Lack of effect of propranolol in the treatment of lymphangioma in two children.

Vascular lesions such as hemangiomas and lymphangiomas can cause significant mortality and morbidity, as well as amblyopia when located in the orbit. Oral propranolol can regress infantile hemangioma during infancy and up to 23 months of age, but its effect on lymphangioma has not been demonstrated. We present two cases of lymphatic malformations treated with oral propranolol. Patient 1 is a 2-year-old boy with macrocystic bilateral cervical lymphangioma extending to the pharynx and larynx and microcystic lymphangioma of the tongue. The patient was started on propranolol 2 mg/kg/day starting at 17 months of age, and after 3 months only a very slight decrease in tongue volume was noted. Patient 2 is a 3.5-year-old boy with magnetic resonance imaging evidence of right facial complex lymphangioma with venous malformation. The patient was placed on oral propranolol 2 mg/kg/day. After 3 months of treatment, no change in the lesion was noted except for a transient decrease in the size of the conjunctival telangiectasia. Propranolol 2 mg/kg/day was not effective in treating lymphatic malformations in two children, both older than 17 months at the time of treatment.

The pp24 phosphoprotein of Mason-Pfizer monkey virus contributes to viral genome packaging.

BACKGROUND: The Gag protein of Mason-Pfizer monkey virus, a betaretrovirus, contains a phosphoprotein that is cleaved into the Np24 protein and the phosphoprotein pp16/18 during virus maturation. Previous studies by Yasuda and Hunter (J. Virology. 1998. 72:4095-4103) have demonstrated that pp16/18 contains a viral late domain required for budding and that the Np24 protein plays a role during the virus life cycle since deletion of this N-terminal domain blocked virus replication. The function of the Np24 domain, however, is not known. RESULTS: Here we identify a region of basic residues (KKPKR) within the Np24 domain that is highly conserved among the phosphoproteins of various betaretroviruses. We show that this KKPKR motif is required for virus replication yet dispensable for procapsid assembly, membrane targeting, budding and release, particle maturation, or viral glycoprotein packaging. Additional experiments indicated that deletion of this motif reduced viral RNA packaging 6-8 fold and affected the transient association of Gag with nuclear pores. CONCLUSION: These results demonstrate that the Np24 domain plays an important role in RNA packaging and is in agreement with evidence that suggests that correct intracellular targeting of Gag to the nuclear compartment is an fundamental step in the retroviral life cycle.

Mason-Pfizer monkey virus Gag proteins interact with the human sumo conjugating enzyme, hUbc9.

Retroviral Gag proteins function during early and late stages of the viral life cycle. To gain additional insight into the cellular requirements for viral replication, a two-hybrid screen was used to identify cellular proteins that interact with the Mason-Pfizer monkey virus Gag protein. One of the cellular proteins found was identified as hUbc9, a nuclear pore-associated E2 SUMO conjugating enzyme. In vitro protein interaction assays verified the association and mapped the interaction domain to the CA protein. In vivo, hUbc9 and Gag colocalized in the cytoplasm as discrete foci near the nuclear membrane. In addition, overexpression of hUbc9 in cells caused a fraction of Gag to colocalize with hUbc9 in the nucleus. These experiments demonstrate that hUbc9 and Gag interact in cells, strengthen the hypothesis that Gag proteins transiently associate with the nuclear compartment during viral replication, and suggest that hUbc9 plays a role in this process.