Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.     

Predicting Home and Work Blood Pressure Measurements from Resting Baselines and Laboratory Reactivity in Black and White Americans

The relationship between blood pressure in the laboratory (both at rest and in response to laboratory tasks) and ambulatory blood pressure at home and at work was evaluated. One hundred nineteen normotensive and unmedicated mild-moderate hypertensive black and white females and males participated in laboratory blood pressure monitoring at rest and during four challenging tasks (structured interview, video game, bicycle exercise, and cold pressor test) as well as ambulatory blood pressure monitoring while at home and at work. Baseline blood pressure taken while subjects were at rest was the strongest predictor of ambulatory systolic blood pressure (r = .64) and diastolic blood pressure (r = .77) at work. Among reactivity tasks the strongest predictors of ambulatory blood pressure in the total population were the structured interview and the video game (both psychological tasks) followed by the cold pressor test. Racial comparisons, however, determined that the cold pressor test predicted diastolic blood pressure significantly better for blacks (r = .73) than for whites (r = .40), suggesting a possible difference in blood pressure regulation.     

THE POTENTIAL USES OF GENOTYPING OF PLASMODIUMFALCIPARUMISOLATESBYTHENESTEDPOLYMERASECHAINREACTION

巢式ＰＣＲ方法被应用于泰国疟区（Ｂｏｒａｉ）恶性疟原虫的基因分型。应用特异的等位基因引物扩增了恶性疟原虫裂殖子表面蛋白１（ＭＳＰ１）基因的１、４变异多态区。以凝胶电泳分析扩增的目的基因片段。结果表明：共分别检测出恶性疟原虫６个ＭＡＤ２０等位基因型、４个Ｋ１和１个ＲＯ３３等位基因型。在９个月的流行季节，上述虫株的等位基因频率没有明显的改变，关存在较高程度的恶性疟原虫不同等位基因株的混合感染。本文进一步阐明了巢式ＰＣＲ技术在疟疾流行病学上的应用前景及优点。     

Decreased depression up to one year following CBSM+ intervention in depressed women with AIDS: the smart/EST women's project

This prospective multisite Phase III clinical trial (Miami, New York, New Jersey) investigated the long-term (one year) effects of a 10-week group cognitive-behavioral stress management/expressive supportive therapy (CBSM+) intervention on disadvantaged minority women living with AIDS. The CBSM+ intervention consisted of 10-weekly group session of stress management, cognitive-behavioral skill training, relaxation techniques and expressive-supportive therapeutic strategies. The primary study outcome was self-reported depression scores as measured by the BDI. The CBSM+ Group intervention significantly decreased depression scores on the BDI for women following the intervention and maintained the decreased level at one-year follow-up.     

Ultrasonographic assessment of human skeletal muscle size

The measurement of human muscle size is essential when assessing the effects of training, disuse and ageing. The considered gold standard for cross-sectional area measurements of muscle size is magnetic resonance imaging (MRI). However, MRI is costly and often inaccessible. The aim of the present study was to test the reproducibility and validity of a more accessible alternative method using ultrasonography (ULT). We examined the cross-sectional areas in the vastus lateralis muscle of six individuals. Axial-plane ULT scans were taken at given levels along the entire muscle length. The ULT scanning was repeated on different days (reliability) and validated against MRI-based measurements. Mean intraclass correlation coefficients were 0.998 for the reliability of ULT and 0.999 for the validity of ULT against MRI. The coefficient of variation values for cross-sectional area measurements assessed by six different experimenters were 2.1% and 0.8% for images obtained with ULT and MRI, respectively. The ULT method is a valid and reliable alternative tool for assessing cross-sectional areas of large individual human muscles. The present findings justify the application of the ULT method for the detection of changes throughout large muscles in response to training, disuse or as a consequence of sarcopenia.     

Viral hemagglutinin augments peptide-specific cytotoxic T cell responses

In attempt to increase the induction of peptide-specific cytolytic T cells (CTL) we investigated the effect of the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) gene product on the activation of peptide-specific CTL. Spleen cells of CH3 mice immunized against the influenza nucleoprotein peptide 50–63 (NP 50–63) were restimulated in vitro (i) with peptide-pulsed syngeneic fibroblast cells (Ltk^?) as antigen-presenting cells, which were in addition (ii) infected with NDV or (iii) stably transfected with the HN cDN A of NDV. A greater than sixfold increase in peptide-specific CTL responses was observed in cultures restimulated with peptide-pulsed Ltk^? cells which co-expressed viral hemagglutinin due to either infection or transfection. A similar augmentation was seen in CTL responses against other types of antigen (major histocompatibility complex alloantigens, minor histocompatibility antigens or tumor antigens) when suboptimal cultures were stimulated with the respective antigen-presenting cells modified by NDV infection. These findings suggest that NDV or viral HN expressed on antigen-presenting cells or tumor cells can exert a T cell co-stimulatory function.     

Phenotypic characterization of regulatory CD4+CD25+ T cells in rats

CD25 has become widely used as a marker for a subset of regulatory CD4(+) T cells present in the thymus and periphery of mice, rats and humans. However, CD25 is also expressed on conventionally activated T cells that are not regulatory and not all peripheral regulatory T cells express CD25. The identification of a stable and unique marker for regulatory T cells would therefore be valuable. This study provides a detailed account of the phenotype of CD4(+)CD25(+) regulatory T cells in rats. In the thymus, CD4(+)CD8(-)CD25(+) cells were found to have a more mature phenotype than the corresponding CD4(+)CD8(-)CD25(-) cells with respect to expression of Thy1 (CD90), CD53 and CD44, suggesting that CD25 expression, and perhaps commitment to regulatory function, might be a late event in thymocyte development. CD4(+)CD25(+) cells in both the thymus and periphery were found to have enriched and heterogeneous expression of activation markers such as OX40 (CD134) and OX48 (an antibody determined in this study to be specific for CD86). CD4(+)CD25(+) T cells were also found to have enriched expression of CD80, at both the mRNA and protein level. However, functional studies in vitro and in vivo showed that neither OX40 or CD86 were useful markers for the further subdivision of regulatory T cells. Our studies indicate that, at present, CD25 remains the most useful marker to enrich for regulatory CD4(+) T cells in rats and no further subdivision of the regulatory component of CD4(+)CD25(-)CD45RC(low) T cells has yet been achieved.