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Showing papers by "University of Düsseldorf published in 2004"


Journal ArticleDOI
TL;DR: A psychometrically well-justified measure of work-related stress (ERI) grounded in sociological theory is available for comparative socioepidemiologic investigations in advanced societies within and beyond Europe.

1,921 citations


Journal ArticleDOI
TL;DR: Genome sequences reveal that a deluge of DNA from organelle DNA has constantly been bombarding the nucleus since the origin of organelles, abolished organelle autonomy and increased nuclear complexity.
Abstract: Genome sequences reveal that a deluge of DNA from organelles has constantly been bombarding the nucleus since the origin of organelles. Recent experiments have shown that DNA is transferred from organelles to the nucleus at frequencies that were previously unimaginable. Endosymbiotic gene transfer is a ubiquitous, continuing and natural process that pervades nuclear DNA dynamics. This relentless influx of organelle DNA has abolished organelle autonomy and increased nuclear complexity.

1,324 citations


Journal ArticleDOI
TL;DR: TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.
Abstract: Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience

1,141 citations


Journal ArticleDOI
TL;DR: A new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described, which grows adherently and can be expanded to 1015 cells without losing pluripotency.
Abstract: Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 1015 cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.

1,075 citations


Journal ArticleDOI
30 Jul 2004-Science
TL;DR: The results provide compelling evidence that prions are infectious proteins and suggest that a novel prion strain was created.
Abstract: Recombinant mouse prion protein (recMoPrP) produced in Escherichia coli was polymerized into amyloid fibrils that represent a subset of beta sheet-rich structures. Fibrils consisting of recMoPrP(89-230) were inoculated intracerebrally into transgenic (Tg) mice expressing MoPrP(89-231). The mice developed neurologic dysfunction between 380 and 660 days after inoculation. Brain extracts showed protease-resistant PrP by Western blotting; these extracts transmitted disease to wild-type FVB mice and Tg mice overexpressing PrP, with incubation times of 150 and 90 days, respectively. Neuropathological findings suggest that a novel prion strain was created. Our results provide compelling evidence that prions are infectious proteins.

1,003 citations


Journal ArticleDOI
22 Apr 2004-Neuron
TL;DR: The results showed that the basic circuit underlying imitation learning consists of the inferior parietal lobule and the posterior part of the superior frontal gyrus plus the adjacent premotor cortex (mirror neuron circuit), plus structures involved in motor preparation (dorsal prem motor cortex, superior parietal lobe, rostral mesial areas).

877 citations


Journal ArticleDOI
TL;DR: Genetic analysis of the wMel genome further supports the hypothesis that mitochondria share a common ancestor with the α-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales.
Abstract: The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the alpha-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for the host, the wMel-D. melanogaster symbiosis is now an ideal system for studying the biology and evolution of Wolbachia infections.

820 citations


Journal ArticleDOI
TL;DR: This analysis suggests the hypothesis that brain networks maximize both the number and the diversity of functional motifs, while the repertoire of structural motifs remains small, and obtains network topologies that resemble real brain networks across a broad spectrum of structural measures, including small-world attributes.
Abstract: Complex brains have evolved a highly efficient network architecture whose structural connectivity is capable of generating a large repertoire of functional states. We detect characteristic network building blocks (structural and functional motifs) in neuroanatomical data sets and identify a small set of structural motifs that occur in significantly increased numbers. Our analysis suggests the hypothesis that brain networks maximize both the number and the diversity of functional motifs, while the repertoire of structural motifs remains small. Using functional motif number as a cost function in an optimization algorithm, we obtain network topologies that resemble real brain networks across a broad spectrum of structural measures, including small-world attributes. These results are consistent with the hypothesis that highly evolved neural architectures are organized to maximize functional repertoires and to support highly efficient integration of information.

793 citations


Journal ArticleDOI
TL;DR: The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age, resulting in similar ACTH responses in elderly men and women, as well as a greater adrenal cortex sensitivity to ACTH signals in young females.

789 citations


Journal ArticleDOI
TL;DR: HDL is identified as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P3-mediated NO release and induces vasodilation in isolated aortae via intracellular Ca2+ mobilization and Akt-mediated eNOS phosphorylation.
Abstract: HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P3 (also known as LPB3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P3-deficient mice, Akt phosphorylation and Ca2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P3-mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.

667 citations


Journal ArticleDOI
TL;DR: A comprehensive update of the diagnostic and therapeutic approaches focusing on endocrine and radiological features as well as surgical options for clinically inapparent adrenal masses is provided.
Abstract: Clinically inapparent adrenal masses are incidentally detected after imaging studies conducted for reasons other than the evaluation of the adrenal glands. They have frequently been referred to as adrenal incidentalomas. In preparation for a National Institutes of Health State-of-the-Science Conference on this topic, extensive literature research, including Medline, BIOSIS, and Embase between 1966 and July 2002, as well as references of published metaanalyses and selected review articles identified more than 5400 citations. Based on 699 articles that were retrieved for further examination, we provide a comprehensive update of the diagnostic and therapeutic approaches focusing on endocrine and radiological features as well as surgical options. In addition, we present recent developments in the discovery of tumor markers, endocrine testing for subclinical disease including autonomous glucocorticoid hypersecretion and silent pheochromocytoma, novel imaging techniques, and minimally invasive surgery. Based on the statements of the conference, the available literature, and ongoing studies, our aim is to provide practical recommendations for the management of this common entity and to highlight areas for future studies and research.

Journal ArticleDOI
TL;DR: This article shows that all of these divergence-time estimates were generated through improper methodology on the basis of a single calibration point that has been unjustly denuded of error.

Journal ArticleDOI
TL;DR: The influence of oxidative stress on protein turnover, protein aggregate formation and the various interactions of protein aggregates with the proteasome are focused on.

Journal ArticleDOI
TL;DR: An analysis of over 1,100 of the ∼10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa reveals potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.
Abstract: We present an analysis of over 1,100 of the approximately 10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa. Seven major areas of Neurospora genomics and biology are covered. First, the basic features of the genome, including the automated assembly, gene calls, and global gene analyses are summarized. The second section covers components of the centromere and kinetochore complexes, chromatin assembly and modification, and transcription and translation initiation factors. The third area discusses genome defense mechanisms, including repeat induced point mutation, quelling and meiotic silencing, and DNA repair and recombination. In the fourth section, topics relevant to metabolism and transport include extracellular digestion; membrane transporters; aspects of carbon, sulfur, nitrogen, and lipid metabolism; the mitochondrion and energy metabolism; the proteasome; and protein glycosylation, secretion, and endocytosis. Environmental sensing is the focus of the fifth section with a treatment of two-component systems; GTP-binding proteins; mitogen-activated protein, p21-activated, and germinal center kinases; calcium signaling; protein phosphatases; photobiology; circadian rhythms; and heat shock and stress responses. The sixth area of analysis is growth and development; it encompasses cell wall synthesis, proteins important for hyphal polarity, cytoskeletal components, the cyclin/cyclin-dependent kinase machinery, macroconidiation, meiosis, and the sexual cycle. The seventh section covers topics relevant to animal and plant pathogenesis and human disease. The results demonstrate that a large proportion of Neurospora genes do not have homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The group of unshared genes includes potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.

Journal ArticleDOI
TL;DR: It is demonstrated that a beam of x-ray radiation can be generated by simply focusing a single high-intensity laser pulse into a gas jet, which has keV energy and lies within a narrow cone angle.
Abstract: We demonstrate that a beam of x-ray radiation can be generated by simply focusing a single high-intensity laser pulse into a gas jet. A millimeter-scale laser-produced plasma creates, accelerates, and wiggles an ultrashort and relativistic electron bunch. As they propagate in the ion channel produced in the wake of the laser pulse, the accelerated electrons undergo betatron oscillations, generating a femtosecond pulse of synchrotron radiation, which has keV energy and lies within a narrow (50 mrad) cone angle.

Journal ArticleDOI
TL;DR: This work hypothesized that the network communicates by means of neural phase synchronization, and used magnetoencephalography to study transient long-range interarea phase coupling in a well studied attentionally taxing dual-target task (attentional blink).
Abstract: Because of attentional limitations, the human visual system can process for awareness and response only a fraction of the input received. Lesion and functional imaging studies have identified frontal, temporal, and parietal areas as playing a major role in the attentional control of visual processing, but very little is known about how these areas interact to form a dynamic attentional network. We hypothesized that the network communicates by means of neural phase synchronization, and we used magnetoencephalography to study transient long-range interarea phase coupling in a well studied attentionally taxing dual-target task (attentional blink). Our results reveal that communication within the fronto-parieto-temporal attentional network proceeds via transient long-range phase synchronization in the beta band. Changes in synchronization reflect changes in the attentional demands of the task and are directly related to behavioral performance. Thus, we show how attentional limitations arise from the way in which the subsystems of the attentional network interact.

Journal ArticleDOI
TL;DR: Since most of the proposed molecular mechanisms underlying particle‐related carcinogenesis have been derived from in vitro studies, there is a need for future studies that evaluate the implication of these mechanisms for in vivo lung cancer development and transgenic and gene knockout animal models may provide a useful tool.
Abstract: Both occupational and environmental exposure to particles is associated with an increased risk of lung cancer. Particles are thought to impact on genotoxicity as well as on cell proliferation via their ability to generate oxidants such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). For mechanistic purposes, one should discriminate between a) the oxidant-generating properties of particles themselves (i.e., acellular), which are mostly determined by the physicochemical characteristics of the particle surface, and b) the ability of particles to stimulate cellular oxidant generation. Cellular ROS/RNS can be generated by various mechanisms, including particle-related mitochondrial activation or NAD(P)H-oxidase enzymes. In addition, since particles can induce an inflammatory response, a further subdivision needs to be made between primary (i.e., particle-driven) and secondary (i.e., inflammation-driven) formation of oxidants. Particles may also affect genotoxicity by their ability to carry surface-adsorbed carcinogenic components into the lung. Each of these pathways can impact on genotoxicity and proliferation, as well as on feedback mechanisms involving DNA repair or apoptosis. Although abundant evidence suggests that ROS/RNS mediate particle-induced genotoxicity and mutagenesis, little information is available towards the subsequent steps leading to neoplastic changes. Additionally, since most of the proposed molecular mechanisms underlying particle-related carcinogenesis have been derived from in vitro studies, there is a need for future studies that evaluate the implication of these mechanisms for in vivo lung cancer development. In this respect, transgenic and gene knockout animal models may provide a useful tool. Such studies should also include further assessment of the relative contributions of primary (inflammation-independent) and secondary (inflammation-driven) pathways.

Journal ArticleDOI
TL;DR: It is concluded that comparable HPA axis and heart rate stress responses to psychosocial stress can be measured in the morning and afternoon and the finding that the TSST-induced mood change was differentially affected by time of day requires further exploration.

Journal ArticleDOI
TL;DR: The case for the robust associations between measures of adverse psychosocial environment and ill health is advanced, as they are based on comparative studies across several European countries and as they combine different types of study designs.

Journal ArticleDOI
TL;DR: The objective is to determine the efficacy and safety of 600 mg of α‐lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy.
Abstract: Aims To determine the efficacy and safety of 600 mg of α-lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. Methods We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of α-lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using α-lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n = 1258 patients (α-lipoic acid n = 716; placebo n = 542) met these eligibility criteria and were included in a meta-analysis based on the intention-to-treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with α-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (≥ 50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS-LL), individual NIS-LL components, and the rates of adverse events. Results After 3 weeks the relative difference in favour of α-lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS-LL. The responder rates were 52.7% in patients treated with α-lipoic acid and 36.9% in those on placebo (P < 0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of α-lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of α-lipoic acid compared with placebo, while among the NIS-LL components pin-prick and touch-pressure sensation as well as ankle reflexes were improved in favour of α-lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. Conclusions The results of this meta-analysis provide evidence that treatment with α-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy. Diabet. Med. 21, 114–121 (2004)

Journal ArticleDOI
TL;DR: The results indicate that the cortisol awakening response occurs on both work and non-work days, but that anticipation of the working day is associated with an enhanced response.

Journal ArticleDOI
01 Jan 2004-Diabetes
TL;DR: C-peptide measurement is the most suitable primary outcome for clinical trials of therapies aimed at preserving or improving endogenous insulin secretion in type 1 diabetes patients, and available data demonstrate that even relatively modest treatment effects on C- peptide will result in clinically meaningful benefits.
Abstract: The underlying cause of type 1 diabetes, loss of β-cell function, has become the therapeutic target for a number of interventions in patients with type 1 diabetes. Even though insulin therapies continue to improve, it remains difficult to achieve normal glycemic control in type 1 diabetes, especially long term. The associated risks of hypoglycemia and end-organ diabetic complications remain. Retention of β-cell function in patients with type 1 diabetes is known to result in improved glycemic control and reduced hypoglycemia, retinopathy, and nephropathy. To facilitate the development of therapies aimed at altering the type 1 diabetes disease process, an American Diabetes Association workshop was convened to identify appropriate efficacy outcome measures in type 1 diabetes clinical trials. The following consensus emerged: While measurements of immune responses to islet cells are important in elucidating pathogenesis, none of these measures have directly correlated with the decline in endogenous insulin secretion. HbA1c is a highly valuable clinical measure of glycemic control, but it is an insensitive measure of β-cell function, particularly with the currently accepted standard of near-normal glycemic control. Rates of severe hypoglycemia and diabetic complications ultimately will be improved by therapies that are effective at preserving β-cell function but as primary outcomes require inordinately large and protracted trials. Endogenous insulin secretion is assessed best by measurement of C-peptide, which is cosecreted with insulin in a one-to-one molar ratio but unlike insulin experiences little first pass clearance by the liver. Measurement of C-peptide under standardized conditions provides a sensitive, well accepted, and clinically validated assessment of β-cell function. C-peptide measurement is the most suitable primary outcome for clinical trials of therapies aimed at preserving or improving endogenous insulin secretion in type 1 diabetes patients. Available data demonstrate that even relatively modest treatment effects on C-peptide will result in clinically meaningful benefits. The development of therapies for addressing this important unmet clinical need will be facilitated by trials that are carefully designed with β-cell function as determined by C-peptide measurement as the primary efficacy outcome.

Journal ArticleDOI
TL;DR: Future research on the importance of NO in ischemia/reperfusion injury will have to focus more precisely on the identification and standardization of potential confounding experimental factors that influence synthesis, transport, and interaction of NO with various targets in blood and tissue.
Abstract: Administration of nitric oxide (NO), NO donors or drugs that enhance NO release (statins, calcium antagonists, ACE-inhibitors, dexamethasone) prior to ischemia protects the myocardium against ischemia/reperfusion injury. While this exogenous administration of NO prior to ischemia can initiate a preconditioning-like phenomenon, endogenous NO-synthase (NOS)-derived NO is not involved in triggering or mediating the early phase of ischemic preconditioning's protection, but does play a pivotal role for initiating and mediating the delayed phase of ischemic preconditioning's protection. The present review now summarizes the importance of endogenous and exogenous NO when given at the time of reperfusion for vascular and myocardial function and morphological outcome following ischemia/reperfusion. Given the inconsistency of the published data, potential confounding factors that might affect experimental results on the role of NO in myocardial ischemia/reperfusion were identified, such as (1) the lack of characterization of the involved NOS isoforms in myocardial ischemia/reperfusion injury in different animal species, (2) the lack of direct measurements of myocardial NO concentration and/or NOS activity to assure sufficient NOS inhibition, (3) the lack of consideration of nonenzymatic NO production as a potential source of NO, and (4) the absence of plasma or blood components in in vitro studies influencing NO delivery and metabolism. Future research on the importance of NO in ischemia/reperfusion injury will have to focus more precisely on the identification and standardization of potential confounding experimental factors that influence synthesis, transport, and interaction of NO with various targets in blood and tissue.

Journal ArticleDOI
TL;DR: This paper tries to extrapolate findings and principles observed in inhalation toxicology into recommendations and methods for testing NP for nanocarrier purposes and recommends a closer interaction between both disciplines to gain insight in the role of NP size and properties and their mechanisms of acute and chronic interaction with biological systems.
Abstract: Nanoparticles (NP), here defined as particles with a diameter smaller then 100 nm, are increasingly used in different applications, including drug carrier systems and to pass organ barriers such as the blood-brain barrier. On the other hand, a large body of know-how is available regarding toxicological effects of nanoparticle (NP) after inhalation. More specifically, a number of effects of inhaled NP are attributed to their (i) direct effects on the central nervous system, (ii) their translocation from the lung into the bloodstream, and (iii) their capacity to invoke inflammatory responses in the lung with subsequent systemic effects. This paper gives a brief review on the toxicology of inhaled NP, including general principles and current paradigms to explain the special case of NP in pulmonary toxicology. Since the evidence for health risks of NP after inhalation has been increasing over the last decade, this paper tries to extrapolate these findings and principles observed in inhalation toxicology into recommendations and methods for testing NP for nanocarrier purposes. A large gap is present between research on NP in inhalation toxicology and in nanoscaled drug carrying. This review recommends a closer interaction between both disciplines to gain insight in the role of NP size and properties and their mechanisms of acute and chronic interaction with biological systems.

Journal ArticleDOI
TL;DR: The performance and fate of these human tumor antigen–specific T cells in vivo suggests that they might be of value for the treatment of EBV+ Hodgkin lymphoma.
Abstract: Epstein Barr virus (EBV)+ Hodgkin's disease (HD) expresses clearly identified tumor antigens derived from the virus and could, in principle, be a target for adoptive immunotherapy with viral antigen-specific T cells. However, like most tumor-associated antigens in immunocompetent hosts, these potential targets are only weakly immunogenic, consisting primarily of the latent membrane protein (LMP)1 and LMP2 antigens. Moreover, Hodgkin tumors possess a range of tumor evasion strategies. Therefore, the likely value of immunotherapy with EBV-specific cytotoxic effector cells has been questioned. We have now used a combination of gene marking, tetramer, and functional analyses to track the fate and assess the activity of EBV cytotoxic T lymphocyte (CTL) lines administered to 14 patients treated for relapsed EBV+ HD. Gene marking studies showed that infused effector cells could further expand by several logs in vivo, contribute to the memory pool (persisting up to 12 mo), and traffic to tumor sites. Tetramer and functional analyses showed that T cells reactive with the tumor-associated antigen LMP2 were present in the infused lines, expanded in peripheral blood after infusion, and also entered tumor. Viral load decreased, demonstrating the biologic activity of the infused CTLs. Clinically, EBV CTLs were well tolerated, could control type B symptoms (fever, night sweats, and weight loss), and had antitumor activity. After CTL infusion, five patients were in complete remission at up to 40 mo, two of whom had clearly measurable tumor at the time of treatment. One additional patient had a partial response, and five had stable disease. The performance and fate of these human tumor antigen-specific T cells in vivo suggests that they might be of value for the treatment of EBV+ Hodgkin lymphoma.

Journal ArticleDOI
TL;DR: In refugees with PTSD, hypocortisolism is associated with increased GC sensitivity of immunologic tissues, whether this pattern reflects an adaptive mechanism and whether this is sufficient to protect from detrimental effects of low cortisol remains to be investigated.

Journal ArticleDOI
TL;DR: It is suggested that primordial biochemistry was housed in an acetate-producing hydrothermal reactor that retained reduced carbon compounds produced within its naturally forming inorganic confines.

Journal ArticleDOI
TL;DR: Results from small-angle neutron scattering data confirm the theory and indicate that dendrimers are model systems of ultrasoft colloids that bridge the gap between polymers and hard spheres.
Abstract: A variety of experimental and theoretical approaches show that, akin to linear polymers, dendrimers in good solvent conditions are best described as flexible macromolecular aggregates with a dense core and fluctuating monomer groups We present theoretical and simulational evidence of how the shape and inner structure of dendrimers depends on the generation number as well as the effective interactions that exist between dendrimers in solution These approaches based on simplified dendritic structures show there is a tunable and ultrasoft interaction between the centers of the solublized dendrimers Results from small-angle neutron scattering data confirm the theory and indicate that dendrimers are model systems of ultrasoft colloids that bridge the gap between polymers and hard spheres Dendrimers can form a class of materials analogous to the related systems of star polymers and block copolymer micelles which exhibit special properties

Journal ArticleDOI
TL;DR: Although both areas participate in verbal fluency, they do so differentially, and area 44 is probably involved in high-level aspects of programming speech production per se, which opens new perspectives for analyzing the cortical networks involved in language.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the inflammogenic potential of coarse (2.5-10 microm) and fine (< 2.5microm) PM from both a rural and an industrial location in Germany, using bronchoalveolar lavage (BAL) of rat lungs 18 h post intratracheal instillation with PM.