Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells

Dendritic cells (DCs) are the most efficient antigen-presenting cells and thus, have a major role in regulating host immune responses. In the present study, we have analyzed the ability of Gram-positive, pathogenic Streptococcus pyogenes and nonpathogenic Lactobacillus rhamnosus to induce the maturation of human monocyte-derived DCs. Stimulation of DCs with S. pyogenes resulted in strong expression of DC costimulatory molecules CD80, CD83, and CD86 accompanied with a T helper cell type 1 (Th1) cytokine and chemokine response. S. pyogenes also induced interleukin (IL)-2 and IL-12 production at mRNA and protein levels. In addition, IL-23 and IL-27 subunits p40, p19, p28, and EBI3 were induced at mRNA level. In contrast, L. rhamnosus-stimulated DCs showed only moderate expression of costimulatory molecules and produced low levels of cytokines and chemokines. Furthermore, no production of IL-2 or IL-12 family cytokines was detected. Bacteria-induced DC maturation and especially cytokine and chemokine production were reduced when bacteria were heat-inactivated. Our results show that human monocyte-derived DCs respond differently to different Gram-positive bacteria. Although pathogenic S. pyogenes induced a strong Th1-type response, stimulation with nonpathogenic L. rhamnosus resulted in development of semi-mature DCs characterized by moderate expression of costimulatory molecules and low cytokine production.     

Vortex Shaped Current Sources in a Physical Torso Phantom

Recent studies reported differential information in human magnetocardiogram and in electrocardiogram. Vortex currents have been discussed as a possible source of this divergence. With the help of physical phantom experiments, we quantified the influence of active vortex currents on the strength of electric and magnetic signals, and we tested the ability of standard source localization algorithms to reconstruct vortex currents. The active vortex currents were modeled by a set of twelve single current dipoles arranged in a circle and mounted inside a phantom that resembles a human torso. Magnetic and electric data were recorded simultaneously while the dipoles were switched on stepwise one after the other. The magnetic signal strength increased continuously for an increasing number of dipoles switched on. The electric signal strength increased up to a semicircle and decreased thereafter. Source reconstruction with unconstrained focal source models performed well for a single dipole only (less than 3-mm localization error). Minimum norm source reconstruction yielded reasonable results only for a few of the dipole configurations. In conclusion active vortex currents might explain, at least in part, the difference between magnetically and electrically acquired data, but improved source models are required for their reconstruction.     

Haplotypic association of DDAH1 with susceptibility to pre-eclampsia

Association between pre-eclampsia (PEE1) and the dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes, which play a role in the regulation of nitric oxide synthesis and release, was studied. In a case-control study design single nucleotide polymorphisms (SNPs) were determined at eight sites in the DDAH1 gene and at one site (Pro231Pro) in the DDAH2 gene from 132 women with pre-eclampsia and 112 healthy controls. Three SNPs in the DDAH1 gene were associated with pre-eclampsia, showing complete linkage disequilibrium with each other, but none of the associations in the allele or genotype data reached statistical significance in either of the genes after the correction for multiple testing. Haplotype frequencies were estimated using a population based on a maximum likelihood method (EM algorithm). Four common DDAH1 haplotypes were present and a significant association of haplotypes H2 and H3 with pre-eclampsia (P=0.03) was found. The risk of pre-eclampsia was greatest in individuals (odds ratio: 3.93; 95% confidence interval: 1.54-9.99) who had two copies of the high-risk haplotypes (H2 or H3). The observed haplotypic association provides the first evidence of the importance of DDAH1 polymorphisms in pre-eclampsia susceptibility.     

Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype mouse: effects of APP/PS1 genotype and ovariectomy

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.     

Difference in cytokine production and cell activation between adenoidal lymphocytes and peripheral blood lymphocytes of children with otitis media

We evaluated the immunological potential of adenoidal lymphocytes from children with recurrent otitis media. Interleukin-4 release and CD69 expression were lower in adenoidal lymphocytes than in peripheral blood lymphocytes (PBL). Our results suggest that there may be a difference between the immunological potential of adenoidal lymphocytes and that of PBL in children with otitis.     

Synthetic env gp41 peptide as a sensitive and specific diagnostic reagent in different stages of human immunodeficiency virus type 1 infection

An enzyme immunoassay (EIA) for serum antibodies to human immunodeficiency virus type 1 (HIV-1), based on the synthetic pentadecapeptide SGKLICT-TAVPWNAS, a segment of the transmembrane glycoprotein (gp41) of the virus, was developed and tested for sensitivity and specificity. Sera of 152 individuals at various stages of HIV-1 infection, including two prospectively and six retrospectively studied patients exposed to HIV-1 but seronegative on initial testing in whole-virus EIA and immunoblotting, were screened with the gp41 peptide antibody EIA. The reference population consisted of 1,000 healthy HIV-1 antibody-negative blood donors. In addition, five individuals with antibodies to HIV-2 were studied. Antibodies to the synthetic peptide were detected in 100% of those with asymptomatic infection. Only one patient with LAS failed to react in the peptide EIA. Patients with HIV-2 infection did not react in this test. The peptide antibodies appeared rapidly after infection, were detectable at the time when seroconversion was observed by immunoblotting, and preceded reactivity in whole-virus EIA. Sera of seven patients with verified HIV-1 infection did not react with gp41 in immunoblotting, although antibodies were readily detectable in the gp41 peptide EIA.     

Signal Characteristics of EMG at Different Levels of Muscle Tension

Electromyographic activity of m. rectus femoris at submaximal and maximal voluntary contractions was quantified by conventional integration technique and also be a more “qualitative” procedure of automated motor unit averaging and frequency spectrum analysis. By relating the EMG parameters to produced muscle tension it was observed that the integrated EMG increased in a slightly nonlinear fashion with the increase in muscle force. The other EMG variables also showed clear changes as a function of muscle tension. The averaged motor unit potential (AMUP) and its specific parameters (number of spikes, amplitude, rise time and amplitude-rise time ratio) showed such changes with muscle tension that they may be useful in estimation of the recruitment pattern of the different types of motor units.     

High intensity exercise decreases global brain glucose uptake in humans

Physiological activation increases glucose uptake locally in the brain. However, it is not known how high intensity exercise affects regional and global brain glucose uptake. The effect of exercise intensity and exercise capacity on brain glucose uptake was directly measured using positron emission tomography (PET) and [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG). Fourteen healthy, right-handed men were studied after 35 min of bicycle exercise at exercise intensities corresponding to 30, 55 and 75% of     on three separate days. [¹⁸F]FDG was injected 10 min after the start of the exercise. Thereafter exercise was continued for another 25 min. PET scanning of the brain was conducted after completion of the exercise. Regional glucose metabolic rate (rGMR) decreased in all measured cortical regions as exercise intensity increased. The mean decrease between the highest and lowest exercise intensity was 32% globally in the brain (38.6 ± 4.6 versus 26.1 ± 5.0 μmol (100 g)⁻¹ min⁻¹, P < 0.001). Lactate availability during exercise tended to correlate negatively with the observed brain glucose uptake. In addition, the decrease in glucose uptake in the dorsal part of the anterior cingulate cortex (37% versus 20%, P < 0.05 between 30% and 75% of     ) was significantly more pronounced in subjects with higher exercise capacity. These results demonstrate that brain glucose uptake decreases with increase in exercise intensity. Therefore substrates other than glucose, most likely lactate, are utilized by the brain in order to compensate the increased energy needed to maintain neuronal activity during high intensity exercise. Moreover, it seems that exercise training could be related to adaptive metabolic changes locally in the frontal cortical regions.