Overcoming cardiac pacemaker "source-sink mismatch"

Instead of complication-prone electronic cardiac pacemakers, biomedical engineers at Georgia Tech and Emory envision the creation of “biological Read more

Hope Clinic part of push to optimize HIV vaccine components

Ten years ago, the results of the RV144 trial– conducted in Thailand with the help of the US Army -- re-energized the HIV vaccine field, which had been down in the Read more

Invasive cancer cells marked by distinctive mutations

What does it take to be a leader – of cancer cells? Adam Marcus and colleagues at Winship Cancer Institute are back, with an analysis of mutations that drive metastatic behavior among groups of lung cancer cells. The findings were published this week on the cover of Journal of Cell Science, and suggest pharmacological strategies to intervene against or prevent metastasis. Marcus and former graduate student Jessica Konen previously developed a technique for selectively labeling “leader” Read more

News

Autism linked to hundreds of spontaneous genetic mutations

Emory genetic researchers Daniel Moreno De Luca, Christa Lese Martin and David Ledbetter were part of a team that produced a landmark result in autism genetics. The team identified hundreds of regions of the genome where spontaneous mutations are implicated in autism. Spontaneous mutations are those that arise for the first time in an individual, rather than being inherited from parents.

Christa Lese Martin, PhD

The team was led by Matthew State at Yale, and their results were published in the journal Neuron. Moreno De Luca discussed the topic in Spanish on a recent edition of the NPR program Science Friday. The June 10 segment was focused on autism genetics.

The team made an intriguing finding on a segment of chromosome 7. Deletion of the region is associated with Williams syndrome, where individuals can exhibit “striking verbal abilities, highly social personalities and an affinity for music.” Duplication of the same region, they found, is associated with autism.

Daniel Moreno De Luca, MD MSc

Companion studies also shed light on the question of why boys are more likely to develop autism than girls, and begin to outline a network of genes whose activity is altered in the brains of individuals with autism.

Ledbetter is now chief scientific officer at Geisinger Health in Pennsylvania.

 

 

 

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Default daydreaming linked to Alzheimer’s amyloid

Cut the daydreaming, and you can lessen the neurodegenerative burden on your brain? Surprising new research suggests that how we use our brains may influence which parts of the brain are most vulnerable to amyloid-beta (Aβ), which forms plaques in the brain in Alzheimer’s disease.

Lary Walker, PhD, has been investigating why amyloid accumulation seems to lead to Alzheimer's in humans but not non-human primates

In the June issue of Nature Neuroscience, Yerkes National Primate Research Center scientist Lary Walker and Mathias Jucker from the Hertie Institute for Clinical Brain Research in Tübingen, Germany summarize intriguing recent research on regional brain activity and Aβ accumulation.

Neuroscientists have described a set of interconnected brain regions called the “default mode network,” which appear to be activated during activities such as introspection, memory retrieval, daydreaming and imagination. When a person engages in an externally directed task, such as reading, playing a musical instrument, or solving puzzles, activity in the default network decreases.

The Nature Neuroscience paper, from David Holtzman and colleagues at Washington University St. Louis, suggests prolonged metabolic activation of the default-mode network in mice can render that system vulnerable to Aβ by accelerating Aβ deposition and plaque growth.

This line of research turns the “use it or lose it” idea upside-down. Use the default network too much, and the effect may be harmful. Walker and Jucker suggest why education, for example, appears to head off Alzheimer’s in epidemiological studies: by getting the brain involved in non-default/externally directed mode activity.

This idea has additional consequences that can be tested in the clinic. For example, by increasing metabolism in default-mode regions of the brain, prolonged wakefulness caused by sleep disorders might increase Aβ burden.

Walker and Jucker conclude: “Meanwhile, perhaps the best strategy for lessening soluble Aβ in the default mode network may be simply to work diligently, play hard and sleep well.”

 

Posted on by Quinn Eastman in Neuro 2 Comments

Low vitamin D in people with HIV: links to heart risk, immune function

In people with HIV, low vitamin D levels have been linked to thicker carotid arteries as well as a weaker comeback for the immune system after starting antiretroviral therapy.

These results, published online recently in the journal Antiviral Therapy, are the first to confirm an association between low vitamin D levels and a measure of higher cardiovascular risk in people with HIV. They also suggest that the benefits of vitamin D supplementation for people with HIV should be evaluated in a clinical trial.

Allison Ross, MD, is an infectious disease specialist in the Department of Pediatrics and the Emory-Children's Pediatric Research Center.

The advent of effective antiretroviral therapy against HIV has dramatically improved life expectancies for people with HIV over the last 15 years. The presence of HIV is known to perturb cardiovascular health, even in the absence of an active infection. Since vitamin D levels are known to have an impact on the immune system and cardiovascular disease risk, that drove infectious disease specialist Allison Ross and her colleagues to probe these connections in people living with HIV. The results were also described on the Web sites AidsMeds and NAM/AidsMap.

Ross studied a group of HIV-positive people enrolled in Case Western Reserve University’s HIV clinic in Cleveland. Colleagues from Emory and Case Western were co-authors.

They tested vitamin D levels, immune function and heart health in 149 HIV-positive people and a matched group of 34 HIV-negative people. Vitamin D levels were significantly lower in the HIV-positive group, even when controlling for known factors that affect vitamin D.

The researchers looked at how much the immune system was able to come back after starting retroviral therapy. This involves comparing someone’s lowest ever CD4 T cell count from the current CD4 count. They found that people with the poorest level of immune restoration were the most likely to have the lowest level of vitamin D. In addition, people with the lowest vitamin D levels were more than 10 times as likely to have thickening of the carotid arteries, as measured by ultrasound.

Inflammation can be a driving factor for heart disease, but in the study, low vitamin D was not linked to higher levels of inflammation markers. Additional research could determine whether those who are starting antiretroviral therapy would see better immune recovery if they took a vitamin D supplement.

Researchers at Emory have been investigating several aspects of low Vitamin D levels and their impact on health, including a connection with Parkinson’s disease. Endocrinologist Vin Tangpricha notes that Emory studies are looking at vitamin D in the context of tuberculosis, sepsis, sickle cell disease, cancer, cystic fibrosis and pain sensitivity.

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Improving the lives of those with rare blood disorders

While many people have never heard of an eosinophil, most people do know what a white blood cell is and have some understanding of its disease and infection-fighting role in the human body.

While these strange-sounding cells play an incredibly important part of the immune system by helping to fight off certain infections, when eosinophils occur in higher than normal numbers in the body without a known cause, a rare eosinophilic disorder may be present.

Typically, eosinophils make up less than five percent of circulating white blood cells in healthy individuals and can vary over time, but when the body wants to attack a substance, , eosinophils respond by moving into the area and releasing a variety of toxins. When the body produces too many eosinophils, they can cause chronic inflammation, resulting in tissue damage within the body.

Emory cardiologist Wendy Book serves as president of the American Partnership for Eosinophilic Disorders (APFED), one of the organizations within the National Organization for Rare Disorders (NORD). Book recently accepted the Abbey S. Meyers Leadership Award on behalf of APFED. The award, named for NORD’s founding president, is presented each year to a NORD Member Organization for demonstrating outstanding leadership and representation of its members.

“I am honored to be part of a collaborative effort among patients, families, physicians, researchers, policy makers and others to develop diagnostics and therapeutics for rare diseases,” says Dr. Book. “We are grateful to work with NORD and other member organizations to provide a voice for those living with rare, and often poorly understood, diseases.”

The awards were presented at the annual NORD Partners in Progress Celebration.  Each year, NORD—a nonprofit organization that represents the 30 million Americans with rare diseases—celebrates pioneering achievements of individuals, organizations, and companies in public policy, patient advocacy, medical research, and product development.

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What cancer researchers can learn from fruit fly genetics

What can scientists studying cancer biology learn from fruit flies?

Quite a lot, it turns out.  At a time when large projects such as the Cancer Genome Atlas seek to define the changes in DNA that drive cancer formation, it is helpful to have the insight gained from other arenas, such as fruit flies, to make sense of the mountains of data.

Drosophila melanogaster has been an important model organism for genetics because the flies are easy to care for, reproduce rapidly, and have an easily manipulated genome. This NCI newsletter article describes how some investigators have used Drosophila to find genes involved in metastasis.

Emory cell biologist Ken Moberg says that he and postdoctoral fellow Melissa Gilbert crafted a Drosophila-based strategy to identify growth-regulating genes that previous researchers may have missed. Their approach allowed them to begin defining the function of a gene that is often mutated in lung cancer. The results are published online in Developmental Cell.

Part of the developing fly larva, stained with an antibody against Myopic. Groups of cells lacking Myopic, which lack green color, tend to divide more rapidly.

Moberg writes:

Many screens have been carried out in flies looking for single gene lesions that drive tissue overgrowth. But a fundamental lesson from years of cancer research is that many, and perhaps most, cancer-causing mutations also drive compensatory apoptosis, and blocking this apoptosis is absolutely required for cancer outgrowth.

We reasoned that this class of ‘conditional’ growth suppressor genes had been missed in prior screens, so we designed an approach to look for them. The basic pathways of apoptosis are fairly well conserved in flies, so it’s fairly straight forward to do this.

Explanatory note: apoptosis is basically a form of cellular suicide, which can arise when signals within the cell clash; one set of proteins says “grow, grow” and another says “brake, brake,” with deadly results.

Gilbert identified the fruit fly gene Myopic as one of these conditional growth regulators. She used a system where mutations in Myopic drive some of the cells in the fly’s developing eye to grow out more – but only when apoptosis is disabled.

Gilbert showed that Myopic is part of a group of genes in flies, making up the Hippo pathway, which regulates how large a developing organ will become. This pathway was largely defined in flies, then tested in humans, Moberg says. The functions of the genes in this pathway have been maintained so faithfully that in some cases, the human versions can substitute for the fly versions.

Myopic’s ortholog (ie different species, similar sequence and function) is the gene His-domain protein tyrosine phosphatase, or HD-PTP for short. This gene is located on part of the human genome that is deleted in more than 90 percent of both small cell and non-small cell lung cancers, and is also deleted in renal cancer cells.

How HD-PTP, when it is intact, controls the growth of cells in the human lung or kidney is not known. Gilbert and Moberg’s findings suggest that HD-PTP may function through a mechanism that is similar to Myopic’s functions in the fly.

Besides clarifying what Myopic does in the fly, their paper essentially creates a map for scientists studying HD-PTP’s involvement in lung cancer, for example, to probe and validate.

Posted on by Quinn Eastman in Cancer 1 Comment

Cardiac alliance seeks improved care and response time for heart attack patients

Approximately 250,000 people each year suffer from a particularly deadly form of heart attack known as a STEMI (ST-Elevation Myocardial Infarction), in which blood flow is completely blocked to the heart. Restoring blood flow quickly is crucial in order to save the patient’s life, yet more than 30 percent of these patients receive no life-saving intervention at all.

Michael Ross, MD

Led by Emory emergency medicine physician Michael Ross, the Society of Chest Pain Centers (SCPC) and the American Heart Association (AHA) recently announced they will be joining efforts to save even more lives. The joint agreement seeks to improve cardiac care, specifically the care of patients suffering from STEMI.

The new collaborative framework for hospital accreditation meets criteria of the AHA initiative “Mission: Lifeline,” established in 2007 to improve the processes surrounding care of the STEMI patient by eliminating the obstacles that keep patients from accessing and receiving appropriate treatments.

Mission: Lifeline systems start with the 9-1-1 call or at the point of entry in the emergency system, continue through the catheterization laboratory and through hospital discharge by promoting best practices that use the latest scientific evidence-based treatment for STEMI.

Mission: Lifeline systems currently cover more than 56 percent of the United States. Mortality rates from STEMI have decreased from 5.8 percent in 2008 to 4.8 percent in 2010.

“SCPC, through their Chest Pain Center accreditation, has already improved cardiac processes in close to 14 percent of hospitals within the U.S. and has moved this accreditation to the international setting,” says Ross, who is immediate-past SCPC president and an associate professor of emergency medicine and medical director for observation medicine at Emory.

“Collaboration between these two non-profit organizations, who share similar missions, will help bring consistency to health care delivery by providing a standard approach to the treatment of STEMI. Providing cardiac accreditation programs is in the best interest of patients, meets the needs of the health care community, and will help to significantly reduce cardiac deaths.”

Both Emory University Hospital and Emory University Hospital Midtown are not only accredited by the Society of Chest Pain Centers, but are also  the only accredited chest pain centers in metropolitan Atlanta to be accredited with PCI (percutaneous coronary intervention), which indicates a higher level of emergency cardiac care services.

Most commonly known as coronary angioplasty, PCI is a therapeutic procedure to treat the narrowed coronary arteries of the heart found in coronary heart disease. The designation is a distinguishing attribute since PCI is now the preferred treatment for heart attack patients.

For more information about heart disease and cardiac care option – from heart transplants and ventricular assist devices to imaging services and minimally-invasive interventional treatments, please visit Emory Healthcare at: http://www.emoryhealthcare.org/heart-center-atlanta/.

 

Posted on by Lance Skelly in Uncategorized 1 Comment

Nitrite: from cured meat to protected heart

Nitrite may be best known as a food additive used in cured meats such as hot dogs, but medical researchers are studying how it could treat several conditions, including preventing damage to the heart after a heart attack.

Leaders in the nitrite field are meeting May 11 -13, 2011 at Emory Conference Center in Atlanta. One of the lead organizers is David Lefer, PhD, professor of surgery at Emory University School of Medicine and director of the Cardiothoracic Research Laboratory. Lefer discusses the beneficial effects of nitrite in the video below. More information about the meeting is available here.

Scientists think supplying a pulse of nitrite can reduce injury to heart tissue coming from the interruption of blood flow. Several clinical trials are now investigating nitrite as a therapy for conditions such as heart attack, ruptured aneurysm, sickle cell pain crisis and cardiac arrest.

Nitrite acts as the body’s reserve for nitric oxide, which turns on chemical pathways that relax blood vessels. Delivering nitric oxide directly into the body is expensive and hard to control. Unlike nitric oxide, whose lifetime in the body is a few seconds, nitrite is stable and stored in the body’s tissues and can be delivered in a variety of ways. It is converted into nitric oxide under conditions when the body needs it: lack of blood or oxygen. In addition, sodium nitrite has been used as part of a cyanide antidote kit. This means that safety data on large doses of nitrite in critically ill people is available.

In a 2005 paper published in the Journal of Clinical Investigation, Lefer and colleagues showed that nitrite can reduce damage to the hearts of mice after a simulated heart attack. More recently, assistant professor John Calvert and Lefer have shown that internally generated and stored nitrite is an important way that exercise protects the heart from a heart attack.

Some blood pressure studies underway in Europe have participants consume large amounts of beet juice as their source of nitrate, which is then converted to nitrite in the body.

A wave of public concern about nitrite and its relative nitrate in the 1970s focused on their presence in cured meats and their ability to form nitrosamines, which can be carcinogenic. Subsequent investigation showed that actually, most of the nitrite and nitrate in the average adult’s diet come from vegetables such as broccoli and spinach, and that antioxidants such as vitamin C can prevent nitrosamine formation.

Nathan Bryan, a speaker at the conference from UT-Houston, was featured in a recent television news story about herbal supplements designed to boost nitrite in the body.

Posted on by Quinn Eastman in Heart 2 Comments

Kidney donation kicks off life-saving chain reaction


In this video, players in this extraordinary transplant exchange tell their story.
You can also watch “The Mother of All Swaps,” a news report from 11 Alive Atlanta

When Jon Pomenville of Anderson, SC, decided to donate a kidney altruistically to someone – anyone in need, anywhere in the country – little did he know his selfless sacrifice would in turn change the lives of not one, but numerous individuals and their families, including one little boy from Atlanta.

And little did he know that the selfless, anonymous act would quickly become not so anonymous. During a recent post-surgical clinic visit to Emory University Hospital, Pomenville met by accident – right in the transplant clinic waiting room – many of the individuals whose lives were changed. Soon the patients – recipients and donors – two father and son combinations and Pomenville, the man who would give to anyone – were hugging, shaking hands, and recounting their backgrounds and experiences.

Pomenville and the others, who were all part of what is called a paired kidney exchange, were unwittingly scheduled for appointments within a short period of one another. As one person began recounting the experience, eyes and ears began to focus on the tale being told from across a crowded room.

People involved in the six-person kidney exchange

A chance meeting in a doctors’ waiting room led to a meeting between most of the people involved in the paired kidney exchange.

The Emory Transplant Center created and opened its innovative Paired Donor Kidney Exchange Program in 2009, providing greater hope for patients in need of kidney transplants. According to Kenneth Newell, MD, director of Emory’s living donor program, a paired exchange donation allows healthy individuals to donate a kidney to either a friend, loved one, or even altruistically to a stranger, despite incompatible blood matches. In paired donation, a donor and recipient are matched with another incompatible donor and recipient and the kidneys are exchanged between the pairs.

The procedure is another form of living donor transplantation. Donated kidneys also come from recently deceased donors. While most kidneys from deceased donors function well, studies have shown that a kidney from a living donor, either a blood relative or an unrelated person, provides the greatest chance for long-term success.

“Paired donor exchanges allow us to cast a much wider net to find compatible donors and recipients,” says Newell. “With a paired kidney transplant, one incompatible donor-pair is able to give a healthy kidney to a compatible recipient. In exchange, the second donor-recipient pair will give a compatible kidney to the first donor-recipient pair, making two compatible living donor transplants possible and increasing the potential number of available donor kidneys. This option can help those patients waiting for kidney transplants who have family members or friends willing to be donors and who are medically suitable, but who have an ABO blood type that is incompatible with the recipient’s blood type.”

Because of Pomenville’s donation, a 7-year-old boy named Zion was able to receive a lifesaving kidney from an unrelated donor because his dad, Mike, was able to donate. His surgery took place at Children’s Healthcare of Atlanta at Egleston.

And Gerald Smith of Five Points, Ala., would receive his life-saving kidney because his son, Matt, a recent University of Alabama graduate, would donate his to Zion. And finally, 20 year-old Edward Hill of Macon, a young man with a history of health challenges, would also receive his transplant at Children’s Healthcare of Atlanta – completing the six-person cycle, although the donor of Edward’s kidney is still unknown.

And Zion and Matt Smith will not only share a common bond and connection throughout life in the form of a kidney, but something even sweeter that that … blue Powerade.

“I’ve always really enjoyed drinking Powerade, particularly the blue flavor,” says Smith. Shortly after Zion awoke from his surgery, he inexplicably began requesting the blue-tinted soft drink too.

Other powerful kidney transplant stories out of Emory:

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Children with Food Allergies Offered Better Diagnosis and Treatment with New Guidelines

Twenty years ago, food allergies had barely been heard of. Now, they are a $500 million health problem that affects more than 12 million Americans, including three million children. New federal guidelines issued by the National Institute of Allergy and Infectious Diseases (NIAID) will help physicians better diagnose and treat food allergies, according to Karen Demuth, MD, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Children’s Healthcare of Atlanta.

Dr. Demuth was a key player in advancing legislation to call attention to the challenges of food allergies in children. She and several of her patients were on hand to witness Governor Nathan Deal signing a proclamation declaring May 8 to 14 Food Allergy Awareness Week in Georgia.

Dr. Demuth (pictured far right) was a key player in advancing legislation to call attention to the challenges of food allergies in children. She and several of her patients were on hand to witness Governor Nathan Deal signing a proclamation declaring May 8 to 14 Food Allergy Awareness Week in Georgia.

“The new NIAID guidelines help providers understand food allergies,” Demuth says. “They address when we should consider a food allergy and the utility of testing for food allergy. In addition, they address the management of food allergies, including acute reactions and follow-up of individuals with food allergy.”

The guidelines are comprised of input from a panel of 25 experts and draw the important distinction between food allergies and food intolerances. Food allergies are defined as “an adverse health effect arising from a specific immune response hat occurs reproducibly on exposure to a given food.” Food intolerances produce an adverse reaction but are likely not related to an immune response.

The most common food allergies are to milk, eggs, peanuts, tree nuts, shellfish, fish and soy. Fortunately, the understanding of food allergies and the best ways to manage them is expanding.

“The gold standard of treatment of food allergies – avoidance – has remained constant throughout the years,” Demuth says. “There are new therapies on the horizon such as oral immunotherapy, vaccines and a Chinese herbal extract; however, these therapies are still considered experimental. At the Emory-Children’s Center, we are active in research and advocacy in pediatric allergies so that we can bring new treatments to our patients when they are ready for widespread use. We are dedicated solely to the care of children with allergic and immunologic disorders and offer multidisciplinary clinics to offer a specialized level of care.”

Video

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Brain enhancement: can and should we do it?

The Emory Center for Ethics and Emory’s Neuroscience Graduate Program recently co-hosted a symposium discussing the ethics of brain-enhancing technologies, both electronic and pharmacological.

Georgia Tech biomedical engineer Steve Potter explained his work harnessing the behavior of neurons grown on a grid of electrodes. The neurons, isolated from rats, produce bursts of electrical signals in various patterns, which can be “tuned” by the inputs they receive.

“The cells want to form circuits and wire themselves up,” he said.

As for future opportunities, he cited the technique of deep brain stimulation as well as clinical trials in progress, including one testing technology developed by the company Neuropace that monitors the brain’s electrical activity for the purpose of suppressing epileptic seizures. Similar technology is being developed to help control prosthetic limbs and could also promote recovery from brain injury or stroke, he said. Eventually, electrical stimulation that is not modulated according to feedback from the brain will be seen as an overly blunt instrument, even “barbaric,” he said.

Mike Kuhar, a neuroscientist at Yerkes National Primate Research Center, introduced the topic of cognitive enhancers or “smart drugs.” He described one particular class of proposed cognitive enhancers, called ampakines, which appear to improve functioning on certain tasks without stimulating signals throughout the brain. Kuhar questioned whether “smart drugs” pose unique challenges, compared to other types of drugs. From a pharmacology perspective, he said there is less distinction between therapy and enhancement, compared to a perspective imposed by regulators or insurance companies. He described three basic concerns: safety (avoiding toxicity or unacceptable side effects), freedom (lack of coercion from governments or employers) and fairness.

“Every drug has side effects,” he said. “There has to be a balance between the benefits versus the risks, and regulation plays an important role in that.”

He identified antidepressants and treatments for attention deficit-hyperactivity disorder or the symptoms of Alzheimer’s disease as already raising similar issues. The FDA has designated mild cognitive impairment associated with aging as an open area for pharmaceutical development, he noted.

James Hughes, a sociologist from Trinity College and executive director of the Institute for Ethics and Emerging Technologies, welcomed new technologies that he said could not only treat disease, but also enhance human capabilities and address social challenges such as criminal rehabilitation. However, he did identify potential “Ulysses problems”, where users of new technologies would need to exercise control and judgment.

In contrast, historian and Judaic scholar Hava Tirosh-Samuelson, from Arizona State University, decried an “overly mechanistic and not culturally-based understanding of what it means to be human.” She described transhumanism as a utopian extension of 19th century utilitarianism as expounded by thinkers such as Jeremy Bentham.

“Is the brain simply a computational machine?” she asked.

The use of military metaphors – such as “the war on cancer” – in the context of mental illness creates the false impression that everything is correctable or even perfectable, she said.

Emory neuroscience program director Yoland Smith said he wants ethics to become a strong component of Emory’s neuroscience program, with similar discussions and debates to come in future years.

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