Before phototransduction, spontaneous activity in the developing mammalian retina is required for the appropriate patterning of retinothalamic connections, and there is growing evidence that this activity influences the development of circuits within the retina itself. We demonstrate here that the neural substrate that generates waves in the mouse retina develops through three distinct stages. First, between embryonic day 16 and birth [postnatal day 0 (P0)], we observed both large, propagating waves inhibited by nicotinic acetylcholine receptor (nAChR) antagonists and small clusters of cells displaying nonpropagating, correlated calcium increases that were independent of nAChR activation. Second, between P0 and P11, we observed only larger propagating waves that were abolished by toxins specific to ␣3 and ␤2 subunit-containing nAChRs. Third, between P11 and P14 (eye opening) we observed propagating activity that was abolished by ionotropic glutamate receptor antagonists. The time course of this developmental shift was dramatically altered in retinas from mice lacking the ␤2 nAChR subunit or the ␤2 and ␤4 subunits.These retinas exhibited a novel circuit at P0, no spontaneous correlated activity between P1 and P8, and the premature induction at P8 of an ionotropic glutamate receptor-based circuit. Retinas from postnatal mice lacking the ␣3 nAChR subunit exhibited spontaneous, correlated activity patterns that were similar to those observed in embryonic wild-type mice. In ␣3Ϫ/Ϫ and ␤2Ϫ/Ϫ mice, the development and distribution of cholinergic neurons and processes and the density of retinal ganglion cells (RGCs) and the gross segregation of their dendrites into ON and OFF sublaminae were normal. However, the refinement of individual RGC dendrites is delayed. These results indicate that retinal waves mediated by nAChRs are involved in, but not required for, the development of neural circuits that define the ON and OFF sublamina of the inner plexiform layer.

Xenopus cDNAs homologous to the Drosophila Mad gene and C. elegans CEM genes have been cloned and functionally analyzed by microinjection into frog embryos. The results show that these genes (Xmad) encode intracellular proteins that act downstream of TGF beta superfamily ligands. Most interesting is the fact that different Xmad proteins produce distinct biological responses. Xmad1 produces ventral mesoderm, apparently transducing a signal for BMP2 and BMP4, whereas Xmad2 induces dorsal mesoderm like Vg1, activin, and nodal. These results suggest that an individual Xmad protein waits poised in the cytoplasm for instruction from a distinct subset of TGF beta ligands and then conveys specific information to the nucleus.

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Studies in adults show that pretreatment with an optimal emollient may improve transmission of ultraviolet-B. In our study, we evaluated whether the preirradiation use of mineral oil enhanced the efficacy of narrow-band ultraviolet-B phototherapy in childhood psoriasis. Twenty children, aged 5 to 14 years with widespread, symmetrical psoriasis involving >20% body surface area were enrolled in a prospective, single-blind, controlled study. Mineral oil was applied prior to irradiation over one half of the body and the other half was emollient-free control. Narrow-band ultraviolet-B phototherapy was administered to whole body twice a week on nonconsecutive days with initial dose of 50 mJ/cm(2) and increment of 10% at each session. Clinical response was evaluated as grades of erythema, scaling and induration, area of involvement and modified psoriasis area severity index score on each side at baseline, 3, 6, 9, and 12 weeks. Two patients dropped out, 18 patients completed the study. Significantly greater improvement (p< 0.05) in scaling, induration, area of involvement, and modified psoriasis area severity index score was seen on the mineral oil pretreated side as early as 3 weeks and was maintained throughout the study. Difference in erythema was noticed later at 6 weeks. The cumulative dose for clearance was significantly lower on the emollient pretreated side. No adverse effects were observed with mineral oil or narrow-band ultraviolet-B phototherapy. We conclude that preirradiation use of mineral oil enhances the therapeutic efficacy of narrow-band ultraviolet-B phototherapy in children with widespread psoriasis.

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