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Biomedical subjects

D Mohren

Publications and source records attributed to D Mohren.

3 recordsLinked to original sources

Complement levels and circulating immune complexes in a controlled, longitudinal, multicentre study on effects of intravenous immunoglobulin in adults with AIDS-related complex/Walter-Reed 5. The ARC-IVIG Study Group.

The complement system, as the effector mechanism of the antigen-antibody reaction, and the levels of circulating immune complexes in a 1-year, double-blind, randomized, placebo-controlled study served as laboratory parameters to assess the effect of long-term high-dose intravenous immunoglobulin (IVIG) therapy in 30 adult patients (2 x 15) with AIDS-related complex/Walter-Reed 5 (ARC/WR5). We obtained no evidence of an adverse effect in such patients of high-dose IVIG administered over a 6-month period: none of the parameters studied showed a significant difference between the two groups of patients. In both groups, using data before the first infusion or using data of the whole study, a correlation between circulating immune complexes and classical complement pathway activation was found. The most striking increase was seen in the two groups of patients for functional serum factor D. The accumulation of serum factor D was not paralleled by an increase in serum creatinine. In patients with disease progressing from ARC to AIDS within the study period, an accumulation of serum factor D was not more or less pronounced than in those who remained in the ARC stage. Accumulation of factor D was not related to the clinical score as assessed in this study.

AIDS-Related Complex↗

Inhibition of the classical and alternative pathways of the human complement system by glycosaminoglycan polysulfate.

Glycosaminoglycan polysulfate (GAGPS) concentration-dependently inhibited the activation of the classical and alternative pathways of the human complement system in vitro. Concentrations of > or = 0.2 mg/ml GAGPS prevented the cleavage of C4 by human aggregated gammaglobulin as evidence of inhibition of the classical pathway. At concentrations of > or = 0.15 mg/ml a concentration-dependent inhibition of the cleavage of factor B, the major step in the activation of the alternative pathway, was seen in the presence of inulin. Concentrations < 0.05 mg/ml did not have a measurable effect on either pathway. The lysis of sheep red blood cells, which is mediated largely by the classical pathway, was significantly inhibited at 3.84 mg/ml GAGPS, with a mean inhibition of 45.7%. On the other hand, the same concentration of GAGPS almost completely inhibited the lysis of rabbit red blood cells, which is mediated by the alternative pathway of complement. Our results suggest that the inhibition by GAGPS is an early event in the activation of complement, occurring before the assembly of the C3 convertases of either pathway. The possible use of this drug in acute life-threatening situations where complement is thought to have a pathogenic role is discussed.

Animals↗

Classical and alternative complement pathway activation in paracoccidioidomycosis.

The following study presents evidence of complement activation in paracoccidioidomycosis (PCM). Twenty-eight untreated patients were studied from endemic areas of Parana in southern Brazil. The activation of the classical pathway, evaluated by the C4d/C4 ratio, was significantly elevated in the patients compared to the control population (p < 0.005). Six patients were examined prospectively with the C4d/C4 assay during treatment and they showed a decrease in this ratio associated with clinical improvement. The activation of the alternative pathway was determined by rocket immunoelectrophoresis of fragment Ba. These levels were also significantly higher in the patient group in comparison to the controls (p < 0.0005). The prospective study also showed a significant variation in the Ba levels associated with clinical improvement (p < 0.01). Furthermore, the levels of C3, C4, CH50 and anti-Paracoccidioides brasiliensis IgG were determined in all patients. The anti-P. brasiliensis IgG levels showed a weak positive correlation with the C4d/C4 ratio (r[S] = 0.45; p < 0.03). The C3, C4 and CH50 levels did not show significant variations from the normal ranges. Our results suggest the involvement of both complement pathways, classical and alternative, in PCM and their association with disease activity.

Adolescent↗