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G Schepers

Publications and source records attributed to G Schepers.

36 records · Page 2Linked to original sources

Thermodynamics of oligosaccharides binding to a dextran-specific monoclonal IgM.

The binding thermodynamics of seven different oligosaccharide haptens to the dextran-specific IgM secreted by the murine plasmacytoma MOPC-104E were studied by direct calorimetric measurements. The enthalpy change values observed for the binding process range between -5 and -16 kcal/mol depending on the hapten and the temp of measurement. The antibody-hapten interactions were characterized by a positive heat capacity change [delta Cp approximately 300 cal/(mol.degree)] and a resultant process of enthalpy-entropy compensation. The calculated change in unitary entropy of the reaction, delta Su, ranged between -20 and -30 eu (4 degrees C), corresponding to an expected entropy loss due to immobilization of the hapten molecules. The entropy of binding increased with rising temp, thus compensating for the decreasing enthalpy contribution to the free energy of binding. The data are consistent with a hapten binding induced conformational transition to a more relaxed state in the immunoglobulin molecule.

Animals↗

Human C1q: rapid isolation and quantitative determination by immunodiffusion.

A simple and rapid 2-step procedure for isolating C1q from human plasma at high yields (about 50%) is described. The purification involves diaminopropane precipitation followed by chromatography on IgG-Sepharose. The final product (obtained at a concentration of about 1.5 mg/ml) was electrophoretically and immunochemically pure and stable at -70 degrees C for long periods. The Mancini technique for the quantitative determination of C1q was reinvestigated and the use of gels containing high salt concentrations (1.0 M NaCl) was found to be absolutely necessary. A value of 0.076 mg/ml C1q in pooled human plasma was obtained.

Chemical Precipitation↗

Naloxone treatment attenuates food but not water intake in domestic pigeons.

Satiated as well as 24 h food-deprived pigeons showed an attenuated consumption of food in response to peripheral injection of the opiate antagonist naloxone. The minimal effective amount of the drug was found to be 1.5 mg in satiated birds and 0.5 mg in fasted birds. The anorexic effect of naloxone was observed for no longer than 3 h in both situations, and it did not differ at doses of either 1.5 mg or 5 mg of the antagonist. By contrast, doses of up to 5 mg of naloxone failed to depress the water intake of pigeons which were either 24 h water-deprived or were loaded with hypertonic saline. Together with previous studies, these results suggest that, in pigeons, endorphinergic naloxone-sensitive mechanisms are involved in the regulation of feeding but play no major role in the control of drinking. Possible modes of action of opiate antagonists on ingestive behaviour are discussed.

Animals↗

Ingestive behaviour of the pigeon: stereoselective influence of the opiate agonist levorphanol and its antagonism by naloxone.

Four experiments evaluated the effect of levorphanol on ingestive behaviour of different groups of non-deprived pigeons. In experiments 1 and 2, levorphanol and its (+)stereoisomer dextrorphan were administered at three doses (0.25, 1 and 2 mg). As compared with control values, levorphanol dose-dependently reduced food intake. This anorexia persisted for at least 5 h post-injection. A late hyperdipsia was also observed. These changes were stereoselective, suggesting that they followed the binding of levorphanol to opiate receptors. In experiments 3 and 4, the anorexic effect of 1 mg levorphanol, but not its hyperdipsic effect, was partly antagonized by the concomitant administration of either 0.25 mg or 1 mg naloxone. Given alone at the dose of 1 mg, naloxone slightly and transiently reduced food, but not water, intake. These results are discussed in terms of the endorphinergic regulation of ingestive behaviour in birds.

Animals↗

Evidence that naloxone attenuates the consumption of food by domestic pigeons through a central influence.

Three experiments were performed on domestic pigeons deprived of food for 24 hr to determine whether the anorexic influence of naloxone, which is observed in this species, results from a central effect of this drug. Injections were given 15 min before the delivery of food, and repeated measures of the consumption of food were obtained during the next 20 min. The systemic administration of either 2 or 10 mumol of naloxone, but not of equimolar amounts of quaternary naloxone, that does not traverse the blood-brain barrier, reduced the consumption of food of the pigeons. At a dose of 20 mumol, quaternary naloxone also slightly attenuated the ingestion of food, possibly because this drug can penetrate the blood-brain barrier when given in large doses. In another experiment, the intraventricular administration of 12.5, 25, 50, or 100 micrograms of naloxone attenuated the food intake in a dose-related fashion. Injection of 25 micrograms of the antagonist was more efficient in this respect when administered intraventricularly rather than systemically. From these experiments, it is concluded that in pigeons, the anorexic influence of naloxone is, at least partly, centrally mediated.

Animals↗

Binding site of a dextran-specific homogeneous IgM: thermodynamic and spectroscopic mapping by dansylated oligosaccharides.

The hapten binding properties of the homogeneous mouse IgM secreted by MOPC-104E were investigated. Hapten-association constants were determined either by equilibrium and displacement equilibrium dialysis or by fluorometric titrations of the protein with the fluorescent derivatives of the haptens. For the latter type of measurements, several oligosaccharides were derivatized to the corresponding dansylhydrazones. The synthesis, generally applicable to oligosaccharides with free reducing ends, is described. Analysis of the thermodynamic parameters for the binding of 18 haptens forms the basis for proposing a model of the binding site of MOPC-104E. This model is supported and refined by results of the measurements of linear and circular polarization of the fluorescence of the dansylated haptens. The binding site is proposed to consist of a cavity with about 12-A depth, complementary to a terminal nonreducing nigerosyl group. At the entrance to this cavity, a further subsite is identified forming interactions of lower specificity with an additional glucose unit.

Binding Sites↗

Toxicological evaluation of an electrically heated cigarette. Part 4: Subchronic inhalation toxicology.

The biological activity of mainstream smoke from an electrically heated cigarette (EHC) with controlled combustion and from the University of Kentucky Reference Cigarette 1R4F was determined in Sprague Dawley rats exposed nose-only for 90 days, 6 h a day, 7 days per week. For an equivalent response comparison between the two cigarette types, two doses were chosen for the EHC where the anticipated results were in the dynamic range of the 1R4F dose-response curve (four concentrations) for most end points. The number of cigarettes smoked per m(3) of diluted smoke resulted in total particulate matter concentrations of 40 and 90 microg l (-1) for the EHC and 40-170 microg l (-1) for the 1R4F. Biomonitoring indicated achievement of target doses. Mainstream smoke yields were lower for the EHC, with the exception of formaldehyde. No smoke-related mortality, remarkable in-life observations or abnormal gross pathological findings were observed. Smoke- and dose-related clinical pathology and organ weight changes included: increases in segmented neutrophils, some liver parameters and lung and adrenal weight relative to body weight; and decreases in lymphocytes, glucose concentration and spleen weight. Smoke-related histopathological findings in the respiratory tract included epithelial cell hyperplasia, squamous metaplasia, atrophy and accumulation of pigmented alveolar macrophages; they were mostly dose-dependent, more pronounced in the upper than lower respiratory tract and completely or partially reversed by 6 weeks post-inhalation. Qualitatively, the biological effects seen for the EHC and the 1R4F were comparable and similar to those observed in other mainstream smoke inhalation studies. Quantitatively, the biological activity of the EHC mainstream smoke was, on average, 65% lower than that of the 1R4F mainstream smoke on an equal cigarette basis and equivalent activity on an equal TPM basis.

Administration, Inhalation↗

Metabolism of S-nicotine in noninduced and aroclor-induced rats.

The urinary excretion of nicotine and its metabolites in noninduced and Aroclor-induced male and female rats has been determined following intravenous administration of 2'-[14C]-labeled S-nicotine at a dose of 4.6 mumol/kg. Complete recovery of the administered radioactivity was achieved: 95% in urine and 4% in feces over 96 h and 1% remaining in the body. More than 40 nicotine metabolites were found by radio-HPLC; 19 were identified including the cis/trans-diastereomers of nicotine-N'-oxide and 3'-hydroxycotinine. The urinary metabolite profile and excretion kinetics of nicotine and its metabolites were significantly different between noninduced and Aroclor-induced rats. The major urinary nicotine metabolite in the noninduced rat was cis-nicotine-N'-oxide. In the Aroclor-induced rat, cotinine metabolites were the major metabolites found. Sex differences were found for the urinary nicotine metabolite profile, mainly expressed in the excretion of cis-nicotine-N'-oxide, 29% in the male and 17% in the female noninduced rat, and the excretion of cotinine, 5% in the male and 12% in the female noninduced rat. High stereoselectivity was found for the formation of the cis/trans-diastereomers of nicotine-N'-oxide as well as of 3'-hydroxycotinine, the stereoselectivity being more pronounced in male rats.

Animals↗

Intracerebroventricular injection of ostrich beta-endorphin to satiated pigeons induces hyperphagia but not hyperdipsia.

Satiated pigeons received intracerebroventricular injections of either ostrich (0.06, 0.3 and 1.5 nmoles) or human (0.06 and 1.5 nmoles) beta-endorphin, or a control solution, and their consumption of food and water was monitored during the half hour after these treatments. At each administered dose, ostrich beta-endorphin enhanced food without altering water intake. By contrast, human beta-endorphin did not induce any reliable alteration either of feeding or drinking. Together with previous studies performed in pigeons with opiate antagonists, these results suggest that the feeding system of pigeons is modulated by an endorphinergic mechanism. By contrast, no evidence exists so far that such a mechanism operates for controlling drinking, as appears to be the case in mammals.

Animals↗

Biomarkers of exposure and potential harm in adult smokers of 3-7 mg tar yield (Federal Trade Commission) cigarettes and in adult non-smokers.

The paper reports levels of 24-h urine nicotine and five of its major metabolites (expressed as nicotine-equivalents) and blood carboxyhaemoglobin as biomarkers of exposure to particulate- and gas-phase cigarette smoke, respectively, from an exploratory pilot study of adult smokers of 3.0-6.9 mg tar delivery (Federal Trade Commission (FTC) method) cigarettes. On multiple occasions over 6 weeks, blood high-sensitivity C-reactive protein (hs-CRP), fibrinogen, HDL- and LDL-cholesterol, and 24-h urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TxB2) were also evaluated as biomarkers of potential harm. All the biomarkers examined, except for LDL-cholesterol, discriminated with high sensitivity and specificity between adult smokers and non-smokers overall. Except for HDL-cholesterol, all biomarker medians were greater in adult smokers than in non-smokers: urine nicotine-equivalents 64.514 versus < 0.034 nmol mg-1 creatinine (p<0.001), carboxyhaemoglobin 4.0 versus 0.4% saturation (p<0.001), hs-CRP 0.27 versus 0.12 mg dl-1 (p=0.05), fibrinogen 292 versus 248 mg dl-1 (p<0.001), HDL-cholesterol 46 versus 53 mg dl-1 (p=0.003), LDL-cholesterol 119 versus 109 mg dl-1 (p=0.18), urine 8-epi-PGF2alpha 1935 versus 1034 pg mg-1 creatinine (p<0.001) and urine 11-dehydro-TxB2 973 versus 710 pg mg-1 creatinine (p<0.001). All the biomarkers of exposure and most of the biomarkers of potential harm showed no time of sampling (by visit week) effect.

Biomarkers↗

Methylated hexitol nucleic acids, towards congeners with improved antisense potential.

In an effort to further improve the hybridisation potential of anhydro-hexitol nucleoside analogues, the 1'-methoxyl and 3'-methoxyl substituents were introduced and evaluated for their antisense potential. In view of the selectivity of pairing with RNA, especially the introduction of a 3'-O-alkyl moiety deserves further study.

Alcohols↗

Consultative total parenteral nutrition teams: the effect on the incidence of total parenteral nutrition-related complications.

A two part, prospective study was undertaken to establish the existing frequency of total parenteral nutrition-(TPN) related mechanical, metabolic, and septic complications in an institution with a consultative TPN team (group A) and to determine if increasing the involvement of the TPN team in patient monitoring and verifying adherence to TPN infection control guidelines would reduce the incidence of these complications (group B). The initial 28 consecutive patients were managed entirely by their primary physicians with the role of the TPN team limited to consultative activities while the next 29 patients receiving TPN were managed jointly by their primary physicians and the TPN team. Analysis of the results show group B to have a significant reduction in metabolic complications, decreased incidence of mechanical abnormalities, and approximately equal incidences of documented sepsis. However, when compared to the results of an institution in which the TPN team has complete control of TPN therapy, even the group B patients had a relatively excessive number of TPN-related complications especially in the categories of mechanical and metabolic abnormalities. Thus, consultative TPN teams do not necessarily ensure optimum TPN therapy and institutions using this approach to provide nutrition parenterally must be prepared to establish the incidence of TPN-related complications and to expand the involvement of the TPN team as required to control the frequency of these anomalies.

Aged↗