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Biomedical subjects

G K Sherer

Publications and source records attributed to G K Sherer.

9 recordsLinked to original sources
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

Surface binding, internalization and degradation by cultured human fibroblasts of low density lipoproteins isolated from type 1 (insulin-dependent) diabetic patients: changes with metabolic control.

A previous study of low density lipoprotein metabolism by cultured cells focused on the metabolism of normal lipoproteins in vitro by fibroblasts isolated from diabetic patients. No abnormalities were found. We have followed the opposite approach. Using normal human fibroblasts as test cells we compared the metabolism in vitro of low density lipoproteins isolated from diabetic patients before and after metabolic control. We found a significant decrease (p less than 0.02) in internalization and degradation of low density lipoproteins isolated from diabetic patients before metabolic control when compared with those isolated from normal control subjects or from the same patients after metabolic control. The observed changes were mainly apparent in intracellular degradation. To evaluate whether the observed differences in low density lipoprotein behaviour were correlated with lipid or apolipoprotein composition, we measured cholesterol, triglyceride, apolipoprotein B and total protein levels in the low density lipoproteins tested. A significant decrease (p less than 0.05) of the triglyceride/protein ratio was found in post-control low density lipoproteins suggesting that a high triglyceride content may interfere with low density lipoprotein metabolism. The present study represents the first observation that metabolic control in diabetes mellitus can alter low density lipoprotein-cell interaction and suggests a possible mechanism for the enhanced incidence of atherosclerosis in diabetic patients.

Adolescent↗
PubMed1982

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

To explore the mechanism of increased collagen synthesis by scleroderma skin fibroblasts in vitro, control and scleroderma fibroblasts were compared in confluent monolayer cultures growth-arrested by serum deprivation; responses to optimal mitogenic doses of platelet-derived growth factor, fibroblast growth factor, epidermal growth factor and nerve growth factor were compared. Platelet-derived growth factor had a selective mitogenic effect on control skin fibroblasts not observed with scleroderma skin fibroblasts. None of the factors studied had a selective effect on collagen synthesis independent of cell replication; scleroderma and control fibroblasts responded similarly. Therefore, the growth factors studied may not be involved in generating the activated scleroderma fibroblast directly; platelet-derived growth factor may play an indirect role in fibroblast replication in human fibrotic disorders.U

Cell Division↗
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↗
PubMed1980

Cultivation of microvascular endothelial cells from human preputial skin.

A procedure is described for the isolation and cultivation of microvascular endothelium from human skin. Neonatal foreskins are pooled, washed, minced, and dissociated by a mixture of collagenase and dispase. Microvascular endothelium, liberated in the form of intact capillary fragments, is incompletely separated from fibroblasts and epidermal cells by sieving through nylon mesh, followed by velocity sedimentation on 5% bovine serum albumin. The endothelium-enriched fraction has been maintained in primary culture for up to 3 weeks. The resulting epithelioid colonies have been characterized morphologically by both light and transmission electron microscopy and manifest all of the structural features that distinguish other, large-vessel endothelia in culture. In addition, immunohistochemical studies using an indirect fluorescent antibody technique demonstrate that these cells contain the endothelium-specific product, Factor VIII antigen.

Blood↗
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↗