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N Hinglais

Publications and source records attributed to N Hinglais.

At least 19 recordsLinked to original sources
PubMed1991

Experimental gold-induced autoimmunity.

The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.

Animals↗
PubMed1990

Expression of CR1 (CD35) mRNA in podocytes from adult and fetal human kidneys.

The presence of CR1 mRNA in podocytes was investigated using a 35S-labeled CR1 cDNA probe and in situ hybridization in sections from fetal and adult human kidneys. CR1 mRNA was only detected in immature podocytes at early stages of glomerular differentiation in the fetal kidney. In contrast, CR1 antigen was abundantly expressed on immature and mature podocytes in fetal kidneys and adult glomeruli. Thus, the expression of the CR1 gene in podocytes is tightly regulated. It is possible that the prolonged life span of adult podocytes is associated with a slow turnover of CR1 and low or intermittent accumulation of CR1 mRNA transcripts.

DNA Probes↗
PubMed1990

Adverse effects of sucrose-rich diets on uraemic rats.

The nature of carbohydrate may affect the tolerance and progression of uraemia. The effects of three diets differing only in their carbohydrate source: namely corn starch (C), glucose (G) or sucrose (S) were examined. Study 1 examined the effects of the three carbohydrate diets on unilaterally nephrectomised control rats and severely uraemic rats. The three carbohydrates produced similar nutritional effects in uninephrectomised rats, whereas sucrose rapidly induced anorexia, stunting and slightly accelerated renal damage in uraemia. Study 2 examined the long-term effects of the three carbohydrates in moderate uraemia under conditions of high and identical carbohydrate intakes. Hyperphagic Zucker uraemic rats (F rats) received a daily allotment of each diet plus pure carbohydrate. Lean uraemic rats (L rats) received the same dietary allotment without the carbohydrate supplement. The F rats fed sucrose showed greater morbidity and mortality but little renal deterioration. Their plasma triglycerides increased dramatically. The L rats fed sucrose had the greatest urinary protein, the least creatinine clearance and the most severe renal damage. Thus, sucrose-rich but not glucose-rich diets have two adverse effects in uraemia: a deterioration in nutritional status, perhaps related to abnormal fructose utilisation, and a long-term effect on the kidney, resulting in accelerated renal deterioration.

Animals↗
PubMed1989

Immunohistochemical localization of S protein/vitronectin in human atherosclerotic versus arteriosclerotic arteries.

The localization of S-protein/Vitronectin as deposits in arterial lesions and as a component of extracellular matrices was investigated by indirect immunofluorescence in ten atherosclerotic samples of carotid endarterectomy compared with ten arteriosclerotic temporal biopsies. Anti-C5b-9 neoantigens, anti-C3, anti-C3d, anti-H, anti-IgG and anti-IgM antibodies were applied on serial sections. In the atherosclerotic plaque, S-protein deposits were observed as irregular granules and spots in the fibrous cap and the internal part of the media at the vicinity of the plaque; they inconstantly colocalized with C5b-9 neoantigens. When present the SC5b-9 complexes were generally associated with cell remnants in the sclerotic matrix. In the temporal artery biopsies, S-protein was bound exclusively to the internal elastic lamina in association with C3d, but was absent from the intimal fibrous thickening. S-protein was not detected as a diffuse component of the extra-cellular matrix of either musculo-elastic or muscular medias, but was clearly demonstrated in smaller arteries; this result suggests a differential distribution of S-protein along the arterial tree.

Arteries↗
PubMed1989

Immunological approach to blockade of the renin-substrate reaction.

To block the renin-substrate reaction by immunological tools is a long-standing dream. Since 1951 active immunization and the passive transfer of antirenin antisera have been successfully carried out in different species and in different experimental models of hypertension and normotension. These studies indicated that renin is a powerful immunogenic protein, capable of breaking down self-tolerance in different species. In this initial period the most significant results were obtained with hog renin. Passive transfer of antisera raised against hog renin or active immunization with hog renin was able to decrease blood pressure in renovascular or essential hypertension in dogs. Renin was semipurified and injected without adjuvant, however, since there was no method for determining plasma renin activity. Recently, complete purification of murine and human renin has allowed an extension of this approach, using the passive transfer of antirenin polyclonal antisera or monoclonal antibodies. Active immunization against pure human renin was successful in normotensive marmosets. This immunization with a nearly homologous renin in a primate model induced a significant decrease in blood pressure, associated with a complete disappearance of plasma renin activity. Unfortunately this powerful immunization was associated with an autoimmune disease that is specific for the kidney, related to self-recognition of the production site of renin by antibodies and lymphocytes. Similar results were reported with the use of mouse submandibular gland renin as an immunogen in spontaneously hypertensive rats (SHR). This manipulation decreased blood pressure in SHR to a level near that of normotensive Wistar-Kyoto control rats. However, again the animals showed a severe autoimmune disease of the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Immunohistochemical study of complement S protein (Vitronectin) in normal and diseased human kidneys: relationship to neoantigens of the C5b-9 terminal complex.

The localization of S protein (Vitronectin) antigen was studied by indirect immunofluorescence and immunoelectron microscopy in normal adult human kidneys and in biopsy specimens from patients with a wide range of renal diseases, and compared with that of neoantigens of the C5b-9 terminal complement complex. S protein antigen was diffusely present in arteriolar perimyocytic matrices, the glomerular basement membrane and mesangial matrix, and tubular basement membranes in the cortex of normal and diseased kidneys without superimposable staining for C5b-9 neoantigens. Cell remnants embedded in normal and sclerotic extracellular matrices expressed S protein antigen and also stained for C5b-9 neoantigens. Several lines of evidence suggested that S protein present in connective matrices most likely represents S protein or C5b-9 complexes trapped from the circulation. Glomerular immune deposits and arteriolar hyalin deposits which contained C5b-9 neoantigens also contained S protein antigen in the same location. In a few specimens from patients with membranous nephritis stage I and IgA nephropathy, immune deposits contained neither detectable C5b-9 neoantigens nor S protein. The observed strong co-staining of immune deposits for S-protein and C5b-9 caution against the generalization that C5b-9 within glomerular immune deposits represent membrane-bound cytolytic complement complexes.

Adult↗
PubMed1989

Human liver Kupffer cells express CR1, CR3, and CR4 complement receptor antigens. An immunohistochemical study.

The expression of complement receptor antigens by human Kupffer cells (KC) was investigated by immunohistochemical techniques in seven normal human liver biopsies. Polyclonal and monoclonal antibodies were revealed by double labeling of cells using indirect immunofluorescence and immunoenzymatic techniques or by using double immunoenzymatic techniques. In most experiments, one antigen was revealed by streptavidin-biotin-peroxidase complexes whose reaction product was examined by light microscopy and the second antigen stained using the alkaline phosphatase antialkaline phosphatase method visualized by fluorescence microscopy using fluorescein isothiocyanate or tetramethylrhodamine isothiocyanate filters. KC were identified using monoclonal antibody EBM11 that recognizes 100% of KC in hepatic lobules and was paired with each antibody directed against complement receptors. CR1 and CR3 (alpha- and beta-chains) were found to be the predominant receptor antigens expressed by human KC. CR4 (p150,95) was expressed on all KC, but staining with anti-CR4 monoclonal antibodies was consistently weaker than that observed with anti-CR3 antibodies. No staining of KC was observed with anti-CR2 (CD 21) antibodies. Expression of CR1, CR3, and CR4 complement receptors on KC provides the cells with an optimal capacity to bind and phagocytize particles or immune complexes coated with any type of ligands for C3 receptors.

Antibodies, Monoclonal↗
PubMed1988

Immunopathological findings in idiopathic nephrosis: clinical significance of glomerular "immune deposits".

Idiopathic nephrosis (IN), which includes minimal change (MCD), diffuse mesangial proliferation (DMP) and focal segmental glomerular sclerosis (FSGS), is classically characterized by the absence of significant deposits by immunofluorescence microscopy (IF), except for the focal lesions of segmental sclerosis and/or hyalinosis of FSGS, which fix IgM and C3 antiserums. Since IF is available in most centres, an increasing number of unexpected findings has been reported. In order to evaluate the clinical significance of the glomerular deposits revealed by IF in some instances, we reviewed the renal biopsy findings of 222 consecutive children presenting with IN and in whom IF microscopy was available. By light microscopy, 122 patients showed MCD, 10 DMP, and 90 FSGS with DMP (11 cases) or without (79 cases). By IF, 125 specimens were negative and served as controls; 54 showed mesangial IgM deposits, 24 mesangial IgG deposits (associated with Clq deposits in 16), 15 scattered granules of C3 and 4 predominant deposits of mesangial IgA. We correlated these findings with initial response to steroid therapy and outcome and could find no significant difference between the various categories defined by IF and the control group. Repeat biopsies, performed in 21 cases, showed the persistence of deposits in 11 and their transformation in 10. The particular problem raised by the patients who present with IN and mesangial IgA deposits is discussed. Our results demonstrate that patients presenting with IN and "positive IF", whether showing IgM, IgG and Clq, C3 or IgA, do not represent distinct clinicopathological entities.

Child↗
PubMed1988

Treatment of the childhood haemolytic uraemic syndrome with plasma. A multicentre randomized controlled trial. The French Society of Paediatric Nephrology.

Seventy-nine children with haemolytic uraemic syndrome (mean age 28 months) were randomly assigned either to a group receiving plasma infusions (plasma group, n = 39) or to a group treated conservatively (control group, n = 40). The duration of haemolysis, thrombocytopenia and anuria was similar in the two groups. Serum creatinine levels were similar in the two groups at the 1-month follow-up but were higher in the control group at 3 months (plasma group 49 +/- 14, control group 66 +/- 28 mumol/l; P less than 0.02) and at 6 months (plasma group 48 +/- 13, control group 63 +/- 21 mumol/l; P less than 0.005). The prevalence of proteinuria was also higher in the control group at the 6-month follow-up (plasma group 17%, control group 46%; P less than 0.02). However, differences were no longer significant after 1 year. Renal tissue was examined in 54 cases (plasma group, n = 27; control group, n = 27). Diffuse cortical necrosis was present in 7 cases in the control group but was absent in the plasma group (P less than 0.02). Taking into consideration the higher serum creatinine levels, the higher prevalence of proteinuria during the first 6 months of follow-up in the control group and the presence of diffuse cortical necrosis in this group compared with the plasma group, we conclude that plasma infusions should be regarded as beneficial. Further study is needed to determine which plasma fraction is involved.

Adolescent↗
PubMed1988

Distinct phenotypic composition of diffuse interstitial and perivascular focal infiltrates in renal allografts: a morphometric analysis of cellular infiltration under conventional immunosuppressive therapy and under cyclosporine A.

Phenotypic analysis of interstitial mononuclear cell infiltrates was undertaken in 40 transplant renal specimens obtained from 38 patients in order to assess the influence of immunosuppressive therapy. Thirteen patients were given conventional immunosuppressive treatment (azathioprine and prednisone) and the other 25 received cyclosporine. The immunostaining was performed using seven antileucocyte antibodies by alkaline phosphatase-anti-alkaline phosphatase method. Interstitial infiltrates were distributed in two patterns: diffuse infiltrates and periglomerular/perivascular aggregates. The phenotypic composition was distinct in these two patterns: in diffuse infiltrates, monocytes/macrophages (EBM 11) represented the predominant inflammatory cell and were associated with a minor component of T cells (T 11). In contrast, aggregates had a major T lymphocyte phenotype in addition with few foci of B cells. T4 subset of T lymphocytes always predominated over T8 subset. The repartition and the proportion of each cell type were not significantly different in rejecting and not rejecting grafts and were not affected by the immunosuppressive regimen.

Administration, Oral↗
PubMed1988

De novo membranous glomerulonephritis in renal allografts in children.

The incidence of de novo membranous glomerulonephritis (MGN) in transplanted kidneys is around 1 to 2%. In our series, of the 310 grafts that were examined by immunofluorescence microscopy (IF), 29 (9.3%) showed subepithelial IgG deposits, a pattern consistent with the diagnosis of MGN. Transplant biopsy had been performed because of the occurrence of proteinuria in 8 patients (pts), for suspected rejection in 16 and systematically in the remaining 9 who had no proteinuria and a normal renal function. In all cases the lesions were identified by IF and were confirmed by electron microscopy (EM) in 14 pts. Granular deposits of IgG were diffuse in 22 cases and segmental in 7. Sequential specimens were available in 17 pts and showed the persistence or the increase of the IgG deposits in all patients but one in whom they had disappeared. Age at transplantation (Tx) ranged from 2 years 3 months to 16 years. Grafts were from cadaveric donors in 27 pts and from living related donors in 2 pts. In none of the recipients was MGN the nephropathy of the native kidneys. With a follow-up of 18 to 74 months, 6 pts never developed a proteinuria. In the remaining 23, proteinuria developed 1 to 70 months after Tx, associated with a nephrotic syndrome (NS) in 6 pts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Cyclosporin in the treatment of idiopathic nephrotic syndrome in children.

Thirty-five children (12 girls, 23 boys), aged from 1 year and 5 months to 14 years at the onset of idiopathic nephrotic syndrome, received cyclosporin A (CyA) because of steroid toxicity or failure to respond to steroids. The initial oral dose was 6 mg/kg per day and this was adjusted to obtain trough plasma levels of 50-150 ng/ml. The duration of treatment was between 2 and 8 months. In patients who responded to CyA treatment, the dosage was tapered off; treatment was stopped if found to be ineffective. Of the 35 children, 20 were frequent-relapsing steroid responders who suffered serious side-effects from steroid therapy. Seventeen of them either went into remission or did not relapse despite the withdrawal of prednisone. Prednisone doses could be lowered but not stopped in 1 patient and the remaining 2 patients relapsed when prednisone was tapered off. At the final examination, 10 of the 12 children in whom CyA was tapered off and who had initially responded to CyA had relapsed. A second course was given to these 10 patients and 3 failed to respond. Five children were partial steroid responders and CyA induced a remission in 1 and a partial remission in another. Among the 10 children who were steroid resistant, only 1 responded to CyA, 2 had a partial response and 7 failed to respond to CyA. A reduction of glomerular filtration rate occurred in 8 patients, 7 of whom had either persistent nephrotic syndrome or were in relapse, which suggests that factors other than CyA nephrotoxicity may have been operative. Complete reversal occurred in only 4 patients. Significant histological changes, likely to be related to CyA, were seen in 2 repeat renal biopsies out of the 11 performed.

Child↗
PubMed1987

Ontogenesis of angiotensin-I converting enzyme in human kidney.

The kidney distribution of angiotensin-I converting enzyme (ACE) was studied in 14 fetuses (11 to 30 weeks old) and 7 children (2 days to 13 years old) by immunohistochemistry using specific antibodies to human kidney ACE. Immunohistochemical techniques included indirect immunofluorescence on cryostat sections of frozen tissue, immunoperoxidase and immunofluorescence of fixed tissue embedded in Paraplast, and immunoelectron microscopy. The ACE distribution in the fetal kidneys was independent of the age of the fetus. ACE was detected in two locations: 1) on the basolateral membranes and primary apical microvilli of epithelial cells from early differentiating proximal tubules; the labeling was intense in brush borders of fully developed proximal tubules; and 2) on glomerular endothelial cells; cells were lined by reaction product as soon as capillaries invaded the inferior cleft of the S-shaped body. Tubular ACE distribution was identical in the postnatal kidneys. The staining of the glomerular endothelium was extremely inconstant. The presence of ACE in proximal tubular cells and glomerular endothelial cells at the beginning of nephron differentiation may indicate that it is involved in the development of nephron function and renal hemodynamic.

Adolescent↗
PubMed1986

Angiotensin I converting enzyme in human intestine and kidney. Ultrastructural immunohistochemical localization.

The localization of immunoreactive angiotensin I-converting enzyme (ACE) has been investigated at the optical and ultrastructural level with anti-human ACE antibodies in the human kidney and small intestine. In both tissues ACE was found in blood vessels and in extravascular situation in the absorptive epithelial cells of intestinal mucosa and renal proximal tubules. Ultrastructural immunohistochemistry showed that in intestinal and renal proximal tubular cells ACE was prominent in microvilli and brush borders. In the kidney ACE was also present on the basolateral part of the plasmalemmal membrane, where it may contribute to the regulation of angiotensin II-dependent absorption processes. Intracellular positivities were also observed inside the renal vascular endothelial and proximal tubular cell in endoplasmic reticulum and nuclear envelope reflecting the synthesis and the cellular processing of ACE. The intestinal microvascular endothelium was strongly labeled suggesting that the mesenteric circulation is an important site for the production of angiotensin II. Vascular endothelial ACE was also detected in the peritubular but not glomerular capillaries of the kidney.

Antibodies↗
PubMed1986

Immunohistochemical analysis of C3 cleavage fragments, factor H, and the C5b-9 terminal complex of complement in de novo membranous glomerulonephritis occurring in patients with renal transplant.

Fifteen renal biopsies from 13 transplanted patients with de novo membranous nephropathy (DNMN) were investigated by immunofluorescence for the presence of C5b-9 neoantigens of the terminal sequence of complement and for antigens expressed by C3 cleavage fragments. DNMN lesions were classified as stage I, II or III upon light and electron microscopy examination. Seven biopsies were classified as stage I DNMN and 8 stage II-III. All patients were proteinuric. In six biopsies with stage I DNMN, staining for C5b-9 neoantigens was restricted to a fine granular labeling in mesangial areas which was analogous to that seen in normal kidneys in contrast with extensive parietal labeling for IgG, C3d and factor H antigens. In eight biopsies with stage II-III DNMN, the pattern of staining with anti-C5b-9 neoantigens antibodies was similar to that obtained with anti-IgG, anti-C3d and anti-factor H antibodies. These results suggest that in situ activation of the whole complement sequence throughout C5b-9 only occurs on large immune deposits (stage II-III DNMN).

Adolescent↗