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Gilbert C Faure

Publications and source records attributed to Gilbert C Faure.

At least 19 recordsLinked to original sources
PubMed2006

Modulation of the triggering receptor expressed on myeloid cells-1 pathway during pneumonia in rats.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell-surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. The aim of the present study was to investigate the effect of the modulation of the TREM-1 pathway during experimental pneumonia in rats. METHODS: Adult male Wistar rats were intratracheally inoculated with Pseudomonas aeruginosa (PAO1 strain) and randomly treated or not treated with an analogue synthetic peptide derived from the extracellular moiety of TREM-1 (LP17). RESULTS: P. aeruginosa induced a severe pneumonia associated with signs of severe sepsis within the first 24 h. In septic rats, LP17 improved hemodynamic status, attenuated the development of lactic acidosis and hypoxemia, modulated lung and systemic inflammatory responses and coagulation activation, reduced lung histological damage, and improved survival. CONCLUSIONS: The modulation of the TREM-1 pathway by the use of such synthetic peptides as LP17 appears beneficial during P. aeruginosa pneumonia in rats in attenuating lung and systemic inflammatory responses.

Amino Acid Sequence↗
PubMed2006

Corticosteroids in patients with antiovarian antibodies undergoing in vitro fertilization: a prospective pilot study.

OBJECTIVE: Antiovarian autoantibodies (AOA) have been associated with reproductive failure, especially in in vitro fertilization (IVF) patients. Thus, the success rate of IVF might be improved by the use of corticosteroids. However, therapeutic trials with these drugs have yielded conflicting results, particularly because of heterogeneous inclusion criteria. Among women with previous IVF failure, we selected those who presented with a positive serum AOA assay, and analysed the efficacy of corticosteroids in improving the IVF outcome in these patients. METHODS: One hundred patients with serum AOA detected by ELISA and at least two previously failed IVF attempts were selected. These patients underwent a further IVF cycle with 0.5 mg/kg prednisolone, started on the first day of the treatment cycle. In patients who became pregnant, corticosteroids were administered until the end of the first trimester of pregnancy and then progressively discontinued. AOA were assessed before and after oocyte retrieval. Clinical data of the corticosteroid-treated cycle were compared with data from the preceding IVF cycle for each patient. RESULTS: No adverse effects resulting from corticosteroids were observed. Post oocyte retrieval antiovarian IgG were significantly lower in corticosteroid-treated attempts when compared with the preceding cycles. Twenty-six pregnancies resulted in the birth of 30 healthy children. The pregnancy rate, implantation rate, and live birth rate were 38.8%, 17.8%, and 26.5% respectively in prednisolone-treated cycles. CONCLUSION: This study confirms the usefulness of corticosteroids in improving the success rate in a subset of patients with previous IVF failure and significant serum AOA levels.

Adrenal Cortex Hormones↗
PubMed2006

Modulation of natural killer (NK) receptors on NK (CD3-/CD56+), T (CD3+/CD56-) and NKT-like (CD3+/CD56+) cells after heart transplantation.

BACKGROUND: After undergoing heart transplantation and the subsequent compulsive immunosuppressive treatments, patients are at risk of rejection episodes, infectious complications or cancer development. Thus, it is probable that the various subsets of peripheral cytotoxic lymphocytes are modulated in such patients. This area of study can now be investigated by examining the numerous recently described natural killer (NK)-cell-related surface receptors. METHODS: A prospective cohort of 60 heart transplant recipients and 60 controls was studied. The partitioning of lymphocyte subsets, especially NK (CD3-/CD56+), T (CD3+/CD56-) and NKT-like (CD3+/CD56+) cells, was compared in both groups using multi-parametric flow cytometry. Moreover, expression of a series of seven NK-related receptors was compared on the three subsets defined by CD56 expression. RESULTS: A significant increase in NK-cell levels was observed in transplanted patients, as compared with controls, whereas T and NKT-like cells were in similar proportions in both groups. Two NK-related receptors showed significantly different levels of expression in heart transplant recipients: the cytotoxic effector, CD244, which was in a significantly increased proportion on T and NKT-like cells; and the activating receptor, CD161, which was expressed significantly less on NK and NKT-like cells, but more on T cells. CONCLUSIONS: These findings indicate that cytotoxic NK-related cells, increased in proportion, also display increased levels of activity-associated markers in heart transplant recipients. Viral infection or the immunosuppressive regimen could be responsible for the modulation of regulatory receptors on NK and NKT-like cells in heart transplant recipients.

Adult↗
PubMed2006

Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock.

The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1beta, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock.

OBJECTIVE: To analyze the pattern of cell-surface expression of the triggering receptor expressed on myeloid cells (TREM) 1 during septic shock. DESIGN AND SETTING: Prospective clinical study in an adult 16-bed medical ICU. PATIENTS AND METHODS: 25 septic shock patients, 15 patients with shock of noninfectious origin and 7 healthy volunteers. Arterial blood was drawn within 12 h of admission and subjected to flow cytometry analysis after staining with anti-TREM-1 and anti-CD14 antibodies. Repeated sampling was performed on days 2, 3, 5, 7, and 14 in septic shock patients. RESULTS: Monocytic TREM-1 expression was significantly higher in septic shock patients (mean fluorescence intensity 2.3+/-0.2) than in nonseptic patients (1.0+/-0.1), and healthy volunteers (1.0+/-0.1). There was no difference in monocytic TREM-1 expression between nonseptic patients and healthy volunteers or between any of the three groups with respect to TREM-1 expression on neutrophils. The time course of TREM-1 expression on monocytes diverged significantly by day 3 between survivors and ns. CONCLUSIONS: The specificity of TREM-1 regulation by infection is highlighted. Moreover, surface TREM-1 expression on monocytes may prove useful in allowing the follow-up of septic patients during the course of the disease.

Aged↗
PubMed2005

Gonadal antibodies interfering with female reproduction.

While the involvement of anti-ovarian antibodies (AOAs) is highly likely, yet still controversial, in patients with patent premature ovarian failure (POF), it is even more difficult--for several reasons--to ascertain the clinical significance of these antibodies in patients without obvious ovarian failure. First, AOAs form a heterogeneous group of antibodies recognizing several different antigenic targets such as granulosa and thecal cells, zona pellucida, oocyte cytoplasm, corpus luteum, as well as gonadotrophins and their receptors. Second, the detection of AOAs in various clinical situations does not readily imply a causal relationship between these antibodies and impaired ovarian function. Third, diagnostic tools for detecting AOAs and their molecular targets have to be improved to yield more reliable data and allow a better comprehension of the pathophysiology of AOAs. Preliminary results with immunosuppressive therapy in selected AOA patients have been encouraging, but randomized trials have to be performed.

Female↗
PubMed2005

Measurement of immunoglobulins G, A, and M levels in B-lymphocytes culture.

Nephelometric immunoassays were developed for human IgG, IgA, and IgM quantitation in B-lymphocytes culture media. They allowed measurement of immunoglobulin (Ig) levels over a broad range of concentrations with good accuracy and precision. The kinetics of Ig production in B-lymphocyte cultures was followed and the mean amount of each Ig was determined in six different samples after three days of culture. The nephelometric immunoassays reported here could be used to study, in vitro, the influence of various molecules (inhibitory or amplifying effect) on B-lymphocytes' functional capacities.

B-Lymphocytes↗
PubMed2005

Surface and soluble triggering receptor expressed on myeloid cells-1: expression patterns in murine sepsis.

OBJECTIVE: To examine the expression patterns of the triggering receptor expressed on myeloid cells (TREM)-1 during experimental septic shock. DESIGN: Animal study. SETTING: Animal research laboratory. SUBJECTS: Male BALB/c mice, 7-9 wks of age. INTERVENTIONS: Septic shock was induced by cecal ligation and puncture in eight mice. Eight additional animals were sham-operated and served as a control group. All animals were resuscitated by fluid infusion and administered antibiotics. Kill was performed under anesthesia 12, 24, or 48 hrs later. MEASUREMENTS AND MAIN RESULTS: Surface expression of TREM-1 was analyzed using flow cytometry on peripheral blood cells, peritoneal macrophages and neutrophils, splenic macrophages, and Kupffer cells. Gene expression was also studied in these same cells using reverse transcription-polymerase chain reaction. Tumor necrosis factor-alpha, interleukin-1beta, and soluble TREM-1 concentrations were determined in plasma and peritoneal lavage fluid. Sepsis strongly induced TREM-1 gene expression, which translated into an up-regulation of TREM-1 surface expression on neutrophils and monocytes/macrophages both at the focus on infection as well as distally. Moreover, sepsis induced the release of significant levels of soluble TREM-1. Plasma soluble TREM-1 concentrations negatively correlated with tumor necrosis factor-alpha and interleukin-1beta levels at 12 hrs. CONCLUSIONS: These results provide new information as to the regulation of TREM-1 during sepsis. Considering that both cell-surface and soluble TREM-1 were strongly up-regulated during infection, this study may add support to the putative usefulness of TREM-1 as a diagnostic tool.

Animals↗
PubMed2005

Comparative T-cell oligoclonality in lung, tumor and lymph nodes in human non-small cell lung cancer.

In lung cancer as in other malignancies, tumor formation induces the development of local and systemic antitumoral immune responses. The tumor itself becomes surrounded by a local stroma reaction containing inflammatory cells, a large part of which being tumor infiltrating T-lymphocytes. This study was designed to investigate the potential clonality of these T-cells in non-small cell lung cancer. Two complementary methods where used: exploration of the Vbeta TCR repertoire usage in flow cytometry and analysis of the Vgamma TCR repertoire in multiplex PCR and gradient gel electrophoresis. These techniques were applied respectively to eluted fresh lymphocytes and extracted DNA from healthy lung tissue, tumor and lymph nodes from 44 patients. There was a good correlation between the two techniques used. An oligoclonal repertoire restriction was noted in most of the cases and in the three types of tissues studied suggesting the presence of tumor-specific clones. Moreover, Vbeta14 appeared to be the most frequent specificity used whatever the tissue considered, while Vbeta13.1 appeared to be selectively used in the stroma reaction of epidermoid lung carcinomas. A restricted TCRgamma band was also present in these tumors, and two more bands of TCRgamma where selectively present in adenocarcinomas. The demonstration of both alpha-beta and gamma-delta TCR restriction suggests both the recruitment of specific T-cells and their local proliferation within the tumoral tissue. The same feature in healthy lung tissue indicates that it might already be the site of specific anti-tumoral T-cell reactivity. In conclusion, this study reports on the presence of oligoclonal T-cell responses in most cases of non-small cell lung cancer. The comparison of tumor, healthy tissue and lymph nodes showed some degree of patient-dependent similarities suggestive of tumor specificity.

Aged↗
PubMed2004

A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis.

The triggering receptor expressed on myeloid cells (TREM)-1 is a recently discovered receptor expressed on the surface of neutrophils and a subset of monocytes. Engagement of TREM-1 has been reported to trigger the synthesis of proinflammatory cytokines in the presence of microbial products. Previously, we have identified a soluble form of TREM-1 (sTREM-1) and observed significant levels in serum samples from septic shock patients but not controls. Here, we investigated its putative role in the modulation of inflammation during sepsis. We observed that sTREM-1 was secreted by monocytes activated in vitro by LPS and in the serum of animals involved in an experimental model of septic shock. Both in vitro and in vivo, a synthetic peptide mimicking a short highly conserved domain of sTREM-1 appeared to attenuate cytokine production by human monocytes and protect septic animals from hyper-responsiveness and death. This peptide seemed to be efficient not only in preventing but also in down-modulating the deleterious effects of proinflammatory cytokines. These data suggest that in vivo modulation of TREM-1 by sTREM peptide might be a suitable therapeutic tool for the treatment of sepsis.

Amino Acid Sequence↗
PubMed2004

Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis.

BACKGROUND: Previous experimental studies have suggested that the triggering receptor expressed on myeloid cells-1 (TREM-1) is specifically upregulated in the presence of microbial products. OBJECTIVE: To evaluate the diagnostic value of plasma levels of the soluble form of TREM-1 in patients admitted with clinical suspicion of infection. DESIGN: Prospective, noninterventional study conducted between July and September 2003. SETTING: Medical adult intensive care unit at a university hospital in France. PARTICIPANTS: 76 consecutive newly admitted patients who presented with clinically suspected infection and fulfilled at least 2 criteria of the systemic inflammatory response syndrome. MEASUREMENTS: Sensitivity and specificity of plasma soluble TREM-1 levels at admission for the diagnosis of infection. Two independent intensivists blinded to the results of soluble TREM-1 assays retrospectively classified patients as having the systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock. RESULTS: The systemic inflammatory response syndrome was diagnosed in 29 patients (38%), and sepsis, severe sepsis, or septic shock was diagnosed in the remaining 47 (62%). A plasma soluble TREM-1 level higher than 60 ng/mL was more accurate than any other clinical or laboratory finding for indicating infection (sensitivity, 96% [95% CI, 92% to 100%]; specificity, 89% [CI, 82% to 95%]; positive likelihood ratio, 8.6 [CI, 3.8 to 21.5]; negative likelihood ratio, 0.04 [CI, 0.01 to 0.2]). LIMITATIONS: The study did not enroll patients with mild infections not requiring intensive care unit hospitalization, patients older than 80 years of age, or patients who were immunocompromised. CONCLUSION: In newly admitted critically ill patients, measurement of plasma levels of soluble TREM-1 could help to rapidly identify those with infection.

Blotting, Western↗
PubMed2004

Tetraspan and beta-1 integrins expression pattern of the epithelial lung adenocarcinoma cell line A549 and its sensitivity to divalent cations.

BACKGROUND: Tetraspans are ubiquitous integral transmembrane molecules associated on the cell surface with such adhesion molecules as integrins. Their expression has been shown to vary in tumors, but has seldom been described on lung tumoral epithelial cells, and the conditions required for a proper association of tetraspans and integrins have not yet been fully explored. METHODS: We investigated the expression of 10 tetraspans and six beta1 integrins on the tumoral lung epithelial cell line A549. Cells were examined both in quantitative flow cytometry and as monolayers, under normal or chelated conditions, in order to determine the cation dependency of their expression. RESULTS: Five tetraspans and four beta1 integrins are expressed on the membrane of A549 cells. Both quantitative and qualitative surface and cytoplasmic modifications of this pattern were induced in chelating conditions, suggesting the importance of divalent cations for the expression of these molecules. CONCLUSIONS: These data indicate that a specific pattern of tetraspans and integrins, relying strongly on the availability of divalent cations in the microenvironment, is expressed by tumoral epithelial cells.

Adenocarcinoma↗
PubMed2004

Clinical involvement of the tonsillar immune system in IgA nephropathy.

The temporal association of tonsillitis and hematuria or proteinuria in IgA nephropathy suggests that there might be a link between the physiological properties of the secondary lymphoid organ that tonsils represent and the mesangial deposition of IgA characteristic of this nephropathy. A number of clinical and ex-vivo data support this hypothesis. One of the earliest was the demonstration of the dimeric nature of mesangial IgA, composed of IgA monomers linked by a J chain, yet lacking the polyIg receptor acquired by secretory IgA during transcytosis through epithelial cells. This molecular structure is that of IgA synthesized in human tonsils, the epithelium of which lacks polyIg receptor. Moreover, tonsils from patients with IgA nephropathy display an abnormal partition of IgG and IgA producing plasma cells associated with a significantly developed web of high endothelial venules. IgA nephropathy could thus be in part related to an alteration of IgA precursors homing in tonsils. Tonsillectomy thus would present the advantage of removing an abnormally functioning source of dimeric IgA. Performed early enough in the course of the renal disease, tonsillectomy could suffice to halt the development of the nephropathy and restore the kidneys to health.

Glomerulonephritis, IGA↗
PubMed2003

Choroid plexus, aging of the brain, and Alzheimer's disease.

Choroid plexus tissues are intraventricular structures composed of villi covered by a single layer of ciliated, cuboid epithelium. The plexuses secrete cerebrospinal fluid (CSF), synthesize numerous molecules, carry nutrients from the blood to CSF, reabsorb brain metabolism by-products and participate in brain immunosurveillance. During ageing, atrophy of epithelium occurs along with thickening of basement membranes. Enzymatic activities of epithelial cells decrease significantly. CSF secretion decreases as much as 50%. These modifications are concurrent with subnormal brain activity. In Alzheimer's disease, epithelial atrophy, thickening of basement membrane and stroma fibrosis are even more prominent. Ig and C1q deposition along the basement membrane can be frequently detected, suggesting immunological processes. Synthesis, secretory, and transportation functions are significantly altered resulting in decreased CSF turnover, reduced beta-amyloid clearance, and increased glycation phenomena as well as oxidative stress. Such modifications may favour fibrillary transformation of beta-amyloid protein and tau protein polymerisation.

Aging↗
PubMed2003

Anti-HBs cellular immune response in kidney recipients before and 4 months after transplantation.

Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.

Adult↗
PubMed2003

Ribosomal immunotherapy for recurrent respiratory tract infections in children.

Recurrent respiratory tract infections are common in children. They reflect the immaturity of the immune system in its encounter with environmental antigens. Little or no specific protective immune response has yet been established. These infections represent an important public health problem in terms of both treatment (anti-inflammatory or antibacterial drugs for children) and economy. Immunotherapy has been proposed as a means of preventing these recurrent infections by providing children with small doses of inactive bacterial antigens liable to trigger specific and protective immune responses. Among such drugs, ribosomal preparations (to which this review is limited) appear to be not only well tolerated, but also ideally targeted to induce mucosal responses. One preparation of ribosomal mucosal vaccine is commercially available in several countries. Numerous clinical trials in the world have confirmed the positive role of this mucosal ribosomal bacterial vaccine in significantly reducing the number of infections, courses of antibacterials, and absenteeism. In vitro and ex vivo investigations have confirmed that such vaccines indeed trigger protective specific immune responses.

Bacterial Vaccines↗
PubMed2002

Eosinophilia and cell activation mediators in nasal secretions.

OBJECTIVES/HYPOTHESIS: In rhinologic disorders such as polyposis or rhinitis, nasal cytology allows differentiation between patients according to the degree of eosinophilia in nasal secretions. The egress of eosinophil and/or neutrophil polymorphonuclears from the underlying mucosa might correlate with the release of soluble mediators of cell activation such as the chemokine IL-8, and such molecules of the innate immunity as the LPS-receptor CD14 or lysozyme. We assayed the levels of these three molecules in nasal secretions in correlation with cytologic findings and especially the degree of eosinophilia. STUDY DESIGN: Fifty-four patients from a prospective study of nasal secretions were enrolled in this work. They constituted two groups of 27 patients each, respectively, with or without more than 20% eosinophils in nasal secretions. Nasal secretions were collected by aspiration, weighed and diluted in a fixed amount of buffer. Classic cytologic analyses were performed on the pelleted cells and IL-8, sCD14, and lysozyme levels were assayed in the cell-free supernatants. METHODS: Cytologic analyses included cell-enumeration in Neubauer's chambers, and differentials performed on May-Grünwald Giemsa-stained cytospins. ELISA tests were used to assay the levels of IL-8 and sCD14. Lysozyme concentrations were assayed in immuno-nephelometry. RESULTS: Significantly lower levels of IL-8 and sCD14 were observed in patients with eosinophilia than in patients with a predominance of neutrophils, whereas no difference was observed in lysozyme concentrations. CONCLUSION: These data show that the egress of neutrophils in nasal secretions is associated with high levels of IL-8 and sCD14.

Adolescent↗