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Biomedical subjects

E C Leroy

Publications and source records attributed to E C Leroy.

At least 19 recordsLinked to original sources
PubMed1999

A disease severity scale for systemic sclerosis: development and testing.

OBJECTIVE: To develop and test a severity scale for individual organ involvements in systemic sclerosis (SSc, scleroderma). METHODS: An international study group completed the following tasks: (1) developed a glossary of terms including all pertinent variables for 9 potentially affected organ systems; (2) collected prospective data to determine the feasibility and practicality of each proposed variable; (3) revised the initial list of variables; (4) determined the association of each variable with mortality (a proxy for morbidity) using 579 patients in an existing comprehensive longitudinal scleroderma databank; (5) developed a severity grading scale for each organ system by discussion and consensus; and (6) externally validated the scale using an independent group of 680 patients from the same databank. RESULTS: Nine organ-specific severity scales were developed from 0 (no documented involvement) to 4 (endstage disease). The data required for scale completion are relatively easy and practical for all physicians to obtain. CONCLUSION: This preliminary severity scale will be useful for assessing disease severity status in individual patients both at one point in time and longitudinally. The severity scale will assist in the design and conduct of clinical trials and the comparison of study populations with one another. The scale will serve as a framework for developing a scleroderma disease activity index.

Humans↗
PubMed1998

Thrombospondin 1 is expressed by mesenchymal cells in mouse post-natal skin and hair follicle development.

Thrombospondin 1 is an extracellular matrix glycoprotein with multiple functions. In the skin, it has been immunolocalized to basement membrane, and its expression increases during embryogenesis and wound healing. Its normal cellular source in the skin is not known, except during wound healing, where macrophages and keratinocytes seem to be the primary source. We have analysed the expression of thrombospondin 1 mRNA in normal mouse skin at different ages by in situ hybridization. It was found that the mRNA is expressed by dermal mesenchymal cells and mature fibroblasts and developmentally regulated during post-natal skin growth and morphogenesis. In adult mouse skin, expression of the thrombospondin is restricted to the mesenchymal cells of hair follicle papilla. These results suggest that the regulation of thrombospondin 1 transcription in mesenchymal cells can play an important role in post-natal skin development. Its mRNA expression is a characteristic of adult dermal papilla cells with a potential role in hair development.

Aging↗
PubMed1997

Quinolinic acid accumulation in injured spinal cord: time course, distribution, and species differences between rat and guinea pig.

Experimental compression injury of the spinal cord in guinea pigs results in delayed neurologic deficits that continue to increase in severity for several days following trauma, coincident with inflammatory responses, including invasion of the lesion by mononuclear phagocytes and increased levels of the neurotoxin quinolinic acid (QUIN). Inflammatory responses and QUIN elevation also occur following spinal cord contusion in rats, but maximal neurologic deficits develop immediately. In this study, somatosensory evoked potentials (SEP) and tissue, serum, and cerebrospinal fluid levels of QUIN were measured in guinea pigs and rats following similar compression injuries of the thoracic spinal cord. SEP changes differed between the species, consistent with other neurological changes. In guinea pigs, increases in QUIN levels at the lesion site began at 1 day postinjury, achieved maximal elevation (100-fold) by 12 days, then declined, but remained above serum levels at 25 days postinjury. A similar increase occurred in adjacent areas of the spinal cord, with lower peak levels. In rats, tissue QUIN at the center of the lesion remained below serum levels at all times, increasing moderately (<10-fold) up to 7 days, then decreasing between 7 and 25 days. These data demonstrate differences in the time course and magnitude of QUIN accumulation and neurological deficit between guinea pig and rat, which may relate to differences in secondary pathological mechanisms. Such profound differences may affect the use of these species for evaluation of experimental therapy in this and other inflammatory conditions of the central nervous system.

Animals↗
PubMed1996

Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis.

OBJECTIVE: To determine the frequency, clinical associations, and any major histocompatibility complex correlations of antifibrillarin antibodies in patients with systemic sclerosis (SSc). METHODS: Antifibrillarin antibodies were determined by indirect immunofluorescence, immunoblotting, and immunoprecipitation, and HLA class II alleles by DNA oligotyping, in a large cohort of SSc patients. RESULTS: Antifibrillarin was found in 8% of 335 SSc sera and was significantly more common in blacks (16%) than whites (5%), in males (33%) than females (14%), and in patients with cardiac, renal, or gut involvement. The HLA class II haplotype DRB1*1302, DQB1*0604 was found significantly more frequently in SSc patients with antifibrillarin compared with race-matched normal controls and 260 SSc patients without antifibrillarin. In addition, 1 or more of the HLA-DQB1 alleles *0604, *0301, *0602, and/or *0302 was found in all antifibrillarin-positive patients, and 62% of the antifibrillarin-positive patients had 2 of these HLA-DQB1 alleles, a highly significant difference from both race-matched normal controls and antifibrillarin-negative SSc patients. CONCLUSION: Antifibrillarin, although an infrequent nucleolar autoantibody, is a marker for severe SSc, especially in blacks and males, and is strongly associated with a unique HLA haplotype, as well as with combinations of certain HLA-DQB1 alleles.

Alleles↗
PubMed1996

Sexual function and erection capability among young men with spina bifida.

In a study of sexual function and erection capability, 15 young men with spina bifida were interviewed, underwent physical examination, and completed two consecutive night recordings of penile tumescence and rigidity with the Rigi-Scan (Dacomed Inc.). Eleven reported erections with stimulation. Rigi-Scan data showed that two subjects (both with lesions at the sacral level) had normal numbers and durations of erections, that seven others had abnormally brief and infrequent nocturnal erections, and that six had none. Ten subjects had at least 'some' glans sensation on physical examination. Self-reported erection capability was related to motor level and glans sensation. The number of nocturnal erections was related to sensory level. The study suggests that lower motor and sensory levels are associated with greater potential sexual function in males with spina bifida.

Adolescent↗
PubMed1995

Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma.

OBJECTIVE: Systemic sclerosis (scleroderma, SSc) frequently affects the lungs, and interstitial pulmonary fibrosis is one of its major complications. The pathophysiology of SSc lung disease s poorly understood, but recent studies document an inflammatory process resembling that of idiopathic pulmonary fibrosis with increased numbers of activated alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid). We determined levels of 2 potentially important mediators of fibroproliferative repair in BAL fluid from patients with SSc. METHODS: Using Western blot and ELISA techniques we measured levels of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta in BAL fluid from patients with SSc and healthy controls. The mitogenic effect of these cytokines on SSc lung myofibroblasts was determined by [3H]thymidine incorporation. RESULTS: SSc BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-beta 1 was significantly elevated in SSc lavage fluid, the amount of TGF-beta 2 was significantly less than that observed in normal lavage fluid. Myofibroblasts cultured from SSc lavage fluid exhibited enhanced [3H]thymidine incorporation upon exposure to the growth factors present in SSc BAL fluid: PDGF and TGF-beta 1. SSc lung myofibroblasts pretreated with TGF-beta 1 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF alpha receptor. CONCLUSION: Our studies support a role for PDGF and TGF-beta 1 in the pathogenesis of SSc lung disease.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Fasciitis (not scleroderma) following prolonged exposure to an organic solvent (trichloroethylene).

We describe 2 cases of diffuse fasciitis with eosinophilia (DFE) associated with prolonged exposure to the industrial solvent trichloroethylene (TCE). The medical and personal histories, examinations, and laboratory and pathological investigations were reviewed and summarized. The 2 case reports, representing the first and 2nd cases of DFE associated with TCE, were compared with 8 reported cases of systemic sclerosis associated with TCE and suggest a direct association between TCE exposure and the development of fasciitis (DFE).

Aged↗
PubMed1993

Differential responses of human papillary and reticular fibroblasts to growth factors.

Differences in the responses to growth factors of normal fibroblasts and scleroderma fibroblasts have been demonstrated previously. Because human dermal fibroblasts are heterogeneous populations, whether known differences between papillary and reticular dermal fibroblasts could account for the noted differences between normal and scleroderma fibroblasts was investigated. Papillary dermal fibroblasts were grown from a dermatome section of normal skin from an adult donor. Reticular dermal fibroblasts were cultured from punch biopsy specimens taken from the same location. In vitro, papillary dermal fibroblasts proliferated more rapidly, had a higher mitotic index and reached greater density at confluence, confirming previous observations. The reticular dermal fibroblasts were more dendritic. Reticular dermal fibroblasts had higher rates of tritiated thymidine uptake and larger increases in mitotic index in response to isoforms of platelet-derived growth factor (PDGF). The characteristic response of scleroderma fibroblasts, potentiation of the mitogenicity of PDGF AA by transforming growth factor-beta (TGF-beta), was not observed in either cell type. Therefore, the phenotypic characteristics of scleroderma fibroblasts cannot be explained by an unusual admixture of papillary and reticular fibroblasts.

Adult↗
PubMed1993

Lupus and its management.

The recognition and treatment of SLE requires an approach similar to other chronic diseases. A thorough initial evaluation with regular monitoring of outwardly silent manifestations (e.g. renal) minimizes potentially devastating complications. For disease which does not threaten the patient's life or carry the threat of end-organ failure, treatment analogous to non-lupus patients is usually appropriate, including minimization of steroids. The widening use of cytotoxic agents promises to continue to decrease the mortality from SLE. These agents must be used sparingly and in consultation with a rheumatologist to reduce the incidence of infection, malignancy and sterility.

Adolescent↗
PubMed1992

Growth and characterization of fibroblasts obtained from bronchoalveolar lavage of patients with scleroderma.

We describe the detection and the growth of fibroblasts with human smooth muscle cell differentiation features from bronchoalveolar lavage (BAL) fluid of 53% of patients with scleroderma, but not from healthy controls. The binding of alpha-actin, vimentin and desmin antibodies by scleroderma lung fibroblasts exceeded that of normal adult lung fibroblasts, indicating that scleroderma lung fibroblasts express some markers of human smooth muscle cell differentiation (myofibroblasts), which may account for differences in biological behavior. A mesenchymal cell phenotype was documented by mRNA analysis, showing high expression of collagen type I and fibronectin in these cells. Fibronectin is also released in significantly higher amounts by scleroderma alveolar macrophages than by macrophages from healthy donors.

Actins↗
PubMed1991

Fibronectin release by systemic sclerosis and normal dermal fibroblasts in response to TGF-beta.

To determine whether enhanced matrix synthesis by systemic sclerosis (SSc) fibroblasts in vitro is due to increased responsiveness to transforming growth factor-beta (TGF-beta), fibronectin release by SSc and normal fibroblasts (7 pairs) was measured at various concentrations of TGF-beta. In the absence of TGF-beta, SSc fibroblasts released 30 +/- 22% more fibronectin than normal fibroblasts. While both SSc and normal fibroblasts increased fibronectin release at all concentrations of TGF-beta tested, the percentage increases were not statistically greater for the SSc fibroblasts even though 4 of the SSc fibroblasts strains were selectively sensitive to low concentrations of TGF-beta. TGF-beta increased cell numbers of both SSc and normal strains equally. Our data confirm abnormal regulation of fibronectin gene expression in SSc fibroblasts and suggest increased sensitivity to TGF-beta by some SSc fibroblast strains.

Blotting, Western↗
PubMed1987

Ascorbate effects on type I procollagen synthesis by human adult skin fibroblasts: different migration positions of type I procollagen chains on SDS polyacrylamide gel after incubation with ascorbate.

The effects of ascorbate and steroids on type I procollagen synthesis by human skin fibroblasts were studied. Ascorbate treatment (50 micrograms/ml) for 24 hours stimulated a 2-3 fold increase in type I procollagen synthesis and an unexpected shift in the mobility of type I procollagen on SDS polyacrylamide gels. The kinetics of the increase in procollagen synthesis (4 hours) and the shift in electrophoretic mobility (1 hour) were dissimilar, suggesting different controlling mechanisms. This was confirmed by the addition of alpha-alpha'-dipyridyl to ascorbate-treated cultures which eliminated the ascorbate-induced shift in electrophoretic mobility without altering the amount of procollagen synthesis. In contrast, hydrocortisone (1.5 microM) reduced the ascorbate-induced stimulation of type I procollagen synthesis by 80% but did not affect the ascorbate-induced shift in electrophoretic mobility. These studies indicate that the ascorbate-induced increase in type I procollagen synthesis is due to increased levels of type I procollagen mRNA and is independent of the level of hydroxylation of the procollagen.

2,2'-Dipyridyl↗