Interaction of rabbit skeletal muscle glycogen synthase I with substrate analogs--oxo-UDP hydrazones]

Inhibition of rabbit skeletal muscle glycogen synthase I was studied by using several synthetic substrate analogs: dansylhydrazone of oxo-UDP, 3-hydroxy-2-naphthoylhydrazone of oxo-UDP, salicyloylhydrazone of oxo-UDP, 1-oxyl-2,2,5,5-tetramethylpyrrolidine-3-carbonylhydrazone of oxo-UDP, N'-(dansyl)hydrazinocarbonylhydrazone of oxo-UDP and N'-(fluorenylidene-9)-hydrazinocarbonylhydrazone of oxo-UDP. All these compounds (with the exception of the nitroxyl-containing hydrazone) were characterized by a nonlinear dependence of the reverse reaction rate on the analog concentration in Dixon coordinates. The parabolic type of inhibition was due to the fact that the analogs tested except for the nitroxyl-containing hydrazone were able to interact both with the active center of the enzyme and with the FMN-binding site. The inhibition constants for oxo-UDP hydrazones were calculated for the both centers; their comparison revealed that the affinity of the analogs for the FMN-binding site increased with an increase in the radical hydrophobicity. These data suggest that the site with a high binding affinity for FMN is hydrophobic in nature. Apparently, isoalloxasine-like compounds display the highest affinity for this site.     

Concomitant Information in Competing Risk Analysis

A competing risk model, accommodating both Type I censoring and random withdrawals, is expanded to incorporate concomitant information by allowing the parameters of the underlying distributions to be a linear function of two covariates. The model is developed for two competing risks, one following a Weibull distribution and the other a Rayleigh distribution, and random withdrawals following a Weibull distribution. A method is developed for testing the equality of the coefficients for a given covariate for each of the competing risks using MLE'.     

PCR-generated conspecific sodium channel gene probe for the house fly.

A segment of the house fly (Musca domestica) homologue of the para (paralytic) sodium channel gene of Drosophila melanogaster was isolated by using mixed sequence oligonucleotide primers in the polymerase chain reaction (PCR). The specificity of the procedure was demonstrated by genomic Southern analysis using the housefly PCR amplification product as a probe and by DNA sequence analysis. The latter showed structural homology to the para gene, but not to the corresponding region of DSC1, another D. melanogaster gene with structural similarity to vertebrate sodium channel genes.     

Essential roles of core starvation-stress response loci in carbon-starvation-inducible cross-resistance and hydrogen peroxide-inducible adaptive resistance to oxidative challenge in Salmonella typhimurium

The starvation-stress response (SSR) of Salmonella typhimurium encompasses the physiological changes that occur upon starvation for an essential nutrient, e.g. C-source. A subset of SSR genes, known as core SSR genes, are required for the long-term starvation survival of the bacteria. Four core SSR loci have been identified in S. typhimuriumrpoSstiAstiB, and stiC. Here we report that in S. typhimurium C-starvation induced a greater and more sustainable cross-resistance to oxidative challenge (15 mM hydrogen peroxide (H₂O₂) for 40 min) than either N- or P-starvation. Of the four core SSR loci, only rpoS and stiC mutants exhibited a defective C-starvation-inducible cross-resistance to H₂O₂ challenge. Interestingly, (unadapted) log-phase S. typhimurium rpoS and stiA mutants were very sensitive to oxidative challenge. Based on this, we determined if these core SSR loci were important for H₂O₂ resistance developed during a 60 min adaptive exposure to 60 μM H₂O₂ (adapted cells). Both unadapted and adapted rpoS and stiA mutants were hypersensitive to a H₂O₂ challenge. In addition, a stiB mutant exhibited normal adaptive resistance for the first 20 mins of H₂O₂ challenge but then rapidly lost viability, declining to a level of about 1.5% of the wild-type strain. The results of these experiments indicate that: (i) the rpoS and stiC loci are essential for the development of C-starvation-inducible cross-resistance to oxidative challenge, and (ii) the rpoSstiA, and, in a delayed effect, stiB loci are needed for H₂O₂-inducible adaptive resistance to oxidative challenge. Moreover, we found that both stiA and stiB are induced by a 60 μM H₂O₂ exposure, but only stiA was regulated (repressed) by (reduced form) OxyR.     

PARATI – a dynamic model for radiological assessments in urban areas

The structure and mathematical model of PARATI, a detailed computer programme developed for the assessment of the radiological consequences of an accidental contamination of urban areas, is described with respect to the scenarios used for the estimation of exposure fields in a village or town, the models for the initial and secondary contamination with the radionuclide ¹³⁷Cs, the concepts for calculating the resulting radiation exposures and the changes with time of the contamination and radiation fields. Kerma rates at various locations in tropical urban areas are given, and the contribution of different contaminated surfaces to these rates after dry or wet deposition are discussed. Received: 12 April 1996 / Accepted in revised form: 30 August 1996     

Randomised,double blind,placebo controlled trial of penicillin V and amoxycillin in treatment of acute sinus infections in adults.

OBJECTIVES--To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis. DESIGN--Randomised, double blind, placebo controlled trial. SETTING--Norwegian general practice. SUBJECTS--130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography. MAIN OUTCOME MEASURES--Subjective status after three and 10 days of treatment, difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner, difference in score from computed tomography on day 0 and day 10, and duration of sinusitis. RESULTS--Amoxycillin and penicillin V led to significantly faster and better recovery than placebo. By day 10, 71 patients receiving antibiotic treatment- (86%) considered themselves to be recovered or much better compared with 25 (57%) receiving placebo. The mean (95% confidence interval) reductions in clinical severity scores by day 10 were 5.4 (5.0 to 5.8) for penicillin V, 5.5 (4.9 to 6.0 for amoxycillin, and 3.4 (2.8 to 4.0) for placebo. For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography (scale 0-16)-that is, score 5-16 on day 10-was 31/83 (37%) compared with 10/44 (23%) receiving placebo. The median duration of the sinusitis was nine days in the amoxycillin group, 11 days in the penicillin V group, and 17 days in the placebo group. CONCLUSION--Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis.