Use of self-operated auditory prompts by workers with moderate mental retardation to transition independently through vocational tasks

The use of single- and multiple-word self-operated auditory prompting systems by five school-age workers with moderate mental retardation to independently transition between an ordered chain of tasks was examined in two vocational settings. The effectiveness of single- and multiple-word self-operated auditory prompts was assessed using an alternating treatment design within a multiple probe across settings. Analysis of the data revealed a significant effect on the number of independent task changes made by workers when using the single- or multiple-word auditory prompting system. When prompting systems were compared with one another, no significant differences were found in the number of independent task changes made by workers. Self-operated auditory prompts served as the stimulus control for desired behavior, they were effective for teaching workers with moderate mental retardation to manage their own task change behavior, and their use generalized across settings without additional training.     

Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene

To identify components involved in nuclear protein import, we used a genetic selection to isolate mutants that mislocalized a nuclear-targeted protein. We identified temperature-sensitive mutants that accumulated several different nuclear proteins in the cytoplasm when shifted to the semipermissive temperature of 30 degrees C; these were termed npl (nuclear protein localization) mutants. We now present the properties of yeast strains bearing mutations in the NPL4 gene and report the cloning of the NPL4 gene and the characterization of the Np14 protein. The npl4-1 mutant was isolated by the previously described selection scheme. The second allele, npl4-2, was identified from an independently derived collection of temperature-sensitive mutants. The npl4-1 and npl4-2 strains accumulate nuclear-targeted proteins in the cytoplasm at the nonpermissive temperature consistent with a defect in nuclear protein import. Using an in vitro nuclear import assay, we show that nuclei prepared from temperature-shifted npl4 mutant cells are unable to import nuclear-targeted proteins, even in the presence of cytosol prepared from wild-type cells. In addition, npl4-2 cells accumulate poly(A)+ RNA in the nucleus at the nonpermissive temperature, consistent with a failure to export mRNA from the nucleus. The npl4-1 and npl4-2 cells also exhibit distinct, temperature-sensitive structural defects: npl4-1 cells project extra nuclear envelope into the cytoplasm, whereas npl4-2 cells from nuclear envelope herniations that appear to be filled with poly(A)+ RNA. The NPL4 gene encodes an essential M(r) 64,000 protein that is located at the nuclear periphery and localizes in a pattern similar to nuclear pore complex proteins. Taken together, these results indicate that this gene encodes a novel nuclear pore complex or nuclear pore complex-associated component required for nuclear membrane integrity and nuclear transport.     

Evidence for the existence of [3H]-trimetazidine binding sites involved in the regulation of the mitochondrial permeability transition pore

1. Trimetazidine is an anti-ischaemic drug effective in different experimental models but its mechanism of action is not fully understood. Data indicate that mitochondria could be the main target of this drug. The aim of this work was to investigate the binding of [3H]-trimetazidine on a purified preparation of rat liver mitochondria. 2. [3H]-trimetazidine binds to two populations of mitochondrial binding sites with Kd values of 0.96 and 84 microM. The total concentration of binding sites is 113 pmol mg(-1) protein. Trimetazidine binding sites are differently distributed. The high-affinity ones are located on the outer membranes and represent only a small part (4%) of total binding sites, whereas the low-affinity ones are located on the inner membranes and are more abundant (96%) with a Bmax=108 pmol mg(-1) protein. 3. Drug displacement studies with pharmacological markers for different mitochondrial targets showed that [3H]-trimetazidine binding sites are different from previously described mitochondrial sites. 4. The possible involvement of [3H]-trimetazidine binding sites in the regulation of the mitochondrial permeability transition pore (MTP), a voltage-dependent channel sensitive to cyclosporin A, was investigated with mitochondrial swelling experiments. Trimetazidine inhibited the mitochondrial swelling induced by Ca2+ plus tert-butylhydroperoxide (t-BH). This effect was concentration-dependent with an IC50 value of 200 microM. 5. Assuming that trimetazidine effectiveness may be related to its structure as an amphiphilic cation, we compared it with other compounds exhibiting the same chemical characteristic both for their ability to inhibit MTP opening and to displace [3H]-trimetazidine bound to mitochondria. Selected compounds were drugs known to interact with various biological membranes. 6. A strong correlation between swelling inhibition potency and low-affinity [3H]-trimetazidine binding sites was observed: r=0.907 (n=24; P<0.001). 7. These data suggest that mitochondrial sites labelled with [3H]-trimetazidine may be involved in the MTP inhibiton.     

Takayasu''s arteritis in Mexico: a clinical review of 44 consecutive cases

Experiments were designed to determine the effects of sub-zero temperatures on the function of the noradrenergic innervation of a peripheral blood-vessel. The central ear-artery of the rabbit was used for this purpose. The ear was exposed to temperatures of -6, -9 or -18 degrees C in vivo for 15 min. After 1 day (24 h) or 6 days in vivo, the central ear-artery was dissected free, incubated in [3H]-noradrenaline (NA) and stimulated in vitro with high potassium (75 mM) for 5 min to evoke release of [3H]-NA. The release of [3H]-NA was Ca(2+)-dependent. One day after exposure to -6, -9 or -18 degrees C, increases of 45-57 and 44-72% and a reduction of 12-35% were observed, respectively, in three successive potassium-evoked NA-releases. After 6 days in vivo an increase of 30-34% was observed following exposure to -6 degrees C, while no alteration was observed after exposure to -9 degrees C. A reduction of 84-89% was recorded after exposure to -18 degrees C. Following this exposure to -18 degrees C, there was also a great reduction in the evoked release of [3H]-NA compared with the spontaneous release, whereas this correlation did not change after exposure to -6 and -9 degrees C. The total uptake of [3H]-NA was unchanged after freezing the tissue at -6 degrees C, but was substantially reduced after exposure to -9 and -18 degrees C. A short period of in vivo restoration (6 days, enhanced the uptake of [3H]-NA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishing orally self-administered cocaine as a reinforcer in rats using home-cage pre-exposure

1. Rats were force-exposed to a cocaine + saccharin solution in their home cage water bottles for five days. They were then given 5 h home-cage access to both cocaine and cocaine-free solutions for 40 days. 2. The subjects consumed large doses of the cocaine solution despite the ad libitum availability of water. 3. The animals were then trained on a task consisting of operant bar pressing rewarded on an intermittent schedule with a liquid cocaine reinforcer. 4. All subjects performed the operant task and consumed doses of cocaine solution which are preferred over water in other paradigms. 5. Levels of responding were significantly reduced in three of four subjects when vehicle was substituted for liquid cocaine as the reward. 6. This demonstrates that orally self-administered cocaine can be used as a reinforcer in rats.     

Development of quinolone-resistant Campylobacter fetus bacteremia in human immunodeficiency virus-infected patients

Campylobacter fetus subspecies fetus has been recognized as a cause of systemic illness in immunocompromised hosts, including relapsing bacteremia in human immunodeficiency virus (HIV)-infected patients. Acquired resistance to quinolone therapy, while reported for a variety of bacteria, including Campylobacter jejuni, has not been previously documented for C. fetus. Two cases of quinolone-resistant C. fetus bacteremia were detected in HIV-infected patients. Cloning and nucleotide sequencing of the C. fetus gyrA gene in the 2 resistant isolates demonstrated a G-to-T change that led to an Asp-to-Tyr amino acid substitution at a critical residue frequently associated with quinolone resistance. In addition, comparison of the pre- and posttreatment isolates from 1 patient documented outer membrane protein changes temporally linked with the development of resistance. Relapsing C. fetus infections in quinolone-treated HIV-infected patients may be associated with the acquisition of resistance to these agents, and this resistance may be multifactorial.     

Effect of resistance exercise training on cortical and cancellous bone in mature male rats

The thermal inactivation kinetics of Salmonella enteritidis PT4 between 49 and 60 degrees C were investigated. Using procedures designed to eliminate methodological artifacts, we found that the death kinetics deviated from the accepted model of first-order inactivation. When we used high-density stationary-phase populations and sensitive enumeration, the survivor curves at 60 degrees C were reproducibly biphasic. The decimal reduction time at 60 degrees C (D60 degrees C) of the tail subpopulation was more than four times that of the majority population. This difference decreased with decreasing temperature; i.e., the survivor curves became more linear, but the proportion of tail cells remained a constant proportion of the initial population, about 1 in 10(4) to 10(5). Z plots (log D versus temperature) for the two populations showed that the D values coincided at 51 degrees C, indicating that the survivor curves should be linear at this temperature, and this was confirmed experimentally. Investigations into the nature of the tails ruled out genotypic differences between the populations and protection due to leakage from early heat casualties. Heating of cells at 59 degrees C in the presence of 5 or 100 micrograms of chloramphenicol per ml resulted in reductions in the levels of tailing. These reductions were greatest at the higher chloramphenicol concentration. Our results indicate that de novo protein synthesis of heat shock proteins is responsible for the observed tailing. Chemostat-cultured cells heated at 60 degrees C also produced biphasic survivor curves in all but one instance. Cells with higher growth rates were more heat sensitive, but tailing was comparable with batch cultures. Starved cells (no dilution input) displayed linear inactivation kinetics, suggesting that during starvation a rapid heat shock response cannot be initiated.     

Do obese women have poorer social relationships than nonobese women? Reports by self, friends, and coworkers

Both theory and research suggest that obese women may have relatively poor social relationships even if their self-reports about their relationships do not differ from the reports of nonobese women. Seventy-seven obese and 78 nonobese women completed self-report measures of social anxiety, social self-esteem, social competence, social network size, and perceived social support from friends and family. Friends and coworkers also rated these women on the same measures. The self-reports of obese and nonobese women did not differ significantly on any of these social measures, and ratings from friends and coworkers of obese women were not different from ratings of nonobese women by friends and coworkers. These results suggest that obese women may be able to overcome prejudice against obese people in their relationships with others.