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排序方式: 共有700条查询结果,搜索用时 46 毫秒
1.
Zumel-Marne Angela Kundi Michael Castaño-Vinyals Gemma Alguacil Juan Petridou Eleni Th Georgakis Marios K. Morales-Suárez-Varela Maria Sadetzki Siegal Piro Sara Nagrani Rajini Filippini Graziella Hutter Hans-Peter Dikshit Rajesh Woehrer Adelheid Maule Milena Weinmann Tobias Krewski Daniel ′t Mannetje Andrea Momoli Franco Lacour Brigitte Mattioli Stefano Spinelli John J. Ritvo Paul Remen Thomas Kojimahara Noriko Eng Amanda Thurston Angela Lim Hyungryul Ha Mina Yamaguchi Naohito Mohipp Charmaine Bouka Evdoxia Eastman Chelsea Vermeulen Roel Kromhout Hans Cardis Elisabeth 《Journal of neuro-oncology》2020,147(2):427-440
Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in... 相似文献
2.
Zeitschrift für Psychodrama und Soziometrie - Dieser Artikel der Zeitschrift für Psychodrama und Soziometrie entwickelt auf drei Ebenen ein psychodramatisches Leitungsverständnis.... 相似文献
3.
Marianne K. Vormann Linda Gijzen Simon Hutter Lisette Boot Arnaud Nicolas Angelique van den Heuvel Jelle Vriend Chee Ping Ng Tom T. G. Nieskens Vincent van Duinen Bjorn de Wagenaar Rosalinde Masereeuw Laura Suter-Dick Sebastiaan J. Trietsch Martijn Wilmer Jos Joore Paul Vulto Henriette L. Lanz 《The AAPS journal》2018,20(5):90
Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating substrates from the body into the urine, leading to high local concentrations of xenobiotics. This makes the proximal tubule a major target for drug toxicity that needs to be evaluated during the drug development process. Here, we describe an advanced in vitro model consisting of fully polarized renal proximal tubular epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules were cultured on this platform that provides access to the basolateral as well as the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin caused a dose-dependent disruption of the epithelial barrier, a decrease in viability, an increase in effluent LDH activity, and changes in expression of tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as detected by immunostaining. Activity and inhibition of the efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated using fluorescence-based transporter assays. In addition, the transepithelial transport function from the basolateral to the apical side of the proximal tubule was studied. The apparent permeability of the fluorescent P-gp substrate rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A. Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by phlorizin. Our results demonstrate that we developed a functional 3D perfused proximal tubule model with advanced renal epithelial characteristics that can be used for drug screening studies. 相似文献
4.
Nastassja Himmelreich Bianca Dimitrov Virginia Geiger Matthias Zielonka Anna‐Marlen Hutter Lars Beedgen Andreas Hüllen Maximilian Breuer Verena Peters Kai‐Christian Thiemann Georg F. Hoffmann Irmgard Sinning Thierry Dupr Sandrine Vuillaumier‐Barrot Catherine Barrey Jonas Denecke Wolfgang Klfen Gesche Düker Rainer Ganschow Michael J. Lentze Stuart Moore Nathalie Seta Andreas Ziegler Christian Thiel 《Human mutation》2019,40(7):938-951
ALG3‐CDG is one of the very rare types of congenital disorder of glycosylation (CDG) caused by variants in the ER‐mannosyltransferase ALG3. Here, we summarize the clinical, biochemical, and genetic data of four new ALG3‐CDG patients, who were identified by a type I pattern of serum transferrin and the accumulation of Man5GlcNAc2‐PP‐dolichol in LLO analysis. Additional clinical symptoms observed in our patients comprise sensorineural hearing loss, right‐descending aorta, obstructive cardiomyopathy, macroglossia, and muscular hypertonia. We add four new biochemically confirmed variants to the list of ALG3‐CDG inducing variants: c.350G>C (p.R117P), c.1263G>A (p.W421*), c.1037A>G (p.N346S), and the intron variant c.296+4A>G. Furthermore, in Patient 1 an additional open‐reading frame of 141 bp (AAGRP) in the coding region of ALG3 was identified. Additionally, we show that control cells synthesize, to a minor degree, a hybrid protein composed of the polypeptide AAGRP and ALG3 (AAGRP‐ALG3), while in Patient 1 expression of this hybrid protein is significantly increased due to the homozygous variant c.160_196del (g.165C>T). By reviewing the literature and combining our findings with previously published data, we further expand the knowledge of this rare glycosylation defect. 相似文献
5.
Bianca Dimitrov Nastassja Himmelreich Agnes L. Hipgrave Ederveen Christian Lüchtenborg Jürgen G. Okun Maximilian Breuer Anna-Marlen Hutter Matthias Carl Luca Guglielmi Andrea Hellwig Kai Christian Thiemann Markus Jost Verena Peters Christian Staufner Georg F. Hoffmann Annette Hackenberg Nagarajan Paramasivam Stefan Wiemann Christian Thiel 《Molecular genetics and metabolism》2018,123(3):364-374
Congenital disorders of glycosylation (CDG) are genetic defects in the glycoconjugate biosynthesis. > 100 types of CDG are known, most of them cause multi-organ diseases. Here we describe a boy whose leading symptoms comprise cutis laxa, pancreatic insufficiency and hepatosplenomegaly. Whole exome sequencing identified the novel hemizygous mutation c.542 T > G (p.L181R) in the X-linked ATP6AP1, an accessory protein of the mammalian vacuolar H+-ATPase, which led to a general N-glycosylation deficiency. Studies of serum N-glycans revealed reduction of complex sialylated and appearance of truncated diantennary structures. Proliferation of the patient's fibroblasts was significantly reduced and doubling time prolonged. Additionally, there were alterations in the fibroblasts' amino acid levels and the acylcarnitine composition. Especially, short-chain species were reduced, whereas several medium- to long-chain acylcarnitines (C14-OH to C18) were elevated. Investigation of the main lipid classes revealed that total cholesterol was significantly enriched in the patient's fibroblasts at the expense of phophatidylcholine and phosphatidylethanolamine. Within the minor lipid species, hexosylceramide was reduced, while its immediate precursor ceramide was increased. Since catalase activity and ACOX3 expression in peroxisomes were reduced, we assume an ATP6AP1-dependent impact on the β-oxidation of fatty acids. These results help to understand the complex clinical characteristics of this new patient. 相似文献
6.
7.
In recent years a flood of new psychoactive substances offered as “legal highs” appeared on the drugs market worldwide. In some parts of the world amphetamine-type stimulants are predominant but in Germany synthetic cannabinoids represent the bigger problem. The high dynamics which are maintained by the “cat and mouse game” of scheduling substances and the producers circumventing the regulations by adding new, chemically modified substances, poses a great challenge for both forensic science and toxicology. 相似文献
8.
Andreas Meryk Gabriele Kropshofer Julia Hutter Josef Fritz Christina Salvador Cornelia Lass-Flörl Roman Crazzolara 《British journal of haematology》2020,191(5):816-824
Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single-centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin-B (L-AMB) and restricted to high-risk patients only. Vincristine-induced neurotoxicity was significantly reduced under L-AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene-treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L-AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia. 相似文献
9.
Hirschl M Hirschl K Lenz M Katzenschlager R Hutter HP Kundi M 《Arthritis and rheumatism》2006,54(6):1974-1981
OBJECTIVE: To assess the early signs, risk factors, and rate of transition from primary Raynaud's phenomenon (primary RP) to secondary RP. METHODS: A clinical sample of 307 consecutive patients with RP was included in a prospective followup study. After an initial screening, 244 patients were classified as having primary RP, of whom 236 were followed up for a mean +/- SD of 11.2 +/- 3.9 years. Patients classified according to the screening as having suspected secondary RP underwent an extended screening program annually until transition to secondary RP occurred. RESULTS: The initial prevalence of secondary RP was 11%. The annual incidence of transition to suspected secondary RP was 2%, and the annual incidence of transition to secondary RP was 1%. Overall, 46 patients were classified as having suspected secondary RP, and 23 of these later were classified as having secondary RP. Older age at onset of RP (hazard ratio 2.59, 95% confidence interval [95% CI] 1.40-4.80), shorter duration of RP at enrollment (hazard ratio 0.87, 95% CI 0.81-0.94), and abnormal findings on thoracic outlet test (hazard ratio 2.69, 95% CI 1.12-6.48) were associated with an increased risk for transition to secondary RP. Compared with patients with suspected secondary RP, those diagnosed as having secondary RP had a higher number and earlier occurrence of pathologic findings. Furthermore, antinuclear antibodies at a titer of > or = 1:320 and positive findings in specific serologic subsets were associated with a significantly increased risk for developing a connective tissue disease. CONCLUSION: Patients diagnosed initially as having primary RP may actually comprise 1 of 3 groups: those with idiopathic RP, those with a rather benign disease course, and those with a more severe course of the disease. 相似文献
10.
Ikeda DD Duan Y Matsuki M Kunitomo H Hutter H Hedgecock EM Iino Y 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(13):5260-5265
Calsyntenins/alcadeins are type I transmembrane proteins with two extracellular cadherin domains highly expressed in mammalian brain. They form a tripartite complex with X11/X11L and APP (amyloid precursor protein) and are proteolytically processed in a similar fashion to APP. Although a genetic association of calsyntenin-2 with human memory performance has recently been reported, physiological roles and molecular functions of the protein in the nervous system are poorly understood. Here, we show that CASY-1, the Caenorhabditis elegans ortholog of calsyntenins/alcadeins, is essential for multiple types of learning. Through a genetic screen, we found that casy-1 mutants show defects in salt chemotaxis learning. casy-1 mutants also show defects in temperature learning, olfactory adaptation, and integration of two sensory signals. casy-1 is widely expressed in the nervous system. Expression of casy-1 in a single sensory neuron and at the postdevelopmental stage is sufficient for its function in salt chemotaxis learning. The fluorescent protein-tagged ectodomain of CASY-1 is released from neurons. Moreover, functional domain analyses revealed that both cytoplasmic and transmembrane domains of this protein are dispensable, whereas the ectodomain, which contains the LG/LNS-like domain, is critically required for learning. These results suggest that learning is modulated by the released ectodomain of CASY-1. 相似文献