0000000000194830
AUTHOR
Stefan Müller
Immunotherapy of Metastasizing Renal Cell Carcinoma
119 patients with stage-IV renal cell carcinoma were treated using immunotherapy with autologous tumor vaccine. The immunization was carried out at monthly intervals, the patients were restaged every
Enhanced Activity of Meprin-α, a Pro-Migratory and Pro-Angiogenic Protease, in Colorectal Cancer
Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)- induced migratory response of meprin-transfected epithelial c…
The Use of Neoadjuvant Chemotherapy in Patients With Urothelial Carcinoma of the Bladder: Current Practice Among Clinicians.
Abstract Introduction Guidelines recommend neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in patients with urothelial carcinoma of the bladder in clinical stages T2-T4a, cN0M0. We examined the frequency and current practice of NAC and sought to identify predictors for the use of NAC in a prospective contemporary cohort. Materials and Methods We analyzed prospective data from 679 patients in the PROMETRICS (PROspective MulticEnTer RadIcal Cystectomy Series 2011) database. All patients underwent RC in 2011. Uni- and multivariable regression analyses identified predictors of NAC application. Furthermore, a questionnaire was used to evaluate the practice patterns of NAC at the PR…
Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli
Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the pre…
In situ detection of stratosphere-troposphere exchange of cirrus particles in the midlatitudes
Airborne trace gas, microphysical, and radiation measurements were performed during the AIRcraft TOwed Sensor Shuttle - Inhomogeneous Cirrus Experiment over northern Germany in 2013. Based on high-precision nitrous oxide (N2O) and carbon monoxide (CO) in situ data, stratospheric air could be identified, which contained cirrus cloud particles. Consistent with the stratospheric N2O data, backward trajectories indicate that the sampled air masses crossed the dynamical tropopause in the last 3 h before the measurement. These air masses contained cirrus particles, which were formed during slow ascent in the troposphere and subsequently mixed with stratospheric air. From the CO-N2O correlation th…
Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis
Abstract Vitamin K antagonists (VKAs) have been used in 1% of the world’s population for prophylaxis or treatment of thromboembolic events for 64 years. Impairment of osteoblast function and osteoporosis has been described in patients receiving VKAs. Given the involvement of cells of the bone marrow microenvironment (BMM), such as mesenchymal stem cells (MSCs) and macrophages, as well as other factors such as the extracellular matrix for the maintenance of normal hematopoietic stem cells (HSCs), we investigated a possible effect of VKAs on hematopoiesis via the BMM. Using various transplantation and in vitro assays, we show here that VKAs alter parameters of bone physiology and reduce funct…
Metalloproteases meprin α and meprin β are C- and N-procollagen proteinases important for collagen assembly and tensile strength.
Type I fibrillar collagen is the most abundant protein in the human body, crucial for the formation and strength of bones, skin, and tendon. Proteolytic enzymes are essential for initiation of the assembly of collagen fibrils by cleaving off the propeptides. We report that Mep1a −/− and Mep1b −/− mice revealed lower amounts of mature collagen I compared with WT mice and exhibited significantly reduced collagen deposition in skin, along with markedly decreased tissue tensile strength. While exploring the mechanism of this phenotype, we found that cleavage of full-length human procollagen I heterotrimers by either meprin α or meprin β led to the generation of mature collagen molecules that s…
Shapes and oscillations of raindrops with reduced surface tensions: Measurements at the Mainz vertical wind tunnel
Abstract Important characteristics of raindrops pertinent to fields in atmospheric sciences such as weather radar or pollution scavenging are drop shape, oscillation frequency and amplitude, as well as the internal circulation. Atmospheric raindrops are never pure water drops but contain additional components like aerosol particles and dissolved species. Surface active substances, when present, reduce the surface tension of raindrops and, thus, increase the drop deformation which in turn affects breakup and coalescence, pollutant scavenging, and, finally, the formation of precipitation. Experiments were performed at the Mainz vertical wind tunnel with raindrops freely suspended at their ter…
The Appendix as a Continence Mechanism
Although we have progressed very well in creating large capacity, low pressure reservoirs, the construction of a simple and reliable continent outlet still remains a problem. The appendix vermiformis serves well as a continence mechanism for either the bladder or intestinal reservoirs for urine. The different surgical techniques described in the literature are reviewed and discussed in this context. Moreover, we report on our clinical and experimental results of using the appendix during the Mainz pouch procedure for continent urinary diversion.
Transport of Antarctic stratospheric strongly dehydrated air into the troposphere observed during the HALO-ESMVal campaign 2012
Abstract. Dehydration in the Antarctic winter stratosphere is a well-known phenomenon that is annually observed by satellites and occasionally observed by balloon-borne measurements. However, in situ measurements of dehydrated air masses in the Antarctic vortex are very rare. Here, we present detailed observations with the in situ and GLORIA remote sensing instrument payload aboard the German aircraft HALO. Strongly dehydrated air masses down to 1.6 ppmv of water vapor were observed as far north as 47° S in an altitude between 12 and 13 km in the lowermost stratosphere. The dehydration can be traced back to individual ice formation events above the Antarctic Peninsula and Plateau, where ice…
Effects of yohimbine on sexual experiences and nocturnal penile tumescence and rigidity in erectile dysfunction.
The therapeutic effect of the alpha 2-antagonist yohimbine in erectile dysfunction was studied in a double-blind placebo-controlled design. Thirty-one male patients underwent extensive clinical, urological, and psychiatric diagnosis and were dichotomically classified into an organic and a nonorganic subgroup. Following a 1-week placebo run-in period, patients were randomly assigned to a placebo or a verum group (yohimbine 15 mg daily) for a treatment period of 7 weeks. The Clinical Global Impression (CGI) scale was used as the primary efficacy parameter. Additionally, nocturnal penile tumescence and rigidity (NPTR) were measured. Global assessment of erectile function applying the CGI scale…
The solubilization site of 5,10,15,20-tetrakis-(2,6-dichlorophenyl)-porphyrin-Mn(III) in DPPC vesicles: A spectrophotometric and tensiometric study
Abstract The solubilization site of 5,10,15,20-tetrakis-(2,6-dichlorophenyl)-porphyrin-Mn(III) (MnTDPPC) in l -α-dipalmitoylphosphatidyl choline (DPPC) vesicles was determined in a systematic UV–vis spectrophotometric study. Measurements of the MnTDPPC absorbance have been conducted at constant temperatures (in the interval 30 °C ≤ T ≤ 48 °C) and varying concentrations of phospholipid. In the entire temperature range, the absorption due to MnTDCCP was found to increase with increasing DPPC concentration, until it reaches a plateau value. The data have been analyzed using a pseudo-phase model yielding the binding constant of MnTDCPP to vesicular aggregates. No significant temperature depende…
A quantitative analysis of stratospheric HCl, HNO3, and O3 in the tropopause region near the subtropical jet
The effects of chemical two-way mixing on the Extratropical Transition Layer (ExTL) near the subtropical jet are investigated by stratospheric tracer-tracer correlations. To this end, in situ measurements were performed west of Africa (25-32 ◦ N) during the Transport and Composition of the Upper Troposphere Lower Stratosphere (UTLS)/Earth System Model Validation (TACTS/ESMVal) mission in August/September 2012. The Atmospheric chemical Ionization Mass Spectrometer sampling HCl and HNO3 was for the first time deployed on the new German High Altitude and Long range research aircraft (HALO). Measurements of O3, CO, European Centre for Medium-Range Weather Forecasts (ECMWF) analysis, and the tig…
Low Urethral Pressure Profile - Clinical Implications
The clinical impact of urethral pressure profilometry (UPP) has been a main urological topic over the past three decades. Exaggareted expectations and differing techniques with incongruent results caused a controversial appearance. However, since the UPP is the only method to measure directly aspects of the urethral closure function, all types of sphincteric urinary incontinence represent indications for this measurement. Based on long-term experience this paper aims to discuss the various complexes regarding the urethral pressure profilometry. The significance of the urethral closure function for urinary continence and the urodynamic relevance of active and passive pressure transmission ar…
Epithelioid Leiomyoma of the Prostate
We report a case of an unusual mesenchymal tumor of the prostate. Rectal-digital palpation and transrectal ultrasound showed a circumscribed and inhomogeneous tumor within the right prostatic lobe. Surgical treatment consisted of transurethral resection of the right prostatic lobe. On the basis of morphology and immunohistochemical detection of desmin and smooth-muscle-type actin, the diagnosis of an epithelioid leiomyoma was made. This is the first report of this entity in the prostate. A definite prediction of the biological potential is currently not yet possible.
40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004
Fast transport from Southeast Asia boundary layer sources to northern Europe: rapid uplift in typhoons and eastward eddy shedding of the Asian monsoon anticyclone
Abstract. Enhanced tropospheric trace gases such as CO, CH4 and H2O and reduced stratospheric O3 were measured in situ in the lowermost stratosphere over northern Europe on 26 September 2012 during the TACTS aircraft campaign. The measurements indicate that these air masses clearly differ from the stratospheric background. The calculation of 40-day backward trajectories with the trajectory module of the CLaMS model shows that these air masses are affected by the Asian monsoon anticyclone. Some air masses originate from the boundary layer in Southeast Asia/West Pacific and are rapidly lifted (1–2 days) within a typhoon up to the outer edge of the Asian monsoon anticyclone. Afterwards, the ai…
The Mainz Pouch II
The Mainz pouch II procedure has proved to be a substantial modification of the classical technique of ureterosigmoidostomy at many institutions. To date we have used this procedure in 72 patients, including 15 children. Detubularization causes a low pressure and eliminates high-pressure contractions. Without the risk of compromising the blood supply the pouch is fixed at the promontory which reduces the risk of ureteral kinking and upper urinary tract dilatation as it is sometimes observed after ureterosigmoidostomy. The technique is not only indicated in cases of failed ureterosigmoidostomy but also for primary urinary diversion. Of the 72 patients operated, all are evaluable with a follo…
A tandem approach for collocated in-situ measurements of microphysical and radiative cirrus properties
Abstract. Microphysical and radiation measurements were collected with the unique AIRcraft TOwed Sensor Shuttle (AIRTOSS) – Learjet tandem platform. It is a combination of a Learjet 35A research aircraft and an instrumented aerodynamic body, which can be detached from and retracted back to the aircraft during flight. Both platforms are equipped with radiative, cloud microphysical, trace gas (CO, N2O, O3 and H2O) and meteorological instruments to study the inhomogeneity of cirrus as well as other layer clouds. Sophisticated numerical flow simulations were conducted in advance in order to optimally integrate a Cloud Combination Probe (CCP) inside the AIRTOSS. The tandem platform was used for …
A tandem approach for collocated measurements of microphysical and radiative cirrus properties
Microphysical and radiation measurements were collected with the novel AIRcraft TOwed Sensor Shuttle (AIRTOSS) – Learjet tandem platform. The platform is a combination of an instrumented Learjet 35A research aircraft and an aerodynamic bird, which is detached from and retracted back to the aircraft during flight via a steel wire with a length of 4000 m. Both platforms are equipped with radiative, cloud microphysical, trace gas, and meteorological instruments. The purpose of the development of this tandem set-up is to study the inhomogeneity of cirrus as well as other stratiform clouds. Sophisticated numerical flow simulations were conducted in order to optimally integrate an axially asymmet…
Impact of the Asian monsoon on the extratropical lower stratosphere: trace gas observations during TACTS over Europe 2012
Abstract. The transport of air masses originating from the Asian monsoon anticyclone into the extratropical upper troposphere and lower stratosphere (Ex-UTLS) above potential temperatures Θ = 380 K was identified during the HALO aircraft mission TACTS in August and September 2012. In situ measurements of CO, O3 and N2O during TACTS flight 2 on 30 August 2012 show the irreversible mixing of aged stratospheric air masses with younger (recently transported from the troposphere) ones within the Ex-UTLS. Backward trajectories calculated with the trajectory module of CLaMS indicate that these tropospherically affected air masses originate from the Asian monsoon anticyclone. These air masses are …
Water vapor increase in the northern lower stratosphere by the Asian monsoon anticyclone observed during TACTS/ESMVal campaigns
Abstract. The impact of air masses from Asia influenced by the Asian monsoon anticyclone on the northern hemispheric stratosphere is investigated based on in-situ measurements. An statistical significant increase in water vapor of about 0.5 ppmv (11 %) and methane up to 20 ppbv (1.2 %) in the extra-tropical stratosphere above a potential temperature of 380 K was detected between August and September 2012 by in-situ instrumentation in the northern hemisphere during the HALO aircraft mission TACTS and ESMVal. We investigate the origin of this water vapor and methane increase with the help of the three-dimensional Lagrangian chemistry transport model CLaMS. We assign the source of the moist ai…