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Biomedical subjects

B Fouqueray

Publications and source records attributed to B Fouqueray.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Glomerular expression of tumor necrosis factor alpha (TNF-alpha) and of its receptors].

TNF alpha is generated in inflammatory lesions of the glomerulus. Both resident mesangial cells and infiltrating macrophages contribute to this generation, when exposed to bacterial lipopolysaccharide and immune complexes, respectively. TNF alpha has multiple actions on glomerular cells and on distant target cells that appear to promote in turn either amplification or limitation of TNF alpha release and TNF alpha binding. For instance, there is in vitro evidence that locally generated reactive oxygen metabolites: 1) cause increased release of TNF alpha into the extracellular space by accelerating the cleavage of its cell-associated precursor, and 2) reduce the expression of both cell-associated and soluble TNF alpha receptors. Thus it might be expected that reactive oxygen metabolites released at the site of glomerular inflammation limit autocrine, juxtacrine and paracrine effects of TNF alpha and simultaneously increase its widespread release into the circulation.

Humans↗
PubMed1993

Protection from tumor necrosis factor-mediated cytolysis by platelets.

Infiltrating macrophages elicit tumor-destructive reactions by releasing cytolytic factors including tumor necrosis factor alpha (TNF-alpha). Because platelets represent another major component of the cell infiltrate in tumors, we examined whether they could affect TNF alpha-induced cell death. Exposure of L-929 fibrosarcoma cells to human platelets reduced TNF alpha-induced cytotoxicity and cytolysis, as determined by 51Cr release assay and DNA fragmentation assay. This inhibitory effect, which depended on the concentration of platelets (0.1 to 10 x 10(6)/0.1 ml), was as high as 50%. The decrease in responsiveness to TNF-alpha reflected neither a degradation of TNF-alpha nor an inability of L-929 cells to bind TNF-alpha. Indeed, even though Scatchard analysis indicated the presence of 100 to 150 125I-TNF-alpha binding sites/platelet with a kd of 3.8 to 6.4 nM, addition of platelets up to 5 x 10(6)/0.1 ml did not compete with 125I-TNF-alpha binding to L-929 cells. Furthermore, addition of platelets 1 or 2 hours after that of TNF-alpha was still protective suggesting that platelets rather promoted hyporesponsiveness of L-929 cells to a postbinding effect of TNF-alpha Platelet-induced reduction of TNF-alpha response could be reproduced with supernatant fluids from platelets incubated at 37 degrees C for 24 hours. The platelet-derived factor responsible for this effect was found to be a lipid of low molecular weight with high affinity for albumin and charcoal. A role for 12(S) hydroxyeicosatetraenoic acid is proposed because this metabolite reduced TNF-alpha-induced cytolysis in a dose-dependent manner, whereas other platelet-derived lipids including thromboxane A2 and platelet activating factor were inactive. These observations indicate that the role of associated platelets has to be considered when analyzing the cytotoxic and cytolytic activity of macrophage-derived TNF-alpha on tumor cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Membrane expression and shedding of tumour necrosis factor receptors during activation of human blood monocytes: regulation by desferrioxamine.

Previous studies have shown that desferrioxamine (DFX), an iron chelator preventing the synthesis of hydroxyl radical (OH.), up-regulates the cell-surface expression of tumour necrosis factor-alpha (TNF-alpha) receptors on unactivated human blood monocytes. In the present study, we investigated the regulatory action of DFX on 125I-TNF-alpha binding to monocytes upon exposure to bacterial lipopolysaccharide (LPS). Exposure to LPS (1 microgram/ml) resulted in almost complete loss of 125I-TNF-alpha binding to the surface of monocytes. This down-regulation was reversible and the recovery observed after 18 hr was enhanced by addition of DFX (5 mM). However, binding studies on monocytes pre-exposed to low pH suggested that the DFX-induced increase of 125I-TNF-alpha binding was not due to differences in the number of receptors available but was probably due to a reduction of receptor occupancy by endogenously generated TNF-alpha. Time-course studies of TNF-alpha release from monocytes confirmed the ability of DFX to reduce the extracellular concentration of bioactive TNF-alpha through a decrease of its synthesis and an increase of its inactivation. The latter process was associated with an increased expression of the soluble form of TNF-alpha receptor type II. These results indicate that, in the presence of LPS, DFX increases the release of soluble TNF-alpha receptors from monocytes. Thus, conversely, OH. generated in situ could reduce the shedding of soluble TNF-alpha receptors and, hence, increase the widespread release of bioactive TNF-alpha.

Cell Membrane↗
PubMed1992

Heat shock prevents lipopolysaccharide-induced tumor necrosis factor-alpha synthesis by rat mononuclear phagocytes.

Tumor necrosis factor-alpha (TNF-alpha), a mononuclear phagocyte-derived peptide is known to participate in the pathogenesis of fever. To determine whether a feedback mechanism exists by which elevated temperatures influence TNF-alpha generation, we have examined the effects of heat shock on the in vitro synthesis of TNF-alpha by rat glomeruli, inflammatory peritoneal macrophages and blood monocytes. Preexposure of peritoneal macrophages to elevated temperatures for 20 min decreased the subsequent lipopolysaccharide-induced release of TNF-alpha bioactivity. The mean reductions were 11.9 +/- 5.0%, 86.3 +/- 12.0%, and 95.2 +/- 3.5% after pretreatment at 39, 41 and 43 degrees C, respectively. Reductions, that were transient, were maximum when lipopolysaccharide was added 0-2 h after heat shock. They correlated with the decreased release of immunoreactive TNF-alpha and the decreased expression of both cell-associated TNF-alpha molecule and TNF-alpha mRNA. Heat shock-induced inhibition of TNF-alpha release was independent of variations of prostaglandin synthesis, but was possibly related to the induction of heat-shock proteins since (a) macrophages exposed to heat shock synthesized the major 70- and 90-kDa heat-shock proteins, and (b) chemical inducers of the heat-shock response were also effective inhibitors of TNF-alpha release. The mean reduction of TNF-alpha release after pretreatment at 41 degrees C was found to be identical in glomerular tissue (82.0 +/- 7.5%), but significantly less in blood monocytes (43.9 +/- 10.9%). This supports the hypothesis that a negative-feedback mechanism exists between elevated temperature and lipopolysaccharide-induced TNF-alpha synthesis, and suggests that this regulation is less active in blood monocytes than in tissue macrophages.

Animals↗
PubMed1992

Up-regulation of tumour necrosis factor-alpha receptors on monocytes by desferrioxamine.

The effect of endogenously generated reactive oxygen metabolites on the interaction of human blood monocytes with tumour necrosis factor-alpha (TNF-alpha) was investigated. Pre-exposure of unactivated human blood monocytes to dimethylthiourea, a scavenger of hydroxyl radical (OH.), or to desferrioxamine (DFX), an iron chelator preventing the synthesis of OH., enhanced the specific binding of 125I-TNF-alpha to its receptors. Scavengers of superoxide anion or hydrogen peroxide were without effect. DFX-induced up-regulation of 125I-TNF-alpha binding depended on the concentration of the drug (1-5 mM) and on the duration of the treatment (1-18 h). It was not due to a reduction of receptor occupancy by endogenously generated TNF-alpha. Scatchard analysis of binding data revealed that DFX caused an approximately two-fold increase in the number of type II TNF-alpha receptors, with no change in their affinity. This up-regulation, that did not require synthesis of new proteins, was associated with a decrease in the internalization rate of TNF-alpha receptors, the half-life of which was doubled. Conversely, these findings suggest that OH. generation by monocytes may have a physiological role in reducing the activity of membrane-associated TNF-alpha receptors.

Binding, Competitive↗
PubMed1992

Reactive oxygen species as glomerular autacoids.

There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases.

Animals↗
PubMed1991

[Emphysematous pyelonephritis associated to urogenital tuberculosis].

Emphysematous pyelonephritis is a rare condition which in most cases occurs as a result of Escherichia coli infection of the urinary tract in patients known as being diabetic. The gas-filled abscesses carry a high mortality rate, especially when the antibiotic treatment is not combined with early surgery. We report a case where the failure of medical treatment led to curative nephrectomy. Unusually, diabetes was revealed by the pyelonephritis. Another particularity of this case was that the emphysematous pyelonephritis was associated with genitourinary tuberculosis. This association, of which no other example could be found in the literature, is discussed.

Adult↗
PubMed1991

Desferrioxamine regulates tumor necrosis factor release in mesangial cells.

Cultured rat mesangial cells have been demonstrated to express tumor necrosis factor alpha (TNF alpha) mRNA and to release TNF activity into the medium upon stimulation by bacterial lipopolysaccharide (LPS). The present study was undertaken to determine whether TNF was only secreted by mesangial cells or was also present as a cell-associated molecule. LPS-activated mesangial cells which had been fixed in paraformaldehyde lysed the TNF-sensitive L-929 fibroblasts, as assessed by 51Cr release. This cytotoxic activity was inhibited by anti-TNF alpha antiserum. Cell-associated TNF expression was demonstrable after less than one hour of exposure to LPS, peaked at two hours and decreased progressively thereafter, while TNF activity increased in the medium. Mesangial cell-associated TNF was localized at the cell surface, as shown by immunohistochemical demonstration and by the ability of plasma membranes purified from LPS-activated mesangial cells to lyse L-929 fibroblasts. Flow cytometry experiments revealed that two-thirds of LPS-activated mesangial cells were stained by anti-TNF alpha antiserum. The major part of these cell-associated TNF molecules persisted after low pH treatment, indicating that they were integral membrane proteins. As assessed by immunoprecipitation analysis, these proteins were 26 kDa molecules, whereas the released forms of TNF were 17 kDa molecules. Pretreatment of mesangial cells with desferrioxamine (DFX), an iron chelator preventing the synthesis of hydroxyl radicals (OH.), delayed the release of TNF from the membranes into the medium, and enhanced its cell surface expression. It also subsequently accelerated its decay in the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Hypercalcemia in blood diseases and cancers].

The clinical classification of malignant hypercalcaemias according to the presence or absence of bone lesions no longer corresponds to the physiopathology of these hypercalcaemias as it is known today. Both focal osteolysis and humoral hypercalcaemia involve a number of substances, such as prostaglandins, cytokines, growth factors, PTH-rp and calcitriol, the action of which is neither specific nor single. A knowledge of their role in the pathogenesis of hypercalcaemia should lead to the development of antagonists for therapeutic purpose and to a better understanding of their individual physiological effects, since some of these mediators are present in non-tumoral tissues. In humoral hypercalcaemia, PTH-rp seems to play a major role on kidneys and bones.

Humans↗
PubMed1988

Maximal PTH secretory rate and set point for calcium in normal subjects and patients with primary hyperparathyroidism. In vivo studies.

The characteristics of PTH secretion, which have been extensively studied in vitro with dispersed cells of normal and abnormal parathyroid glands, remain poorly studied in vivo. We performed ethylenediamine tetraacetate (EDTA) intravenous infusions in 12 normal subjects and 5 patients with hypercalcemia (serum ionized calcium between 2.72 and 2.89 mEq/l) and surgically proven primary hyperparathyroidism (PHPT) to establish the relationship between nephrogenous cyclic AMP (NcAMP) used as an index of PTH secretion and serum ionized calcium. We determined the maximal NcAMP taken as an index of maximal secretory rate for PTH, the set point and sensitivity of parathyroid cells for calcium. In normal subjects, mean values (+/- SD) were 4.04 +/- 0.47 nmol/dl glomerular filtrate (GF) for maximal NcAMP, 2.23 +/- 0.04 mEq/l for set point, and -250 +/- 58 for sensitivity when NcAMP was expressed in percent of maximal value and serum calcium in mEq/l. In patients with PHPT, the differences between maximal and basal values of NcAMP represented 50% or more of maximal NcAMP, indicating that PTH secretion was suppressible. Sensitivity values were within normal limits in all patients. Calculated set point values were abnormally elevated (between 2.64 and 2.83 mEq/l) in all patients. Maximal NcAMP values ranged from low to normal (2.77 nmol/dl GF) to abnormally high (6.64 nmol/dl GF), and a positive linear correlation was observed with parathyroid cell mass. Basal serum calcium concentrations were not correlated with either parathyroid cell mass or maximal NcAMP values, and were close to calculated set point values for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Validation of an self-measurement blood pressure device].

UNLABELLED: The aim of this study was to test the self-blood pressure (Self-BP) measurement device Copal UA-251 (Philips). This device uses auscultatory method for BP measurement. It was compared to reference methods: intraarterial and Hawksley Random Zero in 38 patients, selected in two groups: group RO (n = 18), compared Copal to Random Zero. 20 simultaneous measurements were recorded, with devices inversion at eleventh BP measurement, in 18 treated or untreated hypertensive patients. Group IA (n = 20) included 20 patients and compared Copal to intra-aortic measurement. Three simultaneous measurements were recorded, before a coronarography was performed, in 20 normo or hypertensive patients. RESULTS: (Table: see text). 1) A significant difference was recorded for SBP evaluated by Copal versus RO and for DBP measured by Copal versus IA. 2) A significant correlation was assessed between the different methods of measurement. 3) Differences between couples of RO-Copal values are not correlated to BP level, neither for SBP (r = 0.07), nor DBP (r = 0.05). Same results occur for IA-Copal values (SBP: r = 0.36, DBP: r = 0.30). 4) No order effect was found; no discrepancy between arms occurred in BP measurement. CONCLUSION: comparing intraaortic measure, Copal is efficient for SBP measurement, but overestimate DBP. Compared to R0, Copal overestimates SBP, but is efficient for DBP measurement. Regarding these results, a self-BP measurement is possible with this device.

Adolescent↗
PubMed1988

[Comparison of 3 methods of blood pressure measurement in obesity].

Arm girth and circumference often leads to difficulties in Blood Pressure (BP) measurement in obese patients. In order to assess the best method of BP measurement, we have compared in a triplicate study, Intra-arterial Pressure (INTRA) to indirect measurements: Mercury Sphygmomanometer (SPH) and oscillometric device Bard Sentron (SEN). SPH and SEN were successively connected to the same cuff (inflatable bladder 14 x 31 cm). Cuff was positioned on contralateral arm to arterial puncture. 19 subjects were studied (18 female); mean age was 51.3 +/- 9 years (extremes: 37-69), mean weight 104 +/- 19 kg (84-147), weight index 40 +/- 4.7 kg/m2 (34-49), and brachial circumference 39 +/- 4 cm (33-47). First out-patient mean blood pressure measurement was 182/104 mmHg (148-264/80-132). Mean SPH BP were 158 +/- 34/91 +/- 3 (98-230, 72-112) and mean INTRA: 171 +/- 37/85 +/- 5 (122-256/56-118). Mean systolic and diastolic differences (S, D, mmHg) were: (Table: see text). 1) SPH systolic BP underestimates HUM systolic BP. 2) Mean SEN measurements are very closed to HUM values. 3) A great intra-individual variability occurs since more than 50 per cent systolic SPH values show discrepancy of more than 10 mmHg for systolic and diastolic HUM BP; the same discrepancies occur for SEN vs HUM. 4) Differences between couples of values (HUM-SEN, HUM-SPH) are not correlated to BP level, neither for systolic nor for diastolic BP. 5) No significant correlation occurs when BP deltas are compared to weight index or arm circumference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗