A combination of soluble helper factors bypasses the requirement for stimulator cells and induces nonspecific cytotoxic T cell responses

The specificity of cytotoxic T lymphocyte (CTL) responses generated in the presence of lymphokines was studied. Thymic responder cells were activated in the presence of stimulator cells that differed in their metabolic activity. After 5 days of culture, the cytotoxic response was estimated in a 4-h 51Cr-release test. Coculture of thymic responders with irradiated splenic stimulator cells in the presence of interleukin 2(IL 2) led to preferential cytolysis of target cells that expressed the same histocompatibility antigens as the cells used for sensitization. Addition of T cell cytotoxicity-inducing factor 1 (TCF1), however, to those cultures made the presence of stimulator cells unnecessary and induced cytotoxic responses against all target cells tested, including target cells syngeneic to the responder cells. This activation was neither due to contaminating mitogen nor to the effect of heterologous serum in the assay system. The conclusion of these findings was that either polyclonal activation of CTL was induced by TCF1 or that some specific CTL clones differentiated into unrestricted killer cells under the influence of TCF1

Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis

By intrasplenic immunization we raised a rat mAb (mAb V1q; IgG2a, kappa) with a potent neutralizing activity against natural mouse TNF (1 microgram/ml mAb V1q/100 U/ml TNF). mAb V1q was used to study the role of endogenous TNF in experimental peritonitis induced by sublethal cecal ligation and puncture. mAb V1q persisted for over 5 days in the serum of mice injected with 100 micrograms of the antibody and, therefore, proved useful for in vivo experiments. As little as 20 micrograms mAb V1q/mouse prevented lethal shock of the animals by 400 micrograms LPS/mouse. In sublethal cecal ligation and puncture i.p. injection of mAb V1q directly and up to 8 h after induction of experimental peritonitis lead to death of the animals within 1 to 3 days. The lethal effect of mAb V1q was compensated by injection of recombinant mouse TNF. Similar mAb V1q effects as in immunocompetent mice were shown in severe combined immune deficiency mice deficient of mature functional B and T cells. Taken together, these data suggest that during the early phase of peritonitis endogenous TNF may stimulate nonlymphoid cells such as granulocytes, macrophages, platelets, and fibroblasts to ingest bacteria and to localize inflammation, respectively. These beneficial effects of TNF may determine survival. Thus, our data may have implications for the therapeutic management of a beginning peritonitis

Capacity of different cell types to stimulate cytotoxic T lymphocyte precursor cells in the presence of interleukin 2

Plastic-adherent cells enriched for dendritic cells (AC) were found to be among the most potent stimulator cells for the activation of cytotoxic T lymphocytes (CTL) in vitro in the presence of interleukin 2 (IL 2) and a constant second set of allogeneic stimulator cells. Concanavalin A-activated nylon wool-nonadherent spleen cells ( CNWT ), concanavalin A-activated unfractionated spleen cells ( Cspl ), and some variants of the ESb T lymphoma line were equally effective as stimulator cells, however, and provoked a substantial cytotoxic response at concentrations of 10(4) cells per culture or less. In contrast, nonactivated nylon wool-nonadherent spleen cells ( NWT ) or unfractionated spleen cells (Spl) and cells of the P815 mastocytoma, the Meth A fibrosarcoma, and the T cell lymphomas Ly 5178 Eb and ESb did not stimulate cytotoxic responses at these cell concentrations. The strong stimulatory potential of the Cspl preparation was reduced by treatment with anti-Thy-1 antibody plus complement, whereas the stimulatory activity of the AC preparation was resistant to this treatment. All cell types tested expressed class I major histocompatibility antigens. Nonactivated NWT cells, in contrast to the CNWT preparation, showed no detectable staining with anti-I-E or anti-I-A antibodies and also a slightly weaker staining with class I antisera. Experiments with the tumor cell lines revealed, however, that there was no strict correlation between stimulatory potential and density of class I alloantigens or the expression of I-E determinants. Experiments on primary cytotoxic responses in vivo gave similar results. Experiments in cultures with a single set of stimulator cells and I region-compatible responder cells indicated that AC and Cspl or CNWT also have a markedly stronger capacity than NWT to induce IL 2-dependent DNA synthesis

Induction of IL 2 receptor expression and cytotoxicity of thymocytes by stimulation with TCF1

We investigated the role of T cell cytotoxicity inducing factor 1 (TCF1) in the induction of a cytotoxic T cell response. We found that help-deficient thymocyte cultures supplied with saturating amounts of purified IL 2 did not develop CTL in a 5-day culture. The expression of cytotoxicity was dependent on the addition of TCF1 derived from the T cell hybridoma K15. TCF1 also induced proliferation of thymocytes in the presence of IL 2. Only the PNA- thymocyte subpopulation responded to TCF1 with proliferation and cytotoxicity in the presence of IL 2. The monokine IL 1 also induced proliferation in this subpopulation but failed to induce cytotoxicity. IL 1 was further distinguished from TCF1 by inhibition of IL 1-induced but not TCF1-induced proliferation by anti-IL 1 antibodies. In addition, using anti-IL 2 receptor antibodies (AMT 13), we showed that TCF1 in the presence of IL 2 substantially increased IL 2 receptor expression in thymocytes. IL 1 had the same effect on induction of IL 2 receptor expression as TCF1. Because some effects of IL 1 and TCF1 are distinct and some overlap, we discuss whether IL 1 and TCF1 induce different subsets of PNA- thymocytes

Enhancement of experimental metastasis by tumor necrosis factor

The influence of endogenous and exogenous tumor necrosis factor (TNF) on metastasis was investigated in an experimental fibrosarcoma metastasis model. A single intraperitoneal injection of recombinant human (rh) TNF or recombinant mouse (rm) TNF into mice 5 h before intravenous inoculation of methylcholanthrene-induced fibrosarcoma cells (CFS1) induced a significant enhancement of the number of metastases in the lung. Dose responses of rmTNF and rhTNF demonstrated a stronger metastasis-augmenting effect by rmTNF compared with rhTNF. This effect was time dependent, as administration of rmTNF 5 h before or 1 h but not 24 h after tumor cell inoculation caused an increase of tumor cell colony formation on the lung surface, suggesting an influence of TNF on the vascular adhesion and diapedesis of tumor cells. Since tumor-bearing mice showed an enhanced ability to produce TNF after endotoxin injection compared to control mice, tumor-bearing mice were treated with anti-mTNF antibodies. Neutralization of endogenous tumor-induced TNF led to a significant decrease of the number of pulmonary metastases. Histological analysis of micrometastases in the lung on day 5 by silver staining of proteins associated with nucleolar organizer regions revealed more metastatic foci and augmented proliferative activity of the tumor cells after rmTNF pretreatment of mice. However, no direct effect of rmTNF on the proliferation rate of tumor cells was seen in vitro. These findings suggest that low doses of endogenous TNF or administered TNF during cytokine therapy might enhance the metastatic potential of circulating tumor cells

Stability of condensate in superconductors

According to the BCS theory the superconducting condensate develops in a single quantum mode and no Cooper pairs out of the condensate are assumed. Here we discuss a mechanism by which the successful mode inhibits condensation in neighboring modes and suppresses a creation of noncondensed Cooper pairs. It is shown that condensed and noncondensed Cooper pairs are separated by an energy gap which is smaller than the superconducting gap but large enough to prevent nucleation in all other modes and to eliminate effects of noncondensed Cooper pairs on properties of superconductors. Our result thus justifies basic assumptions of the BCS theory and confirms that the BCS condensate is stable with respect to two-particle excitations

Infants’ vocalizations at 6 months predict their productive vocabulary at one year

Long before their first words, children communicate by using speech-like vocalizations. These protophones might be indicative of infants' later language development. We here examined infants' (n = 56) early vocalizations at 6 months (vocal reactivity scale of the IBQ-R) as a predictor of their expressive and receptive language at 12 months (German version of the CDI). Regression analyses revealed vocalizations to significantly predict expressive, but not receptive language. Our findings in German-learning 6-month-olds extend previous predictive evidence of early vocalizations reported for older infants. Together these findings are informative in light of early assessments monitoring typical and atypical language development

How do enriched speech acoustics support language acquisition in children with hearing loss? A narrative review

Language outcomes of children with hearing loss remain heterogeneous despite recent advances in treatment and intervention. Consonants with high frequency, in particular, continue to pose challenges to affected children's speech perception and production. In this review, the authors evaluate findings of how enriched child-directed speech and song might function as a form of early family-centered intervention to remedy the effects of hearing loss on consonant acquisition already during infancy. First, they review the developmental trajectory of consonant acquisition and how it is impeded by permanent pediatric hearing loss. Second, they assess how phonetic-prosodic and lexico-structural features of caregiver speech and song could facilitate acquisition of consonants in the high-frequency range. Last, recommendations for clinical routines and further research are expressed

Toolbox from the EC FP7 HOSANNA project for the reduction of road and rail traffic noise in the outdoor environment

yesThis paper offers a brief overview of innovative methods for road and rail traffic noise reduction between source and receiver. These include using new barrier designs, planting of trees, treatments of ground and road surfaces and greening of building façades and roofs using natural materials, like vegetation, soil and other substrates in combination with recycled materials and artificial elements. The abatements are assessed in terms of numerically predicted sound level reductions, perceptual effects and cost–benefit analysis. Useful reductions of noise from urban roads and tramways are predicted for 1-m-high urban noise barriers and these are increased by adding inter-lane barriers. A 3 m wide 0.3 m high lattice ground treatment, a carefully planted 15-m-wide tree belt and replacing 50 m of paved areas by grassland are predicted to give similar reductions. Tree belts are shown to be very cost-effective and combining tall barriers with a row of trees reduces the negative impact of wind. Green roofs may significantly reduce the noise at the quiet side of buildings

Fetal dehydroepiandrosterone from hair samples at birth predicts language development

Objective Sex hormones testosterone and estradiol have been related to children’s language development. The shared precursor hormone, dehydroepiandrosterone (DHEA), however, has not yet been considered as a biological marker of language ability, despite emerging evidence that fetal DHEA plays a critical role in the organization of the neonatal brain. The present study investigated whether fetal DHEA, compared to fetal testosterone, is associated with infant language development.Design and methods DHEA and testosterone concentrations were measured in newborn hair strands (n = 56) collected two weeks after birth, capturing fetal long-term hormone secretions during the third trimester of pregnancy. At six months of age, children’s language abilities were assessed using the German version of the Bayley Scales of Infant Development.Results Linear regression analysis revealed fetal DHEA levels to be significantly associated with language abilities at six months of age, with lower DHEA levels corresponding to higher language scores. Control analyses assessing general cognitive abilities showed no association of fetal DHEA levels with infant cognitive function. Testosterone levels were not associated with language nor general cognitive skills.Conclusions The current study identifies fetal DHEA levels extracted from newborn hair samples as a potential biological factor influencing infant language development