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D Nochy

Publications and source records attributed to D Nochy.

At least 19 recordsLinked to original sources
PubMed1998

Podocytes undergo phenotypic changes and express macrophagic-associated markers in idiopathic collapsing glomerulopathy.

Collapsing glomerulopathy (CG), a severe form of focal segmental glomerulosclerosis (FSG), is characterized by tuft retraction and consolidation in numerous glomeruli and changes in podocyte morphology and topography. Other glomeruli are less affected. Collapsing glomerulopathy is also characterized by tubulointerstitial atrophy and fibrosis. The pathophysiology of the glomerular and tubulointerstitial lesions is poorly understood. We studied renal tissue of five Black and three White patients, all human immuno-deficiency virus (HIV) negative, with nephrotic syndrome, renal failure, and histological evidence of CG. Immunohistochemistry identified normal podocyte phenotypes by podocalyxin, vimentin and complement receptor 1 (CR1) labeling. Three monoclonal antibodies were used to further characterize podocyte epitopes: anti-CD68 clone KP1, anti-CD68 clone PG-M1 and anti-M130 clone M18 (Ber-MAC3). Light microscopy of collapsed glomeruli showed podocyte swelling, vacuolization, multinucleation, "cobblestone-like" alignment around the glomerular tuft, and pseudo-crescent formation in Bowman's space. In collapsed glomeruli, podocalyxin, vimentin and CR1 labeling tagged both normal and vacuolated podocytes still attached to the GBM, but labeling was not found in cobblestone-like podocytes or in podocytes detached from the GBM. Conversely, numerous podocytes undergoing detachment and shedding into Bowman's space expressed macrophagic-associated epitopes. Cells with macrophagic-associated epitopes clumped in cystically dilated tubules and were aligned in tubules of smaller caliber. Their appearance was that of viable cells. There was no morphologic indication that these cells expressing macrophage-associated antigens originated from outside the glomeruli or outside the tubules. We conclude that in CG podocytes detach from the GBM, lose their normal podocytic phenotype and acquire macrophage differentiation antigens. The presence of cells with such antigens in tubular lumens suggests that detached metaplastic podocytes progress along the tubule or, alternatively, that CG tubular cells also undergo metaplastic changes into macrophage-like cells.

Adult↗
PubMed1997

Ex vivo lung model of pig-to-human hyperacute xenograft rejection.

OBJECTIVE: Our objective was to study lung hyperacute rejection in the pig-to-human xenotransplantation combination. METHODS: Pig lungs were harvested and continuously ventilated and perfused ex vivo, using a neonatal oxygenating system, with either xenogeneic unmodified human blood (n = 6) or autogeneic pig blood (n = 6). RESULTS: Autoperfused lungs displayed normal hemodynamics, oxygen extraction (arteriovenous oxygen difference), and histologic characteristics throughout the 3-hour study period. By contrast, xenoperfused lungs displayed, within 30 minutes, severe pulmonary hypertension and abolishment of arteriovenous oxygen difference culminating in massive pulmonary edema, hemorrhage, and lung failure after 115 +/- 44.2 minutes of reperfusion. Within 30 minutes, the human blood showed a significant drop of anti-alpha Gal immunoglobulin M and G xenoreactive antibodies (enzyme-linked immunosorbent assay) and complement activity, consumption of clotting factors, and hemolysis; total circulating human immunoglobulins remained substantially normal. Histologically, lungs perfused with human blood were congestive and showed alveolar edema and hemorrhage and multiple fibrin and platelet thrombi obstructing the small pulmonary vessels (arterioles, capillaries, and venules) but not large (segmental or lobar) pulmonary vessels. On immunohistologic examination, deposits of human immunoglobulin M and complement (C1q and C3) proteins were observed on the alveolar capillaries. CONCLUSIONS: This pig-to-human xenograft model suggests that the pig lung perfused with human blood has an early and violent hyperacute rejection that results in irreversible pulmonary dysfunction and failure within approximately 150 minutes of reperfusion.

Acute Disease↗
PubMed1997

[Pefloxacin as a first-line treatment for nephrotic syndrome in minimal glomerular lesions in the adult. Multicenter study of 32 patients].

Minimal change nephrotic syndrome (MCNS) is the most frequent single cause of nephrotic syndrome occurring both in adults and children. Although it appears to be a self-limiting disorder (10% spontaneous remissions within the fortnight following the initial flare), MCNS displays a high rate of complications during the nephrotic period (10 to 15% cases) and prompts one to treat patients as early as possible. Corticosteroids are currently used as first-line treatment. A 16 weeks full-dose steroid course (1 mg/kg/day) usually induces remission in 75% MCNS in adults. Nevertheless, duration of treatment (9 months) and occurrence of relapses despite a slowly tapering dosage schedule, expose patients to steroids side-effects. Immunosuppressive drugs are recommended in case of steroid resistance and their side-effects are not harmless. Therefore, an alternative to steroids or immunosuppressives would lend a serious helping hand in MCNS management. The present work is dealing with pefloxacin efficacy in 40% MCNS in adults. Thirty-two MCNS adult patients were treated in a national multicenter study. A short-duration pefloxacin course (4 to 6 weeks) allowed partial or complete remission in 13 out of 32 cases. Thus far, this effect was undescribed for this class of drugs. Pefloxacin belongs to antibacterial agents of the fluoroquinolone family and is active against Gram negative Enterobacteria species. Fluoroquinolones also act on eukaryotic cells as lymphocytes and chondrocytes and alter IL2, gamma IFN and integrin expression. Although their precise mode of action is unknown in this kind of immunological disorder, fluoroquinolones might represent an alternative to steroids in some adult form of MCNS. However, predictive criteria for sensitivity to fluoroquinolones are currently not available and further controlled studies would be helpful using fluoroquinolones as first-line treatment in all the MCNS.

Adolescent↗
PubMed1997

[Etiologic aspects of nephrotic syndrome in Black African adults in a hospital setting in Abidjan].

We studied nephrotic patients hospitalised in internal medicine service at Treichville Teaching hospital from September 1986 to February 1993 for precising the aetiological aspects of black adult patients and their evolutive biological, clinical and epidemiological profile. Secondary Nephrotic syndrome represented 18% of the whole patients with Nephrotic syndrome hospitalised during the same period. In aetiological field it was about: diabetic nephropathy 11 cases (33%); lupus nephritis 7 cases (21%); renal amyloidosis 5 cases (15%); HIV nephropathy 5 cases (15%); schistosomiasis nephrotic syndrome 1 case (3%); pregnancy nephrotic syndrome 1 case (3%); cryoglobulinemia 1 case (3%); malignancy nephrotic syndrome 1 case (3%); nephrosclerosis 1 case (3%).

Acquired Immunodeficiency Syndrome↗
PubMed1996

Improvement of postischemic renal function by limitation of initial reperfusion pressure.

PURPOSE: This study was designed to determine whether lowering the initial reperfusion pressure can improve renal function after ischemia. MATERIALS AND DESIGN: Sixty minutes of warm renal ischemia was induced in 2 groups of 8 minipigs by clamping the left renal artery. Right kidneys were kept in situ as controls. In the standard reperfusion group, ischemic kidneys were immediately reperfused at systemic pressure. In the controlled reperfusion group, the renal artery reperfusion pressure was maintained at 60 mm. Hg for the initial 20 minutes of reperfusion by use of a regulating pump and then at systemic pressure for the next 100 minutes. RESULTS: On the basis of the postischemic anuria rate, glomerular filtration rate and renal histology, renal tolerance to ischemia was significantly improved in the controlled reperfusion group. CONCLUSION: These findings of improved renal function recovery after warm ischemia by controlled low reperfusion pressure may have clinical relevance to the reperfusion technique used after renal transplantation in humans.

Animals↗
PubMed1996

[Amyloidosis: definition and classification].

Amyloidoses are diseases characterized by deposits of altered proteins in the tissues. The amyloid deposit is always extracellular and presents a fibrillary conformation. 85% of the amyloid protein is constituted of a specific protein of each variety of amyloidosis, while the other 15% consists of other proteins and glycoproteins common to all types of amyloidosis. The same amyloid protein can be associated with various clinical forms and, inversely, different proteins can give the same clinical expression. It is therefore preferable to adopt a biochemical classification of amyloidosis. This classification is based on the identification of the various amyloid proteins by immunohistochemical analysis. About fifteen different amyloid proteins have already been identified. Hereditary amyloidoses are the most heterogeneous forms and amyloidoses of the nervous system are still under investigation. Immunohistochemical analysis of the majority of amyloidoses (represented by amyloidosis AA and AL) can now be performed routinely on tissue samples.

Amyloid↗
PubMed1996

[Cryoglobulinemia].

Cryoglobulinaemias contain seric immunoglobulins which precipitate at low temperatures in some tissues. Based on immunohistochemical analysis of their components (monoclonal or polyclonal), 3 types of cryoglobulinaemias have been identified, and a classification has been proposed. The presence of a paraprotein within the cryoglobulinaemia is due to the proliferation of B cells. Type I is mainly associated with a lymphoproliferative syndrome (myeloma and others...) whereas type II (mixed cryoglobulinaemia) and type III are the result of viral and bacterial infectious diseases, and of autoimmune diseases. Over the last few years, infection by hepatitis C has been found in more than 90% of types II and III cryoglobulinaemias. Cryoprecipitates are pathogenic for kidneys, skin and nervous tissues. In some organs, they are responsible for specific histological lesions, such as necrotizing angeitis with vascular microthrombosis. In kidneys, they occur as endocapillary proliferative glomerulonephrites, accompanied by precipitation of immunoglobulins in the form of intracapillary thrombi. Precipitated immunoglobulins can be identified on frozen specimens. Ultrastructural studies confirm the fibrillar aspect which is characteristic of the cryoprecipitate.

Cryoglobulinemia↗
PubMed1995

Sequential immunological targeting of chronic experimental arterial allograft.

Arterial wall is the main site involved in the chronic rejection process. The rat aortic allograft model was used here to characterize and describe the sequential evolution of the different targets and effectors of arterial wall immunological injury and response during arterial allograft rejection. Rat abdominal aortae were isografted or allografted from Brown-Norway to Lewis rats. Endothelial and smooth muscle cell injury and humoral and cellular immunological effectors were characterized from 0 to 60 days after transplantation using a battery of specific antibodies. The intimal proliferative response was also characterized over this time. Isografted Brown-Norway aorta adventitia had very few cellular components, which suggests that donor adventitia would be poorly antigenic in allografts. In contrast, allograft adventitia was the site of a major inflammatory cell invasion in which the expression of an adhesion molecule by colonizing capillary endothelial cells could play a main role. This adventitial infiltration continued as long as medial smooth muscle persisted. The luminal endothelial cells disappeared early, probably associated with macrophage margination. In contrast, medial smooth muscle cell disappearance occurred later and was specifically targeted by immunoglobulins. Intimal proliferation was the most delayed phenomenon, involving both inflammatory cell infiltration at an early stage and later myofibroblastic proliferation, and could be related to the specific expression of growth factors in this layer. The rat aortic allograft model appeared useful for characterizing specific targets and effectors of chronic arterial graft rejection, demonstrating an early stage of endothelial injury and the presence of immunoglobulins involved in chronic medial smooth muscle cell injury.

Animals↗
PubMed1995

Self-reactive anti-class II T helper type 2 cell lines derived from gold salt-injected rats trigger B cell polycolonal activation and transfer autoimmunity in CD8-depleted normal syngeneic recipients.

Brown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex-type glomerulonephritis in the context of a polyclonal B cell activation that was suspected to be due to the emergence of anti-self major histocompatibility complex (MHC) class II T cells. In the present study, six anti-self MHC class II T cell lines have been derived from six gold salt-treated rats by repeated stimulations with normal syngeneic MHC class II-bearing cells. The T cell lines proliferated in the presence of self MHC class II-positive B cell-enriched or B cell-depleted cells and the proliferation was inhibited by preincubating stimulator cells with an anti-IA monoclonal antibody. The T cell lines produced interleukin (IL)-4 only or IL-4 and some interferon (IFN)-gamma and could, therefore, be considered as T helper type 2 (Th2) and Th0 cells, respectively. They triggered normal syngeneic B cells to produce in vitro IgE, anti-DNA, anti-laminin and anti-2,4-6-trinitrophenol antibodies through, at least in part, cognate interactions. More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than the one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in serum IgE concentration and the production of anti-DNA and anti-laminin antibodies. In addition, all recipients displayed an autoimmune glomerulonephritis due to anti-laminin antibodies, granular IgG deposits in the interstitium, in the vessel walls and along the tubular basement membranes and a severe tubulointerstitial nephritis with marked mononuclear cell infiltration. An anti-ovalbumin T cell line that produced IL-4 and low amounts of IFN-gamma was used as a control and did not induce autoimmunity. These results demonstrate for the first time the ability of autoreactive Th2 as well as Th0 cell lines to induce antibody-mediated autoimmunity. They also show that CD8+ cells play a crucial role in the control of such autoreactive cells. Finally, this work suggests that Th2 cells could initiate cell-mediated reactions either directly or indirectly.

Animals↗
PubMed1995

Improvement of postischemic kidney function by reperfusion with a specifically developed solution (BT01).

Reperfusion is a critical phase of organ preservation. The purpose of this study was to develop a solution specifically for postischemic kidney reperfusion. Unilateral left normothermic kidney ischemia was induced for 60 minutes in two groups of micropigs. In group 1 (control pigs, n = 6) the kidney was reperfused immediately with pure blood at systemic pressure by unclamping the renal artery. In group 2 (test animals, n = 6) the kidney was initially reperfused with an intracellular flush solution enriched with solution BT01 composed of cytoprotectors (natriuretic factor, PGI2), free radical chelating agents (allopurinol, mannitol), and substrates for the mitochondrial respiratory chain (aspartate, glutamate). This solution was mixed immediately before use with blood in a ration of 1:4 parts and injected into the left renal artery with a perfuser at a constant pressure of 60 mm Hg. After 20 minutes, the kidney was reperfused with systemic blood for 100 minutes. Glomerular filtration rate (GFR) was determined by measuring inulin clearance. Kidney blood flow was measured throughout the experiment. After 120 minutes of reperfusion, the kidneys were removed for histologic examination. In the control pigs (group 1) 50% of the animals were anuric. The ratio between GFR measured in the left kidney at the end of perfusion and at equilibrium in the remaining animals was 0.16 +/- 0.01. In test animals (group 2) all animals recovered diuresis. The ratio between GFR measured in the left kidney at the end of perfusion and equilibrium was 0.51 +/- 0.12 (p < 0.001, group 2 vs. group 1). In group 2 postperfusion kidney blood flow was higher than in group 1 (63.0 ml/min vs. 27.4 ml/min; p < 0.05) because of a decrease in renal vascular resistance. Light microscopic examination of kidneys form animals in group 1 revealed tubular necrosis that extended to the parenchyma, with exposure of tubular interstitium. In group 2 only degenerative lesions with edema of tubular cells and disappearance of brush borders were observed. Our findings indicate that flushing the kidneys with BT01 solution mixed with blood improves postischemic kidney function by reducing reperfusion damage.

Animals↗
PubMed1995

Hemophagocytic histiocytosis (HH) in renal transplant recipients under ciclosporin therapy: report of the first two cases.

Hematophagocytic histiocytosis is a clinicopathologic syndrome associating fever, liver dysfunction, blood cytopenia and coagulation abnormalities with hematophagocytosis in bone marrow and lymphoïd organs. This syndrome is found in immunocompromized patients and is triggered by infection. We describe herein the first 2 cases of HH in renal transplant recipients treated with ciclosporin. In our 1st case, H.H. was not recognized early and the patient died. In the 2nd case, prompt diagnosis associated to an anti-infectious treatment led to recovery. The clinician must thus be aware of the possibility of such a syndrome in renal transplant patients. Identification and treatment of the underlying infection is mandatory to avoid a fatal outcome.

Adult↗