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Biomedical subjects

A R Cabral

Publications and source records attributed to A R Cabral.

46 records · Page 3Linked to original sources
PubMed1987

Connective tissue activation. XXXII. Structural and biologic characteristics of mesenchymal cell-derived connective tissue activating peptide-V.

Connective tissue activating peptide-V (CTAP-V) is a single-chain, mesenchymal cell-derived anionic protein with large and small molecular forms (Mr of 28,000 and 16,000, respectively), as defined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins have similar specific activities with respect to stimulation of hyaluronic acid and DNA formation in human synovial fibroblast cultures. S-carboxymethylation or removal of sialic acid residues did not modify CTAP-V biologic activity. Rabbit antibodies raised separately against each of the purified CTAP-V proteins reacted, on immunodiffusion and on Western blot, with each antigen and neutralized mitogenic activity. The amino-terminal amino acid sequence of the CTAP-V proteins, determined by 2 laboratories, confirmed their structural similarities. The amino-terminal sequence through 37 residues was demonstrated for the smaller protein. The first 10 residues of CTAP-V (28 kd) were identical to the N-terminal decapeptide of CTAP-V (16 kd). The C-terminal sequence, determined by carboxypeptidase Y digestion, was the same for both CTAP-V molecular species. The 2 CTAP-V peptides had similar amino acid compositions, whether residues were expressed as a percent of the total or were normalized to mannose. Reduction of native CTAP-V protein released sulfhydryl groups in a protein:disulfide ratio of 1:2; this suggests that CTAP-V contains 2 intramolecular disulfide bonds. Clearly, CTAP-V is a glycoprotein. The carbohydrate content of CTAP-V (16 kd) and CTAP-V (28 kd) is 27% and 25%, respectively. CTAP-V may have significance in relation to autocrine mechanisms for growth regulation of connective tissue cells and other cell types.

Acetylglucosaminidase↗
PubMed1987

Effects of human carbonic anhydrase III (CA III) on synovial and muscle fibroblast glycosaminoglycan metabolism.

We investigated the ability of CA III, isolated from adult human skeletal muscle, to regulate cell growth and glycosaminoglycan (GAG) formation in connective tissue cells derived from various human tissues. Unlike muscle, dermal, and cartilage fibroblasts, synovial connective tissue cells were substantially activated by CA III and showed enhanced hyaluronic acid (HA) synthesis. Cell culture experiments showed that CA III induced a 2- to 11-fold increase in [14C]HA synthesis by human synovial fibroblasts (SF) in a dose-dependent manner (P less than 0.001); erythrocyte CA I and CA II were inactive. Exposure of SF and muscle fibroblasts to CA III also resulted in a 20-45% and 16-70% increased 35S incorporation into proteoglycans, respectively. When adult human skin and cartilage fibroblasts were studied in the presence of CA III, no differences in the level of DNA and GAG formation were noted. These latter cell types were clearly activated by a platelet (CTAP-III) growth factor. The potential physiological implications of these observations are discussed.

Carbonic Anhydrases↗
PubMed1987

Anabolic and catabolic responses of human articular cells to growth factors.

The responsiveness of human synovial cells and chondrocytes to L-ascorbate, CTAP Ib, III, IV and V was assessed by assays which measured DNA and glycosaminoglycan synthesis and plasminogen activator formation. Differences in behavior were noted between synovial and cartilage derived cells and between normal and OA chondrocytes.

Ascorbic Acid↗
PubMedDate not supplied

Clinical, histopathological, immunological and fibroblast studies in 30 patients with subcutaneous injections of modelants including silicone and mineral oils.

OBJECTIVE: To study patients with side effects secondary to the injection of modelants. METHODS: We studied their clinical, serological, histopathological, radiographic, immunoregulatory and fibroblast culture features by standard methods. We studied thirty patients, 24 women, mean age: 38.2 years. Patients had received either mineral oil, guayacol, silicone or a mixture of these substances; some had received unknown material(s). RESULTS: The mean time between the injection and the onset of symptoms was six years (range: 0.1-24 years). All patients had sclerodermatous skin changes, subcutaneous nodules, edema and/or hyperpigmentation at the site(s) of injection(s); five individuals also had skin changes at sites remote from the injection. Thirteen patients had clinical features of an autoimmune disease. Eleven patients gave a history of arthralgias including four that had symmetrical non-erosive polyarthritis. Twenty of 28 patients (71%) had positive anti-nuclear antibodies. We found intracellular spontaneous production of IL-1 (interleukin-1) by patients' macrophages which was almost absent in normal cells (p < 0.001). Silica-stimulated monocytes from patients also secreted more IL-1 than those from normal subjects (p < 0.001) in autologous mixed lymphocyte reaction. Twelve patients had an early proliferative response. At day seven, a decreased proliferative response was seen in 12/19 patients (p < 0.001). Skin fibroblasts from 3/3 patients synthesized 3-to-5-fold more 3H-hyaluronic acid than normal control cells (p < 0.001). CONCLUSIONS: This report confirms the association between the injection of modelants and the development of autoimmune disease (human adjuvant disease, HAD). Our results implicate IL-1 in the amplification of the disease process. The similarities between primary scleroderma and human adjuvant disease now include immunological and connective tissue data. The study of these patients may help to understand the etiopathogenesis of some autoimmune diseases.

Adult↗
PubMedDate not supplied

Identification of four subpopulations of IgG anticardiolipin antibodies in patients with primary antiphospholipid syndrome on the basis of their requirement for beta 2-glycoprotein-I and their unmasking by heat.

Heat-treatment of normal human serum (NHS) results in positive seroconversion of IgG anticardiolipin antibodies (aCL) that do not depend on beta 2-glycoprotein-I (beta 2GP-I) for their detection in vitro as do some IgG aCL from patients with primary antiphospholipid syndrome (PAPS). Other IgC aCL from PAPS depend on beta 2GP-I for phospholipid binding. Here, we studied heat-unmasked aCL from 22 PAPS sera and from eight normal individuals. IgG aCL were detected in standard (using new born calf serum [NBCS] that contains beta 2GP-I as blocking agent and to dilute samples) and in a modified ELISA (using beta 2GP-I-free-bovine serum albumin instead of NBCS). Overt and heat-unmasked IgC aCL were purified from CL micelles alone or mixed with purified beta 2GP-I. NHS had no overt IgG aCL. In contrast, aCL titers increased almost ten-fold after heat-inactivation of NHS, a result which was equally detectable in both assay conditions. As expected, PAPS patients had one population of overt beta 2GP-I-dependent IgG aCL. After heat-treatment of all PAPS sera, we detected IgG aCL in both standard and modified aCL ELISA with an approximately three-fold increase in IgG aCL titers when tested in the standard assay. Two PAPS patients also had a second population of beta 2GP-I-independent overt IgG aCL. Purified IgG from these PAPS sera retained both reactivities.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anticardiolipin↗
PubMedDate not supplied

[New molecular and clinical information about collagens].

Collagen is one of the most abundant proteins in human tissues. Together with other connective tissue components (non-collagenous glycoproteins, proteoglycans, laminins, thrombospondins, entactin and tenascin), collagen promotes cellular adhesion, activates intracellular signals, and regulates the biological activities of growth factors and other proteins. During the past 20 years at least 19 genetically different collagenous proteins coded by 30 distinct genes have been identified. Here, we review some new aspects of the collagens that form fibrils, sheets, or beaded filaments, and of the so-called multiplexin collagens. Whenever possible, we give insights regarding the association of the structural abnormalities of these proteins as they relate with human disease(s).

Anti-Glomerular Basement Membrane Disease↗
PubMedDate not supplied

[Current concepts on cartilage collagens and their association with disease].

The main functional role of the collagenous cartilage fibers is to form a stable network to counteract the hydrodynamic pressure generated by the highly hydrodynamic proteoglycan aggregates. The main collagen present in human cartilage is type II, but other proteins such as type IV, VI, IX, X, XI and XIV are also found albeit in small quantities. Several transgenic mice have been developed to study the structural abnormalities as they relate to human disease. Similarly, the study of these structural abnormalities has renewed the interest regarding their pathogenetic role in some hereditary and acquired diseases of cartilage in humans. It is hoped that gene therapy will help correct these abnormalities. We review here these topics.

Animals↗