Evidence for direct interaction of ketamine with alpha 1- and beta 2-adrenoceptors

1. Ketamine has a number of effects that suggest that it may interact with alpha- and beta-adrenoceptors. To date, the experimental evidence for this has been indirect and has been based on physiological studies using competitive blocking agents. In the present study we sought to determine from receptor binding studies whether ketamine binds directly to alpha- and beta-adrenoceptors. 2. Membrane preparations of alpha 1- and beta 2-adrenergic binding sites were obtained from urinary bladder and urethrae of sheep. These binding sites were characterized by saturation analyses using [3H]-prazosin for alpha 1-adrenoceptor binding sites and [125I]-cyanopindolol (CYP) for the beta 2-adrenoceptor binding sites. The receptors were further characterized by displacement studies using selective and non-selective antagonists. 3. Studies in which ketamine was used to displace [3H]-prazosin revealed a Kd of 3.40 +/- 1.23 x 10(-3) mol/L for ketamine binding to alpha 1-adrenoceptors. Displacement studies of [125I]-CYP by ketamine showed a Kd of 0.35 +/- 0.03 x 10(-3) mol/L for ketamine binding to beta 2-adrenoceptors. 4. We conclude that ketamine interacts directly with both alpha 1- and beta 2-adrenoceptors and that such interactions probably explain the reported effects of this agent on the vasculature and the bronchial tree.     

Synaptic integration of functionally diverse pallidal information in the entopeduncular nucleus and subthalamic nucleus in the rat

To determine the principles of synaptic innervation of neurons in the entopeduncular nucleus and subthalamic nucleus by neurons of functionally distinct regions of the pallidal complex, double anterograde labeling was carried out at both light and electron microscopic levels in the rat. Deposits of the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine were placed in different functional domains of the pallidal complex in the same animals. The tracer deposits in the ventral pallidum and the globus pallidus gave rise to GABA-immunopositive projections to the entopeduncular nucleus, the subthalamic nucleus, and the more medial lateral hypothalamus that were largely segregated but overlapped at the interface between the two fields of projection. In these regions the proximal parts of individual neurons in the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus received synaptic input from terminals derived from both the ventral pallidum and the globus pallidus. Furthermore, the analysis of the afferent synaptic input to the dendrites of neurons in the subthalamic nucleus that cross functional boundaries of the nucleus defined by the pallidal inputs, revealed that terminals with the morphological and neurochemical characteristics of those derived from the pallidal complex make synaptic contact with all parts of the dendritic tree, including distal regions. It is concluded that functionally diverse information carried by the descending projections of the pallidal complex is synaptically integrated by neurons of the entopeduncular nucleus, lateral hypothalamus, and subthalamic nucleus by two mechanisms. First, neurons located at the interface between functionally distinct, but topographically adjacent, projections could integrate diverse information by means of the synaptic convergence at the level of the cell body and proximal dendrites. Second, because the distal dendrites of neurons in the subthalamic nucleus receive input from the pallidum, those that extend across two distinct domains of pallidal input could also provide the morphological basis of integration.     

A Dedicated Line-Processor as Used at the SHF

A hardwired trigger processor was used at the SLAC Hybrid Facility to find evidence for charged tracks originating from the fiducial volume of a 40? rapid-cycling bubble chamber. Straight-line projections of these tracks in the plane perpendicular to the applied magnetic field were searched for using data from three sets of proportional wire chambers (PWC). This information was made directly available to the processor by means of a special digitizing card. The results memory of the processor simulated read-only memory in a 168/E processor and was accessible by it. The 168/E controlled the issuing of a trigger command to the bubble chamber flash tubes. The same design of digitizer card used by the line processor was incorporated into the 168/E, again as read only memory, which allowed it access to the raw data for continual monitoring of trigger integrity. The design logic of the trigger processor was verified by running real PWC data through a FORTRAN simulation of the hardware. This enabled the debugging to become highly automated since a step by step, computer controlled comparison of processor registers to simulation predictions could be made.     

Virus-mediated delivery of antigenic epitopes into dendritic cells as a means to induce CTL

Dendritic cells (DC) are potent inducers of CD8+ T cells and can stimulate protective antitumor immunity when pulsed with an antigenic peptide or protein. We used a replication-deficient adenovirus containing a Kb-restricted antigenic peptide of chicken OVA to study CTL induction in vitro and in vivo after adenovirus-mediated gene transfer into DC. The efficiency of adenovirus-infected DC in eliciting a specific CTL response was compared with immunizations with a recombinant vaccinia virus and DC pulsed with peptide or protein. An immortalized DC line derived from a C57BL/6 mouse and freshly isolated splenic DC from C57BL/6 mice were used in CTL induction. Virus-infected DC elicited the strongest Ag-specific CTL response in vitro and in vivo and induced protective antitumor immunity to a challenge with EG.7 tumors (EL-4 cell line expressing OVA). Direct immunization of mice with recombinant adenovirus resulted in the induction of high titers of neutralizing Abs, which precluded a boost of a CTL response after repeated inoculations. However, repeated injections of virus-infected DC induced only low titers of neutralizing Abs. Furthermore, the presence of neutralizing Abs specific for the virus did not affect the usefulness of infected DC as repeated applications of virus-infected DC boosted the CTL response even in mice previously infected with the recombinant vector. The use of DC infected with a recombinant virus has advantages over other forms of immunization and could provide an alternative approach for designing vaccination therapies.     

Deconvolution of damping forces with a nonlinear microresonator

We report a fully electrical microcantilever device that utilizes capacitance for both actuation and detection and show that it can characterize various gases with a bare silicon microcantilever. We find the motion of the cantilever as it rings down when the oscillating force is removed, by measuring the voltage induced by the oscillating capacitance in the microcantilever∕counterelectrode system. The ringdown waveform was analyzed using an iterative numerical algorithm to calculate the oscillator motion, modeling the cantilever∕electrode capacitance to calculate the electrostatic force. We find that nonlinearity in the motion of the cantilever is not necessarily a disadvantage. After calibration, we simultaneously measure viscosity and density of several gaseous mixtures, yielding viscosities within ±2% and densities within ±6% of NIST values.     

CALCULATION OF VAN DER WAALS FORCES WITH DIFFUSE COATINGS: APPLICATIONS TO ROUGHNESS AND ADSORBED POLYMERS

A novel method using Lifshitz continuum theory to account for the effects of surface roughness was developed. The method treats roughness as a diffuse film whose dielectric properties vary continuously between those of the substrate and those of the solvent: AFM measurements of surface topography are used to deduce the volume-fraction profile of substrate in solvent which in turn is converted into a dielectric-permittivity profile using the Clausius-Mossoti equation as a mixing rule. Calculations show orders of magnitude of reduction in the van der Waals force between rough surfaces at contact compared with smooth surfaces, with the amount of reduction dependent on the shape of the volume-fraction profile as well as the total depth of the roughness. These predictions help account for discrepancies observed previously between the Total Internal Reflection Microscopy (TIRM) data and calculations for smooth polystyrene surfaces in water, with or without physisorbed polymer, without introducing any adjustable parameters.     

An international inter-laboratory trial of the proposed ISO 105-C08 test procedure: a single wash test protocol using a detergent incorporating a lowtemperature bleach activator

A new single wash test procedure, ISO 105-C08, has been developed using a reference detergent, perborate and TAED (a low-temperature bleach activator) in order to better reflect domestic practice. Following an international trial, the procedure has been shown to be fully acceptable for the purpose of inter-laboratory comparisons.     

Effect of incident angle in spectral ellipsometry on composition control during molecular beam epitaxial growth of HgCdTe

The effect of incident angle in spectral ellipsometry (SE) on composition control of Hg_1−xCd_xTe grown by molecular beam epitaxy (MBE) was investigated. Although a small uncertainty in the incident angle tends to have a significant impact on the ellipsometric data, and therefore the composition data, it was found that the incident angle uncertainty could be corrected in the SE model calculation, resulting in an “optimized” incident angle that would give the best fit between measured and calculated ellipsometric data. Experimental data supporting this simple corrective or optimization procedure for the incident angle are presented.