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C Bohuon

Publications and source records attributed to C Bohuon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia.

OBJECTIVES: To determine and compare the respective concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble TNF receptors, nitrite/nitrate (NO2-/NO3-), and procalcitonin in the plasma of patients with septic shock, cardiogenic shock, and bacterial pneumonia without shock; and to assess the predictive value of these mediators in defining patients with septic shock. DESIGN: Cohort study, comparing normal volunteers (controls) and patients with septic shock, cardiogenic shock, and bacterial pneumonia. SETTING: A collaborative study among an intensive care unit, an emergency room, and three research laboratories. PATIENTS: Mediators were measured at various times in 15 patients with septic shock (during the shock phase and during the recovery phase), in seven patients with cardiogenic shock during the shock phase, and in seven patients with severe bacterial pneumonia on day 1 of admission. INTERVENTIONS: Blood samples were collected at various times during the course of the disease. MEASUREMENTS AND MAIN RESULTS: TNF-alpha values were highest in the acute phase of septic shock (53 to 131 pg/mL during septic shock), while patients with bacterial pneumonia had intermediate concentrations (32 pg/mL). TNF-alpha concentrations were normal in patients with cardiogenic shock. IL-6 concentrations were highest in patients with acute septic shock (85 to 385 pg/mL). However, in contrast to TNF-alpha concentrations, IL-6 concentrations were normal in patients with bacterial pneumonia and increased in patients with cardiogenic shock (78 pg/mL). Soluble TNF receptors were increased in all three groups vs. controls, with the highest increase in patients with septic shock. NO2-/NO3- concentrations were highest (72 to 140 mM) in patients with septic shock, and were < 40 mM in the other groups of patients. Procalcitonin concentrations were only markedly increased in patients with septic shock (72 to 135 ng/mL, compared with approximately 1 ng/mL in the three other groups). The best predictive value for septic shock was found to be the measurements of NO2-/NO3- and procalcitonin concentrations. CONCLUSIONS: These observations showed that increase of proinflammatory cytokines was a consequence of inflammation, not of shock. In this study comparing various shock and infectious states, measurements of NO2-/NO3- concentration and procalcitonin concentration represented the most suitable tests for defining patients with septic shock.

Adult↗
PubMed1996

CD28-mediated cytotoxicity of YT natural killer cells on B7-positive targets induces rapid necrotic death independent of granule exocytosis.

The mechanisms leading to target cell killing by the human NK-like cell line YT2C2 have been studied. YT2C2 cells express CD28 antigen and kill B7-expressing targets by a CD28-mediated mechanism which is inhibited by anti-CD28 mAb (CD28.2). The lysis of B7-negative targets, which are also killed by YT2C2, is insensitive to CD28.2, but can be inhibited by cyclosporin A (CsA). CsA reduces degranulation in YT2C2 as measured by BLT-esterase release assays. A total suppression of B7-negative cell lysis was observed in the presence of EGTA, which blocks both degranulation and perforin polymerization, confirming that lysis of this type of target depends solely upon granule exocytosis. In contrast, an additional extracellular EGTA-resistant component in B7-positive target killing was evidenced. These results were consistently obtained with a panel of B7-positive and B7-negative targets, including a Jurkat subclone transfected to express B7 and its parental cell line. Ca2+-independent killing was completed during the first hour of the cytotoxicity assay, whereas EGTA-sensitive lysis increased throughout the whole incubation time. These two lytic mechanisms used by YT2C2 were found to induce two different modes of cell death. Extracellular Ca2+-dependent killing caused apoptotic death in both B7-positive and B7-negative targets, whereas the EGTA-resistant cytolytic pathway, observed exclusively with B7-positive targets, led to necrosis. CD28 triggering in YT2C2 induces, therefore, an additional mechanism of cell killing, independent of granule exocytosis, the nature of which remains to be identified.

Antibodies, Monoclonal↗
PubMed1996

Procalcitonin as a marker for the early diagnosis of neonatal infection.

Serum procalcitonin was determined in newborn infants at the time of admission to the pediatrics or obstetrics unit. Increased levels were found in all neonates with bacterial sepsis. Neonates with viral infection, bacterial colonization, or neonatal distress had normal or slightly increased levels. These data suggest that procalcitonin might be of value in diagnosing neonatal sepsis.

Bacterial Infections↗
PubMed1996

Effects of methyl substitutions on benz[a]anthracene derivatives-induced immunosuppression.

Polycyclic aromatic hydrocarbons are ubiquitous environmental contaminants known to be carcinogenic as well as immunosuppressive. Structure-activity studies have demonstrated that modifications in the number of methyl groups of benzanthracenic compounds lead to major changes in their biological activities such as induction of tumors. In the present study, we investigated the immunosuppressive effects of three benzanthracene derivatives differing by number or position of methyl radicals. 7,12-Dimethylbenz[a]anthracene, 12-methylbenz[a]anthracene, and 7-methylbenz[a]anthracene were tested for their ability to inhibit T-cell proliferation. For this purpose, we employed an in vitro activation model utilizing concanavalin A (ConA) or anti-CD3 monoclonal antibody (anti-CD3 mAb) to induce proliferation of murine T-lymphocytes from B6C3F1 mice. The three compounds inhibited splenocyte proliferation stimulated with anti-CD3 mAb, whereas DMBA and 12-MBA, but not 7-MBA, inhibited ConA-induced lymphoproliferation. Results concerning parameters involving interleukin-2 (IL-2) were correlated with those obtained for lymphoproliferation. IL-2 production and number of IL-2 receptors (IL-2R) per cell were inhibited by the three molecules tested, except for IL-2 production following ConA activation of cells treated with 7-MBA. Only DMBA profoundly affected IL-2 responsiveness, suggesting that this compound may inhibit both G0 to G1 and G1 to S transitions of the cell cycle. Addition of exogenous cytokines such as IL-1 and IL-6 with IL-2, or IL-2 alone, suggested that, for the three compounds tested, IL-1 and IL-6 production are not involved in benz[a]anthracene-induced immunosuppression. These results demonstrate that methylation at both 7 and 12 positions of the benzanthracene ring significantly enhances immunosuppression. In addition, DMBA may act on signal transduction mediated by the T-cell receptor (TCR) and the IL-2R, while this is not the case for 7-MBA and 12-MBA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

The role of histidine 231 in thermolysin-like enzymes. A site-directed mutagenesis study.

In the zinc metallopeptidases produced by the genus Bacillus, an active site histidine has been proposed to either stabilize the transition state in catalysis by donating a hydrogen bond to the hydrated peptide (Matthews, B. W. (1988) Acc. Chem. Res. 21, 333-340) or to polarize a water molecule, which subsequently attacks the peptidyl bond (Mock, W. L., and Aksamawati, M. (1994) Biochem. J. 302, 57-68). Site-directed mutagenesis techniques have been used to change this residue in the zinc endopeptidase from Bacillus stearothermophillus to either phenylalanine or alanine. At pH 7.0, the kcat/Km values of the substrate leucine enkephalin for the phenylalanine and alanine mutants were reduced by factors of 430- and 500-fold, respectively, as compared with the wild-type enzyme, mostly due to changes in kcat. In addition, the enzymatic activities of the mutant enzymes showed little pH dependence in the alkaline range, unlike the wild-type enzyme. The mutations did not greatly alter the binding affinities of inhibitors containing sulfydryl groups to chelate the active site zinc, while those of inhibitors containing hydroxamate or carboxylate zinc-chelating groups were increased between 80- and 250-fold. The largest change in the binding affinity of an inhibitor (> 5 orders of magnitude) was found with the proposed transition state mimic, phosphoramidon. The results are generally in agreement with x-ray crystallography studies and favor the involvement of the active site histidine in transition state binding.

Amino Acid Sequence↗
PubMed1995

Structure-activity relationships in glucocorticoid-induced apoptosis in T lymphocytes.

Glucocorticoid-induced apoptosis in the murine interleukin-2-dependent T-cell line CTLL-2 and in freshly isolated thymocytes was studied. It was demonstrated here that in CTLL-2 cells, dexamethasone (methyl in position 16 alpha) was more efficient in inducing apoptosis than betamethasone (methyl in position 16 beta) or triamcinolone (hydroxyl in position 16). In contrast, no such difference between these three molecules was found in murine thymocytes. In addition, we showed that glucocorticoid-induced apoptosis on the two models was mediated through interaction with the glucocorticoid receptor and did not occur in the presence of inhibitors of transcription, translation or an endonuclease-inhibitor. Furthermore, in CTLL-2 cells, apoptosis took place in the presence of EGTA whereas it was prevented in murine thymocytes, thus indicating that calcium plays a different role in these two models. Finally, higher concentrations of interleukin-2 were needed to protect CTLL-2 cells against dexamethasone-induced apoptosis than that induced by betamethasone or triamcinolone. Thus, structural differences at position 16 of the steroid nucleus correlate with a different apoptosis-inducing activity by glucocorticoids which, however, is only evidenced in the calcium-independent CTLL-2 model.

Animals↗
PubMed1995

Immunotoxicological investigation using pharmaceutical drugs. In vitro evaluation of immune effects using rodent or human immune cells.

In order to evaluate the relevance of in vitro methods for immunotoxicity assessment, the effects of pharmaceutical drugs on lymphoproliferative and cytotoxic functions of mouse splenocytes and human peripheral blood mononuclear cells (hPBMC) were studied. A comparison of sensitivity of immune cells from different origins to an in vitro exposure to different xenobiotics was performed using non-immunosuppressive (cimetidine and furosemide) and immunosuppressive (azathioprine (AZA), cyclosporine A (CSA), and dexamethasone (DEX)) drugs. For CSA, sensitivity of both rat and mouse splenocytes following in vitro exposure was compared to the one of hPBMC. Immune function tests included lymphoproliferative response to mitogenic lectins (concanavalin A (Con A) and phytohemagglutinin (PHA-P)) or to allogeneic cells (mixed leukocyte response (MLR)) and cytotoxicity assays (cytotoxic-T lymphocyte (CTL) and natural killer (NK) cell-mediated cytolysis). Additionally, to evaluate how well in vitro assays represent the in vivo situation, a comparison of the effect of cyclosporine A on the same immune function tests following in vivo or in vitro exposure was performed. The data obtained show numerous similarities in the effects observed following in vitro exposure of rodent or human cells to the drugs and a very similar sensitivity of rat and mouse cells to CSA in vitro. Discrepancies between human and rodent cells such as lymphoproliferative response to PHA-P following exposure to DEX or sensitivity of CTL-mediated cytolysis to CSA do exist. In vitro assays were very representative of the in vivo situation, both in the rat and in the mouse, following CSA exposure, except for NK cell activity in the rat. These data show the usefulness of in vitro systems for immunotoxicity assessment. They allow direct comparison of rodent and human systems, and could be representative, for drugs altering specifically the immune system like CSA does, of the in vivo situation.

Animals↗
PubMed1995

Elevated serum procalcitonin levels in patients with melioidosis.

The prognostic value of serum procalcitonin levels in 43 patients with acute melioidosis, an infection with a wide range of clinical manifestations, was assessed. In eight patients with mild localized infections, the median procalcitonin levels were 0.13 ng/mL (range, 0.02-0.46 ng/mL), which were similar to those in 19 healthy controls (median, 0.07 ng/mL; range, 0.03-0.15 ng/mL). In the patients with severe infections, the initial procalcitonin levels were significantly higher in the patients who died (median, 350 ng/mL; range, 63-3,538 ng/mL) than in the survivors (median, 19 ng/mL; range, 0.55-387 ng/mL) (P < .0001); 16 of 19 patients with procalcitonin levels of > 100 ng/mL died, compared with 2 of 16 patients with levels of < 100 ng/mL (relative risk, 6.7; 95% confidence interval, 1.8-25; P = .0001). In those patients who survived, the subsequent procalcitonin levels reflected closely the clinical course of their infection. The serum concentration of procalcitonin correlates well with the severity of Pseudomonas pseudomallei infection and is comparable with other acute-phase markers. However, this prognostic indicator and marker of continuing disease activity is not specific to melioidosis and could be applied to other severe infections.

Acute Disease↗
PubMed1994

Distribution of VRA09, an ovarian tumor-associated antigen, distinguishing borderline serous tumors.

We recently reported the characterization of an antigen designated VRA09, identified by a monoclonal antibody and overexpressed on the surface of vincristine-resistant human ovarian carcinoma cells. In the present study, we analyze the distribution of this antigen in normal and tumor tissues. Its pattern of expression appears to differ from that described for other drug-resistance- and/or tumor-associated antigens. In normal tissues, the antigen has a restricted histological distribution and appears to be localized in mesoderm-derived tissues. In tumor tissues, VRA09 expression was mainly detected in serous ovarian tumors. Indeed, VRA09 is strongly expressed in papillary serous cystadenocarcinomas and their metastases, and more specifically in the basement membranes of serous tumors of borderline malignancy. In contrast, no immunostaining was observed in normal ovarian tissue or benign tumors. The detection of this antigen may help to identify serous ovarian tumors by distinguishing tumors of low malignancy from cystadenocarcinomas.

Antibodies, Monoclonal↗
PubMed1994

Effects of a primary immune response to T-cell dependent antigen on serotonin metabolism in frontal cortex: in vivo microdialysis study in freely moving Fischer 344 rat.

Antigenic challenge is known to influence brain catecholamine turnover, e.g. hypothalamic norepinephrine activity, but little is known about effects on the activity of serotoninergic neurons, i.e. the release of the neurotransmitter at nerve terminals. In the present study, we first investigated the changes of central serotonin (5-HT) metabolism in Fischer 344 male rats at 2, 3, 4 and 5 days following i.v. immunization with sheep red blood cell (SRBC). Major decreases in 5-HT levels were evident in the hypothalamus (Hy) and cortex (Cx) at a time which corresponded to the late phase of the production of specific antibodies to SRBC measured with a plaque-forming cell assay (PFC). A pretreatment with an immunosuppressive drug, cyclosporin A (CsA; 12.5 mg/kg by gavage for 7 days) prevented the decreases in cortical 5-HT levels. Concomitantly, a 2-fold increase in the basal 5-HT release at frontocortical nerve terminals was observed by using in vivo microdialysis in awake rats on Day 3 following SRBC inoculation. This effect was totally suppressed by CsA. Our data suggest that the decrease in brain 5-HT levels that occurs after antigen administration may reflect a specific short-lasting CsA-dependent-release of 5-HT at frontocortical nerve terminals at a time (Day 3 or 4) when the splenic immune response is maximal.

Animals↗
PubMed1994

Immunotoxicological investigation using pharmaceutical drugs: in vivo evaluation of immune effects.

Traditional methods for toxicological assessment have indicated that the immune system is a frequent target of toxic insult following subchronic or chronic exposure to xenobiotics. However, most of the xenobiotics evaluated in standardized protocols were environmental chemicals and correlation with available clinical data was not possible. The purpose of this work was to evaluate the potential immunosuppressive effects of pharmaceutical drugs using a standardized protocol developed for immunotoxicological assessment. Two groups of pharmaceutical drugs were utilized: (a) drugs without known immunosuppressive effect linked to their utilization in human therapy (cimetidine, furosemide, indomethacin, amoxicillin, and procainamide) and (b) immunosuppressive drugs (azathioprine, cyclosporine A, and dexamethasone). Ex vivo tests using B6C3F1 mice were performed after a 28-day repeat dose regimen and assessed: (a) immunopathology, (b) cell-mediated immunity, (c) humoral immunity, and (d) nonspecific immunity. Host resistance to Listeria monocytogenes was also assessed following exposure to immunosuppressive drugs. The results showed that (a) immunopathology and immune function assays were necessary to detect all immunotoxicants and (b) the effects observed with nonimmunotoxic drugs were sometimes statistically significant but the biological significance of these effects is unlikely.

Animals↗
PubMed1994

Detection of a 45-kilodalton antigen overexpressed in a cisplatin-resistant human ovarian carcinoma cell line.

To characterize the membrane changes associated with cisplatin resistance, we raised monoclonal antibodies (MAbs) against a cisplatin-resistant subline (OV1/DDP) derived from a human ovarian carcinoma cell line (OV1/p). An MAb, designated OCP02, was selected for its particularly high affinity for the resistant cell line. It bound 3.1-fold higher to OV1/DDP cells than to OV1/p cells and recognized an M(r) 45K antigen. This antigen appeared to be present in several normal and tumorous tissues. Its distribution in normal tissues was mainly detected in tissues involved in secretory processes, suggesting that this antigen could be related to a transport mechanism in normal cells as well as in drug-resistant cells.

Animals↗
PubMed1994

Procalcitonin increase after endotoxin injection in normal subjects.

As procalcitonin concentrations have been shown to be elevated in patients with septicemia and gram-negative infections in particular, we proceeded to investigate the effect of endotoxin, a product of gram-negative bacteria, on procalcitonin concentrations in normal human volunteers. Endotoxin from Escherichia coli 0113:H10:k, was injected i.v. at a dose of 4 mg/kg BW into these healthy volunteers. Blood samples were obtained before and 1, 2, 4, 6, 8, and 24 h after injection of the endotoxin. Each patient's cardiovascular and overall clinical status was monitored over this period. The patients developed chills and rigors, myalgia, and fever between 1-3 h. Tumor necrosis factor-alpha levels increased sharply at 1 h and peaked at 90 min, reaching the baseline concentration thereafter by 6 h. Interleukin-6 levels increased more gradually, peaking at 3 h and reaching the baseline concentration at 8 h. The procalcitonin concentration, which was undetectable (< 10 pg/mL) at 0, 1, and 2 h, was detectable at 4 h and peaked at 6 h, maintaining a plateau through 8 and 24 h (4 ng/mL). There was no elevation of calcitonin concentrations, which remained below 10 pg/mL, the lowest sensitivity of the assay. Procalcitonin was measured by a two-antibody immunoradiometric assay specific for this peptide, with no cross-reactivity with calcitonin, katacalcin, or calcitonin gene-related peptide. We conclude that endotoxin induces the release of procalcitonin systemically, that this increase is not associated with an increase in calcitonin, and that the increase in procalcitonin associated with septicemia in patients may be mediated through the effect of endotoxin described here. Whether procalcitonin participates in the mechanisms underlying inflammation remains to be investigated.

Adult↗
PubMed1994

Effect of ketanserin on monoamines and neuropeptide Y in brain and peripheral tissues of normotensive (WKY) and spontaneously hypertensive (SHR) rats.

The effect of one intraperitoneal (i.p.) injection of ketanserin (K) (20mg/kg) on the levels of monoamines and neuropeptide Y (NPY) in some central and peripheral tissues was examined in normotensive (WKY) and spontaneously hypertensive (SHR) rats. In WKY rats, K induced a depletion of norepinephrine (NE) in the hypothalamus, the medulla, the atria and the caudal artery together with a decrease in dopamine level (DA) in the hypothalamus and in serotonin level (5-hydroxytryptamine, 5-HT) in the medulla. The reduction reached 25% to 35%. In SHR, NE and DA levels in the hypothalamus, and NPY levels in the caudal artery were lower than in WKY, while NE was higher in the adrenals. After treatment with K, NE, 5-HT, 5-HIAA (5-hydroxyindoleacetic acid) and NPY in the medulla were increased by about 30% to 50% while NE in the caudal artery was reduced by about the same value as in WKY. These results indicate that K-induced release of monoamines is not linked to NPY release. Moreover, monoamine and NPY sensitivity to K differ in SHR and WKY rats.

Animals↗
PubMed1993

Age-related changes of noradrenergic-NPY interaction in rat brain: norepinephrine, NPY levels and alpha-adrenoceptors.

Noradrenergic-neuropeptide Y interaction, which is implicated in different physiological functions, was studied in senescent rats. Norepinephrine (NE) and neuropeptide Y (NPY) levels were measured in brainstem and hypothalamus, and alpha-adrenergic binding was investigated in brainstem in young (4 months) and old (34 months) Wistar rats. NE concentration was the same in senescent rats, whereas NPY concentration was decreased both in brainstem and hypothalamus compared to levels in young rats. [3H]prazosin binding to alpha 1-adrenoceptors was not modified, but [3H]rauwolscine binding to alpha 2-adrenoceptors was altered with age. In fact, the density of alpha 2-adrenoceptors (Bmax) was lower, while the binding affinity (Kd) was increased in old compared to young rats. These results suggest that the decrease of NPY levels could be one of the possible reasons for changes in [3H]rauwolscine binding to alpha 2-adrenoceptors in old rats. The G-protein-adenylate cyclase system, which is impaired in senescent rats, could be involved in the disorganization of noradrenergic-NPY interaction.

Aging↗
PubMed1993

High serum procalcitonin concentrations in patients with sepsis and infection.

High concentrations of calcitonin-like immunoreactivity have been found in the blood of patients with various extrathyroid diseases. By means of a monoclonal immunoradiometric assay for calcitonin precursors, we have measured serum concentrations of procalcitonin in patients with various bacterial and viral infections. 79 children (newborn to age 12 years) in hospital with suspected infections were investigated prospectively. 19 patients with severe bacterial infections had very high serum concentrations of procalcitonin at diagnosis (range 6-53 ng/mL) in comparison with 21 children found to have no signs of infection (baseline concentrations < 0.1 ng/mL). Serum procalcitonin values decreased rapidly during antibiotic therapy. 11 patients with peripheral bacterial colonisation or local infections without invasive sepsis and 18 (86%) of 21 patients with viral infections had concentrations within or slightly above the normal range (0.1-1.5 ng/mL). Among 9 severely burned patients studied in an intensive care unit, the post-traumatic course of procalcitonin concentrations (range 0.1-120 ng/mL) was closely related to infectious complications and acute septic episodes. Concentrations of mature calcitonin were normal in all subjects, whatever procalcitonin concentrations were found. Concentrations of a substance immunologically identical to procalcitonin are raised during septic conditions. Serum concentrations seem to be correlated with the severity of microbial invasion.

Bacterial Infections↗
PubMed1993

Fasting affects more markedly neuropeptide Y than monoamines in the rat brain.

Monoamine turnover and neuropeptide Y (NPY) levels were evaluated in the CNS of 48- and 72-h-fasting adult, male rats in four brain areas: the hypothalamus, cortex, hippocampus, and striatum. In 48-h-fasted rats, NPY levels increased in the cortex and decreased in the striatum. The dopaminergic turnover increased in the hippocampus. The serotonergic turnover decreased in the hippocampus, striatum, and cortex and was still decreased after 72 h of fasting. In 72-h-fasted rats, an overall significant increase of NPY levels was observed except in the striatum, where it decreased significantly. No relationship appeared between NPY and monoamine levels, suggesting that NPY can act independently in feeding behavior and play, in different brain areas, an important role in its regulation.

Animals↗