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Biomedical subjects

N Blanchard

Publications and source records attributed to N Blanchard.

35 records · Page 2Linked to original sources
PubMed2000

[Thoracic injuries in children].

Chest trauma in children is rare but shows that trauma is severe and the mortality rate is high (30%). Multidisciplinary management of children includes an initial evaluation of respiratory distress, freeing the airways, placing an intercostal tube, stabilizing the chest wall, and analgesia. When vital signs are stable, secondary evaluation includes an etiologic, radiologic and biologic check-up, ending with the therapeutic strategy. Thoracotomy is rarely required, and for most children, only monitoring will be necessary, though this is important because of the risk of secondary decompensation and late diagnosis of potentially fatal lesions.

Age Factors↗
PubMed2000

Hemodynamic and echocardiographic effects of hemofiltration performed during cardiopulmonary bypass.

OBJECTIVE: To evaluate the effects of hemofiltration performed during rewarming before emergence from cardiopulmonary bypass on hemodynamic and echocardiographic parameters. DESIGN: Prospective randomized study; blind analysis of echocardiographic parameters and hemodynamic parameters. SETTING: Single-center study performed in a university hospital. PARTICIPANTS: Two groups of 13 adult patients undergoing coronary artery bypass graft surgery. INTERVENTION: Patients were randomized to conventional procedure or hemofiltration performed with a polysulfone hemofilter. Hemofiltration, started at the time of rewarming on cardiopulmonary bypass, was performed with a flow rate adjusted to achieve an ultrafiltrate volume of 15 mL/kg on completion of rewarming. MEASUREMENTS AND MAIN RESULTS: Hemodynamic (systemic mean arterial pressure, right atrial pressure, heart rate) and echocardiographic parameters (shortening fraction, segmental kinetic score, cardiac output, systemic vascular resistance) were measured before and after hemofiltration and on arrival in the intensive care unit. Heart rate and cardiac index were increased significantly in both groups during the postoperative period. In the control group, systemic vascular resistance was decreased significantly, and cardiac index was increased during the postoperative period, together with significant alterations of segmental kinetic score and shortening fraction. In the hemofiltration group, systemic vascular resistance remained unchanged, associated with a significantly improved segmental kinetic score compared with the control group. CONCLUSIONS: Hemofiltration performed during rewarming before emergence from cardiopulmonary bypass is associated with stability of hemodynamic parameters and improved segmental myocardial kinetics.

Adult↗
PubMed2000

[Interpretations of coordination as an evaluation tool in an experimental gerontologic program].

This article deals with the interpretations of coordination among actors solicited to participate in an experimental programme in the gerontological area of Lunel of the Hérault department of France. The article presents the conclusions of an evaluation report which includes two survey phases: a pre-test and a post-test survey implemented at the end of the programme with a parallel survey implemented in a control site, the Pézenas area of the Hérault department. The analysis of the initial perceptions of coordination and their evolution relies on the theory of the plurality of worlds (L. Boltanski and L. Thevenot). It aims to show that making a move toward coordination is a complex phenomenon that requires the elaboration of a common language. The material collected during this evaluation allows us to suggest that coordination questions the actors on their professional situation. It questions institutions and their internal functioning. Finally, this type of intervention brings to light the stakes in the examined field.

Aged↗
PubMed1996

[Changes in intraocular pressure during anesthesia with intratracheal intubation or laryngeal mask].

OBJECTIVE: To compare the effects of the laryngeal mask airway (LMA), and the tracheal tube (TT) insertion on intra-ocular pressure (IOP) in eye surgery. STUDY DESIGN: Prospective non-randomized study. PATIENTS: Eighty patients scheduled for eye surgery under general anaesthesia were allocated into either a LMA group (n = 37) or a TT group (n = 43). METHODS: After induction of anaesthesia with propofol, vecuronium and phenoperidine, either a TT or a LMA were inserted. IOP, heart rate (HP) and mean arterial pressure (MAP) were measured before (TO) and after induction (T1), after TT or LMA insertion (20 s:T2, 6 min:T3), and before extubation (T4). RESULTS: The HR, MAP and IOP increased significantly at T2 (compared to T1 but not to T0) in the TT group, for a short time, whereas no significant changes occurred in the LMA group. CONCLUSION: LMA insertion does not elicit significant haemodynamic or IOP changes. Conversely, the TT increases HR, MAP and IOP. These changes can be deleterious in case of emergency surgery for perforating eye injuries. The LMA can be recommended as an alternative to TT in eye surgery, provided security rules are followed, because of the risk of displacement of LMA during surgery.

Adult↗
PubMed1996

[Factor XI deficiency, a new way of substitution: human purified concentrates].

Case report of a 26-year-old patient, admitted for severe craniofacial trauma, with facial injuries and intracranial haemorrhage. Preoperative tests showed an aPTT = 64 s (control = 29 s), rapidly recognized as being caused by a major constitutional factor XI deficiency (0.06 Ul.mL-1). Considering the neurological risk and the indication for surgery, concentrates of factor XI were administered at a dosage of 25 Ul.kg-1. This treatment was associated with a biological normalization and uneventful surgery. In patients experiencing a factor XI deficiency, the use of fresh frozen plasma will probably decrease and only administered in emergency cases when factor XI concentrates are not available.

Adult↗
PubMed1995

Proteolysis of the human platelet and endothelial cell thrombin receptor by neutrophil-derived cathepsin G.

Cathepsin G is a neutrophil-derived protease that has been shown to inhibit the effects of thrombin on some cells expressing thrombin receptors while acting as an agonist on others. The present studies examine whether cleavage of the thrombin receptor by cathepsin G can account for these diverse effects. When added to cells that normally respond to thrombin, cathepsin G prevented a subsequent cytosolic Ca2+ increase caused by thrombin, but had no effect on responses to the thrombin receptor agonist peptide, SFLLRN. These effects were observed in cells in which cathepsin G had little or no agonist effect (human umbilical vein endothelial cells and HEL cells), as well as in cells in which cathepsin G acted as an agonist (platelets and CHRF-288 cells). Binding studies using monoclonal antibodies with defined epitopes within the first 60 residues of the thrombin receptor N-terminus showed that incubation of platelets and endothelial cells with cathepsin G abolished the binding of all of the antibodies, while thrombin abolished only the binding of antibodies whose epitopes were N-terminal to the known thrombin cleavage site between Arg41 and Ser42. Analysis of peptide proteolytic fragments identified three potential cleavage sites for cathepsin G: Arg41-Ser42, Phe43-Leu44, and Phe55-Trp56. Cleavage at Phe55-Trp56 would account for both the observed loss of all of the antibody binding sites and the inhibition of receptor activation by thrombin. Two approaches were used to determine whether a solitary cleavage at Arg41-Ser42 could result in receptor activation. In the first, HEL cells were exposed to cathepsin G or thrombin in the presence of an antibody whose epitope includes Phe55. The antibody inhibited responses to thrombin, but augmented the response to cathepsin G. In the second, COS-1 cells were transfected with variant thrombin receptors in which Phe55 and Trp56 were mutated to alanine. Transfected wild-type receptors responded to thrombin, but not cathepsin G, while the variant receptors responded to both proteases. These results 1) suggest that the ability of cathepsin G to inhibit responses to thrombin, but not SFLLRN, is due to cleavage of the receptor at Phe55-Trp56, deleting the tethered ligand domain, and 2) show that cathepsin G can activate thrombin receptors, but only if the cleavage site at Phe55-Trp56 is mutated or otherwise protected.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Regulation of thrombin receptors on human umbilical vein endothelial cells.

Activated thrombin receptors on human umbilical vein endothelial cells rapidly undergo homologous desensitization, leaving the cells unable to respond to thrombin. The present studies examine the fate of activated thrombin receptors on endothelial cells and the mechanisms that restore intact receptors to the cell surface. The results show that: 1) at biologically relevant concentrations, thrombin rapidly cleaves all of its receptors on the cell surface. 2) The cleaved receptors are cleared from the cell surface in a two-phase process, with 60% being internalized within 10 min, the remainder requiring several hours. 3) The restoration of intact, thrombin-responsive receptors on the cell surface initially occurs from an intracellular pool of receptors in a process that is independent of protein synthesis. 4) Recycling of cleaved receptors either does not occur on endothelial cells or is masked by receptor clearance. 5) Subconfluent endothelial cells re-express intact receptors on the cell surface at a slower rate than confluent cells. 6) The agonist peptide, SFLLRN, also causes receptor internalization, although at concentrations greater than those required for receptor activation and desensitization. These results are distinctly different from those observed with megakaryoblastic cell lines, where > 90% of the activated thrombin receptors are internalized rapidly, up to 40% of the cleaved receptors are recycled, and no intracellular pool of intact receptors has been detected. Since the primary structure of the thrombin receptor is the same in all the cell types studied, these results demonstrate that there can be substantial differences between cell types in the mechanisms involved in the clearance of activated receptors and the re-expression on the cell surface of intact receptors capable of responding to thrombin.

Amino Acid Sequence↗
PubMed1994

Changes in the structure and function of the human thrombin receptor during receptor activation, internalization, and recycling.

According to current models, human thrombin receptors are activated when thrombin cleaves the receptor's N terminus, exposing the tethered ligand domain, SFLLRN. In the megakaryoblastic CHRF-288 cell line, thrombin receptor activation is followed by the rapid internalization of > 90% of the receptors. In the present studies, antibodies directed at the site of cleavage by thrombin were used to examine changes in receptor structure during activation, internalization, and recovery. As would be expected, the initial rate of receptor cleavage was directly related to the thrombin concentration. However, even after prolonged incubation, receptor cleavage was incomplete until the thrombin concentration exceeded the receptor concentration. Only cleaved receptors were internalized in response to thrombin and only catalytically active thrombin and active variants of SFLLRN-containing peptides caused receptor internalization. Over a 3-h period following receptor activation by thrombin, there was a gradual recovery of approximately one-quarter of the receptors on the cell surface. These receptors were detectable with antibodies directed at retained portions of the receptor N terminus, but not with antibodies directed at the proposed site of cleavage, confirming that they are recycled, rather than new, receptors. At 4 degrees C two-thirds of the receptors cleaved by thrombin were retained on the cell surface. Like recycled receptors these "cold-cleaved" receptors failed to self-activate when warmed to 37 degrees C, but could be activated by SFLLRN. Unlike recycled receptors, however, the cold-cleaved receptors were also internalized and appeared to be activated by a second addition of thrombin. These results 1) provide strong evidence at the protein level that thrombin cleaves its receptors at the predicted site, 2) show that receptor activation is necessary for internalization, 3) suggest that each thrombin molecule may not activate large numbers of receptors, 4) demonstrate that a substantial fraction of internalized thrombin receptors can be recycled, and 5) suggest that the failure of recycled receptors to be reactivated by thrombin may involve a change in the receptor that does not occur at 4 degrees C. Finally, the inability of cold-cleaved receptors to self activate in the absence of thrombin, suggests that in addition to cleaving the receptor, thrombin may also play an important role in guiding the tethered ligand domain to regions on the remainder of the receptor that mediate activation.

Amino Acid Sequence↗
PubMed1994

Thrombin receptors: turning them off after turning them on.

Recent studies have helped to define the mechanisms by which thrombin activates platelets and other cells. Those studies show that the human thrombin receptor has a structure similar to other G protein-coupled receptors, but is activated by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become temporarily resistant to re-activation. Present evidence suggests that this loss of function is due to a combination of receptor desensitization, phosphorylation and internalization, and that recovery may involve dephosphorylation, as well as receptor recycling and the expression of newly-synthesized receptors. Together these processes provide a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.

Amino Acid Sequence↗
PubMed1992

Survival of human monoclonal anti-Rho (D) antibodies in the rhesus monkey.

In vivo half-life of a 125I-labeled human anti-D monoclonal antibody (mAb) and that of 131I-labeled Rho-GAM was assessed in a rhesus monkey injected simultaneously with both reagents. The half-life of the mAb was 7.9 days, compared to 17 days of Rho-GAM. Survival of the second dose of mAb, given 34 days after the first injection, was identical to that of the first dose, thus showing that the human mAb did not elicit an immune response. The in vitro produced human mAbs appear to be an alternative, unlimited source of anti-D antibodies for possible use in prevention of feto-maternal Rh immunization.

Animals↗
PubMed1987

Murine interstitial nephritis. VII. Suppression of renal injury after treatment with soluble suppressor factor TsF1.

We prepared soluble suppressor T cell factor (TsF1) from donor spleens harvested from mice primed with tubular antigen-derivatized lymphocytes to analyze both its functional interactions with a larger suppressor T cell network and its influence on the nephritogenic effector T cell response producing interstitial nephritis to a parenchymal antigen. Our findings indicate that TsF1 is antigen-specific, genetically restricted by I-J in its direct mediation of suppression, and capable of inhibiting the development of interstitial lesions. TsF1 also provides an inducing signal for the activation of effector Ts-2 suppressors following presentation by accessory cells. The induction of a Ts-2 effect, however, requires that the factor-presenting cell and the recipient of such cells share homology at I-J, and that the TsF1, the precursor Ts-2 cells, and the recipient of the Ts-2 effect share the same Igh-V allotype. Finally, the results of this current report clearly demonstrate a possible therapeutic role for soluble suppressor factors in the management of interstitial renal disease.

Animals↗
PubMed1987

Effector T cell differentiation in experimental interstitial nephritis. I. The development and modulation of effector lymphocyte maturation by I-J+ regulatory T cells.

Because mice susceptible to interstitial nephritis use different effector T cells than nonsusceptible mice, we analyzed the differentiation process of the effector T cell repertoire by using an in vitro culture technique. In the presence of helper T lymphocytes, accessory cells, IL 2, tubular antigen, and precursor effector cells, both Lyt-2+ nephritogenic effector cells and L3T4+ nonnephritogenic effector cells can be initially induced in both susceptible and nonsusceptible strains within 3 days of culture. In nonsusceptible mice, however, the Lyt-2+ nephritogenic cell is inhibited from further development and disappears, whereas in susceptible mice, its presence is preserved with a resulting effect of tissue destruction. This selection of effector T cell preference is regulated by I-J+ T lymphocytes which are co-functionally expressed with effector cell expansion. Unlike precursor effector lymphocytes, however, the maturation of the regulatory process requires a subset of I-J+ accessory cells and structurally intact tubular antigen. Our findings indicate, therefore, that both susceptible and nonsusceptible mice have the potential for the expression of interstitial nephritis, but nonsusceptible mice are formally protected from autoimmunity by the regulation of lymphocyte preference.

Animals↗
PubMed1987

Prostaglandin E1 inhibits effector T cell induction and tissue damage in experimental murine interstitial nephritis.

Immunosuppressive effects of E-series prostaglandins have been demonstrated in many in vitro assays of immune responsiveness as well as in autoimmune diseases. To explore the mechanisms underlying prostaglandin E1 (PGE1)-associated immunosuppression in autoimmunity, we treated SJL mice immunized to produce immune-mediated interstitial nephritis with PGE1, PGF2 alpha, or vehicle alone. Mice receiving PGE1 treatment do not develop interstitial nephritis, nor do they display delayed-type hypersensitivity (DTH) to the immunizing renal tubular antigen preparation. The observed immunosuppression is critically dependent on PGE1 administration during the period of effector T cell induction. We therefore investigated the effect of PGE1 on the in vitro induction of DTH effector T cells reactive to renal tubular antigens (SRTA). PGE1 inhibits effector T cell induction in a dose-dependent, reversible manner, but has no inhibitory effect on fully differentiated DTH effector cells or SRTA-reactive cell lines. The PGE1 effect is indirect and mediated via nonspecific suppressor lymphokines. This suppression can be overcome by recombinant interleukin 1 (IL-1), which suggests a mechanism related to either diminished IL-1 secretion or target cell sensitivity to IL-1.

Alprostadil↗
PubMed1983

Effect of treatment with Copolymer 1 (Cop-1) on the in vivo and in vitro manifestations of experimental allergic encephalomyelitis (EAE).

Injections of Copolymer 1 (Cop-1), a synthetic cathodic polymer, have been reported to prevent and treat successfully acute and recurrent EAE and has been employed in patients with multiple sclerosis (MS). It has been suggested that the therapeutic effect is due to cell-mediated immune (CMI) cross-reactivity between Cop-1 and myelin basic protein (MBP), the antigen that induces EAE. We found that Cop-1 treatment of guinea pigs (GP) sensitized with MBP in adjuvant (20 micrograms/animal): (a) lowers the incidence of clinical disease (8/20 vs 14/15); (b) decreases severity of disease in affected GP; (c) has little effect on pathologic lesions (mean pathology index +/- SEM: 1.2 +/- 0.2 vs 1.6 +/- 0.3; P greater than 0.1). Lymphocytes of MBP-sensitized GP treated with Cop-1 exhibited in vitro proliferative responses to MBP equivalent to lymphocytes of untreated EAE-GP (14,134 +/- 6,532 vs 11,821 +/- 3,874; mean cpm +/- SEM). GP sensitized to MBP or Cop-1 (100 micrograms/animal) showed reactivity to the sensitizing antigen but little in vitro reactivity to the other antigen. There was no correlation between the in vitro lymphocytes response to MBP and Cop-1 in individual GP. Treatment of MBP sensitized GP with calf-thymus histone (CTH) also resulted in a lower incidence of clinical EAE with less severe disease in affected GP. There was little effect on the pathologic index and no evidence of either inhibition of MBP-induced lymphocyte proliferative responses or cross-reactivity between MBP and CTH. Thus, treatment with Cop-1 or CTH inhibits clinical manifestations of acute EAE without suppressing inflammatory cell infiltrates or sensitization to MBP.

Animals↗
PubMed1982

Oligoclonal IgG in the cerebrospinal fluid of guinea pigs with acute experimental allergic encephalomyelitis.

The cerebrospinal fluid (CSF) of guniea pigs with experimental allergic encephalomyelitis was examined for the presence of oligoclonal IgG using polyacrylamide gel electrophoresis. Oligoclonal IgG (greater than or equal to 2 bands) was seen in the CSF obtained from 3/4 animals with experimental allergic encephalomyelitis induced by myelin basic protein and 2/3 with spinal cord-induced disease. It was not seen in CSF of 3 non-sensitized, 4 adjuvant-sensitized and 7 liver-sensitized guinea pigs. Scanning of stained gels confirmed the oligoclonal pattern. The bands were found in the region of gels which bound [125I]Staphylococcal Protein A. The data demonstrate that a non-infectious inflammatory reaction within the central nervous system can result in an oligoclonal IgG pattern in the CSF.

Animals↗