HOUSTON -- (November 17, 2008) -- A "chip" or array that can quickly detect disorders such as Down syndrome or other diseases associated with chromosomal abnormalities proved an effective tool in prenatal diagnosis in a series of 300 cases at Baylor College of Medicine, said researchers in a report that appears in the current issue of the journal Prenatal Diagnosis.

In the report, a team led by Dr. Arthur Beaudet and Dr. Sau Wai Cheung at BCM, described use of array comparative genomic hybridization to analyze samples taken during amniocentesis or chorionic villus sampling for chromosomal abnormalities. Amniocentesis and chorionic villus sampling allow researchers to obtain fetal cells for testing.

"Larger studies of this test will help us decide whether it should be used as a first line measure to detect chromosome abnormalities in fetuses," said Beaudet, chair of molecular and human genetics at BCM and senior author of the report. "They will also enable us to determine whether such testing should be offered more widely to pregnant women."

Cheung is professor of molecular and human genetics at BCM and director of the College's Cytogenetics Laboratory.

Detecting small deletions

"The array enables you to detect smaller deletions or duplications of genetic material that would not be seen on a regular karyotype (a depiction of the size, shape and number of chromosome and any abnormalities in them)," said Dr. Ignatia B. Van den Veyver, associate professor of obstetrics and gynecology and molecular and human genetics at BCM and first author of the report. Each of these deletions or duplications is rare but added together, the rate of event could be as high as that seen in Down Syndrome.

In some of these cases where small amounts of DNA are lost or duplicated, children often have significant learning disabilities or health problems that could not be picked up with an ultrasound or other means of prenatal diagnosis, she said.

"This test adds information we could not detect by any other means right now in prenatal diagnosis," she said.

Quick DNA scan

Array comparative genomic hybridization provides the tools to scan fetal DNA quickly and automatically to identify copy number variation, which indicates the deletion or addition of genetic material at a particular point on the genome.

The array starts with single-stranded fragments of DNA embedded on a glass slide to form the array, which is then exposed to fluorescently labeled single-stranded DNA. Half of the labeled DNA is from the fetus being tested and is labeled with one fluorescent color. The other is reference DNA, which is labeled with another color. The fluorescently labeled DNA – reference and patient – binds to DNA on the array. The color of the fragments will vary based on how much DNA from each binds to the DNA on the array. If the fetus has a DNA duplication, then the patient color on the array will be stronger. If the fetus has a deletion, the reference color will show up stronger. A specialized scanner evaluates the color differences, which are then fed into a computer for analysis.

In this study, most of the women sought prenatal testing because they were older and faced a higher risk of having children with certain chromosomal abnormalities, such as Down Syndrome. Some had had abnormal ultrasounds and needed more information, and still others had had children with a genetic abnormality previously.

The scientists found 58 copy number variations, which indicate that there is either more or less genetic material than one would expect to find at that location on the chromosome.

Genetic counseling part of process

Forty of these variations were interpreted as benign. Thirty-nine of them were inherited from a parent who had no evidence of genetic disease. One had been seen before and had not been associated with disease.

In 15 cases when the array detected something that was significant for patient care, the finding was either suspected because the mother "carried" the change in her DNA, or because another prior test, such as a karyotype, had detected it.

Three cases were classified as uncertain. Two of these involved copy number variations, not seen before and not inherited from the parents, in fetuses with birth defects identified on the prenatal ultrasound. In one, the array findings were interpreted as likely unrelated to the birth defects and in the other they were thought to cause the defects. In the third case, there was a relatively large deletion in an area of chromosome 3, but it was also present in the mother, who had no reported medical problems.

In two cases the array comparative genome hybridization identified disorders that would have been missed otherwise and in seven cases the results added new information about risk of disease valuable in genetic counseling.

"My conclusion is, that providing there is good genetic counseling that accompanies it, the test can be offered to prospective parents who want prenatal diagnosis. There are many parents interested in having this additional diagnostic information," said Van den Veyver. "If we use an array that is targeted and we have parental samples to confirm the meaning of detected changes, in the majority of cases, we will be able to counsel the patients about the significance of the findings."

Others who took part in this research include Ankita Patel, Chad A. Shaw, Amber N. Pursley, Sung-Hae L.Kang, Marcia J. Simovich, Patricia A. Ward, Sandra Darilek, Anthony Johnson, Sarah E Neill, Weimin Bi, Lisa D. White, Christine M. Eng, James R. Lupski and Sau Wai Cheung, all of BCM.

The full article is available at http://www3.interscience.wiley.com/cgi-bin/fulltext/121519430/PDFSTART

For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.

HOUSTON -- (November 17, 2008) -- When a neuron or nerve cell loses the protein ankryin G, its axon, the information output center of the cell, becomes more like a dendrite, which accepts information, a phenomenon that may have implications for brain and nerve injury and disease, said researchers at Baylor College of Medicine in Houston and the University of Connecticut Health Center in Farmington in a report that appears online today in The Journal of Cell Biology.

"If the neuron gets confused, it does not know how to signal properly," said Dr. Matthew N. Rasband, associate professor of neuroscience at BCM and senior author of the report. "Ankyrin G is required for a neuron to maintain the distinction between an axon and a dendrite. This is the first time an axon has been converted into a dendrite in the laboratory." The opposite change – dendrite to axon – has been observed previously in models of nervous system injury.

Dendrites are rough multi-branched extensions from the neuron's cell body that are specialized to receive information. Most neurons have many dendrites. Most neurons only have one axon, a long thread of tissue that extends away from the cell body and only branches when it is far removed. It takes information away from the cell body and transmits it to other neurons or other organs.

One major question is whether this is just an interesting laboratory finding or if this axon-to-dendrite change occurs after disease and injury?

"It's easy to imagine a scenario where an injury disrupts or damages ankyrin G," Rasband said. "The implication of this paper is that if it does occur, then the neuron would get confused and even though it was alive, not know where to send its signals."

He and his collaborators used viruses together with a relatively new technique called RNA interference or RNAi to reduce the amount of ankyrin G produced in a cell culture of neurons.

In the future, they plan to study the effects of the loss of ankryin G in models of diseases that affect the brain and nerves.

Other members of the Rasband laboratory who took part in this research are Dr. Kristian L. Hedstrom, now of the Yale University School of Medicine in New Haven, Connecticut and and Dr. Yasuhiro Ogawa, now of Meiji Pharmaceutical University in Tokyo.

Funding for this work came from the National Institutes of health, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Mission Connect and the National Multiple Sclerosis Society.

This report is available at The Journal of Cell Biology.

If you would like more information about basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.

HOUSTON -- (November 14, 2008) -- The holiday season, also known as the "eating season," is upon us, but you can take control one meal at a time, say experts at Baylor College of Medicine in Houston.

"It all starts with breakfast," said Molly Gee, a registered dietitian at BCM. "This is a great opportunity to set a healthier agenda for the day. Incorporate whole grains and reduce the fat by using low fat or skim milk."

For the rest of the day, it's important to eat colorful foods to maximize health. A rainbow-colored assortment of foods may help get in more fruits and vegetables.

"You have to treat each meal as a separate eating event," said Gee. "It's not over if you eat one super-sized meal, you simply have to balance out your next meals."

Don't punish yourself

According to Gee, skipping a meal and putting yourself in the deprivation mode is a bad strategy. "There's no need to punish yourself. You may end up overcompensating at your next meal and eating even more calories," said Gee.

One of the biggest temptations during the holiday season is eating out, but Gee offers some tips to enjoy your favorite restaurant foods as well.

Dining strategies

"One simple strategy is to ask for the sauce or gravy on the side to cut out a few hundred calories or more," said Gee.

Control those large restaurant portions by asking for a to-go box to with the entrée, and putting half of the food aside immediately. Sharing an entree is a way to cut calories in half.

"You can create your own customized dinner at a restaurant," said Gee. "Pair up an appetizer with a soup or salad. Ask for the lunch portion even at dinnertime. Substitute the French fries that come with an entrée with the vegetable of the day."

Gee emphasizes taking control of your meals and making your requests known, but she also stresses that this is not the time to be sedentary. Maintaining physical activity during the holiday season is a must.

"It's not just the energy in, but also the energy out," said Gee.

HOUSTON -- (November 14, 2008) -- The symptoms of panic attacks are frequently confused by physicians with other problems, indicating a need for better education in the area, said researchers at Baylor College of Medicine in Houston, who surveyed physicians on the topic. A report of their study appears in the online version of the Journal of Clinical Psychology in Medical Settings.

"Because symptoms of panic attacks can be confused with those of other medical problems related to the heart and gastrointestinal tract as well as neurological problems, a lack of knowledge about panic attacks can lead to unnecessary referrals and tests," said Dr. Ellen Teng, assistant professor of psychiatry and behavioral sciences at BCM and clinical research psychologist at the Michael E. DeBakey Veterans Affairs Medical Center.

Survey responses

Researchers evaluated 95 surveys received from cardiologists, gastroenterologists and neurologists in the Houston area. The survey questions included information about those most at risk for panic attacks and treatment options.

The physicians answered only half of the survey questions about panic attacks correctly. There was no difference in knowledge among the three specialty groups.

While 94 percent recognized medication as a way to treat panic and anxiety symptoms, only about 30 percent recognized cognitive behavioral therapy to educate patients about panic attacks and their symptoms and give them tools to deal with the problem as the treatment of choice.

Long-term treatment

"Medication does treat the short-term aspects of panic attacks such as shortness of breath and a racing heart, but cognitive behavioral therapy treats panic disorder in the long-term," said Teng.

Only slightly more than half of the physicians surveyed believed that psychologists could treat panic attacks directly and effectively through this technique.

Teng called for increased awareness of panic disorder among physicians. Teng also recommends providing resources and literature for physicians to make appropriate referrals to psychologists.

Symptoms of panic attack

Common symptoms of a panic attack include heart pounding, shortness of breath, light headedness and trembling. Panic disorder develops when several panic attacks occur out of the blue. Patients then worry about what the attack means and when the next one will take place, which may cause them to avoid certain places or events.

If a panic attack does occur for the first time, Teng recommends seeing a physician to rule out the risk of heart disease or another serious problem.

Others who took part in this research include Drs. Angelic D. Chaison, Sara D. Bailey, Joseph D. Hamilton and Nancy Jo Dunn, all of BCM and the Michael E. DeBakey Veterans Affairs Medical Center.

Funding for this work came from the South Central Mental Illness, Research, Education and Clinical Centers, a part of the United States Department of Veterans Affairs.

The study can be found at http://www.springerlink.com/content/q5718wm131242433/fulltext.pdf.

HOUSTON -- (November 10, 2008) -- By adding the results of an imaging technique to the traditional risk factors for coronary heart disease, doctors at Baylor College of Medicine in Houston found they were able to improve prediction of heart attacks in people previously considered low risk.

The findings are being presented today at the American Heart Association's Scientific Sessions in New Orleans.

Viewing artery walls

Researchers used ultrasound imaging to view the carotid intima media thickness (C-IMT), or thickness of the artery walls.

"The ultrasound added another dimension to the risk factor score and showed us that those with thick arteries in the higher end of low risk group actually are at intermediate risk for coronary heart disease," said Dr. Vijay Nambi, assistant professor of medicine - atherosclerosis and vascular medicine at BCM and lead author of the study.

Risk prediction is traditionally divided into three groups: low, intermediate and high risk. Low risk is defined as having a less than a 10 percent chance of having coronary heart disease in the next 10 years. Intermediate is a 10 percent to 20 percent chance of a coronary event, and high risk is anything greater than 20 percent. This percentage is calculated by doctors using a score based on traditional risk factors which include age, gender, HDL cholesterol (good cholesterol), total cholesterol, hypertension and smoking.

Nambi and his colleagues followed more than 13,000 people already taking part in the Atherosclerosis Risk in Communities study, a large scale study designed to investigate the etiology and natural history of atherosclerosis. Participants in the current study were followed for almost 14 years. After adding imaging to the traditional risk factors, those in the higher end of the low risk group (estimated 10-year risk of 5 percent to 10 percent) were found to have a greater chance of having a heart attack especially if imaging revealed them to have a thicker C-IMT. Nambi said that about 4 percent of those who fell in the zero percent to 5 percent estimated risk had a heart attack, while more than 13 percent of those in the 5 percent to 10 percent suffered from coronary heart events. Furthermore, he pointed out that in the 5 percent to 10 percent risk group, those with the thickest arteries had approximately a 17 percent risk for coronary heart events when followed for 14 years.

"Low risk" needs closer look

"There is a big difference between 4 percent and 13 percent," said Nambi. "These results show us that we need to take a closer look at some of those individuals in the low risk category and even reconsider the definition of "low risk."

"Our goal is to target those in the most need," said Dr. Christie Ballantyne, chief of atherosclerosis and vascular medicine and professor of medicine at BCM. "Being able to pinpoint those more likely to have a heart attack will allow us to take early, more effective preventive action to stop a heart attack before it happens."

Ballantyne, a co-author in this study, is also the director of the Center for Cardiovascular Disease Prevention at the Methodist DeBakey Heart and Vascular Center.

Others who took part in the study include Drs. Lloyd Chambless, University of North Carolina at Chapel Hill; Aaron R. Folsom, University of Minnesota School of Public Health; Yijuan Hu, University of North Carolina; Tom Mosley, University of Mississippi Medical Center; and Kelly Volcik and Eric Boerwinkle, both of The University of Texas Health Sciences Center at Houston.

The ARIC study is funded by the National Heart, Lung and Blood Institute.

For more science news from Baylor College of Medicine in Houston, go to www.bcm.edu/fromthelab.