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Biomedical subjects

E C LeRoy

Publications and source records attributed to E C LeRoy.

17 recordsLinked to original sources
PubMed1992

Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts.

Transforming growth factor beta (TGF-beta), a multifunctional cytokine, is an indirect mitogen for human fibroblasts through platelet-derived growth factor (PDGF), particularly the A ligand-alpha receptor arm of that system. TGF-beta effects on PDGF alpha 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-beta. In newborn foreskin fibroblasts, PDGF alpha receptor number decreased in a dose-dependent manner after exposure to low concentrations of TGF-beta (0.1-1 ng/ml). Responses of normal skin fibroblasts were varied, and mean net receptor number was unchanged. Increases in PDGF alpha receptor number by TGF-beta occurred consistently with SSc fibroblasts and low concentrations of TGF-beta (0.1-1 ng/ml) were particularly stimulatory. Increased surface expression of alpha receptor subunit by TGF-beta in SSc fibroblasts correlated with increased new PDGF alpha 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-beta had no effect on either synthesis or mRNA expression of alpha receptor subunits. Proliferative responses to PDGF-AA after pretreatment with TGF-beta correlated positively with effects of TGF-beta on expression of alpha 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-beta 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/alpha receptor pathway is a characteristic of the SSc fibroblast and may contribute to the expansion of fibroblasts in SSc.

Adult↗
PubMed1992

Differential modulation of bFGF receptors by TGF-beta in adult skin, scleroderma skin, and newborn foreskin fibroblasts.

Effects of transforming growth factor beta (TGF-beta) on proliferative responses to basic fibroblast growth factor (bFGF) were studied in human diploid fibroblasts cell strains derived from three different sources: adult skin, scleroderma, and newborn foreskin. All three types of cell strains were similarly responsive to TGF-beta, whereas adult skin fibroblasts were significantly more responsive to bFGF. Incubation of cells with TGF-beta prior to bFGF addition substantially increased responsiveness of adult skin fibroblasts to this latter cytokine, slightly increased that of scleroderma fibroblasts, and decreased that of foreskin fibroblasts. Modulation of bFGF receptors by TGF-beta correlated positively with these mitogenic effects. Adult skin fibroblasts showed increases of both high- and low-affinity receptors and scleroderma fibroblasts showed small increases of high-affinity receptors only, whereas foreskin fibroblasts showed no changes. Heparitinase treatment of adult skin fibroblasts during TGF-beta pre-incubation resulted in reduced bFGF binding to low-affinity receptors and reduced mitogenic response to bFGF, suggesting that the TGF-beta-stimulated increase of low-affinity receptors in these cells contributes to the observed enhanced mitogenic effects of bFGF. Abnormal responses of scleroderma fibroblasts to TGF-beta/bFGF stimulation, particularly failure to synthesize low-affinity receptors in response to TGF-beta, adds a new characteristic to the fibrotic phenotype of scleroderma fibroblasts.

Adult↗
PubMed1979

Endothelial injury in scleroderma.

Functional and structural vascular lesions have been observed in the organs involved in scleroderma. The etiology of these vascular changes is poorly understood. The ability to isolate, characterize, and maintain endothelial cells in vitro provides a target cell population to study endothelial damage in scleroderma. The present report describes the effect of scleroderma serum on endothelial, smooth muscle, and fibroblast cell types. Sera from patients with scleroderma (31/52) and Raynaud's syndrome (11/19) contain cytotoxic activity, specific for endothelial cells, which is nondialyzable, heat-stable, and elutes with albumin on gel-filtration chromatography.

Adult↗
PubMed1979

Collagen synthesis in the developing chick heart.

We have surveyed the amount and types of collagen synthesized in two regions of the chick heart during embryonic development. Cardiac tissues from successive periods of development were labeled with 3H-proline in short-term organ culture. The fraction of incorporated label present as collagen was estimated by comparison of TCA-soluble radioactivity before and after digestion with purified bacterial collagenase. This measure of collagen synthesis varied only slightly with the length of the labeling period and agreed with values obtained by labeling in ovo. In the developing outflow tract, the fraction of label present as collagen increased sharply during the period of truncal septation (5-9 days), rising from initial values of 6% at 3 days of incubation to a plateau of about 25% (10-19 days). In ventricular myocardium, this fraction rose gradually from 3 to 20% between 3 and 19 days of incubation. The types of collagen synthesized in developing heart were analyzed by limited pepsin digestion and acrylamide gel electrophoresis, using collagens synthesized in tendon, cartilage, skin, and lens capsule for comparison. The types of collagen synthesized in both cardiac regions changed in similar manner during development. During the first week of cardiac function, a substantial but progressively smaller fraction of total collagen synthesized was identified as Type IV. Synthesis of Type I collagen increased sharply during this period and predominated during the second half of development. Type III collagen was synthesized in trace amounts by the middle of development and constituted approximately one-sixth of total collagen synthesis just before hatching. Minor amounts of collagen identified as Type B collagen were synthesized throughout the latter two-thirds of development.

Animals↗
PubMed1978

The management of renal scleroderma: experience with dialysis, nephrectomy and transplantation.

In 25 of 100 patients with scleroderma seen over a five year period irreversible renal failure developed; renal support was instituted in 17. Ten of 17 received peritoneal or hemodialysis, one survived. The remaining seven received hemodialysis plus nephrectomy; three survived. Two of these three underwent renal transplantation; one survived. This experience is presented to encourage improvement of these and other technics to increase the survival rate in the otherwise uniformly fatal renal failure associated with scleroderma (systemic sclerosis).

Adult↗
PubMed1976

Capillary abnormalities in polyvinyl chloride production workers. Examination by in vivo microscopy.

Examination by wide-field capillary microscopy of the hands of 152 workers in vinyl chloride (VC) polymerization plants demonstrated scattered, scleroderma-like microvascular abnormalities in 21 workers and isolated capillary abnormalities in 27, as compared with only three isolated abnormalities in 50 manual workers not exposed to vinyl chloride. Thirteen of 17 VC workers with objective evidence of VC-associated abnormalities (angiosarcoma or fibrosis of liver, acroosteolysis, or scleroderma-like skin lesions) were observed to have microvascular abnormalities. If prospective studies confirm the implications of this study, capillary microscopy may become a useful mass-screening procedure in the early detection and prevention of VC-associated disease.

Adult↗
PubMed1976

Skin capillary abnormalities as indicators of organ involvement in scleroderma (systemic sclerosis), Raynaud's syndrome and dermatomyositis.

Forty-four study patients with scleroderma (systemic sclerosis) (28 patients), Raynaud's syndrome (13 patients) or dermatomyositis (three patients) were observed for skin capillary abnormalities by widefield microscopy and compared with three control groups of 20 subjects each: (1) patients with other rheumatic disease, (2) hospitalized patients with nonrheumatic conditions, and (3) healthy volunteers. The distinctive microvascular pattern (dilated and distorted capillary loops alternating with avascular areas) previously reported in scleroderma and dermatomyositis was observed almost exclusively in the study patients. The severity of capillary abnormalities varied among the diagnostic subgroups, and a positive correlation was found between the degree and extent of abnormal microvascular patterns and multisystem involvement. On this basis, widefield nailfold capillary observations are proposed as a simple, inexpensive, reproducible technic for making an improved early diagnosis and predicting multisystem involvement in scleroderma, Raynaud's syndrome and dermatomyositis, presently a group of loosely associated and overlapping connective tissue disorders which often defy early and precise diagnosis.

Adult↗
PubMed1976

Standstill of nailfold capillary blood flow during cooling in scleroderma and Raynaud's syndrome.

Capillary blood flow in nailfold capillaries, observed continuously by capillary microscopy during standardized cold exposure (16 degrees C) has been compared in 15 patients with scleroderma (SD), 6 patients with Raynaud's syndrome (RS) without known organic pathology, and 9 normal controls. Capillary microscopy affords direct observation of capillary blood flow and allows one to determine if standstill of capillary circulation occurs (as defined by the movement of the red blood cell column), a state impossible to differentiate from near zero flow by conventional methods. Complete standstill of capillary blood flow occurred in 10 of 15 patients with SD and in 1 of 6 patients with RS. Intermittent standstill was observed in 5 of 15 SD and in 4 of 6 RS patients. In all normal subjects and in 1 of 6 patients with RS the capillary blood flow continued throughout the cooling period. Thus all 15 patients with SD and 5 of 6 patients with RS could be distinguished from control subjects by the development of capillary standstill on cooling. It is concluded that capillary microscopy can separate SD and RS patients from control subjects during cold exposure and may be useful in early diagnosis and prognosis of rheumatic syndromes and in the evaluation of therapy designed to improve the nutritional capillary blood flow of the skin. Whereas the complete standstill of capillary blood flow appears to be definitely associated with pathology, the intermittent standstill pattern as defined in this study may be an exaggerated form of flow fluctuation also seen in normal subjects. A larger number of subjects will have to be studied to determine whether patients with RS of the vasopastic type without connective tissue disease can be distinguished from normal subjects with low finger blood flow rates in cold conditions.

Cold Temperature↗
PubMed1975

Association of fibrinogen and microfibrils with trophoblast basement membrane.

Two non-collagenous placental antigens have been detected both in membranes isolated from terminal villi by sieving and sonication and in acetic acid extracts of the villi. One of the antigens is apparently fibrinogen based on immunologic and chemical data. The second, detectable with anti-membrane antiserum after absorption with fibrinogen remained with the fibrinogen-like antigen during isoelectric precipitation at pH 4.7, electrophoresis at pH 8.6 and chromatography on DEAE cellulose. Fractions of villi in which the two antigens occur comprise more than a third of the weight of the villi. The fibrinogen-related antigen was concentrated in placental basement membranes compared to kidney and lung basement membranes. A third antigen common to the membranes, to glomerular basement membrane and to alveolar basement membrane was also detected.

Amino Acids↗