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21.
T Breiderhoff N Himmerkus M Stuiver K Mutig C Will IC Meij S Bachmann M Bleich TE Willnow D Müller 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(35):14241-14246
In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis. 相似文献
22.
Martin Grimm Michael Krimmel Dorothea Alexander Adelheid Munz Susanne Kluba Constanze Keutel Juergen Hoffmann Joachim Polligkeit Siegmar Reinert Sebastian Hoefert 《Clinical oral investigations》2013,17(3):949-955
Objectives
Overexpression of the histamine H1 receptor (H1R) has been described in a variety of tumor models, but experience in oral squamous cell carcinomas (OSCC) is not available. Current adjuvant treatment options for OSCC can be improved by the identification of new targets of therapy. Herein, we evaluated H1R expression in a large patient cohort of OSCC.Materials and methods
H1R immunoexpression was evaluated in 191 cases of OSCC and two OSCC cell lines BICR56 and BICR3. Scanned images were digitally analyzed using ImageJ and the immunomembrane plug-in. The combined score of computer-assisted semiquantitative analysis was correlated with manually counted percentages of tumor cells by Kendall’s tau (т) correlation coefficient. Disease-free survival times were estimated using the Kaplan–Meier method and were compared by using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.Results
H1R was rarely expressed in OSCC but significantly related with advanced tumor stages (n?=?21/191, mean expression 63.5 % of cancer cells in positive tumor samples, 95 % confidence interval of the mean 53.5 to 73.6 %, p?=?0.006). Following univariate analysis, patients with H1R expression showed a significant poorer prognosis (p?=?0.0004). Multivariate analysis revealed H1R expression as an independent prognostic factor (p?=?0.0164). Expression of H1R in cancer cell lines was confirmed by specific staining of OSCC cell lines BICR56 and BICR3.Conclusion
This is the first study focusing on H1R expression showing a significant poorer DFS rate in the H1R+ patient cohort. Based on these data, H1R activation may promote carcinogenesis in OSCC.Clinical relevance
Investigation of H1R regulation and its antagonists shows a clear rationale for future supportive anticancer therapies in OSCCs. 相似文献23.
24.
Constanze Pietsch Susanne Kersten Hana Valenta Sven D?nicke Carsten Schulz Patricia Burkhardt-Holm Ranka Junge 《Toxins》2015,7(9):3465-3480
The mycotoxin zearalenone (ZEN) is frequently contaminating animal feeds including feed used in aquaculture. In the present study, the effects of dietary exposure to ZEN on carp (Cyprinus carpio L.) were investigated. ZEN at three different concentrations (low dose: 332 µg kg−1, medium dose: 621 µg kg−1 and high dose: 797 µg kg−1 final feed, respectively) was administered to juvenile carp for four weeks. Additional groups received the mycotoxin for the same time period but were fed with the uncontaminated diet for two more weeks to examine the reversibility of the ZEN effects. No effects on growth were observed during the feeding trial, but effects on haematological parameters occurred. In addition, an influence on white blood cell counts was noted whereby granulocytes and monocytes were affected in fish treated with the medium and high dose ZEN diet. In muscle samples, marginal ZEN and α-zearalenol (α-ZEL) concentrations were detected. Furthermore, the genotoxic potential of ZEN was confirmed by analysing formation of micronuclei in erythrocytes. In contrast to previous reports on other fish species, estrogenic effects measured as vitellogenin concentrations in serum samples were not increased by dietary exposure to ZEN. This is probably due to the fact that ZEN is rapidly metabolized in carp. 相似文献
25.
Andrea Müns Constanze Mühl Robert Haase Hendrik Möckel Claire Chalopin Jürgen Meixensberger Dirk Lindner 《Acta neurochirurgica》2014,156(6):1237-1243
Background
Brain tumor surgeries are associated with a high technical and personal effort. The required interactions between the surgeon and the technical components, such as neuronavigation, surgical instruments and intraoperative imaging, are complex and demand innovative training solutions and standardized evaluation methods. Phantom-based training systems could be useful in complementing the existing surgical education and training.Methods
A prototype of a phantom-based training system was developed, intended for standardized training of important aspects of brain tumor surgery based on real patient data. The head phantom consists of a three-part construction that includes a reusable base and adapter, as well as a changeable module for single use. Training covers surgical planning of the optimal access path, the setup of the navigation system including the registration of the head phantom, as well as the navigated craniotomy with real instruments. Tracked instruments during the simulation and predefined access paths constitute the basis for the essential objective training feedback.Results
The prototype was evaluated in a pilot study by assistant physicians at different education levels. They performed a complete simulation and a final assessment using an evaluation questionnaire. The analysis of the questionnaire showed the evaluation result as “good” for the phantom construction and the used materials. The learning effect concerning the navigated planning was evaluated as “very good”, as well as having the effect of increasing safety for the surgeon before planning and conducting craniotomies independently on patients.Conclusions
The training system represents a promising approach for the future training of neurosurgeons. It aims to improve surgical skill training by creating a more realistic simulation in a non-risk environment. Hence, it could help to bridge the gap between theoretical and practical training with the potential to benefit both physicians and patients. 相似文献26.
Lionel Nobs Constanze Baranek Sigrun Nestel Akos Kulik Josef Kapfhammer Cordula Nitsch Suzana Atanasoski 《Glia》2014,62(5):829-839
Despite the vast abundance of glial progenitor cells in the mouse brain parenchyma, little is known about the molecular mechanisms driving their proliferation in the adult. Here we unravel a critical role of the G1 cell cycle regulator cyclin D1 in controlling cell division of glial cells in the cortical grey matter. We detect cyclin D1 expression in Olig2‐immunopositive (Olig2+) oligodendrocyte progenitor cells, as well as in Iba1+ microglia and S100β+ astrocytes in cortices of 3‐month‐old mice. Analysis of cyclin D1‐deficient mice reveals a cell and stage‐specific molecular control of cell cycle progression in the various glial lineages. While proliferation of fast dividing Olig2+ cells at early postnatal stages becomes gradually dependent on cyclin D1, this particular G1 regulator is strictly required for the slow divisions of Olig2+/NG2+ oligodendrocyte progenitors in the adult cerebral cortex. Further, we find that the population of mature oligodendrocytes is markedly reduced in the absence of cyclin D1, leading to a significant decrease in the number of myelinated axons in both the prefrontal cortex and the corpus callosum of 8‐month‐old mutant mice. In contrast, the pool of Iba1+ cells is diminished already at postnatal day 3 in the absence of cyclin D1, while the number of S100β+ astrocytes remains unchanged in the mutant. GLIA 2014;62:829–839 相似文献
27.
Luz E. Cabrera Constanze Schmotz Moin A. Saleem Sanna Lehtonen Olli Vapalahti Antti Vaheri Satu Mkel Jukka Mustonen Tomas Strandin 《Viruses》2022,14(3)
Old–world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus–caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS–associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus–infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus–infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria. 相似文献
28.
Mohamed Abdel-Wahab Mohammad Abdelghani Yosuke Miyazaki Erik W. Holy Constanze Merten Dirk Zachow Pim Tonino Marcel C.M. Rutten Frans N. van de Vosse Marie-Angele Morel Yoshinobu Onuma Patrick W. Serruys Gert Richardt Osama I. Soliman 《JACC: Cardiovascular Interventions》2018,11(3):287-297
Objectives
This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR).Background
PVR after TAVR is challenging to quantify, especially during the procedure.Methods
Post-replacement aortograms in 135 TAVR recipients were analyzed offline by videodensitometry to measure the ratio of the time-resolved contrast density in the left ventricular outflow tract to that in the aortic root (videodensitometric aortic regurgitation [VD-AR]). CMR was performed within an interval of ≤30 days (11 ± 6 days) after the procedure.Results
The average CMR-RF was 6.7 ± 7.0% whereas the average VD-AR was 7.0 ± 7.0%. The correlation between VD-AR and CMR-RF was substantial (r = 0.78, p < 0.001). On receiver-operating characteristic curves, a VD-AR ≥10% corresponded to >mild PVR as defined by CMR-RF (area under the curve: 0.94; p < 0.001; sensitivity 100%, specificity 83%), whereas a VD-AR ≥25% corresponded to moderate-to-severe PVR (area under the curve: 0.99; p = 0.004; sensitivity 100%, specificity 98%). Intraobserver reproducibility was excellent for both techniques (for CMR-RF, intraclass correlation coefficient: 0.91, p < 0.001; for VD-AR intraclass correlation coefficient: 0.93, p < 0.001). The difference on rerating was –0.04 ± 7.9% for CMR-RF and –0.40 ± 6.8% for VD-AR.Conclusions
The angiographic VD-AR provides a surrogate assessment of PVR severity after TAVR that correlates well with the CMR-RF. 相似文献29.
30.
Thomas Frodl Eva Maria Meisenzahl Thomas Zetzsche Christine Born Markus J?ger Constanze Groll Ronald Bottlender Gerda Leinsinger Hans-Jürgen M?ller 《Neuropsychopharmacology》2003,53(4):338-344
BACKGROUND: The aim of our study was to test the hypothesis that amygdala volumes are reduced in patients with recurrent major depression compared with first episode patients. METHODS: Using structural magnetic resonance imaging, we compared 30 inpatients with first-episode depression and 27 inpatients with recurrent major depression (DSM-IV) with healthy volunteer subjects from the local community matched for age, gender, and handedness. RESULTS: Patients with first-episode depression showed enlarged amygdala volumes compared with patients with recurrent major depression and healthy control subjects. No significant differences were found between patients with recurrent depression and healthy control subjects. No significant correlations were found between amygdala volumes and age of onset, illness duration, or severity of depression. CONCLUSIONS: Larger amygdala volumes in patients with first-episode depression may result from higher amygdala metabolism and blood flow. Additionally, disease progression with stress-related excitotoxic processes during recurrent depressive episodes might result in decreased amygdala volumes. Prospective investigations to investigate amygdala changes during the course of depression are needed. 相似文献