53 research outputs found

    Quantification of Saquinavir from Lysates of Peripheral Blood Mononuclear Cells Using Microarrays and Standard MALDI-TOF-MS

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    Drug monitoring is usually performed by liquid chromatography coupled with optical detection or electrospray ionization mass spectrometry. More recently, matrix-assisted laser desorption/ionization (MALDI) in combination with triple quadrupole or Fourier-transform (FT) mass analyzers has also been reported to allow accurate quantification. Here, we present a strategy that employs standard MALDI time-of-flight (TOF) mass spectrometry (MS) for the sensitive and accurate quantification of saquinavir from an extract of blood peripheral mononuclear cells. Unambiguous identification of saquinavir in the mass spectra was possible because of using internal mass calibration and by an overall low chemical noise in the low mass range. Exact mass determination of the constant background peaks of the cell extract, which were used for recalibration, was performed by an initial MALDI-FT-MS analysis. Fast and multiplexed sample analysis was enabled by microarray technology, which provided 10 replicates in the lower nL range for each sample in parallel lanes on a chip. In order to validate the method, we employed various statistical tests, such as confidence intervals for linear regressions, three quality control samples, and inverse confidence limits of the estimated concentration ratios. Figure

    Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

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    Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1

    FEED INTAKE OF DAIRY COWS AS AN ECONOMIC SELECTION TRAIT

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    32 pairs of monozygons twins were fed ad lib. with a complete diet feed during the first 20 weeks post partum. The heritablity (in broader sense) for milk yield, feed intake and energy deficit was 0.39, 0.17 and 0.19 resp. the genetic and phenotypic correlations between daily milk yield and feed intake were 0.14 and 0.26 resp. Therefore selection for feed intake should be based on progeny groups of A. J. bulls. To estimate the feed intake under field conditions the content of ketone-bodies in milk at first and second test day p.p. can be combined with the milk yield and fat- and protein content. The correlation between estimated and actual energy deficit in 101 cows was r=0.17. In field data with about 7500 cows there was a genetic varience of the acetone content in milk in cows with two and more lactations with h2=0.17 ± 0.09 and h2=0.09 ± 0.06 for the first and second test day p.p resp., but not in heifers

    Schärer (Martin R.). Deutsche Annexionspolitik im Westen. Die Wiedereingliederung Eupen-Malmedys im Zweiten Weltkrieg

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    Pabst Klaus. Schärer (Martin R.). Deutsche Annexionspolitik im Westen. Die Wiedereingliederung Eupen-Malmedys im Zweiten Weltkrieg. In: Revue belge de philologie et d'histoire, tome 56, fasc. 2, 1978. Histoire (depuis l'Antiquité) — Geschiedenis (sedert de Oudheid) pp. 535-539
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