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Biomedical subjects

A R Cabral

Publications and source records attributed to A R Cabral.

14 recordsLinked to original sources
PubMed1992

Decrease in serum antiphospholipid antibody levels upon development of nephrotic syndrome in patients with systemic lupus erythematosus: relationship to urinary loss of IgG and other factors.

PURPOSE: Having observed a decrease in antiphospholipid antibodies (aPL) upon the development of nephrotic syndrome, as well as a negative association between nephrotic syndrome and secondary antiphospholipid syndrome, in patients with systemic lupus erythematosus (SLE), we sought to determine if this could be due to urinary loss of aPL and/or other factors. SUBJECTS AND METHODS: IgG and IgM aPL as well as other autoantibodies were studied by enzyme-linked immunosorbent assay with cardiolipin as antigen in serum and urine from six patients with SLE who had elevated serum aPL levels and developed nephrotic syndrome (cases). For controls, we studied: (1) three SLE patients with nephrotic syndrome but low aPL levels; (2) three patients with non-SLE nephrotic syndrome; (3) three SLE patients with high-titer aPL but no proteinuria; and (4) 10 healthy volunteers. RESULTS: We found urinary IgG, but no IgM, aPL in all cases and in one control from Group 2. Serum IgG aPL had gradually decreased after the development of nephrotic syndrome and had become normal. IgM aPL had also decreased in the four patients who had elevated levels, having reached normal levels at the time of the study in two. There was an apparent correlation between serum and urine IgG aPL levels but not between urinary IgG aPL and total proteinuria. By Farr's method, we found no urinary anti-DNA despite high serum titers in three cases. The two cases and one of the controls in Group 1 who had serum antibodies to extractable antigens also had these antibodies in the urine. CONCLUSION: Urinary loss of IgG aPL during nephrotic syndrome does not completely explain the reduction in serum aPL, since IgM also decreases. There could also be decreased synthesis and/or increased catabolism of immunoglobulins.

Adult↗
PubMed1992

Phospholipid specificity and requirement of beta 2-glycoprotein-I for reactivity of antibodies from patients with primary antiphospholipid syndrome.

Some disease manifestations are associated with serum antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) in what has been termed antiphospholipid syndrome (aPLS). There are patients with aPLS who do not have SLE or any other illness who have been grouped under the term primary antiphospholipid syndrome (PAPS). However, patients with diverse infections, notably syphilis, may have aPL but do not develop the associated clinical manifestations. This has been attributed, at least in part, to the immunochemical features of their aPL, including the requirement for beta 2-glycoprotein-I (beta 2GP-I) for binding of aPL to phospholipids, but these have not been studied in sera from patients with PAPS. By ELISA we studied 95 sera from 17 patients with PAPS and 100 sera from clinically normal individuals for IgG and IgM antibodies to the main anionic and zwitterionic phospholipids and their related compounds, phosphatidic acid (PA) and synthetic phosphorylcholine (PRC). beta 2GP-I was present, either in newborn calf serum (NBCS) or purified, to block wells and to dilute samples, or was substituted by 0.3% gelatin. Inhibition studies with phospholipid micelles were used to confirm reactivities with the corresponding phospholipids. All 17 patients had IgG and 11 had IgM antibodies to cardiolipin. Antibodies to anionic phospholipids were primarily IgG whereas those to zwitterionic phospholipids were mainly, and often exclusively, IgM. We found a statistically significant difference in the mean levels of antibodies to all anionic phospholipids except aPTS, and to the haptene PA (P < 0.001) between patients and controls. The difference between levels of IgM antibodies to zwitterionic phospholipids was statistically significant with sphingomyelin (P < 0.001) and the haptene (P < 0.001). Levels of most IgG and most IgM aPL correlated significantly among them. The pattern and titers of reactivity are variable between patients, but stable within each patient. Requirement of beta 2GP-I for this reactivity was not an all-or-nothing phenomenon in individual sera. In general, as in lupus sera, antibodies to anionic phospholipids require that this cofactor be present coating the ELISA plates, whereas those to zwitterionic phospholipids do not. It would appear that patients with PAPS have polyclonal mixtures of antibodies that react with various phospholipids and have different requirements for beta 2GP-I for such reactivity.

Adolescent↗
PubMed1991

Presence of a 16/6 related human anti-DNA common idiotype (SA1) in the anticardiolipin antibodies of patients with primary antiphospholipid syndrome.

Patients with primary antiphospholipid syndrome (PAPS) have few or no autoantibodies, other than the antiphospholipid antibodies (aPL) that could be natural autoantibodies encoded by germline genes. Some of the autoantibodies marked by the human anti-DNA common idiotype 16/6 have been found to be encoded by unmutated germline genes. Hence, we tested the sera of 19 patients with PAPS for the presence of the 16/6 idiotype which has also been found to be expressed on antibodies that bind cardiolipin. For this we used an ELISA method with antiserum against the SA1 idiotype which recognizes the 16/6. Five of our patients had the idiotype in at least one serum. Among the patients there was one with a variant of PAPS with hemolytic anemia and an IgM antibody to phosphatidylcholine that is akin to the natural autoantibody of normal mice encoded by germline genes VH11 and VH12. Inhibition studies with ssDNA, dsDNA and cardiolipin revealed that all 3 antigens decreased the serum levels of the SA1 idiotype despite absence of detectable anti-DNA antibodies by other methods. Our findings suggest that within the B cell clones that produce aPL in patients with PAPS there are some that produce immunoglobulins bearing 16/6 related idiotypes. This could indicate that some of the aPL present in patients with PAPS derive from natural autoantibody producing cell clones.

Antibodies↗
PubMed1991

Diabetes insipidus secondary to Wegener's granulomatosis: report and review of the literature.

We describe a 51-year-old woman with Wegener's granulomatosis who developed diabetes insipidus 7 months after the onset of her granulomatous disease and despite apparently good clinical response to prednisone and trimethoprim-sulphametoxazole treatment. A brain computerized tomographic scan taken soon after the onset of polyuria disclosed an enlarged pituitary gland that completely returned to its normal size after 5 months of cyclophosphamide therapy. We review 6 other published cases of diabetes insipidus secondary to Wegener's granulomatosis and discuss the potential pathogenetic mechanisms of this rare combination.

Diabetes Insipidus↗
PubMed1990

Hemolytic anemia related to an IgM autoantibody to phosphatidylcholine that binds in vitro to stored and to bromelain-treated human erythrocytes.

Both normal and autoimmune mice have IgM natural autoantibodies to bromelain-treated erythrocytes in which phosphatidylcholine (PTC) becomes exposed. At one stage this antibody may participate in the genesis of autoimmune hemolytic anemia in the NZB mouse. We have recently studied a patient with hemolytic anemia who had persistently high serum titers of IgM anticardiolipin antibodies (aCL) that were also demonstrated in a hemolysate of his erythrocytes obtained at the time of the anemia. We affinity-purified the antibody and sought its binding to normal human bromelain-treated erythrocytes (BrE) because of the IgM isotype of the antibody, since cardiolipin is not a constituent of the erythrocyte wall, and because the anionic phospholipids, with which aCL are known to cross-react, are not located at the outer leaflet of the erythrocyte membrane. We found binding of the antibody to HBrE in their hemolysates and by flow cytometry. We also demonstrated that the aCL cross-reacted extensively with PTC, as well as with other anionic or zwitterionic phospholipids. The purified IgM antibody lysed BrE in the presence of complement and also bound to in vitro-aged erythrocytes. Because this patient had no other evidence of systemic lupus erythematosus or any other autoimmune condition, his disease may represent a variant of the recently described primary antiphospholipid syndrome.

Adult↗
PubMed1989

Bone remodeling and osteophyte formation after remission of rheumatoid arthritis.

Bone remodeling and osteophyte formation rarely take place in active rheumatoid arthritis (RA). To determine if disease inactivation leads to their occurrence, we studied 38 patients with RA whose disease had gone into drug induced remission. We looked for osteophytes at the metacarpophalangeal (MCP) joints in roentgenograms taken before and after remission, and correlated their presence to that of osteoarthritis of the distal interphalangeal (DIP) joints. There were 21 patients with RA who had a median of 3 (range 1-8) osteophytes in their "remission" films which were rarely present in their "activity" films (p less than 0.0001). The osteophytes were frequently symmetrical and most often located (41%) at the third MCP joint. In addition, we observed a peculiar remodeling of the styloid process in 13 patients, 9 of whom had developed MCP joint osteophytes. There were no other detectable differences between patients who had MCP joint osteophytes and those who did not. Presence of osteoarthritis at the DIP joints did not correlate with development of osteophytes. We were able to classify the MCP osteophytes into 3 types on the basis of their shape: hook-like that were most frequently bilateral and situated on the radial aspect of the metacarpal side of the joint, beak-like that were most often found at the ulnar aspect of the phalangeal side, and nipple-like which occurred equally on either sites. These differences in distribution indicate that they are not stages of the same process. Our findings indicate that paraarticular bone remodeling occurs upon remission of RA, even in joints where osteoarthritis is unusual. Its shape and location may depend on both their site and the mechanism of joint damage.

Adult↗
PubMed1987

Connective tissue activation. XXXI. Identification of two molecular forms of a human mesenchymal cell-derived growth factor, connective tissue activating peptide-V.

We previously identified, in normal urine, a growth factor that stimulated monolayer cultures of human synovial, cartilage, and dermal fibroblasts to synthesize incremental amounts of hyaluronic acid, proteoglycans, and DNA. An isolation procedure guided by bioassays and immunologic methods disclosed 2 anionic bioactive polypeptides with Mr of 28,000 and 16,000, respectively, as judged by single bands with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in reduced and nonreduced samples. Rabbit antibodies raised against each purified protein were shown to react, on immunodiffusion and Western blot, with both antigens. Immunohistochemical and immunobinding studies detected the protein in normal human synovial, dermal, and cartilage fibroblasts and in human saphenous vein endothelial cells. The mesenchymal cell-derived growth factor is now designated connective tissue activating peptide-V (CTAP-V). Monospecific polyclonal anti-CTAP-V antibodies were used in a radial immunodiffusion assay for quantitative determination of the antigen in biologic fluids. In normal human plasma the concentration of CTAP-V was below the limit of detection. The CTAP-V concentration in normal urine was 4.5 +/- 2.0 micrograms/ml, calculated from measurements of 5-18-fold concentrated samples. Joint fluid from patients with rheumatic diseases and normal renal function had CTAP-V levels similar to those found in plasma; 2-15-fold increases were detected in plasma and joint fluid of patients with chronic renal failure. Immunodiffusion or dot-blot analysis revealed a CTAP-V-like material in the plasma or serum of 10 mammalian species. It was not detectable in 2 avian species.

Cartilage↗
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↗