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Biomedical subjects

I F Carvalho

Publications and source records attributed to I F Carvalho.

15 recordsLinked to original sources

CR1 on erythrocytes of Brazilian systemic lupus erythematosus patients: the influence of disease activity on expression and ability of this receptor to bind immune complexes opsonized with complement from normal human serum.

Hypocomplementaemia and low expression of CR1 on erythrocytes (E) of patients with systemic lupus erythematosus (SLE) are associated with defective clearance of circulating immune complexes (IC) and so they may have pathogenic significance. Here, we investigated whether the reduced CR1/E in SLE patients per se might affect the binding of IC to CR1/E. First, we analysed the expression of CR1 on E of active (n=30) and inactive (n=34) SLE patients using a FITC-conjugated mouse anti-CR1 monoclonal antibody E11 and flow cytometry. Both groups of patients had a significantly reduced CR1/E expression compared with healthy controls (n=40). It was also observed that the number of E bearing CR1 was reduced in both groups of SLE patients studied. Second, we determined the functional activity of CR1/E by measuring the binding to E of FITC-bovine serum albumin (BSA)/rabbit anti-BSA complexes, formed at equivalence, which were opsonized with complement from normal human serum (NHS). On the other hand, we did not find differences between the patient and control groups in the ability of E to bind IC/NHS. There was also a positive correlation between the CR1/E expression and the number of E bearing CR1 in control and inactive SLE groups, which was not observed in the group of active SLE patients. Considering the involvement of low levels of complement and CR1/E expression on complex processing, in this in vitro model the results show that an effective coating of the complexes with complement is sufficient to bind them preferentially to CR1 over normal levels of receptor expression.

Antigen-Antibody Complex↗

Fcgamma and complement receptors: expression, role and co-operation in mediating the oxidative burst and degranulation of neutrophils of Brazilian systemic lupus erythematosus patients.

We have investigated the individual role of FcgammaR and CR, as well as their cooperation, in mediating the oxidative burst and degranulation of neutrophils of Brazilian systemic lupus erythematosus (SLE) patients. Neutrophils were stimulated with the immune complexes (IC)-IgG or -F(ab')2, opsonized or not with normal or SLE human serum. The oxidative burst was decreased in neutrophils of active SLE patients compared to healthy controls when this response was mediated by FcgammaR and/or CR, while the degranulation was unaffected. The SLE hypocomplementemia did not affect the oxidative burst mediated only by CR. FcgammaRII and CR1 expression on neutrophils of active SLE patients was reduced, while the expression of FcgammaRIII and CR3 was unaffected. These results suggest that the different FcgammaR and CR may be involved or cooperate in different ways in the mediation of the oxidative burst and the degranulation. Moreover, the decreased oxidative burst of neutrophils of active SLE patients may not depend only on SLE hypocomplementemia for IC opsonization. These observations are directed at the understanding of how each of these immune system components (FcgammaR, CR and complement) influences the precise biological neutrophil responses both in physiological and pathological conditions. Since the Brazilian population comprises many races, these results are important because they are directed at a specific population of SLE patients.

Brazil↗

Association between EcoRI fragment-length polymorphism of the immunoglobulin lambda variable 8 (IGLV8) gene family with rheumatoid arthritis and systemic lupus erythematosus.

The human immunoglobulin lambda variable 8 (IGLV8) subgroup is a gene family containing three members, one of them included in a monomorphic 3.7-kb EcoRI genomic fragment located at the major lambda variable locus on chromosome 22q11.1 (gene IGLV8a, EMBL accession No. Z73650) at 100% frequency in the normal urban population. The second is a polymorphic RFLP allele included in a 6.0-kb EcoRI fragment at 10% frequency, and the third is located in a monomorphic 8.0-kb EcoRI fragment at 100% frequency, the last being translocated to chromosome 8q11.2 and considered to be an orphan gene. Our Southern blot-EcoRI-RFLP studies in normal individuals and in patients with rheumatoid arthritis (RA) or with systemic lupus erythematosus (SLE), using a specific probe for the IGLV8 gene family (probe pVL8, EMBL accession No. X75424), have revealed the two monomorphic genomic fragments containing the IGLV8 genes, i.e., the 3.7-kb fragment from chromosome 22q11.1 and the 8.0-kb fragment from 8q11.2, both occurring at 100% frequency (103 normal individuals, 48 RA and 28 SLE patients analyzed), but absence of the 6.0-kb IGLV8 polymorphic RFLP allele in all RA or SLE patients. As expected, the frequency of the 6.0-kb allele among the normal individuals was 10%. These findings suggest an association between the absence of the 6.0-kb EcoRI fragment and rheumatoid arthritis and systemic lupus erythematosus.

Alleles↗

Augmented plasma and tissue kallikrein like activity in synovial fluid of patients with inflammatory articular diseases.

We studied some of the components of the kininogen-kallikrein-kinin system, simultaneously, in plasma and synovial effusions of patients with inflammatory articular diseases. Plasma and tissue kallikrein like activity and kininogen levels were evaluated. Active plasma and tissue kallikreins in plasma and synovial fluid were detected by their amidase activity upon specific chromogenic substrates. Kininogen levels were determined by a bioassay. Both specific amidase activity of plasma and tissue kallikreins were augmented in synovial effusions in relation to their own plasma activity. Kininogen levels in synovial fluid tended to be diminished in relation to plasma, however statistical significance was not reached. The consumption of kininogen is probably related to kinin production. This finding together with increased activities of plasma and tissue kallikreins reinforce the involvement of kinins in pathogenesis of inflammatory articular diseases.

Adolescent↗

Circulating immune complexes after splenectomy.

Circulating immune complexes were evaluated in 25 patients (age range 10 to 46 years) who had undergone splenectomy for non-malignant conditions by studying a polyethylene glycol insoluble serum fraction. Although the extent of binding to Clq was within normal limits, these patients had increased concentrations of factor B in the immune complex serum fraction. These findings indicate that an unusual type of circulating immune complex may be detected after splenectomy, suggesting a possible role for the spleen in the removal of circulating immune complexes.

Adolescent↗

Circulating immune complexes in sickle cell anaemia.

A polyethylene-glycol insoluble serum fraction was studied in patients with sickle cell anaemia during the steady state of the disease. The levels of C1q-precipitins were normal but increased amounts of proteins, IgM C3 and factor B were detected in this immune complex enriched serum fraction. These findings are a sign that circulating immune complexes can be detected even in the asymptomatic period of the disease.

Adolescent↗

Circulating immune complexes in sickle cell-beta zero thalassemia.

A serum fraction from patients with sickle cell-beta zero thalassemia prepared by treatment with polyethyleneglycol showed increased amounts of C1q-precipitable immune complexes, i.e., 216 micrograms/dl (range, 141-266 micrograms/dl) vs 181 micrograms/dl (range, 152-228 micrograms/dl) for controls (P less than 0.05), as well as increased amounts of protein. Levels of IgG, IgA, IgM, C3, C4 and factor B in the same fraction were within the normal range.

Adolescent↗

Experimental nephropathy induced by human polyclonal light chains.

We describe the nephrotoxic effects of a preparation of light chains (LC) obtained by reduction and alkylation of human IgG. The acute renal lesions in rats are dependent upon the dose and route of LC administration. The kidney alterations were not observed in animals treated with comparable amounts of human albumin or the F(ab')2 fragment of human IgG. Intravenous bolus injection of 120 mg LC into 80-100 g hydropenic rats induced extensive cast formation in distal and collecting renal tubules, which were similar to the human "myeloma kidney". In contrast, the slow infusion of the same amount of LC over 1 h produced degenerative changes in the proximal tubular cells without extensive cast formation. The morphological alterations of the kidney were investigated by classical histological methods, by immunofluorescence and in thin sections stained with toluidine blue. Urinary excretion and kidney content of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase were increased only in the group of animals infused with LC. These findings may be relevant to the pathogenesis of human nephropathy occurring in multiple myeloma and in some autoimmune diseases.

Acute Kidney Injury↗

Crossed-immunoelectrophoresis analysis of the urinary excretion of alpha 1-acid glycoprotein, alpha 1-antitrypsin, albumin, and transferrin in normal subjects and in patients with renal disease.

Urinary excretion of four plasma proteins having molecular weights between 44,100 and 90,000 daltons was studied by two-dimensional immunoelectrophoresis in normal individuals and in patients with different kinds of renal pathology. The proteins studied were: alpha 1-acid glycoprotein, 44,100 molecular weight (MW) and pH 2.7 isoelectric point (IP); alpha 1-antitrypsin, 54,000 MW and 4.0 IP; albumin, 69,000 MW and 4.9 IP; and transferrin, 90,000 MW and 5.6 IP. The proteins were measured in urine with an oligospecific serum produced by the immunization of rabbits with the 4S fraction obtained from normal human plasma by gel filtration on Sephadex G-200. The increase in urinary excretion of these proteins observed both among glomerulopathic and tubulopathic patients did not correlate with MW. Mean renal albumin excretion was 2.9 mg/24 h among normal individuals, 87.38 mg/24 h among patients with tubulopathy, and 3,228 mg/24 among patients with glomerulopathy. Among patients with glomerulopathy, there was a direct correlation between the increased excretion of these proteins and their IP, except for alpha 1-acid glycoprotein.

Acute Kidney Injury↗

K-cell activity in aplastic anaemia.

K-cell activity was measured by specific cytotoxicity and cytotoxic capacity in 29 patients with aplastic anaemia. 9 patients had a reduction of the specific cytotoxicity and 12 had a decreased cytotoxic capacity. The decreased cytotoxic capacity correlates with the severity of aplastic anaemia. Some of the possible causes of the reduction of this activity were investigated.

Adolescent↗

Inhibition of rabbit tissue kininase by anti-(endo-oligopeptidase A) antibodies.

Highly purified rabbit brain endo-oligopeptidase A injected into goats produced, after 60 days of immunization, antisera that specifically inhibit purified rabbit brain endo-oligopeptidase A. An immunoreactive kininase having the same specificity as rabbit brain endo-oligopeptidase A for bradykinin was detected in several rabbit tissues. The highest amount of this immunoreactive kininase was found in the 25000 g supernatant fraction (S fraction) of heart, liver, skeletal muscle, ovary, brain and testis homogenates, corresponding to 89, 86, 78, 59, 56 and 53% respectively of the whole kininase activity found in the S fraction.

Animals↗

Lymphocyte subpopulations and neutrophil function in chronic human Chagas' disease.

The absolute numbers of total leukocytes, lymphocytes. T cells, helper/inducer, suppressor/cytotoxic and B cells were decreased in the peripheral blood of patients with chronic Chagas' disease. Since antilymphocyte antibodies were present only in a minority of patients they probably cannot account for the abnormalities in lymphocyte subsets. Patient neutrophils stimulated with endotoxin-treated autologous plasma showed depressed chemotactic activity and this seems to be an intrinsic cellular defect rather than plasma inhibition. Random migration of neutrophils was normal. Reduction of nitroblue tetrazolium by endotoxin-stimulated neutrophils was also decreased. These findings further document the presence of immunosuppression in human Chagas' disease. They may be relevant to autoimmunity, defense against microorganisms and against tumor cells at least in a subset of patients with more severe abnormalities.

Antilymphocyte Serum↗

Correlation of alternative pathway (AP) lytic activity and AP-dependent neutrophil phagocytosis with factor B levels and consumption in serum.

This work investigated the correlation between serum levels of factor B, AP-lytic activity, ratio of factor B activation by zymosan, and AP-dependent neutrophil phagocytosis in samples of normal human serum (NHS). In addition, since the antithyroid drug propylthiouracil (PTU) induces increased levels of AP lytic activity in rats, groups of these animals were treated with this drug in order to increase AP titers and to evaluate those parameters also in this condition. The results showed no correlation between factor B concentration and AP lytic activity in 18 samples of NHS or between factor B concentration and proportion of consumption by zymosan. Interestingly, this consumption was also not correlated with phagocytosis as measured by the chemiluminescence (CL) response of neutrophils to the opsonized particles. The two biological properties of phagocytosis and lytic activity, dependent of AP, were not correlated to each other in the NHS samples. In the samples of rat serum with increased AP lytic levels a different result was observed. A positive correlation between CL response and lytic activity occurred in serum of animals receiving a low PTU dose, but not in serum of animals receiving a high dose, where CL responses were lower than those of controls. The results are compared to literature data and discussed in terms of individual differences in resistance or susceptibility to infections and or diseases involving the complement system.

Animals↗