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P Gallay

Publications and source records attributed to P Gallay.

At least 37 records · Page 2Linked to original sources
PubMed1994

Bactericidal/permeability-increasing protein inhibits induction of macrophage nitric oxide production by lipopolysaccharide.

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Normal mouse plasma amplified NO synthesis (measured as NO2- release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited NO2- release in the presence of normal mouse plasma. rBPI23 (1 microgram/mL) effectively inhibited LPS-dependent NO2- release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-gamma/LPS-elicited NO2- production or of binding of fluoresceinated LPS was obtained with approximately 0.2 microgram/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gram-negative sepsis.

Animals↗
PubMed1994

Lipopolysaccharide (LPS)-binding protein in human serum determines the tumor necrosis factor response of monocytes to LPS.

Lipopolysaccharide (LPS)-binding protein (LBP) and CD14 represent key elements in monocyte activation by LPS. The mean concentration of LBP was 18.1 microgram/mL in normal serum and 40-60 micrograms/mL in serum of patients with septic shock, independent of the fact that patients had gram-negative or other infections. Ten percent normal serum presented large concentrations of LPS (in the microgram range) to monocytes. Only when diluted 1:100 was LBP in plasma a limiting factor for monocyte activation, as measured by tumor necrosis factor (TNF) release. When LBP was depleted from serum with anti-LBP antibodies, the resulting serum did not support TNF release of monocytes upon LPS challenge. In conclusion, monocyte activation resulting in TNF secretion was related to LBP, which is abundantly present in normal serum, and elevated two to three times in patients with septic shock.

Acute-Phase Proteins↗
PubMed1993

Lipopolysaccharide-binding protein as a major plasma protein responsible for endotoxemic shock.

Because lipopolysaccharide (LPS)-binding protein (LBP) sensitizes monocytes to LPS in vitro, it has been suggested that LBP initiates host defenses against Gram-negative bacteria. The role of LBP in vivo, and particularly in endotoxemic shock, is unknown, however. Therefore an IgG against murine LBP was prepared. It was found to neutralize binding of LPS and subsequent activation of murine macrophages in vitro. This anti-LBP protected mice against the lethal effect of LPS when given at the same time as LPS challenge, but it failed to protect mice when delayed 15 min after LPS challenge. The same preparation was also effective after challenge with lipid A but not after challenge with Staphylococcus aureus enterotoxin. The protection was correlated with a strong decrease of circulating tumor necrosis factor. These data demonstrate that in vivo LBP is a major mediator of the lethal effects of endotoxemia.

Acute-Phase Proteins↗
PubMed1993

Short time exposure to lipopolysaccharide is sufficient to activate human monocytes.

Very little is known about early events in LPS binding and about the duration of LPS exposure required to activate monocytes. In the present study, we have investigated the kinetics of LPS binding to human monocytes and the time of exposure required to trigger the synthesis of TNF-alpha. We directly followed the binding of FITC-labeled LPS to monocytes by flow cytometry or confocal laser microscopy. LPS was able to bind to the cell surface within 1 min of exposure, and was internalized within 5 min. Equilibrium was reached within 15 min at all but the lowest LPS concentration tested (10 ng/ml). Binding was dependent on the presence of LPS-binding protein, supplied either as a plasma component or in purified form, and inhibited by an anti-CD14 mAb (MY4). Polymyxin B, an inhibitor of LPS-mediated activation, essentially abrogated the LPS-binding protein- and CD14-dependent binding of LPS to monocytes. Using either the anti-CD14 mAb or polymyxin B to block further LPS binding, we found that 5 to 10 min of exposure was sufficient to trigger maximal TNF-alpha release. Similarly, monocytes washed after 5 to 15 min exposure to eliminate LPS also produced high levels of TNF-alpha transcripts without further presence of LPS in the medium. We conclude that a few minutes of exposure to physiologically relevant concentrations of LPS are sufficient to trigger both maximal binding and activation of monocytes.

Acute-Phase Proteins↗
PubMed1993

Expression and release of interleukin-1 by human glioblastoma cells in vitro and in vivo.

The present study demonstrates interleukin-1 (IL-1) production by human glioblastoma cells both in vitro and in vivo. The presence of IL-1 alpha and IL-1 beta transcripts was analyzed in 4 cell lines. IL-1 alpha mRNA was expressed constitutively in one cell line whereas constitutive IL-1 beta mRNA could not be detected in any of the cell lines. IL-1 alpha transcripts could be induced with phorbol myristate acetate (PMA) or PMA plus lipopolysaccharide (LPS) in 2 of 4 cell lines and IL-1 beta mRNA in 2 of 4 cell lines. Culture fluid from these cell lines was tested for the presence of IL-1 using a specific radio-immuno-assay for either IL-1 alpha or IL-1 beta. In agreement with the results on RNA, one of 4 cell lines was found to constitutively produce IL-1 alpha but not IL-1 beta. After treatment with PMA and LPS, IL-1 alpha was detected in the culture fluid from two other lines and IL-1 beta in the medium from three lines. That the IL-1 produced by these cell lines was biologically active was confirmed in a two step thymocyte proliferation assay. IL-1 like activity was detected in all samples that were positive in the radio-immuno-assay. Finally, immunohistological analysis on fresh frozen tumour sections provided evidence for IL-1 production by glioblastoma cells in vivo. Fourteen out of 28 glioblastomas were stained with an anti-IL-1 alpha monoclonal antibody while none of them was stained with an anti-IL-1 beta antibody.

Brain Neoplasms↗
PubMed1993

Competition between bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein for lipopolysaccharide binding to monocytes.

The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)-mediated activation of monocytes. Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD14 of monocytes, rBPI23, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP. Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNF alpha) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI23. Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNF alpha release, but this inhibition vanished with delaying the time of addition of rBPI23. These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LPS.

Acute-Phase Proteins↗
PubMed1993

Purification and characterization of murine lipopolysaccharide-binding protein.

The serum protein lipopolysaccharide (LPS)-binding protein (LBP) seems to play an important role in regulating host responses to LPS. Complexes of LPS and LBP form in serum and stimulate monocytes, macrophages, or polymorphonuclear leukocytes after binding to CD14. Previous reports have described the structure and properties of LBP from human and rabbit sera. Since mice are used in some experimental models of endotoxemia or gram-negative bacterial infections, information is needed about the properties of murine LBP. Murine LBP was purified by ion-exchange chromatography and high-pressure liquid chromatography; its NH2-terminal sequence (TNPGLVTRIT) was very similar to those of human and rabbit LBPs (80 to 90% amino acid identity). Murine LBP resembled LBPs from other species in that it promoted the binding of LPS to monocytes and enhanced the sensitivity of monocytes to LPS at least 100-fold. Mouse LBP, like rabbit and human LBPs, was found to be an acute-phase protein. Further in vivo studies with mice and anti-CD14 or anti-LBP reagents should help determine the role of LBP in response to LPS challenges.

Acute-Phase Proteins↗
PubMed1992

Control of lipopolysaccharide (LPS) binding and LPS-induced tumor necrosis factor secretion in human peripheral blood monocytes.

We used flow cytometry to determine how LPS-binding protein (LBP) effects the binding of fluorescein-labeled LPS to human monocytes via receptor-dependent mechanisms. The addition of human, rabbit, mouse, or FCS strikingly increased the binding of LPS to monocytes compared with controls incubated in serum-free medium. This binding was totally prevented by preincubation of monocytes with MY4, an anti-CD14 mAb, or by enzymatic removal of CD14 from monocytes. Depletion of LBP from rabbit serum with anti-LBP antibodies also produced a similar suppression. Solutions of albumin did not support the enhanced binding observed in serum but the addition of purified rabbit LBP to albumin solutions resulted in binding similar to that observed in serum-containing medium. When type-specific anti-LPS mAb was added to human serum, LPS binding to monocytes occurred but was only partly inhibited by anti-CD14 mAb, suggesting that receptors other than CD14 (presumably Fc or complement receptors) were involved. Serum increased by 100- to 1000-fold the sensitivity of monocytes to the triggering by LPS resulting in TNF secretion. TNF secretion was inhibited by anti-CD14 mAb up to 100 ng/ml of LPS and by anti-LPS mAb up to 1 to 10 ng/ml. The inhibition of TNF secretion by anti-LPS mAb appeared to be the result of directing LPS to monocyte receptors other than CD14. In contrast, in medium containing normal as well as acute serum and in the absence of anti-LPS antibodies, the binding of LPS to monocytes and the triggering of TNF secretion appeared to be mediated mainly by interactions between CD14 and LBP-LPS complexes.

Acute-Phase Proteins↗
PubMed1992

Enhancement of murine macrophage binding of and response to bacterial lipopolysaccharide (LPS) by LPS-binding protein.

We have studied the effects of highly purified rabbit lipopolysaccharide (LPS)-binding protein (LBP) on the ability of murine bone marrow-derived macrophages to respond to bacterial LPS. Macrophage responses studied include the secretion of tumor necrosis factor alpha, production of arginine-derived nitrite (NO2-), and killing of an intracellular pathogen, Leishmania enriettii. Macrophages from either CBA or LPS-hyporesponsive C3H/HeJ mice exhibited significantly greater sensitivity to LPS in the presence of LBP. Furthermore, both CBA and C3H/HeJ macrophages demonstrated an LBP-dependent enhancement of LPS binding. These results suggest that C3H/HeJ macrophages are capable of binding LPS-LBP complexes and support the hypothesis that hyporesponsiveness in this strain involves a step subsequent to LPS binding. Furthermore, these findings provide additional evidence of the important role played by the acute-phase plasma protein LBP in modifying host response to LPS.

Acute-Phase Proteins↗
PubMed1992

[Ventricular tachycardia caused by bundle branch reentry].

Ventricular tachycardia by bundle branch reentry is a special type of ventricular tachycardia. A rare arrhythmia, it occurs in very particular conditions of ventricular dilatation and conduction defects. The diagnosis is based on electrophysiological findings associating a His potential preceding the ventriculogramme with a HV interval comparable to that observed in sinus rhythm, and spontaneous variations of the cycle length between two ventriculogrammes preceded by those of the His potentials. Contrary to what is observed in other forms of ventricular tachycardia, pacing is possible from the atrium without changes of the QRS complexes and the presence of fusion complexes excludes the diagnosis. Treatment consists of radiofrequency ablation of the right bundle branch.

Bundle-Branch Block↗
PubMed1991

Positive signal transduction via surface CD4 molecules does not need coexpression of the CD3/TcR complex.

We previously reported that the human CD4 molecule is capable of transducing a positive signal when activated by an anti-CD4 mAb B66. This antibody, in contrast to many other anti-CD4 mAb, induced IL2 production and proliferation of resting CD4+ peripheral blood T lymphocytes in the absence of any other signal. We further reported that anti-CD4 mAb B66 was able to induce IL2 production in murine T-cell hybridoma cells transfected with full-length human CD4 cDNA. In the present study, we extend these findings by demonstrating that anti-CD4 mAb B66 was able to induce Ca2+ mobilization and IL2 production in a CD3/TcR- variant 31-13, of the CD3/TcR+ Jurkat cell line. We further showed that anti-CD4 mAb B66 was able to activate CD4+ cells from the promonocytic cell line U937. In these cells, mAb B66 induced Ca2+ mobilization when cross-linked with a second antibody and, in addition, the production of large quantities of IL1 beta was measured. In essence, our findings provide direct evidence that cross-linking of CD4 may cause T-cell activation in the absence of the coexpression of the CD3/TcR molecular complex and that, in addition, CD4 might transduce a positive signal in CD4+ cells of the myeloid lineage.

Animals↗
PubMed1990

gp33-38, an early human T cell activation antigen.

We describe an activation Ag Me14/D12 that appears early after T cell activation and is absent in resting T lymphocytes. Me14/D12 is a nondisulfide-linked heterodimeric structure containing two polypeptide chains of 33,000 and 38,000 Da. The expression of Me14/D12 on resting T lymphocytes can be induced by different activation stimuli such as the lectins PHA and Con A, the phorbol ester PMA, and anti-CD3 mAb. The induction of mRNA for Me14/D12 (gp33-38) in PHA-activated T lymphocytes precedes that of IL-2R gene transcripts by more than 20 h. Me14/D12 mRNA was detectable as early as 2 h after the onset of activation and mRNA for the IL-2R only after 24 h. The surface expression of Me14/D12 was detectable between 12 and 24 h after activation and was maximal between 24 and 48 h. Several T leukemia cell lines express the Me14/D12 Ag. On Me14/D12- cell lines, PMA and IFN-gamma induced surface expression of Me14/D12. Once Me14/D12 Ag were expressed on Jurkat cells after stimulation with either PMA or IFN-gamma, the binding of mAb Me14/D12 induced the production of significant amounts of IL-2 and of Ca2+ mobilization from internal stores. Comparative biochemical studies clearly demonstrate that Me14/D12 (gp33-38) is different from the CD69 molecular complex defined by mAb MLR3 and AIM.

Antibodies, Monoclonal↗
PubMed1990

[Myocardial infarction and anti-ethinylestradiol antibody. Apropos of a case in an 18-year-old woman].

An 18-year-old woman presented with a large anterior myocardial infarction. Her cardiovascular risk factors were cigarette smoking in moderation and oral contraception with a synthetic oestroprogestative pill prescribed a few months previously. Coronary angiography showed occlusion of the left anterior descending artery but no other lesions. Biological investigations excluded an abnormality of coagulation. Antibodies to synthetic steroids (ethinylestradiol and progesterone) and circulating immune complexes were found in the serum. The role of antiethinylestradiol antibodies in the mechanism of myocardial infarction is discussed. These antibodies are present in 30 per cent of women taking oral contraceptives and their titres are significantly higher in 90 per cent of women who develop vascular thrombosis unrelated to atherosclerosis. The mechanism of the thrombogenic action of the antibodies and circulating immune complexes is also considered.

Adolescent↗
PubMed1990

[Myocardial morphological changes related to sodium intake in normotensive and hypertensive patients never treated before].

Several factors have been implicated in the pathogenesis of myocardial hypertrophy, and the role of sodium has recently been suggested. In the present study, we assessed the influence of dietary sodium on the degree of left ventricular hypertrophy (LVH) and LV structure in 30 normotensive (NT) subjects aged 34 +/- 11 years (mean +/- SD) and 50 patients (39 +/- 10 years) with mild essential hypertension EH (canal blood pressure 154 +/- 16/96 +/- 11 mmHg), who had never received antihypertensive drugs. Posterior wall thickness (PWT) and left ventricular mass (LVM) were measured by M-mode echocardiography and urinary sodium excretion (UNa, mmol/24h) was taken as an index of sodium intake. In NT and EH, LVM was directly correlated with UNa (r = 0.48 and 0.49; p less than 0.006 and 0.002, respectively). A stepwise multiple regression analysis confirmed that UNa was a determinant of LVM independently of sex, age, and body weight in the two groups. In NT the correlation with UNaV was the result of an increase of the end-diastolic diameter without change in PWT whilst in EH it was the consequence of an increase in wall thickness (R = 0.49, p less than 0.0001) without a modification of LV diameter. These results suggest that salt intake may be an important determinant of cardiac structural adaptation in both NT and EH subjects; however, only EH have a salt sensitive LV wall hypertrophy.

Adult↗
PubMed1989

[Evaluation of the left-to-right shunt in interatrial septal defects (ostium secundum) using Doppler echocardiography. Apropos of 12 cases].

In 12 patients with inter-atrial communication (ostium secundum) (IAC-OS), and ages ranging between 8 and 63 years (mean = 21 years), the ratio between pulmonary and systemic flow (QP/QS) was evaluated with the use of Doppler ultrasonography and compared with the QP/QS obtained by oxymetric measurement during catheterization. The pulmonary or systemic flow is evaluated from the diameter of the opening (d) and the velocity curve (ITV) recorded by pulsated Doppler in the aorta and the pulmonary artery; Q = d2/4 x ITV x heart rate both examinations (sonogram and catheterization) are performed in less than 24 hours. The results show a good correlation between both methods (R = 0.948) (Y = 0.756 X + 0.692). There is no significant variation between intra- or inter-observer. The findings of this study are comparable to those already published; the main difficulty in evaluating of the QP/QS by Doppler sonography are related to the measurement of the pulmonary diameter and there recording of good velocity curves. The QP/QS evaluated by Doppler sonography from a simplified calculation method advocated by Oloez et al. (QP/QS = d2 Ap x V max Ap/d2 Ao x V max Ao were compared, in retrospect, to the data provided by catheterization. The correlation is also satisfactory (R = 0.893). The Doppler ultrasonography is therefore a reliable and reproducible method in as far as the measurement of QP/QS in young or adults subjects affected with IAC OS.

Adolescent↗
PubMed1988

A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80.

In 20 patients undergoing coronary arteriography, the hemodynamic effects of an experimental preparation of i.v. amiodarone 5 mg kg-1 without Tween 80 (N) (10 patients) were compared with those of the commercial form with Tween 80 (A) (10 patients). Analysis of variance demonstrated differences during the 3 min of injection and for 3 min afterwards: left ventricular systolic pressure decreased from 110 + 11 to 86 +/- 11 mmHg (P = 0.001) after A and from 114 +/- 22 to 106 +/- 19 (P = 0.05) after N (comparison P = 0.01) while related tachycardia was also more pronounced after A (comparison P = 0.001). Left ventricular end diastolic pressure transiently decreased after A while continuously increasing after N (P = 0.05). During the following 30 min both A and N caused similar bradycardia, increase in ventricular filling pressure, vascular resistance and decrease in cardiac and contractility indexes. Amiodarone blood levels were similar after A or N. These data document a significant initial short duration vasoplegia, mainly related to Tween 80, after A, when amiodarone itself after producing a similar very slight effect causes bradycardia, and a moderate and progressive negative inotropic effect. It was concluded that while the experimental form would be of interest, the risk of severe hypotension after i.v. Cordarone can be largely avoided by using a slower rate of infusion, especially in patients with hypovolemic status.

Adult↗