444 research outputs found
Mischung unterschiedlicher Faserarten für die Vliesherstellung mit Hilfe einer einfachen Laboranlage
Diese Studienarbeit beschäftigt sich mit dem Thema „Mischung unterschiedlicher Faserarten für die Vliesherstellung mit Hilfe einer einfachen Laboranlage“. Zunächst wird grundlegend auf die Herstellung von Fließstoffen und die möglichen Herstellungsverfahren eingegangen. Außerdem werden die Besonderheiten hybrider Vliesstoffe kurz dargestellt. Nach einem Überblick über den Stand der Technik, werden die Überlegungen und die Entwicklungsschritte der Laboranlage erläutert. Im nachfolgendem Kapitel werden die gewonnenen Ergebnisse aus der Faservermischung dokumentiert
Molecular mechanisms of IL-18BP regulation in DLD-1 cells: pivotal direct action of the STAT1/GAS axis on the promoter level
Interleukin (IL)-18, formerly known as interferon (IFN)-γ-inducing factor, is a crucial mediator of host defence and inflammation. Control of IL-18 bioactivity by its endogenous antagonist IL-18 binding protein (IL-18BP) is a major objective of immunoregulation. IL-18BP is strongly up-regulated by IFN-γ, thereby establishing a negative feedback mechanism detectable in cell culture and in vivo. Here we sought to investigate in D.L. Dexter (DLD) colon carcinoma cells molecular mechanisms of IL-18BP induction under the influence of IFN-γ. Mutational analysis revealed that a proximal γ-activated sequence (GAS) at the IL-18BP promoter is of pivotal importance for expression by IFN-γ-activated cells. Use of siRNA underscored the essential role of the signal transducer and activator of transcription (STAT)-1 in this process. Indeed, electrophoretic mobility shift assay and chromatin immunoprecipitation analysis proved STAT1 binding to this particular GAS site. Maximal expression of IL-18BP was dependent on de novo protein synthesis but unaffected by silencing of interferon regulatory factor-1. Altogether, data presented herein indicate that direct action of STAT1 on the IL-18BP promoter at the proximal GAS element is key to IL-18BP expression by IFN-γ-stimulated DLD-1 colon carcinoma cells
Funktion der Pim-1-Kinase in der Zellzyklus-Progression
Mittels eines neuartigen Hefe-Interaktions-Systems (engl.: Ras-Recruitment-System, RRS) wurde ein Protein isoliert, welches mit dem Proto?Onkogen Pim-1 interagiert. Dabei handelte es sich um die Serin/Threonin-Kinase C-TAK1 (CDC twenthy-five associated Kinase 1). C-TAK1 phosphoryliert die Phosphatase CDC25C an der AS Ser216, wodurch diese durch Rekrutierung von 14-3-3-Adapter-Proteinen inaktiviert wird. Pim-1 war ebenfalls in der Lage, im herkömmlichen Hefe-System (engl.: Yeast two hybrid) mit C-TAK1 zu interagieren. Das RRS-System wurde weiterhin zur Erzeugung einer nicht-interagierenden Punktmutante (C-TAK1-L128P) genutzt. Neben dem schon bekannten C-TAK1-wt-Protein konnten zusätzlich noch zwei weitere humane Spleiß-Varianten, C-TAK1-a und b, beschrieben werden.
Die Interaktion zwischen Pim-1 und C-TAK1 wurde in GST-Interaktions-Experimenten, Immunopräzipitationen und Immunfluoreszenzen bestätigt. Dies war unabhängig von der Verwendung des Pim-1-wt-Proteins oder der inaktiven Pim-1-K67M-Mutante. Die zwei C-TAK1-Spleiß-Varianten zeigten dabei keinen Unterschied zum isolierten C-TAK1-wt-Protein. Es konnte auch endogenes Pim-1-Protein mit C-TAK1 in einem Komplex nachgewiesen werden.
In den biochemischen Studien stellte sich heraus, dass Pim-1 nicht nur mit C-TAK1, sondern auch mit der Phosphatase CDC25C interagiert. Die Pim-1/CDC25C-Interaktion konnte ebenfalls in endogenen Komplexen nachgewiesen werden.
In Kinase-Experimenten stellte sich heraus, dass sowohl C-TAK1 als auch CDC25C von Pim-1-wt, aber nicht von der Pim-1-inaktiven Mutante, phosphoryliert wurden. Durch Deletions-Mutanten konnte nicht nur die Pim-1-Interaktions-Domäne in dem C-TAK1- und CDC25C-Protein, sondern ebenfalls mögliche Phosphorylierungs-Bereiche bestimmt werden. In den beiden NLS-Sequenzen im C-Terminus des C-TAK1-Proteins ist ein abgewandeltes und ein Pim-1-Phosphorylierungs-Motiv enthalten. Allerdings liegen die Pim-1-Phosphorylierungs-Stellen in dem C-TAK1-Protein sowohl im N-Terminus als auch im C-Terminus. CDC25C wird an einem oder mehreren Serinen oder Threoninen durch Pim-1 phosphoryliert, nicht aber an der AS Ser216. CDC25C besitzt allerdings kein gegenwärtiges postuliertes Pim-1-Phosphorylierungs-Motiv.
In einem C-TAK1-Inaktivierungs-Experiment konnte gezeigt werden, dass die Kinase-Aktivität von C-TAK1 durch die Pim-1-Phosphorylierung herabgesetzt wird. Die Phosphatase-Aktivität von CDC25C im Phosphatase-Experiment wurde dagegen durch Pim-1-Phosphorylierung erhöht. Demzufolge übt Pim-1 sowohl eine indirekte (über C-TAK1) als auch eine direkte Aktivierung auf CDC25C aus. Diese Ergebnisse deuten darauf hin, dass die Pim-1-Kinase eine wichtige Rolle am G2/M-Kontrollpunkt einnimmt und dass Pim-1 ein wichtiges Bindeglied zwischen Zytokin-/Wachstumssignalwegen und Proliferation darstellt
Complications of laser prostatectomy: a review of recent data
Introduction: Laser techniques for the treatment of bladder outlet obstruction (BOO) due to benign prostate enlargement (BPE) have emerged as an alternative to transurethral resection of the prostate (TURP) and open prostatectomy (OP). Materials and methods: A Medline search over the past 4years was performed to assess the safety, intra- and postoperative morbidity of various laser techniques. Results: Data on holmium laser enucleation of the prostate (HoLEP) show the highest grade of evidence with two meta-analyses available and prove the low intra- and postoperative morbidity with reproducible long-term results. Photoselective vaporization of the prostate (PVP) with the Greenlightlaser (potassium titanyl phosphate, KTP or lithium borate, LBO) is characterized by excellent haemostatic properties in patients with or without oral anticoagulation. Long-term results show a reoperation rate comparable with TURP; however, there is a lack of randomized trials. Various types of diode lasers with different wavelengths are available for laser vaporization; despite their favourable haemostatic properties, a higher invasion depth seems to result in necrosis of the tissue leading to a higher rate of reoperation. Thulium-laser resection of the prostate shows promising intra- and postoperative morbidity, but data are limited and initial results need to be confirmed in large-scale trials. Conclusion: In summary, HoLEP- and KTP-, or LBO-laser vaporization of the prostate are the most mature techniques of laser prostatectomy and treatment alternatives to TURP and OP, whereas the clinical value and durability of procedures with diode laser systems and the thulium laser need to be confirmed in high-quality prospective RCT
Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study
Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far.
Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications.
Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P 18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)).
Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis
Targeting cathepsin C ameliorates murine acetaminophen-induced liver injury
Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3\u27mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication
Improved detection of microbial ureteral stent colonisation by sonication
Purpose: The diagnosis of microbial ureteral stent colonisation (MUSC) is difficult, since routine diagnostic techniques do not accurately detect microorganisms embedded in biofilms. New methods may improve diagnostic yield and understanding the pathophysiology of MUSC. The aim of the present study was to evaluate the potential of sonication in the detection of MUSC and to identify risk factors for device colonisation. Methods: Four hundred and eight polyurethane ureteral stents of 300 consecutive patients were prospectively evaluated. Conventional urine culture (CUC) was obtained prior to stent placement and device removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex and age, indwelling time and indication for stent placement were recorded. Results: Sonicate-fluid culture detected MUSC in 36%. Ureteral stents inserted during urinary tract infection (UTI) were more frequently colonised (59%) compared to those placed in sterile urine (26%; P<0.001). Female sex (P<0.001) and continuous stenting (P<0.005) were significant risk factors for MUSC; a similar trend was observed in patients older than 50years (P=0.16). MUSC and indwelling time were positively correlated (P<0.005). MUSC was accompanied by positive CUC in 36%. Most commonly isolated microorganisms were Coagulase-negative staphylococci (18.3%), Enterococci (17.9%) and Enterobacteriaceae (16.9%). Conclusions: Sonication is a promising approach in the diagnosis of MUSC. Significant risk factors for MUSC are UTI at the time of stent insertion, female sex, continuous stenting and indwelling time. CUC is a poor predictor of MUSC. The clinical relevance of MUSC needs further evaluation to classify isolated microorganism properly as contaminants or pathogen
Microbial colonization and ureteral stent-associated storage lower urinary tract symptoms: the forgotten piece of the puzzle?
Purpose: Ureteral stents are frequently associated with side effects. Most patients suffer from storage lower urinary tract symptoms (LUTS). Storage LUTS are commonly attributed to the irritation of the trigone, smooth muscle spasm or a combination of factors. The relationship between microbial ureteral stent colonization (MUSC) and de novo or worsening storage LUTS has not been investigated yet. Methods: Five hundred ninety-one polyurethane ureteral stents from 275 male and 153 female patients were prospectively evaluated. The removed stents were sonicated to dislodge adherent microorganisms. Urine flow cytometry was performed to detect pyuria. A standardized urinary symptom questionnaire was given to all patients. Results: Thirty-five per cent of male and 28% of female cases showed de novo or worsened storage LUTS. MUSC was more common in patients with storage LUTS compared to patients without storage LUTS (men: 26 vs. 13%, respectively, P<0.05; women: 63 vs. 48%, respectively, P=0.13). Pyuria was significantly more common in patients with storage LUTS compared to patients without storage LUTS (men: 55 vs. 40%, respectively, P<0.05; women: 70 vs. 45%, respectively, P<0.05). No significant correlation was observed between the detected genera of microorganisms and storage LUTS. Conclusions: Our data show a significant association between MUSC- and stent-related de novo experienced or worsened storage LUTS in men. The incidence of MUSC is most common in both female and male patients with storage LUTS and accompanying pyuria. In these patients, a combination of antibiotics and anti-inflammatory drugs may be regarded as treatment optio
Improved detection of microbial ureteral stent colonisation by sonication
Purpose: The diagnosis of microbial ureteral stent colonisation (MUSC) is difficult, since routine diagnostic techniques do not accurately detect microorganisms embedded in biofilms. New methods may improve diagnostic yield and understanding the pathophysiology of MUSC. The aim of the present study was to evaluate the potential of sonication in the detection of MUSC and to identify risk factors for device colonisation. Methods: Four hundred and eight polyurethane ureteral stents of 300 consecutive patients were prospectively evaluated. Conventional urine culture (CUC) was obtained prior to stent placement and device removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex and age, indwelling time and indication for stent placement were recorded. Results: Sonicate-fluid culture detected MUSC in 36%. Ureteral stents inserted during urinary tract infection (UTI) were more frequently colonised (59%) compared to those placed in sterile urine (26%; P<0.001). Female sex (P<0.001) and continuous stenting (P<0.005) were significant risk factors for MUSC; a similar trend was observed in patients older than 50years (P=0.16). MUSC and indwelling time were positively correlated (P<0.005). MUSC was accompanied by positive CUC in 36%. Most commonly isolated microorganisms were Coagulase-negative staphylococci (18.3%), Enterococci (17.9%) and Enterobacteriaceae (16.9%). Conclusions: Sonication is a promising approach in the diagnosis of MUSC. Significant risk factors for MUSC are UTI at the time of stent insertion, female sex, continuous stenting and indwelling time. CUC is a poor predictor of MUSC. The clinical relevance of MUSC needs further evaluation to classify isolated microorganism properly as contaminants or pathogen
Microbial biofilm formation and catheter-associated bacteriuria in patients with suprapubic catheterisation
Purpose: Catheter-associated bacteriuria (CAB) with transurethral catheters is almost inevitable. Suprapubic catheters (SPCs) are widely considered to decrease the risk of CAB. However, SPCs are implants similarly prone to microbial biofilm formation. The spectrum of colonising pathogens has not been investigated. The aim of this prospective study was: (1) to assess the diversity of microbial suprapubic catheter colonisation (MSPCC), (2) to identify risk factors and (3) to investigate its association with CAB and catheter-associated urinary tract infection (CA-UTI). Methods: A total of 218 SPCs from 112 patients were studied. Urine specimens were obtained after device replacement or removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex, age, indwelling time, and underlying disease were recorded. Results: Sonicate-fluid culture (SFC) detected MSPCC in 95%. Increasing indwelling time correlated with MSPCC (p<0.05). Negative SFC was more frequent when antibiotic prophylaxis was applied at time of catheter placement (15 vs. 2%, p<0.05). Most commonly isolated were Enterobacteriaceae (45.8%), followed by Enterococcus spp. (25.7%) and Pseudomonas aeruginosa (10.3%). CAB and CA-UTI were observed in 95 and 11%, respectively. Conclusions: This study provides the first analysis of MSPCC. Indwelling time increases, whereas antibiotic prophylaxis decreases the risk of MSPCC. The spectrum of pathogens is comparable to the one obtained from urethral catheter biofilms. Urine specimens could not demonstrate the microbial diversity of MSPCC. SPCs are not preferable to urethral catheters to reduce CAB. Whether the risk of CA-UTI could be minimised by SPCs remains to be clarifie
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