Antibody production: an endurance sport

To understand recent research from immunologist Jerry Boss’s lab on antibody production, think about the distinction between sprinting and long-distance Read more

Less mucus, more neutrophils: alternative view of CF

A conventional view of cystic fibrosis (CF) and its effects on the lungs is that it’s all about mucus. Rabin Tirouvanziam has an alternative view, centered on Read more

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Exception from informed consent: what patients say

Informed consent is a basic principle of clinical research. Doctors are required to make sure that patients understand what’s involved with experimental treatments, and patients should only participate if they provide consent.

However, an important area of clinical research takes place outside of this general rule, because some life-threatening conditions – seizures, traumatic brain injury and cardiac arrest, as examples — make it impossible for the patient to learn about a clinical trial and make a decision about whether to participate. The urgency of treatment can also mean that seeking proxy consent from a relative is impractical.

A recent editorial in USA Today highlights this area of research, called EFIC (exception from informed consent). The author, Katherine Chretien from George Washington University, cites research from Emory investigators Neal Dickert and Rebecca Pentz.

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The creeping edges of cells: lamellipodia

Lamellipodia with red box
This month’s Image feature highlights lamellipodia, the thin sheet-like regions at the leading edges of migrating cells. Lamellipodia act as tiny creeping motors that pull the cell forward.

To help visualize lamellipodia, Adriana Simionescu-Bankston, a graduate student in Grace Pavlath’s lab, provided us with this photo of muscle cells. The red box shows an example of lamellipodia. Notice the edge of the cell, where the green color is more intense.

The green color comes from FITC-phalloidin, which stains F-actin, the Ray Ban outlet filaments that make up a large part of the cells’ internal skeleton. (Phalloidin is an actin-binding toxin originally isolated from death cap mushrooms, and FITC is what makes it green.) The blue color comes from DAPI, a dye that stains the DNA in the nucleus.

Simionescu-Bankston and Pavlath recently published a paper in the journal Developmental Biology, examining the function of a protein called Bin3 in muscle development and regeneration. They found that Bin3 appears to regulate lamellipodia formation; in mice that lack Bin3, muscle cells have fewer lamellipodia and the muscle tissues regenerate slower after injury. Bin3 is also important in the eye, since the “knockout” mice develop cataracts soon after birth.

 

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From the genetic code to new antibiotics

Biochemist Christine Dunham and her colleagues have a new paper in PNAS illuminating a long-standing puzzle concerning ribosomes, the factories inside cells that produce proteins.

Ribosomes are where the genetic code “happens,” because they are the workshops where messenger RNA is read out and proteins are assembled piece by piece. As a postdoc, Dunham contributed to Nobel Prize-winning work determining the molecular structure of the ribosome with mentor Venki Ramakrishnan.

Ribosomes are the workshops for protein synthesis and the targets of several antibiotics

The puzzle is this: how messenger RNA can be faithfully and precisely translated, when the interactions that hold RNA base pairs (A-U and G-C) together are not strong enough. There is enough “wobble” in RNA base pairing such that transfer RNAs that don’t match all three letters on the messenger RNA can still fit.

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Supreme decision on DNA patents

In these days of political polarization, how often does the United States Supreme Court make a unanimous decision? When the case has to do with human genes and their patentability!

The case concerned patents held by Utah firm Myriad Genetics on the BRCA1 and 2 genes. Mutations in those genes confer an increased risk of breast and ovarian cancer. The patents in dispute claimed the genes themselves rather than just the technology for reading them.

Cecelia Bellcross, director of Emory’s genetics counseling program and an expert on breast cancer genetics counseling, reports that “in general, the clinical genetics community is jumping up and down, as are a lot of genetics lab directors and definitely patient advocacy groups.”

Myriad’s BRCA tests cost more than $3,000. Several competing firms announced that they would offer tests for the BRCA1 and 2 mutations at significantly lower prices.

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An indicator of aberrant stem cell reprogramming

The 2012 Nobel Prize in Medicine was awarded to Shinya Yamanaka and John Gurdon for the discovery that differentiated cells in the body can be reprogrammed. This finding led to the development of “induced pluripotent stem cells.”

These cells were once skin or blood cells. Through a process of artificial reprogramming in the lab, scientists wipe these cells’ slates clean and return them to a state very similar to that of embryonic stem cells. But not exactly the same.

It has become clear that iPS cells can retain some memories of their previous state. This can make it easier to change an iPS cell that used to be a blood cell (for example) back into a blood cell, compared to turning it into another type of cell. The finding raised questions about iPS cells’ stability and whether http://www.troakley.com/ iPS cell generation – still a relatively new technique – would need some revamping for eventual clinical use.

Hotspots where iPS cells differ from ES cells

Chromosomal hotspots where iPS cells differ from ES cells

It turns out that iPS cells and embryonic stem cells have differing patterns of methylation, a modification of DNA that can alter how genes behave even if the underlying DNA sequence remains the same. Some of these differences are the same in all iPS cells and some are unique for each batch of reprogrammed cells.

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Alphabet of modified DNA keeps expanding

Move over, A, G, C and T. The alphabet of epigenetic DNA modifications keeps getting longer.

A year ago, we described research on previously unseen information in the genetic code using this metaphor:

Imagine reading an entire book, but then realizing that your glasses did not allow you to distinguish “g” from “q.” What details did you miss?

Geneticists faced a similar problem with the recent discovery of a “sixth nucleotide” in the DNA alphabet. Two modifications of cytosine, one of the four bases http://www.raybani.com/ that make up DNA, look almost the same but mean different things. But scientists lacked a way of reading DNA, letter by letter, and detecting precisely where these modifications are found in particular tissues or cell types.

Now, a team… has developed and tested a technique to accomplish this task.

Well, Emory geneticist Peng Jin and his collaborator Chuan He at the University of Chicago are at it again.

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Stigma and shame block mental health treatment in Black community

As Dr. Sarah Vinson rotated through her first year of clinical work as a Child Psychiatry Fellow in the Department of Psychiatry and Behavioral Sciences at Emory, she quickly became aware that there are some significant roadblocks in getting people in the African-American community engaged in treatment for mental health problems.

Sarah Vinson, MD, Department of Psychiatry and Behavioral Sciences

“Misinformation, an absence of trust in the system, racism and financial circumstances are some of the forces that can create barriers in making appropriate decisions about seeking treatment,” says Vinson.

In order to take a step toward resolving the problem, Vinson created an online mental health outreach program targeting the Black community. The website serves as an anonymous resource for patients and their families, or anyone who is interested in finding out more about mental illness.

This user-friendly online program provides educational materials, offers links to professional organizations, lists mental health professionals and provides descriptions of different types of mental illnesses as they relate specifically to African-Americans. The website also includes an interactive forum where people can share experiences.

“The Black community’s traditional reluctance to discuss mental health and illness comes at much too high a cost,” says Dr. Vinson.

“People may be fearful of being misjudged by their churches and families, so they don’t discuss their problems,” she explains. “However, it is the support of family and friends that is largely responsible for a successful course of treatment; particularly when it comes to children and adolescents, or people with severe mental illness. Regrettably, when people access care without reinforcement from their loved ones, they often drop out before they are better.

“Untreated, mental illness can cause strained relationships, social dysfunction, and numerous other problems that can end up in divorce, unemployment, and suicide.”

Dr. Vinson is the recipient of an American Psychiatric Association/Substance Abuse and Mental Health Services Administration Fellowship, which provides funds for programming related to minority mental health.

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Emory Cardiologist Helps Rank Top Diets

Laurence Sperling, MD

It’s a new year and shedding pounds is at the top of the resolution list for many Americans. To help dieters lose weight and jump start healthier eating habits, Emory Heart & Vascular Center cardiologist Laurence Sperling, MD served on a U.S. News & World Report panel evaluating some of the country’s most popular diets.

The rankings, released today, include U.S. News’ second annual list of Best Diets, featuring its first-ever ranking of Easiest Diets to Follow. It includes six other rankings first assessed and published in 2011: Best Diets Overall, Best Commercial Diet Plans, Best Weight-Loss Diets, Best Diets for Healthy Eating, Best Diabetes Diets, and Best Heart-Healthy Diets.

According to U.S. News, dieters who choose a diet at or near the top of the new Easiest Diets to Follow list are more likely to succeed in staying on their diet for the long haul. Weight Watchers took the top spot on that list, followed by Jenny Craig, the Mediterranean Diet, Slim-Fast and Volumetrics.

The five new diets added for 2012 are the Abs Diet, Biggest Loser Diet, Dukan Diet, Flat Belly Diet, and Macrobiotic Diet.

Big winners across the rankings included:

  • DASH Diet: ranked #1 in Best Diets Overall, Best Diets for Healthy Eating, and Best Diabetes Diets (tie)
  • Weight Watchers: ranked #1 in Best Weight-Loss Diets, Best Commercial Diet Plans, and Easiest Diets to Follow
  • Biggest Loser Diet: ranked #1 in Best Diabetes Diets (tie)
  • Ornish Diet: ranked #1 in Best Heart-Healthy Diets

To create the rankings, U.S. News turned to Sperling and the same 22 experts for Best Diets 2012 as it did for Best Diets 2011. The panel, which included nutritionists, dietitians, cardiologists and diabetologists, reviewed 25 popular diet profiles that were developed by reporters and editors at U.S. News.

“I can’t say enough about their commitment and hard work,” said Avery Comarow, U.S. News Health Rankings Editor. “They enabled us to provide meaningful, evidence-based rankings.”

Sperling is a professor of medicine at Emory University School of Medicine and director of Emory’s Center for Heart Disease Prevention.

For a complete list of the new diet rankings, please visit:

http://health.usnews.com/best-diet

 

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Esophageal lesions meet their match

Field Willingham, MD, MPH

Once esophageal tumors establish themselves, a patient’s prognosis is grim and morbidity vast. But when lesions are caught early and removed, especially in the premalignant stage, the odds of survival markedly improve.

When a case calls for it, Emory gastroenterologist Field F. Willingham, MD, MPH, uses a hybrid approach to ousting superficial esophageal lesions. Superficial esophageal lesions are commonly caused by acid reflux disease, or GERD. GERD occurs when stomach acid flows into the esophagus and can lead to a condition known as Barrett’s esophagus, where the cells in the lower esophagus become damaged. This in turn can lead to dysplasia, or pre-cancerous cells.

But for superficial cancers, it is now possible to remove a portion of the lining layer of the GI tract, containing the tumor, with an endoscope.  This can help carefully selected patients avoid a major surgery. The technique, known as an EMR, allows the removal of superficial esophageal tumors and pre-cancer with an endoscope, a slender tube-like instrument.

Detecting and removing esophageal tumors early is essential for a favorable outcome. Once tumors firmly establish themselves in esophageal tissue, the prognosis is grim and morbidity vast. In the past, a diagnosis of an esophageal tumor meant the removal of the esophagus and often the stomach. But now EMR can be used in tandem with radio frequency ablation.

In surgical situations in which radio frequency ablation is not feasible, Willingham and his colleagues are beginning to use an alternate technique, known as cryotherpay, in tandem with EMR. Cryotherapy involves freezing superficial cells to rid the esophagus of suspect cells.

“So, if the end of the esophagus is twisted, or if we can’t touch it with this balloon device, then we can use cryotherapy,” says Willingham. “We’re trying to kill the lining layer with the tumor cells without killing the deeper layer.”

Willingham and his colleagues are seeing evidence that using these very three very different, technologies in tandem or alone will provide patients with a better way to rid them of esophageal lesions while preserving their quality of life.

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Smoking’s reach – and risk – even broader than we thought

Smoking’s link to lung cancer has been well-known for decades, but we are still learning about its cancer-causing effects on other organs.

An article in the Journal of the American Medical Association (JAMA) provides solid epidemiological evidence that smoking’s link to bladder cancer is even higher than previously believed. And, the elevated risk factor appears to be the same for men and women.

Viraj Master, MD, PhD

“This is something I see in my practice every day,” says Viraj Master, associate professor of urology, Emory School of Medicine and director of urology clinical research at the Winship Cancer Institute of Emory University. “The dangers of smoking are pervasive. Patients are often surprised to hear of the link between smoking and bladder cancer, but it’s there, and it’s a very real risk.”

The bladder may not be the first organ you think about when you think about the harmful effects of cigarette smoking. After all, when a person inhales cigarette smoke, the mouth, throat and lungs are the primary destination. But, a lethal change in the composition of cigarettes makes the bladder a target for cancer.

Written by researchers at the National Cancer Institute, the study explains that while there is less tar and nicotine in cigarettes now that in years passed, there also has been “an apparent increase in the concentration of specific carcinogens,” including a known bladder cancer carcinogen and tobacco-specific nitrosamines. The study authors also note that epidemiological studies have observed higher relative risk rates associated with cigarette smoking for lung cancer.

“The take-home message, of course, is the same as it long has been – don’t start smoking, and if you do smoke, stop,” says Master. “We need to do everything in our power to both stop people from starting to smoke and to help those already addicted to stop.”

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