Sarkozy’s talent for reinvention
Emma Jane Kirby reflects on why the unpredictability of French President Nicolas Sarkozy means it is difficult to define him.
HOUSTON -- (February 24, 2009) -- Men and women who are being treated for heart disease are being asked to take part in a study of a new experimental drug at Baylor College of Medicine in Houston.
The study will determine whether the as-yet unapproved drug called darapladib can reduce the risk of having a heart attack or stroke in people who already have heart disease.
The study called STABILITY (Stabilization of atherosclerotic plaque by initiation of darapladib therapy) will involve 15,000 patients around the world and between 50 and 100 in Houston.
Darapladib inhibits an enzyme called lipoprotein-associated phospholipase A2 (Lp-PLA2), which may provoke inflammation in the heart vessel wall and be a risk factor for causing heart disease. Doctors already test patients for levels of this enzyme because it is believed to be a marker for heart disease.
"We have conducted previous research that shows an association between high levels of Lp-PLA2 and an increased risk for heart attacks and strokes," said Dr. Christie Ballantyne, professor of medicine and director of The Center for Cardiovascular Disease Prevention at BCM, who will lead the study here.
Patients in the study will remain on their usual heart disease medicines, including statins to lower cholesterol, antiplatelet medications such as aspirin, ticlopidine and clopidgrel to reduce clotting and other medications to lower blood pressure or reduce heart rate. Some of those in the study will receive the experimental drug; others will receive a placebo or inactive medicine.
The doctors hope to see whether inhibiting this enzyme could stabilize the fatty plaques in blood vessels. When these plaques become unstable and erupt, a heart attack or stroke can result.
To be eligible for this study, participants must:
Study medication will be given to patients in addition to their heart medicine schedule. If you are taking medicines for other conditions, the study physician will discuss those with you.
For more information on enrollment, please call 713-798-3330.
The study is being sponsored by GlaxoSmithKline.
Heart disease is the leading cause of death for men and women in the United States.
HOUSTON -- (February 24, 2009) -- A cell can be compared to a computer with DNA as hardware.
However, the cell's software – the network of regulatory elements that govern how it reads the message in the DNA to create proteins – is a critical element of its activity. When there is an error in the hardware or software, the computer does not operate properly. The same can be said of the cell.
Now an international consortium of scientists from Baylor College of Medicine in Houston, the United Kingdom and Japan show that just as errors in DNA can be transmitted from a mother cell to its daughters, errors in the regulatory networks are heritable as well. A report of their research appears online today in the public access journal Public Library of Science Biology.
Sometimes, when a cell divides, DNA is miscopied, resulting in a defect that can be passed through the generations. That is a hardware defect.
"Most people think that errors in transcription (the copying of the information in a gene into a protein) are transient and cannot be inherited," said Dr. Christophe Herman, assistant professor of molecular and human genetics at BCM. "What we show is that errors in transcription have a dramatic heritable consequence when they affect a specific gene network."
In work with the bacteria Escherichia coli, Herman and his colleagues work with a particular phenomenon known as a bi-stable switch, which allows a dividing cell to go into one of two important directions.
"It is important in differentiation," said Herman. A network allows these cells to make their cell fate choice.
"If errors in transcription can change the direction of a network from one fate to another when a mistake is made, that can be heritable," he said.
For example, it is possible that an error in messenger RNA (that carries the protein code to the cell protein manufacturing machinery) can result in the formation of a faulty protein called a prion, which results in faulty protein formation and disorders such as "mad cow" disease. In another likely scenario, a faulty protein can result in the disregulation of the cells' growth cycle leading to cancer.
"Right now you look at a phenotype (the observable characteristics of an organism or cell) and if there is a problem, you assume it came from a mistake in the DNA. We show that we can have cells with different phenotypes, but the DNA is the same. There is no mutation, but the transcription errors are passed on."
Until now, he said, people did not realize that these errors in the genetic network can be transferred from one cell to another. This is a heritable epigenetic system, and, it's now time to identify the factors contributing to the fidelity of these networks, he said.
Others who took part in this research include Alasdair J.E. Gordon, Jennifer A. Halliday and Matthew D. Blankschien, BCM; Philip A. Burns, St. James's University Hospital of Leeds, UK and Fumio Yatagai of RIKEN Institute in Japan.
Funding for this work came from Human Frontier Science Program Organization, which was created to support international research and training at the frontier of the life sciences with particular emphasis on research at the interface between life sciences and the physical sciences and on creating opportunities for young scientists.
The full report can be found at http://biology.plosjournals.org/perlserv/?request=index-html&issn=1545-7885
For more information on basic science research at Baylor College of Medicine, please go www.bcm.edu/fromthelab.
HOUSTON -- (February 23, 2009) -- Cocaine use can have toxic effects on brain cells (neurons) that produce dopamine, say experts at Baylor College of Medicine in Houston in a report that appears today in the journal Psychiatry Research.
Using brain tissue acquired after the subjects died, researchers microscopically compared the number of dopamine cells in the brains of 10 cocaine users to those in the brains of nine people matched for age who did not use the drug.
They found significantly fewer dopamine cells, 16 percent, in the brains of cocaine users.
"Although we have always known that cocaine is a dangerous drug, for the first time we can now physically see that dopamine cells are lost in the brains of cocaine users," said Dr. Karley Little, associate professor in the Menninger Department of Psychiatry and Behavioral Sciences at BCM. Associated measures indicated that the loss of cells was recent and the subjects were not born with this loss.
"Dopamine plays a big role in the awareness of pleasurable things in the environment, including food and sex," said Little, also a staff psychiatrist at the Michael E. DeBakey Veterans Affairs Medical Center in Houston. "The lack of dopamine cells may make a person less responsive to natural rewards, whether it's in the workplace or in a relationship."
The lack of dopamine cells could also lead to withdrawal or depression symptoms, said Little. Although effects of cocaine use vary among users, the study shows the potential dangers of this drug. Cocaine use may theoretically increase the risk of Parkinson's Disease, but the mechanisms involved may be different and not occur in the same individuals.
"This is just the beginning of the story. We can now create a model to understand the biochemistry involved, such as how cocaine is toxic and why it is more toxic in some than others," said Little. Previous work by Little indicated that dopamine uptake is increased by cocaine exposure in the same individuals, which might have contributed to the toxic effects.
Others who participated in the study include Eric Ramssen, Ryan Welchko, Vitaly Volberg , Courtney J. Roland, and Bader Cassin of the University of Michigan.
Funding for this work came from the National Institute of Drug Abuse.
The full report is available at: http://www.sciencedirect.com/science/journal/01651781