In the course of our search for new melanin synthesis inhibitors from plants, 40 new flavonoids and 11 known flavonoids were isolated from the roots of Lespedeza floribunda Bunge. The structures of the new compounds were determined by MS and NMR analyses, and the absolute configurations by CD spectra. Many of the compounds inhibited melanin synthesis in normal human epidermal melanocytes (NHEM), and compounds 3, 7, 8, 11, 16, 24, 27, 29, 33, 43, 45, and 51 were particularly inhibitory. Their activities were stronger than that of hydroquinone, which is known as a major skin-lightening drug.

It has been reported that the gene for murine fibroblast growth factor-5 (Fgf-5) is expressed in the rat hair follicle and that this expression may be associated with catagen induction (Hebert et al, 1994). In this study, we analyzed the Fgf-5 gene product in skin because the gene generates two mRNA that translate into the FGF-5 protein and a short form of the FGF-5 protein (FGF-5S) as a result of an alternative splicing (Hattori et al, 1996; Ozawa et al, 1996). Indeed, we detected both types of FGF-5 mRNA in rat skin samples. Two monoclonal anti-FGF-5 antibodies, one (E723) being specific for FGF-5 long-form protein and the other (B2B6) being reactive with both FGF-5 and FGF-5S proteins, were used to locate these proteins by immunohistochemistry. Staining of the rat skin revealed that only the B2B6 antibody reacted with hair follicles and that both antibodies reacted with macrophage-like round cells, suggesting that the product of the Fgf-5 gene in the hair follicle is FGF-5S. The immunoreactivity of the FGF-5S protein increased during early anagen VI and decreased rapidly during catagen. The density of FGF-5-positive macrophage-like cells in the dermis increased during anagen and decreased during catagen and telogen, whereas the density of these cells in the panniculus adiposus did not change during anagen and increased during catagen and telogen. There was no apparent association between the density of FGF-5-positive macrophage-like cells and that of FGF-5-negative, dendritic macrophage-like cells. Thus, the results suggest the possible involvement of FGF-5S in the hair follicle in anagen VI and catagen development and that the density of FGF-5-positive macrophage-like cells may also be associated with the hair growth cycle.

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Among nephrotic children with frequent relapses at risk for cumulative steroid toxicity, identification of children who may be at high risk for subsequent relapse is very important in making the decision to introduce cytotoxic drugs. We examined the clinical course of 467 relapses in 121 steroid-sensitive nephrotic children to elucidate the risk factors for subsequent relapse, using the Cox proportional-hazards regression model. Gender, age at onset, duration of illness from onset, prednisolone dosage at the most-recent relapse, and regimens of initial steroid therapy at onset were not associated with risk. Relapse within the 1st year was a powerful independent predictor of subsequent relapse irrespective of the duration of illness. The hazard ratio of patients with more than one relapse within the 1st year increased to 1.72-2.12 compared with those without a relapse within the 1st year. The remission period just before the most-recent relapse was also a significant predictor. The risk for patients with a 1-year or longer remission period decreased to 0.57. Patients treated with cyclophosphamide for 12 weeks had a significantly longer remission than those treated with prednisolone alone. Our results suggest that early relapse after onset and/or a short remission period just before recent relapse are independent risk factors for subsequent relapse. Cytotoxic therapy has serious adverse effects and its effect may be limited. Our results may be helpful in deciding on the suitability of cytotoxic drugs.

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