Synergistic antimycobacterial activity between ethambutol and the beta-lactam drug cefepime

The contributions of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and gamma-aminobutyric acid (GABA[A]) receptors in the induction of long-term potentiation (LTP) have been studied in the CA1 region of the rat hippocampus. The results suggest that: (1) in physiological conditions, AMPARs are necessary for the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent LTP since LTP cannot be elicited in the presence of the AMPAR antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Although a NMDAR-dependent LTP occurs in the presence of a GABA(A) antagonist and high concentrations of divalents cations, blockade of AMPARs leads to a voltage-dependent calcium channels (VDCC)-dependent LTP since its induction is blocked by nifedipine and not by APV. (2) The bicarbonate-induced GABA(A) receptor-mediated depolarizing response is not necessary in the induction of NMDAR-dependent or VDCC-dependent LTP since induction of these two types of LTP were not blocked by acetazolamide or in a nominally bicarbonate-free solution.     

Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze-fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage-gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.     

Restoration of X-ray and etoposide resistance, Ku-end binding activity and V(D) J recombination to the Chinese hamster sxi-3 mutant by a hamster Ku86 cDNA

Ku is a heterodimeric protein composed of 86 and 70 kDa subunits that binds preferentially to the double-stranded ends of DNA. Recent molecular characterization of ionizing-radiation sensitive (IRs) mutants belonging to the XRCC5 complementation group demonstrated the involvement of Ku in DNA double-strand break (DSB) repair and lymphoid V(D)J recombination. Here, we describe the isolation of a full-length hamster cDNA encoding the large subunit of the Ku heterodimer and demonstrate that the stable expression of this cDNA can functionally restore IR, Ku DNA end-binding activity and V(D)J recombination proficiency in the Chinese hamster IRs sxi-3 mutant. Moreover, we also demonstrate that sxi-3 cells are hypersensitive to etoposide, a DNA topoisomerase II inhibitor, and that resistance to this drug was restored by the Ku86 cDNA. These experiments suggest that a defect in the large subunit of the heterodimeric Ku protein is the sole factor responsible for the known defects of sxi-3 cells and our data of further support the role of Ku in DNA DSB repair and V(D)J recombination.     

Single photon emission computed tomographic blood flow and magnetic resonance volume imaging of basal ganglia in Huntington''s disease

During oogenesis in Drosophila, germ cells appear in sequential clusters of 16 interconnected cells. The events surrounding the differentiation of these cells are not fully understood. Here we present genetic and morphological analysis of mutations in the gene stand still (stil). Through complementation analyses we have refined the location of this gene to cyological region 49B-C. Our analyses of ovaries from ethylmethane sulfonate (EMS)-induced mutant alleles of this gene suggest that mutations in the stil gene produce a wide range of phenotypic abnormalities, from the absence of germ cells in the most severe alleles, to egg chambers with cytoskeletal defects in the less severe alleles. Our results suggest a role for this gene in specifying or maintaining a cytoskeletal component, with consequences during oogenesis and possibly during germ line sex determination.     

The generation effect and the modeling of associations in memory

The search of associative memory (SAM) model of Gillund and Shiffrin (1984) was applied to data of two experiments that examined the generation effect (Slamecka & Graf, 1978). Subjects studied a list of related word pairs, in which they either read both words in the pair or generated the right- hand response term using the left-hand stimulus term plus the response word fragment as generation cues. Experiment 1 manipulated encoding condition within subjects and used an incidental learning procedure. Experiment 2 manipulated encoding condition between subjects and used an intentional learning procedure. Memory was tested with recognition, cued recall, and free recall. A higher order association model gave a better and more parsimonious fit to the results than did an item-level association model. The relationship between various versions of SAM and current accounts of the generation effect are discussed, particulary the two-factor theory of Hirshman and Bjork (1988).     

Effects of cold stress on survival and reproduction of Haematobia irritans (Diptera: Muscidae)

1. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) increases the stability of the oxazolidine prodrug toward hydrolysis. 2. The binding constant (Kb) and rate constant (Kc) for the hydrolysis of the prodrug-HP-beta-CD complex were calculated from the kinetic data. 3. Ion-spray mass spectra confirmed prodrug-HP-beta-CD complexation. 4. Mass spectral and kinetic data indicated 1:1 stoichiometry for the complex. 5. A significant elevation of locomotor activity in rats was observed when either (-)-ephedrine or the prodrug was administered by either the intraperitoneal or the oral route. 6. Addition of HP-beta-CD potentiated the central nervous system effect of both (-)-ephedrine and the prodrug when administered intraperitoneally. However, when the drugs were administered orally, HP-beta-CD caused a decrease in activity.     

Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF)

Coronary artery angioplasty or bypass is being performed for increasing numbers of patients in their seventh, eighth, ninth and even tenth decades of life. Because of the cost involved, justification for performing these procedures in the elderly has become a topic of daily discussion among those responsible for funding healthcare. Both silent and overt coronary artery disease (CAD) are more common in the population over 65 years of age. Because CAD in the elderly often presents in an atypical manner, diagnosis of the disease is frequently delayed. Partly because of the delayed diagnosis and partly because of cost considerations, coronary arterial bypass (CABG) is more often performed as an emergency procedure in the elderly with the results that both operative mortality and costs are increased over those observed in a younger population. Nevertheless, it is clear that performance of coronary revascularization procedures in the elderly can both prolong life and improve the quality of life beyond what can be achieved using alternative methods of treatment. Greater efforts directed toward detection of ischemic heart disease in the these patients and earlier, elective surgery could significantly reduce both the mortality and disability associated with CAD in the elderly.     

Thermotropic phase properties of the hydroxyceramide/cholesterol system

The interaction of cholesterol with ceramides containing α-hydroxy fatty acyl chains (hydroxyceramides) has been studies as a foundation for characterizing the lipid bilayers of thestratum corneum. A relatively large quantity of cerebrosides was obtained from bovine brain and converted to ceramides through removal of the carbohydrate side chain. The ceramides were separated based on the absence or presence of hydroxy fatty acyl chains. The lyophilized hydroxyceramides showed a broad melting region at 92°C. Hydroxyceramides dispersed in water produced a relatively narrow, thermotropic transition at 75°C. The effect of cholesterol on this thermotropic phase transition of hydroxyceramides was determined by differential scanning calorimetry. With respect to the main transition, cholesterol caused a broadening of the phase transition at relatively low levels as well as a decrease in the peak transition temperature. The presence of cholesterol at levels in excess of 7 wt% gave rise to an additional low-temperature transition at 55°C. Upon immediate rescanning, this transition was exothermic, but with increasing incubation time the area under the excess heat capacity curve as a function of temperature became smaller. After two days or more, the transition observed was endothermic. At cholesterol levels between 40 and 50 wt%, multiple peaks were observed. From comparisons with related systems, the cooperative thermal transitions of hydroxyceramides with cholesterol are suggested to result from changes in hydrogen bonding or be due to phase separation. The composition of isolated brain ceramides is being compared with that reported for thestratum corneum.     

Gas-liquid mass transfer in a circulating jet-loop nitrifying MBR

Based on airlift configuration, a novel circulating jet-loop submerged membrane bioreactor (JLMBR) adapted to ammonium partial oxidation has been developed. Membrane technology and combined air and water forced circulation are adopted to obtain a high biomass retention time and to achieve a separate control of mixing and aeration. This study is intended to determine how gas-liquid mass transfer is affected by operating conditions. In a first approximation, liquid was assumed to be perfectly mixed. A classical non-steady state clean water test, known as the “gas out-gas in” method, was used to determine the gas-liquid mass transfer coefficient k_La. Air and recirculated liquid superficial velocities were gradually increased from 0.013 to and 0.0056 to , respectively. Subsequently, the gas-liquid mass transfer coefficient k_La varied from 0.01 to . It appears to be influenced by the combined action of air and recirculated liquid flowrates in the range and , respectively, for air and liquid. Correlations are proposed to describe this double influence. Experiments were performed on tap water and a culture medium used for the autotrophic growth of nitrifying bacteria, respectively. Oxygen transfer appeared to be not significantly affected by the mineral salt encountered in this medium.     

Does oral experience terminate ingestion?

Using data from studies of ingestive behavior in developing rat pups we demonstrate how oral experience can contribute to the termination of ingestion. In rat pups, repeated oral stimulation with sweet solutions causes a decline in oral responsiveness. The diminished responsiveness is specific to the flavor of the stimulus experienced orally and can persist for several hours. We suggest that this experience-based decrement in responsiveness is best considered "oral habituation" and that oral habituation largely accounts for the onset of satiety. Post-ingestive feedback signals may have their influence through the oral habituation process or act in the context of oral habituation. Oral habituation is also shown to depend on the pattern of stimulus presentation, a phenomenon that adds considerable complexity to assessing the contributions of oral experience to satiety. The concept of oral habituation may be useful in understanding the immediate control of ingestion and the moment-to-moment expression of ingestive behavior in adult animals.