217 research outputs found

    Ethnicity associated microbial and metabonomic profiling in newly diagnosed ulcerative colitis

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    Introduction: Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues. Methods: Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy. Results: We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for Ruminococcus) and 4-cresol sulfate (Clostridia) (p<0.001) with higher concentrations of lactate (negative correlation for Bifidobacteriaceae). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians (p=0.02 and p=0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile. Conclusion: Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response

    IMMUNE RESPONSE IN MALIGNANT GLIOMA

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    Objective: Malignant gliomas are primary brain tumors with excessive mortality and high resistance to chemotherapy and radiotherapy. The survival time for glioblastoma multi­forme is about 6-12 months. As key pathogenetic mechanisms are recognized the massive necrosis, angiogenesis and hypoxia within the tumor, as well as the resistance to apoptosis. It is also suspected that altered immune response might contribute to the fatal clinical outcome.The aim of the present study was to determine the immune status of patients with malignant gliomas.Material and methods: Peripheral blood lymphocytes were collected preoperatively from 9 patients (aged 57-76) diagnosed as anaplastic astrocytoma grade III (n=4) and glioblastoma multiforme (n=5). The following lymphocyte populations were analyzed by flow cytometry: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+, CD3+CD56+, CD3+CD25+, CD8-CD11b+, CD8+CD11b+, CD8+CD11b-. The results obtained were compared to reference values for each cell population.Results: No significant alterations were detected in CD19+, CD3+, CD3+CD4+, CD3+CD8+ cells, but the CD4/CD8 ratio was below the reference range in some cases. No obvious decrease in (CD3-CD56+) NK cells and (CD3-CD56+) NKT cells was observed in most patients. A reproducible phenomenon of increased CD8+CD11b+ and decreased CD8+CD11b- cells was noticed. These preliminary results suggest that the immune response in patients with malignant glioma is seriously disregulated. The rapid clinical deterioration, relapses and high mortality could be at least partially explained with the suppressed activity of NK-cells which are the major cytotoxic antitumoral cells. The increase in the population of activated suppressor-effector cells also contributes to the unfavourable outcome in malignant brain tumors.Conclusion: This pilot study reveals the presence of altered immune response in malignant gliomas and opens possibilities for prospective investigations concerning immune status and clinical outcome

    Volatile Content of 4-Vesta: Evidence from Unequilibrated Eucrites

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    Eucrites are a class of basaltic meteorites that, along with the howardites and diogenites, likely derive from the asteroid 4-Vesta. This asteroid is depleted in moderately volatile elements relative to the Earth and carbonaceous chondrites. Extrapolation of this depletion trend predicts that bulk silicate 4-Vesta (BSV) contains at most 250-1000 g/g H2O, which is approximately a factor of two lower than the H2O content of Earth. To obtain more accurate H2O and F estimates for BSV, we examined four unequilibrated antarctic meteorites, Yamato(Y)-793548, Y-82210, Y-75011, and Y-74450, by EPMA and SIMS. Pyroxenes contain MgO-rich cores and FeO-rich rims, consistent with primary magmatic zoning. Volatile concentrations generally follow patterns expected for growth zoning with lower values in the cores and higher in the rims. These features indicate that thermal metamorphism and other post-crystallization processes did not significantly perturb the volatile contents of these unequilibrated eucrite pyroxenes. We used these data to derive best estimates for the BSV H2O and F content based on experimentally determined pyroxene-melt partition coefficients and models for magma generation on Vesta. In addition, we measured D/H in the early crystallizing pyroxenes and late crystallzing apatites. We find that the D/H of pyroxene and apatite are within error of one another as well as previous measurements of apatite in equilibrated eucrites. These results imply that degassing was minimal or did not fractionate D/H. Degassing may have been limited if eucrites were shallowly emplaced sills or dykes, or the total H2O content of the magmas was too low for vapor saturation. An alternative mechanism for limited D/H fractionation is that degassing did occur, but the H2/H2O of the exsolved vapor was approximately 15:85, as predicted from experiments

    Terrestrial exposure of a fresh Martian meteorite causes rapid changes in hydrogen isotopes and water concentrations

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    Determining the hydrogen isotopic compositions and H2O contents of meteorites and their components is important for addressing key cosmochemical questions about the abundance and source(s) of water in planetary bodies. However, deconvolving the effects of terrestrial contamination from the indigenous hydrogen isotopic compositions of these extraterrestrial materials is not trivial, because chondrites and some achondrites show only small deviations from terrestrial values such that even minor contamination can mask the indigenous values. Here we assess the effects of terrestrial weathering and contamination on the hydrogen isotope ratios and H2O contents of meteoritic minerals through monitored terrestrial weathering of Tissint, a recent Martian fall. Our findings reveal the rapidity with which this weathering affects nominally anhydrous phases in extraterrestrial materials, which illustrates the necessity of sampling the interiors of even relatively fresh meteorite falls and underlines the importance of sample return missions

    Introduction of Macromolecules into Bovine Adrenal Medullary Chromaffin Cells and Rat Pheochromocytoma Cells (PC12) by Permeabilization with Streptolysin O: Inhibitory Effect of Tetanus Toxin on Catecholamine Secretion

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    Conditions are described for controlled plasma membrane permeabilization of rat pheochromocytoma cells (PC12) and cultured bovine adrenal chromaffin cells by Streptolysin O (SLO). The transmembrane pores created by SLO invoke rapid efflux of intracellular 86Rb+ and ATP, and also permit passive diffusion of proteins, including immunoglobulins, into the cells. SLO-permeabilized PC12 cells release [3H]dopamine in response to micromolar concentrations of free Ca2+. Permeabilized adrenal chromaffin cells present a similar exocytotic response to Ca2+ in the presence of Mg2+/ ATP. Permeabilized PC12 cells accumulate antibodies against synaptophysin and calmodulin, but neither antibody reduces the Ca2+-dependent secretory response. Reduced tetanus toxin, although ineffective when applied to intact chromaffin cells, inhibits Ca2+-induced exocytosis by both types of permeabilized cells studied. Omission of dithiothreitol, toxin inactivation by boiling, or preincubation with neutralizing antibodies abolishes the inhibitory effect. The data indicate that plasma membrane permeabilization by Streptolysin O is a useful tool to probe and define cellular components that are involved in the final steps of exocytosis

    Width of the Δ\Delta resonance in nuclei

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    In this work we evaluate the imaginary part of the isobar Δ\Delta self-energy ΣΔ\Sigma_{\Delta} from the two-body absorption process Δ+N2N\Delta+N\rightarrow 2N. This contribution is calculated using a recently developed non-relativistic scheme, which allows for an evaluation of the self-energy with a basis of single-particle states appropriate for both bound hole states and for particle states in the continuum. In order to test the medium dependence of the self-energy, we calculate the two-body absorption term ΣΔA2\Sigma_{\Delta}^{A2} for several finite nuclei with N=ZN=Z, i.e.\ 16^{16}O, 40^{40}Ca and 100^{100}Sn. The resulting self-energy, which is energy dependent and non-local, is compared with a simple parameterization derived from nuclear matter.Comment: 5 pages 3 figures can be obtained from the authors, TU-93-160

    Persistence survey of Toxic Shock Syndrome toxin-1 producing Staphylococcus aureus and serum antibodies to this superantigen in five groups of menstruating women

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    Background: Menstrual Toxic Shock Syndrome (mTSS) is thought to be associated with the vaginal colonization with specific strains of Staphylococcus aureus TSST-1 in women who lack sufficient antibody titers to this toxin. There are no published studies that examine the seroconversion in women with various colonization patterns of this organism. Thus, the aim of this study was to evaluate the persistence of Staphylococcus aureus colonization at three body sites (vagina, nares, and anus) and serum antibody to toxic shock syndrome toxin-producing Staphylococcus aureus among a small group of healthy, menstruating women evaluated previously in a larger study. Methods: One year after the completion of that study, 311 subjects were recalled into 5 groups. Four samples were obtained from each participant at several visits over an additional 6-11 month period: 1) an anterior nares swab; 2) an anal swab; 3) a vagina swab; and 4) a blood sample. Gram stain, a catalase test, and a rapid S. aureus-specific latex agglutination test were performed to phenotypically identify S. aureus from sample swabs. A competitive ELISA was used to quantify TSST-1 production. Human TSST-1 IgG antibodies were determined from the blood samples using a sandwich ELISA method. Results: We found only 41% of toxigenic S. aureus and 35.5% of non-toxigenic nasal carriage could be classified as persistent. None of the toxigenic S. aureus vaginal or anal carriage could be classified as persistent. Despite the low persistence of S. aureus colonization, subjects colonized with a toxigenic strain were found to display distributions of antibody titers skewed toward higher titers than other subjects. Seven percent (5/75) of subjects became seropositive during recall, but none experienced toxic shock syndrome-like symptoms. Conclusions: Nasal carriage of S. aureus appears to be persistent and the best predicator of subsequent colonization, whereas vaginal and anal carriage appear to be more transient. From these findings, it appears that antibody titers in women found to be colonized with toxigenic S. aureus remained skewed toward higher titers whether or not the colonies were found to be persistent or transient in nature. This suggests that colonization at some point in time is sufficient to elevate antibody titer levels and those levels appear to be persistent. Results also indicate that women can become seropositive without experiencing signs or symptoms of toxic shock syndrome
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