Autologous rosette-forming T cells and their relationship to OKT4+ and OKT8+ cells in chronic HBV infection

A percentage of human T lymphocytes forms rosettes with autologous erythrocytes and this property has been considered as a marker for post-thymic precursor suppressor cells capable of providing suppression under the influence of inducer cells. We quantitated autologous rosette-forming T cells (ARFC) in the peripheral blood of 37 patients with chronic HBV infection: 8 healthy carriers, 9 chronic persistent hepatitis (CPH-B) and 20 chronic active hepatitis (CAH-B). Two control groups were studied, one consisting of 26 healthy individuals and the other of 8 individuals with non-HBV-associated CAH. Patients with non-HBV-associated CAH had a significant reduction in the proportion of ARFC, whereas CAH-B patients fell into 2 distinct patterns, one with increased and the other with decreased proportions of ARFC. This was unrelated to the degree of biochemical activity of the disease or to degree of viral replication as defined by HBeAg status and HBV-DNA in the serum. Healthy carriers and CPH-B had no changes in ARFC. Simultaneous quantitation of OKT4 and OKT8+ cells was done and a positive correlation was found between the proportions of ARFC and the proportions of OKT8+ cells. The possible significance of this correlation and the relevance of the bimodal distribution of autologous rosette-forming cells in CAH-B are discussed.     

Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32

Some MCP SNP and aHUS-associated MCP mutation     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.     

Accuracy of an anthropometric estimate of the muscle and bone area in a transversal cross-section of the arm

To standardize the maximal static force (Fo) of the arm flexors, the accuracy of an anthropometric method for estimating the mid-arm cross-sectional muscle and bone area (MBA) was investigated. This was done by comparing the anthropometrically determined area (MBA.A) with the area measured by means of computerized tomography (MBA.S). In the same way, the accuracy of Heymsfield's equations (Heymsfield et al., 1982) for predicting MBA (MBA.H) from anthropometric measures was tested. MBA.A was significantly larger than MBA.S, the relative difference increasing with the thickness of the subcutaneous fat layer. This difference was attributed to a 27% underestimation of the fat layer thickness as measured with the skinfold caliper. Women being fatter than men, this caused the standardized maximal static force (Fo/MBA) to be lower in women than in men. MBA.H was 12% smaller than MBA.S. This may have been due to a difference in the way of measuring the arm circumference between the present authors and Heymsfield et al.     

Probing insulin's secondary structure after entrapment into alginate/chitosan nanoparticles.

The aim of the present study was to probe the structural integrity of insulin after being entrapped into chitosan/alginate nanoparticles produced by ionotropic polyelectrolyte pre-gelation. By manipulating the alginate:chitosan mass ratio and the pH during nanoparticle production, desired nanoparticles with a mean size of 850 (+/-88)nm and insulin association efficiency of 81 (+/-2)% were obtained. Insulin secondary structure was assessed by Fourier transform infrared (FTIR) and circular dichroism (CD) after entrapment into nanoparticles and after release from the particles under gastrointestinal simulated conditions. FTIR second-derivative spectra and area-overlap compared to an insulin standard confirmed that no significant conformational changes of insulin occurred in terms of alpha-helix and beta-sheet content. Far-UV-CD spectra corroborated the preservation of insulin structure during the nanoparticle production procedure. The presented nanoparticulate system is a promising carrier for insulin oral delivery since it preserves insulin structure and therefore also, potentially, its bioactivity.