Sizzled: a secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos

An expression cloning screen was used to isolate a novel gene homologous to the extracellular cysteine-rich domain of frizzled receptors. The gene (which we called sizzled for secreted frizzled) was shown to encode a soluble secreted protein, containing a functional signal sequence but no transmembrane domains. Sizzled (szl) is capable of inhibiting Xwnt8 as assayed by (1) dose-dependent inhibition of siamois induction by Xwnt8 in animal caps, (2) rescue of embryos ventralized by Xwnt8 DNA and (3) inhibition of XmyoD expression in the marginal zone. Szl can dorsalize Xenopus embryos if expressed after the midblastula transition, strengthening the idea that zygotic expression of wnts and in particular of Xwnt8 plays a role in antagonizing dorsal signals. It also suggests that inhibiting ventralizing wnts parallels the opposition of BMPs by noggin and chordin. szl expression is restricted to a narrow domain in the ventral marginal zone of gastrulating embryos. szl thus encodes a secreted antagonist of wnt signaling likely involved in inhibiting Xwnt8 and XmyoD ventrally and whose restricted expression represents a new element in the molecular pattern of the ventral marginal zone.     

Room-to-grow: responding to community cultural needs to support positive parenting

Preventive services to assist parents to understand their children's developmental needs and to devise positive, culturally appropriate strategies for managing them are not recognized as important by most third party health service payers, especially managed care programs. Room-To-Grow is an intervention designed to meet identified community needs in a culturally appropriate and sensitive way. This article discusses the evolution of this intervention and the problems encountered in finding appropriate reimbursement streams.     

Digital ischemia and gangrene due to red blood cell aggregation induced by acquired dysfibrinogenemia

Digital gangrene was observed in a patient who had angiographic findings of digital arterial occlusion. The patient's blood showed a marked red blood cell aggregation with rouleaux formation in long chains, which could not be dispersed at shear rates up to 200 sec-1. Studies of the patient's blood revealed the presence of an abnormal fibrinogen capable of aggregating normal red blood cells. This fibrinogen was found by Raman spectroscopy to have an increased alpha-helical content, whereas the beta-sheet content was decreased. Defibrinogenation therapy with ancrod resulted in a dramatic symptomatic relief. The disappearance of the abnormal fibrinogen 6 months later and an absence of a family history indicate that this dysfibrinogenemia was acquired.