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D C Rees

Publications and source records attributed to D C Rees.

At least 145 records · Page 8Linked to original sources
PubMed1988

Attenuation of the discriminative stimulus properties of ethanol and oxazepam, but not of pentobarbital, by Ro 15-4513 in mice.

The imidazobenzodiazepine Ro 15-4513 has a high affinity for central benzodiazepine binding sites and has been shown to antagonize certain effects of ethanol. The purpose of the present study was to determine if Ro 15-4513 would attenuate the discriminative stimulus properties of ethanol and the other central nervous system depressants pentobarbital and oxazepam. Different groups of mice were trained to discriminate 1.0 or 1.5 g/kg of ethanol, 20 mg/kg of pentobarbital or 10 mg/kg of oxazepam from saline injections in a two-lever operant task. Stimulus generalization tests were conducted with Ro 15-4513 alone (0.01-20 mg/kg) and in combination with the training drugs. The discriminative stimulus effects of ethanol and oxazepam, but not of pentobarbital, were blocked by Ro 15-4513. When given alone in each of the different drug-training groups, Ro 15-4513 did not produce drug-lever responding but decreased overall response rates in a dose-related fashion. Although the alcohols, barbiturates and benzodiazepines share discriminative stimulus properties under many conditions, the selective blockade of their stimulus effects provides further evidence that their actions may be mediated by different cellular mechanisms. These data also show that Ro 15-4513 may attenuate behavioral effects of ethanol relevant to its abuse.

Animals↗
PubMed1987

Discriminative stimulus properties of toluene in the mouse.

Little is known about the nature of the acute intoxication produced by exposure to high concentrations of toluene such as that which occurs with spills and in solvent abusers. The intoxication may be similar to that produced by classic central nervous system depressants such as the barbiturates. To investigate this hypothesis, drug discrimination procedures were used to compare the acute effects produced by toluene and pentobarbital (PB). Mice were trained to discriminate toluene (100 mg/kg, ip) from vehicle in a two-lever task in which responding was under the control of a fixed-ratio 20 (FR20) schedule of food presentation. Generalization tests were conducted after 20-min inhalation exposures to toluene (150-3600 ppm) and 20 min after injections with either PB (5-30 mg/kg) or morphine (3-20 mg/kg). Most mice generalized to inhaled toluene and to PB in a concentration- or dose-related fashion, but not to morphine. These results show that the effects of injected toluene can be established as a discriminative stimulus in mice, and that these stimulus effects are independent of route of administration. Shared discriminative stimulus properties with PB suggest that toluene produces an acute intoxication like that of other classic CNS depressants.

Administration, Inhalation↗
PubMed1987

Structure of the reaction center from Rhodobacter sphaeroides R-26: the cofactors.

The three-dimensional structure of the cofactors of the reaction center of Rhodobacter sphaeroides R-26 has been determined by x-ray diffraction and refined at a resolution of 2.8 A with an R value of 26%. The main features of the structure are similar to the ones determined for Rhodopseudomonas viridis [Michel, H., Epp, O. & Deisenhofer, J. (1986) EMBO J. 5, 2445-2451]. The cofactors are arranged along two branches, which are approximately related to each other by a 2-fold symmetry axis. The structure is well suited to produce light-induced charge separation across the membrane. Most of the structural features predicted from physical and biochemical measurements are confirmed by the x-ray structure.

Bacterial Proteins↗
PubMed1987

Structure of the reaction center from Rhodobacter sphaeroides R-26: the protein subunits.

The three-dimensional structure of the protein subunits of the reaction center (RC) of Rhodobacter sphaeroides has been determined by x-ray diffraction at a resolution of 2.8 A with an R factor of 26%. The L and M subunits each contain five transmembrane helices and several helices that do not span the membrane. The L and M subunits are related to each other by a 2-fold rotational symmetry axis that is approximately the same as that determined for the cofactors. The H subunit has one transmembrane helix and a globular domain on the cytoplasmic side, which contains a helix that does not span the membrane and several beta-sheets. The structural homology with RCs from other purple bacteria is discussed. A structure of the complex formed between the water soluble cytochrome c2 and the RC from Rb. sphaeroides is proposed.

Bacterial Proteins↗
PubMed1987

Structure of the reaction center from Rhodobacter sphaeroides R-26: membrane-protein interactions.

The energetics of membrane-protein interactions are analyzed with the three-dimensional model of the photosynthetic reaction center (RC) from Rhodobacter sphaeroides. The position of the RC in the membrane and the thickness of the membrane were obtained by minimizing the hydrophobic energy with the energy function of Eisenberg and McLachlan. The 2-fold symmetry axis that relates the L and M subunits is, within the accuracy of 5 degrees, parallel to the normal of the membrane. The thickness of the membrane is estimated to be 40-45 A. Residues that are exposed to the membrane are relatively poorly conserved in the sequences of homologous RC proteins. The surface area of the RC is comparable to the surface areas of water-soluble proteins of similar molecular weight. The volumes of interior atoms in the RC are also similar to those of water-soluble proteins, indicating the same compact packing for both types of proteins. The electrostatic potential of the cofactors was calculated. The results show an asymmetry in the potential between the two possible pathways of electron transfer, with the A branch being preferred electrostatically.

Bacteria↗
PubMed1987

Pentobarbital-like discriminative stimulus properties of halothane, 1,1,1-trichloroethane, isoamyl nitrite, flurothyl and oxazepam in mice.

Volatile inhalants represent a diverse group of chemicals which pose a public health problem because of their abuse potential and neurobehavioral toxicity. Although relatively little is known about their pharmacology, they share certain pharmacological properties with classic central nervous system depressants. Drug discrimination procedures were used to compare the effects produced by pentobarbital (PB), oxazepam and several inhalants. Mice were trained to discriminate PB from saline injections in a two-lever operant task. Stimulus generalization was examined after 20-min inhalation exposures to halothane (500-8000 ppm), 1,1,1-trichloroethane (500-12000 ppm), isoamyl nitrite (150-1050 ppm), flurothyl (562-1300 ppm) and injections of oxazepam (0.1-20 mg/kg). Halothane, 1,1,1-trichloroethane and oxazepam produced discriminative stimulus effects similar to those produced by PB. Isoamyl nitrite and flurothyl, while decreasing rates of responding, were not consistently generalized from PB. Differences are apparent in the PB-like discriminative effects of inhalants. Toluene, as shown in a previous study, as well as halothane and 1,1,1-trichloroethane have PB-like discriminative effects which are also shared by oxazepam and may be another common effect of central nervous system depressants. Other chemicals, like isoamyl nitrite and flurothyl, are representative of qualitatively different classes of behaviorally active inhalants.

Administration, Inhalation↗
PubMed1987

Toluene, halothane, 1,1,1-trichloroethane and oxazepam produce ethanol-like discriminative stimulus effects in mice.

Drug discrimination procedures were used to compare the discriminative stimulus properties of ETOH and volatile inhalants. Mice were trained to discriminate between i.p. injections of ETOH (1 g/kg) and saline in a two-lever operant task. Stimulus generalization was examined after 20-min inhalation exposures to toluene (300-5400 ppm), halothane (500-8000 ppm) and 1,1,1,-trichloroethane (TCE; 125-14000 ppm). Oxazepam (10-30 mg/kg i.p.) also was tested. Concentration- or dose-related increases in ETOH-lever responding were observed with toluene, halothane, TCE and oxazepam. Shared discriminative stimulus properties among toluene, halothane, TCE and ETOH indicate that some volatile inhalants share pharmacological properties with ETOH. Previous research has shown that these inhalants also produce pentobarbital-like discriminative stimulus effects in mice. Thus, at least some inhaled anesthetics and abused solvents have behavioral effects in common with abused central nervous system depressant drugs such as ETOH and barbiturates.

Animals↗
PubMed1987

Stimulus control and the development of behavioral tolerance to daily injections of d-amphetamine in the rat.

We examined whether daily d-amphetamine administration affected behavior under the control of external stimuli differently than behavior not under such control. Two variants of a fixed-consecutive-number reinforcement schedule were combined in a multiple schedule. An external discriminative stimulus indicated when the schedule requirement for reinforcement had been satisfied in one component, no such stimulus was used in the other component. Reinforcement frequency was roughly equated between the components by reducing the probability of reinforcement in the added stimulus component. Two groups of animals were given daily i.p. injections with equivalent doses of drug. Tolerance to the drug's behavioral effects developed when injections occurred before behavioral evaluation but did so only to a limited extent when injections were given only after the sessions. This indicated that behaving in the presence of the drug facilitated the development of such tolerance. It developed under both stimulus control conditions at both doses; at 3.0 mg/kg, it developed predominantly in those aspects of behavior that were under the control of external discriminative stimuli. Although drug-related decreases in reinforcement frequency in some animals were correlated with behavioral tolerance development, differential tolerance development was not associated consistently with such reductions. Establishing discriminative control of behavior by external stimuli can both reduce sensitivity to repeated d-amphetamine administration and facilitate the development of tolerance to its behavioral effects.

Animals↗
PubMed1986

Structural homology of reaction centers from Rhodopseudomonas sphaeroides and Rhodopseudomonas viridis as determined by x-ray diffraction.

Crystals of the reaction center (RC) from Rhodopseudomonas sphaeroides with the space group P2(1)2(1)2(1), have been studied by x-ray diffraction. The Patterson search (molecular replacement) technique was used to analyze the data, with the structure of the reaction center from Rhodopseudomonas viridis as a model system. A preliminary electron density map of the reaction center from R. sphaeroides has been obtained. Comparison of the structure of the RC from R. sphaeroides with that from R. viridis showed the following conserved features: five membrane-spanning helices in each of the L and M subunits, a single membrane-spanning helix in the H subunit, a 2-fold symmetry axis, and similar positions and orientations of the cofactors. Unlike the RCs from R. viridis, both quinones are retained in the RCs from R. sphaeroides. The secondary quinone is located near the position related by the 2-fold symmetry axis to the primary quinone.

Bacterial Proteins↗
PubMed1985

Fractal surfaces of proteins.

Fractal surfaces can be used to characterize the roughness or irregularity of protein surfaces. The degree of irregularity of a surface may be described by the fractal dimension D. For protein surfaces defined with probes in the range of 1.0 to 3.5 angstroms in radius, D is approximately 2.4 or intermediate between the value for a completely smooth surface (D = 2) and that for a completely space-filling surface (D = 3). Individual regions of proteins show considerable variation in D. These variations may be related to structural features such as active sites and subunit interfaces, suggesting that surface texture may be a factor influencing molecular interactions.

Carboxypeptidases↗
PubMed1985

Inhaled toluene produces pentobarbital-like discriminative stimulus effects in mice.

The abuse of volatile solvents may be due to their ability to produce an intoxication similar to that produced by classical central nervous system depressants such as the barbiturates and ethanol. To evaluate this hypothesis, mice were trained to discriminate pentobarbital from saline injections in a two-lever operant task. Stimulus generalization was examined following 20-min inhalation exposures to toluene (300-5400 ppm). In 8 of 10 subjects, pentobarbital-lever responding occurred following toluene exposure indicating an overlap in the discriminative stimulus properties of toluene and pentobarbital.

Aerosols↗
PubMed1985

Complex formation between flavodoxin and cytochrome c. Cross-linking studies.

Complex formation between Azotobacter vinelandii flavodoxin and horse cytochrome c has been demonstrated through cross-linking studies with dimethyl suberimidate, dimethyl adipimidate, 1-ethyl-3-(3-di-methylaminopropyl)carbodiimide, and dimethyl-3,3'-dithiobispropionimidate. Essentially quantitative cross-linking of cytochrome c and flavodoxin was observed at low ionic strengths with the carbodiimide cross-linking reagent. An association constant of 4 X 10(4) M-1 was obtained between cytochrome c and flavodoxin at 88 mM ionic strength from analysis of the cross-linking studies. This value is similar to the association constant determined kinetically during the electron transfer reaction between cytochrome c and flavodoxin (Simondsen, R.P., Weber, P.C., Salemme, F.R., and Tollin, G. (1982) Biochemistry 21, 6366-6375), and suggests that the cross-linked complex may be similar to the precursor complex identified kinetically. A structural model for the flavodoxin-cytochrome c complex proposed by these workers is shown to be compatible with the present cross-linking results.

Azotobacter↗
PubMed1985

Electrostatic influence on energetics of electron transfer reactions.

Electron transfer chains in biological systems must operate efficiently to satisfy metabolic energetic requirements. The component proteins in these chains are expected to exhibit characteristic structural features that facilitate electron transfer to the appropriate donor and acceptor proteins. A survey of soluble one-electron carrier proteins indicates a significant tendency for lower potential proteins to be more negatively charged than higher potential proteins. Consideration of the electrostatic consequences of this pattern of charge asymmetry suggests that the reduction potential difference between the two proteins will be minimized in the precursor complex associated with electron transfer. An equivalent statement is that the change in free energy accompanying electron transfer in the complex will approach zero. This behavior is consistent with theoretical arguments advanced by Albery and Knowles [Albery, W. J. & Knowles, J. R. (1976) Biochemistry 15, 5631-5640], which suggest that for the most efficient enzymes, the free energy difference between enzyme-bound species should approach zero. A more general derivation of this prediction is provided. The observed charge asymmetry in electron transfer proteins provides a structural mechanism for satisfying this requirement, thus accelerating the overall rate of electron transfer.

Chemical Phenomena↗
PubMed1985

The roles of stimulus control and reinforcement frequency in modulating the behavioral effects of d-amphetamine in the rat.

The behavioral effects of d-amphetamine have been shown to be modulated by stimulus control, with less impairment of performance occurring when control is great. When the fixed-consecutive-number schedule is used (on which at least a specified consecutive number of responses must be made on one operandum before a single response on another will produce a reinforcer), response rate tends to be invariant but reinforcement frequency is not. This study asks whether the differences in reinforcement frequency that usually accompany changes in stimulus control could themselves be responsible for the performance differences. Two versions of the fixed-consecutive-number schedule of reinforcement were combined into a multiple schedule within which stimulus control was varied but differences in reinforcement frequency were minimized by omitting some reinforcer deliveries during the component that usually had the higher reinforcement frequency. In one component, a compound discriminative stimulus was added with the eighth consecutive response on the first lever; a single response on the second lever was then reinforced. In the other component, no such stimulus was presented. With no added stimulus, large decreases occurred in the number of runs satisfying the minimum requirement for reinforcement at doses of drug that produced only minimal changes when an added stimulus controlled behavior. Thus, increased stimulus control diminishes the behavioral changes produced by d-amphetamine even when the possible contribution by baseline reinforcement rate is minimized.

Animals↗
PubMed1985

Toxicokinetics of toluene in the rat.

Toxicokinetic experiments with toluene that rely on data pooled from several animals have typically provided estimates of rate constants based on single exponential functions; in the present study a within-subject design was used to describe the time course of toluene in the blood to see if additional exponential terms could be resolved. Each rat was exposed for 2 h to either 1 000, 1 780, or 3 000 ppm of toluene. Blood samples were drawn at different times from indwelling jugular cannulae, and blood toluene concentrations were determined by vapor phase equilibrium chromatography. There was substantial variability between the peak blood values of the animals at each exposure concentration. Nonlinear regression was used to determine regression parameters for data drawn from individual animals. A bi-exponential function was found to minimize significantly the residual sum of squares observed during elimination. However, only a single exponential function could be resolved reliably during uptake. The mean half-time during uptake was approximately 34 min; the two half-times for elimination averaged approximately 6 and 90 min. Because of between-subject variability, a more accurate description of the time course of toluene uptake and elimination can be provided by kinetic studies that use a within-subject design.

Animals↗
PubMed1985

Midwives rule--OK!

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Consumer Behavior↗