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Berlin Brandenburg

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  • MEDLINE/PubMed (NLM)  (95)
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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 07 January 2014, Vol.111(1), pp.409-14
    Description: A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.
    Keywords: Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Antineoplastic Agents, Alkylating -- Pharmacology ; Brain Neoplasms -- Drug Therapy ; Cell Cycle Proteins -- Metabolism ; Glioblastoma -- Drug Therapy ; Glioma -- Drug Therapy ; Intracellular Signaling Peptides and Proteins -- Metabolism ; O(6)-Methylguanine-DNA Methyltransferase -- Pharmacology ; Tor Serine-Threonine Kinases -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    In: Chemical Communications, 2014, Vol.50(97), pp.15419-15422
    Description: A chemical route to periodic hole arrays in gold films whose holes are loaded with single gold nanoparticles is presented, paving the road to mass production of highly sensitive plasmonic sensors on large areas.
    Keywords: Nanopores ; Gold -- Chemistry ; Metal Nanoparticles -- Chemistry ; Surface Plasmon Resonance -- Instrumentation;
    ISSN: 1359-7345
    E-ISSN: 1364-548X
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(4), p.e0122539
    Description: Soil microbial communities play an important role in forest ecosystem functioning, but how climate change will affect the community composition and consequently bacterial functions is poorly understood. We assessed the effects of reduced precipitation with the aim of simulating realistic future drought conditions for one growing season on the bacterial community and its relation to soil properties and forest management. We manipulated precipitation in beech and conifer forest plots managed at different levels of intensity in three different regions across Germany. The precipitation reduction decreased soil water content across the growing season by between 2 to 8% depending on plot and region. T-RFLP analysis and pyrosequencing of the 16S rRNA gene were used to study the total soil bacterial community and its active members after six months of precipitation reduction. The effect of reduced precipitation on the total bacterial community structure was negligible while significant effects could be observed for the active bacteria. However, the effect was secondary to the stronger influence of specific soil characteristics across the three regions and management selection of overstorey tree species and their respective understorey vegetation. The impact of reduced precipitation differed between the studied plots; however, we could not determine the particular parameters being able to modify the response of the active bacterial community among plots. We conclude that the moderate drought induced by the precipitation manipulation treatment started to affect the active but not the total bacterial community, which points to an adequate resistance of the soil microbial system over one growing season.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    In: Neurology, 2015, Vol.84(17), pp.1782-1787
    Description: OBJECTIVES:: To investigate whether the human sciatic nerve might have a consistent somatotopic organization according to proximal fascicle input by spinal nerves. METHODS:: Twelve patients (55.3 ± 15.5 years) with confirmed lesions of either the L5 or S1 spinal nerve root underwent magnetic resonance neurography of sciatic nerve fascicles including thigh and knee levels (T2-weighted sequence with fat saturation, repetition time/echo time 7,552/52 milliseconds, voxel size 0.27 × 0.27 × 3.0 mm). Twenty healthy subjects and 12 additional patients with an established diagnosis of peripheral polyneuropathy served as 2 separate age- and sex-matched control groups. Two blinded readers assessed patients and controls for presence of distinct lesion patterns. Spatial maps of normalized T2 signal were rendered after segmentation and coregistration of sciatic nerve voxels to detect fascicle lesion patterns. RESULTS:: A clear somatotopic distribution of nerve fascicles was observed on cross-sections along the entire course of the sciatic nerve and was distinct between patients with L5 and those with S1 lesions. Fascicles emerging from L5 were ordered in anterolateral positions within sciatic nerve cross-sections, while fascicles emerging from S1 appeared posteromedially. Visual assessment discriminated these somatotopic lesions in all cases from both healthy and polyneuropathy controls. CONCLUSION:: A distinct pattern of somatotopy was identified within the sciatic nerve according to proximal fascicle input by L5 and S1 spinal nerves. Knowledge of human nerve somatotopy may have clinically useful implications in imaging-aided diagnosis of neuropathies.
    Keywords: Repetition ; Spinal Nerves ; Sciatic Nerve ; Segmentation ; Image Processing ; N.M.R. ; Maps ; Knee ; Polyneuropathy ; Neuropathy ; Neurology & Neuropathology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 5
    In: New Phytologist, May 2016, Vol.210(3), pp.839-849
    Description: Plants rely primarily on rainfall infiltrating their root zones – a supply that is inherently variable, and fluctuations are predicted to increase on most of the Earth's surface. Yet, interrelationships between water availability and plant use on short timescales are difficult to quantify and remain poorly understood. To overcome previous methodological limitations, we coupled high‐resolution in situ observations of stable isotopes in soil and transpiration water. We applied the approach along with Bayesian mixing modeling to track the fate of 2H‐labeled rain pulses following drought through soil and plants of deciduous tree ecosystems. We resolve how rainwater infiltrates the root zones in a nonequilibrium process and show that tree species differ in their ability to quickly acquire the newly available source. Sessile oak (Quercus petraea) adjusted root uptake to vertical water availability patterns under drought, but readjustment toward the rewetted topsoil was delayed. By contrast, European beech (Fagus sylvatica) readily utilized water from all soil depths independent of water depletion, enabling faster uptake of rainwater. Our results demonstrate that species‐specific plasticity and responses to water supply fluctuations on short timescales can now be identified and must be considered to predict vegetation functional dynamics and water cycling under current and future climatic conditions. See also the Commentary on this article by
    Keywords: Climate Change ; Deciduous Trees ; Ecohydrology ; Laser Spectroscopy ; Plant–Water Relations ; Root Uptake ; Soil Water ; Stable Isotopes
    ISSN: 0028-646X
    E-ISSN: 1469-8137
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  • 6
    Language: English
    In: PLoS ONE, 2012, Vol.7(3), p.e33449
    Description: Hypermethylation in the promoter region of the MGMT gene encoding the DNA repair protein O 6 -methylguanine-DNA methyltransferase is among the most important prognostic factors for patients with glioblastoma and predicts response to treatment with alkylating agents like temozolomide. Hence, the MGMT status is widely determined in most clinical trials and frequently requested in routine diagnostics of glioblastoma. Since various different techniques are available for MGMT promoter methylation analysis, a generally accepted consensus as to the most suitable diagnostic method remains an unmet need. Here, we assessed methylation-specific polymerase chain reaction (MSP) as a qualitative and semi-quantitative method, pyrosequencing (PSQ) as a quantitative method, and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a semi-quantitative method in a series of 35 formalin-fixed, paraffin-embedded glioblastoma tissues derived from patients treated in a prospective clinical phase II trial that tested up-front chemoradiotherapy with dose-intensified temozolomide (UKT-05). Our goal was to determine which of these three diagnostic methods provides the most accurate prediction of progression-free survival (PFS). The MGMT promoter methylation status was assessable by each method in almost all cases ( n  = 33/35 for MSP; n  = 35/35 for PSQ; n  = 34/35 for MS-MLPA). We were able to calculate significant cut-points for the continuous methylation signals at each CpG site analysed by PSQ (range, 11.5 to 44.9%) and at one CpG site assessed by MS-MLPA (3.6%) indicating that a dichotomisation of continuous methylation data as a prerequisite for comparative survival analyses is feasible. Our results show that, unlike MS-MLPA, MSP and PSQ provide a significant improvement of predicting PFS compared with established clinical prognostic factors alone (likelihood ratio tests: p 〈0.001). Conclusively, taking into consideration prognostic value, cost effectiveness and ease of use, we recommend pyrosequencing for analyses of MGMT promoter methylation in high-throughput settings and MSP for clinical routine diagnostics with low sample numbers.
    Keywords: Research Article ; Medicine ; Oncology ; Pathology
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: 2012, Vol.7(11), p.e49742
    Description: Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. ; This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. ; In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p〈0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. ; Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Physiology ; Neurological Disorders ; Radiology And Medical Imaging
    E-ISSN: 1932-6203
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  • 8
    In: Neurology, 2016, Vol.87(18), pp.1884-1891
    Description: OBJECTIVE:: To investigate the spatial pattern of lesion dispersion in posterior interosseous neuropathy syndrome (PINS) by high-resolution magnetic resonance neurography. METHODS:: This prospective study was approved by the local ethics committee and written informed consent was obtained from all patients. In 19 patients with PINS and 20 healthy controls, a standardized magnetic resonance neurography protocol at 3-tesla was performed with coverage of the upper arm and elbow (T2-weighted fat-saturated: echo time/repetition time 52/7,020 milliseconds, in-plane resolution 0.27 × 0.27 mm). Lesion classification of the radial nerve trunk and its deep branch (which becomes the posterior interosseous nerve) was performed by visual rating and additional quantitative analysis of normalized T2 signal of radial nerve voxels. RESULTS:: Of 19 patients with PINS, only 3 (16%) had a focal neuropathy at the entry of the radial nerve deep branch into the supinator muscle at elbow/forearm level. The other 16 (84%) had proximal radial nerve lesions at the upper arm level with a predominant lesion focus 8.3 ± 4.6 cm proximal to the humeroradial joint. Most of these lesions (75%) followed a specific somatotopic pattern, involving only those fascicles that would form the posterior interosseous nerve more distally. CONCLUSIONS:: PINS is not necessarily caused by focal compression at the supinator muscle but is instead frequently a consequence of partial fascicular lesions of the radial nerve trunk at the upper arm level. Neuroimaging should be considered as a complementary diagnostic method in PINS.
    Keywords: 120 ; 181 ; Article;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 9
    In: Neurology, 2014, Vol.82(7), pp.598-606
    Description: OBJECTIVE:: We sought to determine lesion sites and spatial lesion patterns in spontaneous anterior interosseous nerve syndrome (AINS) with high-resolution magnetic resonance neurography (MRN). METHODS:: In 20 patients with AINS and 20 age- and sex-matched controls, MRN of median nerve fascicles was performed at 3T with large longitudinal anatomical coverage (upper arm/elbow/forearm): 135 contiguous axial slices (T2-weighted: echo time/repetition time 52/7,020 ms, time of acquisition: 15 minutes 48 seconds, in-plane resolution: 0.25 × 0.25 mm). Lesion classification was performed by visual inspection and by quantitative analysis of normalized T2 signal after segmentation of median nerve voxels. RESULTS:: In all patients and no controls, T2 lesions of individual fascicles were observed within upper arm median nerve trunk and strictly followed a somatotopic/internal topography: affected were those motor fascicles that will form the anterior interosseous nerve further distally while other fascicles were spared. Predominant lesion focus was at a mean distance of 14.6 ± 5.4 cm proximal to the humeroradial joint. Discriminative power of quantitative T2 signal analysis and of qualitative lesion rating was high, with 100% sensitivity and 100% specificity (p 〈 0.0001). Fascicular T2 lesion patterns were rated as multifocal (n = 17), monofocal (n = 2), or indeterminate (n = 1) by 2 independent observers with strong agreement (kappa = 0.83). CONCLUSION:: It has been difficult to prove the existence of fascicular/partial nerve lesions in spontaneous neuropathies using clinical and electrophysiologic findings. With MRN, fascicular lesions with strict somatotopic organization were observed in upper arm median nerve trunks of patients with AINS. Our data strongly support that AINS in the majority of cases is not a surgically treatable entrapment neuropathy but a multifocal mononeuropathy selectively involving, within the main trunk of the median nerve, the motor fascicles that continue distally to form the anterior interosseous nerve.
    Keywords: Data Processing ; Median Nerve ; Image Processing ; Joints ; Repetition ; Classification ; Segmentation ; Peripheral Nervous System ; N.M.R. ; Elbow ; Forearm ; Neuropathy ; Topography ; Neuroanatomy, Histology & Cytology;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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  • 10
    In: Current Opinion in Neurology, 2012, Vol.25(6), pp.767-773
    Description: PURPOSE OF REVIEW: Recent and ongoing translational studies in neurooncology have investigated the role of molecular markers as potential predictors of outcome in patients with WHO grade I and II gliomas, commonly summarized as low-grade gliomas (LGGs). Here, we seek to highlight the most relevant molecular aberrations associated with these tumour types and update on recent findings on their potential prognostic and predictive value. RECENT FINDINGS: So far, no biomarker discussed has any relevance for the postoperative course of disease without genotoxic treatment. Isocitrate dehydrogenase (IDH) mutations, 1p deletion or 1p/19q codeletion have the strongest prognostic impact on survival of patients with LGG, given a genotoxic treatment is provided. Recent findings from phase III clinical trials on anaplastic oligodendroglial tumours conducted in North America and Europe suggest that the addition of procarbazine, lomustine and vincristine to radiotherapy is beneficial in the treatment of anaplastic gliomas with 1p/19q codeletion. To decipher the role of 1p/19q codeletion in LGG will be challenging. Recent developments in v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-specific small molecule inhibitors and their clinical approval for other cancer types could turn BRAF into a promising molecular predictor of outcome in pilocytic astrocytomas, given a treatment with a mutation-specific BRAF inhibitor is applied. SUMMARY: Clinical prognostic factors such as age, tumour size and the presence or absence of clinical symptoms have long been recognized in the management of patients with LGGs. Molecular biomarkers are increasingly evolving as additional factors that facilitate diagnostics and therapeutic decision-making. However, further prospective randomized studies including multivariate analyses are needed to clearly distinguish between prognostic and predictive effects.
    Keywords: Translation ; Age ; Astrocytoma ; Genotoxicity ; Survival ; Vincristine ; Radiotherapy ; Isocitrate Dehydrogenase ; Biomarkers ; Clinical Trials ; Brain Tumors ; Decision Making ; Oncogenes ; Multivariate Analysis ; Reviews ; Sarcoma ; Glioma ; Mutation ; Procarbazine ; Age ; Astrocytoma ; Brain Tumors ; Clinical Trials ; Decision Making ; Genotoxicity ; Glioma ; Isocitrate Dehydrogenase ; Multivariate Analysis ; Mutation ; Oncogenes ; Radiotherapy ; Reviews ; Sarcoma ; Survival ; Translation ; Vincristine ; Biomarkers ; Procarbazine ; Neurology & Neuropathology;
    ISSN: 1350-7540
    E-ISSN: 14736551
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