Phenotyping of 60 cultured human gliomas and 34 other neuroectodermal tumors by means of monoclonal antibodies against glioma, melanoma and HLA-DR antigens.

The reactivity spectrum of three monoclonal antibodies (Mabs) to human malignant glioma, five Mabs to melanomas and one Mab anti-HLA-DR was investigated by an indirect antibody binding radioimmunoassay on a panel of cells derived from 60 glioma lines, including 47 malignant astrocytomas, 11 low-grade astrocytomas and two malignant ependymomas as well on cells from 12 melanoma, three neuroblastoma, three medulloblastoma, two schwannoma, two retinoblastoma, two choroïd plexus papilloma, ten meningioma and 12 unrelated tumor lines. The anti-glioma Mabs BF7 and GE2 reacted preferentially with gliomas, while the anti-glioma Mab CG12 reacted with gliomas, melanomas, neuroblastomas and medulloblastomas. The five anti-melanoma Mabs reacted with gliomas, neuroblastomas and medulloblastomas. The anti-HLA-DR Mab D1-12 reacted with gliomas, melanomas and some meningiomas. On the basis of the data presented, we describe three different antigenic systems; the first one is glioma-associated, the second one is related to differentiation antigens expressed on cells derived from the neuroectoderm and the third is represented by HLA-DR antigens which are expressed not only on B-lymphoblastoid cells but also on melanomas and gliomas.

CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1.

Cytotoxic T cells that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally impotent in eliciting tumor rejection. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T-cell dysfunction may reveal effective strategies for immune therapy. The inhibitory receptors PD-1 and Tim-3 are known to negatively regulate CD8(+) T-cell responses directed against the well-characterized tumor antigen NY-ESO-1. Here, we report that the upregulation of the inhibitory molecule BTLA also plays a critical role in restricting NY-ESO-1-specific CD8(+) T-cell expansion and function in melanoma. BTLA-expressing PD-1(+)Tim-3(-) CD8(+) T cells represented the largest subset of NY-ESO-1-specific CD8(+) T cells in patients with melanoma. These cells were partially dysfunctional, producing less IFN-γ than BTLA(-) T cells but more IFN-γ, TNF, and interleukin-2 than the highly dysfunctional subset expressing all three receptors. Expression of BTLA did not increase with higher T-cell dysfunction or upon cognate antigen stimulation, as it does with PD-1, suggesting that BTLA upregulation occurs independently of functional exhaustion driven by high antigen load. Added with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. Collectively, our findings indicate that targeting BTLA along with the PD-1 and Tim-3 pathways is critical to reverse an important mechanism of immune escape in patients with advanced melanoma.

How important are interview methods and questionnaire designs in research on self-reported juvenile delinquency? An experimental comparison of internet vs. paper-and-pencil questionnaires and different definitions of the reference period

There has been relatively little change over recent decades in the methods used in research on self-reported delinquency. Face-to-face interviews and selfadministered interviews in the classroom are still the predominant alternatives envisaged. New methods have been brought into the picture by recent computer technology, the Internet, and an increasing availability of computer equipment and Internet access in schools. In the autumn of 2004, a controlled experiment was conducted with 1,203 students in Lausanne (Switzerland), where "paper-and-pencil" questionnaires were compared with computer-assisted interviews through the Internet. The experiment included a test of two different definitions of the (same) reference period. After the introductory question ("Did you ever..."), students were asked how many times they had done it (or experienced it), if ever, "over the last 12 months" or "since the October 2003 vacation". Few significant differences were found between the results obtained by the two methods and for the two definitions of the reference period, in the answers concerning victimisation, self-reported delinquency, drug use, failure to respond (missing data). Students were found to be more motivated to respond through the Internet, take less time for filling out the questionnaire, and were apparently more confident of privacy, while the school principals were less reluctant to allow classes to be interviewed through the Internet. The Internet method also involves considerable cost reductions, which is a critical advantage if self-reported delinquency surveys are to become a routinely applied method of evaluation, particularly so in countries with limited resources. On balance, the Internet may be instrumental in making research on self-reported delinquency far more feasible in situations where limited resources so far have prevented its implementation.

Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37.

The intracellular location of nucleic acid sensors prevents recognition of extracellular self-DNA released by dying cells. However, on forming a complex with the endogenous antimicrobial peptide LL37, extracellular DNA is transported into endosomal compartments of plasmacytoid dendritic cells, leading to activation of Toll-like receptor-9 and induction of type I IFNs. Whether LL37 also transports self-DNA into nonplasmacytoid dendritic cells, leading to type I IFN production via other intracellular DNA receptors is unknown. Here we found that LL37 very efficiently transports self-DNA into monocytes, leading the production of type I IFNs in a Toll-like receptor-independent manner. This type I IFN induction was mediated by double-stranded B form DNA, regardless of its sequence, CpG content, or methylation status, and required signaling through the adaptor protein STING and TBK1 kinase, indicating the involvement of cytosolic DNA sensors. Thus, our study identifies a novel link between the antimicrobial peptides and type I IFN responses involving DNA-dependent activation of cytosolic sensors in monocytes.

Differing trends in the association between obesity and self-reported health in Portugal and Switzerland: data from national health surveys 1992-2007.

BACKGROUND: The escalating prevalence of obesity might prompt obese subjects to consider themselves as normal, as this condition is gradually becoming as frequent as normal weight. In this study, we aimed to assess the trends in the associations between obesity and self-rated health in two countries. METHODS: Data from the Portuguese (years 1995-6, 1998-6 and 2005-6) and Swiss (1992-3, 1997, 2002 and 2007) National Health Surveys were used, corresponding to more than 130,000 adults (64,793 for Portugal and 65,829 for Switzerland). Body mass index and self-rated health were derived from self-reported data. RESULTS: Obesity levels were higher in Portugal (17.5% in 2005-6 vs. 8.9% in 2007 in Switzerland, p < 0.001) and increased in both countries. The prevalence of participants rating their health as "bad" or "very bad" was higher in Portugal than in Switzerland (21.8% in 2005-6 vs 3.9% in 2007, p < 0.001). In both countries, obese participants rated more frequently their health as "bad" or "very bad" than participants with regular weight. In Switzerland, the prevalence of "bad" or "very bad" rates among obese participants, increased from 6.5% in 1992-3 to 9.8% in 2007, while in Portugal it decreased from 41.3% to 32.3%. After multivariate adjustment, the odds ratio (OR) of stating one self's health as "bad" or "very bad" among obese relative to normal weight participants, almost doubled in Switzerland: from 1.38 (95% confidence interval, CI: 1.01-1.87) in 1992-3 to 2.64 (95% CI: 2.14-3.26) in 2007, and similar findings were obtained after sample weighting. Conversely, no such trend was found in Portugal: 1.35 (95% CI: 1.23-1.48) in 1995-6 and 1.52 (95% CI: 1.37-1.70) in 2005-6. CONCLUSION: Obesity is increasing in Switzerland and Portugal. Obesity is increasingly associated with poorer self-health ratings in Switzerland but not in Portugal.

Self-potentials in partially saturated media: the importance of explicit modeling of electrode effects

Self-potential (SP) data are of interest to vadose zone hydrology because of their direct sensitivity to water flow and ionic transport. There is unfortunately little consensus in the literature about how to best model SP data under partially saturated conditions, and different approaches (often supported by one laboratory data set alone) have been proposed. We argue that this lack of agreement can largely be traced to electrode effects that have not been properly taken into account. A series of drainage and imbibition experiments were considered in which we found that previously proposed approaches to remove electrode effects were unlikely to provide adequate corrections. Instead, we explicitly modeled the electrode effects together with classical SP contributions using a flow and transport model. The simulated data agreed overall with the observed SP signals and allowed decomposing the different signal contributions to analyze them separately. After reviewing other published experimental data, we suggest that most of them include electrode effects that have not been properly taken into account. Our results suggest that previously presented SP theory works well when considering the modeling uncertainties presently associated with electrode effects. Additional work is warranted to not only develop suitable electrodes for laboratory experiments but also to assure that associated electrode effects that appear inevitable in longer term experiments are predictable, so that they can be incorporated into the modeling framework.

A new self-expanding aortic stent valve with annular fixation: in vitro haemodynamic assessment.

OBJECTIVE: Balloon-expandable stent valves require flow reduction during implantation (rapid pacing). The present study was designed to compare a self-expanding stent valve with annular fixation versus a balloon-expandable stent valve. METHODS: Implantation of a new self-expanding stent valve with annular fixation (Symetis, Lausanne, Switzerland) was assessed versus balloon-expandable stent valve, in a modified Dynatek Dalta pulse duplicator (sealed port access to the ventricle for transapical route simulation), interfaced with a computer for digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85 mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). RESULTS: A total of 450 cardiac cycles was analysed. Stepwise expansion of the self-expanding stent valve with annular fixation (balloon-expandable stent valve) resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830+/-76 mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient of 11+/-1.5 mmHg (366+/-202 mmHg)*, systolic aortic pressure dropped distal to the valve from 121 to 64.5+/-2 mmHg (123 to 55+/-30 mmHg) N.S., and output collapsed to 1.9+/-0.06 l/min (0.71+/-0.37 l/min* (before complete obstruction)). No valve migration occurred in either group. (*=p<0.05). CONCLUSIONS: Implantation of this new self-expanding stent valve with annular fixation has little impact on haemodynamics and has the potential for working heart implantation in vivo. Flow reduction (rapid pacing) is not necessary.

The human T cell response to melanoma antigens.

The cornerstone of the concept of immunosurveillance in cancer should be the experimental demonstration of immune responses able to alter the course of in vivo spontaneous tumor progression. Elegant genetic manipulation of the mouse immune system has proved this tenet. In parallel, progress in understanding human T cell mediated immunity has allowed to document the existence in cancer patients of naturally acquired T cell responses to molecularly defined tumor antigens. Various attributes of cutaneous melanoma tumors, notably their adaptability to in vitro tissue culture conditions, have contributed to convert this tumor in the prototype for studies of human antitumor immune responses. As a consequence, the first human cytolytic T lymphocyte (CTL)-defined tumor antigen and numerous others have been identified using lymphocyte material from patients bearing this tumor, detailed analyses of specific T cell responses have been reported and a relatively large number of clinical trials of vaccination have been performed in the last 15 years. Thus, the "melanoma model" continues to provide valuable insights to guide the development of clinically effective cancer therapies based on the recruitment of the immune system. This chapter reviews recent knowledge on human CD8 and CD4 T cell responses to melanoma antigens.

Self-Construction, Cognitive Conflicts, and Disordered Eating Attitudes in Young Women

The aim of this study is to identify cognitive variables that predict disordered eating attitudes in a nonclinical sample composed of 50 female university students. Repertory grid technique was used to assess cognitive features of self-construing and cognitive conflicts. Drive for Thinness and Body Dissatisfaction scales from the Eating Disorder Inventory 2 were used as dependent variables, as previous studies suggested that high scores on these scales are associated with the risk of developing or aggravating eating syndromes. Results suggest that drive for thinness can be associated with cognitive conflicts, whereas body dissatisfaction may be higher for those who construct themselves as inadequate and similar to others. In addition, both dependent variables were predicted by being younger and having a higher body mass index.

Photonic characteristics of Langmuir-Blodgett self-assembled monolayers of colloidal silica particles

Monodispersed colloidal crystals based on silica sub-micrometric particles were synthesized using the Stöber-Fink-Bohn process. The control of nucleation and coalescence result in improved characteristics such as high sphericity and very low size dispersion. The resulting silica particles show characteristics suitable for self-assembling across large areas of closely-packed 2D crystal monolayers by an accurate Langmuir-Blodgett deposition process on glass, fused silica and silicon substrates. Due to their special optical properties, colloidal films have potential applications in fields including photonics, electronics, electro-optics, medicine (detectors and sensors), membrane filters and surface devices. The deposited monolayers of silica particles were characterized by means of FESEM, AFM and optical transmittance measurements in order to analyze their specific properties and characteristics. We propose a theoretical calculation for the photonic band gaps in 2D systems using an extrapolation of the photonic behavior of the crystal from 3D to 2D. In this work we show that the methodology used and the conditions in self-assembly processes are decisive for producing high-quality two-dimensional colloidal crystals by the Langmuir-Blodgett technique.

Clonal acquisition of the Ly49A NK cell receptor is dependent on the trans-acting factor TCF-1.

Families of clonally expressed major histocompatibility complex (MHC) class I-specific receptors provide specificity to and regulate the function of natural killer (NK) cells. One of these receptors, mouse Ly49A, is expressed by 20% of NK cells and inhibits the killing of H-2D(d) but not D(b)-expressing target cells. Here, we show that the trans-acting factor TCF-1 binds to two sites in the Ly49A promoter and regulates its activity. Moreover, we find that TCF-1 determines the size of the Ly49A NK cell subset in vivo in a dosage-dependent manner. We propose that clonal Ly49A acquisition during NK cell development is regulated by TCF-1.