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Appendicitis can be tricky to diagnose in children, who often either undergo unnecessary surgery or suffer serious complications when the condition is missed. Now, emergency physicians and scientists at the Children’s Hospital Boston Proteomics Center have identified a urine "biomarker" for appendicitis, the most accurate one known to date, using mass spectrometry, a technique that detects and quantifies proteins in a sample. When 57 potential markers were tested in 67 children, including 25 with proven appendicitis, a protein called LRG showed near-perfect sensitivity and specificity. With a Technology Development Grant from the hospital, the researchers plan to validate their findings and develop tests for clinical use. (Annals of Emergency Medicine, June 25, 2009)
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The challenge in treating autoimmune disease has been suppressing inflammatory attacks without impairing a patient’s immune function. Now, a drug from the hydrangea root, long used in Chinese medicine, is showing promise. Researchers Mark Sundrud, PhD, and Anjana Rao, PhD, of the Program in Cellular Medicine and the Immune Disease Institute at Children’s (PCMM/IDI), with collaborators, show that it prevents the development of Th17 cells, a recently recognized kind of T-cell that’s been implicated in inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis (MS), type 1 diabetes, eczema, psoriasis and other autoimmune disorders. In a mouse model, it reduced the severity of an MS-like autoimmune disease without altering T-cells involved in normal immune function. The drug, called halofuginone, has the potential to be taken orally. (Science, June 5, 2009)
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Too much clotting can cause stroke or heart attack; too little can make a person bleed to death from a wound. To achieve the proper balance, the body relies on a finely-tuned mechanical feedback system. Researchers co-led by Timothy Springer, PhD, of PCMM/IDI, have revealed this system in exquisite detail. Using tiny laser "tweezers" capable of manipulating single molecules, they show that the blood clotting protein von Willebrand factor (VWF) contains a small region called the A2 domain that acts as a force sensor. Miniscule forces applied by blood flow cause it to unfold, enabling VWF to be trimmed to the right length, so neither too much bleeding nor too much clotting occurs. (Science, June 5, 2009; PNAS, June 9, 2009)
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Biologists have long wondered why an embryo’s heart begins beating so early, before the tissues need a blood supply. Researchers Leonard Zon, MD, and George Daley, MD, PhD, of Children’s Stem Cell Program, with collaborators at Brigham and Women’s Hospital, provide one explanation, showing that a beating heart and fluid flow are needed for development of the blood system. The mechanical stress of fluid flow, they found, cues the production of nitric oxide, which in turn stimulates formation of blood stem cells and progenitor cells. Drugs that mimic the effects of blood flow, or affect nitric oxide signaling, might help create new blood cells for patients with diseases like leukemia, immune deficiency and sickle cell anemia. (Cell, May 15 and Nature, June 25, 2009)
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There’s currently no approved treatment for metastasis, the deadly migration of cancer to other sites in the body. But Randoph Watnick, PhD, of Children’s Vascular Biology Program, recently isolated a potent metastasis inhibitor that’s made by tumor cells themselves, called prosaposin. When mice were injected with highly metastatic breast or prostate tumor cells, and then given prosaposin, the cells formed virtually no lung metastases, or, if they did, formed much smaller colonies. The mice also lived significantly longer. Prosaposin apparently works by stimulating the tumor suppressor p53 in the tissue around the tumor, in turn stimulating thrombo-spondin-1, an inhibitor of blood vessel growth, both locally and at the distant location. If further studies bear out, Watnick envisions adding anti-metastasis drugs to cancer therapy. (PNAS, July 21, 2009)
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Rotavirus kills more than half a million children worldwide every year from severe vomiting and diarrhea. Now, using data from X-ray crystallography, researchers led by Stephen Harrison, PhD, chief of Children’s Laboratory of Molecular Medicine, and Harvard graduate student Scott Aoki, have derived an atomic model of a key protein on the virus’s surface, with a neutralizing antibody clamped onto it. The model gives important details about how antibodies interfere with rotavirus infection, and suggests how vaccines might be made that are stabler and easier to administer than the attenuated virus vaccines currently in use. (Science, June 12, 2009). Read more here about rotavirus research at Children's.
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Almost seven million Americans suffer from chronic anxiety. Now, David Clapham, MD, PhD, of Children’s Department of Cardiology, with collaborators, has found a molecular "on-off" switch for innate fear that could potentially lead to a more effective anti-anxiety drug. Unlike fear that’s learned from experience, innate fear is embedded in our genes (enabling us to escape from predators, for example). Innate fear gone awry is thought to be a component of anxiety disorders. In laboratory experiments, the researchers showed that a protein in the brain called TRPC5, which lets calcium into cells, triggers innate fear in mice. Mice lacking TRPC5 had diminished anxiety about exploring new places and in new social interactions-things they typically fear instinctively. (Cell, May 15, 2009). Click here to listen to a Cell podcast interview with Clapham.
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Stroke is the leading cause of adult disability in the United States, and most victims suffer life-long impairment. In 2002, Larry Benowitz, PhD, director of Children’s Laboratories for Neuroscience Research in Neurosurgery, discovered that inosine, a compound naturally occurring in cells, stimulates neuron growth and improves motor function in stroke-impaired rodents, but he didn’t know how it worked. Now, Benowitz and colleagues have discovered that inosine alters gene activity in neurons, enhancing their ability to form new neural connections and helping to restore function to the damaged areas. This discovery brings inosine a step closer to clinical use and may lead to the discovery of other compounds with potential therapeutic value. (Journal of Neuroscience, June 24, 2009). Read more about inosine here.
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