Epilepsy locus in focus
The electrical brainstorms of epilepsy can be attributed to a number of underlying causes — traumatic injury, disease and a small but growing number of genetic factors.
In the journal Neurology, Peter Hedera, M.D., and colleagues report a novel genetic locus associated with familial mesial temporal lobe epilepsy, an inherited form of epilepsy in which intense and frequent déjà vu may be the only symptom.
The researchers identified 11 living affected members spread across four generations of a single family. In a genome-wide scan, the researchers found a strong linkage to a locus on chromosome 4 (4q13.2-q21.3). However, there were no ion channel genes and no mutations in the other likely candidate genes in the region.
While the precise genes in this locus have yet to be identified, the awareness of this genetic locus could provide important clues to the nature of this type of epilepsy, the authors suggest.
— Melissa Marino
Tailoring heart rhythm treatments
Medications used to treat abnormal heart rhythms (arrhythmias) are notorious for not being very effective and for causing a wide range of side effects, including actually worsening the heart rhythm. Prescribing antiarrhythmic drugs based on a patient's particular genetic makeup — “personalized medicine” — may improve therapy.
A team led by Dawood Darbar, M.D., Ph.D., reports in the journal Heart Rhythm that variation in a particular gene affects antiarrhythmic therapy in atrial fibrillation, the most common arrhythmia observed in clinical practice. The investigators studied 213 patients enrolled in the Vanderbilt Atrial Fibrillation Registry.
They found that patients with atrial fibrillation who carry a common variation in the angiotensin-converting enzyme (ACE) gene were more likely to respond to antiarrhythmic medications than patients who did not carry the variant. The findings support using ACE genotype to guide therapeutic approaches.
— Leigh MacMillan
Cancer’s post-surgery spread
When colorectal cancer has metastasized to the liver, surgical removal of the intruder is the treatment of choice, but liver recurrence of the cancer is common. Studies suggest that the liver surgery itself, through ischemia/reperfusion (I/R) injury, can cause cellular damage and promote tumor growth.
In the March 15 Cancer Research, Ian Nicoud, Ravi Chari, M.D., Lee Gorden, M.D., and colleagues propose a mechanism for this injury-induced tumor growth. They report that liver I/R injury significantly increased tumor number and volume and levels of the matrix metalloproteinase MMP9 in a mouse model of liver tumor metastasis. Administration of an MMP inhibitor starting at the time of injury reduced MMP9 levels and tumor number and volume. Mice lacking the MMP9 gene had similarly reduced tumor numbers.
The findings suggest that I/R injury-induced elevation of MMP9 contributes to the growth of metastatic colorectal cancer in the liver and that MMP9 inhibition may be clinically beneficial in preventing cancer recurrence following liver surgery.
— Leigh MacMillan
To make insulin, add MafB
Stem cells may hold therapeutic promise for diabetes. But to turn embryonic or adult stem cells into insulin-producing pancreatic cells requires identification of the complete set of factors that will elicit that conversion.
Roland Stein, Ph.D., and colleagues bring a new factor to the mix. They report in the March 6 Proceedings of the National Academy of Sciences that the transcription factor MafB is required for pancreatic islet alpha and beta cell maturation. In studies of MafB knockout mice, the investigators demonstrated a greater than 50 percent reduction in the number of glucagon-positive and insulin-positive cells, with no change in the total number of endocrine cells.
MafB did not affect the expression of genes found in all islet cell types, just those selectively present in alpha or beta cells. MafB appears to be a key regulator of alpha and beta cell maturation and the principal regulator of glucagon and insulin expression during development.
— Leigh MacMillan
Past Aliquots
June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012