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Biomedical subjects

E C Leroy

Publications and source records attributed to E C Leroy.

36 records · Page 2Linked to original sources
PubMed1983

Endothelial injury in scleroderma. A protease mechanism.

The mechanism of action of the previously reported serum ECA in patients with scleroderma has been studied. Gel filtration (Sephadex G-200) followed by ion exchange chromatography (DEAE-Sephadex A-50, Tris buffer, pH 8, 1.5M NaCl) yielded a 13-fold enriched fraction. ECA biological activity was abolished by preincubating the active fraction with several protease inhibitors (STI, aprotinin, TLCK, and PMSF); exposure of target cells to protease inhibitors did not inhibit ECA. ECA-rich fractions have esterolytic activity (3H-TAME), which was irreversibly inhibited by TLCK and PMSF in a time-, temperature-, concentration-, and pH-dependent fashion. In separate studies, functional protease inhibitor activity in scleroderma sera was determined by the capacity of serum to inhibit BAPNA hydrolysis by trypsin (TIC). TIC was 1.32 +/- 0.15 (milligrams of trypsin inhibited by 1 ml of serum +/- S.D.) in 20 control sera, and 0.54 +/- 0.18 (p less than 0.001) in 38 scleroderma sera. A positive correlation was found between TIC and percent inhibition of endothelial cell 3HTdR uptake induced by the same serum (r = 0.94, p less than 0.001). These studies suggest that ECA is mediated in vitro via a protease mechanism associated with a functional deficiency of protease inhibitors in scleroderma sera.

Cells, Cultured↗
PubMed1982

Fibroblast selection in scleroderma. An alternative model of fibrosis.

Human preputial skin fibroblasts were cloned in vitro, and studies in 21 clones were shown to exhibit a 3-fold difference in collagen synthesis; this heterogeneity of phenotypic expression was conserved over multiple population doublings. When the clones were exposed to sera from 10 scleroderma patients, selective growth of high-collagen-producing fibroblasts was observed. Prostaglandin E2 abrogated the selective effect of scleroderma serum on high-collagen-producing fibroblast clones. Besides enhanced collagen synthesis, these clones of normal fibroblasts shared an insensitivity to feeding schedule with fibroblasts from scleroderma skin. These data raise the possibility that scleroderma represents a process of selection of fibroblasts programmed to produce increased amounts of collagen.

Clone Cells↗
PubMed1982

Variable response to oral angiotensin-converting-enzyme blockade in hypertensive scleroderma patients.

Twelve scleroderma patients with hypertension, seven of whom had malignant hypertension and renal failure of scleroderma renal crisis, were treated with captopril. The first dose lowered mean pressure in all patients by 21.3 mmHg; in 6 patients it relieved encephalopathy. Blood pressure was controlled in all patients. Two of 7 patients with scleroderma renal crisis had improvement in renal function; the 5 patients who did not have malignant hypertension improved or stabilized. Despite good pressure control, however, renal failure developed in 5 patients with scleroderma renal crisis. The data indicated that captopril is effective antihypertensive therapy in scleroderma and, when given early, may prevent renal failure and death.

Administration, Oral↗
PubMed1982

A prospective study of Raynaud phenomenon and early connective tissue disease. A five-year report.

To define features of patients with Raynaud phenomenon that predict the evolution of connective tissue disorders, a prospective study was initiated. Patients with history or physical evidence of Raynaud phenomenon without causal or associated disorders underwent initial multisystem evaluation. Scleroderma (systemic sclerosis) of less than five years' duration was included for comparison. Patients were classified as having Raynaud phenomenon "only," undifferentiated connective tissue syndrome or scleroderma. Nailfold capillary microscopy was performed, and patterns were scored blindly from coded photographs. Of 91 patients with Raynaud phenomenon entered (Raynaud phenomenon only, n = 49; undifferentiated connective tissue syndrome, n = 22; scleroderma, n = 20), abnormal "scleroderma pattern" capillaries were noted in seven of 49, 19 of 22 and 19 of 20, respectively (p less than 0.005). Of 39 patients with Raynaud phenomenon only followed (mean duration, 23.7 months) undifferentiated connective tissue syndrome developed in three. Of 17 patients with undifferentiated connective tissue syndrome followed (mean duration, 27.6 months), six patients had transitions (four scleroderma; one scleroderma-systemic lupus erythematosus overlap; one SLE). Nailfold capillary abnormalities best identified transitional patients in both groups (eight of nine) and were more sensitive than ANA (six of nine), presence of digital ulcers (four of nine) or decreased esophageal motility (two of nine). This prospective study documents a useful role for capillary examinations in evaluating Raynaud phenomenon. Abnormal capillaries indicate an increased risk for connective tissue disease; normal capillaries favor idiopathic Raynaud phenomenon.

Capillaries↗
PubMed1982

Precursor-size components are the basic collagenous subunits of murine tumor basement membrane.

The acid-insoluble fraction of murine tumor basement membrane produced by the EHS sarcoma was extracted following reduction of disulfide bonds under non-denaturing conditions. Extracts prepared from tumors grown in either lathyritic or normal animals contain two procollagen-like chains as well as cross-linked oligomers of these chains. Extracted monomeric chains behave almost exactly like reduced, radiolabeled EHS collagen precursor chains on SDS-PAGE and SDS-agarose suggesting that they are very similar collagens. Since the collagen extracted after reduction represented a significant proportion of the total tumor collagen, it is likely that tumor basement membrane is assembled from precursor-size Type IV collagen molecules.

Amino Acids↗
PubMed1982

Elevated levels of circulating platelet aggregates and beta-thromboglobulin in scleroderma.

Levels of circulating platelet aggregates and plasma beta-thromboglobulin reflect the degree of platelet activation in vascular injury and repair. Both values were evaluated in 38 patients with scleroderma and 18 control subjects matched for age, sex, and race. Circulating platelet aggregates (expressed as percentage of total platelet count) were 7.2 +/- 5.5% (mean +/- SD) in the control group and 31.2 +/- 13% in the scleroderma group (p less than 0.0005). Beta-thromboglobulin levels in the control groups were 20 +/- 10 ng/mL and 72.7 +/- 50 ng/mL in the group with scleroderma (p less than 0.0005). A positive correlation was found between the two values (r = 0.6, p less than 0.0005). Significant reductions in circulating platelet aggregates and beta-thromboglobulin levels were achieved in 10 patients by dipyridamole and aspirin therapy. These results show in-vivo activation of platelets in scleroderma with release of platelet granule constituents. Antiplatelet therapy in adequate doses returned both values to normal; however, its long-term effect on scleroderma is not yet known.

Aspirin↗
PubMed1981

Chromosome breakage and sister chromatid exchange frequencies in scleroderma.

Peripheral lymphocytes from 3 scleroderma patients with systemic disease and from 3 normal controls were examined for frequencies of chromosomal aberration and sister chromatid exchange (SCE). Significant increases in the levels of chromosomal anomaly and SCE were found for all 3 patients. These results are discussed in terms of the diagnostic potential of SCE in scleroderma and the possible etiologic role of cytogenetic instability in this disease.

Adult↗
PubMed1979

DNA binding activity of serum from patients with systemic lupus erythematosus.

The reaction conditions essential for reproducible use of the cellulose ester membrane filter assay for anti-DNA antibody levels in patients with systemic lupus erythematosus are described. A dependence of DNA-binding capacity on serum concentration was observed in the assay, requiring that serum concentrations be comparable in determinations of DNA-binding activity of different sera and when comparing different published studies. The DNA-binding capacity of serum from lupus patients was found to be significantly different from that of healthy controls. However, the binding capacities were not significantly different between lupus patients with and without nephritis. The relative avidity of the anti-DNA antibodies were estimated from plots of 1/DNA bound vs 1/DNA free and these data indicate that the avidities of the antibodies from the two groups of lupus patients are not significantly different. This observation suggests that the tightness of binding between the DNA and the serum anti-DNA antibodies cannot be used to predict immune complex-induced nephritis in lupus patients.

Antibodies↗
PubMed1978

In vivo observations of skin capillaries in workers exposed to vinyl chloride. An English-American comparison.

An unselected sample of vinyl chloride (VC)-exposed individuals, all employees of a polyvinyl chloride production plant in England (129 subjects), were examined by in vivo capillary microscopy. Results were compared with those previously obtained from a similar study in the USA to determine whether an association between VC exposure and capillary abnormalities could be found in different environments. The results showed a similar distribution of capillary abnormalities among the VC workers in both countries (39.5% in England compared with 36% in the USA). These capillary abnormalities were significantly more frequent among VC-exposed subjects than among control industrial workers (7.7%, 6%). In vivo microscopy also showed a higher incidence of papular lesions (13.5%) than had been detected clinically (1%).

Adolescent↗
PubMed1975

Blood viscosity, plasma proteins, and Raynaud syndrome.

The rheology of the blood was studied in 20 patients with Raynaud syndrome. Sixteen patients had scleroderma, two had nonspecific angiitis, one had systemic lupus erythematosus, and one had Raynaud disease. Viscosity measurements were performed on whole blood, plasma, and suspensions of 45% red blood cells (RBCs). In autologous plasma, over a wide range of shear rates. The relative viscosity, an index of RBC aggregation, was obtained by dividing the RBC viscosity in autologous plasma (at a hematocrit value of 45%) by the plasma viscosity. Concentrations of the plasma globulins and fibrinogen were also measured. The mean plasma viscosity was significantly (P less than .01) elevated over established normal controls. The mean RBC viscosity and the relative viscosity were significantly (P less than .01) elevated over normal controls, as were fibrinogen and the globulins. These studies demonstrate increased blood viscosity and red blood cell aggregation, which may constitute an important hindrance to flow.

Adolescent↗
PubMed1972

Connective tissue synthesis by scleroderma skin fibroblasts in cell culture.

Skin fibroblasts from subjects with scleroderma and control subjects were grown in tissue culture to compare the characteristics of connective tissue metabolism. A striking increase in soluble collagen (media hydroxyproline) was observed in eight of nine scleroderma cultures when they were compared with identically handled control cultures matched for the age and sex of the donor and the anatomic site of the donor skin. Glycoprotein content as estimated by hexosamine and sialic acid was also significantly increased in the scleroderma cultures. Estimations of protein-polysaccharide content by uronic acid determinations were low in all cultures and not significantly increased in scleroderma cultures. This report demonstrates the feasibility of using fibroblast cell cultures to study chronic rheumatic and connective tissue disorders. The initial results suggest a net increase in collagen and glycoprotein synthesis in scleroderma fibroblast cultures. The implications of an abnormality of connective tissue metabolism by skin fibroblasts propagated in vitro in the acquired disorder scleroderma are discussed.

Cell Count↗