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T Sauter

Publications and source records attributed to T Sauter.

At least 19 recordsLinked to original sources
PubMed2004

Modeling and experimental validation of the signal transduction via the Escherichia coli sucrose phospho transferase system.

Bacterial signal processing was investigated concerning the sucrose phosphotransferase system (sucrose PTS) in the bacterium Escherichia coli as an example. The about 20 different phosphotransferase systems (PTSs) of the cell fulfill besides the transport of various carbohydrates, also the function of one signal processing system. Extra- and intracellular signals are converted within the PTS protein chain to important regulatory signals affecting, e.g. carbon metabolism and chemotaxis. A detailed dynamical model of the sucrose PTS was developed describing transport and signal processing function. It was formulated using a detailed description of complex formation and phosphate transfer between the chain proteins. Model parameters were taken from literature or were identified with own experiments. Simulation studies together with experimental hints showed that the dynamic behavior of phosphate transfer in the PTS runs within 1 s. Therefore a description of steady state characteristics is sufficient for describing the signaling properties of the sucrose PTS. A steady state characteristic field describes the degree of phosphorylation of the PTS protein EIIACrr as a function of the input variables extracellular sucrose concentration and intracellular phosphoenolpyruvate (PEP):pyruvate ratio. The model has been validated with different experiments performed in a CSTR using a sucrose positive E. coli W3110 derivative. A method for determining intracellular metabolite concentrations has been developed. A sample preparation technique using a boiling ethanol buffer solution was successfully applied. The PTS output signal degree of phosphorylation of EIIACrr was also measured. Steady state conditions with varying dilution rate and dissolved oxygen concentration and dynamical variations applying different stimuli to the culture were considered. Pulse, and stop feeding experiments with limiting sucrose concentrations were performed. Simulation and experimental results matched well. The same holds for the expanded sucrose PTS and glycolysis model.

Cyclic AMP↗
PubMed2004

Time hierarchies in the Escherichia coli carbohydrate uptake and metabolism.

The analysis of metabolic pathways with mathematical models contributes to the better understanding of the behavior of metabolic processes. This paper presents the analysis of a mathematical model for carbohydrate uptake and metabolism in Escherichia coli. It is shown that the dynamic processes cover a broad time span from some milliseconds to several hours. Based on this analysis the fast processes could be described with steady-state characteristic curves. A subsequent robustness analysis of the model parameters shows that the fast part of the system may act as a filter for the slow part of the system; the sensitivities of the fast system are conserved. From these findings it is concluded that the slow part of the system shows some robustness against changes in parameters of the fast subsystem, i.e. if a parameter shows no sensitivity for the fast part of the system, it will also show no sensitivity for the slow part of the system.

Escherichia coli↗
PubMed2004

Reduction of mathematical models of signal transduction networks: simulation-based approach applied to EGF receptor signalling.

Biological systems and, in particular, cellular signal transduction pathways are characterised by their high complexity. Mathematical models describing these processes might be of great help to gain qualitative and, most importantly, quantitative knowledge about such complex systems. However, a detailed mathematical description of these systems leads to nearly unmanageably large models, especially when combining models of different signalling pathways to study cross-talk phenomena. Therefore, simplification of models becomes very important. Different methods are available for model reduction of biological models. Importantly, most of the common model reduction methods cannot be applied to cellular signal transduction pathways. Using as an example the epidermal growth factor (EGF) signalling pathway, we discuss how quantitative methods like system analysis and simulation studies can help to suitably reduce models and additionally give new insights into the signal transmission and processing of the cell.

Algorithms↗
PubMed2003

A phase II trial of pemetrexed in patients with metastatic renal cancer.

BACKGROUND: Metastatic renal cell carcinoma (RCC) is rising in incidence but remains difficult to treat. This clinical trial evaluated the effects of pemetrexed (multitargeted antifolate, ALIMTAR) for the treatment of metastatic RCC. PATIENTS AND METHODS: Patients were required to have histological diagnosis of metastatic RCC with measurable disease and no prior chemotherapy. In addition, patients were required to have a World Health Organization (WHO) performance status of 0-2 and adequate bone marrow reserve. Patients received pemetrexed at a dose of 600 mg/m2 as a 10 min infusion every 3 weeks. Patients did not receive folic acid or vitamin B12 supplementation. RESULTS: Thirty-nine patients were enrolled and thirty two were evaluable for response. Three patients had a partial response for a response rate of 9% (95% CI 2-25%). The median time to progressive disease was 10.5 months. Of the nonresponders, twenty two had stable disease (median duration was 5.8 months; range 1.5-27.7) and seven had progressive disease (median time to progression was 5.4 months). Median time to progression for all qualified patients was 5.7 months. Common toxicities experienced were diarrhea and infection. Fatigue, stomatitis, and rash were also reported. The most common hematologic toxicity was grade 3/4 lymphopenia in 76% of patients. Leukopenia, granulocytopenia, and thrombocytopenia were also frequently reported. CONCLUSION: Single-agent pemetrexed has moderate activity in the treatment of metastatic RCC and should be investigated in combination with other potential active agents, as first-line treatment.

Aged↗
PubMed2001

[Minimally invasive bone anchor in therapy of female stress incontinence. A good concept?].

Transvaginal pubic bone anchoring represents a minimally invasive technique for cystourethropexy or urethral sling suspension. This study assesses the results of this procedure. Cystourethropexy was performed in 4 and a sling procedure in 13 of 17 patients. The stress incontinence showed a median improvement from grade 2 to 1.35 (p = 0.01). Nine patients had impaired vaginal wound healing with urge symptoms. Revision was necessary in eight of them. An unfavorable outcome could not be significantly correlated with the surgical technique, the surgeon, the patient's age or the number of previous operations. The technique of minimally invasive bone anchoring must be regarded as unsuitable in view of the largely poor wound healing associated with irritation symptoms.

Adult↗
PubMed2000

Efficacy and tolerability of tolterodine in children with detrusor hyperreflexia.

OBJECTIVES: To investigate the urodynamic effects and tolerability of the new antimuscarinic drug tolterodine in children with detrusor hyperreflexia. METHODS: Twenty-two children (12 boys and 10 girls; age range 3 months to 15 years, mean age 5.7 years) with detrusor hyperreflexia resulting in maximum detrusor pressures exceeding 40 cm H(2)O during filling cystotonometry were enrolled to receive tolterodine tartrate (a total of 0.1 mg/kg orally daily, divided into two doses) either as a first-line therapy (n = 12, group 1) or replacing oxybutynin chloride therapy (n = 10, group 2). Within 3 months, all patients underwent urodynamic re-evaluation during ongoing tolterodine treatment. RESULTS: In group 1, the mean maximum bladder capacity increased from 120.2 to 173.0 mL (+44%), the mean detrusor compliance increased from 8.7 to 13.5 mL/cm H(2)O (+55%), and the mean maximum detrusor pressures decreased from 70.1 to 37.9 cm H(2)O (-46%); the differences were significant (P < 0.001). In group 2, no differences in the urodynamic effects of oxybutynin versus tolterodine were noted. Only 1 patient experienced a transient and moderately adverse effect with tolterodine. CONCLUSIONS: Although based on a limited number of subjects, these data indicate that in pediatric patients with detrusor hyperreflexia, tolterodine may be better tolerated than and equally effective as the standard drug oxybutynin chloride.

Adolescent↗
PubMed1999

Quantitative detection of human complement factor H-related protein in transitional cell carcinoma of the urinary bladder.

OBJECTIVE: The purpose of this study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), human complement factor H-related protein (hCFHrp, BTA TRAK). METHODS: Urine samples of 298 individuals (76 healthy volunteers, 118 patients with benign urologic disorders, 104 patients with histologically proven bladder cancer) were examined for the presence of hCFHrp. Samples of all patients were obtained prior to therapy. RESULTS: In comparison to healthy volunteers, patients with TCC had significantly higher urinary levels of hCFHrp (117.60 vs. 2.05 U/ml; p < 0.001). HCFHrp levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of hCFHrp than patients with superficial TCC (p = 0.001). Marker levels in superficial bladder cancer at high risk of tumor progression (pT1G3) were significantly higher as compared to low and intermediate grade superficial cancers. Elevated levels of hCFHrp were also found in patients with benign urologic disorders (median: 72.65 vs. 117.60 U/ml in cancer patients). Using a cutoff of 17.1 U/ml, hCFHrp had a sensitivity of 72.1% and, due to a high rate of false-positive determinations in patients with benign urologic disorders, a total specificity of 50.5%. CONCLUSIONS: HCFHrp (BTA TRAK) is a sensitive test for detection of bladder cancer and for identification of patients at high risk. Due to a high rate of false-positive results in patients with benign urologic diseases, the test should not be used in an unselected population.

Adult↗
PubMed1998

Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4.

1. The metabolism of Meloxicam (ME) and the cytochrome(s) P450 (CYPs) involved were analysed by using primary human hepatocytes, human liver microsomes and microsomes from recombinant human B-lymphoblastoid cell lines. 2. While human hepatocytes were capable of converting ME to a 5-hydroxymethyl metabolite (M7) and then to a 5-carboxyderivative (M5), human liver microsomes formed mostly only the 5-hydroxymethylderivative. The kinetics of the formation of M7 by human liver microsomes were biphasic with Km = 13.6 +/- 9.5 and 381 +/- 55.2 microM respectively. The corresponding Vmax were 33.7 +/- 24.2 and 143 +/- 83.9 pmol/min/mg protein respectively. 3. CYP2C9 and, to a much lesser extent, CYP3A4 were found to convert ME to M7. The involvement of 2C9 was demonstrated by inhibition of tolbutamide hydroxylase activity in the presence of ME, inhibition of ME metabolism by sulphaphenazole, correlation between ME metabolism and tolbutamide hydroxylase activity and active metabolism of ME by recombinant 2C9. The involvement of 3A4 was shown by inhibition of ME metabolism by ketoconazole, correlation between ME metabolism and nifedipine oxidase activity and metabolism of ME by recombinant 3A4. Kinetics of the formation of M7 by the individual enzymes resulted in a Km = 9.6 microM and Vmax = 8.4 pmol/min/mg protein for 2C9 and a Km = 475 microM and Vmax = 23 pmol/min/mg protein for 3A4.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Rapid pharmacokinetic screening of salbutamol in plasma samples by column-switching high-performance liquid chromatography-electrospray mass spectrometry.

In order to obtain pharmacokinetic data from studies in humans, a sensitive and selective assay for the quantification of salbutamol in human plasma samples was required. This report describes an automated high-performance liquid chromatography-mass spectrometry assay with pre-column enrichment using internal standard calibration for the quantification of salbutamol and the validation of the assay. The lower limit of quantitation is 0.2 ng/ml with an accuracy and imprecision of less than 7%. The analysis time is 8 min per sample.

Adrenergic beta-Agonists↗
PubMed1995

Metabolism of pimobendan in long-term human hepatocyte culture: in vivo-in vitro comparison.

The aim of this study was to investigate further the potential of a new hepatocyte culture based on the hypothesis that liver cells in an appropriate in vitro environment (immobilizing gel technique) maintain high metabolic activity comparable with that in vivo. Pimobendan (UD-CG 115), a pyridazinone derivative, is a cardiotonic vasodilator that increases myocardial contractility through calcium sensitization and relaxation of vascular smooth muscle, probably due to phosphodiesterase inhibition. In man, pimobendan is O-demethylated to UD-CG 212. This latter is metabolized to O- and N-glucuronides. Pimobendan itself is also glucuronidated to a N-glucuronide. Human hepatocytes immobilized in collagen gel were incubated with pimobendan to investigate their metabolic activity in the long-term and to compare the results to the data from clinical trials. 14C-labelled pimobendan was incubated at two concentrations (10 and 100 microM) at day 3, 11 and 22 of culture, and samples were analysed after 4, 24 and 48-h incubation. Metabolic patterns were evaluated by hplc with radioactivity-, diode array-, and mass spectral-detection. In vitro, pimobendan was O-demethylated and subsequently O-glucuronidated. The rate of metabolism of pimobendan could be maintained in this culture system for > 3 weeks. However, the relative amount of a putative N-glucuronide under in vitro conditions was lower than in vivo.

Biotransformation↗
PubMed1994

Transplantation in utero of fetal human hematopoietic stem cells into mice results in hematopoietic chimerism.

Allogeneic and xenogeneic hematolymphoid chimerism has been achieved in large and small animals using varied techniques to circumvent immune mediated graft rejection by the recipient. We show here the establishment of long-term chimerism in normal mice transplanted in utero with human fetal hematopoietic stem cells (HSC). HSCs from fetal (13-20 weeks' gestation) human livers were injected into fetal mouse peritoneal cavities on days 11-13 of gestation. Histologic examination demonstrated human chimerism in 29% of 38 live born mice using fluorescein conjugated antibodies to both the CD45 and CD14 antigens present on human peripheral blood (PB) cells. Further investigation using flow cytometric analysis of cells from 70 mice transplanted in utero revealed 28% of mice greater than 16 weeks of age contained human cells in at least one organ at the following frequencies: 14% PB, 8% bone marrow, 8% spleen and 12% thymus. These data indicate that human fetal HSC can be engrafted into mouse fetuses. Additionally, the identification of circulating human cells 18 months following transplantation supports the engraftment and proliferation of a primitive hematopoietic progenitor.

Animals↗
PubMed1990

ESWL monotherapy for large stones and staghorn calculi.

From December 1986 through March 1988, 52 renal units (RU) with large stone burden have been treated by ESWL monotherapy. In all patients a ureteral stent was placed prior to lithotripsy, to provide drainage of the kidney during the period of stone passage. Data of 43 RU were collected for the present report. Complications ; following treatment were infrequent (2%), whereas auxiliary measures became necessary in 32% of the patients. After a mean follow-up of 9.1 months, 54% of the patients were found stone-free. Stratification according to different stone types and compositions revealed that none of the 7 patients with complete staghorns could be completely cleared and that struvite stones had a significantly better outcome than calcium oxalate stones (75 vs. 25%). Consequently, for a large but not excessive stone burden in a normal or only slightly dilated renal collecting system, ESWL monotherapy under the protection of a ureteral stent may be a comparably safe alternative to percutaneous surgery.

Adult↗
PubMed1989

[Surgical urinary bladder replacement in cancer].

Radical cystectomy, where necessary combined with systemic chemotherapy, is currently regarded to be the treatment of choice in invasive bladder cancer. Compared with such procedures as colonic or ileal conduit the construction of a continent intestinal bladder substitution is not associated with any higher risks but offers a considerably better quality of life without significantly extending the duration of surgery. Our experience with the ileal-neobladder with non-reflux uretero-intestinal implantation described by LeDuc, and Kock's the thoroughgoing application principles to form a low pressure reservoir for bladder substitution, encouraged us to believe that a good long-term prognosis with respect to renal function can be expected. About 90% of all patients with ileal-neobladder are continent day and night. About half of them have sensory function and are capable of voiding urine completely by abdominal straining. For invasive bladder cancer, therefore, continent bladder substitution must be generally regarded to be the superior alternative to urinary diversion by conduit.

Colon, Sigmoid↗
PubMed1989

[Role of extracorporeal shockwave lithotripsy without anesthesia in the treatment of ureteral calculi].

With anesthesia-free lithotripsy recently being available, the discussion upon the treatment of choice of ureteral calculi has been renewed: is a preliminary retrograde manipulation still preferable for proximal calculi? Is ureteroscopy the better treatment for stones in the lower ureter? The retrospective evaluation of our patients with ureteral calculi (January-August 1988) failed to reveal a significantly compromised efficiency with the modified HM-3 lithotripter (40 nF. generator, 17 cm. ellipsoid): 70% (including 11% with repeated sessions) of the patients with proximal stones and 90% (including 28% with repeated sessions) of the patients with distal calculi were successfully treated in situ without the need for anesthesia, auxiliary measures, or ureteroscopy. These results do not substantially differ from those obtained with the old HM-3 in 1987, and confirm, that the majority of patients with ureteral calculi can bypass the discomfort of retrograde manipulation or the risks of ureteroscopy.

Anesthesia↗
PubMed1989

[Current therapy of ureteral calculus].

Since lithotripsy requiring no anesthesia recently became available, the discussion revolving around the treatment of choice for ureteral calculi has been renewed: is a preliminary retrograde manipulation still preferable for proximal calculi? Is ureteroscopy the better treatment for stones in the lower ureter? The retrospective evaluation of our patients with ureteral calculi (January to August 1988) failed to reveal a compromised efficiency with the modified HM3 Lithotripter (40 nF generator, 17 cm ellipsoid): 70% (including 11% with repeated sessions) of patients with proximal stones and 90% (including 28% with repeated sessions) of patients with distal calculi were successfully treated by in situ ESWL with no need for anesthesia, auxiliary measures, or ureteroscopy. These results do not significantly differ from those obtained with the old HM3, and they confirm that the majority of patients with ureteral calculi can bypass the discomfort of retrograde manipulation and the risks of ureteroscopy.

Combined Modality Therapy↗