The effects of anabolic steroids on driving performance as assessed by the Iowa Driver Simulator

The effect of physiologic (100 mg/wk) and supraphysiologic (250 and 500 mg/wk) doses of testosterone cypionate (TC) on automobile driving were studied using the Iowa Driver Simulator. Six normal subject volunteers were studied off TC and on TC once steady-state concentrations were achieved after at least three weeks of dosing. Despite the administration of supraphysiologic testosterone doses, an increase in aggressive driving behavior was not detected. Likewise, corresponding psychometric testing using the Buss-Durkee Hostility Inventory to assess aggression was unable to detect any change in aggression in the test subjects. Although aggressive driving behavior may be increased by testosterone administration, the drug itself may not be responsible for these effects. Supraphysiologic doses greater than 500 mg/wk and a semi-controlled research environment may be necessary to produce this effect since case reports of AAS abuse causing altered driving behavior may be multifactorial in nature.     

The syndecan family of proteoglycans. Novel receptors mediating internalization of atherogenic lipoproteins in vitro

Cell-surface heparan sulfate proteoglycans have been shown to participate in lipoprotein catabolism, but the roles of specific proteoglycan classes have not been examined previously. Here, we studied the involvement of the syndecan proteoglycan family. First, transfection of CHO cells with expression vectors for several syndecan core proteins produced parallel increases in the cell association and degradation of lipoproteins enriched in lipoprotein lipase, a heparan-binding protein. Second, a chimeric construct, FcR-Synd1, that consists of the ectodomain of the IgG Fc receptor Ia linked to the highly conserved transmembrane and cytoplasmic domains of syndecan-1 directly mediated efficient internalization, in a process triggered by ligand clustering. Third, internalization of lipase-enriched lipoproteins via syndecan-1 and of clustered IgGs via the chimera showed identical kinetics (t1/2 = 1 h) and identical dose-response sensitivities to cytochalasin B, which disrupts microfilaments, and to genistein, which inhibits tyrosine kinases. In contrast, internalization of the receptor-associated protein, which proceeds via coated pits, showed a t1/2 < 15 min, limited sensitivity to cytochalasin B, and complete insensitivity to genistein. Thus, syndecan proteoglycans can directly mediate ligand catabolism through a pathway with characteristics distinct from coated pits, and might act as receptors for atherogenic lipoproteins and other ligands in vivo.     

Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells

Activation of the high affinity IgE receptor (Fc epsilon RI) of mast cells, a member of the antigen receptor family, leads to the release of allergic mediators, a critical event in the onset of immediate hypersensitivity. Stimulation of Fc epsilon RI results in the rapid association and activation of the Syk tyrosine kinase. Using Syk-deficient mast cells we show that they fail to degranulate, synthesize leukotrienes and secrete cytokines when stimulated through Fc epsilon RI, conclusively demonstrating an essential role for Syk in Fc epsilon RI signalling. Furthermore, our data strongly supports a model of Fc epsilon RI engagement leading to the sequential activation of the tyrosine kinases Lyn and then Syk. A similar mechanism is likely to apply to signal transduction through all members of the antigen receptor family.     

Cell-free extract(s) of Pseudomonas putida catalyzes the conversion of cyanides, cyanates, thiocyanates, formamide, and cyanide-containing mine waters into ammonia

Our isolate, Pseudomonas putida, is known to be capable of utilizing cyanides as the sole source of carbon (C) and nitrogen (N) both in the form of free cells and cells immobilized in calcium alginate. In the present study, the cell-free extract(s) were prepared from the cells of P. putida grown in the presence of sodium cyanide. The ability of enzyme(s) to convert cyanides, cyanates, thiocyanates, formamide and cyanide-containing mine waters into ammonia (NH3) was studied at pH 7.5 and pH 9.5. The kinetic analysis of cyanide and formamide conversion into NH3 at pH 7.5 and pH 9.5 by the cell-free extract(s) of P. putida was also studied. The Km and Vmax values for cyanide/formamide were found to be 4.3/8 mM and 142/227 mumol NH3 released mg protein-1 min-1 respectively at pH 7.5 and 5/16.67 mM and 181/434 mumol NH3 released mg protein-1 h-1 respectively at pH 9.5. The study thus concludes that the cell-free extract(s) of P. putida is able to metabolize not only cyanides, cyanates, thiocyanates, and formamide but also cyanide-containing mine waters to NH3.     

Increased neuronal nitric oxide synthase expression in brain following portacaval anastomosis

The long-sleep (LS) and short-sleep (SS) mice were selected for differences in sensitivity to ethanol but also differ in response to propofol and some neurosteroids. To determine the role of strychnine-sensitive glycine receptors in genetic differences between these mice, effects of propofol, ethanol and pregnenolone sulfate on glycine responses were compared in Xenopus oocytes expressing mRNA extracted from spinal cord of LS and SS mice. The two lines of mice did not differ in sensitivity to glycine, ethanol or pregnenolone sulfate. However, receptors expressed from LS mRNA were more sensitive to the potentiation induced by propofol than those from SS. Binding of [3H]strychnine to spinal cord membranes demonstrated a similar affinity and density of receptors in LS and SS. These results suggest that glycine receptor function could account for differences in propofol sensitivity between LS and SS mice, but may not be responsible for the differences in behavioral sensitivity to ethanol or steroids previously reported.     

Prognostic value of treadmill exercise testing: a population-based study in Olmsted County, Minnesota

BACKGROUND: The prognostic value of treadmill exercise testing (TMET) has been studied in selected populations. The generalizability of these data to different populations and to women is uncertain. METHODS AND RESULTS: A retrospective, population-based cohort study of all persons (1452 men and 741 women) who underwent TMET in years 1987 to 1989 in Olmsted County, Minnesota, was undertaken. Individuals were followed up for all-cause mortality and cardiac events (cardiac deaths, nonfatal myocardial infarction, or congestive heart failure). Sex-specific analyses were performed to determine whether the predictors of outcome and the magnitude of the associations were similar in both sexes. In men, 77 deaths and 106 cardiac events occurred during 8956 person-years of observation; in women, 46 deaths and 54 cardiac events occurred during 4801 person-years of follow-up. Exercise-induced angina, ECG changes, and workload achieved on the TMET were strongly associated with all-cause mortality and cardiac events in both sexes, and the strength of the association was similar. After adjustment, workload was the only TMET variable associated with outcome. A higher workload was associated with a reduction in the risk of cardiac events and of all-cause mortality; the protective effect of exercise capacity was strong and was similar in both sexes. CONCLUSIONS: In this population-based cohort, exercise capacity was the TMET variable that exhibited the strongest association with all-cause mortality and cardiac events. This protective effect of exercise capacity was observed in both sexes.     

Antimicrobial-resistant Salmonella spp isolated from healthy broiler chickens after slaughter

Of 105 Salmonella organisms of any serotype selected from a sample of 1,824 serotyped salmonellae isolated during a nationwide bacteriologic survey of healthy broiler chickens after slaughter, 60 (57%) were resistant to 1 or more antimicrobial agents and 47 (45%) were resistant to 2 or more agents. Highest resistance was to tetracycline (45%), streptomycin (41%), sulfisoxazole (19%), gentamicin (10%), and trimethoprim/sulfamethoxazole (8%). Additional isolates of S typhimurium, heidelberg, agona, and enteritidis were selected from the sample of 1,824 isolates for testing because of the high frequency with which these 4 serotypes are isolated from human patients. The highest frequency of resistance among 104 isolates of S heidelberg, 92 isolates of S typhimurium, and 30 isolates of S agona was to streptomycin (33 to 57%), sulfisoxazole (33 to 50%), tetracycline (26 to 50%), and gentamicin (13 to 40%); 51 to 63% of these isolates were resistant to 1 or more agents and 37 to 59% were resistant to 2 or more agents. Resistance to ampicillin among these 3 serotypes was uncommon (0 to 4%). In contrast, 15 of 19 tested isolates (79%) of S enteritidis were resistant to ampicillin and 13 of the 19 isolates (68%) were resistant only to ampicillin. This pattern of resistance was associated with a specific bacteriophage type and indicated the potential role of bacterial clones in determining the frequency and patterns of antimicrobial resistance in populations of broiler chickens. Resistance to gentamicin and trimethoprim/sulfamethoxazole was higher than that previously reported and is of public health concern because of the frequency with which these drugs are used to treat bacterial infections in human patients.