Insights into Parkinson's balance problems

In PD, disorganized sensorimotor signals cause muscles in the limbs to contract, such that both a muscle promoting a motion and its antagonist muscle are Read more

Cajoling brain cells to dance

“Flicker” treatment is a striking non-pharmaceutical approach aimed at slowing or reversing Alzheimer’s disease. It represents a reversal of EEG: not only recording brain waves, but reaching into the brain and cajoling cells to dance. One neuroscientist commentator called the process "almost too fantastic to believe." With flashing lights and buzzing sounds, researchers think they can get immune cells in the brain to gobble up more amyloid plaques, the characteristic clumps of protein seen in Read more

Research

Pediatric liver disease on the rise

Miriam Vos, MD with patient.

Miriam Vos, MD with patient.

Miriam Vos, MD treats a growing number of children with nonalcoholic fatty liver disease. Yet little research has been conducted into the development of the illness. Nonalcoholic fatty liver disease in children, which often is associated with obesity, occurs when fat deposits itself in the liver. It eventually can lead to inflammation, cirrhosis and even liver failure.

In the hopes of preventing the disease in children, Vos, a pediatric hepatologist at Emory University School of Medicine

and Children’s Healthcare of Atlanta, is conducting research into the origins of this disorder in children. She suspects a diet high in sugar and too little exercise are tied to its onset.

In fact, a recent study led by Vos found that Americans are getting more than 10 percent of their daily calories from fructose, used mainly in sugar-sweetened beverages and processed foods.

The study analyzed the amount and sources of dietary fructose consumption among U.S. children and adults from 1988 to 1994. The researchers found that U.S. children and adults consumed 54.7 grams of fructose per day, an almost 50 percent increase from a national study sample conducted in 1977-1978.

Fructose occurs naturally in fruits and vegetables, however, it is added to many processed foods as table sugar (sucrose) and high-fructose corn syrup.

Vos has written a book aimed at helping children and their families shed pounds and achieve better nutrition through changes in lifestyle and diet.

To hear Vos’s own words about nonalcoholic fatty liver disease in children, listen to Emory University’s Sound Science podcast.

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New heart valve replacement option under study

A new option for heart valve replacement is under study at Emory University Hospital. Cardiologists at the Emory Heart & Vascular Center are conducting groundbreaking research to study a non-surgical treatment option for patients with severe aortic stenosis, a narrowing of the aortic valve opening that affects tens of thousands of people each year. It is most common among elderly patients over 70 years of age, but can surface earlier in life in those with rheumatic heart disease or congenital abnormalities of the valve. Patients often develop symptoms of chest pain, shortness of breath, fainting spells and heart failure.

Peter Block, MD

Peter Block, MD

Emory cardiologists, led by Peter Block, MD, FACC, professor of medicine, Emory School of Medicine, are performing percutaneous aortic valve replacement as part of a clinical trial, comparing this procedure with traditional, open-heart surgery or medical therapy in high-risk patients with aortic stenosis. It provides a new way for doctors to treat patients who are too ill or frail to endure the traditional surgical approach. So far, 115 people have participated in the phase II clinical trial.

In this new procedure, doctors create a small incision in the groin or chest wall and then feed a wire mesh valve through a catheter and place it where the new valve is needed. The standard therapy, which has been used to treat aortic stenosis for more than 30 years, is to remove the diseased valve through open-heart surgery.

Block says the results seen so far in this clinical trial show great promise for this procedure. He says this is especially important since tens of thousands of Americans are diagnosed with failing valves each year and that number is expected to increase substantially in the coming years as baby boomers pass the age of 70.

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Strategies to target cancer stem cells

A story in last Friday’s New York Times highlights research on “cancer stem cells”: a fraction of cells in a tumor that are especially resistant to chemotherapy and resemble the body’s non-cancerous stem cells in their ability to renew themselves.

The story describes work by a team at the Broad Institute, who reported in the journal Cell that they had identified compounds that specifically kill cancer stem cells. The hope is that compounds such as these could be combined with conventional treatments to more effectively eliminate cancers.

However, scientists disagree on whether the phenomenon of cancer stem cells extends to different kinds of cancer and what is the best way to target them. Previously not much was known about how to attack these cells.

Work at Emory’s Winship Cancer Institute has been tracking how some biomarkers in cancer cells resemble or differ from those found in stem cells. These markers may help researchers home in on the cancer stem cells.

 

Anticancer therapy must target more than one type of cell. TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor

If "cancer stem cells" play the critical roles some scientists think they do, anticancer therapy must target more than one type of cell. In this figure from Van Meir + Hadjipanayis' review, TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor cells.Â

 

 

In a recent review, Emory brain cancer specialists Erwin Van Meir and Costas Hadjipanayis write:

The “cancer stem cell” hypothesis has invigorated the neuro-oncology field with a breath of fresh thinking that may end up shaking the foundation of old dogmas, such as the widely held belief that glioblastoma tumors are incurable because of infiltrative disease. If the infiltrated cells are in fact differentiated tumor cells, their dissemination beyond the surgical boundary may not be the primary cause of tumor recurrence.

Van Meir, the editor of a new book on brain cancer, adds this comment:

Clearly a lot more work needs to be done to understand the precise cause of glioblastoma recurrence after surgery and chemotherapy and how to prevent it.  The possibility of developing therapeutics that can specifically target the brain cancer stem cells is an exciting new development but will have to proceed with caution to spare normal stem cells in the brain. Developing new imaging tools that can track cancer stem cells in the brain of treated patients is also an important objective and some of the Emory investigators are evaluating the use of nanoparticles to this purpose.

A new faculty member at Winship, Tracy-Ann Read, recently published her research on a molecule that could be used to identify “tumor-propagating cells” in medulloblastoma, a form of brain cancer. She says:

Although cancer stem cells have been identified in many different types of cancer, it is becoming increasingly clear that the properties of these cells may vary greatly among the different tumor types. It is unlikely that one  therapeutic agent will be able to target the cancer stem cells in for example all types brain tumors. Hence  much work still needs to be done in terms of analyzing the properties of these cells in each tumor type and identifying the genes that are responsible for their unique ability to propagate the tumors. 

Winship’s director Brian Leyland-Jones has also reported at the San Antonio Breast Cancer Symposium that molecules that distinguish a hard-to-treat form of breast cancer resemble those that maintain stem cells.

Nice round-up from Nature’s stem cell blog editor Monya Baker

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Leverage universities for growth of metro Atlanta

Emory University President James W. Wagner, PhD

Emory University President James W. Wagner, PhD

In an Aug. 12 opinion piece published in The Atlanta Journal-Constitution, Emory University President James W. Wagner, PhD, says that if Atlanta is to move forward, it must recognize the important role that its colleges and universities play and put them front and center in public and private economic development plans.

Wagner notes that colleges and universities like Emory create the human capital needed to advance the economic, social and cultural lifeblood of a community.

“Work in the area of sustainable development creates an opportunity for the production of new ideas that can be applied as far away as a remote village in Africa or as close as the crowded corridors of metro Atlanta,” says Wagner.

“Whether the goal is creating world-class facilities for the research and treatment of cancer in Atlanta or a healthier economic climate through sustainable development on another continent, America’s most successful communities have come to rely heavily on their universities and colleges to sustain economic and social progress.”

Visit AJC.com to read Wagner’s opinion piece on the impact that Emory and other colleges and universities have on the communities they serve and how they can help move the region and state forward.

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Relocating central vision

Susan Primo, MD

Susan Primo, MD

The patients seen by Emory low vision specialist Susan Primo, OD, MPH, have already exhausted most of their treatment options. They’ve completed medication regimens or had surgery to slow advanced age-related macular degeneration (AMD), a leading cause of blindness in the elderly. But still they don’t see well.

That’s where Primo comes in. At the Emory Eye Center, she’s studying whether behavioral modifications can lead to a change in brain activity to maximize use of remaining vision.

In macular degeneration, the macula—a layer of tissue on the inside back wall of the eyeball—gradually deteriorates. That delicate tissue is responsible for visual acuity, particularly in the center of the retina. Central vision is needed for seeing small and vivid details such as words on a page or the color of a traffic light, which means it is vital for common daily tasks such as reading or driving.

In more than two decades of working with patients who are visually impaired, Primo realized that people typically use their peripheral vision to compensate for loss in central vision. Studies have shown that people with progressive central vision loss compensate by spontaneously adopting a preferred retinal location (PRL) that takes over responsibility for visual clarity.

Normal vision

Normal vision

Vision with macular degeneration

But Primo and Georgia Tech psychologist Eric Schumacher wanted to know whether using these peripheral regions causes a change in how the brain is organized. Armed with Schumacher’s expertise in functional magnetic resonance imaging (fMRI) and Primo’s clinical experience, the researchers did indeed discover continued activity in the part of the brain that maps to the macula. The brain scans of people with AMD who had developed their peripheral vision showed substantially more activity than those of people who had not developed a PRL. Their study appeared in the December 2008 edition of Restorative Neurology and Neuroscience.

In a current study, Primo and Schumacher are exploring whether occupational training and biofeedback can help people with AMD focus on using good retinal cells and in turn speed up the brain’s reorganization.

“Although others have tried to study this reorganization of macular degeneration before, no one, to our knowledge, has tried to influence it,” says Primo. “Yet it’s important to begin to come up with therapies, treatments, and technology to help patients begin to use their residual vision faster and better than they could before.”

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Aspirin may aid colorectal cancer survival

This week’s Journal of the American Medical Association (JAMA) reports on the potential benefits of aspirin following a colorectal cancer diagnosis.

Dr. Vincent Yang

Vincent Yang, MD, PhD

Emory digestive disease expert Vincent W. Yang, MD, PhD, professor and director of the Division of Digestive Diseases, Emory School of Medicine, comments on the new study:

A large body of evidence shows that regular aspirin use can reduce the formation of colorectal cancer. Aspirin inhibits the activity of an enzyme called cyclooxygenase-2, or COX-2, that is often over-expressed in colorectal cancer.

In the Aug. 12 issue of JAMA, a study led by Andrew Chan, MD, MPH, of the Harvard Medical School, shows that regular aspirin use reduces deaths in patients who had been diagnosed with colon cancer. The study includes two large, diverse groups of individuals who were followed for more than 20 years for various health-related issues.

The individuals who developed colorectal cancer during the follow–up period and had used aspirin regularly had a lower death rate than those patients who developed colon cancers and did not take aspirin. More importantly, the benefit patients received from regularly using aspirin was more apparent if their cancers were positive for COX-2.

The results of this new study are consistent with the earlier finding reported in medical journals about aspirin’s chemopreventive effect on colorectal cancer. However, it should be noted that this study is observational by nature and that regular aspirin use can result in significant toxicities.

To learn more about the routine use of aspirin as an adjunct treatment for colorectal cancer, studies that are blinded and randomized placebo-controlled are necessary. Such clinical trials have been conducted which proved that aspirin taken at 81 mg or 325 mg per day is effective in preventing the recurrence of colorectal adenomas (polyps) after they are removed during screening colonoscopy.

A similar clinical trial could be conducted to test the ability of aspirin to prevent colorectal cancer recurrence. Perhaps patients could first be classified based on the COX-2 levels in their tumors before being randomized into the trial. A potential outcome would be that patients with COX-2-positive tumors would receive more benefit from aspirin use than those with tumors that are COX-2-negative. Chan’s JAMA findings are a catalyst for further study.

Yang is also professor of hematology and oncology at Emory Winship Cancer Institute.

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H1N1 flu clinical studies start at Emory today

Emory doctors discuss H1N1 studies

Emory doctors discuss H1N1 studies

Today Emory researchers began vaccinating volunteer participants in the first of several planned clinical trials of a new H1N1 vaccine. A morning press briefing attended by Atlanta and national media provided Emory a platform to inform the public.

The clinical trials are expected to gather critical information that will allow the National Institutes of Health to quickly evaluate the new vaccines to determine whether they are safe and effective in inducing protective immune responses. The results will help determine how to begin a fall 2009 pandemic flu vaccination program.

Emory began signing up several hundred interested volunteers about two weeks ago and has been screening the volunteers to make sure they fit certain criteria. Volunteers will receive their first vaccinations over the first week of the trial and will return several times over the course of nine weeks to receive additional vaccinations and blood tests.

H1N1 clinical trial volunteer

H1N1 clinical trial volunteer

The clinical trials are in a compressed timeframe because of the possible fall resurgence of pandemic H1N1 flu infections that may coincide with the circulation of seasonal flu strains.

The clinical trials are being conducted by the eight Vaccine and Treatment Evaluation Units (VTEUs), supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

For more information about the Emory flu clinical trials, call 877-424-HOPE (4673) for the adult and senior studies, or 404-727-4044 for the pediatric studies.

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Discerning a prelude to Alzheimer’s

Imagine that an elderly relative has been having difficulty remembering appointments and acquaintances’ names, or even what happened yesterday. Memory problems can be signs of mild cognitive impairment (MCI), a prelude to Alzheimer’s disease.

Scientists believe that the outward effects of the slow damage that comes from Alzheimer’s only show up after the damage has been accumulating for years. However, memory difficulties can also be the result of stress or another health problem. Patients thought to have MCI at an initial doctor’s visit sometimes improve later.

That’s why researchers at Emory’s Alzheimer’s Disease Research Center have been testing noninvasive imaging approaches to distinguishing MCI from healthy aging and Alzheimer’s. Their goal is to identify individuals at risk of developing Alzheimer’s, at a time when intervention can make a difference in how the disease progresses.

“We believe that imaging technology may help us find the signature changes in brain structure that are specific to MCI,” says Felicia Goldstein, PhD, associate professor of neurology.

Color coded diffusion tensor image (DTI) of a brain section from a healthy individual (A) showed a thick and intact corpus callosum (orange color), a white matter fiber bundle connecting left and right hemisphere as illustrated in the 3D rendering of the tractograph derived from DTI (B). However, a thin and narrow corpus callosum is seen in an AD patient (C) due to the degeneration of this white matter structure

Color coded diffusion tensor image (DTI) of a brain section from a healthy individual (A) showed a thick and intact corpus callosum (orange color). However, a thin and narrow corpus callosum is seen in an AD patient (C) due to the degeneration of this white matter structure. Courtesy of Hui Mao.

Two recent papers highlight the use of diffusion tensor imaging, an advanced form of magnetic resonance imaging.

The first paper was published by Brain Imaging and Behavior with Goldstein as first author, in collaboration with Hui Mao, PhD, associate professor of radiology, and ADRC colleagues.

It examines diffusion tensor imaging as a way to probe the integrity of the brain’s white matter, and compares it with tests of memory and behavior traditionally used to diagnose MCI and Alzheimer’s.

White matter appears white because of the density of axons, the signal-carrying cables allowing communication between different brain regions responsible for complicated tasks such as language and memory.

Diffusion tensor imaging allows researchers to see white matter by gauging the ability of water to diffuse in different directions, because a bundle of axons tends to restrict the movement of water in the brain.

Goldstein and her colleagues found that patients diagnosed with “amnestic” MCI showed greater loss of white matter integrity in a certain part of the brain — the medial temporal lobe – than cognitively normal controls of similar age. This loss of white matter was linked with poor recall of words and stories.

The second paper, with Liya Wang, PhD, a senior research associate in Mao’s laboratory as first author, was published by the American Journal of Neuroradiology in April. Here the authors try combining probing white matter integrity with a MRI measure of whether the brain has shrunk as a result of disease.

Combining the two methods improves the accuracy of MCI diagnosis with respect to either alone, the authors found.

Mao notes that Emory has been participating in a multi-center study called ADNI (Alzheimer’s Disease Neuroimaging Initiative). Diffusion tensor imaging is a relatively new technique and could add information to future large-scale Alzheimer’s imaging studies, he says.

The Dana Foundation’s BrainWorks newsletter had an article recently on Alzheimer’s and brain imaging.

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A new and faster way to diagnose and fight flu

flu imageA new method of rapidly producing highly targeted monoclonal antibodies could soon be used to rapidly diagnose H1N1 influenza. Just a month after vaccinating people with a seasonal flu vaccine, the researchers were able to use just a few tablespoons of the vaccinated individuals’ blood to generate antibodies against that specific strain of flu. The research was published last spring in Nature.

The scientists believe their discovery could be applied to any infectious disease. By using a few drops of blood from infected people, they could isolate antibodies to rapidly diagnose a newly emerging flu strain such as H1N1.

There are many variations of H1N1, says Rafi Ahmed, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar, but this technology could be used to identify a very specific strain, such as the one we’re dealing with in the current pandemic. The diagnostic tests available now are not specific to any particular H1N1 strain.

Ahmed and his colleagues, including postdoctoral fellow Jens Wrammert, and Patrick Wilson from the University of Chicago, hope their work will lead to a new, specific test for H1N1 within the next several months.

Conventional methods of making human monoclonal antibodies are time-consuming and laborious, says Ahmed. For example, one method involves sifting through human B cells —white blood cells that make human antibodies—and then looking for specific cells that make the right antibodies.

Not only is the new method quicker and less cumbersome, it could be applied to almost any infectious disease. In any kind of emerging infection, speed is essential, says Ahmed.

To listen to Ahmed describe the new monoclonal antibody method, listen to Emory’s Sound Science podcast.

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Lampreys’ alternative immune system

Lampreys are primitive creatures – basically, tubes with teeth. Their primitive nature makes them a fascinating entry-point for studying the evolution of the immune system.

At Emory, Max Cooper and his colleagues have been studying lampreys’ versions of white blood cells. In a recent Nature paper, they show that lampreys have two kinds of cells that look very much like B and T cells in mammals, birds and fish.

Non-immunologists may shrug at this revelation.  But consider: lampreys have a completely different set of tools for fighting infections. They have proteins in their blood that glob on to invaders, but they don’t look anything like the antibodies found in mammals, birds and fish.

Lampreys in a laboratory tank

Lampreys in a laboratory tank. Courtesy of Masa Hirano.

Similarly, lampreys have cells that look like T Ray Ban outlet cells, in terms of some of the genes that are turned on. However, they don’t have MHC genes, which are important in human transplant medicine because they determine how and when T cells get excited and reject transplanted organs.

Lampreys are thought to be an early offshoot on the evolutionary tree, before sharks and fish, and way before critters that crawl on land. This suggests that the categories (B or T) came first even though the characteristic features of the cells (antibodies/responding to MHC) are different.

“Lampreys have the same types of cells, but they just use different building blocks to put them together,” Cooper says.

Cooper, now a Georgia Research Alliance Eminent Scholar and a member of Emory’s pathology department, made pioneering studies defining the role the thymus plays in immune development at the University of Minnesota in the 1960s. The thymus is where T cells develop and where they get their name.

He says he is now collaborating with Thomas Boehm in Freiburg, Germany to better understand the evolution of the thymus. Again, lampreys don’t have a thymus, but they may have an area next to their gills where the T-like cells develop.

John Travis at Science has a more extensive discussion of this research.

In a Darwin-anniversary essay, Travis tells the story of how the evolution of the immune system was a centerpiece of the 2005 Kitzmiller v. Dover trial, when a Pennsylviania school district’s requirement to teach intelligent design was successfully challenged.

Link to Sound Science podcast with Cooper

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