We have constructed a reference model to facilitate comparison of serum IGF-I values among children, and thereby to improve the value of IGF-I measurements for diagnosis. The data set consists of serum values measured in 969 samples from 468 healthy children and adolescents (232 males, 236 females; ages, 1.1-18.3 yr). One sample per child was used for the model, each being selected so as to provide sufficient observations for each stage of puberty. The samples not selected were used to validate the reference data. The IGF-I values were log transformed, and multiple regression analysis was used in the model-building process. The best linear model, which converts serum IGF-I concentrations into SD scores and explains 66% of the variation in logIGF-I values, includes the variables of age, gender, and puberty, and takes the interactions among these variables into account. In prepubertal and early pubertal children, the relationship between age and logIGF-I was positive, with greater effect in girls older than 8 yr. In mid-puberty, logIGF-I values were higher in girls than in boys of the same age, up to 16 yr of age. Among boys, the most pronounced positive relationship between age and logIGF-I occurred in mid-puberty, whereas the relationship between age and logIGF-I among girls in mid-puberty is fairly constant. In late puberty, logIGF-I values were higher than earlier in puberty, and there was a negative relationship with age in both boys and girls. Instead of separate models for each combination of puberty and gender, estimating a single regression model permits simultaneous estimation of all explanatory variables and uses all observations in the data set, thereby making it easier to select those variables that have a significant effect on logIGF-I. Our model shows that IGF-I levels are related to age during each stage of puberty. The model also accounts for the fact that serum IGF-I concentrations during puberty are different for boys and girls.
Ultraviolet (UV) radiation is an etiologic agent for malignant melanoma and non-melanoma skin cancer, but the spectral range responsible for tumor induction is still to be elucidated. In this study, we compared effects of UVA and UVB irradiation on normal human melanocytes (MCs) and keratinocytes (KCs) in vitro. We demonstrate that UVA irradiation induces immediate loss of reduced glutathione (GSH) in both MCs and KCs. Exposure to UVA also causes reduced plasma membrane stability, in both cell types, as estimated by fluorescein diacetate retention and flow cytometry. Furthermore, we noted reduction in proliferation and higher apoptosis frequency 24 h after UVA irradiation. UVB irradiation of KCs caused instant reduction of reduced GSH and impaired plasma membrane stability. We also found decline in proliferation and increased apoptosis after 24 h. In MCs, on the other hand, UVB had no effect on GSH level or plasma membrane stability, although increased apoptotic cell death and reduced proliferation was detected. In summary, MCs and KCs showed similar response towards UVA, while UVB had more pronounced effects on KCs as compared to MCs. These results might have implications for the induction of malignant melanoma and non-melanoma skin cancer.
To facilitate the diagnosis of GH deficiency and monitor GH therapy, we constructed two reference models to allow comparison of serum IGF binding protein (IGFBP)-3 concentrations and IGF-I to IGFBP-3 ratios among children throughout childhood and adolescence. This report presents equations for determining the sd score of IGFBP-3 and IGF-I to IGFBP-3 measurements for individual patients. The data set contains serum values from 468 healthy children and adolescents (232 males, 236 females; ages 1.1-18.3 yr) whose height, weight, and body mass index were within +/- 3 sd of means. Puberty was classified according to breast development (B) and testicular volume into pre-, early, mid-, and late puberty. The values of IGFBP-3 and IGF-I to IGFBP-3 ratios were log transformed, and multiple linear regression analysis was used to identify models for converting serum concentrations into sd scores. The models include the variables of age, gender, and puberty and take into account the interactions among these variables. The best linear models explain 42% of the variation in serum IGFBP-3 concentrations and 50% of the variation in serum IGF-I to IGFBP-3 concentrations. The relationship between age and log(IGFBP-3) was positive for boys in pre-, early, and midpuberty. In late puberty, values were higher than earlier in puberty, and there was a negative relationship with age. For girls the relationship between age and log(IGFBP-3) also was positive in pre- and early puberty, with larger effect for girls older than 8 yr. Values for girls in midpuberty were relatively constant, and in late puberty values were higher than earlier in puberty, and there was a negative relationship with age. The relationship between age and log(IGF-I to IGFBP-3 ratio) was positive for boys in pre-, early, and early midpuberty (volume = 9-14 ml). In late midpuberty (volume = 15-19 ml), the relationship between age and IGF-I to IGFBP-3 ratio was negative. In late puberty, values were relatively constant and higher than earlier in puberty. For girls in prepuberty, the relationship with age was positive, with a larger effect in girls older than 8 yr. In early puberty, the girls' values were relatively constant. In early midpuberty (B = 3), log(IGF-I to IGFBP-3 ratio) values were higher for girls than boys of the same age. In late midpuberty (B = 4), the relationship with age was negative, and in late puberty values were relatively constant and higher than earlier in puberty.
beta-Carotene is one of the carotenoids that has been considered to play a role in the natural defense against ultraviolet-induced skin cancer. It is not known whether epidermal cells are able to accumulate beta-carotene and, subsequently, convert it to vitamin A. We used normal cultured human keratinocytes and melanocytes to study the uptake, and possible bioconversion to retinol, of authentic or [14C]beta-carotene. The uptake was much higher in melanocytes than in keratinocytes, corresponding to a fivefold difference in the intracellular fraction after two days of incubation. An increased level of cellular retinol was noted after one day of beta-carotene incubation. The conversion of [14C]beta-carotene to [14C]retinol peaked at 24 hours of incubation in keratinocytes and melanocytes. The results suggest that beta-carotene can function as a local supply of vitamin A in the skin and that melanocytes are especially likely to store beta-carotene.
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