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Per Karlsson Lars Farde Christer Halldin Carl-Gunnar Swahn Göran Sedvall Christian Foged Kristian Tage Hansen Birte Skrumsager 《Psychopharmacology》1993,113(2):149-156
The benzazepines NNC 687 and NNC 756 have in animal studies been described as selective D1-dopamine receptor antagonists. Both compounds have been labeled with11C for examination by positron emission tomography (PET). In the present study central receptor binding was studied in monkeys and healthy men. After IV injection of both radioligands in Cynomolgus monkeys radioactivity accumulated markedly in the striatum, a region with a high density of D1-dopamine receptors. This striatal uptake was displaced by high doses of the selective D1-antagonist SCH 23390 (2 mg/kg) but not by the 5HT2-antagonist ketanserin (1.5 mg/kg) or the selective D2-antagonist raclopride (3 mg/kg). The cortical uptake after injection of [11C]NNC 687 was not reduced in displacement experiments with ketanserin. The cortical uptake of [11C]NNC 756 was reduced in displacement and protection experiments with ketanserin by 24–28% (1.5 mg/kg), whereas no reduction could be demonstrated on striatal uptake. In healthy males both compounds accumulated markedly in the striatum. For [11C]NNC 687 the ratio of radioactivity in the putamen to cerebellum was about 1.5. For [11C]NNC 756 the ratio was about 5. This ratio of 5 for [11C]NNC 756 is the highest obtained so far for PET radioligands for the D1-dopamine receptor. 相似文献
3.
Tursun B Schlüter A Peters MA Viehweger B Ostendorff HP Soosairajah J Drung A Bossenz M Johnsen SA Schweizer M Bernard O Bach I 《Genes & development》2005,19(19):2307-2319
LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics. 相似文献
4.
Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes 总被引:8,自引:0,他引:8
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Bamberger C Schärer A Antsiferova M Tychsen B Pankow S Müller M Rülicke T Paus R Werner S 《The American journal of pathology》2005,167(3):733-747
The transforming growth factor-beta family member activin is a potent regulator of skin morphogenesis and repair. Transgenic mice overexpressing activin in keratinocytes display epidermal hyper-thickening and dermal fibrosis in normal skin and enhanced granulation tissue formation after wounding. Mice overexpressing the secreted activin antagonist follistatin, however, have the opposite wound-healing phenotype. To determine whether activin affects skin morphogenesis and repair via activation of keratinocytes and/or stromal cells, we generated transgenic mice expressing a dominant-negative activin receptor IB mutant (dnActRIB) in keratinocytes. The architecture of adult skin was unaltered in these mice, but delays were observed in postnatal pelage hair follicle morphogenesis and in the first catagen-telogen transformation of hair follicles. Although dnActRIB-transgenic mice showed slightly delayed wound re-epithelialization after skin injury, the strong inhibition of granulation tissue formation seen in follistatin-transgenic mice was not observed. Therefore, although endogenous activin appeared to affect skin morphogenesis and repair predominantly via stromal cells, overexpressed activin strongly affected the epidermis. The epidermal phenotype of activin-overexpressing mice was partially rescued by breeding these animals with dnActRIB-transgenic mice. These results demonstrate that activin affects both stromal cells and keratinocytes in normal and wounded skin and that the effect on keratinocytes is dose-dependent in vivo. 相似文献
5.
Hemifacial microsomia is a congenital asymmetrical malformation of the skull and the face. As a congenital malformation of the face hemifacial microsomia is second in prevalence after cleft lip and palate disorders. Combinations and degrees of underdevelopment of craniofacial structures vary greatly. Therapy varies and depends on the different anomalies, but mostly contains orthodontic and surgical treatment to improve symmetry. It is generally accepted that children with asymmetrical facial malformations are best treated in multidisciplinary craniofacial centres. 相似文献
6.
Serum microRNA profiles as prognostic/predictive markers in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction
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Ines Gockel Leila Sisic Jolly Schmitz Nikolas H. Stoecklein Christiane Driemel Birte Möhlendick Thomas Schmidt Wolfram T. Knoefel Hauke Lang Reinhard Büttner Daniel Vallböhmer 《International journal of cancer. Journal international du cancer》2015,137(1):230-237
Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis of locally advanced adenocarcinomas of the gastroesophageal junction. This study aimed to asses if serum microRNA profiles are useable as response indicators in this therapeutic setting. Fifty patients with locally advanced adenocarcinomas of the gastroesophageal junction were included in the study. All patients received neoadjuvant therapy and subsequently underwent surgical resection. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10% vital residual tumor cells. Circulating RNA was isolated from pretherapeutic/post‐neoadjuvant blood serum samples. RNA from nine patients was applied to PCR microarray analyses Based on these findings possible predictive miRNA markers were validated by quantitative RT‐PCR analyses. Depending on the histomorphologic regression, a differential serum microRNA profile was identified by microarray analyses. Based on the divergent miRNA pattern, miR‐21, miR‐192, miR‐222, miR‐302c, miR‐381 and miR‐549 were selected for further validation. During neoadjuvant therapy, there was a significant increase of miR 222 and miR‐549. Although on an expanded patient cohort, the six microRNAs could not be validated as markers for therapy response, there was a significant correlation between a high miR‐192 and miR‐222 expression with a high T‐category as well as miR‐302c and miR‐222 expression significantly correlated with overall survival. Comprehensive miRNA profiling showed a differential microRNA expression pattern depending on the histomorphologic regression in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction. Moreover, using single RT‐PCR analyses a prognostic impact of miR‐222 and miR‐302c was detected. 相似文献
7.
8.
Genomic characterization of pediatric B‐lymphoblastic lymphoma and B‐lymphoblastic leukemia using formalin‐fixed tissues
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9.
T. Sonia Boender Wei Cai Madlen Schranz Theresa Kocher Birte Wagner Alexander Ullrich Silke Buda Rebecca Zllner Felix Greiner Michaela Diercke Linus Grabenhenrich 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(27)
BackgroundThe COVID-19 pandemic expanded the need for timely information on acute respiratory illness at population level.AimWe explored the potential of routine emergency department data for syndromic surveillance of acute respiratory illness in Germany.MethodsWe used routine attendance data from emergency departments, which continuously transferred data between week 10 2017 and 10 2021, with ICD-10 codes available for > 75% of attendances. Case definitions for acute respiratory infection (ARI), severe acute respiratory infection (SARI), influenza-like illness (ILI), respiratory syncytial virus infection (RSV) and COVID-19 were based on a combination of ICD-10 codes, and/or chief complaints, sometimes combined with information on hospitalisation and age.ResultsWe included 1,372,958 attendances from eight emergency departments. The number of attendances dropped in March 2020 during the first COVID-19 pandemic wave, increased during summer, and declined again during the resurge of COVID-19 cases in autumn and winter of 2020/21. A pattern of seasonality of respiratory infections could be observed. By using different case definitions (i.e. for ARI, SARI, ILI, RSV) both the annual influenza seasons in the years 2017–2020 and the dynamics of the COVID-19 pandemic in 2020/21 were apparent. The absence of the 2020/21 influenza season was visible, parallel to the resurge of COVID-19 cases. SARI among ARI cases peaked in April–May 2020 (17%) and November 2020–January 2021 (14%).ConclusionSyndromic surveillance using routine emergency department data can potentially be used to monitor the trends, timing, duration, magnitude and severity of illness caused by respiratory viruses, including both influenza viruses and SARS-CoV-2. 相似文献
10.
Dominik N?rz Susanne Pfefferle Thomas Brehm Gefion Franke Ilka Grewe Birte Knobling Martin Aepfelbacher Samuel Huber Eva M. Klupp Sabine Jordan Marylyn M. Addo Julian Schulze zur Wiesch Stefan Schmiedel Marc Lütgehetmann Johannes K. Knobloch 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(26)