Inside this issueCover storiesCouple with a causeSlow readers, creative thinkersNew faculty prize will recognize superb patient carePartnershipsStudent-run auction benefits seven New Haven-area charitiesAwards support research on health disparities, depressionGrants & contractsPeopleLifelines: Pasko RakicRenowned teacher, researcher named dean of engineeringAlumnus is winner of Yale's highest honorExpert on women's health is honored for leadershipAdvocates for universal preschool share education prizeOut & aboutScienceGene-hunters search the world for treatmentsAdvances: Raising the Rae-1 flag | Early treatment could quiet epilepsy | Running depression out of our lives | Arthritis therapy stops diabetes in its tracksHealthImplant lets patients put the best foot forwardFamily sharing a risky mutation now shares newfound hope  
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ADVANCESRaising the Rae-1 flag
Raising a flag is a good way to send a message. In fact, that’s all it takes for a stressed-out, potentially cancerous cell to get the attention of the ever-watchful immune system. Until now, models of immune surveillance have assumed that only foreign danger signals or well-established inflammation could trigger a protective response. But a new Yale study published in the February issue of Nature Immunology reports that cell-surface expression of Rae-1, a protein associated with milder forms of cell dysregulation, is enough to kick the immune system into action. When the Rae-1 flag was raised in the skin cells of transgenic mice, local T cells and Langerhans cells became activated, changed their shape, communicated and moved out of the area to launch an immune response. It may be the earliest identified immune response to a potentially cancerous cell, says Michael Girardi, M.D., associate professor of dermatology, whose team worked with researchers from King’s College London School of Medicine and the University of Minnesota. “Now that we have a starting point for the immune surveillance of cancer,” says Girardi, “we can begin to look at how it all unfolds.” Early treatment could quiet epilepsyEpilepsy can be controlled by medication, but not cured. Scientists have wondered whether early drug intervention could suppress the development of certain forms of genetic epilepsy, and a new School of Medicine study backs this idea. Using a rat model of genetic epilepsy, a team led by Hal Blumenfeld, M.D., Ph.D., associate professor of neurology, neurobiology and neurosurgery, showed that early treatment with ethosuximide–an anti-epileptic drug sold by Pfizer under the name Zarontin–reduced the severity of epilepsy in adulthood. Surprisingly, as reported in the December 2007 issue of Epilepsia, the effect persisted after therapy was discontinued. The researchers began treating the rats at 21 days of age, before they had had any seizures, and continued the treatment until they were 5 months old. The early treatment suppressed the seizures and blocked changes in the expression of several ion channels involved in susceptibility to seizures. The findings support the idea that seizures have to occur at a critical stage of development for the full epileptic profile to develop, but that this ruthless cycle can be stopped by early intervention. Running depression out of our lives
Feeling down? Go for a run and put your genes to work. According to a new Yale study, the well-known antidepressant effects of exercise may be due to genes in the brain that are switched on by physical activity. In the December 2007 issue of Nature Medicine, former graduate student Joshua Hunsberger, Ph.D., and a team led by Ronald S. Duman, Ph.D., Elizabeth Mears and House Jameson Professor of Psychiatry and Professor of Pharmacology, reports that exercise reduced depression-like behavior in mice and also boosted the activity of a gene called VGF in the hippocampus, a brain region that has been strongly implicated in depression in humans. Mice given free access to a running wheel had higher levels of VGF expression in the hippocampus than sedentary mice. These results were bolstered by experiments showing that infusing a synthetic form of VGF directly into the hippocampus had potent antidepressant effects; conversely, mice in which the VGF gene had been knocked down showed more depression-like behavior than those with the gene. The authors say that the development of new therapies that target VGF could have “superior efficacy to existing chemical antidepressants.” Arthritis therapy stops diabetes in its tracksIn type 1 diabetes, an autoimmune disease, the T cells of the immune system attack the cells of the pancreas that produce insulin, making it impossible for the body to control blood sugar levels. B cells are also involved in the process but their exact role is unclear. Drugs that deplete B cells have been effective in controlling other autoimmune diseases, such as rheumatoid arthritis, and some forms of lymphoma. Li Wen, M.D., Ph.D., senior research scientist in the Department of Medicine, wondered if the same approach might be useful in treating type 1 diabetes. Using mice that were specially bred to be predisposed to the disease, Wen and her colleagues found that rituximab, an antibody that binds to B cells, could delay the onset of diabetes in mice that had not yet developed it. As reported in the December issue of The Journal of Clinical Investigation, in additional experiments, some mice with diabetes no longer needed insulin after they had received the antibody treatment.  |
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