Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients

The dorsolateral prefrontal cortex (DLPFC) plays an essential role in mood regulation and integration of cognitive functions that are abnormal in major depressive disorder (MDD). Few neuroimaging studies have evaluated the still maturing DLPFC in depressed children and adolescents. We conducted single voxel proton magnetic resonance spectroscopy ((1)H MRS) of the left DLPFC in 14 depressed children and adolescents (13.3 +/- 2.3 years old, 10 males) and 22 matched healthy controls (13.6 +/- 2.8 years old, 13 males). Depressed subjects had significantly lower levels of glycerophosphocholine plus phosphocholine (GPC + PC; or choline-containing compounds) and higher myo-inositol levels in the left DLPFC compared to healthy controls. In the depressed subjects, we found significant inverse correlations between glutamate levels and both duration of illness and number of episodes. In healthy controls there was a significant direct correlation between age and glutamine levels, which was not present in the patient group. Lower GPC + PC levels in pediatric MDD may reflect lower cell membrane content per volume in the DLPFC. Increased myo-inositol levels in MDD may represent a disturbed secondary messenger system. GPC + PC and myo-inositol abnormalities further demonstrate the involvement of DLPFC in pediatric MDD.     

Antigen-specific down-regulation of immunopathological events in an experimental autoimmune kidney disease

Heymann nephritis (HN) is an experimental autoimmune disease of rats characterized by immune-complex (IC) depositions on the epithelial side of the glomerular basement membrane (GBM) and by proteinuria. Several forms of HN have been produced by various investigators, but one thing has been common to all of them, namely their inducement by the development of pathogenic IgG autoantibodies (aabs). The aim of this review is to describe how pathogenic IgG aab production (which initiates and maintains the disease) in slowly progressive HN (SPHN) can be specifically terminated by injections of ICs made up of native rat renal tubular antigens and IgM antibodies directed against them.     

The myofibrillar complex and fatigue: a review.

The basis for all biological movement is the conversion of chemical energy to mechanical energy by different classes of motor proteins. In skeletal muscle this motor protein is myosin II, a thick filament-based molecule that harnesses the free energy furnished by ATP hydrolysis to perform mechanical work against actin proteins of the thin filament. The cyclic attachment and detachment of myosin with actin that generates muscle force and shortening is Ca2+ regulated. Intense muscle activity may lead to metabolically induced inhibitions to the function of these myofibrillar proteins when Ca2+ regulation is normal, a phenomenon referred to as myofibrillar fatigue. Studies using single muscle fibers at room temperature or lower have shown that myosin motor function is inhibited by the accumulation of the ATP-hydrolysis products ADP, Pi, and H+ as well as by excess generation of reactive oxygen species (ROS). These metabolically induced impairments to myosin motor function reduce muscle work and power output by impairing maximal Ca2+ activated force, the Ca2+ sensitivity of force, and/or unloaded shortening velocity. Based on uncertainties about their inhibitory effect on muscle function at more physiological temperatures, the influence of ATP-hydrolysis product and ROS accumulation on myofibrillar protein function of human skeletal muscle remains to be clarified.     

Presence of immunoglobulin M antibodies around the glomerular capillaries and in the mesangium of normal and passive Heymann nephritis rats

Summary Diffuse distribution of small, faintly staining, beaded deposits of rat immunoglobulin M (IgM) around the glomerular capillary blood vessels, and a more intensely staining larger deposition in the mesangium, were observed on the kidney sections of normal rats. As glomerular-fixed nephritogenic antigens are known to be present on the epithelial aspect of the glomerular basement membrane (GBM), especially at the soles of foot processes and at the slit pores, it was assumed that the IgM antibodies were directed against these antigens. Investigation by immunofluorescent antibody double-staining techniques of rat kidney sections obtained from normal and rabbit anti-FX1A-injected rats stained for the nephritogenic antigen showed that a number of antigenic sites in the glomeruli and in the mesangium shared antibody hits by heterologous rabbit IgG and autologous rat IgM antibodies. Most sites in the glomeruli stained specifically for rat IgM or rabbit IgG, but preferentially for the latter. The intensely fluorescent mesangial deposits stained mainly for rat IgM, indicating that at these sites the antigenic material was virtually saturated, while areas at the entry to the mesangial space also stained for rabbit IgG, indicating that at these locations free nephritogenic epitopes were still available for reaction with the anti-FX1A antibody. Western blot analysis have shown that the rabbit anti-rat FX1A IgG and the rat anti-rat KF3 IgM antibodies are directed against the same renal tubular-derived antigen with a molecular weight of 70,000. These experimental findings collectively demonstrate that the heterologous IgG and autologous IgM antibodies are directed against the same nephritogenic antigen, which is found in the glomeruli, the mesangium and the proximal convoluted tubules. Thus, the IgM autoantibody has a possible physiological role but, in addition, there is evidence of active immunophagocytic events, manifested in a rapid and continuous entrapment and expulsion of macromolecules after their processing by the mesangial cells of normal and passive Heymann nephritis rats.     

Combination of PCR targeting the VD2 of omp1 and reverse line blot analysis for typing of urogenital Chlamydia trachomatis serovars in cervical scrape specimens

In this study we developed and evaluated a new PCR-based typing assay, directed to the VD2 region of the omp1 gene, for the detection and typing of urogenital Chlamydia trachomatis infections. A nested VD2 PCR-reverse line blot (RLB) assay was developed for the typing of nine different urogenital serovars of C. trachomatis. The assay developed was tested with reference strains of C. trachomatis serovars and cervical scrapes of 86 Colombian women previously found to be positive for C. trachomatis by using plasmid PCR. Two sets of primers directed to the VD2 region of the omp1 gene of C. trachomatis were designed, and fragments of 220 and 166 bp were generated in the primary and nested PCRs, respectively. In addition, an RLB assay was developed to identify nine different urogenital serovars of C. trachomatis (Ba, D, E, F, G, H, I, J, and K) and group controls, including group B (Ba, D, and E), group C (I, J, K, and H), and an intermediate group (F and G). Using this assay, we were able to type 81 of the 86 samples (94.2%). Of these samples, 91.3% were single C. trachomatis infections, and 8.7% were multiple infections. The most common serovars identified were serovars D (22.2%), F (18.5%), G (13.6%), and E (12.3%). Of the women with multiple C. trachomatis infections, >50% contained both serovars D and E. The nested VD2 PCR-RLB developed is a simple, fast, and specific method for the identification of individual urogenital C. trachomatis serovars previously detected by using plasmid PCR. Moreover, it is an appropriate method for studying multiple C. trachomatis infections and for use in large epidemiological studies.     

IL-12 and IL-23: master regulators of innate and adaptive immunity

Summary: Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell‐derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)‐23, a new member of the IL‐12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL‐12 and IL‐23 promote two distinct immunological pathways that have separate but complementary functions. IL‐12 is required for antimicrobial responses to intracellular pathogens, whereas IL‐23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression.     

The emergence of Y-chromosome haplogroup J1e among Arabic-speaking populations

Haplogroup J1 is a prevalent Y-chromosome lineage within the Near East. We report the frequency and YSTR diversity data for its major sub-clade (J1e). The overall expansion time estimated from 453 chromosomes is 10 000 years. Moreover, the previously described J1 (DYS388=13) chromosomes, frequently found in the Caucasus and eastern Anatolian populations, were ancestral to J1e and displayed an expansion time of 9000 years. For J1e, the Zagros/Taurus mountain region displays the highest haplotype diversity, although the J1e frequency increases toward the peripheral Arabian Peninsula. The southerly pattern of decreasing expansion time estimates is consistent with the serial drift and founder effect processes. The first such migration is predicted to have occurred at the onset of the Neolithic, and accordingly J1e parallels the establishment of rain-fed agriculture and semi-nomadic herders throughout the Fertile Crescent. Subsequently, J1e lineages might have been involved in episodes of the expansion of pastoralists into arid habitats coinciding with the spread of Arabic and other Semitic-speaking populations.     

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.     

International quality assurance study for characterization of Streptococcus pyogenes

Surveillance of group A streptococcal (GAS) infections was undertaken as a major component of the European Commission-funded project on severe GAS disease in Europe (strep-EURO). One aim of strep-EURO was to improve the quality of GAS characterization by standardization of methods. An external quality assurance study (EQA) was therefore carried out to evaluate current global performance. Eleven strep-EURO and seven other streptococcal reference centers received a panel of 20 coded GAS isolates for typing. Conventional phenotypic typing (based on cell surface T and M protein antigens and opacity factor [OF] production) and molecular methods (emm gene typing) were used either as single or combined approaches to GAS typing. T typing was performed by 16 centers; 12 centers found one or more of the 20 strains nontypeable (typeability, 89%), and 11 centers reported at least one incorrect result (concordance, 93%). The 10 centers that tested for OF production achieved 96% concordance. Limited availability of antisera resulted in poor typeability values from the four centers that performed phenotypic M typing (41%), three of which also performed anti-OF typing (typeability, 63%); however, concordance was high for both M (100%) and anti-OF (94%) typing. In contrast, the 15 centers that performed emm gene sequencing achieved excellent typeability (97%) and concordance (98%), although comparison of the performance between centers yielded typeability rates from 65 to 100% and concordance values from 83 to 100%. With the rapid expansion and use of molecular genotypic methods to characterize GAS, continuation of EQA is essential in order to achieve international standardization and comparison of type distributions.