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Biomedical subjects

L Bolduc

Publications and source records attributed to L Bolduc.

7 recordsLinked to original sources

Dimethyl sulfoxide affects the selection of splice sites.

Depending on the cell lines and cell types, dimethyl sulfoxide (Me2SO) can induce or block cell differentiation and apoptosis. Although Me2SO treatment alters many levels of gene expression, the molecular processes that are directly affected by Me2SO have not been clearly identified. Here, we report that Me2SO affects splice site selection on model pre-mRNAs incubated in a nuclear extract prepared from HeLa cells. A shift toward the proximal pair of splice sites was observed on pre-mRNAs carrying competing 5'-splice sites or competing 3'-splice sites. Because the activity of recombinant hnRNP A1 protein was similar when added to extracts containing or lacking Me2SO, the activity of endogenous A1 proteins is probably not affected by Me2SO. Notably, in a manner reminiscent of SR proteins, Me2SO activated splicing in a HeLa S100 extract. Moreover, the activity of recombinant SR proteins in splice site selection in vitro was improved by Me2SO. Polar solvents like DMF and formamide similarly modulated splice site selection in vitro but formamide did not activate a HeLa S100 extract. We propose that Me2SO improves ionic interactions between splicing factors that contain RS-domains. The direct impact of Me2SO on alternative splicing may explain, at least in part, the different and sometimes opposite effects of Me2SO on cell differentiation and apoptosis.

3' Untranslated Regions↗

Identification of extracellular matrix components and their integrin receptors in the human fetal adrenal gland.

The development of the human fetal adrenal gland is characterized by a gradient of mitotic activity, cell migration, and cell apoptosis, all of which dictate its particular function. Such plasticity may possibly be under the control of the extracellular environment. The goal of this study was to identify components of the extracellular matrix in second-trimester fetal adrenal glands. Whereas collagen IV was expressed evenly throughout the gland, both fibronectin and laminin demonstrated a mirror-imaged distribution, with higher expression of fibronectin in the central portion and laminin at the periphery of the gland. The integrin subunit alpha1 was found mainly in the definitive zone and the alpha2-subunit mainly in the transitional zone, whereas integrin alpha3 (which binds both fibronectin and laminin) was detected only in the fetal zone. The beta2-subunit was observed solely in chromaffin cells. Such specific gradients of integrin and MEC component expression suggest that the extracellular environment does play a definite role during adrenal gland development. Indeed, compared with that in untreated plastic dishes, ACTH stimulation of dehydroepiandrosterone sulfate and cortisol was enhanced by collagen IV. In addition, fibronectin enhanced dehydroepiandrosterone sulfate but decreased cortisol secretion, compared with collagen IV substrates. These results provide fundamental insight into the contribution of the microenvironment in cellular processes leading to fetal adrenal gland development.

Adrenal Glands↗

Enhancement of the biodegradability of model wastewater containing recalcitrant or inhibitory chemical compounds by photocatalytic pre-oxidation.

m-Dinitrobenzene, diphenylamine and resorcinol, three aromatic compounds found inhibitory or recalcitrant to biological treatments, were chosen as model chemicals for this study on the integration of photocatalytic-biological treatments. The degradation of each of these compounds was achieved by ultraviolet photocatalytic oxidation, leading to the formation of intermediate compounds. The photocatalytic treatment was performed in a TiO2 slurry reactor containing an aqueous solution of one of the three chemicals. The biodegradability of model wastewater treated photocatalytically was measured in terms of BOD1/TOC. Intermediate compounds that appeared at early stages of the photocatalytic degradation of m-dinitrobenzene or diphenylamine seemed to be more inhibitory than the parent compounds but this was not the case for resorcinol. A substantial improvement in BOD1/TOC could be achieved, but it required the mineralization of at least 80% of the organic carbon originally in the water. Microtox toxicity results confirmed the BOD1/TOC trends for diphenylamine.

Biodegradation, Environmental↗

Effect of inhibition of hepatic fatty acid oxidation on metabolic and hormonal responses to exercise in rats.

The purpose of the present study was to assess the effects of 2-mercaptoacetate (MA), an inhibitor of hepatic fatty acid oxidation, on the metabolic and pancreatic hormone response to a prolonged (3 h) swimming exercise. All rats were first adrenodemedullated and were either submitted for 3 weeks to a normal (5% fat) or a medium-fat diet (MF; 18% fat). After being submitted to an exercise swimming habituation programme for one week, rats under both dietary conditions were either injected with a bolus dose of MA (600 mumol/kg; ip) or with a saline solution. MA and saline injected rats were either sacrificed after a 3-h swimming exercise or after a 3-h resting period. Administration of MA was associated with a lower level of beta-hydroxybutyrate after exercise in rats fed the MF diet, higher resting and exercising blood glucose levels in rats fed the MF diet, and higher resting and exercising levels of hepatic glycogen in rats fed a normal diet. There were, however, no significant effects of MA on free fatty acid, insulin, glucagon, epinephrine, and norepinephrine concentrations in both dietary conditions either at rest or after exercise. Therefore, the present data do not provide any evidence that the administration of MA, an inhibitor of hepatic fatty acid oxidation, influences the pancreatic hormonal response to exercise. There was also no evidence of a lowering effect of MA on blood glucose levels during exercise.

3-Hydroxybutyric Acid↗

The endometrial ablator: a new instrument.

A thermal balloon and control system designed to produce endometrial ablation blindly is described. A latex balloon on a plastic catheter is inserted into the uterus and connected to a control unit. The unit monitors the pressure and temperature of 5% dextrose in water, which has been injected into the balloon to make it conform to the size and shape of the endometrial cavity. The balloon contains a shielded heating element that is activated to heat the liquid in the balloon to a temperature of 92C. The pressure control deactivates the heating element if the pressure falls below 45 mmHg or rises above 165 mmHg. A timer controls and measures the elapsed interval of heating. The device was tested in human uterine specimens for the potential for uterine perforation, uterine rupture, and thermal effects. Subsequently, the device was tested in six patients in Mexico and four patients in London during hysterectomy just after the abdomen was opened. Thermistor probes were placed at various loci in the uterus to monitor temperature during activation of the thermal balloon. Serosal temperatures were unchanged and endometrial temperatures rose to about 90C. The extent of uterine tissue damage was determined in Mexico City by the zone of visible coagulation of the cut wall of the uterus following removal. In London, tissue diaphorase was measured to determine the depth of destruction of the cellular oxidative enzymes. These measurements varied from 3.3-10 mm under the conditions of time and temperature used. The safety features and the potential for clinical application are discussed.

Catheter Ablation↗