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Berlin Brandenburg

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  • 1
    In: PLoS ONE, 2014, Vol.9(1)
    Description: Many animals change their body pigmentation according to illumination of their environment. In aquatic vertebrates, this reaction is mediated through aggregation or dispersion of melanin-filled vesicles (melanosomes) in dermal pigment cells (melanophores). The adaptive value of this behavior is usually seen in camouflage by allowing the animal to visually blend into the background. When exposed to visible light from below, however, dark-adapted zebrafish embryos at the age of 2 days post fertilization (dpf) surprisingly display dispersal instead of aggregation of melanosomes, i.e. their body coloration becomes dark on a bright background. Melanosomes of older embryos and early larvae (3–5 dpf) on the other hand aggregate as expected under these conditions. Here we provide an explanation to this puzzling finding: Melanosome dispersion in larvae 3 dpf and older is efficiently triggered by ultraviolet (UV) light, irrespective of the visual background, suggesting that the extent of pigmentation is a trade-off between threats from predation and UV irradiation. The UV light-induced dispersion of melanosomes thereby is dependent on input from retinal short wavelength-sensitive (SWS) cone photoreceptors. In young embryos still lacking a functional retina, protection from UV light predominates, and light triggers a dispersal of melanosomes via photoreceptors intrinsic to the melanophores, regardless of the actual UV content. In older embryos and early larvae with functional retinal photoreceptors in contrast, this light-induced dispersion is counteracted by a delayed aggregation in the absence of UV light. These data suggest that the primary function of melanosome dispersal has evolved as a protective adaption to prevent UV damage, which was only later co-opted for camouflage.
    Keywords: Research Article ; Biology
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Gut, 29 March 2011, Vol.60(3), p.387
    Description: Hepatocyte-specific NEMO/NF-κB deleted mice (NEMO) develop spontaneous non-alcoholic steatohepatitis (NASH). Free fatty acids and bile acids promote DR5 expression. TRAIL/NK cell-mediated activation of TRAIL-R2/DR5 plays an important role during acute injury in NEMO mice.
    Keywords: Bile Acid ; Nonalcoholic Steatohepatitis ; Nuclear Factor Kappa
    ISSN: 0017-5749
    ISSN: 00175749
    E-ISSN: 1468-3288
    E-ISSN: 14683288
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  • 3
    Language: English
    In: Urologia Internationalis, January 2016, Vol.96(1), pp.39-45
    Description: Introduction: Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). Materials and Methods: We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Results: Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both - NMIBC and MIBC - had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Conclusions: Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis.
    Keywords: Original Paper ; Yap1 ; Pyap1 ; Urothelial Bladder Cancer ; Immunhistochemistry ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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  • 4
    Language: English
    In: PLoS ONE, 2012, Vol.7(2), p.e32168
    Description: Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro , were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Oncology
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: Urologia Internationalis, October 2016, Vol.97(3), pp.369-372
    Description: Primary urethral solitary plasmacytoma is a very rare variant of extramedullary plasmacytoma. In total, only 9 cases have been reported so far. Patients were treated either by surgery or by external radiation therapy. Here, we report on a 22-year-old man, initially presenting with a palpable induration at the penis, intermittent dysuria and haematospermia, which was due to histologically confirmed solitary urethral kappa-restricted plasmacytoma. The patient subsequently underwent percutaneous and endo-urethral high-dose-rate brachytherapy with a total dose of 42 Gy applied in 14 fractions. Besides an uncomplicated urinary tract infection and hyperpigmentation of the penis, the patient tolerated the radiotherapy well and is still free of disease after 15 months follow-up.
    Keywords: Case Report ; Brachytherapy ; Extramedullary Plasmacytoma ; Urethra ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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  • 6
    In: International Journal of Urology, September 2013, Vol.20(9), pp.866-871
    Description: Byline: Stephan Buse, Thomas Hofner, Stephan C Muller, Edwin Hermann, Wolf F Wieland, Matthias May, Christian G Stief, Patrick J Bastian, Markus Hohenfellner, Axel Haferkamp Keywords: age; cystoprostatectomy; incidence; prostate cancer; transitional cell carcinoma Objective To describe the prevalence of incidental prostate cancer in patients undergoing radical cystoprostatectomy for bladder malignancy; to quantify the association between incidental prostate cancer and mortality in these patients; and to quantify the association between incidental prostate cancer and age in radical cystoprostatectomy specimens. Methods Consecutive patients undergoing radical cystoprostatectomy for bladder malignancy at six academic institutions were assessed. End-points were the histological diagnosis of prostate cancer in the radical cystoprostatectomy specimens and mortality. The association between incidental prostate cancer and mortality was calculated by multivariable Cox regression, and the association between age and the occurrence of prostate cancer was calculated by logistic regression. Results A total of 1122 patients (aged 65.6[+ or -]10years) were included in this analysis. Prostate cancer was detected in 17.8% (n=200) of the cystoprostatectomy specimens. After multivariable adjustment, prostate cancer was significantly associated with mortality (hazard ratio 1.27, 95% confidence interval 1.03-1.56). There was a significant association between age and the presence of prostate cancer in the cystoprostatectomy specimen. The odds ratio for the presence of prostate cancer was 1.028 (95% confidence interval 1.011-1.045; P 0.001) per each year after the age of 40years. Conclusions Concomitant prostate cancer is an independent prognostic factor for mortality after radical cystoprostatectomy for bladder cancer. When considering a prostate-sparing technique, urologists should consider that every fifth to sixth patient will present with a concomitant prostate cancer, and that after the age of 40years, the odds of a concomitant prostate cancer increases by 2.8% per year, thus warranting a careful balance between the oncological risks and quality of life issues.
    Keywords: Age ; Cystoprostatectomy ; Incidence ; Prostate Cancer ; Transitional Cell Carcinoma
    ISSN: 0919-8172
    E-ISSN: 1442-2042
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  • 7
    Language: English
    In: Urologia Internationalis, January 2016, Vol.96(1), pp.57-64
    Description: Introduction: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. Materials and Methods: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. Results: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p 〈 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p 〈 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p 〈 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. Conclusion: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.
    Keywords: Original Paper ; Bladder Cancer ; Radical Cystectomy ; Nomogram ; Outcome ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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  • 8
    Language: English
    In: Urologia Internationalis, July 2018, Vol.101(1), pp.16-24
    Description: Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). Methods: Clinical and histopathological parameters of patients have been prospectively collected within the “PROspective MulticEnTer RadIcal Cystectomy Series 2011”. BMI was categorized as normal weight (〈25 kg/m2), overweight (≥25–29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. Results: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the ­American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). Conclusions: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled ­accordingly.
    Keywords: Original Paper ; Urothelial Carcinoma ; Bladder Cancer ; Obesity ; Radical Cystectomy ; Prognosis ; Survival ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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  • 9
    Language: English
    Description: Introduction: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. Materials and Methods: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. Results: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980;p 〈 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1;OR 3.367;p 〈 0.001), presence of hydronephrosis (OR 1.844;p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378;p 〈 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. Conclusion: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters. (C) 2015 S. Karger AG, Basel
    Source: Open Access LMU (Universitätsbibliothek der LMU München)
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  • 10
    In: Neurology, 2016, Vol.87(3), pp.295-298
    Description: OBJECTIVE:: We prospectively screened a large European cohort of patients presenting with hyperCKemia and/or limb-girdle muscular weakness (LGMW) for acid α-glucosidase (GAA) deficiency by dried blood spot (DBS) investigation. METHODS:: DBS were collected from 3,076 consecutive adult patients from 7 German and British neuromuscular centers. All specimens were investigated for GAA deficiency by fluorometry. Samples with reduced enzyme activity were subsequently investigated for GAA gene mutations. RESULTS:: Of 3,076 patients with DBS samples, 232 patients (7.6%) showed low GAA enzyme activity. Of these 232 patients, 55 (24%) presented with isolated hyperCKemia and 176 (76%) with hyperCKemia and LGMW. With both features present, 94% of the patients showed a low enzymatic activity. Mutational analysis found GAA gene mutations in 74 patients (2.4%); herein 70 patients were heterozygote for the common GAA gene splice-site mutation c.-32-13T〉G. The most common clinical presentation in the confirmed Pompe cohort was a limb-girdle phenotype (85.3%) combined with ventilatory insufficiency (61%). Isolated hyperCKemia was found in 12%, while 2.7 had hyperCKemia and ventilatory insufficiency only. CONCLUSIONS:: In a large cohort of unselected adult patients with hyperCKemia and/or LGMW, we found a prevalence of late-onset Pompe disease of 2.4%. Therefore, targeted screening of such a population should be encouraged in clinical practice.
    Keywords: Medicine;
    ISSN: 0028-3878
    E-ISSN: 1526632X
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