The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells

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The Genetic Relationship Between Social Cognition and Conduct Problems

Studies of children and adolescents with conduct problems suggest both genetic and environmental influences on population variance. Any genetic influence is likely to be complex and to act via mediating attributes of personality or cognitive style. One potential mediating attribute is social cognitive ability, as conduct problems have been shown to be associated with deficient social cognitive skills. The current investigation has examined the correlation between conduct problems and social cognition and has investigated the genetic and environmental influences on these measures and their covariation using a twin design. A population-based sample of twins aged 5-17 was used to examine the genetic relationship between conduct problems and social cognition using parent-report questionnaires. Conduct problems and social cognition were found to be highly correlated and to share common genetic influences that accounted for about half the covariation in scores. Each phenotype was subject to its own environmental influences that were not shared.     

Hepatitis C virus particles of different density in the blood of chronically infected immunocompetent and immunodeficient patients: Implications for virus clearance by antibody

The purpose of this study was to analyse the influence of the humoral immune response on the generation and clearance of hepatitis C virus (HCV) RNA containing particles in the blood of chronically infected patients. Blood samples were fractionated by sequential flotation ultracentrifugation and HCV RNA was recovered in three fractions: low density of < 1.063 g/ml, intermediate density of 1.063-1.21 g/ml, and high density of > 1.21 g/ml. Serum low-density lipoproteins co-fractionated with the low-density particles, and high-density lipoproteins co-fractionated with the intermediate-density particles. Immunoglobulins were found exclusively in the high-density fractions. In patients with congenital immunodeficiencies, with no or low serum antibodies to the virus, mean HCV RNA titres were equal in each fraction, at approximately 10(5) IU/ml. In antibody-positive, immunocompetent patients, however, virus titres in the low-density fraction and those in the high-density fraction were reduced or absent in most patients, suggesting that virus particles in these fractions are subject to antibody-mediated clearance. Particles of intermediate density were approximately equal in titre in both patient groups, suggesting that these particles are neither generated by, nor cleared, as a result of the humoral immune response. Immunoprecipitation experiments indicated that particles of intermediate density were not complexed with either high-density lipoprotein or immunoglobulins. Elucidation of the mechanisms by which these particles are generated and maintained in the blood may provide valuable insight into the mechanism of virus persistence.     

Long-term functional impairment of hemopoietic progenitor cells engineered to express the S1 catalytic subunit of pertussis toxin

OBJECTIVE: A large body of data suggests that pertussis toxin (PTX)-sensitive G protein signals in mature and immature hemopoietic cells control their migration patterns in vitro and in vivo. These effects were derived after treatment of cells or animals with PTX. To circumvent several inherent problems of PTX holotoxin treatment, we expressed the S1 catalytic activity of PTX, thus blocking Gi protein signaling, in 32D murine myeloid progenitor cells and in primary human CD34+ cells, and studied its functional consequences. METHODS: S1 was expressed using viral vectors. Effects of Gi protein blockade on proliferation, migration, adhesion, and gene expression were tested in vitro. RESULTS: S1 expression was nontoxic for the cells; expression and function were stable long-term and not overridden by compensatory mechanisms. S1-transduced 32D cells and primary CD34+ cells migrated poorly and did not contract their cytoskeleton upon treatment with the chemoattractant stromal cell-derived factor -1 (SDF-1), similar to the phenotype induced by PTX treatment. Gene expression studies comparing S1-transduced and control 32D cells uncovered four genes, expression of which was regulated by Gi protein blockade. Of interest, although SDF-1 signaling was inhibited, comparison between SDF-1-treated and untreated cells suggests that SDF-1 stimulation does not depend on de novo gene expression in these cells. Furthermore, when injected into nonobese diabetic/severe combined immunodeficient mice, seeding of S1-expressing 32D cells to bone marrow was largely blocked. CONCLUSION: Expression of S1 is an effective approach for studying long-term functional consequences of Gi protein blockade in hemopoietic cells in vitro and in vivo.     

Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells.

It was previously reported that treatment with the sulfated polysaccharide fucoidan or the structurally similar dextran sulfate increased circulating mature white blood cells and hematopoietic progenitor/stem cells (HPCs) in mice and nonhuman primates; however, the mechanism mediating these effects was unclear. It is reported here that plasma concentrations of the highly potent chemoattractant stromal-derived factor 1 (SDF-1) increase rapidly and dramatically after treatment with fucoidan in monkeys and in mice, coinciding with decreased levels in bone marrow. In vitro and in vivo data suggest that the SDF-1 increase is due to its competitive displacement from heparan sulfate proteoglycans that sequester the chemokine on endothelial cell surfaces or extracellular matrix in bone marrow and other tissues. Although moderately increased levels of interleukin-8, MCP1, or MMP9 were also present after fucoidan treatment, studies in gene-ablated mice (GCSFR(-/-), MCP1(-/-), or MMP9(-/-)) and the use of metalloprotease inhibitors do not support their involvement in the concurrent mobilization. Instead, SDF-1 increases, uniquely associated with sulfated glycan-mobilizing treatments and not with several other mobilizing agents tested, are likely responsible. To the authors' knowledge, this is the first published report of disrupting the SDF-1 gradient between bone marrow and peripheral blood through a physiologically relevant mechanism, resulting in mobilization with kinetics similar to other mobilizing CXC chemokines. The study further underscores the importance of the biological roles of carbohydrates.     

ConfidenHT™ System for Diagnostic Mapping of Renal Nerves

Purpose of Review

To summarize the evidence regarding the distribution of renal nerves and their patterns of anatomic variations in animal and human settings. Moreover, the methodology and results of studies regarding renal nerve stimulation (RNS) in both preclinical and clinical models are presented.

Recent Findings

There are differences regarding the number and the size of renal fibers, as well as their distance from the lumen in the diverse parts of the main renal arteries and the branches. In both animals and humans, RNS is safe and results in an increase of blood pressure (BP) while the effect on heart rate varies. In this context, the ConfidenHT? system constitutes an integrated solution for effective RNS in humans.

Summary

Due to the diversity of renal nerve anatomy in humans, arterial areas for more effective renal denervation cannot be homogenously defined. The concept of mapping of renal nerves can improve completeness of renal denervation therapies by means of integrated RNS solutions such as the ConfidenHT? system.