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131.
Eliana Cordero Jan Rüger Dominik Marti Abdullah S. Mondol Thomas Hasselager Karin Mogensen Gregers G. Hermann Jürgen Popp Iwan W. Schie 《Journal of biophotonics》2020,13(2)
Existing approaches for early‐stage bladder tumor diagnosis largely depend on invasive and time‐consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real‐time tumor diagnosis can enable immediate laser‐based removal of tumors using flexible cystoscopes in the outpatient clinic. Therefore, novel diagnostic modalities are required that can provide real‐time in vivo tumor diagnosis. Raman spectroscopy provides biochemical information of tissue samples ex vivo and in vivo and without the need for complicated sample preparation and staining procedures. For the past decade there has been a rise in applications to diagnose and characterize early cancer in different organs, such as in head and neck, colon and stomach, but also different pathologies, for example, inflammation and atherosclerotic plaques. Bladder pathology has also been studied but only with little attention to aspects that can influence the diagnosis, such as tissue heterogeneity, data preprocessing and model development. The present study presents a clinical investigative study on bladder biopsies to characterize the tumor grading ex vivo, using a compact fiber probe‐based imaging Raman system, as a crucial step towards in vivo Raman endoscopy. Furthermore, this study presents an evaluation of the tissue heterogeneity of highly fluorescent bladder tissues, and the multivariate statistical analysis for discrimination between nontumor tissue, and low‐ and high‐grade tumor. 相似文献
132.
Dominik Thimm Melanie Knospe Aliaa Abdelrahman Miguel Moutinho Bernt B. A. Alsdorf Ivar von Kügelgen Anke C. Schiedel Christa E. Müller 《Purinergic signalling》2013,9(3):415-426
The nucleobase adenine has previously been reported to activate G protein-coupled receptors in rat and mouse. Adenine receptors (AdeR) thus constitute a new family of purine receptors, for which the designation “P0-receptors” has been suggested. We now describe the cloning and characterization of two new members of the AdeR family from mouse (MrgA10, termed mAde1R) and hamster (cAdeR). Both receptors were expressed in Sf9 insect cells, and radioligand binding studies were performed using [3H]adenine. Specific binding of the radioligand was detected in transfected, but not in untransfected cells, and K D values of 286 nM (mAde1R, B max 1.18 pmol/mg protein) and 301 nM (cAdeR, B max 17.7 pmol/mg protein), respectively, were determined. A series of adenine derivatives was investigated in competition binding assays. Minor structural modifications generally led to a reduction or loss of affinity, with one exception: 2-fluoroadenine was at least as potent as adenine itself at the cAdeR. Structure–activity relationships at all AdeR orthologs and subtypes investigated so far were similar, but not identical. For functional analyses, the cAdeR was homologously expressed in Chinese hamster ovary (CHO) cells, while the mAde1R was heterologously expressed in 1321N1 astrocytoma cells. Like the previously described AdeRs from rat (rAdeR) and mouse (mAde2R), the mAde1R (EC50 9.77 nM) and the cAdeR (EC50 51.6 nM) were coupled to inhibition of adenylate cyclase. In addition, the cAdeR from hamster expressed in CHO cells produced an increase in intracellular calcium concentrations (EC50 6.24 nM) and was found to be additionally coupled to Gq proteins. 相似文献
133.
Ifey Alio Mirja Gudzuhn Pablo Pérez García Dominik Danso Marie Charlotte Schoelmerich Uwe Mamat Ulrich E. Schaible J?rg Steinmann Daniel Yero Isidre Gibert Thomas A. Kohl Stefan Niemann Matthias I. Gr?schel Johanna Haerdter Thomas Hackl Christel Vollstedt Mechthild B?meke Richard Egelkamp Rolf Daniel Anja Poehlein Wolfgang R. Streit 《Applied and environmental microbiology》2020,86(24)
134.
135.
Lorena Esposito-Bauer Tobias Saam Iman Ghodrati Jaroslav Pelisek Peter Heider Matthias Bauer Petra Wolf Angelina Bockelbrink Regina Feurer Dominik Sepp Claudia Winkler Peter Zepper Tobias Boeckh-Behrens Matthias Riemenschneider Bernhard Hemmer Holger Poppert 《PloS one》2013,8(7)
Purpose
The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I–VIII). Within these lesion types, lesion types IV–V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones.Methods
Eighty-three consecutive patients (45 male (54.2%); age 54–88 years (mean 73.2 years)) presenting with an asymptomatic carotid stenosis of 50–99% according to ECST-criteria were recruited. Patients were imaged with a 1.5-T scanner. T1-, T2-, time-of-flight-, and proton-density weighted studies were performed. The carotid plaques were classified as lesion type I–VIII. Clinical endpoints were ischemic stroke, TIA or amaurosis fugax. Survival analysis and log rank test were used to ascertain statistical significance.Results
Six out of 83 patients (7.2%) were excluded: 4 patients had insufficient MR image quality; 1 patient was lost-to-follow-up; 1 patient died shortly after the baseline MRI plaque imaging. The following results were obtained by analyzing the remaining 77 patients. The mean time of follow-up was 41.1 months.During follow-up, n = 9 (11.7%) ipsilateral ischemic cerebrovascular events occurred. Only patients presenting with the high-risk lesion types IV–V and VI developed an ipsilateral cerebrovascular event versus none of the patients presenting with the stable lesion types III, VII, and VIII (n = 9 (11.7%) vs. n = 0 (0%) during follow-up). Event-free survival was higher among patients with the MRI-defined stable lesion types (III, VII, and VIII) than in patients with the high-risk lesion types (IV–V and VI) (log rank test P<0.0001).Conclusions
MRI plaque imaging has the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of developing future cerebral ischemia. MRI could improve selection criteria for invasive therapy in the future. 相似文献136.
Martin Krueger Wolfgang H?rtig Andreas Reichenbach Ingo Bechmann Dominik Michalski 《PloS one》2013,8(2)
The term blood-brain barrier (BBB) relates to the ability of cerebral vessels to hold back hydrophilic and large molecules from entering the brain, thereby crucially contributing to brain homeostasis. In fact, experimental opening of endothelial tight junctions causes a breakdown of the BBB evidenced as for instance by albumin leakage. This and similar observations led to the conclusion that BBB breakdown is predominantly mediated by damage to tight junction complexes, but evidentiary ultrastructural data are rare. Since functional deficits of the BBB contribute to an increased risk of hemorrhagic transformation and brain edema after stroke, which both critically impact on the clinical outcome, we studied the mechanism of BBB breakdown using an embolic model of focal cerebral ischemia in Wistar rats to closely mimic the essential human pathophysiology. Ischemia-induced BBB breakdown was detected using intravenous injection of FITC-albumin and tight junctions in areas of FITC-albumin extravasation were subsequently studied using fluorescence and electron microscopy. Against our expectation, 25 hours after ischemia induction the morphology of tight junction complexes (identified ultrastructurally and using antibodies against the transcellular proteins occludin and claudin-5) appeared to be regularly maintained in regions where FITC-albumin massively leaked into the neuropil. Furthermore, occludin signals along pan-laminin-labeled vessels in the affected hemisphere equaled the non-affected contralateral side (ratio: 0.966 vs. 0.963; P = 0.500). Additional ultrastructural analyses at 5 and 25 h after ischemia induction clearly indicated FITC-albumin extravasation around vessels with intact tight junctions, while the endothelium exhibited enhanced transendothelial vesicle trafficking and signs of degeneration. Thus, BBB breakdown and leakage of FITC-albumin cannot be correlated with staining patterns for common tight junction proteins alone. Understanding the mechanisms causing functional endothelial alterations and endothelial damage is likely to provide novel protective targets in stroke. 相似文献
137.
Christopher J. Bockisch Elham Khojasteh Dominik Straumann Stefan C. A. Hegemann 《PloS one》2012,7(12)
The nystagmus in patients with vestibular disorders often has an eye position dependency, called Alexander’s law, where the slow phase velocity is higher with gaze in the fast phase direction compared with gaze in the slow phase direction. Alexander’s law has been hypothesized to arise either due to adaptive changes in the velocity-to-position neural integrator, or as a consequence of processing of the vestibular-ocular reflex. We tested whether Alexander’s law arises only as a consequence of non-physiologic vestibular stimulation. We measured the time course of the development of Alexander’s law in healthy humans with nystagmus caused by three types of caloric vestibular stimulation: cold (unilateral inhibition), warm (unilateral excitation), and simultaneous bilateral bithermal (one side cold, the other warm) stimulation, mimicking the normal push-pull pattern of vestibular stimulation. Alexander’s law, measured as a negative slope of the velocity versus position curve, was observed in all conditions. A reversed pattern of eye position dependency (positive slope) was found <10% of the time. The slope often changed with nystagmus velocity (cross-correlation of nystagmus speed and slope was significant in 50% of cases), and the average lag of the slope with the speed was not significantly different from zero. Our results do not support the hypothesis that Alexander’s law can only be observed with non-physiologic vestibular stimulation. Further, the rapid development of Alexander’s law, while possible for an adaptive mechanism, is nonetheless quite fast compared to most other ocular motor adaptations. These results suggest that Alexander’s law may not be a consequence of a true adaptive mechanism. 相似文献
138.
Jan-Peter Sowa ?zgür Atmaca Alisan Kahraman Martin Schlattjan Marion Lindner Svenja Sydor Norbert Scherbaum Karoline Lackner Guido Gerken Dominik Heider Gavin E. Arteel Yesim Erim Ali Canbay 《PloS one》2014,9(7)
Background & Objective
Currently, a major clinical challenge is to distinguish between chronic liver disease caused by metabolic syndrome (non-alcoholic fatty liver disease, NAFLD) from that caused by long term or excessive alcohol consumption (ALD). The etiology of severe liver disease affects treatment options and priorities for liver transplantation and organ allocation. Thus we compared physiologically similar NAFLD and ALD patients to detect biochemical differences for improved separation of these mechanistically overlapping etiologies.Methods
In a cohort of 31 NAFLD patients with BMI below 30 and a cohort of ALD patient with (ALDC n = 51) or without cirrhosis (ALDNC n = 51) serum transaminases, cell death markers and (adipo-)cytokines were assessed. Groups were compared with One-way ANOVA and Tukey''s correction. Predictive models were built by machine learning techniques.Results
NAFLD, ALDNC or ALDC patients did not differ in demographic parameters. The ratio of alanine aminotransferase/aspartate aminotransferase - common serum parameters for liver damage - was significantly higher in the NAFLD group compared to both ALD groups (each p<0.0001). Adiponectin and tumor necrosis factor(TNF)-alpha were significantly lower in NAFLD than in ALDNC (p<0.05) or ALDC patients (p<0.0001). Significantly higher serum concentrations of cell death markers, hyaluronic acid, adiponectin, and TNF-alpha (each p<0.0001) were found in ALDC compared to ALDNC. Using machine learning techniques we were able to discern NAFLD and ALDNC (up to an AUC of 0.9118±0.0056) or ALDC and ALDNC (up to an AUC of 0.9846±0.0018), respectively.Conclusions
Machine learning techniques relying on ALT/AST ratio, adipokines and cytokines distinguish NAFLD and ALD. In addition, severity of ALD may be non-invasively diagnosed via serum cytokine concentrations. 相似文献139.
Arango-Gonzalez B Schatz A Bolz S Eslava-Schmalbach J Willmann G Zhour A Zrenner E Fischer MD Gekeler F 《PloS one》2012,7(4):e35687
Objectives
To explore the effect of ketamine-xylazine anesthesia on light-induced retinal degeneration in rats.Methods
Rats were anesthetized with ketamine and xylazine (100 and 5 mg, respectively) for 1 h, followed by a recovery phase of 2 h before exposure to 16,000 lux of environmental illumination for 2 h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosin staining, TUNEL assay) and immunohistochemistry (GFAP and rhodopsin staining) were performed at baseline (ERG), 36 h, 7 d and 14 d post-treatment. Non-anesthetized animals treated with light damage served as controls.Results
Ketamine-xylazine pre-treatment preserved retinal function and protected against light-induced retinal degeneration. In vivo retinal imaging demonstrated a significant increase of outer nuclear layer (ONL) thickness in the non-anesthetized group at 36 h (p<0.01) and significant reduction one week (p<0.01) after light damage. In contrast, ketamine-xylazine pre-treated animals showed no significant alteration of total retinal or ONL thickness at either time point (p>0.05), indicating a stabilizing and/or protective effect with regard to phototoxicity. Histology confirmed light-induced photoreceptor cell death and Müller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazine treated rats showed reduced photoreceptor cell death (TUNEL staining: p<0.001 after 7 d), thicker ONL and longer IS/OS. Fourteen days after light damage, a reduction of standard flash induced a-wave amplitudes and a-wave slopes (p = 0.01) and significant alterations in parameters of the scotopic sensitivity function (e.g. Vmax of the Naka Rushton fit p = 0.03) were observed in non-treated vs. ketamine-xylazine treated animals.Conclusions
Our results suggest that pre-treatment with ketamine-xylazine anesthesia protects retinas against light damage, reducing photoreceptor cell death. These data support the notion that anesthesia with ketamine-xylazine provides neuroprotective effects in light-induced cell damage. 相似文献140.