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Biomedical subjects

G Dupuis

Publications and source records attributed to G Dupuis.

At least 91 records · Page 5Linked to original sources

Reducing property of some slow acting antirheumatic drugs.

Many slow acting antirheumatic drugs and several other drugs without antirheumatic activity possess a potential thiol function, i.e., a free SH group or one that is generated by hydrolysis. Since drugs with effective SH activity may react with intracellular disulfides, we evaluated their reducing properties by measuring their redox potential and their ability to react with glutathione, the most prevalent intracellular thiol, and dithiobis (nitrobenzoic acid), a specific reactant for thiols. Drugs containing aromatic thiols are poor reducers and are generally devoid of antirheumatic activity. Antirheumatic drugs, such as D-penicillamine, levamisole, gold salts, thiopronine and captopril, are potential aliphatic thiols with strong reducing properties. These different antirheumatic drugs may therefore operate by a common mechanism through an altered cellular redox equilibrium and sulfide-disulfide exchanges.

Anti-Inflammatory Agents↗

[Mortality in 131 episodes of gram-negative septicemia at the University Hospital of Lausanne in 1979].

The prognosis of gramnegative septicemias depends on established factors which the authors have researched among adult patients presenting with 131 episodes of gramnegative septicemia during the year 1979 in the Departments of Medicine and Surgery of the University Hospitals of Lausanne, Switzerland. This study confirms that the principal prognostic factor for gramnegative septicemia is the presence of an associated severe condition. Neither age, sex, place where contracted, treatment, nor origin of the septicemia (with the possible exception of sepsis from endovascular catheter) have a determining influence on mortality.

Age Factors↗

Electrophoretic studies of the protein constituents of pig spleen lymphocyte plasma membrane and of a non-ionic detergent extract of intact cells.

This report describes a study of the protein constituents of pig spleen lymphocyte plasma membrane, separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analyzed under reducing and non-reducing conditions. The electrophoretic patterns of purified plasma membranes, of the endoplasmic reticulum fraction and of a non-ionic detergent (Nonidet P-40) extract of intact lymphocytes are compared. The lymphocytes were ruptured by the nitrogen cavitation method and the plasma membranes were purified by differential centrifugation in sucrose gradients. Plasma membranes were enriched in marker enzymes and appeared, in electron micrographs, as vesicles of various sizes and as fragmented membranes. The protein constituents were resolved into more than 60 bands which appeared, except in the endoplasmic reticulum fraction, as discrete Coomassie-positive bands. Characteristic bands were present in each of the three fractions when samples were not reduced. However, the majority of Coomassie-stained proteins migrated with the same relative mobility in all three fractions. Interestingly, all Coomassie-positive bands stained (some weakly) for glycoproteins. When samples were reduced and alkylated prior to electrophoresis, the electrophoretogram of each fraction differed from the non-reduced samples. In general, we observed that the fastest migrating portion of each gel was more intensively stained, when compared to non-reduced extracts. In addition, some bands characteristic of each fraction were evident, although most bands were common to each fraction. Coomassie-positive bands also stained with a glycoprotein staining reagent. Activity of alkaline phosphatase was demonstrated in the electrophoretograms of the non-reduced plasma membrane extracts. The results suggest that each of the three fractions analyzed under the conditions described here possesses a characteristic glycoprotein content. Furthermore, the data show that a Nonidet P-40 extract of lymphocytes is effective in solubilizing the glycoproteins from pig lymphocyte plasma membranes. Comparison of electrophoretic patterns with those reported for lymphocytes of other lymphoid organs of the pig suggests close similarities.

Animals↗

Separation and localization on sodium dodecyl sulfate polyacrylamide gels of pig spleen lymphocyte plasma membrane proteins which bind 125I-labelled phytohemagglutinin.

The protein constituents of splenic pig lymphocytes derived from the plasma membranes, the endoplasmic reticulum or from a non-ionic (Nonidet P-40) detergent of whole cells have been separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, under reducing and non-reducing conditions. The binding of Phaseolus vulgaris (red kidney bean) phytohemagglutinin to these constituents has been studied by incubation of the labelled lectin with the undried electrophoretograms. Results show characteristic phytohemagglutinin-reactive components in each cell fraction, although the majority of the lectin-binding bands are common to the three fractions. Comparison of binding patterns for the reduced and non-reduced electrophoretograms does not reveal significant differences between the binding profiles. The components which bind the lectin in the largest amounts are located in the upper halves of the gels, which correspond to a molecular range of (75-250) . 10(3) daltons. Our data suggest that pig spleen lymphocyte plasma membranes contain at least 25-30 glycoproteins which can bind phytohemagglutinin. Iodine-labelled phytohemagglutinin binds to the vesicles prepared from lymphocyte plasma membranes and the Scatchard plot shows a non-linear upward concave curve.

Animals↗

[Bilateral parotid gland tumors. Report on 3 cases (author's transl)].

Three cases of rarely observed bilateral parotid gland tumors are reported. In two cases the tumors were of different histological types (mixed tumor on one side and an adenocarcinoma on the other side) while in the third case they were both of the mixed variety. No clear explanation for the possible bilateral nature of these tumors was found, diagnosis being made either during the initial examination or after an interval of several years.

Adenocarcinoma↗

[Neurinoma of the third portion of the facial nerve. About a case cured after hypoglosso-facial anastomosis (author's transl)].

The authors report a case of a neurinoma of the third portion of the facial nerve, revelated by a progressive palsy completed four months later (but the muscle of the stapes was still working). After removing the neurinoma which was in the middle of the mastoïde an anastomosis between the XII and the VII nerves was performed and successful. The authors emphasize two facts: --The possibility of active reinervation by this method of the facial muscles even after a long delay of complete interruption of the facial nerve. --The advantage of performing the micro-anastomosis as close as possible to the myo-neural synapsis (just before the bifurcation of the facial nerve.

Cranial Nerve Neoplasms↗

Impairment by covalent modification of the ability of Phaseolus vulgaris phytohemagglutinin to stimulate cultured human lymphocytes: a comparison of different forms of covalent modification.

Phytohemagglutinin (PHA) isolated from Phaseolus vulgaris has been modified by treatment with various chemical reagents and the modified proteins have been tested for their ability to stimulate peripheral lymphocytes from two healthy human donors, in vitro. Reaction of PHA with citraconic anhydride, S-methyl isothiourea, or 2-hydroxy-5-nitrobenzyl bromide produced derivatives which retained the ability to stimulate lymphocytes, at low concentrations. Acylation of the lectin with acetic anhydride or masking of the carboxyl side chains by reaction with glycinamide-carbodiimide impaired stimulation. When PHA was treated with N-bromosuccinimide or with tetranitromethane, the derivatives were ineffective as lymphocyte stimulants. Chemical modifications affected, in some cases, the quaternary structure of the lectin. Glycinamide-, homoarginine-, and nitro-PHA were tetramers whereas acetyl-, citraconyl-, and N-bromosuccinimide-treated lectin were dimers. Antinative lectin antiserum cross-reacted with all the modified proteins, except in the case of the N-bromosuccinimide derivative. The results show that, in the human lymphocyte transformation assay, the mitogenic property of PHA may depend on intact aspartic, glutamic, and tyrosine residues whereas lysine residues do not appear to be essential.

Acetylation↗

Binding of chemical derivatives of Phaseolus vulgaris phytohemagglutinin to pig spleen lymphocytes.

The mitogenic activity of Phaseolus vulgaris phytohemagglutinin (PHA) and its acetyl, citraconyl, glycinyl, homoarginyl, N-bromosuccinimide, and nitro derivatives has been assayed using pig spleen lymphocytes. Nitrated and N-bromosuccinimide-treated PHA were not mitogenic. Whereas the mitogenicity of acetyl PHA was impaired, the other derivatives were as active as untreated lectin. Binding studies of [125I]PHA and derivatives to purified pig spleen lymphocytes were performed at 37 degrees C. Results show that the lymphocytes bound various amounts of lectin derivatives. Maximum amounts were observed in the case of mitogenic lectins. Data were analyzed by Scatchard plots and two kinds of binding sites were found for PHA and the mitogenic derivatives. High affinity and low affinity binding sites have been characterized in terms of (apparent) association constant and (apparent) number of sites. Binding of PHA or its chemical derivatives to a small fraction (4.6--9.0%) of all available lectin binding sites was sufficient for maximal lymphocyte stimulation. Nonmitogenic PHA derivatives (nitro or N-bromosuccinimide) bound, with low affinity, to one kind of binding site. The relevancy of these findings to lymphocyte activation is discussed.

Animals↗

Studies on poison ivy. In vitro lymphocyte transformation by urushiol-protein conjugates.

The isolation and purification of poison ivy urushiol is described. The preparation of urushiol-ski protein and urushiol human serum albumin is also described. Lymphocytes from eleven donor naturally sensitized to poison ivy and from four non-sensitive individuals have been cultured for 5 days in the presence of urushiol-carrier conjugates. Lymphocytes from seven of the eleven sensitive donors responded with a stimulation index greater than 3.0 to urushiol-albumin conjugate. When urushiol-skin protein conjugate was used as a stimulant, lymphocytes from only three of the eleven sensitive donors responded. The results suggest that urushiol-protein conjugates can stimulate sensitive lymphocytes in vitro, although a response is not observed in every individual naturally sensitized to poison ivy.

Adult↗

Toxic effect of alantolactone and dihydroalantolactone in in vitro cultures of leukocytes.

Alantolactone, an allergenic sesquiterpene lactone, is toxic to leukocytes in in vitro cultures. Cell (1 X 10(6) cells/ml of culture) stimulation by pokeweed mitogen (PWM) decreases with increasing amounts of terpene. A concentration of 1 mug/ml of culture decreases stimulation by 50%. The reduced terpene, dihydro-11,13-alantolactone (DHA) is also toxic. A concentration of 1.7 mug/ml of culture of DHA brings about a 50% decrease in stimulation. Both compounds affect cell viability as measured by dye exclusion. It is suggested that the toxicity of alantolactone is not due to the presence of the alpha-methylene group conjugated to the carbonyl function of the gamma-lactone system.

Benzofurans↗

The binding of phytohemagglutinin M to rat spleen lymphocytes. Quantitative studies.

Phytohemagglutinin M (PHAM) has been purified from the commercial mixture of proteins produced by Phaseolus vulgaris, using a Sepharose-thyroglobulin column. The protein gave one band on gel electrophoresis and two bands on SDS-gel electrophoresis (mol. wt. 33 700 and 32 100, respectively). Molecular weight determination by ultracentrifugation gave a value of 61 200 +/- 700. The protein had a minimum sugar content of 16%. Binding studies of PHAM to purified rat spleen lymphocytes have been performed at 0, 25, and 37 degrees C. It was shown that the cells bound about the same amount of lectin at 0 and 37 degrees C, but less protein was bound at 25 degrees C. The binding phenomenon showed saturability at all temperatures. Data were analyzed by Scatchard plots and two kinds of binding sites were found. High-affinity sites and low-affinity sites have been characterized in terms of association constants and (apparent) number. It was also shown that cells treated with trypsin or sodium azide bound less lectin. Bound concanavalin A did not appear to affect the amount of bound PHAM, but its influence was reflected in the value of the association constant for the binding of PHAM. Unlabelled PHAM was shown to displace radioactive PHAM from the cells, but could not remove bound concanavalin A. The significance of these results is discussed in terms of the fluid plasma membrane model and cellular metabolism.

Amino Acids↗

Metabolic behaviour of water-soluble fluorescent whitening agents in the rat and bean plant.

The behaviour of three representative water-soluble fluorescent whitening agents (FWAs) was studied in rats and bean plants using 14C-labelled compounds. Following oral doses of 5 mg/kg of each of the FWAs to rats, rapid and complete excretion of radioactive material was observed, with an excretion half life ranging from 7-13 hours. Faeces were practically the only route of excretion, indicating, in combination with the short half life times, that no significant amounts of whitener were absorbed from the digestive tract. No radioactive residues were found in blood, liver, kidney, brain, muscle, or fat 96 hours after dosing (limit of quantitative determination 0.005-0.01 ppm Fwa equivalents). Whereas, after application of compound (1) and compound (3), radioactive material was completely extractable from faeces in the form of unchanged parent compounds, that in the compound (2) experiments was not extractable. When bean plants (Phaseolus vulgaris) were grown in the presence of 14C-labelled compound (3) in nutrient solution (11.5 ppm) and in soil (,7.5 ppm), approximately 55% and 2% of the applied radioactive material, respectively, was absorbed by the plants. More than 90% of thie material was bound to the roots in both experiments 40 days after the application. Eight percent of the radioactive material absorbed in the soil experiment was translocated mainly into the stems whereas only trace amounts of the order of less than 0.1 ppm reached the leaves and bean pods. It is concluded from these experiments with extremely high concentrations of compound (3) that under the conditions which may occur in practice residues of water-soluble FWAs do not appear in substantial amounts in edible parts of crops.

Animals↗