Background: Although there have been several reports on the prevalence of atopic dermatitis(AD)inJapaneseschoolchildren based on questionnaires, there has been no nation- wide study of the frequency of this condition ...Background: Although there have been several reports on the prevalence of atopic dermatitis(AD)inJapaneseschoolchildren based on questionnaires, there has been no nation- wide study of the frequency of this condition diagnosed by dermatologists in regular health check- ups of schoolchildren. Objectives: The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check- ups by dermatologists. Methods: In 2001/2, elementary schoolchildren: first graders (age 6- 7 years) and sixth graders (age 11- 12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700× 4× 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease. Results: The point prevalence of AD was 11 2% overall (2664 of 23 719) ranging from 7 4% (Iwate) to 15 0% (Fukuoka) in the eight areas. Seventy- four per cent, 24% , 1 6% and 0 3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11 8% vs. 10 5% , P < 0 01). There was no apparent difference in prevalence between urban and rural districts, or between boys and girls. Conclusions: The prevalence of AD in Japanese elementary schoolchildren was about 10% , three- quarters of those being mildly affected. This is the first nation- wide study made of Japanese elementary schoolchildren examined by dermatologists to evaluate the frequency of AD.展开更多
Fibrosis, the hallmark of scleroderma, is characterized by excessive synthesis of collagen and extracellular matrix proteins and accumulation of myofibroblasts. Transforming growth factor-β(TGF-β), a potent inducer ...Fibrosis, the hallmark of scleroderma, is characterized by excessive synthesis of collagen and extracellular matrix proteins and accumulation of myofibroblasts. Transforming growth factor-β(TGF-β), a potent inducer of collagen synthesis, cytokine production, and myofibroblast transdifferentiation, is implicated in fibrosis. Profibrotic TGF-βresponses are induced primarily via the type I activin-like receptor kinase 5 (ALK5) TGF-βreceptor coupled to Smad signal transducers. Here, we investigated the effect of blocking ALK5 function with SM305, a novel small-molecule kinase inhibitor, on fibrotic TGF-βresponses. In normal dermal fibroblasts, SM305 abrogated the ligandinduced phosphorylation, nuclear import, and DNA-binding activity of Smad2/3 and Smad4, and inhibited Smad2/3-dependent transcriptional responses. Furthermore, SM305 blocked TGF-β-induced extracellular matrix gene expression, cytokine production, and myofibroblast transdifferentiation. In unstimulated scleroderma fibroblasts, SM305 caused a variable and modest reduction in type I collagen levels, and failed to abrogate constitutive nuclear accumulation of Smad2/3, or alter the proportion of smooth muscle actin stress fiber-positive fibroblasts. In vivo, SM305 prevented TGF-β-induced Smad2/3 phosphorylation type I collagen (COL1)A2 promoter activation in dermal fibroblasts. Taken together, these results indicate that SM305 inhibits intracellular TGF-βsignaling through selective interference with ALK5-mediated Smad activation, resulting in marked suppression of profibrotic responses induced by TGF-βin vivo and in vitro.展开更多
文摘Background: Although there have been several reports on the prevalence of atopic dermatitis(AD)inJapaneseschoolchildren based on questionnaires, there has been no nation- wide study of the frequency of this condition diagnosed by dermatologists in regular health check- ups of schoolchildren. Objectives: The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check- ups by dermatologists. Methods: In 2001/2, elementary schoolchildren: first graders (age 6- 7 years) and sixth graders (age 11- 12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700× 4× 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease. Results: The point prevalence of AD was 11 2% overall (2664 of 23 719) ranging from 7 4% (Iwate) to 15 0% (Fukuoka) in the eight areas. Seventy- four per cent, 24% , 1 6% and 0 3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11 8% vs. 10 5% , P < 0 01). There was no apparent difference in prevalence between urban and rural districts, or between boys and girls. Conclusions: The prevalence of AD in Japanese elementary schoolchildren was about 10% , three- quarters of those being mildly affected. This is the first nation- wide study made of Japanese elementary schoolchildren examined by dermatologists to evaluate the frequency of AD.
文摘Fibrosis, the hallmark of scleroderma, is characterized by excessive synthesis of collagen and extracellular matrix proteins and accumulation of myofibroblasts. Transforming growth factor-β(TGF-β), a potent inducer of collagen synthesis, cytokine production, and myofibroblast transdifferentiation, is implicated in fibrosis. Profibrotic TGF-βresponses are induced primarily via the type I activin-like receptor kinase 5 (ALK5) TGF-βreceptor coupled to Smad signal transducers. Here, we investigated the effect of blocking ALK5 function with SM305, a novel small-molecule kinase inhibitor, on fibrotic TGF-βresponses. In normal dermal fibroblasts, SM305 abrogated the ligandinduced phosphorylation, nuclear import, and DNA-binding activity of Smad2/3 and Smad4, and inhibited Smad2/3-dependent transcriptional responses. Furthermore, SM305 blocked TGF-β-induced extracellular matrix gene expression, cytokine production, and myofibroblast transdifferentiation. In unstimulated scleroderma fibroblasts, SM305 caused a variable and modest reduction in type I collagen levels, and failed to abrogate constitutive nuclear accumulation of Smad2/3, or alter the proportion of smooth muscle actin stress fiber-positive fibroblasts. In vivo, SM305 prevented TGF-β-induced Smad2/3 phosphorylation type I collagen (COL1)A2 promoter activation in dermal fibroblasts. Taken together, these results indicate that SM305 inhibits intracellular TGF-βsignaling through selective interference with ALK5-mediated Smad activation, resulting in marked suppression of profibrotic responses induced by TGF-βin vivo and in vitro.
