Subverting Hedgehog Protein Autoprocessing by Chemical Induction of Paracatalysis.

Hedgehog proteins, a family of vital cell signaling factors, are expressed in precursor form, which requires specialized autoprocessing, called cholesterolysis, for full biological activity. Cholesterolysis occurs in cis through the action of the precursor's C-terminal enzymatic domain, HhC. In this work, we describe HhC activator compounds (HACs), a novel class of noncovalent modulators that induce autoprocessing infidelity, diminishing native cholesterolysis in favor of precursor autoproteolysis, an otherwise minor and apparently nonphysiological side reaction. HAC-induced autoproteolysis generates hedgehog protein that is cholesterol free and hence signaling deficient. The most effective HAC has an AC50 of 9 µM, accelerates HhC autoproteolytic activity by 225-fold, and functions in the presence and absence of cholesterol, the native substrate. HACs join a rare class of "antagonists" that suppress native enzymatic activity by subverting mechanistic fidelity.

Ovarian teratoma with torsion masquerading as intussusception in 4-year-old child.

BACKGROUND: Ovarian torsion (OT) occurs primarily in women of child-bearing age, but is rare in the pediatric population. The clinical presentation often consists of nonspecific abdominal complaints making the diagnosis difficult. Radiologic and sonographic evidence can be misleading. Although the delay in diagnosis from symptom onset is common, rapid diagnosis of ovarian torsion is imperative to prevent morbidity. CASE REPORT: We present the case of a four-year-old female who presented to the emergency department (ED) with a five-day history of intermittent abdominal pain and emesis. Initial diagnosis was suspicious for intussusception; however, on operative exploration, she was found to have a right adnexal torsion secondary to an ovarian teratoma. A right salpingo-oophorectomy was performed. CONCLUSION: Early diagnosis of ovarian torsion may increase ovarian salvage and reduce morbidity. Faced with abdominal pain of uncertain etiology in a female child, emergency physicians should include ovarian torsion secondary to an ovarian mass in the differential diagnosis.