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Biomedical subjects

C Dubois

Publications and source records attributed to C Dubois.

At least 91 records · Page 5Linked to original sources
PubMed1994

The protective role of endogenously synthesized nitric oxide in staphylococcal enterotoxin B-induced shock in mice.

Nitric oxide (NO) synthesis during experimental endotoxemia has been shown to have both deleterious and beneficial effects. In the present study, we analyzed the in vivo production and the regulatory role of NO in the shock syndrome induced by staphylococcal enterotoxin B (SEB) in mice. First, we found that intraperitoneal administration of 100 micrograms SEB in BALB/c mice induced a massive synthesis of NO as indicated by high serum levels of nitrite (NO2-) and nitrate (NO3-) peaking 16 h after SEB injection. The inhibition of NO2- and NO3- release in mice injected with anti-tumor necrosis factor (TNF) and/or anti-interferon gamma (IFN-gamma) monoclonal antibody (mAb) before SEB challenge revealed that both cytokines were involved in SEB-induced NO overproduction. In vitro experiments indicated that NO synthase (NOS) inhibition by N-nitro-L-arginine methyl ester (L-NAME) enhanced IFN-gamma and TNF production by splenocytes in response to SEB. A similar effect was observed in vivo as treatment of mice with L-NAME resulted in increased IFN-gamma and TNF serum levels 24 h after SEB challenge, together with persistent expression of corresponding cytokine mRNA in spleen. The prolonged production of inflammatory cytokines in mice receiving L-NAME and SEB was associated with a 95% mortality rate within 96 h, whereas all mice survived injections of SEB or L-NAME alone. Both TNF and INF-gamma were responsible for the lethality induced by SEB in L-NAME-treated mice as shown by the protection provided by simultaneous administration of anti-IFN-gamma and anti-TNF mAbs. We conclude the SEB induces NO synthesis in vivo and that endogenous NO has protective effects in this model of T cell-dependent shock by downregulating IFN-gamma and TNF production.

Amino Acid Oxidoreductases↗
PubMed1994

Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells.

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AMLs) characterized by the presence of the t(15,17) translocation and the resulting promyelocytic myeloid leukemia/retinoic acid receptor alpha (PML/RAR alpha) fusion proteins. To date APL is the only AML that is sufficiently sensitive to all-trans retinoic acid's (ATRA) differentiating effect. In vivo ATRA alone achieves complete remission in most APL patients. However, failure or partial responses are observed and the molecular basis of the absence of ATRA response in these patients has not been determined. To gain insights in the cell growth and differentiation of APL cells, expression of hematopoietic growth factors (HGF) shown to be produced by leukemic cells (interleukin-1 beta [IL-1 beta], IL-6, tumor necrosis factor alpha (TNF alpha), granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and IL-3) was studied in 16 APL samples. Twelve APL cases expressed IL-1 beta, IL-6, and TNF alpha, but not G-CSF, GM-CSF, and IL-3. These cases achieved complete remission with ATRA therapy. The four remaining patients (either TNF alpha negative or G-CSF, GM-CSF or IL-3 positive) did not achieve complete remission with ATRA. In all cases, in vivo response to ATRA therapy was correlated to the in vitro differentiation effect of all-trans retinoic acid 10(-6) mol/L. Thus, ATRA differentiation induction was strongly correlated to the HGF expression (P < .0001). These results suggest that the presence or absence of HGF's expression by APL cells may contribute to the therapeutic effect of ATRA in this disease.

Cell Differentiation↗
PubMed1994

Myocardial viability assessment in ischemic cardiomyopathy: benefits of coronary revascularization.

Patients with ischemic heart disease, congestive heart failure, and low ejection fraction are usually referred for orthotopic heart transplantation. Based on results of myocardial viability assessment, we have prospectively used either coronary artery bypass grafting or orthotopic heart transplantation. From January 1990 to June 1992, among 50 patients initially referred for heart transplantation, 46 showing myocardial viability underwent bypass grafting. Forty-five of these 46 patients were men, and the mean age was 58 +/- 12 years (range, 40 to 70 years). Congestive heart failure was present in all patients, and dyspnea was the main symptom in 80% (37/46). Patients were selected according to three criteria. (1) Myocardial viability was primarily assessed by thallium scintigraphy for up to 24 hours (28/46 patients). When results were negative, patients underwent positron emission tomography (20/46 patients). (2) Regional left ventricular function was assessed using gated blood pool single-photon emission computed tomography combined with (3) full hemodynamic evaluation. Results were as follows: end-diastolic volume, 129 +/- 35 mL/m2; ejection fraction, 0.23 +/- 0.06; cardiac index, 2.4 +/- 0.62 L.min-1.m-2; mean pulmonary artery pressure, 26 +/- 0.90 mm Hg; and mean pulmonary capillary wedge pressure, 16 +/- 1.10 mm Hg. Operative mortality was 2.17% (1/46). During follow-up (mean duration, 18 months), there were three late cardiac-related deaths (arrhythmias) and two noncardiac-related deaths. The 40 long-term survivors are in New York Heart Association class II. Angiography (15 patients) or gated blood pool single photon emission tomography (32) showed improvement in mean ejection fraction to 0.39 +/- 0.13 (range, 0.22 to 0.46).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Expression of NCAM and its polysialylated isoforms during mdx mouse muscle regeneration and in vitro myogenesis.

In order to understand the mechanism of the muscular regenerative process which occurs in mdx mice, the expression of neural cell adhesion molecule (NCAM) isoforms and their polysialylated (PSA) derivatives were studied during the postnatal development of normal and mdx mice in relation to the stage of the regeneration of muscle fibres, in the quadriceps. NCAM expression was also examined during in vitro differentiation of satellite cells isolated from both mdx and normal muscles. The immunohistochemical and biochemical analyses were done using antibodies for the different isoforms. The data presented here suggest that before the onset of necrosis and regeneration, the expression of NCAM isoforms in the quadriceps of mdx mice was similar to normal mice. Later, NCAM and PSA-NCAM expression in mdx mice increased and was related to the muscular regenerative process, and the overall level of NCAM expression can be considered as a good index of muscle regeneration. Young regenerative fibres expressed NCAM and PSA-NCAM, while mature regenerative fibres, in which myonuclei remained centrally located, did not express either NCAM or the PSA isoforms. Therefore, in terms of NCAM expression, the fibres in mdx muscle with centrally located nuclei appeared similar to mature fibres found in normal adult muscle. A major form of 145 kDa and a minor form of 115 kDa were detected in mdx regenerative muscle. The 145 kDa NCAM was sialylated, as demonstrated by its sensibility to exoneuraminidase which generates a desialoform of 125 kDa, but not polysialylated since it was not recognized by the anti-MenB antibody, specific for PSA-NCAM. In contrast, the molecular forms of NCAM migrating as a broad band from 160 kDa to 220 kDa were identified as PSA-NCAM. The comparison of in vitro differentiation of normal and mdx satellite cells showed that the expression of NCAM isoforms by mdx cells was similar to that expressed by normal cells. Both our in vivo and in vitro data concerning NCAM expression show that regeneration in mdx mice does not differ from that observed in other necrotic diseases. In other words, NCAM is unlikely to be a dystrophin-associated molecule since lack of dystrophin does not affect its expression.

Animals↗
PubMed1994

Effects of moderate amounts of emulsified dietary fat on postprandial lipemia and lipoproteins in normolipidemic adults.

Eight normolipidemic males ingested a meal containing either 42 g fat or 31 g fat in the form of emulsions (9.0 and 9.2 m2) and a fixed amount of retinyl palmitate. Fasting and postmeal blood samples were obtained for 7 h. Serum and chylomicron triglyceride responses were related to the amount of fat ingested and peaked after 2-3 h. The chylomicron retinyl palmitate response was lower (P < or = 0.05) with the 31-g fat supply. After the 42-g fat intake, but not after the 31-g fat intake, serum free cholesterol and phospholipids increased and esterified cholesterol decreased postprandially. Significantly different responses were observed after both meals for low-density-lipoprotein (LDL) free cholesterol, very-low-density-lipoprotein (VLDL) and LDL esterified cholesterol, and high-density-lipoprotein (HDL) phospholipids. These data show that ingesting 31 g instead of 42 g fat in a meal reduces postmeal lipoprotein variations and suggest that a threshold level of dietary fat should be overcome to promote significant postprandial changes in lipoprotein particles.

Adult↗
PubMed1994

Response to desipramine treatment in adolescent depression: a fixed-dose, placebo-controlled trial.

OBJECTIVE: To determine the efficacy and tolerability of the tricyclic antidepressant desipramine (DMI) in the treatment of DSM-III-R-diagnosed major depressive disorder in adolescents. METHOD: Sixty adolescents (42 female, 18 male; aged 15 to 19 years) diagnosed with major depressive disorder using clinical interview and Schedule for Affective Disorders and Schizophrenia for School-Age Children were randomized to receive either DMI (200 mg daily in divided doses) or placebo for six consecutive weeks following a 1-week placebo period. Treatment outcome was determined using the Hamilton Depression Rating Scale and the Beck Depression Inventory. Tolerability was determined using a symptom side effects scale. In addition, a variety of laboratory and cardiovascular monitoring was performed. RESULTS: No significant differences in treatment outcome between DMI- and placebo-treated groups were determined. Neither DMI, nor its metabolite 2-hydroxy-DMI, nor their ratio, was positively correlated to treatment outcome. The DMI group endorsed more side effects but there were no significant between-group differences in any laboratory, electrocardiographic, or other cardiovascular parameters apart from heart rate, which was increased in the DMI-treated group (p = .03). CONCLUSIONS: Given the findings of this study and our review of previously published reports of tricyclic antidepressant treatment in this population, the routine use of short-term (6 weeks) DMI in the treatment of adolescent depression is not supported by the data on hand. Further investigations into what constitutes optimal psychopharmacological treatment of adolescent depression are warranted.

Adolescent↗
PubMed1994

Late reoperations in patients with aortic dissection.

Aortic dissection is an evolving process that may require one or several reoperations after the initial emergency repair. From January 1977 to September 1993, 148 patients underwent emergency surgery for type A acute aortic dissection. The replacement of the ascending aorta was extended to include the transverse arch in 43 patients (29%). One hundred fifteen patients (78%) survived surgery. During the same period, 37 patients required reoperation once (28), twice (7), or three times (2), for a total of 48 reoperations. Twenty-one patients had undergone initial repair in our institution; 16 patients had been operated on elsewhere. Reoperation was indicated for: aortic valve disease (4); a new dissecting process (7); threatening aneurysmal evolution of a persisting dissection (34); or false aneurysm (3). The re-do procedure involved: the aortic root and/or ascending aorta in 12 cases (group I); the ascending aorta and the transverse arch in 6 cases (group II); the transverse arch alone in 8 cases (group III); the transverse arch and descending aorta, or the descending aorta alone in 11 cases (group IV); and the thoracoabdominal aorta in 11 cases (group V). Risk factors for reoperation were analyzed in the 115 survivors initially operated on at our institution. Seven of 20 Marfan patients (35%) versus 12 of 95 non-Marfan patients (12.6%) required reoperation (p < 0.02). None of the 31 patients surviving arch replacement at initial repair required a reoperation, versus 21 of 84 (25%) patients surviving replacement limited to the ascending aorta (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Characterization of emulsions and lipolysis of dietary lipids in the human stomach.

Fasting subjects were intragastrically intubated and received a coarsely emulsified test meal. Gastric aspirates were collected after 1, 2, 3, and 4 h. During digestion in the stomach, unemulsified lipids (> or = 100 microns) represented a minor fraction. A significant amount of the large 70- to 100-microns lipid droplets disappeared, and fine 1- to 10-microns droplets were generated. The median lipid droplet diameter significantly decreased (21.9 vs. 52.9 microns) after 1 h and kept intermediate values for longer periods of time. The emulsion surface area was 100-120 m2/l and was basically provided by 1- to 100-microns droplets. Lipolysis catalyzed by gastric lipase primarily occurred within the first hour of digestion (11.9%). Smaller droplets were enriched in triglyceride lipolytic products. The free fatty acid concentrations were in the range of 5.6-8.2 mM over 1-4 h. The present finding demonstrates for the first time that in the human stomach most dietary lipids are present in the form of emulsified droplets, in the range of 20-40 microns, and that gastric lipolysis can help to increase emulsification in the stomach.

Dietary Fats↗
PubMed1994

Enoximone vs nicardipine during the early postoperative course of patients undergoing cardiac surgery. A prospective study of two therapeutic strategies.

The hemodynamic effects of enoximone and nicardipine were compared during the early postcardiac surgery period in 40 patients with systemic hypertension and moderate cardiac dysfunction. Patients were prospectively randomized into two groups. Mean right atrial pressure was maintained above 7 mm Hg. The drug infusion rate was adjusted to maintain mean systemic artery pressure (SAP) within the 65 to 80 mm Hg range. Complete hemodynamic evaluations were performed before any drug infusion and during the following 24 h with special attention to O2-related variables. Oxygen consumption, cardiac index, and stroke index improved significantly and similarly in the two groups. The SAP and systemic vascular resistance decreased more rapidly in the enoximone group but whole body lactate level increased after the second hour of infusion. Furthermore, this was paralleled by an arteriovenous O2 contents difference deficit. In our study, nicardipine was found superior over enoximone in terms of recovery from intraoperative tissue hypoxia. Furthermore, enoximone's inotropic effects were not found to be clinically relevant.

Cardiac Surgical Procedures↗
PubMed1994

Modulation of IL-8, IL-1 beta, and G-CSF secretion by all-trans retinoic acid in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a homogeneous subgroup of acute myeloid leukemias (AML) characterized by the presence of the t(15;17) translocation and the resulting PML/RAR alpha fusion proteins. To date APL is the only AML which is sufficiently sensitive to all-trans retinoic acid (ATRA) differentiating effect. We have recently reported that APL express and secrete hematopoietic growth factors (HGF) such as IL-1 beta, TNF alpha, and IL-6. In vivo ATRA alone allows achievement of complete remission in APL patients. One of ATRA therapy's drawbacks is the increase of peripheral blast cells often associated with the ATRA leukocyte activation syndrome. To determine if this specific side-effect was linked to an increase of HGF release by APL cells, we studied the modulation of cytokine production by APL cells, we studied the modulation of cytokine production by APL samples (n = 12) before and after incubation with ATRA. ATRA failed to modulate TNF alpha, IL-6 or GM-CSF secretion levels; however, IL-8 levels decreased in 11 cases, and in four cases up-regulation of IL-1 beta and G-CSF protein expression was observed. These modulations were found to be linked to ATRA sensitivity as ATRA failed to modulate cytokine production in non-APL cells (n = 8). Interestingly, the increase of IL-1 beta and G-CSF production in the presence of ATRA was highly correlated to an increase in APL cell count in vitro and in vivo hyperleukocytosis, resulting in fatal outcome. IL-1 beta, TNF alpha, IL-6, and IL-8 are known to be implicated in leukocyte activation. The results of this study suggest that ATRA-induced hyperleukocytosis and ATRA leukocyte activation syndrome in APL may be inherent to the secretion of specific hematopoietic growth factors by the APL cells.

Blotting, Northern↗
PubMed1994

Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects.

Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.

Adult↗
PubMed1994

Induction of high-affinity GM-CSF receptors during all-trans retinoic acid treatment of acute promyelocytic leukemia.

Differentiation of normal myeloid cells is accompanied by the increase of high-affinity GM-CSF receptors necessary for progenitor proliferation/differentiation and mature neutrophil function. All-trans retinoic acid (ATRA) induces terminal differentiation of acute promyelocytic leukemia cells (AML3 subtype). We report in this study that AML3 cells, like other AML subtypes, harbor high-affinity GM-CSF R (n = 138.3 +/- 69.3 sites/cell, Kd = 76.9 +/- 68.8 pM). In all cases, incubation with ATRA induces either an increase in the number of affinity of GM-CSF R (n = 212.7 +/- 116.2 sites/cell, Kd = 43.2 +/- 22.5 pM). The data presented show that modulation of GM-CSF receptors cells is correlated to the degree of ATRA-induced granulocytic differentiation but not to increased cell growth.

Cell Differentiation↗
PubMed1994

Aortic dissection. Prevalence, cause, and results of late reoperations.

From January 1977 to September 1992, 143 patients underwent an emergency operation for type A acute aortic dissection. Because of the location of the intimal tear, the replacement of the ascending aorta was extended to the transverse arch in 42 patients (29.3%). One hundred ten patients (78%) survived the operation. During the same period, 32 patients had to be reoperated on once (n = 24) twice (n = 6), or three times (n = 2) for a total of 42 reoperations. Nineteen patients had had the initial repair in our institution, and 13 had been operated on elsewhere. Reoperation was indicated for aortic valve disease (n = 4), recurring dissection (n = 7) threatening aneurysmal evolution of a persisting dissection (n = 28), or false aneurysm (n = 3). The redo procedure involved the aortic root and/or ascending aorta in 15 cases (group I), the transverse arch alone in 7 cases (group II), the transverse arch and the descending aorta or the descending aorta alone in 10 cases (group III), or the thoracoabdominal aorta in 10 cases (group IV). The risk factors for reoperation have been analyzed in the 110 survivors initially operated on in our institution. Seven of 18 patients with Marfan's syndrome (38.8%) versus 12 of 92 without Marfan's syndrome (13%) were reoperated on (p = 0.023). None of the 30 patients surviving arch replacement at initial repair required a reoperation, versus 19 of 80 (23.7%) patients surviving a replacement limited to the ascending aorta (p = 0.013). The overall mortality rate of reoperation was 21.8% (7/32) with a risk of 16.6% (7/42) at each procedure (group I, 13.3%; group II, 0%; group III, 20%; group IV, 30%). Hospital mortality was influenced by emergency operation (5/10) (p < 0.005) and thoracoabdominal replacement (3/10) (p < 0.035). The late survivals after reoperation are 65.1% +/- 17.6% at 1 year and 55% +/- 19.63% at 5 years (Kaplan-Meier, confidence interval 95%). The late survivals, after the initial repair, of the patients undergoing reoperation are 89.6% +/- 11.0%, 79.3% +/- 14.7%, 53.9% +/- 18.1%, and 35.9% +/- 21.8% at 1, 5, 10, and 12 years, respectively. In conclusion, aortic dissection is an evolving process that may require one or several reoperations after the initial repair. At initial emergency operation, the resection of the entry site, when located on or extending to the transverse arch, has reduced the risk of reoperation, in our experience. Elective reoperation must be considered before the occurrence of complications, especially in patients with Marfan's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1994

Famotidine in the management of gastro-oesophageal reflux.

Famotidine has been used for the treatment of peptic ulcers and Zollinger Ellison syndrome and is also useful in reflux and erosive oesophagitis. To evaluate the effects of Famotidine 20 mg given twice daily in the symptomatic relief of gastro-oesophageal reflux disease with normal oesophagus or mild endoscopic oesophagitis, patients were followed over a period of six weeks. 70% of the patients had complete day-time heartburn relief during the study and 75% had complete night-time heartburn relief during the study. Famotidine was found to be safe and there were no serious clinical or laboratory adverse experiences.

Adult↗
PubMed1994

Poor response to all-trans retinoic acid therapy in a t(11;17) PLZF/RAR alpha patient.

All-trans retinoic acid (ATRA) is a potent inducer of differentiation and cell death in malignant cells. Its effect is known to be mediated through binding to specific nuclear (RARs and RXRs) or cytoplasmic (CRABP) proteins. ATRA is strikingly effective in acute promyelocytic leukemia (the AML3 subtype) inducing a high incidence of complete remissions. Paradoxically, most AML3 cells harbor an abnormal retinoic acid receptor (PML/RAR alpha) resulting from the t(15;17) translocation. Though few AML3 patients do not respond to ATRA therapy, individualization of these cases is of practical importance. Recently the RAR alpha gene has been demonstrated to be involved in a novel fusion transcript (PLZF/RAR alpha) through a t(11;17) translocation. We describe here the second case of such a patient with a t(11;17)-PLZF/RAR alpha leukemic clone. Southern analysis revealed that the breakpoint in the RAR alpha gene was within the second intron (as for PML/RAR alpha) and the intron separating the second and third zinc finger of the PLZF gene. In vitro, the leukemic cells did not show increased NBT reduction or loss of self-renewal after incubation with ATRA. After therapy with ATRA, only partial remission was obtained. These results suggest that the t(11;17) (PLZF/RAR alpha) case of this study was less responsive to ATRA therapy than t(15;17) (PML/RAR alpha) cases and raises the question of the definition of this novel AML subtype.

Aged↗
PubMed1993

In vivo induction of interleukin 10 by anti-CD3 monoclonal antibody or bacterial lipopolysaccharide: differential modulation by cyclosporin A.

We investigated the in vivo effects of cyclosporin A (CsA) on the production of interleukin (IL) 10, a cytokine with major immunosuppressive properties. To elicit IL-10 production in vivo, BALB/c mice were injected either with the anti-mouse CD3 145-2C11 monoclonal antibody (mAb) (25 micrograms) or with bacterial lipopolysaccharide (LPS) (20 micrograms). A systemic release of IL-10 was observed in both models, IL-10 serum levels reaching 1.60 +/- 0.32 U/ml (mean +/- SEM) and 0.67 +/- 0.09 U/ml 6 h after injection of 145-2C11 mAb and LPS, respectively. Experiments in nude mice indicated that T cells are involved in the induction of IL-10 by anti-CD3 mAb, but not by LPS. Pretreatment with CsA (total dose: 50 mg/kg) before injection of 145-2C11 mAb completely prevented the release of IL-10 in serum as well as IL-10 mRNA accumulation in spleen cells. In contrast, CsA markedly enhanced LPS-induced IL-10 release (IL-10 serum levels at 6 h: 8.31 +/- 0.43 vs. 0.71 +/- 0.15 U/ml in mice pretreated with CsA vehicle-control, p < 0.001), as well as IL-10 mRNA accumulation in spleen. We conclude that CsA differentially affects IL-10 production in vivo depending on the nature of the eliciting agent. This observation might be relevant to clinical settings, especially in organ transplantation.

Animals↗