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Biomedical subjects

A R Cabral

Publications and source records attributed to A R Cabral.

At least 37 records · Page 2Linked to original sources

Visceral larva migrans mimicking rheumatic diseases.

OBJECTIVE: To report rheumatologic or rheumatologic-like manifestations of the visceral larva migrans (VLM) syndrome. METHODS: We carried out a prospective study of patients with VLM seen in a private practice setting in Mexico City between 1990 and 1993. RESULTS: From a population of 600 patients we identified 6 patients (5 women) with VLM. Three patients complained of arthralgia; in 4 a history of migratory cutaneous lesions was elicited, and in one monoarthritis of the right knee was found. One patient had deep edema that suggested thrombophlebitis of the right arm; the man in our series had right testicular swelling during followup. In 2 cases, panniculitis was documented by biopsy and in one, small vessel vasculitis. Four patients had frequent contact with dogs and one with cats; 4 patients frequently ate raw fish. The diagnosis of VLM was confirmed either by the clinical picture, biopsy, or ELISA: CONCLUSION: The spectrum of rheumatological manifestations in VLM may be wider than previously thought.

Adult↗

Antibodies to phospholipid-free beta 2-glycoprotein-I in patients with primary antiphospholipid syndrome.

OBJECTIVE: To investigate serum anti-beta 2-glycoprotein-I antibodies (a beta 2 GP-I) in patients with primary antiphospholipid syndrome (APS). METHODS: We studied a beta 2 GP-I by Western blot, dot blot, and ELISA in the sera of 15 patients with primary APS with high titers of immunoglobulin G (IgG) and/or immunoglobulin M (IgM) anticardiolipin antibodies (aCL) at the time of study and compared findings with the sera of 13 aCL positive patients with syphilis and 76 healthy controls. Sera were also inhibited with cardiolipin micelles and tested for aCL and a beta 2 GP-I activities. RESULTS: Twelve patients with primary APS but no syphilis patient or control subject had IgG to phospholipid-free beta 2 GP-I (p < 0.0001) for both comparisons). The aCL activity was inhibited with cardiolipin micelles but this treatment had less effect on a beta 2 GP-I activity. We found no IgM a beta 2 GP-I in any serum. Nine of 14 patients had had lupus anticoagulant activity; 8 of these had a beta 2 GP-I. CONCLUSION: Patients with primary APS frequently have IgG a beta 2 GP-I that appear to differ from aCL. If aCL present in patients with primary APS actually react with a phospholipid induced neoepitope on beta 2 GP-I, as recently proposed, patients with primary APS have autoantibodies against 2 epitopes on beta 2 GP-I. Lack of a beta 2 GP-I in patients with syphilis might also contribute to protection from developing the APS.

Adult↗

Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies.

OBJECTIVE: To investigate antibodies to phospholipid-free beta 2-glycoprotein-I (a beta 2 GP-I) in the serum of patients with systemic lupus erythematosus (SLE). METHODS: We studied alpha beta 2 GP-I by Western blot, dot blot, and ELISA in 94 patients with SLE. Twenty-one had antiphospholipid syndrome (APS) by clinical and serological criteria, 33 had neither of these features, 18 had the clinical criteria for APS but no serum antiphospholipid antibodies (aPL). and 22 had positive aPL but no related clinical manifestations. As controls, we also studied 76 normal sera. Sera were also inhibited with cardiolipin micelles and tested for anticardiolipin antibodies (aCL) or a beta GP-I activities. RESULTS: Thirty-five of 39 patients with SLE with clinical manifestations of APS has serum a beta 2 GP-I, while only 2 of 55 patients with SLE without such clinical manifestations had them (p = 0.000000001). Sixteen patients with SLE with clinical APS but aPL negative were a beta GP-I positive. All 35 patients with SLE who were a beta 2 GP-I positive had vascular manifestations, but these antibodies were present in only 4 of 55 patients with SLE without vascular manifestations (p = 0.00000001). No patient having either aPL or a beta 2 GP-I had clinical manifestations of APS, whereas all 19 patients positive for both antibodies had clinical APS. The a beta 2 GP-I positive, aPL negative patients with SLE had clinical APS more frequently (16/18) than did a beta GP-I negative, aPL positive patients with SLE (2/24) (p = 0.000000001). The association of clinical manifestations of APS with a beta 2 GP-I was stronger than with aPL. Inhibition studies also indicate that aPL and a beta 2 GP-I are 2 different antigen/antibody systems. CONCLUSIONS: Our findings indicate that the so called APS associates strongly with antibodies recognizing phospholipid-free beta 2 GP-I. There are patients' sera that also recognize cardiolipin and/or its cofactor beta 2 GP-I, the latter perhaps by reacting with a neoepitope on this protein that appears after its interaction with cardiolipin. These would be the previously considered (beta 2 GP-I dependent) aCL.

Adolescent↗

Tween 20 detaches cardiolipin from ELISA plates and makes anticardiolipin antibodies undetectable regardless of the presence of beta 2-glycoprotein-I.

We investigated the effects of polyoxyethylene sorbitan monolaurate (Tween 20) in the detection of IgG anticardiolipin antibodies (aCL) by the CL-beta 2-glycoprotein-I and the standard aCL solid-phase immunoassays. We found that Tween 20 disengages cardiolipin from a variety of microtiter wells rendering aCL undetectable by both methods. Our results agree with a previous report but are discordant with others. We offer rationale that may explain some of the discrepancies. Based in our findings, we do not recommend the use of Tween 20 for the detection of aCL.

Antibodies, Anticardiolipin↗

Antiphospholipid antibodies in patients with idiopathic autoimmune haemolytic anemia.

Isolated cases of anti-phospholipid antibody (aPL)-associated idiopathic autoimmune haemolytic anemia (IAHA) have been recently described. To assess the significances of this association, we studied by ELISA the presence of aPL in sera from 18 patients with IAHA and 14 patients with non-autoimmune haemolysis (NON-AH). Four IAHA cases and none of the NON-AH controls showed IgM anticardiolipin antibodies (aCL) that crossreacted extensively with zwitterionic as well as with other anionic phospholipids. IgG aCL were detected in 6 patients with IAHA and in 1 patient with NON-AH; there was little cross-reactivity with other phospholipids. Our results suggest that antiphospholipid antibodies are present in a substantial number of patients with IAHA. This humoral response does not seem to be secondary to the haemolysis proper. The potential pathogenic significance of this finding is discussed.

Adolescent↗

Listeriosis in patients with connective tissue diseases.

OBJECTIVE: Patients with connective tissue diseases (CTD) are prone to infections, either from the disease itself or secondary to treatment. The incidence of listeriosis in immunosuppressed patients is increasing. We therefore evaluated the frequency of listeriosis, an otherwise rarely reported infection in the rheumatologic literature, in patients with CTD. METHODS: Retrospective analysis of listeria positive cultures in patients with CTD between 1982 and 1992 at a tertiary care center in Mexico City. RESULTS: We identified 8 patients: 7 with systemic lupus erythematosus and one with dermatomyositis. At the time of the infection, 5 had active disease, 6 were receiving prednisone and/or other immunosuppressive drugs and 2 were receiving hemodialysis. L. monocytogenes was isolated from cerebrospinal fluid (5 patients), from blood (one patient) and from both sites (2 patients). Patients had bacteremia without a known focus of infection or meningitis as the 2 most common clinical forms of listeriosis. In spite of appropriate antibiotic therapy, 4 patients died. CONCLUSION: As in other immunosuppressed individuals, listeriosis is an aggressive infection in patients with CTD. Although rare, listeriosis should be included in the differential diagnosis of meningitis in patients with CTD and appropriate aggressive therapy rapidly instituted. To determine its frequency in rheumatic patients, multicentric prospective studies are required.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗