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As has previously been reported by many investigators the anticentromere antibody is considered to be a useful serologic marker for the CREST (calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly and telangiectasia) variant of systemic sclerosis. However, this antibody also appears in other conditions. By screening antinuclear antibody tests using HEp-2 cells as substrate, 39 patients were shown to have the anticentromere antibody. These patients were divided into 4 groups: group 1 = 17 patients with systemic sclerosis; group 2 = 9 patients with Raynaud’s phenomenon alone; group 3 = 7 patients with other connective-tissue diseases, and group 4 = 6 patients with conditions other than those present in groups 1–3. Follow-up over years revealed that some patients suffering solely from Raynaud’s phenomenon (group 2) developed the symptoms of systemic sclerosis. In contrast, of the patients who did not have Raynaud’s phenomenon (group 4), none developed any symptom suggesting systemic sclerosis. We suggest that the simultaneous presence of Raynaud’s phenomenon and the anticentromere antibody predicts the occurrence of systemic sclerosis. In contrast, the presence of the anticentromere antibody alone cannot necessarily be used to predict the development of systemic sclerosis.

Clinical significance of specific antinuclear antibodies (ANA) in Japanese patients with systemic sclerosis was studied. The patients with systemic sclerosis were classified into four groups according to ANA: (1) anticentromere antibody-positive; (2) anti-Scl-70 antibody-positive; (3) anti-nRNP antibody-positive, and (4) others. The mean score (the number of positive signs in six selected specific signs) of the patients with anti-Scl-70 antibody was significantly higher than those of the other three groups. More frequent contracture of phalanges in the patients with anti-Scl-70 antibody less diffuse pigmentation in the patients with anti-nRNP antibody and less pulmonary fibrosis in the patients with anticentromere antibody were revealed. As shown above the detection of specific ANA in systemic sclerosis is clinically important.

The present invention provides a novel polypeptide, Connective Tissue Growth Factor (CTGF), polynucleotides encoding CTGF and polynucleotides regulating CTGF expression. The invention also provides agents that modulate CTGF and therapeutic methods for using the agents. Also provided are diagnostic methods for using CTGF and assays for identifying agents which affect the expression of CTGF polynucleotide.

• Three patients with systemic lupus erythematosus had positive antiribosomal P protein antibodies. The patients are women who had mild diseases that did not involve prominent internal organs. By using an immunofluorescence method for the detection of antinuclear antibodies that employs HEp-2 cells, these serum samples produced intense stainings on cytoplasm and nucleoli that were digested with RNase. With the use of an immunoblotting technique, these serum samples recognized three ribosomal P proteins, called PO (38 kd), P1 (19 kd), and P2 (17 kd). We suggest that antiribosomal P protein antibodies can be detected in patients with systemic lupus erythematosus and associated mild clinical features. (Arch Dermatol.1990;126:1184-1186)

The effects of various growth factors on endothelial cell survival in vitro were studied. Using rat heart endothelial cells, the cell survival curves were obtained; the cells were cultured until confluent, the medium was changed to serum-free medium with or without growth factors, and the cells were counted after 3, 6, 9, and 12 days. Transforming growth factor-beta, which is known as a potent growth inhibitor for vascular endothelial cells, shortened the rat heart endothelial cell's survival period, while epidermal growth factor or transforming growth factor-alpha prolonged survival. Insulin did not affect the rat heart endothelial cell's survival. Our data indicate that growth factors play a role not only in cell proliferation but also in cell survival in vitro. In addition, elevated levels of growth inhibitors such as transforming growth factor-beta may cause tissue damage in vivo by affecting cell survival.

Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor-like activities and is produced by skin fibroblasts after activation with transforming growth factor-beta. Coordinate expression of transforming growth factor-beta followed by CTGF during wound repair suggests a cascade process for control of tissue regeneration. We recently reported a significant correlation between CTGF mRNA expression and histologic sclerosis in systemic sclerosis. To confirm the relation between CTGF and skin fibrosis, we investigated CTGF gene expression in tissue expression in tissue sections from patients with localized scleroderma, keloid, other sclerotic skin disorders using nonradioactive in situ hybridization. In localized scleroderma, the fibroblasts with positive signals for CTGF mRNA were scattered throughout the sclerotic lesions with no preferential distribution around the inflammatory cells or perivascular regions, whereas the adjacent nonaffected dermis was negative for CTGF mRNA. In keloid tissue, the fibroblasts positive for CTGF mRNA were diffusely distributed, especially in the peripheral expanding lesions. In scar tissue, however, the fibroblasts in the fibrotic lesions showed partially positive signals for CTGF mRNA. In eosinophilic fasciitis, nodular fasciitis, and Dupuytren's contracture, CTGF mRNA was also expressed partially in the fibroblasts of the fibrotic lesions. Our findings reinforce a correlation between CTGF gene expression and skin sclerosis and support the hypothesis that transforming growth factor-beta plays an important role in the pathogenesis of fibrosis, as it is the only inducer for CTGF identified to date.

The clinical efficacy and safety of Roxithromycin (RU 28965, RU), a new macrolide preparation, were compared with those of Josamycin (JM) in superficial suppurative skin infections. The study was designed as double-blind controlled trial with daily dosages of 300 mg in RU group and 1200 mg in JM group. A total of 209 cases (RU:105; JM:104) was analyzed and the final global improvement rating was 82.9% in the RU group and 80.8% in the JM group; there was no significant difference between the two groups. Slight adverse reactions were observed in 3.6% (4 cases) of the RU group and in 4.6% (5 cases) of the JM group. In conclusion, RU at daily doses of 300 mg is as effective as JM at daily doses of 1200 mg in superficial suppurative skin infections.

A four-month-old Japanese girl with bullous pemphigoid of childhood (BPC) was reported. The characteristics of BPC antigen were studied by immunofluorescent technique using the serum of this patient with variously treated normal human skin as substrate. This study showed that her BPC antigen was quite similar to bullous pemphigoid antigen seen in adult patients and that this BPC antigen was differed from epidermolysis bullosa acquisita (EBA) antigen.

Mitogenic activities for adult skin fibroblasts in 17 sera from untreated patients with scleroderma at the early stage were studied. Mitogenic activities in 10% test sera were measured by the [3H]-thymidine incorporation assay using confluent fibroblasts; there was no significant difference between scleroderma-affected and normal controls. Growth-stimulatory activities for subconfluent fibroblasts in 10% test sera were measured by increased cell numbers; again, there was no significant difference between scleroderma-affected and normal controls. There have been contradictory reports on growth-stimulatory activities in scleroderma sera; our data do not suggest the presence of a specific mitogen in scleroderma sera.