptical and very reluctant to take any medication that could lower their resolve to refrain from eating,” Le Grange said. “There are long-standing resistances, and I think researchers and clinicians have been very reluctant to embark on that course, since it’s just littered with obstacles.”

Both fluoxetine and olanzapine have been tried clinically to supplement interventions such as family-based treatment and cognitive-behavioral therapy. But their direct effect on anorexia nervosa behavior — in humans or animals — is lacking in sufficient data.

To test the effectiveness of these drugs in laboratory mice, Klenotich adapted the ABA protocol from previously published rat studies: Mice given 24-hour access to a running wheel but only six hours a day of food access become hyperactive, eat less and rapidly lose weight, with a 25 percent reduction from baseline considered to be the “drop-out” survival point.

In Klenotich’s study, mice were pretreated with fluoxetine, olanzapine or saline before starting the ABA protocol, and treatment continued throughout the ABA period. Researchers then measured how many mice in each group reached the drop-out point for weight loss over 14 days of food restriction and exercise wheel access. Treatment with the antipsychotic olanzapine significantly increased survival over the control group, while fluoxetine treatment produced no significant effects on survival.

Importantly, a low dose of olanzapine did not decrease overall running activity in the mice, indicating that sedative effects of the drug were minimal. In future experiments, the researchers hope to use different drugs and genetic methods to determine exactly how olanzapine is effective against symptoms of anorexia nervosa, perhaps pointing toward a better drug without the negative image or side effects of an antipsychotic.

“We can dissect the effect of olanzapine and hopefully identify the mechanisms of action, and identify what receptor systems we want to target,” Klenotich said. “Hopefully, we can develop a newer drug that we can aim towards the eating disorders clinic as an anorexic-specific drug that might be a little more acceptable to patients.”

The study offers support for the clinical use of olanzapine, for which clinical trials are already under way to test in patients. Le Grange said the development of a pharmacological variant that more selectively treats anorexia nervosa could be a helpful way to avoid the “stigma” of taking an antipsychotic while giving clinicians an additional tool for helping patients.

“I think the clinical field is certainly very ready for something that is going to make a difference,” Le Grange said. “I’m not saying there’s a ‘magic pill’ for anorexia nervosa, but we have been lacking any pharmacological agent that clearly contributes to the recovery of our patients. Many parents and many clinicians are looking for that, because it would make our job so much easier if there was something that could turn symptoms around and speed up recovery.”

Additionally, the study demonstrated the innovative experimental design and translational results that can come from a collaboration of laboratory and clinical experts.

“We don’t talk to one another often enough in basic science and clinical science,” Le Grange said. “More of that would be helpful for clinicians to understand the neurobiology of this disease. I’m very excited about the way this project is going, and I think it’s going to be clinically very informative.”

The paper, “Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice,” was published online March 7 by Neuropsychopharmacology (doi: 10.1038/npp.2012.7). In addition to Klenotich, Dulawa and Le Grange, authors include Mariel Seiglie and Priya Dugad of the University of Chicago and Matthew S. McMurray and Jamie Roitman of the University of Illinois at Chicago. Funding for the research was provided by the National Institute of Mental Health.

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March 28, 2012

Chicago-area residents gathering at the Sheraton Hotel on April 20 will have one thing in common: They either have celiac disease or they know someone who does.

This year at the Spring Flours Benefit for the University of Chicago Medicine’s Celiac Disease Center, guests will have the opportunity to visit gluten-free tasting stations offering savory and delicious dishes, talk with 28 of Chicago’s finest chefs and restaurant owners, and bid on a variety of auction items — all while raising money for the Celiac Disease Center. The event is expected to draw a sell-out crowd of more than 500 attendees.

Most attendees at the benefit are not on a gluten-free diet by choice. Rather, they have celiac disease, the world’s most common genetic autoimmune disease, and must stay away from foods that contain gluten. Celiac disease affects more than 3 million Americans and can develop at any age. Currently, a strict gluten-free diet is the only known treatment for the disease. Gluten is a protein found in wheat, barley and rye.

“I was diagnosed with celiac disease three years ago. After going gluten-free, my health turned around. I’m now healthier and stronger than I’ve ever been,” said Rachel O’Konis, a Chicago resident and Celiac Disease Center board member. “To me, Spring Flours is really a celebration of my health. It’s a great opportunity to connect with other celiacs and to thank local chefs who are committed to serving me safe gluten-free food.”

For Chicago-area chefs and restaurant owners, the Spring Flours Benefit has become a way to showcase their gluten-free menu items and better understand some of their most loyal customers.

“We make safe, gluten-free eating a priority in our restaurant. That way, parents don’t have to worry and kids can enjoy pizza and pasta, just like everyone else,” said Bill Bauer, owner of Marcello’s. “We love participating in this event every year. Not only is it a great cause, but it’s worth it just to see the kids’ eyes light up!”

Participating restaurants donate all of the food and staff to support the annual event, which is the largest fundraiser for the University of Chicago Medicine’s Celiac Disease Center. The center uses its funds to provide diagnosis, care, awareness and research of celiac disease. In fact, University of Chicago Medicine researchers have made recent breakthroughs that are likely to lead to a cure for the disease in the next 10 to 15 years.

“Spring Flours is not only critical to our financial existence, but a fabulous way to help increase the quality of life for those with celiac disease,” said Carol Shilson, the center’s executive director. “We are thrilled that so many can experience this event and are engaged in our work to find a cure.”

The 2012 Spring Flours Benefit is at 6 p.m. Friday, April 20, in the Chicago Ballroom at the Sheraton Hotel and Towers downtown. The event will feature gluten-free tasting stations staffed by Chicago-area chefs, a specialty martini, and a live auction. Tickets are available through April 10.

The restaurants showcased at Spring Flours include: Café Ba-Ba-Reeba, Centered Chef, Chicago q, The Claim Company, City Park Grill, Cooper’s Hawk Winery and Restaurants, Da Luciano Restaurant, Deerfields Bakery, Harry Caray’s Restaurant Group, Marcello’s Restaurant, Mastro’s Steakhouse, Maya Del Sol, Mity Nice Grill, Mon Ami Gabi, Nacional 27, OMG It’s Gluten Free, Osteria Via Stato, Pinstripes, RL, Real Urban Barbecue, Rose’s Wheat Free Bakery, Roy’s Hawaiian Fusion Cuisine, Salpicon, Senza, Sweet Ali’s Gluten-Free Bakery, Swirlz Cupcakes, Wildfire, Zapatista – Cuisines of Mexico, and ZED451. The martinis will be provided by 4 Rebels Vodka.

About the University of Chicago Medicine’s Celiac Disease Center
The University of Chicago Medicine’s Celiac Disease Center has improved the care, diagnosis and awareness of celiac disease. In addition, it provides the infrastructure and support needed to advance cutting-edge celiac research, including recent ground-breaking investigations that show great promise of a cure for the disease. As part of the University of Chicago Medicine, the Celiac Disease Center is a 501-c3 non-profit organization, completely funded by donor contributions. For more information, please visit cureceliacdisease.org

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March 22, 2012

How often does your doctor ask about your sexual life?

Unfortunately, the answer may be: not often enough. Leaving the subject off the check-up checklist could mean missing an important link to overall wellness.

Results of a comprehensive national survey of U.S. obstetrician-gynecologists regarding communication with patients about sex have found that too often doctors aren’t having “the talk” with their patients. And when the topic of sex does find its way into a doctor’s office or exam room, chances are the discussion only skims the surface.

The report, “What We Don’t Talk about When We Don’t Talk about Sex,” uncovers the shortfalls in doctor-patient communication around sexual matters and examines the barriers that may be limiting the range of dialogue in a typical evaluation of a woman’s general health. The study is being published today in the Journal of Sexual Medicine.

The survey, conducted by a team of University of Chicago researchers, found that while nearly two-thirds of OB-GYNs routinely inquire about patients’ sexual activity, other aspects of female sexuality are not routinely addressed. Only 40 percent of those surveyed routinely ask questions to assess for sexual problems or dysfunction. Far fewer, 29 percent, routinely ask patients about satisfaction with their sexual lives and 28 percent routinely confirm a patient’s sexual orientation.

Given the well-established link between a sexual function and overall health, the study’s authors say their findings point to a clear need for stronger guidelines for doctors on conducting a thorough sexual history.

“As a practicing OB-GYN, many of my patients say I’m the first physician to talk with them about sexual issues,” said Stacy Tessler Lindau, MD, associate professor of obstetrics and gynecology at the University of Chicago Medicine, and the study’s lead author. “Sexuality is a key component of a woman’s physical and psychological health. Obviously, OB-GYNs are well positioned among all physicians to address female sexual concerns. Simply asking a patient if she’s sexually active does not tell us whether she has good sexual function or changes in her sexual function that could indicate underlying problems.”

There is strong evidence of a high prevalence of sexual function concerns among women. Recent studies estimate that roughly a third of young and middle-age women and about half of older women experience some sort of sexual problem such as low desire, pain during intercourse or lack of pleasure.

For most, the concerns go beyond physical — in fact, the impact of sexual dysfunction can be far reaching. In addition to strained relationships, many women experience worry, shame, guilt and feelings of isolation. If the doctor doesn’t ask, patients often assume the topic is not welcome for discussion.

“Many women are suffering in silence,” Lindau said. “Patients are often reluctant to bring up sexual difficulties because of fear the physician will be embarrassed or will dismiss their concerns. Doctors should be taking the lead. Sexual history taking is a fundamental part of gynecologic care. Understanding a patient’s sexual function rounds out the picture of her overall health and can reveal underlying issues that may otherwise be overlooked.”

The study also takes a close look at whether factors such as gender, age, race, medical school location, immigration status, religious affiliation or type of practice play a role in the likelihood an OB-GYN will broach sexual matters. Not surprisingly, female doctors are more likely to address sexual activity with female patients. Doctors who see more patients for gynecology versus prenatal care tend to screen for sexual dysfunction more frequently than their colleagues. OB-GYNs age 60 and older are less likely to delve into a patient’s sexual orientation or identity.

Generally, less than a third of all OB-GYNs surveyed routinely ask patients about their sexual orientation. Assuming heterosexuality can alienate a lesbian or bisexual patient and result in misinterpretation of symptoms and misdiagnosis. The report suggests this remains an important area for further research.

“One explanation for the findings may be a deficit in physician training about diagnosis and treatment of female sexual problems,” said first author Janelle Sobecki, MA, a second-year medical student at Wayne State University.  ”Like patients, physicians may worry that raising the topic could offend or embarrass the patient. Physicians, especially OB-GYNs, are better positioned than patients to open the door for discussion.”

For many women grappling with a sexual problem, the underlying cause may be treatment for another medical condition. Drugs regularly prescribed for conditions from depression to breast cancer can have a negative effect on sexual function in some women, including low libido. Patients may be better able to tolerate these side effects if they know to expect them.

An emerging area of concern for Lindau — a specialist in maintaining sexual function in cancer survivors — is prevention measures for patients at high risk for developing breast cancer. Drugs such as aromatase inhibitors and tamoxifen, which interfere with the activity of estrogen and therefore reduce breast cancer risk, are becoming more widely used, including among younger women.

“Women are not being counseled on the potential sexual side effects of these treatments, and we have limited data to appropriately counsel them,” Lindau said. “For men with prostate cancer, in comparison, the impact of treatment on sexual function is typically discussed as part of deciding which therapy to try.”

One reason doctors may feel more comfortable discussing sex with men is the availability of FDA-approved treatments for erectile dysfunction, while medical treatments for female sexual dysfunction are limited.

The good news is that women are seeking and demanding more information about their personal health, oftentimes turning to the anonymity of the Internet as a first resource. Ideally, Lindau adds, these women are empowered by reputable online and other media sources to know that they are not alone in their concerns and will gather the courage to begin a conversation with a physician.

“If you have a doctor you trust who has not brought this topic up, give it a try,” Lindau adds. “If you are waiting for the doctor to start the conversation, it may never happen. Communication is key.”

This study was supported by grants from the Greenwall Foundation, John Templeton Foundation, the National Center for Complementary and Alternative Medicine and the National Institute on Aging. Additional authors of the study include Farr Curlin, MD, and Kenneth Rasinski, PhD.

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March 21, 2012

Opioid drugs used to relieve pain in postoperative and chronic cancer patients may stimulate the growth and spread of tumors, according to two studies and a commentary in the 2012 annual Journal Symposium issue of Anesthesiology, the academic journal of the American Society of Anesthesiologists.

“Epidemiologic findings suggest that the type of anesthesia we do for cancer surgery influences recurrence rate, and laboratory studies demonstrate that opioids influence tumor progression and metastasis,” said Jonathan Moss, MD, PhD, professor of anesthesiology and critical care at the University of Chicago Medicine and co-author of the commentary, a summary of research on the topic. “These studies have caused anesthesiologists to re-evaluate how best to do anesthesia and pain control for cancer patients.”

New studies provide new clues
Opioid-based painkillers, such as morphine, have been the gold standard for treatment of postoperative and chronic cancer pain for 200 years. Several studies published since 2002, however, suggest that opioids can stimulate the growth and spread of cancer cells. Laboratory research from the University of Chicago Medicine and a genetic study from the University of North Carolina Medical Center both argue that the mu opioid receptor plays an important role in tumor progression and support a therapeutic role for opioid antagonists.

One study presented in the journal — from a group led by Patrick Singleton, PhD, assistant professor of medicine at the University of Chicago Medicine — shows how opioids already present in the body can enhance the malignant tendencies of human lung cancer cells transplanted into mice, even without the addition of morphine.

Singleton’s team found that cells from various types of human lung cancers have five to 10 times as many opioid receptors as non-cancerous lung cells. They mapped out two of the biochemical pathways — Akt and mTOR, both targets for current chemotherapeutics — triggered by contact between endogenous opioids and the receptors. They also show how this interaction can increase proliferation, migration and invasion of tumor cells, three hallmarks of cancer growth and spread.

In this study, human lung cancer cells with additional copies of the opioid receptor grew more than twice as fast as tumor cells that lacked extra receptors when transplanted into mice. More troubling, they were 20 times more likely to spread to distant sites. Medications that block the opioid receptors, such as naloxone or methylnaltrexone, reduced tumor growth and spread. “Our findings,” they conclude, “suggest the mu opioid receptor may be a therapeutic target.”

The other paper in the journal, a retrospective study by Andrey Bortsov, MD, PhD, assistant professor of anesthesiology and colleagues at the University of North Carolina, used human data to bolster the opioid-cancer link.

Bortsov’s team looked at survival rates from an earlier study of more than 2,000 breast cancer patients. Women being treated for invasive breast cancer who had a tiny genetic mutation that made them less sensitive to opioids were much more likely to be alive 10 years after cancer treatment. Women with one copy of the protective mutation were nearly twice as likely to have survived; those with two copies were four times as likely.

“The results of this study,” the authors wrote, “provide support for the hypothesis that endogenous and/or exogenous opioids, acting via the mu opioid receptor, may influence cancer outcomes.”

Emergence of concern
The notion that opioids could encourage cancer growth started with a 2002 laboratory report from the University of Minnesota. Later, a randomized palliative-care trial from Virginia Commonwealth University found that patients who received spinal opiates (OK) rather than systemic pain relief survived longer. Then two retrospective studies showed that breast or prostate cancer patients who received local or regional anesthesia rather than systemic morphine had improved survival after surgery. More recent epidemiologic studies in colon cancer, however, failed to confirm the relationship.

Moss and University of Chicago colleagues approached the issue from a similar angle. They were involved in clinical trials of methylnaltrexone, a drug developed at the University of Chicago and approved by the Food and Drug Administration in 2008. This drug, marketed as Relistor™, was designed to block the peripheral side effects of opioids, such as nausea and constipation, without disrupting pain relief, which occurs in the brain. Following an early clinical study, Moss and colleagues noted that cancer patients receiving this peripheral opioid blocker in a compassionate-use protocol lived longer than expected.

“These were patients with advanced cancer and a life expectancy of one to two months,” Moss recalled, “yet several lived for another five or six months. It made us wonder whether this was just a consequence of better GI function, or could there possibly be an effect on the tumors?”

They began a series of studies looking at the many peripheral effects of opioids and the potential benefits of blocking those effects. They found that those opioids enhanced tumor growth, angiogenesis, vascular permeability and metastasis. Drugs that blocked the opioid receptor reduced cancer growth and helped prevent invasion and metastasis. Tumors did not grow in mice that lacked the mu opioid receptor.

In a commentary in the journal, Moss, Singleton and Frances Lennon, PhD, summarize results from multiple studies to argue that opioids — drugs like morphine or the body’s own opioids, such as endorphins — appear to have a significant and direct proliferative effect on cancer cells, aside from their effect suppressing immunity. They suggest a possible therapeutic role for mu opioid receptor antagonists on cancer growth and metastasis, but caution that “there are no clinical trials in humans demonstrating a direct effect.”

Funding for the studies was provided by the National Cancer Institute, the University of North Carolina and the University of Chicago. Moss, one of the developers of methylnaltrexone, receives royalties from its sale and is a paid consultant for its distributor, Salix Pharmaceuticals Inc.

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March 13, 2012

The University of Chicago’s Pritzker School of Medicine has been named one of the Top 10 medical schools in the United States, by U.S. News & World Report‘s annual “Best Graduate Schools” survey.
                                                                                  
The latest rankings of the nation’s graduate programs, available online beginning Tuesday, placed Pritzker at No. 10, up from the 12th spot last year and from 22nd in 2004. Pritzker tied with two other medical schools, the University of Michigan at Ann Arbor and the University of Washington, for the 10th-place ranking. No other medical school in Illinois made the Top 10 list.

Pritzker ranks second in the country on research funding per faculty member, according to the magazine, with average annual grant support per researcher from the National Institutes of Health of $328,000, behind only Stanford University. Pritzker is also among the leaders in the U.S. in student selectivity. The medical school has dramatically increased its ability to attract the best students, rising from 41st in the United States in 2004 to fourth in the latest survey.

“It is an honor to be considered one of the leading medical education programs in the country,” said Kenneth S. Polonsky, MD, dean of the Pritzker School of Medicine and executive vice president for Medical Affairs at the University of Chicago Medicine. “It is gratifying to know that we scored near the top on the research achievements of our faculty as well as on student selectivity.”

U.S. News & World Report surveyed all 149 medical schools and ranked them based on two types of data: expert opinions about program excellence and statistical indicators that measure the quality of a school’s faculty, research and students. Medical school rankings, for example, are based on a weighted average of research activity, student selectivity, admission statistics (MCAT, grade point average, and acceptance rate) and faculty-to-student ratio.

“The ranking of our school is one measure of the excellence of our students and faculty,” said Holly Humphrey, MD’83, dean for medical education at the University of Chicago Pritzker School of Medicine. ”By bringing together bright, motivated students with a talented, world-class faculty, we enjoy an intellectually rich and stimulating environment for learning medicine.”

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