Biomedical subjects

C Dubois

Publications and source records attributed to C Dubois.

At least 19 recordsLinked to original sources

PubMed1992

Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain.

Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4-galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30-Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi.

Amino Acid Sequence↗

PubMed1992

Mediastinitis due to Nocardia asteroides after cardiac transplantation.

Nocardia infection classically occurs in immuno-compromized patients. Only a few cases of mediastinal infection due to this pathogen have been described in the literature. We report a patient who developed mediastinitis due to Nocardia asteroides after cardiac transplantation. The treatment was surgical debridement, dressing, sugaring and antibiotic therapy. The emergence of a severe acute renal failure possibly induced by drug interaction between Cyclosporin, cyclines and aminoglycosides, led us to modify the antimicrobial treatment. The intravenous use of Imipenem 2 g per day and Ciprofloxacin 400 mg per day for four weeks and then oral Ciprofloxacin 1.5 g per day for 1 year, was effective and allowed a good outcome, without any drug interaction with Cyclosporin, adverse effect, graft rejection episode or infection relapse.

Anti-Bacterial Agents↗

PubMed1992

[Etomidate modifies hemodynamic response to fentanyl in patients with impaired left ventricular function].

The haemodynamic effects and the side-effects of anaesthesia using high doses of fentanyl were compared in two groups of 12 patients each. All the patients had poor left ventricular function and were scheduled for elective coronary artery bypass graft surgery or valvular replacement. Patients were randomly assigned to either group. In group EF, patients were given 5 micrograms.kg-1 of fentanyl, followed by 0.3 mg.kg-1 of etomidate. Once they had lost consciousness, they were given 15 mg of pancuronium and 25 micrograms.kg-1 of fentanyl over a 5 min period. Patients in group F received the full 30 micrograms.kg-1 dose of fentanyl over a 5 min period, followed by 15 mg of pancuronium. The patients were intubated 2 min after the end of the fentanyl infusion. They were mechanically ventilated with 100% oxygen. Anaesthesia was maintained with a continuous infusion of fentanyl (total dose 100 micrograms.kg-1). The usual haemodynamic parameters were monitored and calculated, as well as pain during injection of the drugs, myoclonia, chest wall rigidity and the time to loss of consciousness. The two groups were comparable with respect to age, weight, height and surgery. One third of the patients in group EF complained of pain during etomidate injection. The time required to loose consciousness was shorter in group EF (55 +/- 16 sec) than in group F (177 +/- 56 sec) (p < 0.001). The cardiac index decrease in group EF (2.0 +/- 0.4 l.min-1.m-2 vs. 1.9 +/- 0.4 l.min-1.m-2) (p < 0.05), respectively between the time just before tracheal intubation (T1), and 10 min after tracheal intubation (T3).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

PubMed1992

Effects of oat bran, rice bran, wheat fiber, and wheat germ on postprandial lipemia in healthy adults.

Six normolipidemic males ingested on separate days a low-fiber test meal [2.8 g dietary fiber (TDF)] containing 70 g fat and 756 mg cholesterol, enriched or not with 10 g TDF as oat bran, rice bran, or wheat fiber or 4.2 g TDF as wheat germ. Fasting and postmeal blood samples were obtained for 7 h and chylomicrons were isolated. Adding fibers to the test meal induced no change in serum glucose or insulin responses. The serum triglyceride response was lower (P less than or equal to 0.05) in the presence of oat bran, wheat fiber, or wheat germ and chylomicron triglycerides were reduced with wheat fiber. All fiber sources reduced chylomicron cholesterol. Cholesterolemia decreased postprandially for 6 h and was further lowered in the presence of oat bran. Serum apolipoprotein (apo) A-1 and apo B concentrations were not affected. Thus, dietary fibers from cereals may reduce postprandial lipemia in humans to a variable extent.

Adult↗

PubMed1992

Clinical, cognitive, and neurophysiological effects of alprazolam in children and adolescents with overanxious and avoidant disorders.

In a double-blind, placebo-controlled study, the efficacy and safety of alprazolam was investigated in childhood and adolescent anxiety disorders. Thirty patients (mean, 12.6 years) diagnosed with overanxious or avoidant disorders participated in the study. Evaluations included clinical, laboratory, cognitive, and qualitative EEG measurements. On a clinical global rating, there was no statistical difference between alprazolam and placebo. Relative to baseline EEG, acute alprazolam administration increased beta power in the right occipital lead, and chronic administration increased beta power in both leads. Alprazolam was well tolerated, and adverse effects were few, mild, and transient.

Adolescent↗

PubMed1992

Penetration of vancomycin in uninfected sternal bone.

Concentrations of vancomycin in sternal bones of 10 patients undergoing cardiac surgery were studied at steady state, 48 h after starting intravenous prophylaxis. A sample of sternal bone was taken before (group I) or after (group II) cardiopulmonary bypass. The mean vancomycin concentrations in sternal bones were not significantly different between the groups and were 9.3 +/- 3.0 micrograms/g. The concentrations of vancomycin in sternal bones were always above the MICs for staphylococci, streptococci, and enterococci.

Adult↗

PubMed1992

[Early postoperative thrombolysis of Saint-Jude aortic valve prosthesis].

The authors report a case of thrombolytic therapy with streptokinase in the early postoperative period after aortic valve replacement with a Saint Jude medical prosthesis. After good initial progress, the patient had to be reoperated on the 12th postoperative day for sternal disunion. Reoperation was followed rapidly by progressive thrombosis of the aortic prosthesis demonstrated by repeated Doppler echocardiographic examination. The impossibility of eliminating mediastinitis led to medical thrombolysis. The outcome was favourable after a regressive cerebral embolic event. This case illustrates the value of Doppler echocardiographic examination in the postoperative period. Thrombolysis may constitute an alternative to reoperation when the operative risk is high. The risk of thrombolysis may not be as great as some believe.

Echocardiography, Doppler↗

PubMed1991

[Natural history of renal calcium lithiasis. Data obtained from a cohort of 667 patients].

Between January 1st, 1988 and May 31st, 1989, 667 patients (419 men, 248 women) with radioopaque, non cystinic and apparently idiopathic (lack of severe renal disease) renal stones were entered in a prospective study. The data obtained at entry enabled us to build up, retrospectively, a quantified presentation of the natural history of calcium nephrolithiasis. At the time the disease was discovered the patients' mean age was 40.4 years, and its presence had been known for 7.9 years on average in both sexes. The mean number of stones formed by the patients was 3.5. In 218 of the 277 patients who had only one stone the nephrolithiasis had been present for less than 3 years, as compared with at least 6 years in the 184/252 patients who had 3 stones or more; this suggests that in many of the patients studied the stones had rapidly become symptomatic. Women had a significantly (chi 2: P less than 10(-3)) more frequent history of urinary tract infection than men, and notably more frequent episodes of febrile infection (31.5 percent in women, 7.1 percent in men). A familial history of nephrolithiasis was found in 34.7 percent of women and 31 percent of men, but its presence had no influence on the number of stones formed or on the duration of the disease. On the other hand, the stones were discovered significantly earlier in men who has a familial history of nephrolithiasis (37.3 years) than in those who had no such history (42 years; P less than 10(-3)). These data will be used as baselines to a prospective evaluation of the course of nephrolithiasis in these patients.

Adult↗

PubMed1991

In vivo and in vitro effects of TGF-beta 1 on normal and neoplastic haemopoiesis.

TGF-beta 1 and TGF-beta 2 are equipotent selective inhibitors of murine and human haemopoiesis in vitro. Primitive haemopoietic cells such as the high proliferative potential progenitor cell and the colony-forming unit (CFU)-GEMM are directly inhibited by TGF-beta whereas the more differentiated CFU-G, CFU-M and CFU-E are not. Recombinant TGF-beta 1 administered intraperitoneally or intravenously to mice selectively inhibits haemopoietic colony formation in a time- and dose-dependent manner to the same extent as seen in vitro. The progenitors are reversibly prevented from entering the cell cycle. This inhibitory action of TGF-beta functions on at least two levels: (1) down-modulation of the cell surface expression of receptors for growth stimulatory molecules and (2) interference with the intracellular signalling pathways of these molecules. In addition, expression of TGF-beta receptors is regulated during cytokine stimulation of haemopoiesis. Neoplastic B lymphocytes can proliferate by escaping from a TGF-beta-mediated autocrine inhibitory loop. Activation signals (e.g. phorbol esters) inhibit tumour cell growth by stimulating active TGF-beta production and inducing cell surface expression of TGF-beta receptors. These results indicate that TGF-beta may be useful as a bone marrow protective and/or an antitumour agent.

Animals↗

PubMed1991

Purification and properties of sialoadhesin, a sialic acid-binding receptor of murine tissue macrophages.

Macrophage subpopulations in the mouse express a lectin-like receptor, sialoadhesin (originally named sheep erythrocyte receptor, SER), which selectively recognizes sialoglycoconjugates and is likely to be involved in cellular interactions of stromal macrophages in haematopoietic and lymphoid tissues. In this report we describe the purification and ligand specificity of sialoadhesin isolated from mouse spleen. Purified sialoadhesin, a glycoprotein of 185 kd apparent Mr, agglutinated sheep or human erythrocytes at nanomolar concentrations in a sialic acid-dependent manner. Low angle shadowing and electron microscopy showed that sialoadhesin consisted of a globular head region of approximately 9 nm and an extended tail of approximately 35 nm. To investigate the specificity for sialic acid, we studied the interaction of sialoadhesin with derivatized human erythrocytes, glycoproteins, and glycolipids. In conclusion, sialoadhesin specifically recognizes the oligosaccharide sequence Neu5Ac alpha 2----3Gal beta 1----3GalNAc in either sialoglycoproteins or gangliosides. These findings imply that specific sialoglycoconjugates carrying this structure may be involved in cellular interactions between stromal macrophages and subpopulations of haematopoietic cells and lymphocytes.

Animals↗

PubMed1991

Comparison of nicardipine and sodium nitroprusside in the treatment of paroxysmal hypertension following aortocoronary bypass surgery.

In an open, randomized, multicenter trial, intravenous nicardipine was compared with sodium nitroprusside in 74 patients with hypertension (mean arterial pressure [MAP] greater than or equal to 100 mm Hg) following coronary artery bypass surgery. Nicardipine was administered as a 2.5- to 12.5-mg bolus followed by a 2 to 4 mg/h infusion, and nitroprusside as a 0.5 to 6.0 micrograms/kg/min infusion. The aim was to reduce MAP to less than 90 mm Hg within 50 minutes and maintain it stable at 85 +/- 5 mm Hg. Nicardipine was effective in 35 of 38 patients (92%), and nitroprusside in 29 of 36 (81%) (NS). The decrease in MAP was not statistically different, but time until reaching the therapeutic end-point was shorter with nicardipine (P less than 0.01). Significant differences follow: increase in heart rate and decreases in mean pulmonary artery, right atrial, and pulmonary capillary wedge pressures were more marked with nitroprusside (P less than 0.01 and P less than 0.05, respectively), whereas elevation of cardiac index and depression of systemic vascular resistance were more marked with nicardipine (P less than 0.01 and P less than 0.05, respectively). Postreduction MAP was more stable with nicardipine, 51% +/- 24% of readings falling within the range 85 +/- 5 mm Hg versus 41% +/- 18% on nitroprusside (P = 0.058). Dose adjustment during the following 24 hours was less frequent with nicardipine, 1.1 +/- 1.6 versus 2.7 +/- 2.6 (P less than 0.01). Transfused blood volume was lower with nicardipine (924 +/- 644 mL) than nitroprusside (1,306 +/- 901 mL) (P = 0.08), despite similar postoperative blood losses.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

PubMed1991

High-dose alfentanil for myocardial revascularization: a hemodynamic and pharmacokinetic study.

It has been suggested that high plasma levels of alfentanil are required in order to control hemodynamic responses to noxious stimuli in patients undergoing myocardial revascularization. The present study was designed to determine the hemodynamic profile in 10 patients and the time course of alfentanil plasma concentrations and pharmacokinetics (7 patients) during and following coronary artery surgery using alfentanil administration based on an overdosage principle. Premedication consisted of lorazepam, 0.07 mg/kg, given 2 hours before surgery. Ten milligrams of alfentanil was given over 5 minutes for anesthesia induction, followed by an infusion of 60 mg/h until sternotomy and 30 mg/h up to skin closure. Additional 5-mg boluses were given prior to noxious intraoperative events. Hemodynamic measurements were performed prior to cardiopulmonary bypass. Blood was sampled simultaneously prebypass and then during the postbypass period for determination of alfentanil plasma levels. The very high alfentanil plasma concentrations achieved provided satisfactory intraoperative conditions in most, but not all, patients. Recovery time was short, despite the large amounts of narcotic used. It is concluded that very high doses of alfentanil associated with lorazepam premedication resulted in hemodynamic stability and markedly elevated narcotic plasma concentrations in most patients. Such plasma levels seem to provide satisfactory anesthetic conditions.

Alfentanil↗

PubMed1991

Role of transforming growth factor-beta 1 in regulation of hematopoiesis.

The data presented above suggest that one possible clinical use of TGF-beta would be to protect the bone marrow from the effects of myelosuppressive chemotherapeutic drugs by preventing entry or removing primitive stem cells from the cell cycle. It may also have the additional benefit of reducing the drug-induced neutrophil nadir by stimulating granulopoiesis. The availability of large quantities of recombinant TGF-beta will allow study of the pharmacokinetics with different routes of administration, dosage effects, and details of the pleiotropic effects on other cell systems. Experiments are in progress to determine whether TGF-beta will allow the delivery of higher amounts or more frequent doses of chemotherapeutic drugs and thus allow increased antitumor efficacy in tumor-bearing animals.

Animals↗

PubMed1991

Platelet-activating factor (PAF-acether) enhances the concomitant production of tumour necrosis factor-alpha and interleukin-1 by subsets of human monocytes.

The production of the cytokines tumour necrosis factor (TNF) and interleukin-1 (IL-1) by human monocytes was analysed following their stimulation with muramyl dipeptide (MDP; 1 microgram/ml), in the absence or presence of graded concentrations of platelet-activating factor (PAF). Significantly enhanced production of both TNF and IL-1 was observed at two concentration ranges of PAF: a major enhancement was observed at 10(-8)-10(-6) M and this was blocked by the PAF antagonist BN 52021 (10(-4) M). A second enhancement was observed at 10(-15)-10(-14) M PAF, which was not blocked by BN 52021. Monocytes isolated either by adherence or counterflow elutriation had similar responses to PAF. The biologically inactive precursor-metabolite, lyso-PAF, had no effect on cytokine production. PAF was shown to augment the production of both bioactive TNF and IL-1 and immunoreactive TNF-alpha and IL-1 alpha and beta. Fractionation of monocytes on a discontinuous Percoll gradient yielded a denser subpopulation, which responded preferentially to higher PAF concentrations, while the less dense subpopulation responded to both concentration ranges. These data indicate that PAF can modulate monocyte functions as related to cytokine production, and may thus contribute to amplification of inflammatory reactions and regulation of immune responses by interacting with subsets of human monocytes.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1991

Cold cerebroplegia. A new technique of cerebral protection during operations on the transverse aortic arch.

Profound hypothermia associated with circulatory arrest is the commonest method of cerebral protection during operations on the aortic arch. This technique allows a limited time to perform the aortic repair, however. It also necessitates prolonged cardiopulmonary bypass to rewarm the patient. This may be the cause of coagulation disorders or infection. Selective perfusion of the carotid arteries can also be used. When the perfusion is derived from the main arterial line, however, the repair of the aorta requires that the vessel be crossclamped, and cannot be performed in an "open, bloodless" manner. To avoid the disadvantages of both techniques, we have developed a new technique of cerebral protection. After a regular cardiopulmonary bypass has been established, the carotid arteries are cannulated and perfused with blood cooled at 6 degrees to 12 degrees C, through a separate heat exchanger, while the core temperature is maintained at moderate hypothermia (25 degrees to 28 degrees C, rectal). To perform the "open" distal repair, the cardiopulmonary bypass is discontinued while the carotid perfusion is maintained (250 to 350 ml/min). When the distal repair is completed, cardiopulmonary bypass is resumed and the carotid perfusion is discontinued. Between 1984 and June 1989, 54 patients (mean age 55 years) were operated on with this method (45 elective operations, 9 emergency procedures). Mean duration of cardiopulmonary bypass was 121 minutes (65 to 248), and mean duration of circulatory arrest was 22 minutes (10 to 51). The electroencephalogram, routinely recorded, showed return of the cerebral activity after a mean time of 12 minutes and normal activity after a mean time of 66 minutes. There was no intraoperative death. Hospital mortality rate was 13% (7/54). One death was related to neurologic disorders. All patients but one awakened normally within 8 hours after operation. Two patients (4.3%) experienced a transient neurologic episode (lateral hemianopia) 9 and 11 days postoperatively. There was no hemorrhagic complication (24-hour average blood loss: 840 +/- 540 ml). In our experience the technique of "cold cerebroplegia" has been demonstrated to provide excellent cerebral protection. It requires no prolonged cardiopulmonary bypass and does not limit the time necessary to perform the aortic repair. It may be considered as a safe alternative to profound hypothermia associated with circulatory arrest.

Adult↗

PubMed1990

Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience.

In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method. The overall efficacy rate was 96.0 percent (95 percent confidence interval, 95.0 to 96.8). The failures included persisting pregnancies (1.0 percent), incomplete expulsions (2.1 percent), and the need for hemostatic procedure (0.9 percent). The mean time to expulsion was significantly shorter when sulprostone was given in the high dose (4.5 hours) than when it was given in the two lower doses (13.1 and 19.3 hours) or when gemeprost was given (22.7 hours). The mean duration of uterine bleeding was 8.9 days (range, 1 to 35); one woman received a blood transfusion. Most women had transient abdominal pain after receiving prostaglandin, but there were few other side effects. We conclude that the administration of mifepristone followed by a small dose of a prostaglandin analogue is an effective and safe method for the early termination of pregnancy.

Abortifacient Agents↗

PubMed1990

Monoclonal antibody A2B5, which detects cell surface antigens, binds to ganglioside GT3 (II3 (NeuAc)3LacCer) and to its 9-O-acetylated derivative.

The monoclonal antibody A2B5 recognizes antigens at the surface of neuronal and glial cells but also at the surface of thymus epithelia and pancreatic islet cells. Although these antigens have been characterized as polysialogangliosides, A2B5 also reacts with other unidentified gangliosides. In order to characterize further the epitope of A2B5, two new ganglioside antigens isolated from chicken brain are identified in this study. One is the ganglioside NeuAc alpha 2-8NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1ceramide (GT3) and the other is a 9-O-acetylated derivative of GT3). This derivative was purified from 10-day embryonic chicken brain. Acetyl groups substituted on sialic acid were removed either by alkali treatment or by incubation with influenza virus C, which contains receptor-destroying enzyme (a neuraminidate 9-O-acetyl esterase). The product of alkali treatment or viral action was detected by the antibody 18B8 which is specific for GT3. The deacetylated product still reacts with A2B5. These data and the results of mild oxidation of the antigen with sodium periodate suggest that the epitope recognized by antibody A2B5 contains the trisialyl structure found in GT3 but does not include the polyalcohol chain of the terminal sialic acid which can be oxidized by periodate or acetylated without modifying the affinity for the antibody. The epitope recognized by A2B5 is different from the epitope recognized by the antibody 18B8 in that 18B8 requires the three sialic acids with an intact and unsubstituted polyalcohol chain. Antibody 18B8 does not bind to 9-O-acetylated GT3 or GT3 oxidized by sodium periodate.

Acetylation↗

PubMed1990

Inhibition of alveolar macrophage cytotoxicity by asbestos: possible role of prostaglandins.

Asbestosis and silicosis are chronic, fibrosing lung diseases due to prolonged inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile asbestos and silica on 18-h cytotoxicity of AM against tumor necrosis factor (TNF)-resistant P815 target cells or TNF-sensitive L929 target cells. Rat AM, obtained by bronchoalveolar lavage, were incubated for 2 h with 20, 50, or 100 micrograms/ml chrysotile or silica before the addition of target cells. AM cytotoxicity was significantly inhibited at greater than 20 micrograms/ml of chrysotile. In contrast, silica did not inhibit AM-mediated cytotoxicity at any concentration used. Asbestos, but not silica, caused significant production of PGE2 by macrophages and target cells. Addition of the cyclooxygenase inhibitor indomethacin to our system abolished all inhibition by asbestos. These results suggest that the inhibition of AM-mediated cytotoxicity by chrysotile was caused by prostaglandins, and that fibrogenic particles differ in their capacity to modulate AM function.

Animals↗