Deoxyribonucleic acid vaccines encoding antigens with rapid proteasome-dependent degradation are highly efficient inducers of cytolytic T lymphocytes

We generated plasmid expression vectors encoding ubiquitin and beta-galactosidase (beta-gal) with different intervening amino acids, allowing for the production of processed protein products that have either stabilizing or destabilizing residues at their N-termini. P815 cells transfected with plasmids encoding beta-gal with a destabilizing N-terminus did not have detectable expression beta-gal unless they were treated with inhibitors specific for the proteasome. Inhibitors of other proteolysis pathways had no such effect. Nevertheless, transfectants expressing beta-gal with different amino acid residues were equally sensitive to cytolysis by a CTL clone specific for a beta-gal peptide presented in the context of H-2Ld. In contrast to vectors encoding native beta-gal, plasmid vectors encoding beta-gal with a destabilizing residue did not induce detectable anti-beta-gal Abs when injected into skeletal muscle of BALB/c mice. However, such vectors were significantly more effective than vectors encoding native beta-gal or beta-gal with a stabilizing residue in stimulating CTL specific for P13.2, a lacZ transfectant of P815. We conclude that incorporation of strategies that enhance proteasome-dependent degradation may generate DNA vaccines that are more effective in inducing cellular immunity against targeted Ags.     

Evaluation of a commercial process for collection and cooling of beef offals by a temperature function integration technique.

The hygienic adequacy of a commercial process for the collection and cooling of beef offals was assessed by a temperature function integration technique. The diverse operations for collection of offals were inspected. The rates of product movement through those operations, and the temperatures of products at the time of their being packed, were determined. From that information, four of the nine product types were selected for examination of their temperature histories during the assembly and cooling of the cartoned products. The products selected encompassed product at near-body and near-air-ambient temperatures at the time of packaging, product in the largest and smallest cartons used in the process, and product with relatively short and long residence times in an unchilled carton stack assembly area. Twenty-one temperature histories were collected for each of the products, and the possible proliferation of an indicator organism, Escherichia coli, calculated for each temperature history. The results were assessed against a temperature function integration criterion derived from studies of beef carcass and cartoned meat cooling processes. Products packaged at near-ambient temperature readily met with the criterion, but products packed at near-body temperatures did not comply. The latter non-compliance was extreme for product packaged in large cartons. However, the principal cause of non-compliance was identified as highly variable cooling conditions in the carton freezing facility. A brief survey of air speeds and temperatures within that facility indicated means by which product cooling could be better controlled.     

Modelling direct sequence pseudonoise(dspn) satellite reception with directional antennas in the dense scatterer mobile environment

A geometric propagation model is developed for simulating the reception of direct sequence pseudonoise (DSPN) satellite signals by a directional or omni antenna in the dense scatterer mobile environment. The model is first validated for narrowband signals by a direct comparison of both simulated cumulative signal strength statistics and simulated diffuse Doppler spectra with classical theory. The model is then used to predict fading statistics for DSPN signaling, either with omni or directional antennas. As expected, the mitigation of fading is closely related to the ratio of DSPN chip duration to delay spread of the scatterer medium for both the omni and directional antennas.     

Porphyromonas (Bacteroides) endodontalis: its role in endodontal infections

Porphyromonas endodontalis (formerly Bacteroides endodontalis) is a black-pigmented anaerobic Gram-negative rod which is associated with endodontal infections. It has been isolated from infected dental root canals and submucous abscesses of endodontal origin. The presence of P. endodontalis in infected dental root canals has been correlated with symptoms of an acute infection. It is occasionally found on oral mucous membranes and periodontal pockets. P. endodontalis has shown relatively low virulence in experimental monoinfections. In anaerobic mixed infections it can play an essential role. Differences in virulence between strains have been related to capsular material. On the basis of different types of capsules, three serotypes have been described. P. endodontalis is sensitive to a wide range of antibiotics, including the penicillins, the tetracyclines, and metronidazole.     

Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women

OBJECTIVE: To assess the effect on various aspects of carbohydrate and lipid metabolism of administering a quick-release formulation of bromocriptine (Ergoset) to obese, nondiabetic, hyperinsulinemic women. RESEARCH DESIGN AND METHODS: Hourly concentrations of prolactin, glucose, insulin, free fatty acid (FFA), and triglyceride were measured for 24 h before and after approximately 8 weeks of treatment with Ergoset. In addition, fasting lipid and lipoprotein concentrations and the steady-state plasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose were determined before and after Ergoset administration. RESULTS: Circulating prolactin concentrations were dramatically decreased (P < 0.001) following treatment, associated with a significant fall (P < 0.05) in 24-h-long plasma glucose, FFA, and triglyceride concentrations. Neither circulating plasma insulin concentrations nor the ability of insulin to mediate glucose disposal changed with treatment. Finally, fasting total cholesterol fell (P < 0.05) and the ratio of total to HDL cholesterol decreased (P = 0.06) in association with Ergoset treatment. CONCLUSIONS: The fact that significant metabolic improvement was seen in the obese nondiabetic hyperinsulinemic women studied suggests that Ergoset could be of therapeutic benefit in clinical conditions of hyperglycemia and/or dyslipidemia.     

Antimicrobial activity and spectrum of LB20304, a novel fluoronaphthyridone

Compound LB20304 is a fluoronaphthyridone carboxylic acid with a novel pyrrolidine substituent. This drug was compared with ciprofloxacin, levofloxacin, ofloxacin, and trovafloxacin against over 800 pathogens, most from blood stream infections, by National Committee for Clinical Laboratory Standards reference methods. LB20304 was the most active agent against gram-positive species including strains observed to be resistant to other fluoroquinolones and glycopeptides. The potency of LB20304 (MIC50, 0.03 micrograms/ml) against the Enterobacteriaceae was exceeded only by that of ciprofloxacin (0.015 micrograms/ml). It has limited activity against gram-negative anaerobes.     

A set of electrophoretic molecular markers for strain typing and population genetic studies of Histoplasma capsulatum

A set of eleven biallelic and three multiallelic molecular markers have been developed to analyze populations of Histoplasma capsulatum. All markers are amplified by polymerase chain reaction (PCR) and can be readily scored using minimal amounts of template DNA. The 11 biallelic loci have polymorphic restriction endonuclease sites or small insertions or deletions which may be assessed by agarose gel electrophoresis. These markers are inherited in an unambiguous manner and are ideal for assessing structure and gene flow within US populations of H. capsulatum, but are monomorphic in non-US populations. Both length and sequence variation are present in the multiallelic loci, which can be scored by direct sequencing, polyacrylamide gel electrophoresis, or single-strand conformation polymorphism (SSCP): As they are hypervariable, the multiallelic loci can be used to type isolates and to assess the level of genetic variation within populations. Preliminary results indicate that the three multiallelic markers presented are sufficient to distinguish isolates at the individual level and are polymorphic in both US and non-US populations. This collection of molecular markers will be a useful tool in population and epidemiology studies of H. capsulatum.     

Determination of tryptophan in feedstuffs: Comparison of two methods of hydrolysis prior to HPLC analysis

The tryptophan content of nine samples of commercial feed was determined using two procedures (I and II) differing mainly in the hydrolysis conditions used prior to analysis. With I, hydrolysis was performed with 4 M LiOH in the presence of maltodextrin with 5-methyltryptophan used as internal standard at 110°C for 24 h; with II. oxygen-free 1.3 M Ba(OH)₂ was used at 125°C for 16 h. The two procedures gave identical results for a given sample indicating that the corrections for the incomplete recovery of tryptophan 5-methyltryptophan quantitation were satisfactory.     

Tracking musical patterns using joint accent structure.

Joint Accent Structure (JAS) is a construct that uses temporal relationships between different accents in a melodic pattern as indices of its complexity. The present study examines the role of different JASs in real time, attending to simple musical events. 39 adults with or without musical training were told to selectively attend to and synchronize finger taps with accents in 2 experiments that examined attentional tracking to musical patterns having a concordant or discordant JAS. Results indicate that tapping was more variable with discordant than with concordant JAS patterns, both with respect to produced inter-accent time periods and with respect to the phase of taps relative to accent onsets. These findings are interpreted in terms of real time attending and its control by event time structure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)