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Biomedical subjects

C Leroy

Publications and source records attributed to C Leroy.

At least 73 records · Page 4Linked to original sources

Adhesive properties of human erythroblastic precursor cells.

Interactions between hematopoietic precursor cells and their surrounding marrow environment are essential for hematopoietic differentiation. These occur in part through the production of regulatory molecules by marrow stromal cells and their local concentration by components of the extracellular matrix (ECM), but direct cell-cell or cell-matrix contacts are likely to also play an essential role. During the past several years, we have characterized the adhesive properties of human hematopoietic precursor cells on two substrates, marrow fibroblastic ECM and purified plasma fibronectin (Fn). We have shown that adhesion to marrow ECM and Fn was a selective property of erythroblastic cells and was expressed by normal erythroblastic progenitors (CFU-E and BFU-E), as well as by erythroleukemic cell lines (K 562), but only by a small proportion of CFU-GM. Furthermore, attachment to Fn was very precisely regulated during erythroblastic differentiation as shown by the loss of Fn-adhesion in reticulocytes derived from purified immature erythroblasts induced to differentiate in vitro. The physiological relevance of these results is not well understood, but we speculate that adhesion to ECM components helps stem cells to locate in a favorable environment, and that loss of this property in reticulocytes is required before they cross the marrow-blood barrier.

Cell Adhesion↗

Loss of attachment to fibronectin with terminal human erythroid differentiation.

Human erythroblastic progenitors (colony-forming unit-erythroid [CFU-E] and burst-forming unit-erythroid [BFU-E]) have been shown to attach to fibronectin (Fn), a property that might be involved in the local regulation of erythropoiesis. In this study, we have investigated changes in cell attachment to Fn upon terminal erythroid differentiation. We first purified CFU-E from human marrow by avidin-biotin immune rosetting. This negative selection procedure yielded a cell population containing approximately 80% blasts that, after characterization by colony-assays and electron microscopy, appeared to consist of CFU-E (10% to 15%) and their immediate progeny (85% to 90%), here defined as "preproerythroblasts." In the presence of erythropoietin, purified cells differentiated into reticulocytes in 7 to 10 days. Cell attachment to Fn was inversely correlated to the stage of differentiation of the erythroid cell: more than 50% of the CFU-E population reproducibly adhered to Fn, whereas at most 30% of the preproerythroblasts had the same capacity. Adhesion was further lost at late maturation stages, and a constant finding was the inability of reticulocytes to adhere to Fn. Finally, CFU-E adhesion to Fn was blocked by polyclonal lgG raised against the Fn receptor and by a monoclonal antibody against VLA-5. These results demonstrate that adhesion to Fn is developmentally regulated during normal human erythropoiesis. Restriction of its expression to CFU-E and its first divisions strikingly correlates with the migratory capacity of these cells.

Antibodies↗

[Primary open-angle glaucoma. Effects of an eyedrop combining timolol and pilocarpine on the ocular pressure].

In a limited group of open angle glaucoma patients treated twice daily with timoptol 0.5% and having by this treatment a mean intra-ocular pressure of 21-22 mmHg, the association of timoptol 0.5% with pilocarpine 2% respectively, lowered the intra-ocular pressure to an average of 17.8 mmHg and 16.6 mmHg after one and three weeks of continuous treatment. For this study, the patients have been divided into 3 groups: A group treated with timoptol 0.5% alone throughout the 49 days of the study. A group treated with timoptol 0.5%-pilocarpine 2% (timpilo 2) from day 21 to day 49. A final group treated with timoptol 0.5% until day 21 and then with timoptol 0.5%-pilocarpine 4% (timpilo 4) through out day 49. These patients stopped the treatment before the end of the study. Intra-ocular pressures were measured on days 0, 21 and 49. We found a higher drop of pressure (-4.8 mmHg) in the timpilo 2 group than in the timoptol 0.5% group (-1 mmHg) before instillation as well as 2 hours afterwards (-5.25 mmHg and -2 mmHg respectively). The secondary local effects were due to miotics agents. The secondary systemic effects were those inherent to beta-blockers. These results are comparable with a multicentric study of 220 patients, therefore statistically significant.

Aged↗

[Atypical heart transplantation. Technical considerations. Apropos of a case].

A heterotopic heart transplantation was performed on a patient placed on circulatory assistance with a Biomedicus pump for ten days using a heart taken from a donor with situs inversus. In relation to this case, the authors describe the technical procedures allowing transplantation of a heart obtained from a donor with situs inversus into a heterotopic position and an orthotopic position or a normal heart in a recipient with situs inversus. Lastly, in the case of complex cardiac malformations with preservation of the lungs, they present the procedures allowing heart transplantation in cases of situs incertus, anomalies of venous return and transposition of the great vessels.

Adult↗

Granulopoietic differentiation in long-term bone marrow cultures from children with congenital neutropenia.

The capacity of granulopoietic precursor cells (CFU-GM) to differentiate in vitro was evaluated in five children with congenital neutropenia using short-term colony assays and long-term marrow cultures. In all five children, methylcellulose assays revealed normal numbers of CFU-GM, which displayed an appropriate response to various sources of GM-CSF and differentiated up to the polymorphonuclear leukocyte state (PMN). In contrast, neutrophil PMN were not observed in long-term bone marrow cultures from three patients, despite a normal production of CFU-GM, myeloblasts, and promyelocytes during the 5-6 week culture period. Thus, in these patients, the characteristic "block" in granulocytic maturation observed in vivo was reproduced in vitro in long-term cultures. Granulocytic differentiation proceeded normally in long-term cultures from the two other patients, thus indicating heterogeneity in the expression of the defect. These results might indicate abnormal interactions between stromal and hematopoietic cells in long-term marrow cultures from some patients with congenital neutropenia. Furthermore, our results showed some correlation between the granulocytic defect in vitro and the clinical outcome in vivo.

Agranulocytosis↗

Lineage- and stage-specific adhesion of human hematopoietic progenitor cells to extracellular matrices from marrow fibroblasts.

Local regulation of hematopoietic differentiation in the marrow requires close interactions with components of the microenvironment. In this study, we explored the capacity of human marrow hematopoietic progenitor cells to adhere in vitro to the extracellular matrix (ECM) secreted by human marrow fibroblasts. When marrow mononuclear cells were incubated on ECM-coated dishes, all types of progenitors adhered to this substrate through an active process requiring divalent cations and serum factors. The proportion of erythropoietic progenitors attached to ECM in two hours was at least twofold higher than that of granulopoietic progenitors. Moreover, in the erythroid lineage, the capacity to adhere to ECM increased with the degree of differentiation of the progenitor: 28% of CFU-E adhered to ECM as compared with 13% of immature BFU-E. Thus, ECM-mediated adherence varied both with the cell lineage and the maturation stage of the progenitor. Purified fibronectin could substitute for ECM in the adhesion assay, and ECM-mediated adhesion of CFU-E and BFU-E was partially inhibited by a polyclonal antifibronectin antibody, which implies that fibronectin may be one ECM component involved in progenitor cell adhesion. Incomplete inhibition of progenitor adhesion to ECM by the antifibronectin antibody, however, as well as the lower proportion of precursors attaching to purified fibronectin as compared with ECM suggest that other matrix molecules may also mediate erythroid progenitors attachment to ECM. These observations support the idea that hematopoietic progenitor cells may regulate their differentiation in part through the modulation of adhesive interactions with a number of constituents of the microenvironment.

Cell Adhesion↗

Circulating activities during constant infusion of heparin or a low molecular weight derivative (enoxaparine): failure to demonstrate any circadian variations.

We compared in six patients successively treated with an unfractionated heparin (UFH) and a low molecular weight heparin (LMWH) the variations in plasma anti-Xa activity, measured in a chromogenic assay, during a 36 h constant infusion. The values varied in a wider range during UHF infusion, but remained in the therapeutic range except once in one patient. No circadian rhythm could be demonstrated in our six patients. LMWH infusion yielded very constant anti-Xa circulating activities. In both cases, there were no significant modifications of three proteins with high heparin affinity (antithrombin III, heparin cofactor II, histidine-rich glycoprotein). Our results suggest that the circadian rhythm of the biological activities previously observed in patients treated with constant heparin infusion using clotting method is due to other factors than heparin itself.

Adult↗

Taurine supplementation of a premature formula improves fat absorption in preterm infants.

The predominance of taurine (Tau) conjugated over glycine conjugated bile acids in infants fed human milk as opposed to those on formulas without added Tau could account for a more complete absorption of fat. Fifteen low birth weight infants were randomized to either Enfamil Premature or to Enfamil Premature added with 40 mumol/dl of Tau and compared to a third group made up of nine low birth weight infants fed their own mother's preterm milk. Formulas and human milk were fed according to tolerance and constituted the sole nutrition for 3 months. A metabolic study was carried out at 3 wk of age and control of growth was done periodically. Urinary Tau excretion (mumol/dl) was very low (p less than 0.001) in the group fed Enfamil Premature (0.3 +/- 0.1) when compared to the values obtained in infants supplemented with Tau (51.6 +/- 12.5) and in those on human milk (36.3 +/- 7.9). Infants supplemented with Tau (92.5 +/- 1.2) had a coefficient of fat absorption which was higher (p less than 0.05) than the unsupplemented group (87.5 +/- 7.9) and comparable to the human milk-fed group (91.6 +/- 1.4). The effect was more pronounced on the saturated fatty acids and varied inversely with their individual water solubility. There was no effect of Tau on nitrogen retention and growth was identical in the three groups. These data show that the addition of Tau to formula had no effect on growth but improved the absorption of fat especially saturated fatty acids which require higher concentrations of bile acids to form mixed micelles.

Absorption↗

[When the psychiatric hospital "sleeps"...].

This paper is the conclusion of a study on nursing's transactions during the night, in a mental hospital. It is demonstrated that therapeutical premises and nursing attitudes are defined by the position of the nurse into the institutional structure. It is also demonstrated that medical prescription doesn't depend exclusively of clinical criteria but it also cares for keeping institutional order.

France↗

[The microenvironment and hematopoiesis].

Successive steps in hematopoietic differentiation occur in the bone marrow in close contact with non hematopoietic components of the microenvironment. The crucial importance of these interactions in the regulation of early hematopoietic events has been convincingly demonstrated in vivo in the mutated steel mouse, and confirmed more recently in vitro in long-term cultures. Parts of the signal mediating these interactions are represented by locally secreted CSF-like growth factors or more recently characterized inhibitors of proliferation. more importantly however appears to be direct cell-cell communication, especially in the regulation of erythropoiesis and recent data suggest that specific adhesion processes might be required initially. As neoplastic clonal dominance is usually not maintained in vitro, experimental evidence for the involvement of the microenvironment in the regulation of leukemic hemopoiesis is still pending. However, it has been shown recently that in some conditions stromal cells may be manipulated in vitro and alter growth properties of leukemic cells. Understanding mechanisms regulating the interactions between hematopoietic and stromal cells may be of considerable importance since it should be possible to delineate and subsequently modulate in vitro the factors affecting stem cell properties. This might lead to alternative therapeutic strategy.

Animals↗

Taurine improves the absorption of a fat meal in patients with cystic fibrosis.

The effect of taurine supplementation on the absorption of a fat meal was evaluated in patients with cystic fibrosis. In a cross-over design study, five patients with cystic fibrosis (12.1 +/- 2.6 years of age) and three control subjects received either placebo or taurine (30 mg/kg/d) for two 1-week periods, a month apart, followed by a fat meal test. Blood samples were drawn 0, 1, 2, 3, 5, 8 hours after the meal. Four patients with cystic fibrosis and severe steatorrhea despite appropriate enzyme therapy showed a significant (P less than .05) improvement in the absorption of triglycerides, total fatty acids, and linoleic acid while receiving taurine supplements. Three control subjects and one child with cystic fibrosis and mild steatorrhea receiving enzyme therapy did not experience such an effect. The difference in triglyceride absorption, when calculated as the area under the curve, receiving and not receiving taurine was significantly (P less than .05) correlated with the degree of steatorrhea. Furthermore, in contrast to control subjects, the fatty acid composition of chylomicrons in these four study patients showed important discrepancies with that of the fat meal and was corrected, in part, by taurine supplementation. These results suggest that taurine supplementation could be a useful adjunct in the management of patients with cystic fibrosis with ongoing fat malabsorption and essential fatty acid deficiency.

Adult↗

Effect of dietary fat and residues on fecal loss of sterols and on their microbial degradation in cystic fibrosis.

Although various etiologic factors have been implicated, the mechanism responsible for bile acid malabsorption in CF remains unknown. Eight CF children studied twice on a normal diet supplemented with pancreatic enzymes and once during a one-month period of Vivonex administered by continuous nasogastric infusion were compared to age-matched controls. On the fat and residue-free elemental diet, there was a modest decrease in steatorrhea and no change in the daily excretion of nitrogen and neutral sterols. However, normalization of bile acid output (485.6 +/- 65.0 to 160.6 +/- 29.2 mg/24 hr) to control levels (150.2 +/- 60.7) was noted. Diminished microbial degradation of both neutral and acidic sterols and a smaller amount of bile acids adsorbed to decreased residues were also found. The data do not support the possibility of a bile acid ileal transport defect and suggest that the most important single factor responsible for the intraluminal sequestration of bile acids in CF is dietary residues. Because of significant ongoing losses of nitrogen and lipids, pancreatic enzymes should be given to CF patients on elemental diets.

Bile Acids and Salts↗