PubMed HealthSearch

Biomedical subjects

F Fernandez-Madrid

Publications and source records attributed to F Fernandez-Madrid.

7 recordsLinked to original sources

Proteoglycans from osteoarthritic human articular cartilage influence type II collagen in vitro fibrillogenesis.

Collagen fibrils were formed in the presence of dermatan sulfate (DSPG) and high density (HDPG) proteoglycans isolated from human adult knee femoral articular cartilage. Eroded cartilage had a higher percentage of DSPGs in the extracted proteoglycans than normal cartilage (p = .018). The dermatan sulfate proteoglycans (DS-PGI and DS-PGII) were detected in normal and osteoarthritic cartilage. DSPGs compared to HDPG inhibited in vitro collagen fibrillogenesis producing a longer lag phase (p less than .05) and a slower rate of fibril formation (p less than .05). DSPGs from eroded osteoarthritic cartilage alone or in combination with HDPG produced a longer lag phase than DSPGs from normal cartilage alone or in combination with HDPG (p less than .05). The inhibition of fibrillogenesis by DSPGs suggests that collagen fibril formation in vivo may be abnormal due to the influence of molecular changes in proteoglycan as well as an increased proportion of DSPGs occurring in osteoarthritic cartilage. Abnormal fibril formation may produce a weakened cartilage matrix, thus contributing to an accelerated process of cartilage degeneration in osteoarthritis.

Cartilage, Articular

The immunoregulation of rheumatoid factor by the CD8 T lymphocyte subset in rheumatoid arthritis.

Flow cytometric analysis on 81 peripheral blood samples from patients with rheumatoid arthritis (RA) showed that levels of serum IgM rheumatoid factor (RF) were associated with the CD8+ cell level. A significant elevation of natural killer (CD56) cell levels was also observed in RA peripheral blood. Using in vitro antibody production techniques, CD8+ cells from patients with RA appeared to act as suppressors of RF production. Paired blood and synovial fluid samples from 9 patients with RA indicated a significant increase in SF CD8+ cells and DR+ T cells over the corresponding peripheral blood levels. The data suggest that CD8+ cells in RA may respond to immunological abnormalities occurring during the course of the disease.

Antigens, CD

Pristane induced arthritis in mice. IV. Immunotherapy with monoclonal antibodies directed against lymphocyte subsets.

Pristane induced arthritis (PIA), a seropositive experimental disease model in mice, was used to investigate the influence of immunotherapy with monoclonal antibodies against lymphocyte subsets. Treatment with L3T4, a monoclonal antibody specific for murine CD4+ T cells, significantly reduced the incidence of pristane arthritis, and delayed the disease onset. Monoclonal antibody to Lyt2, the murine CD8+ T cell marker, significantly reduced the levels of rheumatoid factor in pristane injected animals compared with controls, but did not influence the clinical course of PIA. Our experiments demonstrate the ability of anti-CD4 antibodies to modify the course of PIA, and provide support for the hypothesis that CD4+ T lymphocytes have an important role in the pathogenesis of this experimental autoimmune arthritis.

Animals

Deoxythymidine kinase activity of human implanted sponge connective tissue in zinc deficiency.

The activity of deoxythymidine kinase was assayed in implanted sponge connective tissue in three groups of subjects: 1) five normal controls (having normal levels of plasma and red cell zinc); 2) four patients with sickle cell anemia who had low zinc in red cells and hair; and 3) two volunteers (under strict dietary controls), after 6 mo of zinc restriction (2.7 mg/day) and repeated after 3 mo of zinc repletion (30 mg/day). Total protein, total collagen, RNA/DNA, and deoxythymidine kinase activity were measured by techniques reported previously. In sickle cell anemia patients, deoxythymidine kinase activity was not detected, and RNA/DNA, total collagen, and total protein contents were decreased compared to normal controls (statistically significant). In human volunteers deoxythymidine kinase activity was not detected during the zinc restriction phase. After supplementation with zinc, deoxythymidine kinase activity became 70% of normal control levels, and RNA/DNA, total collagen, and total protein contents of sponge connective tissue increased. In conclusion, an adverse effect of zinc deficiency on deoxythymidine kinase activity of implanted sponge connective tissue of man has been demonstrated for the first time.

Anemia, Sickle Cell

Antinuclear antibodies (ANA): immunologic and clinical significance.

The methods currently used for the detection of ANA have been analyzed, with emphasis on their practical application to the diagnosis of the CTD. The use of the indirect IF-ANA test was recommended as a screening procedure to detect ANA. The need to standardize the technique using a single substrate and fluorescent conjugates with uniform F/P ratios was stressed. Most importantly, the value of titrating ANA for the diagnosis of the CTD was discussed. ANA titers higher than 1/500 are usually very significant clinically, often found in spontaneous or drug-induced SLE and few other CTD. The immunologic aspects of ANA and their potential value as aids in the diagnosis and management of the CTD were discussed. Anti-nDNA antibodies have been found to have a high degree of specificity for SLE and high titers of these antibodies correlate well with low levels of serum complement and severity of kidney involvement. The spectrum of ANA in the sera from patients with SLE has been expanded with the finding of anti-Sm antibodies which, when detected by gel precipitation with prototype serum, have been found so far only in SLE. Some of these antibodies have been found to have prognostic significance. Patients with MCTD and a group of patients with SLE have high titers of serum ANA with specificity for an RNase-sensitive component of ENA. The group of SLE patients defined by the presence of these antibodies (anti-Mo) have a better prognosis and in general develop only mild nephritis or have no kidney involvement at all. High titers of pure antinucleolar antibodies probably are found almost exclusively in the sera of patients with scleroderma. Some ANA have organ specificity, and GS-ANA have been found in all patients with Felty's syndrome and in a large proportion of patients with RA. One of the great advances in the field has been the recognition that ANA can be induced in the human and in experimental animals by the use of a number of therapeutic agents. Some of these agents can also induce a clinical picture resembling spontaneous SLE, though kidney involvement does not occur or is extremely mild. It is interesting that the whole spectrum of ANA can be found in drug-induced LE except anti-nDNA antibodies which have been associated to the pathogenesis of immune complex nephritis in spontaneous SLE. There is no doubt that research on ANA has contributed a great deal to the understanding of the CTD and will continue to be a valuable tool for the clinician and the investigator.

Animals