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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.


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Journal ArticleDOI
18 Dec 2014-Nature
TL;DR: It is demonstrated that adenosine–A2A signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity.
Abstract: Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies. Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of β-adrenergic receptors. Because BAT therapies based on cold exposure or β-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat. However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A2A receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A2A receptors in mice causes a decrease in BAT-dependent thermogenesis, whereas treatment with A2A agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A2A receptors or injection of lentiviral vectors expressing the A2A receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A2A agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A2A signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.

320 citations

Journal ArticleDOI
TL;DR: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV, indicating that HPV contribution in invasive vulvar cancer has probably been overestimated.

320 citations

Journal ArticleDOI
TL;DR: Therapeutic hypothermia revealed hints for tissue protective impact and might be a useful tool for intensive care after polytrauma, but the chosen length for therapeutichypothermia was too short.
Abstract: Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia.

320 citations

Journal ArticleDOI
TL;DR: It is suggested that during the learning phase of this movement sequence, the basal ganglia were critically involved in the establishment of the final motor programme.
Abstract: The cerebral structures participating in learning of a manual skill were mapped with regional cerebral blood flow (rCBF) measurements and positron emission tomography in nine healthy volunteers. The task was a complicated right-hand finger movement sequence. The subjects were examined at three stages: during initial practice of the finger movement sequence, in an advanced stage of learning, and after they had learnt the finger movement sequence. Quantitative evaluation of video tapes and electromyographic records of the right forearm and hand muscles demonstrated that the finger movements significantly accelerated and became more regular. Significant mean rCBF increases were induced in the left motor hand area, the left premotor cortex, the left supplementary motor area, the left sensory hand area, the left supplementary sensory area and the right anterior lobe of the cerebellum. During the learning process significant depressions of the mean rCBF occurred bilaterally in the superior parietal lobule, the anterior parietal cortex and the pars triangularis of the right inferior frontal cortex. The mean rCBF increases in these structures during the initial stage of learning were related to somatosensory feedback processing and internal language for the guidance of the finger movements. These activations disappeared when the subjects had learnt the finger movement sequence. Conversely, the mean rCBF significantly rose during the course of learning in the midsector of the putamen and globus pallidus on the left side. It is suggested that during the learning phase of this movement sequence, the basal ganglia were critically involved in the establishment of the final motor programme.

320 citations

Journal ArticleDOI
01 Feb 2004-Cancer
TL;DR: In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery.
Abstract: BACKGROUND Desmoid tumors are mesenchymal nonmetastasizing neoplasms. Although rare in the general population, they are a common extracolonic manifestation of familial adenomatous polyposis (FAP). Because of high tumor recurrence rates, surgery has been less than satisfactory in the treatment of desmoid tumors. In the current study, high doses of tamoxifen in combination with sulindac were used to treat severe desmoid tumors to avoid surgery. METHODS Since 1992, 25 patients at Heinrich Heine University (Dusseldorf, Germany) were treated with a combination of tamoxifen and sulindac. In the current study, 17 patients with FAP-associated and 8 patients with sporadic desmoid tumors received 120 mg of tamoxifen and 300 mg of sulindac daily. Every 6 months, the protracted course of desmoid growth was measured by computed tomography and/or magnetic resonance imaging scans. Tumor responses were characterized as progressive disease, stable disease (SD), partial regression (PR), and complete regression (CR). RESULTS Of the group of patients who received tamoxifen and sulindac as a primary treatment, all three patients with sporadic desmoid tumors demonstrated cessation of growth, and 10 of the 13 patients with FAP-associated tumors achieved either a PR or CR. In the sporadic desmoid tumor group, eight of nine patients developed tumor recurrences after undergoingsurgery at other institutions. Of these, two patients had SD and two patients had a PR to CR. CONCLUSIONS The patients with desmoid tumors who were managed conservatively with high-dose tamoxifen and sulindac had the best outcome. Desmoid tumor recurrence after surgery was high and in the FAP-associated tumor group, therapy with tamoxifen and sulindac was found to be less successful. Based on this experience, the authors recommended high-dose tamoxifen and sulindac as the primary treatment for patients with FAP-associated desmoid tumors. However, to our knowledge, the best approach after surgical intervention for patients with sporadic desmoid tumors remains to be determined. Cancer 2004. © 2003 American Cancer Society.

320 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
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023139
2022470
20213,130
20202,720
20192,507
20182,439