Browsing by Subject "Galactose"

Now showing 1 - 6 of 6
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    Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast.
    (Mol Cell Biol, 2015-11) Rienzo, Alessandro; Poveda-Huertes, Daniel; Aydin, Selcan; Buchler, Nicolas E; Pascual-Ahuir, Amparo; Proft, Markus
    Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.
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    Improving the rates of Aspergillus detection: an update on current diagnostic strategies.
    (Expert review of anti-infective therapy, 2019-01) Jenks, Jeffrey D; Salzer, Helmut JF; Hoenigl, Martin

    Introduction

    The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches.
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    Point-of-care diagnosis of invasive aspergillosis in non-neutropenic patients: Aspergillus Galactomannan Lateral Flow Assay versus Aspergillus-specific Lateral Flow Device test in bronchoalveolar lavage.
    (Mycoses, 2019-03) Jenks, Jeffrey D; Mehta, Sanjay R; Taplitz, Randy; Aslam, Saima; Reed, Sharon L; Hoenigl, Martin

    Background

    We compared new Aspergillus Galactomannan Lateral Flow Assay with the newly formatted Aspergillus-specific Lateral Flow device tests for the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients.

    Methods

    We performed both tests in 82 bronchoalveolar lavage fluid samples from 82 patients at risk for IPA but without underlying haematologic malignancy. Samples were collected between September 2016 and September 2018 at the University of California San Diego, United States. IPA was classified following two published consensus criteria.

    Results

    Classification of cases varied widely between the two consensus criteria. When using criteria established for the intensive care unit, 26/82 patients (32%) met criteria for proven or putative IPA. Both point-of-care assays showed sensitivities ranging between 58% and 69%, with specificities between 68% and 75%. Sensitivity increased up to 81% when both tests were combined.

    Conclusion

    The study outlines the need for updated, unified and more broadly applicable consensus definitions for classifying IPA in non-neutropenic patients, a work that is currently in progress. Both point-of-care tests showed comparable performance, with sensitivities and specificities in the 60%-70% range when used alone and increasing to 80% when used in combination. The new point-of-care tests may serve a role at the bedside in those with clinical suspicion of IPA.
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    Serum Lateral Flow assay with digital reader for the diagnosis of invasive pulmonary aspergillosis: A two-centre mixed cohort study.
    (Mycoses, 2021-10) Hoenigl, Martin; Egger, Matthias; Boyer, Johannes; Schulz, Eduard; Prattes, Juergen; Jenks, Jeffrey D

    Background

    Detection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non-neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients.

    Methods

    We performed a retrospective two-centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same-sample GM was calculated using Spearman correlation analysis and kappa statistics.

    Results

    In total, 122 serum samples from 122 patients were analysed, including proven IA (n = 1), probable IA or coronavirus-associated pulmonary aspergillosis (CAPA) (n = 27), and no IA/CAPA/non-classifiable (n = 94). At a 0.5 ODI cut-off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p < .0001). Kappa was 0.611 when both LFA and GM were used with a 0.5 ODI cut-off, showing substantial agreement (p < .001).

    Discussion

    The LFA with digital read out from serum showed good performance for the diagnosis of probable/proven aspergillosis, with substantial agreement to GM from serum. Like the LFA from BALF, the LFA from serum may serve as a more rapid test compared to conventional GM, particularly in settings where GM is not readily available.
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    Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.
    (Frontiers in immunology, 2019-01) Rawlings, Stephen A; Heldt, Sven; Prattes, Juergen; Eigl, Susanne; Jenks, Jeffrey D; Flick, Holger; Rabensteiner, Jasmin; Prüller, Florian; Wölfler, Albert; Neumeister, Peter; Strohmaier, Heimo; Krause, Robert; Hoenigl, Martin
    Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.