@article{d5b60138777a432398c21f8341d45c8c,
title = "Stimulation of fibroblast biosynthetic activity by serum of patients with pretibial myxedema",
abstract = "Skin fibroblasts from the shoulder and lower extremities of normal individuals, as well as from patients with pretibial myxedema (PTM) were grown in culture. When cells reached the monolayer stage, they were labeled with 3H-glucosamine and tested for hyaluronic acid synthesis in the presence of either serum from PTM patients or normal human serum. All the fibroblasts from the pretibial area synthesized 2 to 3 times more hyaluronic acid when incubated with PTM sera than when incubated in normal human serum. Fibroblasts cultured from skin of the back or prepuce did not respond to PTM sera. This heat-stable, protease-sensitive, and dialyzable, fibroblast-stimulating factor is not a 7 Sγ-globulin. The enhanced sensitivity to PTM sera exhibited by fibroblasts from the lower extremities may explain why the lesions in this disease are restricted primarily to that area.",
author = "Cheung, {H. S.} and Nicoloff, {J. T.} and Kamiel, {M. B.} and L. Spolter and Nimni, {M. E.}",
note = "Funding Information: Reprint requests to: Marcel E. Nimni, Ph.D., Department of Medicine and Biochemistry, Rheumatic Disease Section, University of Southern California School of Medicine, Los Angeles, California 90033. This work was supported by grants (AM 16404, AM 10358, AM 11727, GCRCRR-43, and fellowship grant AM 02036-03) from the National Institutes of Health, Bethesda, Maryland 20014. Dr. Cheung is currently at the Medical College of Wisconsin, Rheumatology Section, Milwaukee Wisconsin 53226, and Dr. Spolter is at the Veterans Administration Hospital, Sepulveda, California 91343. Abbreviations: PTM: pretibial myxedema SDS: sodium dodecyl sulfate Only recently have we learned that not all collagen molecules within a given species are identical [1-5]. Most of the earlier work on collagen relied on skin, tendon, and bone as sources of readily available material for study. When investigators began to examine other tissues, such as cartilage, blood vessels, and basement membranes, it became apparent that different molecular species of collagen could be isolated from such tissues. The Table shows the molecular form and chain composition of a variety of collagens identified in different tissues. Fig 1, on the other hand, illustrates the differences in chain composition as well as degree of glycosylation of the hydroxy lysine residues in 2 distinct forms of collagen. The other major structural component of the extracellular matrix of connective tissues is the ground substance. This material results from the complex interactions, mostly of proteoglycans, protein links, and hyaluronate, involved in the formation of aggregates [6-9]. The basic macromolecular structure, the proteoglycan, consists of a core protein to which a large number of chondroitin sulfate and keratan sulfate chains are covalently attached (Fig 2) [10-14]. Each protein core carries approximately 100 chondroitin sulfate chains with an average molecular weight of about 2 x 10'1, and 30 to 60 keratan sulfate chains each of a molecular weight of about 4 to 8 X 103• The average molecular weight of the proteoglycan monomer is 2.3 x 106• Chondroitin sulfate chains are not evenly distributed along the peptide core but occur in clusters. Much of the proteoglycans have some protein, the hyaluronic-acid-binding region located at one end of the core. About 65% of the keratan sulfate chains occur in the keratan-sulfate-enriched region adjacent to the hyaluronic-acid-binding region. More than 90% of .the chondroitin sulfate chains are attached to the chondroitinsulfate-enriched region located further from the hyaluronicacid-binding region. In the proteoglycan molecules, from bovine nasal cartilage, there seems to be a wide polydispersity in molecular weight since these can range from a few hundred thousand to more than 4 million. This range of molecular weights apparently results from a variation in the number of chondroitin sulfate chains bound to each core protein (Fig 2). The polysaccharide chains are constrained by their attachment at one end to the core protein. For this reason, the intact macromolecules have hydrodynamic properties that are different from those of the isolated polysaccharide chains. That the highly anionic chains, which extend out from the core in a radial fashion, cause these macromolecules to occupy large molecular domains in turn contributes to the retention of large amounts of fluid, an important function of the dermis. These physicochemical properties of proteoglycans provide such other tissues as cartilage with their essential properties of resilience and stiffness [6]. Most of our knowledge about the structure and function of proteoglycans comes from studies of cartilagenous structures. Information available on the proteoglycans in skin suggests that they are, in general, homologous. In cartilage the primary sulfated polysaccharide components are chondroitin and keratan sulfates; in skin the major component is dermatan sulfate. The repeating disaccharide unit of dermatan sulfate is L-iduronosyl-N-acetyl galactosamine 4-sulfate (Fig 3) [15]. We do not know whether the unique presence of this hybrid glycosa-",
year = "1978",
doi = "10.1111/1523-1747.ep12543646",
language = "English (US)",
volume = "71",
pages = "12--17",
journal = "Scientific Computing and Instrumentation",
issn = "1078-8956",
publisher = "Springer Wien",
number = "1",
}