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Biomedical subjects

E C LeRoy

Publications and source records attributed to E C LeRoy.

At least 55 records · Page 3Linked to original sources
PubMed1990

Persistent effect of TGF-beta 1 on extracellular matrix gene expression in human dermal fibroblasts.

TGF-beta, a potent inducer of the extracellular matrix, is also known to stimulate its own synthesis. In this report we have analyzed long term effects of TGF-beta 1 on its own expression and on the expression of extracellular matrix genes. We demonstrated that 24 hours of incubation of human dermal fibroblasts with TGF-beta 1 (1 ng/ml) under serum free conditions resulted in an elevated expression of TGF-beta 1, collagen alpha 2(I) and fibronectin mRNAs that persisted at least 96 hours after removal of TGF-beta 1. These data suggest the possibility of persistent in vivo activation of target cells following exposure to TGF-beta 1.

Cells, Cultured↗
PubMed1990

Mitogenic effect of transforming growth factor beta 1 on human fibroblasts involves the induction of platelet-derived growth factor alpha receptors.

Platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta), potent modulators of mesenchymal cell growth and differentiation, are often colocalizable in vivo. Previous in vitro studies in fibroblastic cell lines have shown variable, even antagonistic effects of TGF-beta on the mitogenic action of PDGF. This study demonstrates that in diploid human dermal fibroblasts, TGF-beta 1 is weakly mitogenic in the absence of serum or purified growth factors, and that TGF-beta 1 potentiates DNA synthesis in PDGF-stimulated fibroblasts with delayed kinetics when compared to stimulation with PDGF alone. TGF-beta 1 enhances mitogenic potency of all three PDGF isoforms and increases receptor binding of both 125I PDGF-AA and 125I PDGF-BB, consistent with the increased expression of the alpha type PDGF receptor. The induction of PDGF alpha receptor subunits by TGF-beta may play a role in enhancing the proliferative potential of human fibroblasts in certain physiologic and pathologic conditions.

DNA Replication↗
PubMed1990

A possible role for transforming growth factor-beta in systemic sclerosis.

The cause of systemic sclerosis remains unknown, but cellular and molecular mechanisms possibly responsible for the characteristic clinical manifestations of fibrosis and vascular damage (Raynaud's phenomenon, telangiectasis, digital infection, and renal arteriopathy) are becoming understood in greater detail. One possibly important cytokine is transforming growth factor-beta (TGF-beta); its involvement is reviewed here. With regard to vascular lesions, TGF-beta has variably been shown to inhibit endothelial cell growth in vitro but to promote angiogenesis in vivo, a paradox that remains unresolved. Nonetheless, an injurious activity of TGF-beta on microvascular endothelial cells could help to explain the intimal proliferation and microvascular obliteration seen. Whether as a result of or as a cause of endothelial cell damage, platelet activation has been well documented in systemic sclerosis and the platelet alpha granule pool contains a large quantity of TGF-beta. TGF-beta is also produced by activated macrophages and T cells, both of which are known to occur within systemic sclerosis lesions. An important effect of TGF-beta is its stimulation of fibroblast collagen and fibronectin synthesis and their deposition into the extracellular matrix. Stimulation by TGF-beta may therefore account for the fibrosis seen in the dermis and in the internal organs. Direct evidence of TGF-beta involvement in systemic sclerosis is scanty, and awaits discovery of either an abnormal expression of or response to TGF-beta. The biologic effects of TGF-beta appear to be regulated at the level of activation from a latent polypeptide precursor form. Descriptions of the importance of this cytokine in pathologic conditions will need to account for this activation and its regulation. Nonetheless, the physiologic effects so far attributed to TGF-beta make its involvement in systemic sclerosis an attractive possibility to explain some of the manifestations of this enigmatic disease.

Chemotactic Factors↗
PubMed1990

Major clinical diagnoses found among patients with Raynaud phenomenon from the general population.

This study of 62 individuals with Raynaud phenomenon (RP) drawn from the general population of South Carolina shows a profile of associated diseases that is different from the one reported from hospital based studies. We found that connective tissue diseases affect a much smaller fraction of patients with RP than previously reported. Compared to RP negative controls, our RP positive group was found to suffer more frequently from a variety of diseases, both RP related and not RP related.

Connective Tissue Diseases↗
PubMed1990

Ketotifen prevents skin fibrosis in the tight skin mouse.

Mast cells in the skin of the tight-skin mouse show an enhanced degranulation compared to those of syngeneic litter mates. Oral treatment with ketotifen, an inhibitor of mast cell degranulation, at a dose comparable to that recommended for man, was associated with a decrease in both mast cell degranulation and in skin fibrosis, suggesting the potential for its use in human scleroderma.

Animals↗
PubMed1989

Interleukin-2 in scleroderma: correlation of serum level with extent of skin involvement and disease duration.

STUDY OBJECTIVE: To assess whether interleukin-2 has a role in the pathogenesis of scleroderma. DESIGN: Observe serum effect on the in-vitro growth of an interleukin-2-dependent cytotoxic T-cell line and determine serum level by an enzyme-linked immunosorbent assay. SETTING: Outpatient rheumatology clinic of a university medical center. PATIENTS: Sera were collected from 47 patients with scleroderma, 20 patients with rheumatoid arthritis, and 14 matched control subjects. MEASUREMENTS AND MAIN RESULTS: A significant mitogenic effect was observed in sera from patients with scleroderma of recent onset; a lower proliferative response was seen in rheumatoid sera. Matched control sera had no mitogenic activity. Sera from patients with scleroderma of recent onset supported the in-vitro growth of an interleukin-2-dependent cytotoxic T-cell line. Matched control sera had no similar mitogenic activity. Interleukin-2 was found in sera from 41 of 47 patients with scleroderma (204 +/- 356 U/mL, mean +/- SD), in 9 of 20 patients with rheumatoid arthritis (2.04 +/- 5.16), and in none of 14 matched control subjects. There was a positive correlation between serum level and the skin progression index (skin score/disease duration). CONCLUSIONS: The presence of interleukin-2 in scleroderma sera strongly supports a role for T-cell activation in scleroderma. The association between serum levels and disease progression indicates that this T-cell process may participate in the progression of the disease.

Adult↗
PubMed1989

Spontaneous production of fibronectin by alveolar macrophages in patients with scleroderma.

Interstitial pulmonary fibrosis is a common manifestation of systemic sclerosis (SSc) and is a pathologic feature shared by a variety of other diseases. In these other disease processes, the glycoprotein fibronectin (FN) has been shown to be released by the alveolar macrophage, and is thus implicated in the development of fibrosis. We therefore studied the release of FN by alveolar macrophages obtained by bronchoalveolar lavage of 17 patients with SSc and 14 controls. We found that SSc alveolar macrophages released significantly more FN than did those of controls. Furthermore, the level of FN correlated positively with the level of inflammation determined by cellular analysis of lavage fluid and negatively with carbon monoxide diffusing capacity. FN may therefore play a role in the development of lung fibrosis in SSc and may be a marker of alveolitis.

Adult↗
PubMed1989

Prevalence of scleroderma spectrum disorders in the general population of South Carolina.

The prevalence of scleroderma spectrum disorders (including systemic sclerosis [SSc] meeting the American Rheumatism Association criteria and the less typical disorders meeting only our study criteria) was determined in a random sample of 6,998 subjects from the general population of South Carolina. The results suggest that the prevalence of these disorders may range from 67 to 265 per 100,000, which is 4.9 to 19.2 times higher than previously reported for definite SSc. The ratio of nondefinite cases to definite cases of SSc (those meeting American Rheumatism Association criteria) was 2.5. Most of the nondefinite cases were unrecognized prior to our study, which suggests the need for improved early diagnosis of scleroderma spectrum disorders. Brief histories of the 7 patients with scleroderma spectrum disorders whose cases formed the basis for our calculation of prevalence rates are included in this report.

Adult↗