Activation induces apoptosis in Herpesvirus saimiri-transformed T cells independent of CD95 (Fas,APO-1)

Signaling via the T cell receptor (TCR)/CD3 complex of pre-activated T cells induces apoptosis. Such an activation-induced cell death (AICD) is thought to play an important role in the regulation of cellular immune responses. In this study we analyzed pathways of AICD by using human T cells transformed by Herpesvirus saimiri. These growth-transformed T cells show the phenotype of activated mature T cells and continue to express a functionally intact TCR. We show that human H. saimiri-transformed T cell clones readily undergo cell death upon signaling via the TCR/CD3 complex or via phorbol 12-myristate 13-acetate (PMA) + ionomycin. The AICD in H. saimiri-transformed T cells was detectable a few hours after activation and it was not affected by the presence of interleukin (IL)-2 or by anti-CD4 cross-linking. However, AICD required tyrosine phosphorylation, since it could be blocked by herbimycin A. Cyclosporin A (CsA) did not block the development of AICD, but other consequences of activation in H. saimiri-transformed T cells like the production of interferon-γ. Surprisingly, the development of AICD was not reduced by neutralizing antibodies to tumor necrosis factor (TNF)-α or blocking antibodies directed to CD95 (Fas, APO-1), although H. saimiri-transformed T cells were sensitive to CD95 ligation. To confirm that this form of AICD is really independent of CD95, we have established an H. saimiri-transformed T cell line from a patient with a homozygous deletion in the CD95 gene. This CD95-deficient T cell line was as sensitive to AICD as other CD95-expressing H. saimiri-transformed T cells. In conclusion, we describe here a type of AICD in H. saimiri-transformed T cells that is independent of CD95 and TNF-α, not sensitive to CsA, but requires tyrosine phosphorylation. This system should be useful for the investigation of CD95-independent forms of AICD.     

Adolescents' wellbeing and functioning: relationships with parents' subjective general physical and mental health

Background  

This study aimed at examining the relationship between parental subjective health status and adolescents' health-related quality of life (HRQoL) as well as the role of gender, socioeconomic status, presence of chronic health care needs and social support on the above interaction.     

Radio frequency radiation exposure standards: considerations for harmonization

Radio frequency radiation exposure standards vary in origin, development process, legal status, and in the actual exposure limits. To identify the sources of differences in limits, we evaluated technical aspects of eight standards that included supporting information on the scientific data and rationale. Comparisons were made among the standards by examining the scope of the underlying database, the rationales for safety factors and other issues underlying exposure limits in the energy-deposition range (0.1 MHz to 10.0 GHz) and in the surface-heating range (about 10 or 15 GHz to 300 GHz). The framework for this assessment was based on the methods recommended by the scientific and regulatory organizations for developing health-based exposure limits. General guidelines for performing risk assessments for threshold acting agents have been developed by the U.S. Environmental Protection Agency, Health Canada's Environmental Health Directorate, and the International Program on Chemical Safety of the World Health Organization. This general methodology was applied to radiofrequency radiation for this assessment. Because these methods strive to identify scientific issues and separate them from risk management or policy, they provide a basis for evaluation of standards in this paper. This distinction can provide a foundation for the longer-term goal of global harmonization of radio frequency radiation standards. Each of the standards evaluated in the energy-deposition range was found to use the same basic restriction, based on biological data and a 10-fold safety factor, yet explanations reflect different interpretations of the underlying biological data. Rationales differ for the magnitude of the safety factor, for the circumstances of exposure, for the nature of sensitive populations, and for the presumed health status of the individuals for whom the basic restriction is applicable. In the surface-heating range, broad variability in exposure limits are seen in the limit itself, as well as in the approach to time averaging and frequency dependence. Averaging times differ among standards, as do tissue geometries for defining partial-body exposures. The differences in approaches to develop the standards do not completely explain differences among the exposure limits, and methods for computing exposure limits from basic restrictions are not always defined. This analysis suggests harmonization of standards will require more detailed review and coordination of biological and engineering data and of policy options.     

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.OCIS codes: (170.5280) Photon migration, (170.7050) Turbid media, (170.3890) Medical optics instrumentation     

Identifying the sociodemographic determinants of subjective health complaints in a cross-sectional study of Greek adolescents

Background

Experience of common health symptoms without a clear physical or psychological cause, such as headache or dizziness, is often reported in adolescence. The present study attempted to investigate associations of self-reported subjective health complaints (SHC) with a number of sociodemographic factors of Greek adolescents.

Methods

Questionnaires were administered to a Greek nationwide random school-based sample of adolescents aged 12 to 18 years and their parents in 2003. Data from 922 adolescent-parent pairs were analyzed (response rate?=?63%). Adolescents?? reported subjective health complaints were assessed for their association with a number of sociodemographic factors: age, sex, type of area of residence according to level of urbanization, immigration background, parental education and employment status, family socioeconomic status and perceived quality of financial resources (PQFR). Multiple linear regression analysis was used to assess the association of the aforementioned factors with subjective health complaints as the dependent variable.

Results

Most sociodemographic variables, apart from area of residence and immigration background, were independently associated with subjective health complaints in the univariate analyses. The multiple linear regression analysis, however, limited the factors that could predict adolescents?? subjective health complaints to four (age, sex, Family Affluence Scale score and perceived quality of financial resources). Some considerations regarding parental employment status and immigration background are highlighted.

Conclusions

Our study highlights the sociodemographic components of subjective health complaints in the Greek adolescent population. The need to include adolescent-specific measures when collecting information on adolescents?? social background is underlined. Identifying vulnerable adolescent populations could lead to effective health promoting and preventive interventions.     

Infectious pulmonary complications after stem cell transplantation or chemotherapy: diagnostic yield of bronchoalveolar lavage

Hematologic patients are at high risk for infectious pulmonary complications after stem cell transplantation (SCT) or chemotherapy. The aim of this study was to detect the range of pulmonary pathogens in these patients, analyzing 95 bronchoalveolar lavage (BAL) samples with classic and molecular (polymerase chain reaction [PCR]) detection methods. Human cytomegalovirus (HCMV) was detected in 33, herpes simplex virus in 21, human herpesvirus 6 in 24, and other viruses in 16 samples. Aspergillus species were detected in 19, Candida species in 25, and Gram-positive bacteria in 29 samples. The additional use of PCR detection methods increased the diagnostic yield from 56% to 73%, especially concerning viral and fungal infections in BAL samples. No infectious agent was detected in 26 samples. Interestingly, a high incidence of polymicrobial infections (50/95) was detected, dominated by HCMV co-infections, especially after allogeneic SCT. Within 3 years of follow-up, a poor outcome of co-infections of Aspergillus species with HCMV in 9 of 10 cases could be documented, whereas only 7 of 20 patients died with noninfectious BAL results. Herpesviruses, fungi, and Gram-positive bacteria were detected most frequently, and in 53%, polymicrobial infections were diagnosed.     

Depression and changed pain perception: hints for a central disinhibition mechanism

Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n=20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). In depressive disorder (to a lesser extent also in FMS), significantly decreased cold pain thresholds and an increased wind-up were found, although the mechanical pain thresholds and pain sensitivity were comparable to those of the healthy controls. All the detection thresholds were within the normal range in all the groups. In depressive disorder, there were no significant side differences in the detection and pain thresholds. The results contradict the former assumption of a general insensitivity to experimental pain in depressive disorder. In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.     

Electromagnetic field standards in Central and Eastern European countries: current state and stipulations for international harmonization

Electromagnetic field standards in the West are based on well-established acute biological effects that could be considered as signaling a potentially adverse health effect. The specific absorption rate, which is proportional to the tissue heating (thermal effects), represents the basic restriction of exposure to Radio-Frequency (RF) fields. On the other hand, Eastern European standards are designed to protect from potential non-thermal effects that might be caused by chronic exposure to very low intensities, where a so-called "power load" (a product of field intensity and duration of exposure) represents the basic limitation. Thus, electromagnetic field standards in Eastern European countries differ considerably from those which are proposed by the International Commission of Non-ionizing Radiation Protection and the Standards Coordinating Committee 28 of the Institute of Electrical and Electronics Engineers, Inc. In the present paper, the strategies for development of exposure limit values in electromagnetic fields standards currently in force in Eastern and Central European countries are discussed. Some differences as well as similarities of the national health and safety standards and the main obstacles to harmonization of these standards with those being established by Western national and international organizations and agencies are presented.     

Puromycin: two distinct behavioral effects with different temporal parameters in the pigeon.

Pigeons were injected intracerebrally with either puromycin (PM) or control saline solution following training for one 12-min session on a visual discrimination. Injections were made either immediately following training, 1 hr later or 24 hr later. Retention testing 3 days after training showed that PM produced marked amnesia in the first two groups, but had no effect in the 24 hr condition. However, all PM groups were retarded subsequently in the number of days required to reach a 90% discimination criterion. This differentiation of two separate behavioral effects with different temporal gradients suggests that PM may be working through two distinct physiological mechanisms.