SummaryTransforming growth factor B (TGF-~), a multifunctional cytokine, is an indirect mitogen for human fibroblasts through platelet-derived growth factor (PDGF), particularly the A ligand-c~ receptor arm of that system. TGF-~ effects on PDGF ot receptor expression were studied in vitro using ligand binding techniques in three human dermal fibroblast strains: newborn foreskin, adult skin, and scleroderma (systemic sclerosis, SSc). Each cell strain responded differently to TGF-~. In newborn foreskin fibroblasts, PDGF c~ receptor number decreased in a dose-dependent manner after exposure to low concentrations of TGF-B (0.1-1 ng/ml). Responses of normal skin fibroblasts were varied, and mean net receptor number was unchanged. Increases in PDGF c~ receptor number by TGF-B occurred consistently with SSc fibroblasts and low concentrations of TGF-~/(0.1-1 ng/ml) were particularly stimulatory. Increased surface expression of ot receptor subunit by TGF-~ in SSc fibroblasts correlated with increased new PDGF ot receptor synthesis as demonstrated by radioimmunoprecipitation analysis of metabolically labeled cells and with increased steady-state levels of corresponding mRNAs. In normal adult skin fibroblasts, TGF-B had no effect on either synthesis or mRNA expression of c~ receptor subunits. Proliferative responses to PDGF-AA after pretreatment with TGF-B correlated positively with effects of TGF-~ on expression of o~ receptor subunit. Decreased mitogenic responses to PDGF-AA were observed in foreskin fibroblasts, small changes in responses in adult fibroblasts, and significant increases in SSc fibroblasts. Thus, costimulation with PDGF-AA and TGF-B selectively enhanced proliferation of fibroblasts with the SSc phenotype. Immunohistochemical examination of SSc and control skin biopsies revealed the presence of PDGF-AA in SSc skin. Data obtained by ligand binding, immunoprecipitation, mRNA, and mitogenic techniques are consistent with the hypothesis that activation of the PDGF-AA ligand/ol receptor pathway is a characteristic of the SSc fibroblast and may contribute to the expansion of fibroblasts in SSc.

1,25-Dihydroxyvitamin D is the biologically active form of vitamin D for the treatment of skin eruptions in patients with psoriasis. 1,25-(OH)(2)D(3) elicits its action on skin eruptions through the vitamin D receptor (VDR). Allelic frequencies of VDR were studied in 86 normal subjects and 50 patients with psoriasis. Genomic DNA was extracted from peripheral blood leukocytes and the VDR gene was amplified using a heminested polymerase chain reaction (PCR). The products were digested with respective restriction enzymes ApaI, TaqI and BsmI. The restriction fragment length polymorphisms (RFLP) were coded as Aa, Tt or Bb. The frequencies of ApaI, BsmI and TaqI RFLP genotypes in psoriasis patients showed no significant differences compared with normal controls. The frequency of the AA genotype was significantly higher in pustulosis palmaris et plantaris patients than in psoriasis vulgaris patients ( P<0.05), and in psoriasis vulgaris patients than in psoriasis pustulosa patients ( P<0.01). In patients with psoriasis, the levels of serum alanine 2-oxoglutarate aminotransferase (ALT) were significantly higher in patients with the AA genotype (54.0+/-22.0 IU/l, n=4) than in those with the aa genotype (24.0+/-15.9 IU/l, n=27; P<0.02). The distribution of ApaI, BsmI, TaqI RFLP VDR genotypes showed no significant relationship to the PASI score, serum aspartate 2-oxoglutarate aminotransferase or triglyceride levels, or age at onset. These results show that the VDR genotype contributes to the liver dysfunction in patients with psoriasis, although no correlation was found between VDR genotype and the skin eruptions of psoriasis.

Our data suggest that nailfold capillary changes reflect microvascular changes of psoriasis and that the nailfold capillary pattern is a useful tool in evaluating nail involvement and the severity of psoriasis.

A new occupational disorder characterized by skin sclerosis is described. This disease developed acutely in workmen exposed to the vapor of epoxy resins. Based on animal experiments, an amine [bis(4-amino-3-methyl-cyclohexyl) methane] is suspected of being the causative agent of the skin sclerosis.

A glycosaminoglycan with scleroderma-inducing effect was isolated and partially purified from the urine of patients with systemic scleroderma. The glycosaminoglycan was an N-sulfated glycosaminoglycuronan and its high total sulfate and 2,5-anhydromannose contents suggest that the glycosaminoglycan is a degradation product of heparin or polysulfated heparan sulfate. Furthermore, the composition of the above glycosaminoglycan was similar to that of the N-sulfated glycosaminoglycan which we observed previously in uninvolved skin of scleroderma.

Our data suggest that in patients with SSC, nailfold capillary abnormalities correlate with pulmonary arterial hypertension as well as with clinical and laboratory findings indicating pulmonary hypertension.

It has been reported that more male DNA of presumed fetal origin is present in the blood and skin of women with systemic sclerosis (SSc) as compared with healthy controls after delivery, but these findings are controversial. We sought to determine whether male cell DNA is present in SSc using a quantitative polymerase chain reaction for Y chromosome DNA. The study groups comprised 57 healthy women, 49 patients with SSc and 30 patients with connective tissue diseases other than SSc who had given birth to at least one son and/or had experienced fetal loss. The intensity of the PCR bands on negatives of gel photographs was quantified with a video densitometer linked to a computer analysis system. Positive Y chromosome DNA was found in 20 healthy women, 14 SSc patients and 6 patients with connective tissue diseases other than SSc. The occurrence rate of DNA equivalents of male cells among the three groups showed no significant differences. The number of male cell DNA equivalents per 80 ng tissue DNA in SSc patients (4.59+/-9.63), however, was significantly higher than in healthy women (1.83+/-4.96; P < 0.05) and in patients with connective tissue diseases other than SSc (0.27+/-0.64; P < 0.01). The occurrence rate of fetal loss in male cell DNA-positive SSc (eight) was significantly higher than in male cell DNA-negative SSc patients (four; P < 0.01). No correlation was found between the number of male cell DNA equivalents and birth of sons or clinicolaboratory findings. These results indicate that the elevated amount of male cell DNA in SSc skin tissue may contribute to the pathogenesis of SSc.

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