scispace - formally typeset
Search or ask a question
Institution

University of Düsseldorf

EducationDüsseldorf, Germany
About: University of Düsseldorf is a education organization based out in Düsseldorf, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 25225 authors who have published 49155 publications receiving 1946434 citations.


Papers
More filters
Journal ArticleDOI
TL;DR: Prenatal stress resulted in a reduced hippocampal volume and an inhibition of neurogenesis in the dentate gyrus, which indicates that the prenatal environment can alter behavior, dysregulate neuroendocrine systems, and affect the hippocampal structure of primates in a persistent manner.

447 citations

Journal ArticleDOI
TL;DR: The even rarer recurrent GBS, in which acute relapses appear after complete recovery, is usually considered to be more closely tied to GBS than to CIDP by most authorities, since time course and treatment response of single recurrences are identical to typical monophasic GBS.
Abstract: Approximately 3% of inflammatory demyelinating polyneuropathy cases progress for longer than 4 weeks, the arbitrary cut-off point for the diagnosis of GBS, or they relapse and fluctuate. Such cases are referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). In CIDP, the nadir of illness is usually reached after several months, either after a chronic monophasic, a stepwise progressing, or a relapsing course. In contrast, the even rarer recurrent GBS, in which acute relapses appear after complete recovery, is usually considered to be more closely tied to GBS than to CIDP by most authorities, since time course and treatment response of single recurrences are identical to typical monophasic GBS.

447 citations

Journal ArticleDOI
TL;DR: This trial, which to the best of the authors' knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL.
Abstract: Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.

446 citations

Journal ArticleDOI
TL;DR: Both the stable silencing of BRAF through shRNA lentiviral transduction and pharmacological inhibition of MEK1/2, the immediate downstream phosphorylation target of BRAf, blocked the proliferation and arrested the growth of cultured tumor cells derived from low-grade gliomas and suggest inhibition of the MAPK pathway as a potential treatment.
Abstract: The molecular pathogenesis of pediatric astrocytomas is still poorly understood. To further understand the genetic abnormalities associated with these tumors, we performed a genome-wide analysis of DNA copy number aberrations in pediatric low-grade astrocytomas by using array-based comparative genomic hybridization. Duplication of the BRAF protooncogene was the most frequent genomic aberration, and tumors with BRAF duplication showed significantly increased mRNA levels of BRAF and a downstream target, CCND1, as compared with tumors without duplication. Furthermore, denaturing HPLC showed that activating BRAF mutations were detected in some of the tumors without BRAF duplication. Similarly, a marked proportion of low-grade astrocytomas from adult patients also had BRAF duplication. Both the stable silencing of BRAF through shRNA lentiviral transduction and pharmacological inhibition of MEK1/2, the immediate downstream phosphorylation target of BRAF, blocked the proliferation and arrested the growth of cultured tumor cells derived from low-grade gliomas. Our findings implicate aberrant activation of the MAPK pathway due to gene duplication or mutation of BRAF as a molecular mechanism of pathogenesis in low-grade astrocytomas and suggest inhibition of the MAPK pathway as a potential treatment.

446 citations

Journal ArticleDOI
TL;DR: Tissue-specific deletion, or hypomorphic knock-in, of Adam17 demonstrates an in vivo role for ADAM17 in controlling inflammation and tissue regeneration and the potential ofADAM17 as therapeutic target is discussed.

446 citations


Authors

Showing all 25575 results

NameH-indexPapersCitations
Karl J. Friston2171267217169
Roderick T. Bronson169679107702
Stanley B. Prusiner16874597528
Ralph A. DeFronzo160759132993
Monique M.B. Breteler15954693762
Thomas Meitinger155716108491
Karl Zilles13869272733
Ruben C. Gur13674161312
Alexis Brice13587083466
Michael Schmitt1342007114667
Michael Weller134110591874
Helmut Sies13367078319
Peter T. Fox13162283369
Yuri S. Kivshar126184579415
Markus M. Nöthen12594383156
Network Information
Related Institutions (5)
Ludwig Maximilian University of Munich
161.5K papers, 5.7M citations

97% related

Heidelberg University
119.1K papers, 4.6M citations

96% related

University of Zurich
124K papers, 5.3M citations

95% related

University of Pittsburgh
201K papers, 9.6M citations

94% related

National Institutes of Health
297.8K papers, 21.3M citations

94% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023139
2022470
20213,130
20202,720
20192,507
20182,439