Institution
University of Hamburg
Education•Hamburg, Germany•
About: University of Hamburg is a education organization based out in Hamburg, Germany. It is known for research contribution in the topics: Population & Laser. The organization has 45564 authors who have published 89286 publications receiving 2850161 citations. The organization is also known as: Hamburg University.
Topics: Population, Laser, Transplantation, Large Hadron Collider, Higgs boson
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Data suggest that mid regions of the dmPFC/dACC are part of a "core" fear network that is activated irrespective of how fear was learnt, and allow for maintaining the theory that the rostral dMPFC is involved in conscious threat appraisal.
378 citations
••
TL;DR: It is postulated that the liquid biopsy concept will contribute to a better understanding and clinical management of drug resistance in patients with cancer.
Abstract: Distant metastases harbor unique genomic characteristics not detectable in the corresponding primary tumor of the same patient and metastases located at different sites show a considerable intrapatient heterogeneity. Thus, the mere analysis of the resected primary tumor alone (current standard practice in oncology) or, if possible, even reevaluation of tumor characteristics based on the biopsy of the most accessible metastasis may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, analysis of therapeutic targets and drug resistance-conferring gene mutations on circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA) released into the peripheral blood from metastatic deposits. We discuss the current challenges and future perspectives of CTCs and ctDNA as biomarkers in clinical oncology. Both CTCs and ctDNA are interesting complementary technologies that can be used in parallel in future trials assessing new drugs or drug combinations. We postulate that the liquid biopsy concept will contribute to a better understanding and clinical management of drug resistance in patients with cancer.
377 citations
••
Boston Children's Hospital1, University of Southern Denmark2, University of Tübingen3, University of Pavia4, University of Copenhagen5, Lyon College6, French Institute of Health and Medical Research7, HCL Technologies8, Aix-Marseille University9, University of Paris10, Paris Diderot University11, University of Hamburg12, Utrecht University13, Erasmus University Medical Center14, Mayo Clinic15, University of Genoa16, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico17, University of Michigan18, Université libre de Bruxelles19, University of Kiel20, Detmold21, Aarhus University Hospital22, University Hospital Heidelberg23, University of Tartu24, University of Colorado Denver25, Centre Hospitalier de Luxembourg26, Cairo University27, Ghent University Hospital28, Katholieke Universiteit Leuven29, University of Antwerp30, Leipzig University31, Children's Hospital of Philadelphia32
TL;DR: Clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy, and suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function.
Abstract: Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more frequent than previously reported; (ii) distinct phenotypes can be seen within the late onset group, including myoclonic-atonic epilepsy (two patients), Lennox-Gastaut not emerging from West syndrome (two patients), and focal epilepsies with an electrical status epilepticus during slow sleep-like EEG pattern (six patients); and (iii) West syndrome constitutes a common phenotype with a major recurring mutation (p.Arg853Gln: two new and four previously reported children). Other known phenotypes include Ohtahara syndrome, epilepsy of infancy with migrating focal seizures, and intellectual disability or autism without epilepsy. To assess the response to antiepileptic therapy, we retrospectively reviewed the treatment regimen and the course of the epilepsy in 66 patients for which well-documented medical information was available. We find that the use of sodium channel blockers was often associated with clinically relevant seizure reduction or seizure freedom in children with early infantile epilepsies (<3 months), whereas other antiepileptic drugs were less effective. In contrast, sodium channel blockers were rarely effective in epilepsies with later onset (≥3 months) and sometimes induced seizure worsening. Regarding the genetic findings, truncating mutations were exclusively seen in patients with late onset epilepsies and lack of response to sodium channel blockers. Functional characterization of four selected missense mutations using whole cell patch-clamping in tsA201 cells—together with data from the literature—suggest that mutations associated with early infantile epilepsy result in increased sodium channel activity with gain-of-function, characterized by slowing of fast inactivation, acceleration of its recovery or increased persistent sodium current. Further, a good response to sodium channel blockers clinically was found to be associated with a relatively small gain-of-function. In contrast, mutations in patients with late-onset forms and an insufficient response to sodium channel blockers were associated with loss-of-function effects, including a depolarizing shift of voltage-dependent activation or a hyperpolarizing shift of channel availability (steady-state inactivation). Our clinical and experimental data suggest a correlation between age at disease onset, response to sodium channel blockers and the functional properties of mutations in children with SCN2A-related epilepsy.
377 citations
••
TL;DR: In this paper, the authors report on a survey of the innovation activities and characteristics of 153 users of outdoor-related consumer products and find a high level of innovation by these consumers.
376 citations
••
TL;DR: In rats with hereditary hypothalamic diabetes insipidus (Brattleboro rats) the gene for the vasopressin precursor lacks a single G residue in the protein-coding region, which gives rise to an open reading frame predicting a hormone precursor having a different C-terminus.
Abstract: In rats with hereditary hypothalamic diabetes insipidus (Brattleboro rats) the gene for the vasopressin precursor lacks a single G residue in the protein-coding region. The mutation gives rise to an open reading frame predicting a hormone precursor having a different C-terminus.
376 citations
Authors
Showing all 46072 results
Name | H-index | Papers | Citations |
---|---|---|---|
Rudolf Jaenisch | 206 | 606 | 178436 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Stefan Schreiber | 178 | 1233 | 138528 |
Chris Sander | 178 | 713 | 233287 |
Dennis J. Selkoe | 177 | 607 | 145825 |
Daniel R. Weinberger | 177 | 879 | 128450 |
Ramachandran S. Vasan | 172 | 1100 | 138108 |
Bradley Cox | 169 | 2150 | 156200 |
Anders Björklund | 165 | 769 | 84268 |
J. S. Lange | 160 | 2083 | 145919 |
Hannes Jung | 159 | 2069 | 125069 |
Andrew D. Hamilton | 151 | 1334 | 105439 |
Jongmin Lee | 150 | 2257 | 134772 |
Teresa Lenz | 150 | 1718 | 114725 |
Stefanie Dimmeler | 147 | 574 | 81658 |