One HLA haplo-identical transfusion in first renal allograft recipients: effect on alloimmunisation, acute rejection episodes, and graft survival.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Zaoui.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In addition to azurophil and specific granules, a third storage compartment is known to exist in the neutrophils. This compartment which consists of morphologically heterogeneous particles is characterized by a high specific activity in gelatinase. A gelatinase enriched fraction was prepared by subcellular fractionation of neutrophil homogenates using rate zonal centrifugation. This fraction was enriched in diamine oxidase. Among the proteins released from the neutrophils upon stimulation by formyl peptides, those belonging to the gelatinase enriched fraction were determined after removal of the proteins from specific and azurophil granules by selective immunoadsorption. Gelatinase was recovered together with tetranectin, beta 2-microglobulin and diamine oxidase in the same fraction. Differences in the kinetics of release of gelatinase and diamine oxidase versus vitamin B-12-binding protein suggest that the proteins belong to distinct subcellular structures.
The immune response requires the coordinated release of a network of cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF), and IL-2. The potential role of the dialysis membrane on the elaboration of these cytokines by peripheral blood mononuclear cells (PBMNC) harvested from hemodialysis patients was investigated in a prospective crossover study. Eight hemodialysis patients, chronically dialyzed with a biocompatible membrane, were sequentially dialyzed for 2 wk with new cuprophane membranes (Phase I), 2 wk with a low-flux, low-complement-activating membrane (Phase II), and then switched back for a further 2 wk of dialysis with a cuprophane membrane (Phase III). At the end of 2 wk of exposure to the cuprophane membrane, during both Phase I and Phase III, the ability of PBMNC to elaborate IL-1 beta, tumor necrosis factor-alpha, and IL-2, as well as soluble IL-2 receptors, in response to phytohemagglutinin was significantly reduced compared with their respective levels at the beginning of the phase; dialysis with a biocompatible membrane increased these levels, and at the end of 2 wk, the response of the PBMNC to phytohemagglutinin was close to that in normal controls. These findings may explain some of the conflicting results in the measurement of cytokine levels in hemodialysis patients and may have clinical implications.
Secreted gelatinase from human neutrophils was purified as a 94 kDa polypeptide. Gelatinolytic and type IV collagenolytic activities of the purified protein were measured and compared. Immunoglobulins purified from antisera raised against gelatinase inhibited both the gelatinase and type IV collagenase activities. There was no cross-reaction in the inhibition with type I collagenase while the three metalloproteases were similarly inhibited by recombinant tissue inhibitor of metalloproteases. Purified gelatinase degraded denatured type I and native type IV collagens; there was no proteolysis of native type I collagen.
Natural killer (NK) cells are specific peripheral blood lymphocytes which are involved in the lysis of malignant and virally transformed cells. In a prospective study of eight hemodialysis patients, we investigated the effects of recurrent exposure to the cuprophane (CU) membrane on the number and functional ability of NK cells, against both their classical in vitro target, K562 cell line, as well as the beta 2m/HLA negative cells that emerge during dialysis with CU membrane. The percent of NK cells, defined by the CD56 epitope, increased from 27.7 +/- 7.9% of cells at baseline to 59.2 +/- 12.0% after two weeks of dialysis with new CU membrane (P < 0.01). The ability of these cells to lyse K562 cells decreased from 28.7 +/- 16.5% at baseline to 12.5 +/- 6.2% (P < 0.001) after two weeks of dialysis with CU membrane, while their cytotoxicity against beta 2m negative cells increased during the same period from 32.5 +/- 12.4% to 61.3 +/- 23.7% (P < 0.001). These results are consistent with the observation that the cytolytic ability of NK cells is inversely related to target cell expression of HLA antigens and beta 2m expression on cell surfaces. In addition, the results of these studies confirm in vitro observations of the decrease in cytolytic activity of the NK cells when exposed to the CU membrane, and may explain the emergence of these beta 2m/HLA negative cells during dialysis with CU membrane. It is possible that these observations may also have a clinical relevance to the immune defects and increased incidence of malignancy in uremia.
Explore the source record for details and available documents.
Hemodialysis with first-use cellulosic dialysis membranes results in activation of the alternative pathway of complement and profound neutropenia followed by rebound leukocytosis. The neutropenia has been shown to be associated with increased expression of adhesion receptors and pulmonary sequestration of granulocytes. However, the mechanism underlying the return of the granulocytes has not been elucidated. We determined simultaneously the changes in the granulocyte adhesion receptor MAC-1 (CD11b-CD18) and the selectin LAM-1 receptor during dialysis using a complement activating and a non-complement activating membrane, in a randomized, cross-over study. With initiation of dialysis with cellulosic membranes, there was a rapid and prominent increase in the expression of MAC-1 receptors. At the nadir of granulocyte count, 15 minutes after initiation of dialysis with the complement activating membrane, there was a four-fold increase in the MAC-1 receptor expression. At the same time, there was a two-fold decrease in LAM-1 expression. There were no changes in the expression of two other granulocyte receptors CD11a and CD15 which are known not to be modulated during granulocyte activation. Granulocytes harvested during dialysis and which had high MAC-1 and low LAM-1 expression had a significantly decreased adherence to endothelial cell monolayers. Dialysis of the same patients with non-complement activating membranes resulted in no significant change in the expression of these receptors on granulocytes nor in their adherence to endothelial cells. These results shed new light on the mechanism of the cyclical granulocytopenia and rebound granulocytosis during dialysis with new cellulosic membranes.
Chronic dialysis patients have several indices of immune deficiency. We examined the hypothesis that the biocompatibility of dialysis membranes may influence the ability of lymphocytes to express interleukin-2 (IL-2) receptors on their surface, a key event in cellular immune response. We investigated the potential role of the dialysis membrane in eight chronic hemodialysis patients. The study design was a cross-over study using cuprophane and polymethylmethacrylate (PMMA) membranes. Chronic dialysis with new cuprophane membrane leads to an increase in baseline expression of the two subunits of IL-2 receptors. IL2R alpha (p55, CD25) and IL-2R beta (p70), in peripheral blood mononuclear cell (PBMC). However, Phytohemagglutinin (PHA) stimulation of PBMC harvested after two weeks of dialysis with cuprophane membrane showed a markedly decreased expression of high affinity IL-2 receptors. These findings are reversed when patients were dialyzed with a PMMA membrane which is also associated with minimal complement activation. The increased expression of IL-2 receptor subunits are reproduced in vitro by direct contact of PBMC with cuprophane membrane and by the addition of the anaphylatoxin C5a. This study confirms the participation of lymphocytes in the complex blood-membrane interactions that occurs during dialysis; the results may be relevant to observations of immune deficiency in dialysis patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
90% of the injected dose of succinylcholine is hydrolysed by serum cholinesterase (E.C.3.I.I.8) Abnormal variants of serum cholinesterase lead to prolonged apnea. This report presents the results of 62 serum cholinesterase phenotyping including 12 cases of prolonged apneas. One clinical case of prolonged apnea in a patient homozygous for the atypical cholinesterase gene is presented with a study of his genealogy. The phenotypes were established on the basis of dibucaïne, fluorure, chloride and propranolol differential inhibition. The frequency and significance of the various phenotypes is discussed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The zinc metalloproteinases (MMPs or matrixins) are capable of damaging most of the constituents of the extra-cellular matrix and the basement membrane. The matrix proteolysis is the result of an imbalance both in the turnover of these constituants and in the ratio of the tissue inhibitors of metalloproteinases (TIMPs) versus metalloproteinases. After a brief description of the nature and structure of MMPs and TIMPs, this article reports on recent progress concerning the intra and extra-cellular activation mechanisms of proenzymes (proMMPs) which bring into play a series of proteolytic activations involving different proteinase families. Two points are stressed: 1) the main sites of focalized matrix proteolysis regulation, illustrated in the cellular interaction of inflammation, and 2) the wide phenotypic variety of MMPs and TIMPs.