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L H Noel

Publications and source records attributed to L H Noel.

At least 19 recordsLinked to original sources
PubMed1992

Determination of anti-neutrophil cytoplasm antibodies (ANCA) specificity by immunofluorescence on chronic myelocytic leukemia cells.

ANCA positive sera, detected by the standard immunofluorescence method, derived from 37 patients with vasculitis were studied using formalin-acetone fixed chronic myelocytic leukemia cells (CML). All 37 sera were positive on CML cell smears. Furthermore formalin-actone fixation selectively impaired antinuclear antibody binding without reducing ANCA staining and thus facilitated differentiation of these autoantibodies which is often difficult with the standard immunofluorescence method. Two unequivocal and mutually exclusive ANCA binding patterns were identified using the CML smears: (1) type I with diffuse granular binding confined to the polymorphonuclear (PMN) cell lineage and preferentially staining immature cells; (2) type II with similar binding to the PMN cell lineage and, in addition, granular staining of the basophils. All type I antibodies were associated with a c-ANCA pattern suggesting that the major antigen recognized by these antibodies, recently identified as proteinase 3, is not detectable in basophils. The type II pattern was detected in both p-ANCA (84%) and c-ANCA (16%) positive sera. The type I sera remained positive on PMN cells from a myeloperoxidase (MPO) deficient subject and anti-MPO antibodies could not be detected in this group by ELISA. Conversely the type II pattern occurred in the presence of anti-MPO antibodies identified by immunofluorescence, ELISA and dot-blot with the exception of a single serum with antilactoferrin antibody. Type I binding only was observed in Wegener's granulomatosis (WG) but both patterns were found in microscopic polyarteritis (MPA) and rapidly progressive glomerulonephritis (RPGN).

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Antineutrophil cytoplasmic antibodies in IgA nephropathy and Henoch-Schönlein purpura.

The frequency, isotype, and specificity of antineutrophil cytoplasmic antibodies were investigated in a cross-sectional study of 100 patients with IgA nephropathy and 30 children with Henoch-Schönlein purpura. Two of the patients with IgA nephropathy had high titres of antineutrophil cytoplasmic antibodies which were of IgG isotype and confirmed as antimyeloperoxidase antibodies in solid-phase ELISA and inhibition experiments. Antineutrophil cytoplasmic antibodies were not detected in the children with Henoch-Schönlein purpura and none of the patients in either group had IgA antineutrophil cytoplasmic antibodies. A further 20 IgA nephropathy and 10 Henoch-Schönlein purpura patients were studied longitudinally in different clinical phases at 4-monthly intervals over a 2-year period. None of these patients had or developed antineutrophil cytoplasmic antibodies. We conclude that IgA antineutrophil cytoplasmic antibodies are not involved in the vasculitis of Henoch-Schönlein purpura or in the pathogenesis of glomerular injury in IgA nephropathy. The detection of IgG antimyeloperoxidase antibodies in a small minority of IgA nephropathy patients extends the spectrum of diseases associated with autoimmunity to this antigen but is of uncertain significance.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1991

[Necrotizing extracapillary glomerulonephritis without immunoglobulin deposits. Renal localization of systemic vasculitis with anti-cytoplasm polynuclear antibodies].

Necrotizing and crescentic glomerulonephritis without immunoglobulin deposits (also called pauci-immune glomerulonephritis) is the cause of approximately 50 percent of acute renal failures of glomerular origin. Our study, based on 40 case-records selected on histological criteria, and on data from the literature, shows that in most cases, if not all, this type of glomerulonephritis is part of a wider systemic vasculitis which predominantly affects the glomerular capillaries. Anti-neutrophil cytoplasm antibodies are detected in three-quarters of the cases, with a specific distribution that varies according to the clinical features. In spite of the patients' age (mean: 62 years), the severity of glomerular lesions and the extra-renal diffusion of the disease, 60 percent of these patients can be cured and recover a normal, or at least acceptable renal function, provided the corticosteroid and sometimes immunosuppressive therapy is initiated at an early stage.

Adolescent↗
PubMed1991

Kidney biopsy findings in cyclosporine-treated patients with insulin-dependent diabetes mellitus.

Renal biopsy specimens of 40 patients with recent-onset insulin-dependent diabetes mellitus treated with cyclosporine (CSA) for 6-29 months were examined. Cyclosporine-associated chronic vascular interstitial toxicity of moderate intensity was found in 10 patients (25%). The most prominent lesions were interstitial fibrosis and tubular atrophy. Arteriolopathy was less pronounced and glomerular damage unremarkable. A significant correlation exists between the extent of tubular atrophy and CSA trough whole blood levels. These data indicate that the development of CSA-associated chronic nephropathy is dose-dependent.

Adolescent↗
PubMed1991

Differential in situ expression of cytokines in renal allograft rejection.

The expression of the interleukin 6, tumor necrosis factor alpha, and interferon gamma (IFN-gamma) genes was studied in human renal biopsies from individuals without evidence of kidney disease and from patients undergoing acute renal allograft rejection using a method of in situ hybridization capable of detecting 1-5 copies of a specific cellular messenger RNA in individual cells. IL-6, TNF-alpha, and IFN-gamma RNA transcripts were not detected in any of the sections of normal human kidneys. Elevated levels of IL-6 mRNA but not IFN-gamma were, however, detected in the sections of the renal biopsies from six of eight patients exhibiting acute rejection. A uniform level of expression of IL-6 mRNA was observed in all the cells examined, including glomerular cells, tubular epithelia, smooth muscle cells, and vascular endothelia, as well as the interstitial mononuclear infiltrate. Juxtatabular clusters of TNF-alpha mRNA were detected in the absence of IL-6 mRNA in one patient exhibiting acute rejection. Only a small number of grains (1-5 per high-power field) was detected in the urinary space or in the tubular or vascular lumen following hybridization with the IL-6 or TNF-alpha probes. In contrast, in kidney transplant patients with stable renal function no significant labeling was observed with the IL-6, TNF-alpha, or IFN-gamma probes. A similar level of expression of actin mRNA was observed in all the sections of normal and transplanted kidneys studied, suggesting that the overall level of RNA synthesis was similar in both groups. These results suggest that cytokines such as IL-6 play a role in acute allograft rejection.

Cytokines↗
PubMed1991

[Longitudinal study of histocompatibility antigen expression in renal transplants followed for 10 years].

Using monoclonal antibodies against class I and class II (DR antigen) major histocompatibility complex antigens, 65 renal transplant biopsies from 21 recipients whose renal transplants survived ten years or more were studied. Seven biopsies were performed while acute rejection of the renal transplant was under way. The other biopsies were carried out on a routine basis, 6 months (10 biopsies), 2 years (15 biopsies), 4 years (12 biopsies), and 10 years (21 biopsies) after transplantation. Semiquantitative evaluation of fibrous tubulointerstitial lesions was carried out on the biopsies taken after ten years. During episodes of acute rejection, strong expression of class I and class II HLA molecules by transplant tubule epithelial cells was found. When there was no acute rejection, tubule expression of class I and class II HLA molecules was more common in earlier biopsies as compared with later biopsies. In the long-term, persistence of DR antigen in tubule epithelium was associated with increased severity of fibrous tubulointerstitial lesions. A last remarkable finding in some patients was loss of expression of class I antigens in tubule cells from transplants with the longest survivals.

Adolescent↗
PubMed1990

Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation.

In vivo injection of the hamster anti-murine CD3 monoclonal antibody 145 2C11 into BALB/c mice induces a massive systemic release of several cytokines. Very high circulating levels of tumor necrosis factor are detected both by enzyme-linked immunosorbent assay and L-929 bioassay 90 min following a single injection of 10 micrograms/mouse 145 2C11. Peak circulating levels of exclusively T cell-derived products such as interferon-gamma, interleukin 2 and interleukin 3 are also detected 90 min to 8 h post-injection. Importantly, this cytokine release is transient since none of these cytokines are still present 12 to 24 h post-injection. In parallel to cytokine release, 145 2C11-treated mice (10 micrograms/mouse) exhibit somnolence, hypomotility (quantified by actimetry), hypothermia, diarrhea and piloerection. At this dosage, the physical reaction is not lethal and reverses in all mice by 48 h post-injection. Severe but again reversible anatomopathological changes are also observed: massive cellular depletion, necrosis and edema of lymphoid organs, leakage syndrome and inflammatory cell infiltrates of the lung, cell vacuolization, necrosis and vascular congestion of the liver. All these data are similar to the clinical and immunological manifestations of the OKT3-induced reaction in patients and, thus, provide an invaluable experimental tool to study its mechanisms and explore its prevention.

Animals↗
PubMed1990

Systemic AA amyloidosis induced by liver cell adenoma.

Systemic AA amyloidosis is a rare complication of benign tumours. This report describes a patient with hepatocellular adenoma associated with reactive AA amyloidosis. He had a nephrotic syndrome with deteriorating renal function and an increase of serum concentrations of acute phase proteins, mainly C-reactive protein. Resection of the tumour was followed by improvement in renal function and a marked decrease of the serum concentrations of acute phase proteins.

Amyloidosis↗
PubMed1990

The OKT3 immunosuppressive effect. In situ antigenic modulation of human graft-infiltrating T cells.

OKT3 exerts its in vivo immunosuppressive effects by inducing major peripheral T cell depletion as well as antigenic modulation of the T3/Ti T cell receptor complex. Modulated cells, which reversibly lose the expression of the CD3 T cell receptor molecular complex but still share the CD4 and CD8 antigens, have been shown to be functionally immunoincompetent. Antigenic modulation is maintained as long as significant OKT3 serum levels are present. Cells infiltrating renal allografts from seven OKT3 treated patients were studied by double immunofluorescence to assess whether antigenic modulation could affect cells located in profound organs such as renal allografts. Needle biopsies were obtained in patients given OKT3 (5 mg/day) for at least 10 consecutive days in association with conventional immunosuppressive drugs for treatment of a rejection episode (5 cases) or prophylactically (2 cases). In all patients at the time of biopsy, CD3 positive cells were absent from the circulation, significant OKT3 serum levels were present, and neither IgG nor IgM anti-OKT3 antibodies were detected. Infiltrating cells were double-labeled using a combination of either anti-CD3 and anti-CD4 or anti-CD3 and anti-CD8 monoclonal antibodies. Following 7-14 consecutive days of treatment, all patients given OKT3 for a rejection episode showed a significant decrease in the number of graft-infiltrating lymphocytes. Importantly, all T cells still infiltrating the allograft were CD3-CD4+ or CD3-CD8+ cells, which is exactly the same phenotypical pattern of CD3 circulating modulated T cells. In 6 out of the 7 patients, this phenotypical pattern was associated with clinically normal graft function. These results further underline the fact that antigenic modulation is an important mechanism mediating the immunosuppressive effect of OKT3 both in peripheral blood and in renal allografts.

Antibodies, Monoclonal↗