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Biomedical subjects

G Senaldi

Publications and source records attributed to G Senaldi.

At least 37 records · Page 2Linked to original sources

Reflection of disease activity in rheumatoid arthritis by indices of activation of the classical complement pathway.

Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 77 patients with rheumatoid arthritis and 30 healthy subjects. Disease activity was judged according to Ritchie's articular index to be mildly active in 31 (group 1), moderately active in 29 (group 2), and severely active in 17 patients (group 3). Plasma levels of C3d, a fragment of C3, and serum levels of C4, C3, and immune complexes were also measured. The ratios C4d/C4 and C3d/C3 were calculated. The C4d/C4 and C3d/C3 ratios and the levels of circulating immune complexes correlated with the degree of disease activity without significantly departing from linear trend and discriminated between patients with different grades of disease activity. C4d, C3d, C4, and C3 also correlated with disease activity but in a non-linear relationship. A significant correlation was found between C4d and C3d, and between C4d/C4 and C3d/C3. C4d and C4d/C4 also correlated with circulating immune complexes. These results indicate that indices of C4 and C3 activation, in particular the ratios C3d/C3 and C4d/C4, provide a sensitive assessment of disease activity in rheumatoid arthritis, and confirm the major part played by the classical complement pathway in the pathogenesis of this disease.

Adult

Correlation of the activation of the fourth component of complement (C4) with disease activity in systemic lupus erythematosus.

Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 48 patients with systemic lupus erythematosus, 11 with inactive (group 1), 23 with mildly active (group 2), 14 with moderately/severely active disease (group 3), and 30 healthy subjects. Levels of C3d, C4, and C3 were also measured and the C4d/C4 and C3d/C3 ratios calculated. C4d levels correlated with the degree of disease activity, being higher in group 3 than in group 2, in group 2 than in group 1, and in group 1 than in controls. C4d/C4 gave a similar result. Activation indices of the common complement pathway, C3d and C3d/C3, also correlated with disease activity, but in a non-linear relationship, failing to discriminate between patient groups. C4 and C3 showed no correlation with disease activity. These results indicate that indices of C4 activation, C4d and C4d/C4, provide a laboratory measure of disease activity in lupus patients, for whom an objective assessment of the severity of the disease is not readily available.

Adult

Low serum haemolytic function of the fourth complement component (C4) in insulin dependent diabetes.

Low serum concentrations of the fourth component of complement (C4) are found in insulin dependent diabetes, and may be important in the aetiology of the disease. To ascertain whether function of C4 is also impaired both its haemolytic activity and its concentration were measured in 34 insulin dependent diabetics, 15 non-insulin dependent diabetics, 20 healthy subjects, and 12 pairs of monozygotic twins discordant for insulin dependent diabetes. C4 function was measured by a radial immune haemolytic assay, and C4 concentration by laser nephelometry. Both measurements were significantly lower in insulin dependent diabetics (C4 function: median 47%, range 4-100%; C4 concentration: 0.22 g/l, 0.10-0.38 g/l) than in non-insulin dependent diabetics (67%, 33-138%, p less than 0.01; 0.27 g/l, 0.16-0.50 g/l, p less than 0.02) and controls (74%, 33-138%, p less than 0.01; 0.27 g/l, 0.18-0.40 g/l, p less than 0.03). C4 function and concentration were lower in both diabetic (48%, 12-100%; 0.17 g/l, 0.08-0.31 g/l) and non-diabetic twins (47%, 12-100%; 0.17 g/l, 0.07-0.36 g/l) than controls (p less than 0.01; p less than 0.01). Thirteen (38%) of the insulin dependent diabetics had a reduction in either C4 function or concentration, but in only five were both features reduced. Values of function and concentration were strongly correlated in both diabetic and non-diabetic twins (r = 0.95, p less than 0.001; r = 0.92, p less than 0.001). These results show defects in C4 function and concentration in insulin dependent diabetes, which--being present in the non-diabetic co-twin of diabetics--may represent a genetic predisposition to the disease.

Adult

Clinical application of new technique that measures C4d for assessment of activation of classical complement pathway.

A new laser nephelometric technique that measures C4d for the assessment of the activation of the classical complement pathway was developed. C4d was isolated from other larger C4 related molecules at a final concentration of polyethylene glycol of 12% and then quantitated by laser nephelometry using a commercially available antiserum, which reacts with C4d determinants. C4d standard (100%) was produced by exhaustive activation of the classical pathway in pooled normal human serum using heat aggregated human immunoglobulin. Serial dilutions of the standard provided a reference curve against which clinical samples were read. Patients with rheumatoid arthritis showed significantly higher C4d values (mean 53.8%) than controls (21.7%; p less than 0.001). The technique proved accurate, rapid, and suitable for the routine laboratory evaluation of complement activation through the classical pathway, and it may be useful in the management of those conditions in which complement activation has a pathogenic role.

Adolescent

Detection of HTLV-III-specific IgG bands in the CSF from a patient with AIDS and encephalitis.

Recent evidence would suggest that HTLV-III may be neurotropic. We have found oligoclonal IgG bands by isoelectric focusing in the CSF of a homosexual man with AIDS and encephalitis. Subsequent analysis revealed that such bands contained anti-HTLV-III activity, suggesting that neurologic symptoms in AIDS patients may be caused by replication of HTLV-III inside the CNS.

Acquired Immunodeficiency Syndrome

Quantification of C3d in biological fluids by an enzyme-linked immunosorbent assay.

Using a commercial source of peroxidase-labelled anti-C3d antibody (Dakopatts), an enzyme-linked immunosorbent assay (ELISA) has been developed to quantify the complement fragment C3d. The technique enables the detection of C3d in plasma, urine and cerebrospinal fluid (CSF). The C3d-ELISA therefore provides a very sensitive technique for the evaluation of complement activation in biological fluids. In both plasma and urine the technique is able to discriminate between samples from normal controls and patients with rheumatoid arthritis in whom complement activation is known to occur. A good correlation was found between results obtained by ELISA and those by laser nephelometry (r = 0.91, P less than 0.0001). Microtitre plates pre-coated with anti-C3d antibody and subsequently stored at -70 degrees C retained the ability to perform in this assay. The sensitivity, short assay time and use of commercial reagents and pre-coated plates give this technique numerous potential applications in the evaluation of complement activation.

Arthritis, Rheumatoid

Activation of the alternative complement pathway: clinical application of a new technique to measure fragment Ba.

A new laser nephelometric technique for the measurement of the alternative complement pathway fragment Ba has been developed. Activation of the alternative complement pathway was assessed in 16 patients with Gram negative bacteraemia, six with Gram positive bacteraemia, 20 with rheumatoid arthritis, and 18 healthy subjects. Patients with Gram negative bacteraemia had significantly higher values of Ba (median 14.8%) than controls (9.3%) (p less than 0.01), while patients with Gram positive bacteraemia and rheumatoid arthritis had values similar to those of controls (10.1% and 9.5%). The technique proved sensitive and precise, and is suitable for the routine laboratory evaluation of complement activation through the alternative pathway.

Adolescent

Peripheral blood lymphocyte subpopulations after splenectomy for trauma.

Absolute and percent numbers of peripheral blood lymphocyte (PBL) subpopulations were evaluated using monoclonal antibodies in 20 subjects splenectomised for trauma. A significant increase was observed in the absolute counts of total PBL, B, null and Leu 7+ cells and in the percent counts of null and Leu 7+ lymphocytes. The percent numbers of OKT11+, OKT4+ and OKT8+ lymphocytes were significantly reduced, but the OKT4+/OKT8+ ratio was not statistically different from normal controls. The increase in B and killer/natural killer cells may provide a compensatory mechanism responsible for surveillance against infections and tumors in splenectomised patients, despite the numerous humoral and cellular abnormalities they commonly display.

Adolescent

Dynamic and ultrastructural studies of in vitro interaction between Toxoplasma gondii and cultured cell lines. I. Adhesion and cellular penetration.

Toxoplasma gondii is a protozoan parasite that requires an intracellular environment for growth and replication. This study describes the early phase of the interaction between the parasite and its host cell. With the aid of phase contrast microcinematography, it has been possible to observe adhesion to cell membrane, and the closely following intracellular penetration. This report also reviews the ultrastructural and biochemical grounds that could account for the infecting process.

Animals

Characterization of circulating T-lymphocyte subsets in alcoholic liver disease by monoclonal antibodies: correlation with the absolute lymphocyte count.

Peripheral blood T-lymphocytes from 27 patients with alcoholic liver disease were assessed on the basis of their ability to react with OKT monoclonal antibodies. A significant positive correlation was observed between the absolute numbers of T-lymphocytes and suppressor/cytotoxic T cells and the absolute lymphocyte count. These data suggest that quantitative changes in T-lymphocyte subsets in alcoholic liver disease do not necessarily reflect an imbalance in T immunoregulatory mechanisms.

Antibodies, Monoclonal