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Biomedical subjects

R Fischel

Publications and source records attributed to R Fischel.

28 records · Page 2Linked to original sources

A central anti-DNA idiotype in human and murine systemic lupus erythematosus.

The monoclonal anti-DNA autoantibody A52 (IgG2b) was obtained from a (NZB X NZW)F1 (B/W) hybridoma. Two rabbits were immunized with the pure monoclonal antibody and produced anti-idiotypic (Id) antibodies. The purified anti-Id reacted with three different B/W monoclonal anti-DNA antibodies at or close to their DNA binding sites. Moreover, the rabbit antibodies had a profound inhibitory effect on the polyclonal anti-DNA activity in the majority of sera derived from B/W mice and human systemic lupus erythematosus (SLE) patients. The A52 IgG must, therefore, represent a major cross-reactive Id of anti-DNA immunoglobulins. In addition, the rabbit anti-Id antibodies may act as the "internal image" of antigen and should prove useful in modulation of the autoimmune response to DNA in SLE.

Animals↗

Autoantibodies to anti-DNA with anti-allotypic and anti-idiotypic specificities in (NZB X NZW)F1 mice.

The monoclonal A52 (IgG2b, kappa) anti-DNA autoantibody represents a major cross-reactive idiotype in the murine and human autoimmune response to DNA. Examination of sera and purified IgG derived from (NZB X NZW)F1 mice showed that these mice develop an age-dependent binding reactivity with the pure anti-DNA IgG. Three monoclonal antibodies possessing this reactivity were prepared from unprimed female (NZB X NZW)F1 mice. One of these monoclonal antibodies appeared to be directed against allotypic determinants present in the NZB IgG2b; the other two antibodies exhibited a marked preference for idiotypic determinants of the A52 IgG. The IgG anti-allotype and anti-idiotype activities in (NZB X NZW)F1 mice may, therefore, represent the products of a deregulated immune system and/or constitute the normal elements of a functional immune regulation system.

Animals↗

Antibodies to RNA from autoimmune NZB/NZW mice recognize a similar antigenic determinant and show a large idiotypic diversity.

We have identified two RNA-specific hybridoma autoantibodies in fusions of spleen cells from unimmunized NZB/NZW female mice with BALB/c myeloma cells. The two fusion experiments were carried out 2 years apart with different myeloma partners. Specificity analyses showed that the two monoclonal antibodies and the total RNA-binding IgG in NZB/NZW serum recognize a G,C-rich sequence of ribonucleotides. The isolated heavy and light chains of the two antibodies and their papain Fab fragments could be distinguished by NaDodSO4/polyacrylamide gel electrophoresis. Rabbit anti-idiotypic antibodies prepared against the two monoclonal proteins showed unique specificities for the antigen-binding sites of their cognate auto-antibodies. Moreover, the anti-idiotypic antisera had little effect on the RNA-binding capacity of the total IgG from NZB/NZW serum. These results suggest that a wide range of different idiotypes is involved in the autoimmune response to a similar antigenic determinant.

Animals↗

Albumin-immunoglobulin complexes in human serum: classification and immunochemical analysis.

A complex between serum albumin and immunoglobulins was observed on immunoelectrophoresis in six patients. Two patients with multiple myeloma had monoclonal IgA-albumin complexes; one of these complexes was formed by covalent bonds and the other by non-covalent bonds. Four patients displayed non-covalent IgG-albumin complexes: of these, one had multiple myeloma, two had been treated with nitrofurantoin for prolonged periods, and one had diabetes mellitus. The IgG-albumin complex of the last patient was subjected to a detailed immunochemical analysis. The albumin-specific antibodies were isolated by affinity chromatography and analysed, using a sensitive tritium labelling technique. The antibodies were polyclonal, complexed with serum albumin through their Fab portion, and showed a high specificity for the human albumin as compared with bovine and rabbit albumins. The serum albumin of two patients displayed an abnormal behaviour in reduced SDS-polyacrylamide gel electrophoresis (PAGE). The abnormal albumins had an apparent molecular weight of 52,000 and could react with rabbit anti-human serum albumin like the normal protein. No abnormal albumin could be detected in 20 other patients' sera, including nitrofurantoin-treated patients and normal controls. These findings suggest a possible role for an altered self-component in the triggering of a specific autoimmune reaction.

Animals↗

Effect of lung volume reduction surgery in a rabbit model of bullous lung disease.

Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.

Animals↗

Circulating immune complexes in recurrent polyserositis. (Familial mediterranean fever, periodic disease).

Increased levels of circulating immune complexes (CIC) were demonstrated by the Clq binding assay in 22 (27%) out of 81 patients with recurrent polyserositis. The prevalence of increased CIC was significantly higher in Jewish patients of North African origin (42%) than in subjects of other ethnic groups (6%). North African patients also manifested an increased familial incidence, earlier onset of symptoms and a higher frequency of arthritis. There was no correlation between increased CIC levels and disease activity. These findings suggest that the immune response of North African patients differs from that of subjects of other ethnic groups and that this difference is possibly genetically determined.

Adolescent↗

Circulating immune complexes in patients with rheumatoid arthritis: correlation with disease activity.

Circulating immune complexes (CIC) have been detected in the majority of patients with rheumatoid arthritis (RA). Their usefulness in monitoring disease activity is still controversial. Thirty-five patients with RA have been studied for the presence of CIC by the C1q binding assay. Abnormally high levels of CIC were detected in 83% of the patients and in 76% of 46 serum samples. Mean C1q binding activity for all serum samples was 27.4 +/- 25 compared to 7.5 /+- 2% in a control group of healthy individuals. A highly significant correlation was observed between C1q binding activity and the following indices of disease activity: the erythrocyte sedimentation rate, the latex and Rose-Waaler tests and a systemic index. The level of CIC in RA patients seems to be a reliable index of disease activity.

Antigen-Antibody Complex↗