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Biomedical subjects

B Weil

Publications and source records attributed to B Weil.

At least 55 records · Page 3Linked to original sources

Long-term cyclosporin A therapy for severe idiopathic membranous nephropathy.

Fifteen patients with nephrotic idiopathic membranous nephropathy (MN) with predictors of poor outcome were treated with a long cyclosporin A (CyA) regimen at the dose of 4-5 mg/kg/day for a median period of 15 months (range 12-30). Four of the 15 patients did not respond to CyA, and the therapy was discontinued after 4 months. A partial remission (proteinuria < 2 g/day) was observed in 7 of 15 patients and a complete remission (proteinuria < 0.2 g/day) in 4 of 15 patients; good results (partial+complete remission) were, thus, obtained in 11 of 15 patients (73%). Two patients are still receiving therapy. A relapse of the nephrotic syndrome occurred in 3 of 9 patients on withdrawal of CyA, but the relapse remained sensitive to CyA. Side effects were mild. We conclude that CyA may be efficient in the treatment of MN and should be evaluated in controlled trials.

Adult↗

Proteinuria selectivity index--prognostic value in lipoid nephrosis and related diseases.

In order to predict the steroid response in lipoid nephrosis (LN), we studied age, sex, proteinuria level, histological features and proteinuria selectivity index (SI; ratio between IgG and transferrin clearances) in 52 LN cases (minimal-change disease: n = 39; focal glomerulosclerosis+IgM nephropathy: n = 13). The multivariate analysis showed that age, sex and proteinuria level were not contributive, whereas histology and SI were. The predictive value of SI was much higher than that of histological type (McFadden's r2: 47% vs. 22%, p < 0.001). Thus, SI should be systemically assessed in idiopathic nephrotic syndrome for reviewing the pathologic classification obtained by histology. However, if its prognostic value is lower than that of selectivity, initial renal biopsy remains necessary for diagnosis in adults.

Adolescent↗

Absence of correlation between graft-versus-host associated immunosuppression and cytotoxic T cell activity in response to major histocompatibility antigens.

Studies in mice suggest that the T cell subset involved in graft-versus-host-reaction (GvHR) across the major histocompatibility complex (MHC) depends on the class of MHC antigens recognized by the donor cells. However, the correlation between phenotype and function is not absolute. Using a functional approach, we investigated in a parent --> F1 hybrid model differing at the whole MHC, whether graft-versus-host (GvH) associated immunosuppression was correlated with donor cytotoxic T cell activity. The immunodeficiency was tested by the ability of the F1 mice to generate a cytotoxic T cell response against trinitrophenyl-modified syngeic cells (TNF-self) or an alloantigen. F1 specific parental cytotoxic T cells, generated in vitro, induced less immunosuppression than naive parental cells. Specific in vivo priming increased the cytotoxicity of parental spleen cells, but decreased their capacity to induce GvH-associated immunosuppression. In contrast, nonspecific priming resulted in the usual immunodeficiency. In conclusion, there was no correlation between GvH-associated immunosuppression and cytotoxic T cell activity of the parental cells.

Animals↗

Monoclonal immunoglobulins in patients with renal transplants: characterization, evolution and risk factors.

Gammopathies were found to be present in 25 (13%) of 192 HIV-negative renal transplant recipients with more than 30 months follow-up prospectively investigated for monoclonal or oligoclonal immunoglobulins (mIg) by agarose gel electrophoresis and immunofixation. Eleven patients had only one monoclonal band, whereas 14 had two or more bands. Of these bands, 60% were IgG kappa, 29% IgG lambda and 11% IgM lambda or kappa, and 90% did not exceed 2 g/l. Most gammopathies occurred early post-transplant (median 5 months) and they were always transient. Some predisposing factors for mIg emergence could be identified: 1. age, but only in women, 2. duration of dialysis, 3. occurrence of prior cytomegalovirus infection, and 4. immunosuppressive regimen including cyclosporine. Serological evidence for active EBV infection was obtained in ten patients, but in six cases infection occurred subsequent to the finding of mIg. In eight patients, the clinical course was characterised by severe infection or tumours (one Kaposi's sarcoma, one B-cell brain lymphoma). The present findings and experimental studies support the view that the development of mIg in renal transplant patients is associated with a failure of regulatory T-cell function. This T-B-cell imbalance requires a careful follow-up in these patients.

Antibodies, Monoclonal↗

Secretory IgA are elevated in both saliva and serum of patients with various types of primary glomerulonephritis.

Secretory immunoglobulin A (IgA) was determined by means of an enzyme-linked immunosorbent assay (using as capture antibody an MoAb specific for secretory component) in saliva and serum from 46 patients with IgA mesangial nephritis (IgAGN), 36 with an idiopathic nephrotic syndrome (INS), 30 with an idiopathic membranous nephropathy (MGN) and 40 healthy controls. Secretory IgA levels were elevated in both saliva and serum of patients with primary glomerulonephritis (P < 0.05; Mann-Whitney test) regardless of the histological type of the primary glomerulonephritis. Salivary IgA1 and IgA2 levels were increased in the saliva of patients with IgAGN, INS and MGN (P < 0.05; Mann-Whitney test). The monomeric/total IgA ratio, and interferon-gamma and soluble IL-2 receptor levels, in saliva did not differ between the patients and controls (P > 0.05; Mann-Whitney test). We conclude that the mucosal immune system is activated in forms of glomerulonephritis other than IgAGN.

Glomerulonephritis↗

Asymptomatic renal-vein thrombosis in adult nephrotic syndrome ultrasonography and urinary fibrin-fibrinogen products: a prospective study.

OBJECTIVES: The diagnosis of renal vein thrombosis (RVT), a frequent complication of adult nephrotic syndrome (NS), is generally made by means of invasive methods, i.e. renal venography, venous time of renal arteriography and, more recently, computed tomography (CT). We undertook a prospective study to evaluate the use of Doppler ultrasonography (DUS) and urinary fibrin-fibrinogen degradation products (FDPU) for the diagnosis of asymptomatic RVT. METHODS: Thirty-one adult NS with non proliferative glomerulonephritis were studied. Reference procedures [(selective renal arteriography (n = 18) and renal vein CT (n = 13)] were performed blindly within a few days (48 hours in 17 patients) of renal vein DUS (search for a lack of venous flow) and measurement of FDPU (5 micrograms/min) (in 24 patients). RESULTS: DUS was not interpretable in one patient and positive in nine. Of these 9 patients, RVT was detected by reference methods in only two (sensitivity: 1, specificity: 0.75; positive predictive value: 0.22; negative predictive value: 1). Increased FDPU was observed in 4 patients, 2 of whom had an RVT (sensitivity: 1, specificity: 0.9; positive predictive value: 0.5; negative predictive value: 1). CONCLUSION: We conclude that DUS and FDPU are helpful for screening of RVT in asymptomatic NS patients; their negativity allow further radiological investigations to be avoided while positive results must be confirmed by reference methods.

Adolescent↗

[Immune deficiency associated with experimental graft-versus-host reaction. Lack of correlation with T-cell cytotoxic activity].

Graft-versus-host reactions (GvHR) are initiated by T lymphocytes. In mice, the T cell subset involved depends on the incompatibility for minor or major histocompatibility antigens between donor and host. However, the correlation between phenotype and function is not absolute, and anti-host cytotoxic T cells can be detected in recipients without GvHR. We have presently investigated in a P----F1 model differing at the MHC, whether GvH associated immunosuppression was correlated with donor cytotoxic T cell activity. The immunodeficiency was tested by the ability of the F1 mice to generate a cytotoxic T cell response against TNP self or an alloantigen. F1 specific parental cytotoxic T cells generated in vitro induced less immunosuppression than naive parental spleen cells. Specific in vivo priming increased the cytotoxicity of parental spleen cells, but decreased their capacity to induce GvH associated immunosuppression. In contrast, non specific priming resulted the usual immunodeficiency. Spleens of the F1 mice injected with specific cytotoxic T cells were very enlarged, suggesting that these cells remained capable of inducing a GvHR without generating immunosuppression.

Animals↗

Na(+)-dependent succinate uptake in Corynebacterium glutamicum.

Succinate is effectively taken up by washed cells of Corynebacterium glutamicum. The apparent Km value of uptake is about 150 microM and the Vmax 4-7 nmol (mg dry weight)-1 min-1 and uptake can be competetively inhibited by fumarate and oxaloacetate. The activation energy was determined to be 50 kJ/mol. The transport activity is clearly dependent on the presence of Na+ ions in the incubation medium and on the membrane potential and has a pH optimum around 8.5. It is concluded that succinate is taken up in C. glutamicum via a specific carrier by a secondary active, Na+ coupled mechanism.

Binding, Competitive↗

Mucosal immunity in primary glomerulonephritis: II. Study of the serum IgA subclass repertoire to food and airborne antigens.

IgA specific for 7 food and 6 airborne antigens were sought in the serum of 30 adult patients with IgA mesangial nephropathy (IgA GN), 23 with membranous nephropathy (MGN), 20 with idiopathic nephrotic syndrome (INS), 11 with membranoproliferative GN (MPGN) and 22 healthy controls by means of an enzyme-linked immunoassay. The IgA subclass was determined using monoclonal antibodies. Increased levels of IgA specific for gliadin, bovine serum albumin (BSA), ovalbumin, lysozyme and alpha-lactalbumin were found in IgA GN, while increased levels of IgA to BSA, ovalbumin, lysozyme and alpha-lactalbumin were observed in MGN; IgA specific for alpha-lactalbumin were increased in INS, and MPGN patients had reduced levels of IgA to BSA and increased levels of IgA to beta-lactoglobulin and alpha-lactalbumin. These specific IgA to food antigens were restricted to the IgA1 subclass. Patients with IgA GN had significantly increased levels of IgA specific for Dermatophagoides pteronyssinus (DP) and Dactil while the MGN group showed increased levels of IgA specific for DP, feathers, Dactil and mold. INS patients had increased levels of IgA specific for DP, feathers, Dactil, mold and dog hairs, while MPGN patients had increased levels of IgA specific for feathers, Dactil, dog hairs and mold. All these specific IgA to airborne antigens were restricted to the IgA1 subclass. Patients with the four types of primary glomerulonephritis had decreased IgA specific for cat hairs which were of both the IgA1 and IgA2 subclasses. We conclude that anomalies of the IgA repertoire to environmental antigens are also encountered in primary glomerulonephritis other than IgA GN.

Adult↗

Mucosal immunity in adult primary glomerulonephritis. I. Evaluation of salivary IgA subclasses and components.

Salivary components (proteins, albumin, IgA1, IgA2, IgG, IgM, beta 2-microglobulin, neopterin and peroxidase) were investigated in 3 adult types of primary glomerulonephritis (PGN): IgA mesangial glomerulonephritis (IgAGN; n = 14); idiopathic membranous glomerulonephritis (n = 8); idiopathic nephrotic syndrome (INS; n = 14), and a control group (n = 11). Salivary IgA1 levels were significantly increased in all these PGN whereas salivary IgA2 levels were only higher than controls in INS. Albumin and proteins did not differ between PGN and controls, while the IgA1 + IgA2/protein ratio was significantly increased in these 3 PGN. Salivary neopterin levels were enhanced in the 3 types of PGN, whereas beta 2-microglobulin levels were not. The other salivary components did not differ from controls. These results demonstrate the nonspecificity of the IgA increase at mucosal sites previously found in IgAGN and raise the hypothesis of an activation of mucosal immunity of PGN or of a disturbed isotypic network or lymphokine secretion in these diseases.

Adult↗