Possibility of a resonating-valence-bond state in the high-Tc superconductor Bi4Ca3Sr3Cu4O16+x.
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Biomedical subjects
Publications and source records attributed to M Tang.
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The administration of drugs with anxiolytic action to rehydrating rats augments the intake of 1.5% NaCl solution. In order to clarify the status of caffeine as an anxiolytic agent and its possible interaction with a benzodiazepine having high potency and efficacy in this regard, caffeine (0.78-100 mg/kg) alone and caffeine (0.78-50 mg/kg) plus clonazepam (0.05 or 0.50 mg/kg) injections (IP) were administered to rehydrating rats prior to 1-hr sessions during which they drank 1.5% NaCl solution. When given alone, caffeine, within a particular dose range, and clonazepam at both doses, augmented NaCl solution intake, but when administered in combination, caffeine antagonized the effects of clonazepam.
Groups of rats were given differential histories of drinking either water, cocaine (0.15 mg/ml), or ethanol (2.5%) solutions under fixed-time (FT) 1-min schedule-induced polydipsia conditions in daily, 3-hr sessions. The session solution for all groups was then changed to chlordiazepoxide (0.25 mg/ml), and after daily session intakes had stabilized, FT values of 3 and 5 min were probed for single sessions. Probe-session chlordiazepoxide intakes were greater for the Ethanol History Group than for Cocaine History and Water History Groups. Previous research showed that probe conditions elevated intakes for agents with abuse potential (cocaine, ethanol, midazolam), but not for those lacking such potential (water, chlordiazepoxide, flurazepam). The present study demonstrated that a history of ethanol overindulgence yielded elevated probe intakes for chlordiazepoxide, while a history of cocaine or water overindulgence did not. This is consistent with animal and human evidence indicating that a history of either alcohol or sedative abuse increases the probability that benzodiazepines will function as reinforcers and/or be abused.
Three XbaI restriction fragment length polymorphisms (RFLPs) can be detected using the factor VIII-intron 22 probe (p482.6) in a XbaI-KpnI double digest of genomic DNA. The XbaI (A) site had been reported by Wion et al (1986) to be in intron 22, while the two additional sites. XbaI (B) and XbaI (C), are shown here to be X-linked and close to the XbaI (A) site. The frequencies of heterozygosity for these three sites are 0.49, 0.18 and 0.30 respectively. In 75 females the observed heterozygosity rate for the XbaI (A) site is 0.41 and this increased to 0.57 with the two additional sites. Care should be exercised when interpreting the XbaI RFLPs, since the 1.4 kb XbaI/KpnI fragment and the 4.8 kb XbaI fragment are associated with both positive XbaI (A) and XbaI (B) sites. By the combined use of the multiple XbaI polymorphisms with the BclI site in intron 18, the carrier detection rate would increase to 67%. Four prenatal diagnoses had been performed using the multiple XbaI polymorphisms.
A protein with a tetragonal pattern, defined as RS protein, was found on the wall surface of an alkaline phosphatase secretion-deficient mutant (NM 105) of Bacillus licheniformis 749/C. The protein was present on the wall surface of the exponential-growth-phase cells, but at the stationary growth phase it was overproduced and hypersecreted. This protein was precipitated to homogeneity from the culture fluid by 80% ammonium sulfate saturation and chilled acetone. The molecular mass of the protein was 98 kilodaltons, and it had a single subunit in a sodium dodecyl sulfate gel. Specific anti-RS antibody was generated in rabbits and used to immunolabel the RS protein on the cells at different growth phases. In early-exponential-growth-phase cells, the outside surface of the wall, the cytoplasm, and the inside surface of the cytoplasmic membrane were labeled. In stationary-growth-phase cells, the cytoplasm was poorly labeled, but the labeling on the outside surface of the wall was high. AB. licheniformis NM 105 gene library was made by using the lambda phage EMBL3. The RS protein expression from this gene library was detected by a modified autoradiographic procedure. One of the amplified RS protein-positive plaques (4213-1) containing recombinant DNA was chosen, and the restriction map of this DNA was prepared. The RS protein expressed in Escherichia coli NM 539 infected with 4213-1 recombinant phage had a lower molecular mass than the purified authentic RS protein. The 4.5-kilobase-pair (kbp) SalI-EcoRI fragment of the recombinant DNA was cloned in the shuttle plasmid pMK4 to construct pMK462, which was expressed in B. subtilis MI112 and produced the RS protein identical in molecular mass to the purified authentic RS protein. The RS protein expression was also demonstrated in cryosections of transformed E. coli and B. subtilis cells by immunoelectron microscopy. The 1.2-kbp SalI-HindIII and 1.8-kbp HindIII-HindIII recombinant DNA restriction enzyme fragments, respectively, from the right of the restriction map produced anti-RS antibody cross-reacting proteins. The expression of the 1.2-kbp SalI-HindIII DNA fragment cloned in pUC8 could be induced with isopropyl-beta-D-thiogalactopyranoside. The 1.8-kbp DNA restriction fragment hybridized with both the chromosomal DNA of strain NM 105 and the recombinant phage 4213-1 DNA. The RS gene expression was finally demonstrated in transformed E. coli 539 cells by in situ hybridization of frozen thin sections with the 1.8-kbp HindIII biotin-dATP probe and immunolabeling these with anti-biotin immunoglobulin G and protein A-gold.
In previous research, two groups of rats exposed to a fixed time (FT) 1-min schedule of food-pellet delivery exhibited equal schedule-induced polydipsia for water vehicle and a 0.05 mg/ml solution of midazolam, respectively. Exposure to FT schedule values greater than 1 min (3 and 5 min) resulted in greater milliliter per pellet intakes of midazolam than of water, perhaps reflecting the reinforcing efficacy of the drug. To determine if drugs with unequivocal reinforcing efficacy display similar elevations at the larger FT values, solutions of cocaine and ethanol, but also of the equivocally reinforcing agents chlordiazepoxide and flurazepam, as well as water, were offered to groups of rats at concentrations isoacceptable under FT 1-min schedule-induction conditions. Under the FT 1-min schedule, separate groups of rats drank equal and excessive amounts of water, cocaine (0.15 mg/ml), ethanol (2.5% v/v), chlordiazepoxide (0.25 mg/ml) and flurazepam (0.175 mg/ml). Differential group milliliter per pellet intakes occurred under larger FT values: ethanol, cocaine and midazolam yielded greater values than water, chlordiazepoxide or flurazepam. Schedule-induced drug intake perhaps offers a method for evaluating the oral abuse potential of a drug under conditions which generate a variety of behavioral excesses and may potentiate intrinsic reinforcing efficacy.
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Two groups of rats were given different initial histories before exposing them to daily, 2-hr fixed-interval 1-min (FI 1-min) food-pellet sessions with water freely available. For the initial-history phase (approximately 17 weeks), a Schedule-History Group had no water available during FI 1-min sessions, while a Home-Cage-History Group was maintained at the same body weight (80% of free feeding) in home cages. When water then became available for both groups during FI 1-min sessions, the Schedule-History Group was retarded in their rate of acquisition and final level of schedule-induced polydipsia relative to the Home-Cage-History Group. Substitution of 5% ethanol solution for session water in the final phase produced a like intake level for both groups typical for these inducing conditions. It was concluded that the probability of drinking water in a session situation is reduced by a lengthy history of water unavailability, thereby attenuating the acquisition rate and final level of schedule-induced water overdrinking.
Two 1,4 benzodiazepines bind preferentially to the central- and peripheral-type benzodiazepine receptor in the brain, clonazepam and Ro 5-4864, respectively. They were administered to rats to determine if the relation between known anxiolytic action and efficacy in augmenting NaCl solution ingestion in rehydrating rats would remain the case for these prototypic agents. Clonazepam (0.062-32.0 mg/kg, PO) was highly potent and efficacious and increased 1.5% NaCl solution intake in a dose-related fashion. Water intake could also be increased, but to a relatively minor degree. Ro 5-4864 (4-8 mg/kg, IP) did not affect 1.5% NaCl solution ingestion, nor did this dose range suppress the augmenting effect of clonazepam (0.5-2.0 mg/kg, PO) on the solution intake. Since clonazepam does, and Ro 5-4864 does not, possess punishment-attenuation properties in other tests, drug augmentation of NaCl solution ingestion by rehydrating rats continues to correlate well with known anxiolytic action.
An animal model of chronic and excessive voluntary (unforced) alcohol ingestion is presented in which, by drinking, animals produce repeated, substantial elevations in blood ethanol concentration and develop physical dependence. The overindulgence is elective in that ethanol is chosen in preference to certain other fluid-ingestive alternatives. Beside the usual demonstrations of acutely compromised motor performance, tolerance development, cross-tolerance, etc., the model demonstrates that the consequences of even short, but continued, daily drinking episodes results in the disruption of reinforced behavior that occurs later in the day when blood ethanol is absent (impaired general functioning). The conditions which induce the ethanol overindulgence can generate a variety of behavioral excesses which places alcoholism in a context of environmentally determined malfunctions that are subject to therapeutic change by altering situational parameters. Efficacious experiments utilizing therapeutic and preventive strategies are described that may serve as suggestions for corresponding human alcoholism intervention strategies.
1. The influence of alpha-adrenoceptor stimulation on mechanical and electrophysiological parameters was investigated in ventricular preparations from guinea-pigs and rabbits. Action potential and force of contraction were measured in papillary muscles and ionic currents were measured in isolated myocytes. 2. The effects of alpha-adrenoceptor stimulation were compared with those of beta-adrenoceptor stimulation. 3. In the guinea-pig the stimulation of alpha-adrenoceptors caused a small increase in the force of contraction (less than 10% of the response to beta-adrenoceptor stimulation) which was not accompanied by any increase of the slow calcium inward current. beta-Adrenoceptor stimulation produced large increases in both force of contraction and slow inward calcium current. The noradrenaline-induced increase in the slow inward calcium current was not affected by phentolamine. 4. In the rabbit, alpha-adrenoceptor stimulation produced large increases in the force of contraction (about two thirds of those seen in response to beta-adrenoceptor stimulation). Whereas beta-adrenoceptor stimulation also produced large increases in both maximal upstroke velocity of slow-response action potentials and slow inward calcium current, there was almost no change of both parameters in response to alpha-adrenoceptor stimulation. 5. We conclude that, first, the contribution of alpha-adrenoceptors to adrenoceptor-mediated changes of force of contraction is minimal in the guinea-pig ventricle, and second, the pronounced changes of force of contraction in the rabbit ventricle in response to alpha-adrenoceptor stimulation are unrelated to changes in the slow inward calcium current.