The content of type I and III collagen in normal human skin from subjects of different ages was studied by means of a new high performance liquid chromatography method and by SDS-polyacrylamide gel electrophoresis and scanning electron microscopy. The ratio of types I and III collagen in covered skin remained constant throughout childhood and young adult life and the proportion of type III was shown to be the same as previously reported. However, in the elderly, the proportion of type III collagen in the dermis increased to a variable degree. Scanning electron microscopic examination showed a decrease in the number of collagen fibre bundles with age. Average bundle width varied significantly with age. These results may reflect an impaired synthesis of type I collagen in aged skin.

Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis.Rheumatoid arthritis is a chronic inflammatory disease of synovial joints leading to destruction of cartilage and erosion of bone (1). Currently, the mechanisms underlying the perpetuation of the chronic inflammation and the consequent tissue damage are poorly understood. It is widely considered that the immune system is a major participant in these processes, perhaps through the activation of complement by immune complexes containing rheumatoid factor (2) or by activated immunocompetent cells (3) releasing protein mediators such as interleukin 1 (IL-1), tumor necrosis factor, and interferon-y.Study of cell-surface markers and cellular organization has shown that there is a predominance of T lymphocytes in the synovial infiltrate (4) Here we report the cloning of the activated T cells from a patient with active erosive rheumatoid arthritis. In two operative samples, 21 months apart, collagen type II-specific clones were detected at a frequency of -'12%. In a third sample, the uncloned joint T cells also responded to collagen type II. This persistent response suggests a possible role of these T cells in maintaining the chronic inflammatory state in rheumatoid arthritis, since in these joints there is abundant HLA class II and collagen type II available to restimulate the T cells. MATERIALS AND METHODS Patient. C.L., a Caucasian female (HLA DR-1,-6), developed polyarthritis diagnosed as rheumatoid arthritis in 1975.Laboratory investigations have shown a consistent lack of IgM rheumatoid factor. There was a low titer of anti-nuclear antibody with activity against DNA-histone and singlestranded DNA. She was treated with gold salts. After 4 years, she relapsed with severe symptoms. A right knee synovectomy was performed, which was the source of the first cloning procedure; 21 months later, because of severe pain, cartilage damage, and loss of mobility, a knee prosthesis was inserted, providing the s...

The difference between the concave and convex side of the scoliotic curve indicates that mechanical loads might influence the expression of these enzymes. The increased expression of these enzymes in both degenerative disc disease and scoliosis strongly suggests that they may affect the progressive nature of these diseases.

Ains-The age-related changes in the biochemical composition of the collagenous matrix of the human lamina cribrosa were investigated. Methods-An age range (3 weeks to 92 years old) of human laminae cribrosae, dissected free of any surrounding structures which contained collagen, were analysed for collagen solubility (n= 58) total collagen content (n=46), proportion of collagen types (n=38), and collagen cross linking (n=30), using hydroxyproline analysis, scanning densitometry of peptides after cyanogen bromide digestion, and high performance liquid chromatography, respectively. Results-Age-related changes included an increase in total collagen and a decrease in the proportion of type III collagen within the lamina cribrosa. The collagen cross link pyridinoline was present at low levels, but demonstrated no trend with age. An age-related increase was found in pentosidine, an advanced glycation product. Conclusion-These changes in collagen composition imply that the mechanical properties of the lamina cribrosa are altered, resulting in a stiffer, less resilient structure with age. Such alterations in structure may contribute to the increased susceptibility of the elderly to axonal damage in chronic open angle glaucoma. (Br_7 Ophthalmol 1995; 79: 368-375)