The influence of glucan polymer structure and solution conformation on binding to (1-->3)-beta-D-glucan receptors in a human monocyte-like cell line.

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Efficacy and tolerance of roxithromycin versus clarithromycin in the treatment of lower respiratory tract infections.

In an open, randomized, parallel group study, the efficacy and tolerance of roxithromycin 300 mg po od was compared with clarithromycin 500 mg po bd in the treatment of 60 patients with lower respiratory tract infections (LRTI). The two groups were well-matched demographically. Fifty patients (25 per group) were clinically evaluable at the end of the study and a satisfactory response was found in 88% of those given roxithromycin and 80% of those given clarithromycin. All had received treatment for a minimum of 3 days. Only one (3.3%) of 30 patients in the roxithromycin group reported adverse events compared with seven (23.3%) of 30 in the clarithromycin group. Thus both roxithromycin and clarithromycin are effective in the treatment of LRTI but roxithromycin is better tolerated (P < 0.05) with the advantage of a once-daily dose.

Lysozyme aggregation studied by light scattering. I. Influence of concentration and nature of electrolytes.

Static and dynamic light scattering have been employed to investigate the behaviour of lysozyme solutions when varying the concentration of (NH(4))(2)SO(4) and NaCl for screening the repulsive forces between the monomers. At the initial aggregation stages clusters, which can be classified as mass-fractals undergoing diffusion limited-like aggregation, coexist with monomers or small lysozyme oligomers. The kinetics of fractal growth deliver observables that exhibit distinct tendencies when examined as a function of the concentration and nature of the electrolyte. The behaviour of the observables changes drastically above 0.84 M (NH(4))(2)SO(4) and 0.60 M NaCl. Static light scattering revealed a progressive restructuring of the fractals to compact structures at the latter stages of the reaction. Based on the correlations between the various observables an attempt is made to predict the long-term fate of the nucleating solutions.

Lysozyme aggregation studied by light scattering. II. Variations of protein concentration.

Static and dynamic light scattering have been employed to investigate the behaviour of nucleating lysozyme solutions in the range between 0.34 and 3.08 mM. Preselected concentrations of NaC1 and (NH(4))(2)SO(4) have been used to screen the repulsive Coulombic interactions and trigger aggregation. Initially, mass-fractals undergoing diffusion limited-like aggregation coexist with monomers or small lysozyme oligomers. The growth kinetics of the fractals deliver observables that exhibit distinct tendencies when examined as a function of lysozyme concentration. The behaviour of the observables changes drastically around 2.0 mM lysozyme. Static light scattering experiments revealed progressive restructuring or growth of compact structures at later stages of the aggregation. Based on the correlations between the observables an attempt is made to predict whether the examined solutions will crystallize or not. A tentative scheme, involving the most prominent structures observed in nucleating lysozyme solutions, is discussed.