Auflistung nach Autor:in "Gygax, Daniel"

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Allosteric targeting resolves limitations of earlier LFA-1 directed modalities
(Elsevier, 05/2023) Mancuso, Riccardo V.; Schneider, Gisbert; Hürzeler Müller, Marianne; Gut, Martin; Zurflüh, Jonas; Breitenstein, Werner; Bouitbir, Jamal; Reisen, Felix; Atz, Kenneth; Ehrhardt, Claus; Duthaler, Urs; Gygax, Daniel; Schmidt, Albrecht G.; Krähenbühl, Stephan; Weitz-Schmidt, Gabriele
01A - Beitrag in wissenschaftlicher Zeitschrift
Clinical Characterisation of Eleven Lateral Flow Assays for Detection of COVID-19 Antibodies in a Population
(Cold Spring Harbor Laboratory, 25.08.2020) Rudolf, Fabian; Gygax, Daniel
01A - Beitrag in wissenschaftlicher Zeitschrift
Entwicklung einer Point-of-Care Applikation zur Überwachung des Medikamenten-spiegels im Blut nach Organtransplantation
HLA antibody affinity determination. From HLA‐specific monoclonal antibodies to donor HLA specific antibodies (DSA) in patient serum
(Wiley, 16.05.2023) Hug, Melanie N.; Keller, Sabrina; Marty, Talea; Gygax, Daniel; Meinel, Dominik; Spies, Peter; Handschin, Joëlle; Kleiser, Marc; Vazquez, Noemi; Linnik, Janina; Buchli, Rico; Claas, Frans; Heidt, Sebastiaan; Kramer, Cynthia S. M.; Bezstarosti, Suzanne; Lee, Jar‐How; Schaub, Stefan; Hönger, Gideon
Organs transplanted across donor‐specific HLA antibodies (DSA) are associated with a variety of clinical outcomes, including a high risk of acute kidney graft rejection. Unfortunately, the currently available assays to determine DSA characteristics are insufficient to clearly discriminate between potentially harmless and harmful DSA. To further explore the hazard potential of DSA, their concentration and binding strength to their natural target, using soluble HLA, may be informative. There are currently a number of biophysical technologies available that allow the assessment of antibody binding strength. However, these methods require prior knowledge of antibody concentrations. Our objective within this study was to develop a novel approach that combines the determination of DSA‐affinity as well as DSA‐concentration for patient sample evaluation within one assay. We initially tested the reproducibility of previously reported affinities of human HLA‐specific monoclonal antibodies and assessed the technology‐specific precision of the obtained results on multiple platforms, including surface plasmon resonance (SPR), bio‐layer interferometry (BLI), Luminex (single antigen beads; SAB), and flow‐induced dispersion analysis (FIDA). While the first three (solid‐phase) technologies revealed comparable high binding‐strengths, suggesting measurement of avidity, the latter (in‐solution) approach revealed slightly lower binding‐strengths, presumably indicating measurement of affinity. We believe that our newly developed in‐solution FIDA‐assay is particularly suitable to provide useful clinical information by not just measuring DSA‐affinities in patient serum samples but simultaneously delivering a particular DSA‐concentration. Here, we investigated DSA from 20 pre‐transplant patients, all of whom showed negative CDC‐crossmatch results with donor cells and SAB signals ranging between 571 and 14899 mean fluorescence intensity (MFI). DSA‐concentrations were found in the range between 11.2 and 1223 nM (median 81.1 nM), and their measured affinities fall between 0.055 and 24.7 nM (median 5.34 nM; 449‐fold difference). In 13 of 20 sera (65%), DSA accounted for more than 0.1% of total serum antibodies, and 4/20 sera (20%) revealed a proportion of DSA even higher than 1%. To conclude, this study strengthens the presumption that pre‐transplant patient DSA consists of various concentrations and different net affinities. Validation of these results in a larger patient cohort with clinical outcomes will be essential in a further step to assess the clinical relevance of DSA‐concentration and DSA‐affinity.
01A - Beitrag in wissenschaftlicher Zeitschrift
How technical innovations may help to prevent drug shortages in switzerland
(Schweizerische Chemische Gesellschaft, 2023) Gygax, Daniel; Eigenmann, Kaspar; Suter, Christian; Hürzeler Müller, Marianne; Mahmoud, Ahmed; Mosbacher, Johannes; Pöllinger, Norbert
In this work, we investigated the technical feasibility of 'on-demand' production of selected drugs to cover their demand for a time window of 90 days. We focused on two sub-processes 'automated chemical synthesis' and 'formulation in micropellets' to enable personalized dosing. The production of drugs 'on-demand' is challenging, important, but also attractive. Switzerland could thus gain access to an additional instrument for increasing resilience for supply-critical drugs. The biggest challenge in the case study presented here is the scalability of automated chemical synthesis and the application range of micropellet formulations.
01A - Beitrag in wissenschaftlicher Zeitschrift
In-vitro-Diagnostik
Targeted screening of succinic semialdehyde dehydrogenase deficiency (SSADHD) employing an enzymatic assay for γ-hydroxybutyric acid (GHB) in biofluids
(Elsevier, 2016) Wernli, Cédric; Finochiaro, S; Büttler, André; Gygax, Daniel; Vogel, Kara R.; Ainslie, Garrett R.; Gibson, K. Michael; Volken, Carmen; Andresen-Streichert, Hilke; Salomons, Gajja S.; Jansen, Erwin E.
Hypothesis An enzymatic assay for quantification of γ-hydroxybutyric acid (GHB) in biofluids can be employed for targeted screening of succinic semialdehyde dehydrogenase deficiency (SSADHD) in selected populations. Rationale We used a two-tiered study approach, in which the first study (proof of concept) examined 7 urine samples derived from patients with SSADHD and 5 controls, and the second study (feasibility study) examined a broader sample population of patients and controls, including plasma. Objective Split samples of urine and plasma (anonymized) were evaluated by enzymatic assay, gas chromatography alone (proof of concept) and gas chromatography–mass spectrometry, and the results compared. Method Multiple detection methods have been developed to detect GHB. We evaluated an enzymatic assay which employs recombinant GHB dehydrogenase coupled to NADH production, the latter quantified on a Cobas Integra 400 Plus. Results: In our proof of concept study, we analyzed 12 urine samples (5 controls, 7 SSADHD), and in the feasibility study we evaluated 33 urine samples (23 controls, 10 SSADHD) and 31 plasma samples (14 controls, 17 SSADHD). The enzymatic assay carried out on a routine clinical chemistry analyzer was robust, revealing excellent agreement with instrumental methods in urine (GC-FID: r = 0.997, p ≤ 0.001; GC–MS: r = 0.99, p ≤ 0.001); however, the assay slightly over-estimated GHB levels in plasma, especially those in which GHB levels were low. Conversely, correlations for the enzymatic assay with comparator methods for higher plasma GHB levels were excellent (GC–MS; r = 0.993, p ≤ 0.001). Conclusion We have evaluated the capacity of this enzymatic assay to identify patients with SSADHD via quantitation of GHB. The data suggests that the enzymatic assay may be a suitable screening method to detect SSADHD in selected populations using urine. In addition, the assay can be used in basic research the elucidate the mechanism of the underlying disease or monitor GHB- levels for the evaluation of drug candidates. Synopsis An enzymatic assay for GHB in biofluids was evaluated as a screening method for SSADHD and found to be reliable in urine, but in need of refinement for application to plasma.
01A - Beitrag in wissenschaftlicher Zeitschrift