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Biomedical subjects

M Boulanger

Publications and source records attributed to M Boulanger.

At least 19 recordsLinked to original sources

Latent autoimmune diabetes mellitus in adult humans with non-insulin-dependent diabetes: is Psammomys obesus a suitable animal model?

Recent data suggest that in a proportion of NIDDM patients there is a slowly evolving insulitis which results in a latent autoimmune diabetes leading to full insulin-dependence. Many animal models exist of NIDDM but none have reported the spontaneous existence of a similar phenomenon. We have re-examined the histology of pancreata from a few Psammomys obesus who had become insulin-dependent in the late stages of NIDDM. We report here the unexpected finding of the presence of insulitis in these animals and suggest that they could be a model for the clinical observation of latent IDDM in NIDDM patients.

Adult

Synthesis of 1,2-diacyl-3-nicotinoyl glycerol derivatives and evaluation of their acute effects on plasma lipids in the rat.

Nicotinic acid (CAS 59-67-6) is the only hypolipidemic agent whose activity has been shown both on atherosclerotic lesions and on long term mortality. Unfortunately, its use is hindered by the frequent occurrence ( > 70%) of adverse reactions (i.e. cutaneous rash, pruritus and, most significantly, flush). New prodrugs of nicotinic acid have been prepared by the use of diacylglycerol esters. In the rat, after acute oral administration of these products, a significant decrease of the free fatty acid plasma levels was obtained without the dramatic increase in nicotinic acid plasma levels observed after the oral administration of an equimolecular dose of nicotinic acid. The most interesting ester, S 16961 ((d,l)-1,2-dipalmitoyl-3-nicotinoyl glycerol, CAS 160555-46-4) is undergoing clinical trials.

Animals

S15261, a new compound for the treatment of the insulin resistance syndrome.

A new oral agent, S15261 (the L-isomer of 3-[2-[2-[4-[2-[alpha-fluorenyl acetyl amino ethyl] benzoyloxy] ethyl amino] 1-methoxy ethyl] trifluoromethyl-benzene), has been developed for the treatment of the so-called "insulin resistance syndrome". In obese, insulin-resistant ageing Sprague-Dawley rats, chronic treatment with S15261 (0.5-2.5 mg.kg-1.day-1 twice per day, for 14 days) resulted in dose-dependent decreases in plasma insulin (43%), and triglyceride levels (36%), and in an increase of the glucose disposal rate during an intravenous glucose tolerance test (IVGTT) (48.5%). An increase in peripheral insulin sensitivity produced by S15261 was revealed by the glucose clamp technique. Thus, the glucose infusion rate was increased by 20% whilst steady-state insulin levels decreased by 15%. At the higher doses S15261 led to a decrease in body weight (3%), plasma glucose (13%) and blood pressure (8 mm Hg) in mildly hypertensive animals. At the doses used to achieve these results, the compound has no hypoglycaemic activity in normoglycaemic animals. Acute administration of S15261 directly into the portal vein provoked a marked increase in glucose disappearance rate during an intravenous glucose tolerance test (60%) and also in the pancreatic response to the glucose challenge. Thus, acute administration of the compound has a direct effect on glucose metabolism. These data suggest that S15261 could be a useful agent for the treatment of the insulin resistance syndrome.

Animals

An empirical comparison between the DSM and psychodynamic approaches for assessment of child disorders in children attending outpatient clinics.

The DSM and psychodynamic approaches provide different perspectives on child psychiatric diagnoses. Taking advantage of the recent publication of a psychodynamically oriented classification of child disorders, correspondences between these approaches were studied in a sample of outpatient clinic children. Clinician judges and a psychiatric interview schedule provided for diagnoses. Classifications of child psychopathology are still imperfect to a large extent. As a result, statistical comparisons can only yield limited relationships and caution is necessary when using classification tools. Methodological difficulties notwithstanding, various associations showed that DSM and psychodynamic constructs, while different, are not entirely independent.

Affective Symptoms

Effect of aging and drug-induced weight reduction on rat vascular reactivity.

We determined the effects of D-fenfluramine treatment on the changes in vascular reactivity induced by aging. Nine- and 49-week-old Sprague-Dawley rats (a strain known to develop hyperinsulinemia and glucose intolerance during the aging process) were treated for 3 weeks either with D-fenfluramine 2.5 mg/kg twice daily orally or with vehicle. The rats were then exsanguinated and the abdominal aorta was carefully removed, cut into rings, and suspended in organ chambers for isometric tension recording. Control old rats (vehicle) had a significantly lower glucose infusion rate (an index of insulin resistance), and higher blood pressure (BP), glycemia, and insulinemia than young rats. The D-fenfluramine treatment in the aged animals produced a significant decrease in insulinemia and body weight. In aorta from the older treated and nontreated animals, the contraction to alpha-adrenergic stimulation and to the thromboxane analogue U46619 was significantly reduced as compared with that in young animals, but the response to KCl was unaffected. In contrast, in the old nontreated rats, the aorta was hyperresponsive to serotonin. D-Fenfluramine abolished this hyperreactivity. The response to beta-adrenergic stimulation and to forskolin was inhibited in the older animals but was not influenced by the treatment. Endothelium-dependent relaxations to acetylcholine were not statistically different in the various groups, but the endothelium-dependent relaxation to ADP was reduced in the control group of older animals. D-Fenfluramine treatment restored the response to ADP.

Administration, Oral

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Anesthesiology

T cell-derived factor alone or in combination with immunosuppressive drugs augments prolongation of allogeneic skin graft survival in mice receiving donor-specific transfusion.

Limiting dilution cytotoxicity or proliferation assays were performed with cells taken from A/J mice pretransfused with BALB/c blood. The data obtained indicate that donor-specific transfusion decreased both the frequency of reactive precursors and their proliferative potential after activation. Additional studies implied that these changes may be associated with a serum- or cell-mediated antigen-specific suppressive mechanism. Further manipulations aimed at preferentially sparing or enhancing the activity of suppressor T cells prolonged skin graft survival in pretransfused mice and led to the presence of suppressor T cells in the spleen of such mice, which were active upon adoptive transfer. These manipulations included the use of pretransplant donor-specific transfusion, administration of ALS or cyclosporin-A, or the use of posttransplant injection with a T suppressor activating factor (SAF). Optimum graft survival was associated with combined treatment when using transfusion, SAF, and cyclosporin-A.

Animals

Role of natural killer (NK) cells in the production of the murine T lymphocyte allorecognition repertoire.

Limiting dilution cultures of alloreactive (anti-H2Kb) CTL were established from thymocyte or spleen cell pools of C3H/HeJ and their congenic bg/bg partner, or of SJL/J and their congenic bg/bg partner. CTL populations in these cultures were assayed for cross-reactive lysis of a panel of splenic Con A blasts of H2Kbm mutant mice. There was some slight elevation of frequency of CTLp in the thymocyte lymphoid pool of bg/bg mice; more strikingly, the repertoire of anti-H2Kb specificities was clearly altered in both strains in the bg/bg animals. There was apparently an increased diversity (more specificities represented at higher frequencies) in the thymocyte pool and a decreased diversity in the spleen cell CTLp pool in animals with the bg/bg marker. Similar shifts in the allorecognition repertoire of normal C3H/HeJ mice were produced by inoculation of neonatal mice with a rabbit anti-NK heteroantibody (antiasialo GM1). Preabsorption of this serum such that it lost anti-NK activity also abolished this effect of in vivo neonatal injection. Furthermore, injection of bg/bg bone marrow-reconstituted C3H/HeJ (bg/+) mice with a C3H spleen cell-derived NK line also caused a shift in the allorecognition repertoire toward that seen in the normal littermate control animals.

Animals

Cell-specific localization of prostaglandin E2-sensitive adenylate cyclase in rabbit endometrium.

Epithelial and stromal cells were isolated from endometrium of Day 1 pseudopregnant rabbits by enzymatic digestion with trypsin or trypsin:collagenase:deoxyribonuclease. Dispersed cells were grown in RPMI 1640 supplemented with 10% whole or steroid-depleted fetal bovine serum (FBS). Epithelial and stromal cells reached confluency after 6 to 7 days in culture and showed specific characteristics. Cells could be differentiated according to morphology, growth patterns, electrophoretic patterns, and response to estrogen or progesterone. Hormonal stimulation of adenylate cyclase activity was measured in broken cell preparations by catalytic transformation of alpha-32P-adenosine triphosphate into 32P-adenosine 3'-5' cyclic monophosphate (cAMP). Adenylate cyclase activity was present in fresh endometrial tissue and in dispersed cells after 7 days in culture. The enzyme activity was significantly higher in stromal than in epithelial cells at all stimulation levels: basal (9.2 +/- 1.0 vs. 2.3 +/- 0.6, p less than 0.001) and guanosine triphosphate (GTP, 300 microM) (25.4 +/- 2.9 vs. 7.0 +/- 1.6, p less than 0.001). Net response to prostaglandin E2 (PGE2, 10 microM) was three times higher (p less than 0.001) in stromal (17 +/- 2) than in epithelial (5.0 +/- 1) cells. These results suggest that PGE2 can stimulate adenylate cyclase in rabbit endometrium and that the enzyme is preferentially localized in the stroma. Our results are in agreement with the hypothesis that cAMP formed in endometrium in response to PGE2 might be involved in the decidual reaction.

Adenylyl Cyclases

NMR monitoring of intracellular sodium in dog and rabbit kidney-tubules.

23Na-nuclear magnetic resonance (NMR) was used to monitor intra- and extracellular sodium in suspensions of dog cortical tubules, rabbit cortical tubules, and dog thick ascending limbs. The NMR visibility of the intracellular sodium was determined by comparing the NMR and flame photometry results and by redistributing the sodium ions between the intra- and extracellular compartments using the ionophore nystatin (influx) or sodium substitution for choline in the extracellular fluid (efflux). The intracellular sodium visibility was approximately 30% for the total sodium and 58% for the transportable sodium. Addition of sodium to sodium-depleted homogenates of dog renal cortex also showed a loss of visibility. The values of the relaxation times T1 and T2 were determined but could not be correlated with the visibility measurements. The intracellular sodium concentration in dog cortical tubules incubated in optimal biochemical conditions was estimated at 51 mM and was dependent on the extracellular sodium concentration.

Animals

Pharmacological properties of a new antiasthmatic xanthine derivative devoid of central stimulatory activity.

The bronchodilating effect and other related pharmacological properties of an 8-amino alkyl substituted xanthine (S 9795) were compared with those of reference drugs, in particular theophylline. The in vitro studies using the tracheal ring, taenia coli, rat peritoneal mastocytes and enzymic preparations demonstrated the potency of S 9795 as an antiasthmatic drug, possessing protective activity superior to that of theophylline and enprofylline. S 9797 was 100 times more active as a cAMP phosphodiesterase inhibitor than theophylline. The compound also protected against mast cell degranulation and consequent release of spasmogen due to antigen-antibody reaction or induced by Ca2+ movements. Given orally or intravenously. S 9795 had a highly selective protective effect against bronchoconstriction induced by pharmacological reagents or allergic reactions with no demonstrable effect on the central nervous or cardiovascular systems. The pharmacological effects of S 9795 were of longer duration than those of theophylline and enprofylline. These studies demonstrate the potential therapeutic value of S 9795 in the therapy of bronchospastic disorders.

3',5'-Cyclic-AMP Phosphodiesterases

Protection of adult BALB/c mice against MOPC 315 myeloma by neonatal administration of monoclonal anti-idiotypic antibody to MOPC 315 IgA.

Ascitic fluid containing monoclonal anti-idiotypic antibody (AIA) to MOPC 315 IgA was administered to newborn BALB/c mice, and the mice were challenged in adulthood with IgA-producing MOPC 315 myeloma cells. Administration of AIA D10 (a hybrid molecule containing IgG1 and IgG2a heavy chains), G3 (IgG2b), and A2 (IgG1), all of which reacted with MOPC 315 cells in a cell-binding radioimmunoassay, prolonged survival and reduced the percentage of IgA-producing spleen fragments derived from mice challenged with MOPC 315 myeloma cells, but not with cells of a related IgA-producing myeloma, MOPC 460. Reduction in the percentage of IgA-producing spleen fragments was prevented by treatment of spleen cells prior to culture with anti-Thy 1.2 antibody and complement. Administration of AIA F1 (IgG2a), which did not react with MOPC 315 cells in vitro, or of an antibody with no AIA activity did not produce a similar protection. These results suggest that administration of AIA to MOPC 315 IgA to neonatal BALB/c mice induces idiotype-specific T-lymphocytes that protect these mice against a challenge with MOPC 315 myeloma cells in adulthood.

Animals

End-tidal carbon dioxide tension and temperature changes after coronary artery bypass surgery.

Variations in end-tidal carbon dioxide partial pressure (PETCO2) and temperature were measured for six hours following coronary artery bypass surgery in twenty patients. In the recovery room, the patients were mechanically ventilated with a tidal volume of 12 ml X kg-1. Arterial blood gases were drawn every two hours, and the respiratory frequency was adjusted to maintain arterial carbon dioxide pressure (PaCO2) in the range of 30-45 mmHg. Naso-pharyngeal temperature was recorded every 30 minutes, and PETCO2 was measured continuously. The mean difference between temperature-corrected arterial and end-tidal CO2 pressure measurements was 3.2 mmHg (SD = 2.8; r = 0.963). This difference did not vary with time, temperature or PCO2. The largest temperature increases (mean 1.7 degree C/hour) occurred at a mean of 253 minutes after the end of surgery. End-tidal PCO2 increased markedly as temperature rose, in spite of a coincident increase in ventilation and then decreased as temperature stabilized. Large increases in CO2 production, caused by the metabolic demands during rewarming, most likely account for these changes. It is concluded that end-tidal CO2 recordings are reliable, and can help in maintaining normocarbia during the short but unstable period associated with rewarming following cardiac surgery.

Aged

[Anesthetic induction with Althesin or diazepam in patients undergoing an aortocoronary bypass].

The haemodynamic effects of induction of anaesthesia with diazepam (group D) and Althesin (group A) were studied in 25 coronary patients under betablockers with good myocardial function. Haemodynamic variables monitored were vascular pressures, cardiac output and systolic time intervals. The effects of both drugs were observed when used alone (time I) and in combination with fentanyl, pancuronium and nitrous oxide (time II). The results seemed to show that Althesin (12.51% fall in SI and 10.79% increase in PEP/LVET) depressed myocardial function more than diazepam (no significant difference), but the introduction of fentanyl, pancuronium and nitrous oxide removed the differences between the drugs as to their effect on myocardial performance. These drugs added a depressant effect to diazepam (13.83% fall in SI and 15.77% increase in PEP/LVET) without increasing Althesin's negative inotropic effect. However, in group A at time II, the pulmonary arterial pressure, the wedge pressure and the pulmonary vascular resistance were significantly reduced, while they remained stable in the diazepam group.

Adrenergic beta-Antagonists

A role for self-recognizing T cells in the regulation of antibody-forming and cell-mediated cytotoxic responses in the mouse.

Mitogen- or antigen-activated murine spleen and thymus cell blasts have been used as inducer cells to stimulate production of suppressor T cells (Ts) in autologous mixed leucocyte culture. Ts cells were induced in an MHC-restricted fashion and produced suppression of cell-mediated lympholysis and antibody synthesis from fresh spleen cells sharing MHC haplotypes with the Ts pool. Ts were Thy 1+, Lyt 1+ cells. Induction of Ts depended upon expression of class II MHC antigens on stimulating cells, but the level of Ts induced by different populations of suppressor inducer cells was not correlated with the level of Ia antigen expression. Activity of suppressor inducer cells was correlated with the functional activity of the inducer pool. The data are interpreted to favour a model in which Ts are induced by associative recognition on stimulator cells of class II MHC antigens and lymphocyte recognition receptors as nominal antigen (i.e. Ts are auto anti-idiotypic in nature). Using as stimulator/responder cells in AMLR lymphocytes taken from normal (8-week) or aged (greater than 24-month) mice, data were obtained consistent with this model and with earlier evidence for an altered expression of both lymphocyte recognition receptors and/or class II antigens in senescence.

Age Factors

[Superior venacavography at the patient's bedside].

Acute onset of superior vena cava syndrome in critically ill patients, hours after cardiac surgery, needs angiographic documentation without delay in order to proceed with appropriate treatment. Bedside diagnostic venacavography was done for two patients in the surgical intensive care unit with a simple and safe method using a central venous catheter already in place.

Aged