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排序方式: 共有1230条查询结果,搜索用时 15 毫秒
1.
Georg Prokop Benedikt Wiestler Daniel Hieber Fynn Withake Karoline Mayer Jens Gempt Claire Delbridge Friederike Schmidt-Graf Nicole Pfarr Bruno Märkl Jürgen Schlegel Friederike Liesche-Starnecker 《International journal of cancer. Journal international du cancer》2023,153(9):1658-1670
Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered. 相似文献
2.
3.
The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis 总被引:5,自引:0,他引:5
Wolfram Kessler Tobias Traeger Alexandra Westerholt Friederike Neher Marlene Mikulcak Antje Müller Stefan Maier Claus-Dieter Heidecke 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2006,391(2):83-87
Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed
serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.”
Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly
influenced.
Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete
vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival
and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model.
Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals
(34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from
septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6,
IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis.
Conclusion The vagal nerve is therefore an important modulator of the immune system.
W. Kessler and T. Traeger contributed equally to this work
Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany 相似文献
4.
Haupt SS Spengler F Husemann R Dinse HR 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2004,155(4):485-499
We recorded neurons extracellularly in layers II/III, IV, and V of the hindpaw representation of primary somatosensory cortex in anesthetized rats and studied laminar features of receptive fields (RFs) and representational maps. On average, RFs were smallest in layer IV and largest in layer V; however, for individual penetrations we found substantial deviations from this rule. Within the hindpaw representation, a distinct rostrocaudal gradient of RF size was present in all layers. While layer V RFs were generally largest independent of this gradient, layer IV RFs recorded caudally representing the proximal portions of the paw were larger than layer II/III RFs recorded rostrally representing the digits. The individual scatter of the locations of RFs across laminar groups was in the range of several millimeters, corresponding to about 25% of the average RF diameter. The cutaneous representations of the hindpaw in extragranular layers were confined to the areal extent defined by responsive sites in layer IV. Comparison between RFs determined quantitatively and by handplotting showed a reliable correspondence. Repeated measurements of RFs revealed spontaneous fluctuations of RF size of no more than 5% of the initial condition over an observation period of several hours. The topography and variability of cortical maps of the hindpaw representation were studied with a quantitative interpolation method taking into account the geometric centers of RFs and the corresponding cortical recording sites. On average, the overall topography in terms of preservation of neighborhood relations was present in all layers, although some individual maps showed severe distortions of topography. Factors contributing to map variability were overall position of the representation on the cortical surface, internal topography and spatial extent. Interindividual variability of map layout was always highest in the digit representations. Local topographic orderliness was lowest in layer V, but comparable in layers II/III and IV. Within layer IV, the lowest orderliness was observed in the digit representations. Our data emphasize a substantial variability of RF size, overlap and position across layers and within layers. At the level of representational maps, we found a similar degree of variability that often co-varied across layers, with little evidence for significant layer specificity. Laminar differences are likely to arise from the specific input-output pattern, layer-specific cell types and the connectivity between different layers. Our findings emphasizing similarities in the variability across layers support the notion of tightly coupled columnar interactions between different layers. 相似文献
5.
Karch R Neumann F Neumann M Szawlowski P Schreiner W 《Annals of biomedical engineering》2003,31(5):548-563
Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number N
f
of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001). The distributions of N
f
, V, and S of the CCO models are reasonably well approximated by two-parameter gamma distributions. We study scaling of intravascular blood volume and arterial cross-sectional area with the volume of supplied tissue, the latter being represented by the VP of the respective terminal segments. We observe scaling exponents from 1.20 ± 0.007 to 1.08 ± 0.005 for intravascular blood volume and 0.77 ± 0.01 for arterial cross-sectional area. Setting terminal flows proportional to the associated VP volumes during tree construction yields a relative dispersion of terminal flows of 37% and a coefficient of skewness of 1.12. © 2003 Biomedical Engineering Society.
PAC2003: 8719Uv, 8710+e, 4720Ky, 0260Pn, 0230Oz 相似文献
6.
High diversity of ankA sequences of Anaplasma phagocytophilum among Ixodes ricinus ticks in Germany
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von Loewenich FD Baumgarten BU Schröppel K Geissdörfer W Röllinghoff M Bogdan C 《Journal of clinical microbiology》2003,41(11):5033-5040
In Germany humans with acute granulocytic ehrlichiosis have not yet been described. Here, we characterized three different genes of Anaplasma phagocytophilum strains infecting German Ixodes ricinus ticks in order to test whether they differ from strains in other European countries and the United States. A total of 1,022 I. ricinus ticks were investigated for infection with A. phagocytophilum by nested PCR and sequence analysis. Forty-two (4.1%) ticks were infected. For all positive ticks, parts of the 16S rRNA and groESL genes were sequenced. The complete coding sequence of the ankA gene could be determined in 24 samples. The 16S rRNA and groESL gene sequences were as much as 100% identical to known sequences. Fifteen ankA sequences were >/=99.37% identical to sequences derived from humans with granulocytic ehrlichiosis in Europe and from a horse with granulocytic ehrlichiosis in Germany. Thus, German I. ricinus ticks most likely harbor A. phagocytophilum strains that can cause disease in humans. Nine additional sequences were clearly different from known ankA sequences. Because these newly described sequences have never been obtained from diseased humans or animals, their biological significance is currently unknown. Based on this unexpected sequence heterogeneity, we propose to use the ankA gene for further phylogenetic analyses of A. phagocytophilum and to investigate the biology and pathogenicity of strains that differ in the ankA gene. 相似文献
7.
An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes (TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent (RAD) wild-type yeast and several radiation-sensitive mutants. Either a DNA double-strand break (DSB) or a double-strand gap of 169 bp (DSG) was introduced by restriction enzymes in-vitro within the coding sequence of the URA3 gene of this vector. To eliminate transfer artefacts, selection was first applied for the undamaged TRP1 gene followed by counter selection for URA3 gene activity, which indicated correct repair of the DSB and DSG. Correct repair of the damaged URA3 gene was found to be about 90% in RAD cells (normalized for the expression of undamaged URA3 in TRP
+ transformants). Plasmids isolated from the transformants (URA
+
TRP
+) carry both unique sites (ApaI and NcoI) within the URA3 gene indicating the precise restitution of the 169-bp gap. An excision-repair-defective rad4-4 mutant repaired these lesions as correctly as RAD cells, whereas the mutants rad50-1, rad51-1 and rad54-1, proven to be defective in DSB repair and mitotic recombination, showed less than 5% correct repair of such lesions. In contrast, a representative of the RAD6 epistasis group of genes, the rev2-1 mutant which is sensitive towards UV and ionizing radiation, had a significantly reduced ability (about 20%) for the correct repair of both DSBs and DSGs. 相似文献
8.
Molecular Approaches to Diagnosis of Pulmonary Diseases Due to Mycoplasma pneumoniae 总被引:8,自引:0,他引:8
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Marianne Abele-Horn Ulrich Busch Hans Nitschko Enno Jacobs Ralph Bax Friederike Pfaff Beatrix Schaffer Jürgen Heesemann 《Journal of clinical microbiology》1998,36(2):548-551
In this prospective study, the use of a culture-enhanced PCR assay for the detection of Mycoplasma pneumoniae, followed by hybridization with a specific probe (MP-HPCR) or without hybridization (MP-PCR), and the use of a nested PCR (MP-NPCR) were evaluated. Clinical samples (190 specimens) from 190 patients with respiratory complaints were incubated in culture broth overnight and then subjected to PCR. The results of the PCR were compared to those obtained by culture, the direct antigen test, and serologic testing by microparticle agglutination and by immunoblotting in unclear cases. The sensitivities were 19 CFU for MP-PCR, 1.9 CFU for MP-HPCR, and 0.019 CFU for MP-NPCR. PCR amplification of the β-globin gene was possible in 98% of cases: after dilution of the β-globin-negative samples, all samples were reactive. Correlation between negative MP-NPCR results and negative serology results was found in 89% of cases; a positive correlation was found with 10% of the patients. Samples from three immunocompromised patients were MP-NPCR positive but serologically negative. High respiratory colonization by M. pneumoniae (>105 CFU/ml) in patients with acute respiratory disease could be detected by culture, MP-PCR, and MP-NPCR. These results indicate that MP-PCR and MP-NPCR are reliable methods for the detection of M. pneumoniae in respiratory tract samples of patients with respiratory complaints. 相似文献
9.
Boehlen Friederike H. Maatouk Imad Friederich Hans-Christoph Schoettker Ben Brenner Hermann Wild Beate 《Quality of life research》2022,31(7):2023-2033
Quality of Life Research - Health-related quality of life (HRQOL) in older persons is influenced by physical and mental health, as well as by their social contacts and social support. Older women... 相似文献
10.
Aftahy A. Kaywan Barz Melanie Wagner Arthur Liesche-Starnecker Friederike Negwer Chiara Meyer Bernhard Gempt Jens 《Neurosurgical review》2021,44(4):2099-2110
Neurosurgical Review - Exposure of the anterior skull base is challenging due to strategic structures. The interhemispheric approach (IHA) has turned out to be a feasible technique. We report our... 相似文献