Search

Your search keyword '"Leon Soltesz"' showing total 3 results
Start Over Author "Leon Soltesz"
3 results on '"Leon Soltesz"'

1. Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience

Author

Lukas Schroeder, Leon Soltesz, Judith Leyens, Brigitte Strizek, Christoph Berg, Andreas Mueller, and Florian Kipfmueller

Subjects
monochorionic, twin pregnancies, pulmonary hypertension, ventricular dysfunction, vasoactive management, Pediatrics, RJ1-570
Abstract

Objectives: Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. Methodology: In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children’s Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). Results: The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive–inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). Conclusion: Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

Published
2024
Full Text
View/download PDF

2. Immune sensing of synthetic, bacterial and protozoan RNA by TLR8 requires coordinated processing of RNA substrates by RNaseT2 and RNase2

Author

Eva Sarah Bartok, Thomas Ostendorf, Thomas Zillinger, Katarzyna Andryka, Thais Marina Guimaraes, Saskia Schmitz, Samira Marx, Kübra Bayrak, Rebecca Linke, Sarah Salgert, Tatjana Grasser, Sonja Baersachs, Marc Hübner, Leon Soltesz, Matthias Kettwig, Maximilian Nastaly, Ingo Roehl, Marco Henneke, Winfried Barchet, Jutta Gärtner, Martin Schlee, and Gunther Hartmann

Subjects
Immunology, Immunology and Allergy
Abstract

Human TLR8 is an essential sensor of bacterial RNA which induces proinflammatory and Th1 cytokines. Crystallography revealed that TLR8 binds both uridine and short single-stranded RNA, but the RNases that process the RNA are still unknown. Herein, we demonstrate that two endosomal endoribonucleases, RNaseT2 and RNase2, can process RNA for TLR8 recognition. In the endosome, RNase2 and -T2 act synergistically to release uridine from oligoribonucleotides, with RNaseT2 cleaving preferentially before and RNase2 after uridines. Live bacteria, P. falciparum-infected red blood cells, purified pathogen RNA, and synthetic ligands all required RNase processing for TLR8 activation, and uridine supplementation restored RNA recognition in RNASE2−/− or RNASET2−/− but not double knockout cells. Strikingly, peripheral blood mononuclear cells from RNaseT2 hypomorphic patients did not respond to bacterial RNA but did to small-molecule TLR8 agonists. Our data provide a novel insight into TLR8 activation and its differences between cell types and species.

Published
2020

3. Immune Sensing of Synthetic, Bacterial, and Protozoan RNA by Toll-like Receptor 8 Requires Coordinated Processing by RNase T2 and RNase 2

Author

Thomas Ostendorf, Christoph Coch, Maximilian Nastaly, Saskia Schmitz, Leon Soltesz, Tatjana Grasser, Thomas Zillinger, Samira Marx, Julia Wegner, Rebecca Linke, Achim Hoerauf, Eva Bartok, Sonja Bauersachs, Marc P. Hübner, Matthias Kettwig, Winfried Barchet, Marco Henneke, Thais Marina Schlee-Guimaraes, Sarah Salgert, Martin Schlee, Jutta Gärtner, Gunther Hartmann, Katarzyna Andryka, Kübra Bayrak, and Ingo Roehl

Subjects
0301 basic medicine, Staphylococcus aureus, Erythrocytes, Neutrophils, THP-1 Cells, RNase P, RNA Stability, Plasmodium falciparum, Primary Cell Culture, Immunology, Biology, Monocytes, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endoribonucleases, Escherichia coli, Humans, Immunology and Allergy, Oligoribonucleotides, Binding site, Serratia marcescens, Gene Editing, Toll-like receptor, Innate immune system, Streptococcus, RNA, TLR8, Listeria monocytogenes, Uridine, RNA, Bacterial, 030104 developmental biology, Infectious Diseases, chemistry, Biochemistry, Toll-Like Receptor 8, 030220 oncology & carcinogenesis, CRISPR-Cas Systems, RNA, Protozoan
Abstract

Summary Human toll-like receptor 8 (TLR8) activation induces a potent T helper-1 (Th1) cell response critical for defense against intracellular pathogens, including protozoa. The receptor harbors two distinct binding sites, uridine and di- and/or trinucleotides, but the RNases upstream of TLR8 remain poorly characterized. We identified two endolysosomal endoribonucleases, RNase T2 and RNase 2, that act synergistically to release uridine from oligoribonucleotides. RNase T2 cleaves preferentially before, and RNase 2 after, uridines. Live bacteria, P. falciparum-infected red blood cells, purified pathogen RNA, and synthetic oligoribonucleotides all required RNase 2 and T2 processing to activate TLR8. Uridine supplementation restored RNA recognition in RNASE2−/− or RNASET2−/− but not RNASE2−/− RNASET2−/− cells. Primary immune cells from RNase T2-hypomorphic patients lacked a response to bacterial RNA but responded robustly to small-molecule TLR8 ligands. Our data identify an essential function of RNase T2 and RNase 2 upstream of TLR8 and provide insight into TLR8 activation.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results