Research news (InTouch Spring 2008)

Mayanilsm_spring08.jpgChandra S.K. Mayanil, PhD, and colleagues have published a study in the journal Developmental Biology that investigates whether the paired-box gene transcription factor, Pax3, plays a role in regulating key transcription factors, Hairy and enhancer of split homolog-1 (Hes1) and Neurogenin2 (Ngn2), which are responsible for proper maintenance of neural stem cells and sensory neuronal differentiation. The group found that in the absence of functional Pax3, the neural crest cells undergo premature neurogenesis in comparison with wild-type. They also showed that Pax3 regulates Hes1 and Ngn2 by directly binding to their promoters. These observations suggest that Pax3 may play a crucial role in neural stem cell maintenance and neurogenesis. Clinically, this finding may be important for neural tube defects associated with spina bifida and exencephaly. Mayanil is research assistant professor in Neurological Surgery at Northwestern University's Feinberg School of Medicine and director of Neural Tube Research and a member of the Developmental Biology Program of Children's Memorial Research Center.

devdynamics_spring08Robert Dettman, PhD, and colleagues have published a study in the journal Developmental Dynamics. Formation of the visceral pericardium or epicardium is critical to normal heart development. Their research shows that the integrin alpha4beta1 controls many aspects of early epicardial development in the chick heart. It does so in part by regulating other integrins in epicardial cells that are important for cell adhesion and migration. When the function of integrin alpha4beta1 is altered, epicardial cells cannot normally bind to extracellular matrix ligands bound by other integrins such as alphavbeta3. Also, epicardial cells expressing a variant of alpha4 integrin cannot incorporate soluble fibronectin into a mesh-like fibronectin matrix. Dettman is assistant professor of Pediatrics at Northwestern University's Feinberg School of Medicine, a member of the Feinberg Cardiovascular Research Institute and a member of the Developmental Biology Program of Children's Memorial Research Center.

Lauren PachmanLauren M. Pachman, MD, and colleagues have found a difference in absorption of a drug administered to juvenile dermatomyositis (JDM) patients when given orally as opposed to intravenously. More aggressive therapies for JDM have been linked to improved outcomes in patients. The hallmark of JDM, the most common autoimmune muscle disease of children, is destruction of nailfold capillaries. By counting the capillary and loops, clinicians can monitor drug absorption. A study published in the February issue of Arthritis Care & Research shows that loss of capillaries is directly associated with decreased absorption of orally administered prednisone, the drug of choice to treat JDM, compared with the same dose given intravenously. This study provides evidence that intravenous administration of steroids may be needed to achieve disease control. Kelly Rouster-Stevens, MD, PharmD, assistant professor of Pediatrics at Wake Forest University Baptist Medical Center, was first author on the study. Pachman is professor of pediatrics at Northwestern University's Feinberg School of Medicine, an attending physician in the Division of Rheumatology at Children’s Memorial Hospital and director of the Molecular and Cellular Pathobiology Program of Children's Memorial Research Center. The study was supported by the National Center for Research Resources, National Institutes of Health, and by The Cure Juvenile Myositis Foundation.

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