PubMed Health⌕ Search

Biomedical subjects

Thomas Jung

Publications and source records attributed to Thomas Jung.

12 recordsLinked to original sources

Adsorption and dynamics of long-range interacting fullerenes in a flexible, two-dimensional, nanoporous porphyrin network.

Herein, a detailed investigation of the adsorption and dynamics of C60 and C70 fullerenes hosted in a self-assembled, two-dimensional, nanoporous porphyrin network on a solid Ag surface is presented. Time-resolved scanning tunneling microscopy (STM) studies of these supramolecular systems at the molecular scale reveal distinct host-guest interactions giving rise to a pronounced dissimilar mobility of the two fullerenes within the porphyrin network. Furthermore, long-range coverage-dependent interactions between the all-carbon guests, which clearly affect their mobility and are likely mediated by a complex mechanism involving the Ag substrate and the flexible porphyrin host network, are observed. At increased fullerene coverage, this unprecedented interplay results in the formation of large fullerene chains and islands. By applying a lattice gas model with nearest-neighbor interactions and by evaluating the fullerene-pair distribution functions, the respective coverage-dependent guest-guest interaction energies are estimated.

Journal Article↗

Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line.

In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1muM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified.

Apoptosis↗

Developing quantitative, multiscale models for microgravity crystal growth.

Crystal growth conducted under microgravity conditions has had a profound impact on improving our understanding of melt crystal growth processes. Here, we present a brief history of microgravity crystal growth and discuss the development of appropriate models to interpret and optimize these growth experiments. The need for increased model realism and predictive capability demands new approaches for describing phenomena important at several disparate length scales. Of special importance is the ability to represent three-dimensional and transient continuum transport (flows, heat, and mass transfer), phase-change phenomena (thermodynamics and kinetics), and system design (such as furnace heat transfer during melt growth). An overview of mathematical models and numerical algorithms employed to represent such multiscale effects is presented.

Journal Article↗

Impact of influenza treatment with oseltamivir on health, sleep and daily activities of otherwise healthy adults and adolescents.

OBJECTIVE: To determine the effect of oseltamivir (75mg twice daily) on time to return to baseline health, sleep and activity in patients with laboratory-confirmed influenza infection. PATIENTS AND METHODS: Data from 1642 otherwise healthy adults (aged 13-64 years), who had experienced a febrile influenza-like illness (>38 degrees C) of up to 36 hours' duration together with at least one respiratory and one systemic/constitutional symptom, were pooled from four randomised, double-blind, placebo-controlled clinical trials. Patients in these trials had been randomised to receive either oseltamivir or placebo for 5 days and had been allowed unlimited use of symptom-relief medications. The primary analysis examined the effect of oseltamivir treatment on patients' general health status, sleep and normal activities as measured by visual analogue scales. Secondary analyses examined the possible effects of gender, influenza type, smoking, employment status and time to treatment (< or = or >24 hours) on these endpoints. RESULTS: Oseltamivir significantly reduced the time taken to return to baseline health, sleep and activity across all pooled patients (p < 0.0001) and increased the proportion of patients returning to full activity within the first 7 days following treatment start. Gender, smoking status, time to treatment, influenza subtype and employment status had no appreciable effect on the effectiveness of oseltamivir. CONCLUSIONS: In otherwise healthy adults, oseltamivir reduces the time to return to pre-illness levels of health, sleep and activity, and may help to decrease the overall burden of influenza on society. This provides an important rationale for the early use of antiviral treatment, such as oseltamivir, for the treatment of influenza in otherwise healthy adults and adolescents.

Activities of Daily Living↗

CD45 isoform expression is associated with different susceptibilities of human naive and effector CD4+ T cells to respond to IL-4.

Interleukin-4 (IL-4) is the major factor promoting the development of T helper type 2 (Th2) cells from naive precursor T cells. Minute amounts of IL-4 produced by naive T cells seem to be sufficient; however, the molecular mechanisms explaining this efficient utilization of IL-4 are not yet known. Here, we show that human CD4+ CD45RA+ naive T cells, in contrast to CD4+ CD45R0+ effector T cells, show responsiveness to endogenous as well as exogenous IL-4 to proliferate and differentiate towards Th2 cells in vitro. Despite production levels of IL-4 below conventional detection limits, CD45RA+ T cell-derived IL-4 could clearly activate STAT6. Although the expression levels of IL-4R and STAT6 were not different between naive and effector T cells, only naive T cells responded to IL-4 in a STAT6-dependent reporter gene assay. Transfecting a trans-dominant negative form of STAT6 abrogated IL-4-induced proliferation in CD45RA+ cells. A significantly higher protein tyrosine phosphatase (PTPase) activity was detected in CD45R0+ T cells as compared to CD45RA+ T cells. Cross-linking CD45 potently reduced PTPase activity in CD45R0+ T cells and restored their ability to proliferate in response to IL-4. Thus, CD45 PTPase activity contributes to the susceptibility of naive and memory T cells to respond to IL-4.

CD4 Antigens↗

Deficient translocation of c-Rel is associated with impaired Th1 cytokine production in T cells from atopic dermatitis patients.

Decreased production of T helper type 1 (Th1) cytokines, such as interferon-gamma (IFN-gamma) or interleukin-2 (IL-2), is a hallmark of atopic diseases. While accessory signals from antigen-presenting cells may be missing, T cells themselves may be suppressed in their ability to produce substantial amounts of Th1 cytokines. We show, in this study, that T cell receptor (TCR)-activated T cells from atopic dermatitis (AD) patients proliferate less than control T cells and produce lower amounts of IFN-gamma and IL-2, but comparable amounts of IL-4. Because mice lacking the nuclear factor kappa B (NF-kappaB) transcription factors - p65 or c-Rel - show reduced Th1, but undisturbed Th2 responses, we investigated the role of c-Rel and p65 for Th1 cytokine production in T cells from healthy and severe AD patients. TCR-activated primary T cells from healthy donors treated with c-Rel antisense oligonucleotides produced lower levels of IL-2 and IFN-gamma and proliferated less efficiently than the corresponding control T cells. Moreover, transfection of primary T cells with c-Rel or p65 enhanced proliferation and production of IL-2 and IFN-gamma. Nuclear extracts of activated primary T cells from AD donors bound weakly to NF-kappaB-specific oligonucleotides, compared to extracts from healthy control T cells. Western blotting studies revealed that nuclear, but not cytosolic, extracts from T cells of AD patients lacked significant amounts of c-Rel and p65. T cell clones derived from AD patients failed to sufficiently translocate c-Rel and p65 into the nucleus following activation. Thus, impaired nuclear translocation of c-Rel and p65 may determine an impaired Th1 cytokine response in AD.

Active Transport, Cell Nucleus↗

Interleukin 10 regulates cell surface and soluble LIR-2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro.

Dendritic cells (DC) are unique in their ability to stimulate naive T cells to proliferate and to differentiate into effector T cells. DC, however, can also inhibit T cell activation and play a role in central and peripheral tolerance. IL-10 has been shown to render DC tolerogenic by unknown mechanisms. Using a combined monoclonal antibody/retroviral expression cloning approach, we show here that the inhibitory receptor LIR-2 (leukocyte immunoglobulin-like receptor-2, CD85d) is specifically up-regulated by IL-10 on maturing human DC. LPS-stimulated, LIR-2-transfected DC inhibited the proliferation of T cells in autologous, as well as allogeneic culture systems in vitro. In addition, overexpression of LIR-2 on resting T cells, which lack LIR-2 expression, inhibited T cell proliferation induced by TCR activation. A novel soluble form of LIR-2 was detected in culture supernatants of maturing DC. IL-10 treatment of DC potently inhibited the production of soluble LIR-2. Recombinant soluble LIR-2 was able to completely restore the proliferation of T cells activated with LPS-plus IL-10-treated DC. Thus, IL-10 renders DC hypostimulatory by up-regulating cell surface LIR-2 and by inhibiting soluble LIR-2 in vitro.

Animals↗

Phytophthora alni sp. nov. and its variants: designation of emerging heteroploid hybrid pathogens spreading on Alnus trees.

In 1993 a destructive new Phytophthora pathogen of riparian Alnus trees was discovered in the UK and subsequently shown to be present in other parts of Europe. The new Phytophthora comprised a group of emergent heteroploid hybrids, probably between P. cambivora and a species related to P. fragariae. These included a common, near tetraploid standard hybrid, the presumptive allopolyploid; and four scarcer major variant types with chromosome numbers intermediate between diploid and tetraploid, named the Swedish, Dutch, German and UK variants. The standard hybrid type is formally designated here as Phytophthora alni subsp. alni. The Swedish variant is designated as P. alni subsp. uniformis; and the Dutch, German and UK variants collectively as P. alni subsp. multiformis. The properties of the Dutch, German and UK variants within subsp. multiformis are informally described. The problems of designating emergent species hybrids under the International Code of Botanical Nomenclature and the reasons for the taxonomic choices made are discussed.

Alnus↗

Phytophthora pseudosyringae sp. nov., a new species causing root and collar rot of deciduous tree species in Europe.

In several studies of oak decline in Europe, a semi-papillate homothallic Phytophthora taxon was consistently isolated, together with other Phytophthora species, from rhizosphere soil samples. It was also found associated with necrotic fine roots and stem necroses of Fagus sylvatica and Alnus glutinosa. Due to morphological and physiological similarities, the semi-papillate isolates were previously identified as P. syringae by various authors. The morphology, physiology and pathogenicity against fine roots of Quercus robur, Q. petraea and F. sylvatica, bark of A. glutinosa, leaves of Ilex aquifolium and apple fruits of this Phytophthora species are described and compared with those of related and similar Phytophthora species, namely P. ilicis, P. psychrophila, P. quercina, P. citricola and P. syringae. The phylogenetic placement on the basis of ITS and mtDNA sequence data was also examined. Isolates of this taxon produce colonies with stellate to rosaceous growth patterns and limited aerial mycelium on various agar media. Antheridia are predominantly paragynous. In water culture catenulate hyphal swellings and semi-papillate caducous sporangia, that are usually limoniform, ellipsoid or ovoid, are formed abundandly, mostly in lax or dense sympodia. This taxon is a moderately slow growing, low temperature species with optimum and maximum temperatures around 20 and 25 degrees C, respectively. Tested isolates are moderately aggressive to fine roots of oaks and beech, highly aggressive to holly leaves and apple fruits, and slightly pathogenic to alder bark. Thirteen tested isolates had an identical and distinct ITS sequence which was more similar to that of P. ilicis and P. psychrophila than any other known taxa. On the basis of their unique combination of morphological characters, colony growth patterns, cardinal temperatures for growth, growth rates, pathogenicity to oaks, beech, alder, apple and holly, their host range, and ITS and mtDNA sequences the semi-papillate caducous Phytophthora isolates from oaks, beech and alder are clearly separated from related and similar Phytophthora spp., and described as a new species, P. pseudosyringae sp. nov.

Alnus↗

Expansion and proliferation of skin-homing T cells in atopic dermatitis as assessed at the single cell level.

BACKGROUND: Sensitization to aeroallergens is a frequent event in patients with atopic dermatitis (AD). The role of allergen-specific T cells in the pathogenesis of AD is, however, not fully clear. A detailed immunological characterization of allergen-specific T cells able to migrate to inflamed skin might therefore be helpful in determining the relevance of allergen-specific T cells to clinical symptoms. OBJECTIVE: To establish a simple assay to simultaneously monitor the expression of skin-related homing molecules and their proliferative response to an allergen on peripheral T cells. To evaluate whether this assay is able to identify AD patients in whom exposure to an allergen induces dermatitis. METHODS: The expression of CLA, CD7 and CD4 was simultaneously measured by flow cytometry with the DNA content as a parameter of proliferation at the single cell level. House dust mite antigen (DerP) and tetanus toxoid (TT) were used as antigens. RESULTS: CD4+ CLA+ CD7-, but not CLA- T cells from patients with AD proliferated and expanded following DerP stimulation. In contrast, TT stimulation resulted in proliferation of both, CLA+ and CLA- T cells from both, atopic and healthy donors. CONCLUSIONS: Single cell analysis revealed a predominant localization of allergen-reactive T cells within the CD7- CLA+ CD4+ T cell subset in AD. Thus, this simple assay not only confirms previously published results, but also extends our knowledge on the biology of CLA and CD7 cells in AD. Ultimately, this will be helpful in classifying those patients who might benefit from allergen avoidance therapies.

Adult↗

IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses.

IL-10 is a potent inhibitor of T-cell activation and has tolerizing effects on these cells. These effects are primarily mediated via modulation of antigen presenting cell function. Here, it is demonstrated that IL-10 completely inhibits LPS-induced DC maturation, resulting in altered DC-T-cell interactions and reduced T-cell responses. IL-10 inhibited LPS-induced upregulation of costimulatory molecules, MHC Class II, and the secretion of IL-12, TNF-alpha, IL-6, and IL-1beta by DCs, although it upregulated the SLAM (CD150) expression at both the mRNA and protein levels. IL-10 pre-treated DC did not respond to subsequent LPS activation and its stimulatory ability for allogeneic and antigen-specific T-cells was severely impaired. Importantly, T-cells derived from co-cultures with Ag-pulsed, IL-10-treated DC were impaired in their responses to subsequent Ag-specific restimulation. Transwell and DC-derived plasma membrane experiments indicated that the capacity of IL-10-treated DC to induce T-cell unresponsiveness results from alterations in the cell surface molecules rather than modulation of cytokine secretion.

Animals↗